Billy W. Loo, Jr., MD, PhD, DABR

All Publications

• Normal Tissue Constraints for Abdominal and Thoracic Stereotactic Body Radiotherapy. Seminars in radiation oncology Pollom, E. L., Chin, A. L., Diehn, M., Loo, B. W., Chang, D. T. 2017; 27 (3): 197-208

  Abstract

  Although stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy has become an established standard of care for the treatment of a variety of malignancies, our understanding of normal tissue dose tolerance with extreme hypofractionation remains immature. Since Timmerman initially proposed normal tissue dose constraints for SBRT in the 2008 issue of Seminars of Radiation Oncology, experience with SBRT has grown, and more long-term clinical outcome data have been reported. This article reviews the modern toxicity literature and provides updated clinically practical and useful recommendations of SBRT dose constraints for extracranial sites. We focus on the major organs of the thoracic and upper abdomen, specifically the liver and the lung.

  View details for DOI 10.1016/j.semradonc.2017.02.001

  View details for PubMedID 28577827

• Pulmonary function after lung tumor stereotactic ablative radiotherapy depends on regional ventilation within irradiated lung. Radiotherapy and oncology Binkley, M. S., King, M. T., Shrager, J. B., Bush, K., Chaudhuri, A. A., Popat, R., Gensheimer, M. F., Maxim, P. G., Henry Guo, H., Diehn, M., Nair, V. S., Loo, B. W. 2017; 123 (2): 270-275

  Abstract

  To determine if regional ventilation within irradiated lung volume predicts change in pulmonary function test (PFT) measurements after stereotactic ablative radiotherapy (SABR) of lung tumors.We retrospectively identified 27 patients treated from 2007 to 2014 at our institution who received: (1) SABR without prior thoracic radiation; (2) pre-treatment 4-dimensional computed tomography (4-D CT) imaging; (3) pre- and post-SABR PFTs <15months from treatment. We defined the ventilation ratio (VR20BED3) as the quotient of mean ventilation (mean Jacobian-based per-voxel volume change on deformably registered inhale/exhale 4-D CT phases) within the 20Gy biologically effective dose (α/β=3Gy) isodose volume and that of the total lung volume (TLV).Most patients had moderate to very severe COPD by GOLD criteria (n=19, 70.1%). Higher VR20BED3 significantly predicted worse change in Forced Expiratory Volume/s normalized by baseline value (ΔFEV1/FEV1pre, p=0.04); n=7 had VR20BED3>1 (high regional ventilation) and worse ΔFEV1/FEV1pre (median=-0.16, range=-0.230 to -0.20). Five had VR20BED3<1 (low regional ventilation) and improved ΔFEV1/FEV1pre (median=0.13, range=0.07 to 0.20). In a multivariable linear model, increasing VR20BED3 and time to post-SABR PFT predicted decreasing ΔFEV1/FEV1pre (R(2)=0.25, p=0.03).After SABR to high versus low functioning lung regions, we found worsened or improved global pulmonary function, respectively. If pre-SABR VR20BED3 is validated as a predictor of eventual post-SABR PFT in larger studies, it may be used for individualized treatment planning to preserve or even improve pulmonary function after SABR.

  View details for DOI 10.1016/j.radonc.2017.03.021

  View details for PubMedID 28460826

• Optimal Radiation Therapy for Small Cell Lung Cancer. Current treatment options in oncology Gensheimer, M. F., Loo, B. W. 2017; 18 (4): 21-?

  Abstract

  Radiation therapy plays an important role in the management of both limited stage and extensive stage small cell lung cancer. For limited stage disease, there has been a trend toward reduced size of thoracic radiation fields, which has the potential to reduce toxicity. FDG-PET staging helps make this possible by more accurately identifying areas of nodal and metastatic involvement. Trials have demonstrated similar outcomes using a range of radiation fractionation schedules, allowing flexibility in individualizing treatment. Using advanced radiation therapy techniques such as intensity-modulated radiation therapy, it may be possible to deliver fewer, higher dose fractions and achieve similar results to the hyperfractionated regimen. For extensive stage disease, consolidative thoracic radiation therapy after chemotherapy was recently shown to improve overall survival in certain patient subsets. Prophylactic cranial irradiation continues to play an important role in management of all stages of small cell lung cancer. Debate continues about the neurocognitive effects of this treatment, and whether MRI surveillance is an acceptable alternative. Strategies such as hippocampal avoidance may reduce the cognitive effects of prophylactic cranial irradiation in the future. Finally, in the last few years stereotactic ablative radiation therapy followed by chemotherapy has emerged as a promising treatment for stage I small cell lung cancer. This radiation treatment is usually given over 1-5 fractions and appears to provide a good rate of local control with a low rate of serious toxicity.

  View details for DOI 10.1007/s11864-017-0467-z

  View details for PubMedID 28391424

• Non-Small Cell Lung Cancer, Version 5.2017 Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Ettinger, D. S., Wood, D. E., Aisner, D. L., Akerley, W., Bauman, J., Chirieac, L. R., D'Amico, T. A., DeCamp, M. M., Dilling, T. J., Dobelbower, M., Doebele, R. C., Govindan, R., Gubens, M. A., Hennon, M., Horn, L., Komaki, R., Lackner, R. P., Lanuti, M., Leal, T. A., Leisch, L. J., Lilenbaum, R., Lin, J., Loo, B. W., Martins, R., Otterson, G. A., Reckamp, K., Riely, G. J., Schild, S. E., Shapiro, T. A., Stevenson, J., Swanson, S. J., Tauer, K., Yang, S. C., Gregory, K., Hughes, M. 2017; 15 (4): 504-535

  Abstract

  This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.

  View details for Web of Science ID 000399398700009

  View details for PubMedID 28404761

• Very high-energy electron (VHEE) beams in radiation therapy; Treatment plan comparison between VHEE, VMAT, and PPBS. Medical physics Schüler, E., Eriksson, K., Hynning, E., Hancock, S. L., Hiniker, S. M., Bazalova-Carter, M., Wong, T., Le, Q., Loo, B. W., Maxim, P. G. 2017

  Abstract

  The aim of this study was to evaluate the performance of very high-energy electron beams (VHEE) in comparison to clinically derived treatment plans generated with volumetric modulated arc therapy (VMAT) and proton pencil beam scanning (PPBS) technology. We developed a custom optimization script that could be applied automatically across modalities to eliminate operator bias during IMRT optimization.Four clinical cases were selected (prostate cancer, lung cancer, pediatric brain tumor, and head and neck cancer (HNC)). The VHEE beams were calculated in the EGSnrc/DOSXYZnrc Monte Carlo code for 100 and 200 MeV beams. Treatment plans with VHEE, VMAT, and PPBS were optimized in a research version of RayStation using an in-house developed script to minimize operator bias between the different techniques.The in-house developed script generated similar or superior plans to the clinically used plans. In the comparisons between the modalities, the integral dose was lowest for the PPBS-generated plans in all cases. For the prostate case, the 200 MeV VHEE plan showed reduced integral dose and reduced organ at risk (OAR) dose compared to the VMAT plan. For all other cases, both the 100 and the 200 MeV VHEE plans were superior to the VMAT plans, and the VHEE plans showed better conformity and lower spinal cord dose in the pediatric brain case and lower brain stem dose in the HNC case when compared to the PPBS plan.The automated optimization developed in this study generated similar or superior plans as compared to the clinically used plan and represents an unbiased approach to compare treatment plans generated for different modalities. In the present study, we also show that VHEE plans are similar or superior to VMAT plans with reduced mean OAR dose and increased target conformity for a variety of clinical cases, and VHEE plans can even achieve reductions in OAR doses compared to PPBS plans for shallow targets. With increased VHEE energy, better conformity and even higher reductions in mean OAR doses are achieved. On the whole, VHEE was intermediate between photon VMAT and PPBS for OAR sparing.

  View details for DOI 10.1002/mp.12233

  View details for PubMedID 28339108

• Tumor control probability modeling for stereotactic body radiation therapy of early-stage lung cancer using multiple bio-physical models. Radiotherapy and oncology Liu, F., Tai, A., Lee, P., Biswas, T., Ding, G. X., El Naqa, I., Grimm, J., Jackson, A., Kong, F. S., LaCouture, T., Loo, B., Miften, M., Solberg, T., Li, X. A. 2017; 122 (2): 286-294

  Abstract

  This work is to analyze pooled clinical data using different radiobiological models and to understand the relationship between biologically effective dose (BED) and tumor control probability (TCP) for stereotactic body radiotherapy (SBRT) of early-stage non-small cell lung cancer (NSCLC). The clinical data of 1-, 2-, 3-, and 5-year actuarial or Kaplan-Meier TCP from 46 selected studies were collected for SBRT of NSCLC in the literature. The TCP data were separated for Stage T1 and T2 tumors if possible, otherwise collected for combined stages. BED was calculated at isocenters using six radiobiological models. For each model, the independent model parameters were determined from a fit to the TCP data using the least chi-square (χ(2)) method with either one set of parameters regardless of tumor stages or two sets for T1 and T2 tumors separately. The fits to the clinic data yield consistent results of large α/β ratios of about 20Gy for all models investigated. The regrowth model that accounts for the tumor repopulation and heterogeneity leads to a better fit to the data, compared to other 5 models where the fits were indistinguishable between the models. The models based on the fitting parameters predict that the T2 tumors require about additional 1Gy physical dose at isocenters per fraction (⩽5 fractions) to achieve the optimal TCP when compared to the T1 tumors. In conclusion, this systematic analysis of a large set of published clinical data using different radiobiological models shows that local TCP for SBRT of early-stage NSCLC has strong dependence on BED with large α/β ratios of about 20Gy. The six models predict that a BED (calculated with α/β of 20) of 90Gy is sufficient to achieve TCP⩾95%. Among the models considered, the regrowth model leads to a better fit to the clinical data.

  View details for DOI 10.1016/j.radonc.2016.11.006

  View details for PubMedID 27871671

• Dynamic CT imaging of volumetric changes in pulmonary nodules correlates with physical measurements of stiffness. Radiotherapy and oncology Lartey, F. M., Rafat, M., Negahdar, M., Malkovskiy, A. V., Dong, X., Sun, X., Li, M., Doyle, T., Rajadas, J., Graves, E. E., Loo, B. W., Maxim, P. G. 2017; 122 (2): 313-318

  Abstract

  A major challenge in CT screening for lung cancer is limited specificity when distinguishing between malignant and non-malignant pulmonary nodules (PN). Malignant nodules have different mechanical properties and tissue characteristics ('stiffness') from non-malignant nodules. This study seeks to improve CT specificity by demonstrating in rats that measurements of volumetric ratios in PNs with varying composition can be determined by respiratory-gated dynamic CT imaging and that these ratios correlate with direct physical measurements of PN stiffness.Respiratory-gated MicroCT images acquired at extreme tidal volumes of 9 rats with PNs from talc, matrigel and A549 human lung carcinoma were analyzed and their volumetric ratios (δ) derived. PN stiffness was determined by measuring the Young's modulus using atomic force microscopy (AFM) for each nodule excised immediately after MicroCT imaging.There was significant correlation (p=0.0002) between PN volumetric ratios determined by respiratory-gated CT imaging and the physical stiffness of the PNs determined from AFM measurements.We demonstrated proof of concept that PN volume changes measured non-invasively correlate with direct physical measurements of stiffness. These results may translate clinically into a means of improving the specificity of CT screening for lung cancer and/or improving individual prognostic assessments based on lung tumor stiffness.

  View details for DOI 10.1016/j.radonc.2016.11.019

  View details for PubMedID 27989402

  View details for PubMedCentralID PMC5319913

• Metabolic tumor volume predicts overall survival and local control in patients with stage III non-small cell lung cancer treated in ACRIN 6668/RTOG 0235 EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Bazan, J. G., Duan, F., Snyder, B. S., Horng, D., Graves, E. E., Siegel, B. A., Machtay, M., Loo, B. W. 2017; 44 (1): 17-24

  View details for DOI 10.1007/s00259-016-3520-4

  View details for Web of Science ID 000389242200004

• Role of KEAP1/NRF2 and TP53 Mutations in Lung Squamous Cell Carcinoma Development and Radiation Resistance CANCER DISCOVERY Jeong, Y., Hoang, N. T., Lovejoy, A., Stehr, H., Newman, A. M., Gentles, A. J., Kong, W., Diana Truong, D., Martin, S., Chaudhuri, A., Heiser, D., Zhou, L., Say, C., Carter, J. N., Hiniker, S. M., Loo, B. W., West, R. B., Beachy, P., Alizadeh, A. A., Diehn, M. 2017; 7 (1): 86-101

  View details for DOI 10.1158/2159-8290.CD-16-0127

  View details for Web of Science ID 000396017700024

• Thermal limits on MV x-ray production by bremsstrahlung targets in the context of novel linear accelerators. Medical physics Wang, J., Trovati, S., Borchard, P. M., Loo, B. W., Maxim, P. G., Fahrig, R. 2017; 44 (12): 6610–20

  Abstract

  To study the impact of target geometrical and linac operational parameters, such as target material and thickness, electron beam size, repetition rate, and mean current on the ability of the radiotherapy treatment head to deliver high-dose-rate x-ray irradiation in the context of novel linear accelerators capable of higher repetition rates/duty cycle than conventional clinical linacs.The depth dose in a water phantom without a flattening filter and heat deposition in an x-ray target by 10 MeV pulsed electron beams were calculated using the Monte-Carlo code MCNPX, and the transient temperature behavior of the target was simulated by ANSYS. Several parameters that affect both the dose distribution and temperature behavior were investigated. The target was tungsten with a thickness ranging from 0 to 3 mm and a copper heat remover layer. An electron beam with full width at half maximum (FWHM) between 0 and3 mm and mean current of 0.05-2 mA was used as the primary beam at repetition rates of 100, 200, 400, and 800 Hz.For a 10 MeV electron beam with FWHM of 1 mm, pulse length of 5 μs, by using a thin tungsten target with thickness of 0.2 mm instead of 1 mm, and by employing a high repetition rate of 800 Hz instead of 100 Hz, the maximum dose rate delivered can increase two times from 0.57 to 1.16 Gy/s. In this simple model, the limiting factor on dose rate is the copper heat remover's softening temperature, which was considered to be 500°C in our study.A high dose rate can be obtained by employing thin targets together with high repetition rate electron beams enabled by novel linac designs, whereas the benefit of thin targets is marginal at conventional repetition rates. Next generation linacs used to increase dose rate need different target designs compared to conventional linacs.

  View details for DOI 10.1002/mp.12615

  View details for PubMedID 28983960

  View details for PubMedCentralID PMC5734638

• A 3-D Riesz-Covariance Texture Model for Prediction of Nodule Recurrence in Lung CT IEEE TRANSACTIONS ON MEDICAL IMAGING Cirujeda, P., Cid, Y. D., Muller, H., Rubin, D., Aguilera, T. A., Loo, B. W., Diehn, M., Binefa, X., Depeursinge, A. 2016; 35 (12): 2620-2630

  Abstract

  This paper proposes a novel imaging biomarker of lung cancer relapse from 3-D texture analysis of CT images. Three-dimensional morphological nodular tissue properties are described in terms of 3-D Riesz-wavelets. The responses of the latter are aggregated within nodular regions by means of feature covariances, which leverage rich intra- and inter- variations of the feature space dimensions. When compared to the classical use of the average for feature aggregation, feature covariances preserve spatial co-variations between features. The obtained Riesz-covariance descriptors lie on a manifold governed by Riemannian geometry allowing geodesic measurements and differentiations. The latter property is incorporated both into a kernel for support vector machines (SVM) and a manifold-aware sparse regularized classifier. The effectiveness of the presented models is evaluated on a dataset of 110 patients with non-small cell lung carcinoma (NSCLC) and cancer recurrence information. Disease recurrence within a timeframe of 12 months could be predicted with an accuracy of 81.3-82.7%. The anatomical location of recurrence could be discriminated between local, regional and distant failure with an accuracy of 78.3-93.3%. The obtained results open novel research perspectives by revealing the importance of the nodular regions used to build the predictive models.

  View details for DOI 10.1109/TMI.2016.2591921

  View details for Web of Science ID 000391547700011

  View details for PubMedID 27429433

• Hypofractionated Intensity-Modulated Radiotherapy for Patients With Non-Small-Cell Lung Cancer. Clinical lung cancer Pollom, E. L., Qian, Y., Durkee, B. Y., von Eyben, R., Maxim, P. G., Shultz, D. B., Gensheimer, M., Diehn, M., Loo, B. W. 2016; 17 (6): 588-594

  Abstract

  Alternative treatment regimens are needed for patients with non-small cell lung cancer (NSCLC) who cannot receive definitive treatment with concurrent chemoradiotherapy, surgery, or stereotactic ablative radiotherapy (SABR).We report survival, patterns of failure and toxicity outcomes for patients with NSCLC who were not eligible for surgical resection, concurrent chemoradiotherapy, or SABR and underwent hypofractionated intensity-modulated radiotherapy (IMRT). Kaplan-Meier survival analysis was used to evaluate the progression-free and overall survival. Competing risk analysis was used to evaluate in-field, locoregional, and distant failure.A total of 42 patients treated to 52.5 to 60 Gy in 15 fractions were included. Most of the patients had metastatic or recurrent disease (64%) and a relatively large, centrally located tumor burden (74%). The median follow-up period was 13 months (interquartile range, 6-18 months). All patients received the total prescribed dose. The median survival was 15.1 months. The overall and progression-free survival rates at 1 year were 63% and 22.5%, respectively. The pattern of failure was predominantly distant, with only 2% of patients experiencing isolated in-field recurrence. The cumulative incidence of in-field failure at 6 and 12 months was 2.5% (95% confidence interval, 0.4%-15.6%) and 16.1% (95% confidence interval, 7.5%-34.7%), respectively. The risk of esophageal toxicity was associated with the esophageal mean dose, maximal point dose, and dose to the 5 cm(3) volume. The risk of pneumonitis was associated with the lung mean dose and volume receiving 18 Gy.Hypofractionated IMRT without concurrent chemotherapy provides favorable rates of local control and survival for well-selected patients with NSCLC who cannot tolerate standard definitive therapy.

  View details for DOI 10.1016/j.cllc.2016.05.024

  View details for PubMedID 27378172

• Prognostic value of midtreatment FDG-PET in oropharyngeal cancer. Head & neck Pollom, E. L., Song, J., Durkee, B. Y., Aggarwal, S., Bui, T., von Eyben, R., Li, R., Brizel, D. M., Loo, B. W., Le, Q., Hara, W. Y. 2016; 38 (10): 1472-1478

  Abstract

  Prognostic metabolic imaging indices are needed for risk stratification for patients with locally advanced oropharyngeal cancer.We retrospectively examined pretreatment and midtreatment fluorodeoxyglucose-positron emission tomography (FDG-PET) parameters in patients with locally advanced oropharyngeal cancer who were treated with definitive chemoradiation.A total of 74 patients were evaluated. Pretreatment metabolic tumor volume (MTV) using threshold of 50% standardized uptake value (SUV) maximum (MTV50% ) was associated with progression-free survival (PFS; p = .003; hazard ratio [HR] = 1.57 per 10 cc; 95% confidence interval [CI] = 1.17-2.11) and overall survival (OS; p = .01; HR = 1.36 per 10 cc; 95% CI = 1.07-1.74). Midtreatment MTV using a threshold of SUV 2.0 (MTV2.0 ) was associated with PFS (p < .001; HR = 1.24 per 10 cc; 95% CI = 1.10-1.39) and OS (p = .009; HR = 1.21 per 10 cc; 95% CI = 1.05-1.39). Nodal total lesion glycolysis (TLG) velocity >5% decrease/week was associated with improved PFS (p = .04; HR = 0.37; 95% CI = 0.15-0.95).Metabolic response during chemoradiation is associated with survival in locally advanced oropharyngeal cancer and may aid with risk-adapting treatment. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.

  View details for DOI 10.1002/hed.24454

  View details for PubMedID 27043927

• Intratumor Partitioning of Serial Computed Tomography and FDG Positron Emission Tomography Images Identifies High-Risk Tumor Subregions and Predicts Patterns of Failure in Non-Small Cell Lung Cancer After Radiation Therapy 58th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Wu, J., Gensheimer, M. F., Dong, X., Rubin, D. L., Napel, S., Diehn, M., Loo, B. W., Li, R. ELSEVIER SCIENCE INC. 2016: S100–S100

  View details for Web of Science ID 000387655804563

• Early-Stage Non-Small Cell Lung Cancer: Quantitative Imaging Characteristics of (18)F Fluorodeoxyglucose PET/CT Allow Prediction of Distant Metastasis. Radiology Wu, J., Aguilera, T., Shultz, D., Gudur, M., Rubin, D. L., Loo, B. W., Diehn, M., Li, R. 2016; 281 (1): 270-278

  Abstract

  Purpose To identify quantitative imaging biomarkers at fluorine 18 ((18)F) positron emission tomography (PET) for predicting distant metastasis in patients with early-stage non-small cell lung cancer (NSCLC). Materials and Methods In this institutional review board-approved HIPAA-compliant retrospective study, the pretreatment (18)F fluorodeoxyglucose PET images in 101 patients treated with stereotactic ablative radiation therapy from 2005 to 2013 were analyzed. Data for 70 patients who were treated before 2011 were used for discovery purposes, while data from the remaining 31 patients were used for independent validation. Quantitative PET imaging characteristics including statistical, histogram-related, morphologic, and texture features were analyzed, from which 35 nonredundant and robust features were further evaluated. Cox proportional hazards regression model coupled with the least absolute shrinkage and selection operator was used to predict distant metastasis. Whether histologic type provided complementary value to imaging by combining both in a single prognostic model was also assessed. Results The optimal prognostic model included two image features that allowed quantification of intratumor heterogeneity and peak standardized uptake value. In the independent validation cohort, this model showed a concordance index of 0.71, which was higher than those of the maximum standardized uptake value and tumor volume, with concordance indexes of 0.67 and 0.64, respectively. The prognostic model also allowed separation of groups with low and high risk for developing distant metastasis (hazard ratio, 4.8; P = .0498, log-rank test), which compared favorably with maximum standardized uptake value and tumor volume (hazard ratio, 1.5 and 2.0, respectively; P = .73 and 0.54, log-rank test, respectively). When combined with histologic types, the prognostic power was further improved (hazard ratio, 6.9; P = .0289, log-rank test; and concordance index, 0.80). Conclusion PET imaging characteristics associated with distant metastasis that could potentially help practitioners to tailor appropriate therapy for individual patients with early-stage NSCLC were identified. (©) RSNA, 2016 Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.2016151829

  View details for PubMedID 27046074

• Experimental Platform for Ultra-high Dose Rate FLASH Irradiation of Small Animals Using a Clinical Linear Accelerator. International journal of radiation oncology, biology, physics Schüler, E., Trovati, S., King, G., Lartey, F., Rafat, M., Villegas, M., Praxel, A. J., Loo, B. W., Maxim, P. G. 2016

  Abstract

  A key factor limiting the effectiveness of radiation therapy is normal tissue toxicity, and recent preclinical data have shown that ultra-high dose rate irradiation (>50 Gy/s, "FLASH") potentially mitigates this effect. However, research in this field has been strongly limited by the availability of FLASH irradiators suitable for small animal experiments. We present a simple methodologic approach for FLASH electron small animal irradiation with a clinically available linear accelerator (LINAC).We investigated the FLASH irradiation potential of a Varian Clinac 21EX in both clinical mode and after tuning of the LINAC. We performed detailed FLUKA Monte Carlo and experimental dosimetric characterization at multiple experimental locations within the LINAC head.Average dose rates of ≤74 Gy/s were achieved in clinical mode, and the dose rate after tuning exceeded 900 Gy/s. We obtained 220 Gy/s at 1-cm depth for a >4-cm field size with 90% homogeneity throughout a 2-cm-thick volume.We present an approach for using a clinical LINAC for FLASH irradiation. We obtained dose rates exceeding 200 Gy/s after simple tuning of the LINAC, with excellent dosimetric properties for small animal experiments. This will allow for increased availability of FLASH irradiation to the general research community.

  View details for DOI 10.1016/j.ijrobp.2016.09.018

  View details for PubMedID 27816362

• The impact of audiovisual biofeedback on 4D functional and anatomic imaging: Results of a lung cancer pilot study. Radiotherapy and oncology Yang, J., Yamamoto, T., Pollock, S., Berger, J., Diehn, M., Graves, E. E., Loo, B. W., Keall, P. J. 2016; 120 (2): 267-272

  Abstract

  The impact of audiovisual (AV) biofeedback on four dimensional (4D) positron emission tomography (PET) and 4D computed tomography (CT) image quality was investigated in a prospective clinical trial (NCT01172041).4D-PET and 4D-CT images of ten lung cancer patients were acquired with AV biofeedback (AV) and free breathing (FB). The 4D-PET images were analyzed for motion artifacts by comparing 4D to 3D PET for gross tumor volumes (GTVPET) and maximum standardized uptake values (SUVmax). The 4D-CT images were analyzed for artifacts by comparing normalized cross correlation-based scores (NCCS) and quantifying a visual assessment score (VAS). A Wilcoxon signed-ranks test was used for statistical testing.The impact of AV biofeedback varied widely. Overall, the 3D to 4D decrease of GTVPET was 1.2±1.3cm(3) with AV and 0.6±1.8cm(3) for FB. The 4D-PET increase of SUVmax was 1.3±0.9 with AV and 1.3±0.8 for FB. The 4D-CT NCCS were 0.65±0.27 with AV and 0.60±0.32 for FB (p=0.08). The 4D-CT VAS was 0.0±2.7.This study demonstrated a high patient dependence on the use of AV biofeedback to reduce motion artifacts in 4D imaging. None of the hypotheses tested were statistically significant. Future development of AV biofeedback will focus on optimizing the human-computer interface and including patient training sessions for improved comprehension and compliance.

  View details for DOI 10.1016/j.radonc.2016.05.016

  View details for PubMedID 27256597

• Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study. International journal of radiation oncology, biology, physics Wu, J., Gensheimer, M. F., Dong, X., Rubin, D. L., Napel, S., Diehn, M., Loo, B. W., Li, R. 2016; 95 (5): 1504-1512

  Abstract

  To develop an intratumor partitioning framework for identifying high-risk subregions from (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer.In this institutional review board-approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP).Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05).We propose a robust intratumor partitioning method to identify clinically relevant, high-risk subregions in lung cancer. We envision that this approach will be applicable to identifying useful imaging biomarkers in many cancer types.

  View details for DOI 10.1016/j.ijrobp.2016.03.018

  View details for PubMedID 27212196

• NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016. Journal of the National Comprehensive Cancer Network Ettinger, D. S., Wood, D. E., Akerley, W., Bazhenova, L. A., Borghaei, H., Camidge, D. R., Cheney, R. T., Chirieac, L. R., D'Amico, T. A., Dilling, T., Dobelbower, M., Govindan, R., Hennon, M., Horn, L., Jahan, T. M., Komaki, R., Lackner, R. P., Lanuti, M., Lilenbaum, R., Lin, J., Loo, B. W., Martins, R., Otterson, G. A., Patel, J. D., Pisters, K. M., Reckamp, K., Riely, G. J., Schild, S. E., Shapiro, T. A., Sharma, N., Swanson, S. J., Stevenson, J., Tauer, K., Yang, S. C., Gregory, K., Hughes, M. 2016; 14 (7): 825-836

  Abstract

  These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category 1) for patients with MPM. The NCCN panel also now recommends bevacizumab/cisplatin/pemetrexed as a first-line therapy option for patients with unresectable MPM who are candidates for bevacizumab. The complete version of the NCCN Guidelines for MPM, available at NCCN.org, addresses all aspects of management for MPM including diagnosis, evaluation, staging, treatment, surveillance, and therapy for recurrence and metastasis; NCCN Guidelines are intended to assist with clinical decision-making.

  View details for PubMedID 27407123

• Pre-treatment non-target lung FDG-PET uptake predicts symptomatic radiation pneumonitis following Stereotactic Ablative Radiotherapy (SABR). Radiotherapy and oncology Chaudhuri, A. A., Binkley, M. S., Rigdon, J., Carter, J. N., Aggarwal, S., Dudley, S. A., Qian, Y., Kumar, K. A., Hara, W. Y., Gensheimer, M., Nair, V. S., Maxim, P. G., Shultz, D. B., Bush, K., Trakul, N., Le, Q., Diehn, M., Loo, B. W., Guo, H. H. 2016; 119 (3): 454-460

  Abstract

  To determine if pre-treatment non-target lung FDG-PET uptake predicts for symptomatic radiation pneumonitis (RP) following lung stereotactic ablative radiotherapy (SABR).We reviewed a 258 patient database from our institution to identify 28 patients who experienced symptomatic (grade ⩾ 2) RP after SABR, and compared them to 57 controls who did not develop symptomatic RP. We compared clinical, dosimetric and functional imaging characteristics between the 2 cohorts including pre-treatment non-target lung FDG-PET uptake.Median follow-up time was 26.9 months. Patients who experienced symptomatic RP had significantly higher non-target lung FDG-PET uptake as measured by mean SUV (p < 0.0001) than controls. ROC analysis for symptomatic RP revealed area under the curve (AUC) of 0.74, with sensitivity 82.1% and specificity 57.9% with cutoff mean non-target lung SUV > 0.56. Predictive value increased (AUC of 0.82) when mean non-target lung SUV was combined with mean lung dose (MLD). We developed a 0-2 point model using these 2 variables, 1 point each for SUV > 0.56 or MLD > 5.88 Gy equivalent dose in 2 Gy per fraction (EQD2), predictive for symptomatic RP in our cohort with hazard ratio 10.01 for score 2 versus 0 (p < 0.001).Patients with elevated pre-SABR non-target lung FDG-PET uptake are at increased risk of symptomatic RP after lung SABR. Our predictive model suggests patients with mean non-target lung SUV > 0.56 and MLD > 5.88 Gy EQD2 are at highest risk. Our predictive model should be validated in an external cohort before clinical implementation.

  View details for DOI 10.1016/j.radonc.2016.05.007

  View details for PubMedID 27267049

• SU-D-207B-05: Robust Intra-Tumor Partitioning to Identify High-Risk Subregions for Prognosis in Lung Cancer. Medical physics Wu, J., Gensheimer, M., Dong, X., Rubin, D., Napel, S., Diehn, M., Loo, B., Li, R. 2016; 43 (6): 3349-?

  View details for DOI 10.1118/1.4955673

  View details for PubMedID 28046308

• Integrated digital error suppression for improved detection of circulating tumor DNA NATURE BIOTECHNOLOGY Newman, A. M., Lovejoy, A. F., Klass, D. M., Kurtz, D. M., Chabon, J. J., Scherer, F., Stehr, H., Liu, C. L., Bratman, S. V., Say, C., Zhou, L., Carter, J. N., West, R. B., Sledge, G. W., Shrager, J. B., Loo, B. W., Neal, J. W., Wakelee, H. A., Diehn, M., Alizadeh, A. A. 2016; 34 (5): 547-555

  Abstract

  High-throughput sequencing of circulating tumor DNA (ctDNA) promises to facilitate personalized cancer therapy. However, low quantities of cell-free DNA (cfDNA) in the blood and sequencing artifacts currently limit analytical sensitivity. To overcome these limitations, we introduce an approach for integrated digital error suppression (iDES). Our method combines in silico elimination of highly stereotypical background artifacts with a molecular barcoding strategy for the efficient recovery of cfDNA molecules. Individually, these two methods each improve the sensitivity of cancer personalized profiling by deep sequencing (CAPP-Seq) by about threefold, and synergize when combined to yield ∼15-fold improvements. As a result, iDES-enhanced CAPP-Seq facilitates noninvasive variant detection across hundreds of kilobases. Applied to non-small cell lung cancer (NSCLC) patients, our method enabled biopsy-free profiling of EGFR kinase domain mutations with 92% sensitivity and >99.99% specificity at the variant level, and with 90% sensitivity and 96% specificity at the patient level. In addition, our approach allowed monitoring of NSCLC ctDNA down to 4 in 10(5) cfDNA molecules. We anticipate that iDES will aid the noninvasive genotyping and detection of ctDNA in research and clinical settings.

  View details for DOI 10.1038/nbt.3520

  View details for Web of Science ID 000375735000036

  View details for PubMedID 27018799

  View details for PubMedCentralID PMC4907374

• Assessment of the quality of very high-energy electron radiotherapy planning RADIOTHERAPY AND ONCOLOGY Palma, B., Bazalova-Carter, M., Hardemark, B., Hynning, E., Qu, B., Loo, B. W., Maxim, P. G. 2016; 119 (1): 154-158

  Abstract

  To assess the quality of very-high energy electron (VHEE) scanning pencil beam radiation therapy in relation to state-of-the-art volumetric modulated arc therapy (VMAT) and to determine the extent of its application.We planned five clinical cases with VHEE scanning pencil beams of 100 and 120MeV, equally distributed in a coplanar arrangement around the patient. The clinical cases included acoustic neuroma, and liver, lung, esophagus, and anal cancer cases. We performed Monte Carlo (MC) dose calculations and we optimized the dose in a research version of RayStation. VHEE plan performance was compared against clinically delivered VMAT.With equal target coverage, mean doses to organs at risk (OARs) were on average 22% lower for the VHEE plans compared to the VMAT plans. Dose conformity was equal or superior compared to the VMAT plans and integral dose to the body was in average 14% (9-22%) lower for the VHEE plans.The dosimetric advantages of VHEE as demonstrated for a variety of clinical cases, combined with the theoretical ultra fast treatment delivery, afford VHEE scanning pencil beam radiotherapy a suitable and potentially superior alternative for cancer radiotherapy.

  View details for DOI 10.1016/j.radonc.2016.01.017

  View details for Web of Science ID 000375822700027

  View details for PubMedID 26898508

• Dosimetric Factors and Toxicity in Highly Conformal Thoracic Reirradiation. International journal of radiation oncology, biology, physics Binkley, M. S., Hiniker, S. M., Chaudhuri, A., Maxim, P. G., Diehn, M., Loo, B. W., Shultz, D. B. 2016; 94 (4): 808-815

  Abstract

  We determined cumulative dose to critical structures, rates of toxicity, and outcomes following thoracic reirradiation.We retrospectively reviewed our institutional database for patients treated between 2008 and 2014, who received thoracic reirradiation with overlap of 25% prescribed isodose lines. Patients received courses of hyperfractionated (n=5), hypofractionated (n=5), conventionally fractionated (n=21), or stereotactic ablative radiation therapy (n=51). Doses to critical structures were converted to biologically effective dose, expressed as 2 Gy per fraction equivalent dose (EQD2; α/β = 2 for spinal cord; α/β = 3 for other critical structures).We identified 82 courses (44 for retreatment) in 38 patients reirradiated at a median 16 months (range: 1-71 months) following initial RT. Median follow-up was 17 months (range: 3-57 months). Twelve- and 24-month overall survival rates were 79.6% and 57.3%, respectively. Eighteen patients received reirradiation for locoregionally recurrent non-small cell lung cancer with 12-month rates of local failure and regional recurrence and distant metastases rates of 13.5%, 8.1%, and 15.6%, respectively. Critical structures receiving ≥75 Gy EQD2 included spinal cord (1 cm(3); n=1), esophagus (1 cm(3); n=10), trachea (1 cm(3); n=11), heart (1 cm(3); n=9), aorta (1 cm(3); n=16), superior vena cava (1 cm(3); n=12), brachial plexus (0.2 cm(3); n=2), vagus nerve (0.2 cm(3); n=7), sympathetic trunk (0.2 cm(3); n=4), chest wall (30 cm(3); n=12), and proximal bronchial tree (1 cm(3); n=17). Cumulative dose-volume (D cm(3)) toxicity following reirradiation data included esophagitis grade ≥2 (n=3, D1 cm(3) range: 41.0-100.6 Gy), chest wall grade ≥2 (n=4; D30 cm(3) range: 35.0-117.2 Gy), lung grade 2 (n=7; V20combined-lung range: 4.7%-21.7%), vocal cord paralysis (n=2; vagus nerve D0.2 cm(3) range: 207.5-302.2 Gy), brachial plexopathy (n=1; D0.2 cm(3) = 242.5 Gy), and Horner's syndrome (n=1; sympathetic trunk D0.2 cm(3) = 130.8 Gy). No grade ≥4 toxicity was observed.Overlapping courses of reirradiation can be safely delivered with acceptable toxicity. Some toxicities occurred acutely at doses considered safe for a single course of therapy (esophagus). We observed rib fracture, brachial plexopathy, and Horner's syndrome for patients receiving high cumulative doses to corresponding critical structures.

  View details for DOI 10.1016/j.ijrobp.2015.12.007

  View details for PubMedID 26831903

• NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 4.2016. Journal of the National Comprehensive Cancer Network Ettinger, D. S., Wood, D. E., Akerley, W., Bazhenova, L. A., Borghaei, H., Camidge, D. R., Cheney, R. T., Chirieac, L. R., D'Amico, T. A., Dilling, T. J., Dobelbower, M. C., Govindan, R., Hennon, M., Horn, L., Jahan, T. M., Komaki, R., Lackner, R. P., Lanuti, M., Lilenbaum, R., Lin, J., Loo, B. W., Martins, R., Otterson, G. A., Patel, J. D., Pisters, K. M., Reckamp, K., Riely, G. J., Schild, S. E., Shapiro, T. A., Sharma, N., Stevenson, J., Swanson, S. J., Tauer, K., Yang, S. C., Gregory, K., Hughes, M. 2016; 14 (3): 255-264

  Abstract

  These NCCN Guidelines Insights focus on recent updates in the 2016 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC; Versions 1-4). These NCCN Guidelines Insights will discuss new immunotherapeutic agents, such as nivolumab and pembrolizumab, for patients with metastatic NSCLC. For the 2016 update, the NCCN panel recommends immune checkpoint inhibitors as preferred agents (in the absence of contraindications) for second-line and beyond (subsequent) therapy in patients with metastatic NSCLC (both squamous and nonsquamous histologies). Nivolumab and pembrolizumab are preferred based on improved overall survival rates, higher response rates, longer duration of response, and fewer adverse events when compared with docetaxel therapy.

  View details for PubMedID 26957612

• CT ventilation functional image-based IMRT treatment plans are comparable to SPECT ventilation functional image-based plans. Radiotherapy and oncology Kida, S., Bal, M., Kabus, S., Negahdar, M., Shan, X., Loo, B. W., Keall, P. J., Yamamoto, T. 2016; 118 (3): 521-527

  Abstract

  To investigate the hypothesis that CT ventilation functional image-based IMRT plans designed to avoid irradiating highly-functional lung regions are comparable to single-photon emission CT (SPECT) ventilation functional image-based plans.Three IMRT plans were created for eight thoracic cancer patients using: (1) CT ventilation functional images, (2) SPECT ventilation functional images, and (3) anatomic images (no functional images). CT ventilation images were created by deformable image registration of 4D-CT image data sets and quantitative analysis. The resulting plans were analyzed for the relationship between the deviations of CT-functional plan metrics from anatomic plan metrics (ΔCT-anatomic) and those of SPECT-functional plans (ΔSPECT-anatomic), and moreover for agreements of various metrics between the CT-functional and SPECT-functional plans.The relationship between ΔCT-anatomic and ΔSPECT-anatomic was strong (e.g., R=0.94; linear regression slope 0.71). The average differences and 95% limits of agreement between the CT-functional and SPECT-functional plan metrics (except for monitor units) for various structures were mostly less than 1% and 2%, respectively.This study demonstrated a reasonable agreement between the CT ventilation functional image-based IMRT plans and SPECT-functional plans, suggesting the potential for CT ventilation imaging to serve as a surrogate for SPECT ventilation in functional image-guided radiotherapy.

  View details for DOI 10.1016/j.radonc.2016.02.019

  View details for PubMedID 26922488

• Tracheal Diverticulum Following Paratracheal Hypofractionated Radiotherapy in the Setting of Prior and Subsequent Bevacizumab. Cure¯us Chaudhuri, A. A., Chen, J. J., Carter, J. N., Binkley, M. S., Kumar, K. A., Dudley, S. A., Sung, A. W., Loo, B. W. 2016; 8 (4)

  Abstract

  We present the case of a 63-year-old woman with limited metastatic colorectal cancer to the lungs and liver treated with FOLFIRI-bevacizumab, followed by consolidative hypofractionated radiotherapy to right paratracheal metastatic lymphadenopathy. We treated the right paratracheal site with 60 Gy in 15 fractions (70 Gy equivalent dose in 2 Gy fractions). The patient tolerated the treatment well, and six months later started a five-month course of FOLFIRI-bevacizumab for new metastatic disease. She presented to our clinic six months after completing this, complaining of productive cough with scant hemoptysis, and was found to have localized tracheal wall breakdown and diverticulum in the region of prior high-dose radiation therapy, threatening to progress to catastrophic tracheovascular fistula. This was successfully repaired surgically after a lack of response to conservative measures. We urge caution in treating patients with vascular endothelial growth factor (VEGF) inhibitors in the setting of hypofractionated radiotherapy involving the mucosa of tubular organs, even when these treatments are separated by months. Though data is limited as to the impact of sequence, this may be particularly an issue when VEGF inhibitors follow prior radiotherapy.

  View details for DOI 10.7759/cureus.578

  View details for PubMedID 27226939

  View details for PubMedCentralID PMC4873316

• Stereotactic Arrhythmia Radioablation (STAR) of Ventricular Tachycardia: A Treatment Planning Study. Cure¯us Wang, L., Fahimian, B., Soltys, S. G., Zei, P., Lo, A., Gardner, E. A., Maguire, P. J., Loo, B. W. 2016; 8 (7)

  Abstract

  The first stereotactic arrhythmia radioablation (STAR) of ventricular tachycardia (VT) was delivered at Stanford on a robotic radiosurgery system (CyberKnife® G4) in 2012. The results warranted further investigation of this treatment. Here we compare dosimetrically three possible treatment delivery platforms for STAR.The anatomy and target volume of the first treated patient were used for this study. A dose of 25 Gy in one fraction was prescribed to the planning target volume (PTV). Treatment plans were created on three treatment platforms: CyberKnife® G4 system with Iris collimator (Multiplan, V. 4.6)(Plan #1), CyberKnife® M6 system with InCise 2(TM) multileaf collimator (Multiplan V. 5.3)(Plan #2) and Varian TrueBeam(TM) STx with HD 120(TM) MLC and 10MV flattening filter free (FFF) beam (Eclipse planning system, V.11) (Plan #3 coplanar and #4 noncoplanar VMAT plans). The four plans were compared by prescription isodose line, plan conformity index, dose gradient, as well as dose to the nearby critical structures. To assess the delivery efficiency, planned monitor units (MU) and estimated treatment time were evaluated.Plans #1-4 delivered 25 Gy to the PTV to the 75.0%, 83.0%, 84.3%, and 84.9% isodose lines and with conformity indices of 1.19, 1.16, 1.05, and 1.05, respectively. The dose gradients for plans #1-4 were 3.62, 3.42, 3.93, and 3.73 with the CyberKnife® MLC plan (Plan #2) the best, and the TrueBeam(TM) STx co-planar plan (Plan #3) the worst. The dose to nearby critical structures (lung, stomach, bowel, and esophagus) were all well within tolerance. The MUs for plans #1-4 were 27671, 16522, 6275, and 6004 for an estimated total-treatment-time/beam-delivery-time of 99/69, 65/35, 37/7, and 56/6 minutes, respectively, under the assumption of 30 minutes pretreatment setup time. For VMAT gated delivery, a 40% duty cycle, 2400MU/minute dose rate, and an extra 10 minutes per extra arc were assumed.Clinically acceptable plans were created with all three platforms. Plans with MLC were considerably more efficient in MU. CyberKnife® M6 with InCise 2(TM) collimator provided the most conformal plan (steepest dose drop-off) with significantly reduced MU and treatment time. VMAT plans were most efficient in MU and delivery time. Fluoroscopic image guidance removes the need for additional fiducial marker placement; however, benefits may be moderated by worse dose gradient and more operator-dependent motion management by gated delivery.

  View details for DOI 10.7759/cureus.694

  View details for PubMedID 27570715

• Time course and predictive factors for lung volume reduction following stereotactic ablative radiotherapy (SABR) of lung tumors. Radiation oncology Binkley, M. S., Shrager, J. B., Chaudhuri, A., Popat, R., Maxim, P. G., Shultz, D. B., Diehn, M., Loo, B. W. 2016; 11 (1): 40-?

  Abstract

  Stereotactic ablative volume reduction (SAVR) is a potential alternative to lung-volume reduction surgery in patients with severe emphysema and excessive surgical risk. Having previously observed a dose-volume response for localized lobar volume reduction after stereotactic ablative radiotherapy (SABR) for lung tumors, we investigated the time course and factors associated with volume reduction.We retrospectively identified 70 eligible patients receiving lung tumor SABR during 2007-2013. We correlated lobar volume reduction (relative to total, bilateral lung volume [TLV]) with volume receiving high biologically effective doses (VXXBED3) and other pre-treatment factors in all patients, and measured the time course of volume changes on 3-month interval CT scans in patients with large V60BED3 (n = 21, V60BED3 ≥4.1 % TLV).Median CT follow-up was 15 months. Median volume reduction of treated lobes was 4.5 % of TLV (range 0.01-13.0 %), or ~9 % of ipsilateral lung volume (ILV); median expansion of non-target adjacent lobes was 2.2 % TLV (-4.6-9.9 %; ~4 % ILV). Treated lobe volume reduction was significantly greater with larger VXXBED3 (XX = 20-100 Gy, R (2)  = 0.52-0.55, p < 0.0001) and smaller with lower pre-treatment FEV1% (R (2)  = 0.11, p = 0.005) in a multivariable linear model. Maximum volume reduction was reached by ~12 months and persisted.We identified a multivariable model for lobar volume reduction after SABR incorporating dose-volume and pre-treatment FEV1% and characterized its time course.

  View details for DOI 10.1186/s13014-016-0616-8

  View details for PubMedID 26975700

  View details for PubMedCentralID PMC4791793

• Severe Chest Wall Toxicity From Cryoablation in the Setting of Prior Stereotactic Ablative Radiotherapy. Cure¯us Chaudhuri, A. A., Binkley, M. S., Aggarwal, S., Qian, Y., Carter, J. N., Shah, R., Loo, B. W. 2016; 8 (2)

  Abstract

  We present the case of a 42-year-old woman with metastatic synovial sarcoma of parotid origin, treated definitively with chemoradiation, who subsequently developed oligometastatic disease limited to the lungs. She underwent multiple left and right lung wedge resections and left lower lobectomy, followed by right lower lobe stereotactic ablative radiotherapy (SABR), 54 Gy in three fractions to a right lower lobe lesion abutting the chest wall. Two years later, she was treated with cryoablation for a separate right upper lobe nodule abutting the chest wall. Two months later, she presented with acute shortness of breath, pleuritic chest pain, decreased peripheral blood O2 saturation, and productive cough. A computed tomography (CT) scan demonstrated severe chest wall necrosis in the area of recent cryoablation that, in retrospect, also received a significant radiation dose from her prior SABR. This case demonstrates that clinicians should exercise caution in using cryoablation when treating lung tumors abutting a previously irradiated chest wall. Note: Drs. Loo and Shah contributed equally as co-senior authors.

  View details for DOI 10.7759/cureus.477

  View details for PubMedID 27004154

  View details for PubMedCentralID PMC4780688

• Outcomes of Modestly Hypofractionated Radiation for Lung Tumors: Pre- and Mid-Treatment Positron Emission Tomography-Computed Tomography Metrics as Prognostic Factors. Clinical lung cancer Harris, J. P., Chang-Halpenny, C. N., Maxim, P. G., Quon, A., Graves, E. E., Diehn, M., Loo, B. W. 2015; 16 (6): 475-485

  Abstract

  Modestly hypofractionated radiation therapy (HypoRT; 60-66 Gy in 3-Gy fractions) allows patients with locally advanced thoracic tumors and poor performance status to complete treatment within a shorter period without concurrent chemotherapy. We evaluated the outcomes and imaging prognostic factors of HypoRT.We retrospectively reviewed the data from all patients with primary and metastatic intrathoracic tumors treated with HypoRT from 2006 to 2012. We analyzed the survival and toxicity outcomes, including overall survival (OS), progression-free survival (PFS), local recurrence (LR), and distant metastasis. We also evaluated the following tumor metrics in an exploratory analysis: gross tumor volume (GTV), maximum standardized uptake value (SUVMax), and metabolic tumor volume using a threshold of ≥ 50% of the SUVMax (MTV50%) or the maximum gradient of fluorine-18 fluorodeoxyglucose uptake (MTVEdge). We assessed the association of these metrics and their changes from before to mid-RT using positron emission tomography-computed tomography (PET-CT) with OS and PFS.We identified 29 patients, all with pre-RT and 20 with mid-RT PET-CT scans. The median follow-up period was 15 months. The 2-year overall and non-small-cell lung cancer-only rate for OS, PFS, and LR, was 59% and 59%, 52% and 41%, and 27% and 32%, respectively. No grade ≥ 3 toxicities developed. The median decrease in GTV, SUVMax, and MTVEdge was 11%, 24%, and 18%, respectively. Inferior OS was associated with a larger pre-RT MTVEdge (P = .005) and pre-RT MTV50% (P = .007). Inferior PFS was associated with a larger mid-RT SUVMax (P = .003).These findings add to the growing body of data demonstrating promising outcomes and limited toxicity with HypoRT. The pre- and mid-RT PET-CT metrics could be useful for prognostic stratification in future clinical trials.

  View details for DOI 10.1016/j.cllc.2015.01.007

  View details for PubMedID 25770888

• Pruritus as a Paraneoplastic Symptom of Thymoma JOURNAL OF THORACIC ONCOLOGY Padda, S. K., Shrager, J. B., Riess, J. W., Pagtama, J. Y., Tisch, A. J., Kwong, B. Y., Liang, Y., Schwartz, E. J., Loo, B. W., Neal, J. W., Hardy, R., Wakelee, H. A. 2015; 10 (11): E110-E112

  View details for DOI 10.1097/JTO.0000000000000623

  View details for Web of Science ID 000363312300001

  View details for PubMedID 26536199

  View details for PubMedCentralID PMC4720251

• Optimization of an on-board imaging system for extremely rapid radiation therapy. Medical physics Cherry Kemmerling, E. M., Wu, M., Yang, H., Maxim, P. G., Loo, B. W., Fahrig, R. 2015; 42 (11): 6757-?

  Abstract

  Next-generation extremely rapid radiation therapy systems could mitigate the need for motion management, improve patient comfort during the treatment, and increase patient throughput for cost effectiveness. Such systems require an on-board imaging system that is competitively priced, fast, and of sufficiently high quality to allow good registration between the image taken on the day of treatment and the image taken the day of treatment planning. In this study, three different detectors for a custom on-board CT system were investigated to select the best design for integration with an extremely rapid radiation therapy system.Three different CT detectors are proposed: low-resolution (all 4×4 mm pixels), medium-resolution (a combination of 4×4 mm pixels and 2×2 mm pixels), and high-resolution (all 1×1 mm pixels). An in-house program was used to generate projection images of a numerical anthropomorphic phantom and to reconstruct the projections into CT datasets, henceforth called "realistic" images. Scatter was calculated using a separate Monte Carlo simulation, and the model included an antiscatter grid and bowtie filter. Diagnostic-quality images of the phantom were generated to represent the patient scan at the time of treatment planning. Commercial deformable registration software was used to register the diagnostic-quality scan to images produced by the various on-board detector configurations. The deformation fields were compared against a "gold standard" deformation field generated by registering initial and deformed images of the numerical phantoms that were used to make the diagnostic and treatment-day images. Registrations of on-board imaging system data were judged by the amount their deformation fields differed from the corresponding gold standard deformation fields--the smaller the difference, the better the system. To evaluate the registrations, the pointwise distance between gold standard and realistic registration deformation fields was computed.By most global metrics (e.g., mean, median, and maximum pointwise distance), the high-resolution detector had the best performance but the medium-resolution detector was comparable. For all medium- and high-resolution detector registrations, mean error between the realistic and gold standard deformation fields was less than 4 mm. By pointwise metrics (e.g., tracking a small lesion), the high- and medium-resolution detectors performed similarly. For these detectors, the smallest error between the realistic and gold standard registrations was 0.6 mm and the largest error was 3.6 mm.The medium-resolution CT detector was selected as the best for an extremely rapid radiation therapy system. In essentially all test cases, data from this detector produced a significantly better registration than data from the low-resolution detector and a comparable registration to data from the high-resolution detector. The medium-resolution detector provides an appropriate compromise between registration accuracy and system cost.

  View details for DOI 10.1118/1.4934377

  View details for PubMedID 26520765

• Anatomic optimization of lung tumor stereotactic ablative radiation therapy. Practical radiation oncology Yu, A. S., von Eyben, R., Yamamoto, T., Diehn, M., Shultz, D. B., Loo, B. W., Maxim, P. G. 2015; 5 (6): e607-13

  Abstract

  The purpose of this study was to demonstrate that anatomic optimization through selection of the degree of breath hold that yields the largest separation between the target and nearby organ at risk could result in dosimetrically superior treatment plans.Thirty patients with 41 plans were included in this planned secondary analysis of a prospective trial. Fifteen plans were created for treatment with use of natural end exhale (NEE), and 26 plans used deep inspiration breath hold (DIBH). To evaluate whether the original plan was dosimetrically optimal, we replanned treatment using the opposite respiratory state with the same beam configuration as the original plan. A treatment plan was deemed superior if it met protocol constraints when the other did not. If both plans met or violated the constraints, the plans were deemed equivalent.Of the 26 plans originally planned with DIBH and replanned with NEE, 3 plans were dosimetrically superior with NEE, 1 plan was dosimetrically superior with DIBH, and 22 plans were dosimetrically equivalent. Of the 15 plans originally planned with NEE, 4 plans were dosimetrically superior with NEE, 2 plans were dosimetrically superior with DIBH, and 9 plans were dosimetrically equivalent.For 10 of 41 plans, planning with 1 respiratory state was superior. To obtain uniformly optimal plans, individual anatomic optimization would be needed.

  View details for DOI 10.1016/j.prro.2015.05.008

  View details for PubMedID 26231596

• Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial. International journal of radiation oncology, biology, physics Westover, K. D., Loo, B. W., Gerber, D. E., Iyengar, P., Choy, H., Diehn, M., Hughes, R., Schiller, J., Dowell, J., Wardak, Z., Sher, D., Christie, A., Xie, X., Corona, I., Sharma, A., Wadsworth, M. E., Timmerman, R. 2015; 93 (1): 72-81

  Abstract

  Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC.Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy.Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P=.24). The median overall survival was 6 months with no significant differences between dose levels (P=.59).Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long-term safety and efficacy of this therapy are warranted.

  View details for DOI 10.1016/j.ijrobp.2015.05.004

  View details for PubMedID 26279026

• Colorectal Histology Is Associated With an Increased Risk of Local Failure in Lung Metastases Treated With Stereotactic Ablative Radiation Therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Binkley, M. S., Trakul, N., Jacobs, L. R., von Eyben, R., Quynh-Thu Le, Q. T., Maxim, P. G., Loo, B. W., Shultz, D. B., Diehn, M. 2015; 92 (5): 1044-1052

  Abstract

  Stereotactic ablative radiation therapy (SABR) is increasingly used to treat lung oligometastases. We set out to determine the safety and efficacy of this approach and to identify factors associated with outcomes.We conducted a retrospective study of patients treated with SABR for metastatic lung tumors at our institution from 2003 to 2014. We assessed the association between various patient and treatment factors with local failure (LF), progression, subsequent treatment, systemic treatment, and overall survival (OS), using univariate and multivariate analyses.We identified 122 tumors in 77 patients meeting inclusion criteria for this study. Median follow-up was 22 months. The 12- and 24-month cumulative incidence rates of LF were 8.7% and 16.2%, respectively; the 24-month cumulative incidence rates of progression, subsequent treatment, and subsequent systemic treatment were 75.2%, 64.5%, and 35.1%, respectively. Twenty-four-month OS was 74.6%, and median OS was 36 months. Colorectal metastases had a significantly higher cumulative incidence of LF at 12 and 24 months (25.5% and 42.2%, respectively), than all other histologies (4.4% and 9.9%, respectively; P<.0004). The 24-month cumulative incidences of LF for colorectal metastases treated with a biologically effective dose at α/β = 10 (BED10) of <100 Gy versus BED10 of ≥100 Gy were 62.5% and 16.7%, respectively (P=.08). Toxicity was minimal, with only a single grade 3 or higher event observed.SABR for metastatic lung tumors appears to be safe and effective with excellent local control, treatment-free intervals, and OS. An exception is metastases from colorectal cancer, which have a high LF rate consistent with a radioresistant phenotype, suggesting a potential role for dose escalation.

  View details for DOI 10.1016/j.ijrobp.2015.04.004

  View details for Web of Science ID 000357900600024

  View details for PubMedID 26025776

• 3D Riesz-wavelet based Covariance descriptors for texture classification of lung nodule tissue in CT. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference Cirujeda, P., Muller, H., Rubin, D., Aguilera, T. A., Loo, B. W., Diehn, M., Binefa, X., Depeursinge, A. 2015; 2015: 7909-7912

  Abstract

  In this paper we present a novel technique for characterizing and classifying 3D textured volumes belonging to different lung tissue types in 3D CT images. We build a volume-based 3D descriptor, robust to changes of size, rigid spatial transformations and texture variability, thanks to the integration of Riesz-wavelet features within a Covariance-based descriptor formulation. 3D Riesz features characterize the morphology of tissue density due to their response to changes in intensity in CT images. These features are encoded in a Covariance-based descriptor formulation: this provides a compact and flexible representation thanks to the use of feature variations rather than dense features themselves and adds robustness to spatial changes. Furthermore, the particular symmetric definite positive matrix form of these descriptors causes them to lay in a Riemannian manifold. Thus, descriptors can be compared with analytical measures, and accurate techniques from machine learning and clustering can be adapted to their spatial domain. Additionally we present a classification model following a "Bag of Covariance Descriptors" paradigm in order to distinguish three different nodule tissue types in CT: solid, ground-glass opacity, and healthy lung. The method is evaluated on top of an acquired dataset of 95 patients with manually delineated ground truth by radiation oncology specialists in 3D, and quantitative sensitivity and specificity values are presented.

  View details for DOI 10.1109/EMBC.2015.7320226

  View details for PubMedID 26738126

• Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy. International journal of radiation oncology, biology, physics Pollom, E. L., Deng, L., Pai, R. K., Brown, J. M., Giaccia, A., Loo, B. W., Shultz, D. B., Le, Q. T., Koong, A. C., Chang, D. T. 2015; 92 (3): 568-576

  Abstract

  Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become established for the treatment of a variety of malignancies, and it has been increasingly used in combination with biologic agents, including those targeting angiogenesis-specific pathways. Multiple reports have emerged describing unanticipated toxicities arising from the combination of SBRT and angiogenesis-targeting agents, particularly of late luminal gastrointestinal toxicities. In this review, we summarize the literature describing these toxicities, explore the biological mechanism of action of toxicity with the combined use of antiangiogenic therapies, and discuss areas of future research, so that this combination of treatment modalities can continue to be used in broader clinical contexts.

  View details for DOI 10.1016/j.ijrobp.2015.02.016

  View details for PubMedID 26068491

• Analysis of Long-Term 4-Dimensional Computed Tomography Regional Ventilation After Radiation Therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS King, M. T., Maxim, P. G., Diehn, M., Loo, B. W., Xing, L. 2015; 92 (3): 683-690

  Abstract

  To determine whether regional ventilation, as measured using 4-dimensional computed tomography (4D-CT), declines after radiation therapy (RT).We analyzed pretreatment 4D-CT scans associated with 2 RT courses. We quantified regional pulmonary function over equivalent dose in 2 Gy (EQD2α/β=3) intervals of 0 to 5 Gy, 5 to 20 Gy, 20 to 40 Gy, and >40 Gy using percentile-normalized intensity-based (VentInt) and Jacobian-based (VentJac) ventilation metrics. We modeled the impact of dose on mean ventilation (Vent¯) and regional tidal volume (rTV: tidal volume [TV] within a dose interval normalized to total lung TV). We also identified clinical and dosimetric factors that affected regional ventilation changes (ΔVent¯ and ΔrTV) after RT for the >20 Gy dose interval.After RT, Vent¯Int exhibited statistically significant dose-dependent declines within the 20 to 40 Gy (-5.0%; P=.03) and >40 Gy (-6.8%; P<.01) intervals. Vent¯Jac exhibited a declining trend after RT only for the >40 Gy interval (-4.6%; P=.07). Factors associated with ΔVent¯Int for the >20 Gy dose interval included airway stenosis progression (P=.03) and gross tumor volume (P=.09). Both rTVInt and rTVJac were associated with small (<2%) but significant declines after RT for 20 to 40 Gy and >40 Gy intervals. Factors associated with declining rTVInt (P<.05) for the >20 Gy dose interval included airway stenosis progression, greater V20 (volume of lung receiving >20 Gy), and smaller fraction of emphysema in V20. The association between the absence of chronic obstructive pulmonary disease and declining rTV trended toward significance (P=.09).Regional ventilation, as measured using 4D-CT, demonstrates a dose-dependent decline after RT. Our results support the use of 4D-CT ventilation imaging for monitoring regional pulmonary function change after RT.

  View details for DOI 10.1016/j.ijrobp.2015.02.037

  View details for Web of Science ID 000355636800032

  View details for PubMedID 25936813

• Stereotactic ablative radiotherapy (SABR) for treatment of central and ultra-central lung tumors LUNG CANCER Chaudhuri, A. A., Tang, C., Binkley, M. S., Jin, M., Wynne, J. F., von Eyben, R., Hara, W. Y., Trakul, N., Loo, B. W., Diehn, M. 2015; 89 (1): 50-56

  Abstract

  Treatment of central and ultra-central lung tumors with stereotactic ablative radiotherapy (SABR) remains controversial due to risks of treatment-related toxicities compared with peripheral tumors. Here we report our institution's experience in treating central and ultra-central lung tumor patients with SABR.We retrospectively reviewed outcomes in 68 patients with single lung tumors, 34 central and 34 peripheral, all treated with SABR consisting of 50 Gy in 4-5 fractions. Tumor centrality was defined per the RTOG 0813 protocol. We defined "ultra-central" tumors as those with GTV directly abutting the central airway.Median follow-up time was 18.4 months and median overall survival was 38.1 months. Two-year overall survival was similar between ultra-central, central, and peripheral NSCLC (80.0% vs. 63.2% vs. 86.6%, P=0.62), as was 2-year local failure (0% vs. 10.0% vs. 16.3%, P=0.64). Toxicity rates were low and comparable between the three groups, with only two cases of grade 3 toxicity (chest wall pain), and one case of grade 4 toxicity (pneumonitis) observed. Patients with ultra-central tumors experienced no symptomatic toxicities over a median follow-up time of 23.6 months. Dosimetric analysis revealed that RTOG 0813 central airway dose constraints were frequently not achieved in central tumor treatment plans, but this did not correlate with increased toxicity rate.Patients with central and ultra-central lung tumors treated with SABR (50 Gy in 4-5 fractions) experienced few toxicities and good outcomes, similar to patients with peripheral lung tumors.

  View details for DOI 10.1016/j.lungcan.2015.04.014

  View details for Web of Science ID 000356546300010

  View details for PubMedID 25997421

• Stereotactic ablative radiotherapy for the treatment of refractory cardiac ventricular arrhythmia. Circulation. Arrhythmia and electrophysiology Loo, B. W., Soltys, S. G., Wang, L., Lo, A., Fahimian, B. P., Iagaru, A., Norton, L., Shan, X., Gardner, E., Fogarty, T., Maguire, P., Al-Ahmad, A., Zei, P. 2015; 8 (3): 748-750

  View details for DOI 10.1161/CIRCEP.115.002765

  View details for PubMedID 26082532

• TU-G-BRA-04: Changes in Regional Lung Function Measured by 4D-CT Ventilation Imaging for Thoracic Radiotherapy. Medical physics Nakajima, Y., KADOYA, N., Kabus, S., Loo, B., Keall, P., Yamamoto, T. 2015; 42 (6): 3630-?

  Abstract

  To test the hypothesis: 4D-CT ventilation imaging can show the known effects of radiotherapy on lung function: (1) radiation-induced ventilation reductions, and (2) ventilation increases caused by tumor regression.Repeat 4D-CT scans (pre-, mid- and/or post-treatment) were acquired prospectively for 11 thoracic cancer patients in an IRB-approved clinical trial. A ventilation image for each time point was created using deformable image registration and the Hounsfield unit (HU)-based or Jacobian-based metric. The 11 patients were divided into two subgroups based on tumor volume reduction using a threshold of 5 cm(3). To quantify radiation-induced ventilation reduction, six patients who showed a small tumor volume reduction (<5 cm(3)) were analyzed for dose-response relationships. To investigate ventilation increase caused by tumor regression, two of the other five patients were analyzed to compare ventilation changes in the lung lobes affected and unaffected by the tumor. The remaining three patients were excluded because there were no unaffected lobes.Dose-dependent reductions of HU-based ventilation were observed in a majority of the patient-specific dose-response curves and in the population-based dose-response curve, whereas no clear relationship was seen for Jacobian-based ventilation. The post-treatment population-based dose-response curve of HU-based ventilation demonstrated the average ventilation reductions of 20.9±7.0% at 35-40 Gy (equivalent dose in 2-Gy fractions, EQD2), and 40.6±22.9% at 75-80 Gy EQD2. Remarkable ventilation increases in the affected lobes were observed for the two patients who showed an average tumor volume reduction of 37.1 cm(3) and re-opening airways. The mid-treatment increase in HU-based ventilation of patient 3 was 100.4% in the affected lobes, which was considerably greater than 7.8% in the unaffected lobes.This study has demonstrated that 4D-CT ventilation imaging shows the known effects of radiotherapy on lung function: radiation-induced ventilation reduction and ventilation increase caused by tumor regression, providing validation for 4D-CT ventilation imaging. This study was supported in part by a National Lung Cancer Partnership Young Investigator Research grant.

  View details for DOI 10.1118/1.4925754

  View details for PubMedID 26129054

• MO-FG-303-06: Evaluation of the Performance of Very High-Energy Electron (VHEE) Beams in Radiotherapy: Five Clinical Cases. Medical physics Palma, B., Bazalova-Carter, M., Hardemark, B., Hynning, E., Qu, B., Loo, B., Maxim, P. 2015; 42 (6): 3568-?

  Abstract

  To evaluate the performance of 100-120 MeV very-high energy electron (VHEE) scanning pencil beams to radiotherapy by means of Monte Carlo (MC) simulations.We selected five clinical cases with target sizes of 1.2 cm(3) to 990.4 cm(3). We calculated VHEE treatment plans using the MC EGSnrc code implemented in a MATLAB-based graphical user interface developed by our group. We generated phase space data for beam energies: 100 and 120 MeV and pencil beam spot sizes of 1, 3, and 5 mm at FWHM. The number of equidistant beams considered in this work was 16 or 32. Dose was calculated and then imported into a research version of RayStation where treatment plan optimization was performed. We compared the VHEE plans with the clinically delivered volumetric modulated arc therapy (VMAT) plan to evaluate VHEE plans performance.VHEE plans provided the same PTV coverage and dose homogeneity than VMAT plans for all the cases. In average, the mean dose to organs at risk (OARs) was 24% lower for the VHEE plans. The structures that benefited the most from using VHEE were: large bowel for the esophagus case, chest wall for the liver case, brainstem for the acoustic case, carina for the lung case, and genitalia for the anal case, with 23.7-34.6% lower dose. VHEE dose distributions were more conformal than VMAT solution as confirmed by conformity indices CI100 and CI50. Integral dose to the body was in average 19.6% (9.2%-36.5%) lower for the VHEE plans.We have shown that VHEE plans resulted in similar or superior dose distributions compared to clinical VMAT plans for five different cases and a wide range of target volumes, including a case with a small target (1.2 cm(3)), which represents a challenge for VMAT planning and might require the use of more complex non-coplanar VMAT plans. B Palma: None. M Bazalova: None. B Hardemark: Employee, RaySearch Laboratories AB. E Hynning: Employee, RaySearch Laboratories AB. B Qu: None. B Loo Jr.: Research support, RaySearch, Varian. P Maxim: Research support, RaySearch, Varian.

  View details for DOI 10.1118/1.4925419

  View details for PubMedID 26128721

• TU-AB-201-06: Evaluation of Electromagnetically Guided High- Dose Rate Brachytherapy for Ablative Treatment of Lung Metastases. Medical physics Pinkham, D. W., Shultz, D., Loo, B. W., Sung, A., Diehn, M., Fahimian, B. P. 2015; 42 (6): 3595-?

  Abstract

  The advent of electromagnetic navigation bronchoscopy has enabled minimally invasive access to peripheral lung tumors previously inaccessible by optical bronchoscopes. As an adjunct to Stereotactic Ablative Radiosurgery (SABR), implantation of HDR catheters can provide focal treatments for multiple metastases and sites of retreatments. The authors evaluate a procedure to deliver ablative doses via Electromagnetically-Guided HDR (EMG-HDR) to lung metastases, quantify the resulting dosimetry, and assess its role in the comprehensive treatment of lung cancer.A retrospective study was conducted on ten patients, who, from 2009 to 2011, received a hypo-fractionated SABR regimen with 6MV VMAT to lesions in various lobes ranging from 1.5 to 20 cc in volume. A CT visible pathway was delineated for EM guided placement of an HDR applicator (catheter) and dwell times were optimized to ensure at least 98% prescription dose coverage of the GTV. Normal tissue doses were calculated using inhomogeneity corrections via a grid-based Boltzmann solver (Acuros_BV_1.5.0).With EMG-HDR, an average of 83% (+/-9% standard deviation) of each patient's GTV received over 200% of the prescription dose, as compared to SABR where the patients received an average maximum dose of 125% (+/-5%). EMG-HDR enabled a 59% (+/-12%) decrease in the aorta maximum dose, a 63% (+/-26%) decrease in the spinal cord max dose, and 57% (+/-23%) and 70% (+/-17%) decreases in the volume of the body receiving over 50% and 25% of the prescription dose, respectively.EMG-HDR enables delivery of higher ablative doses to the GTV, while concurrently reducing surrounding normal tissue doses. The single catheter approach shown here is limited to targets smaller than 20 cc. As such, the technique enables ablation of small lesions and a potentially safe and effective retreatment option in situations where external beam utility is limited by normal tissue constraints.

  View details for DOI 10.1118/1.4925544

  View details for PubMedID 26128845

• SU-F-207-13: Comparison of Four Dimensional Computed Tomography (4D CT) Versus Breath Hold Images to Determine Pulmonary Nodule Elasticity. Medical physics Negahdar, M., Loo, B., Maxim, P. 2015; 42 (6): 3544-?

  Abstract

  Elasticity may distinguish malignant from benign pulmonary nodules. To compare determining of malignant pulmonary nodule (MPN) elasticity from four dimensional computed tomography (4D CT) images versus inhale/exhale breath-hold CT images.We analyzed phase 00 and 50 of 4D CT and deep inhale and natural exhale of breath-hold CT images of 30 MPN treated with stereotactic ablative radiotherapy (SABR). The radius of the smallest MPN was 0.3 cm while the biggest one was 2.1 cm. An intensity based deformable image registration (DIR) workflow was applied to the 4D CT and breath-hold images to determine the volumes of the MPNs and a 1 cm ring of surrounding lung tissue (ring) in each state. Next, an elasticity parameter was derived by calculating the ratio of the volume changes of MPN (exhale:inhale or phase50:phase00) to that of a 1 cm ring of lung tissue surrounding the MPN. The proposed formulation of elasticity enables us to compare volume changes of two different MPN in two different locations of lung.The calculated volume ratio of MPNs from 4D CT (phase50:phase00) and breath-hold images (exhale:inhale) was 1.00±0.23 and 0.95±0.11, respectively. It shows the stiffness of MPN and comparably bigger volume changes of MPN in breath-hold images because of the deeper degree of inhalation. The calculated elasticity of MPNs from 4D CT and breath-hold images was 1.12±0.22 and 1.23±0.26, respectively. For five patients who have had two MPN in their lung, calculated elasticity of tumor A and tumor B follows same trend in both 4D CT and breath-hold images.We showed that 4D CT and breath-hold images are comparable in the ability to calculate the elasticity of MPN. This study has been supported by Department of Defense LCRP 2011 #W81XWH-12-1-0286.

  View details for DOI 10.1118/1.4925257

  View details for PubMedID 26128555

• SU-E-T-514: Investigating the Dose Distributions of Equiangular Spaced Noncoplanar Beams. Medical physics Mitchell, T., Maxim, P., Hadsell, M., Loo, B. 2015; 42 (6): 3453-?

  Abstract

  It has been demonstrated that the use of noncoplanar beams in radiation therapy may Result in dose distributions that are comparable or better than standard coplanar beams [Pugachev, 2001]. A radiation therapy system designed with a noncoplanar beam geometry could allow for a full ring diagnostic quality imaging system to be placed around the patient. Additionally, if the noncoplanar beams were fixed in number and in their angle with respect to the patient's axial plane, then both treatment and imaging could be achieved concurrently without the need for moving parts, which could greatly reduce treatment times. For such a system to be designed, it is necessary to determine the appropriate number of beams and the beam angles to achieve optimal dose distributions. For simplicity, the beam angles are assumed to be equiangular in the patient's axial plane, and only the beam angle with respect to the axial plane are varied. This study aims to investigate the dose distributions produced by equiangular noncoplanar beams for multiple beam numbers and beam angles, and to compare these dose distributions with distributions achieved in coplanar volumetric arc therapy (VMAT).Dose distributions produced by noncoplanar beams were calculated using the Varian Eclipse treatment planning system by varying the gantry, collimator, and couch angles to simulate the noncoplanar delivery method. Noncoplanar intensity-modulated (NC-IMRT) beams using 8, 12, and 16 beams with angles varying from 45 degrees to 54 with respect to the patient's axial plane were studied.The NC-IMRT beams produced dose distributions comparable to VMAT plans for a number of treatment sites, and were capable of meeting similar dose-volume histogram constraints.This study has demonstrated that a noncoplanar beam delivery method with fixed beam numbers and beam angles is capable of delivering dose distributions comparable to VMAT plans currently in use.

  View details for DOI 10.1118/1.4924876

  View details for PubMedID 26128177

• TU-AB-BRA-10: Prognostic Value of Intra-Radiation Treatment FDG-PET and CT Imaging Features in Locally Advanced Head and Neck Cancer. Medical physics Song, J., Cui, Y., Pollom, E., Durkee, B., Aggarwal, S., Bui, T., Le, Q., Loo, B., Hara, W., Li, R. 2015; 42 (6): 3588-?

  Abstract

  To predict response to radiation treatment using computational FDG-PET and CT images in locally advanced head and neck cancer (HNC).68 patients with State III-IVB HNC treated with chemoradiation were included in this retrospective study. For each patient, we analyzed primary tumor and lymph nodes on PET and CT scans acquired both prior to and during radiation treatment, which led to 8 combinations of image datasets. From each image set, we extracted high-throughput, radiomic features of the following types: statistical, morphological, textural, histogram, and wavelet, resulting in a total of 437 features. We then performed unsupervised redundancy removal and stability test on these features. To avoid over-fitting, we trained a logistic regression model with simultaneous feature selection based on least absolute shrinkage and selection operator (LASSO). To objectively evaluate the prediction ability, we performed 5-fold cross validation (CV) with 50 random repeats of stratified bootstrapping. Feature selection and model training was solely conducted on the training set and independently validated on the holdout test set. Receiver operating characteristic (ROC) curve of the pooled Result and the area under the ROC curve (AUC) was calculated as figure of merit.For predicting local-regional recurrence, our model built on pre-treatment PET of lymph nodes achieved the best performance (AUC=0.762) on 5-fold CV, which compared favorably with node volume and SUVmax (AUC=0.704 and 0.449, p<0.001). Wavelet coefficients turned out to be the most predictive features. Prediction of distant recurrence showed a similar trend, in which pre-treatment PET features of lymph nodes had the highest AUC of 0.705.The radiomics approach identified novel imaging features that are predictive to radiation treatment response. If prospectively validated in larger cohorts, they could aid in risk-adaptive treatment of HNC.

  View details for DOI 10.1118/1.4925515

  View details for PubMedID 26128812

• TU-CD-304-01: FEATURED PRESENTATION and BEST IN PHYSICS (THERAPY): Trajectory Modulated Arc Therapy: Development of Novel Arc Delivery Techniques Integrating Dynamic Table Motion for Extended Volume Treatments. Medical physics Chin, E., Otto, K., Hoppe, R., Million, L., Loo, B., Koong, A., Xing, L., Hsu, A., Fahimian, B. 2015; 42 (6): 3598-?

  Abstract

  Integration of coordinated robotic table motion with inversely-planned arc delivery has the potential to resolve table-top delivery limitations of large-field treatments such as Total Body Irradiation (TBI), Total Lymphoid Irradiation (TLI), and Cranial-Spinal Irradiation (CSI). We formulate the foundation for Trajectory Modulated Arc Therapy (TMAT), and using Varian Developer Mode capabilities, experimentally investigate its practical implementation for such techniques.A MATLAB algorithm was developed for inverse planning optimization of the table motion, MLC positions, and gantry motion under extended-SSD geometry. To maximize the effective field size, delivery trajectories for TMAT TBI were formed with the table rotated at 270° IEC and dropped vertically to 152.5cm SSD. Preliminary testing of algorithm parameters was done through retrospective planning analysis. Robotic delivery was programmed using custom XML scripting on the TrueBeam Developer Mode platform. Final dose was calculated using the Eclipse AAA algorithm. Initial verification of delivery accuracy was measured using OSLDs on a solid water phantom of varying thickness.A comparison of DVH curves demonstrated that dynamic couch motion irradiation was sufficiently approximated by static control points spaced in intervals of less than 2cm. Optimized MLC motion decreased the average lung dose to 68.5% of the prescription dose. The programmed irradiation integrating coordinated table motion was deliverable on a TrueBeam STx linac in 6.7 min. With the couch translating under an open 10cmx20cm field angled at 10°, OSLD measurements along the midline of a solid water phantom at depths of 3, 5, and 9cm were within 3% of the TPS AAA algorithm with an average deviation of 1.2%.A treatment planning and delivery system for Trajectory Modulated Arc Therapy of extended volumes has been established and experimentally demonstrated for TBI. Extension to other treatment techniques such as TLI and CSI is readily achievable through the developed platform. Grant Funding by Varian Medical Systems.

  View details for DOI 10.1118/1.4925570

  View details for PubMedID 26128865

• Non-Small Cell Lung Cancer, Version 6.2015. Journal of the National Comprehensive Cancer Network Ettinger, D. S., Wood, D. E., Akerley, W., Bazhenova, L. A., Borghaei, H., Camidge, D. R., Cheney, R. T., Chirieac, L. R., D'Amico, T. A., Demmy, T. L., Dilling, T. J., Dobelbower, M. C., Govindan, R., Grannis, F. W., Horn, L., Jahan, T. M., Komaki, R., Krug, L. M., Lackner, R. P., Lanuti, M., Lilenbaum, R., Lin, J., Loo, B. W., Martins, R., Otterson, G. A., Patel, J. D., Pisters, K. M., Reckamp, K., Riely, G. J., Rohren, E., Schild, S. E., Shapiro, T. A., Swanson, S. J., Tauer, K., Yang, S. C., Gregory, K., Hughes, M. 2015; 13 (5): 515-524

  Abstract

  These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC). Appropriate targeted therapy is very effective in patients with advanced NSCLC who have specific genetic alterations. Therefore, it is important to test tumor tissue from patients with advanced NSCLC to determine whether they have genetic alterations that make them candidates for specific targeted therapies. These NCCN Guidelines Insights describe the different testing methods currently available for determining whether patients have genetic alterations in the 2 most commonly actionable genetic alterations, notably anaplastic lymphoma kinase (ALK) gene rearrangements and sensitizing epidermal growth factor receptor (EGFR) mutations.

  View details for PubMedID 25964637

• Non-Small Cell Lung Cancer, Version 6.2015 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Ettinger, D. S., Wood, D. E., Akerley, W., Bazhenova, L. A., Borghaei, H., Camidge, D. R., Cheney, R. T., Chirieac, L. R., D'Amico, T. A., Demmy, T. L., Dilling, T. J., Dobelbower, M. C., Govindan, R., Grannis, F. W., Horn, L., Jahan, T. M., Komaki, R., Krug, L. M., Lackner, R. P., Lanuti, M., Lilenbaum, R., Lin, J., Loo, B. W., Martins, R., Otterson, G. A., Patel, J. D., Pisters, K. M., Reckamp, K., Riely, G. J., Rohren, E., Schild, S. E., Shapiro, T. A., Swanson, S. J., Tauer, K., Yang, S. C., Gregory, K., Hughes, M. 2015; 13 (5): 515-524

  View details for Web of Science ID 000354283800004

• Treatment planning for radiotherapy with very high-energy electron beams and comparison of VHEE and VMAT plans MEDICAL PHYSICS Bazalova-Carter, M., Qu, B., Palma, B., Hardemark, B., Hynning, E., Jensen, C., Maxim, P. G., Loo, B. W. 2015; 42 (5): 2615-2625

  Abstract

  The aim of this work was to develop a treatment planning workflow for rapid radiotherapy delivered with very high-energy electron (VHEE) scanning pencil beams of 60-120 MeV and to study VHEE plans as a function of VHEE treatment parameters. Additionally, VHEE plans were compared to clinical state-of-the-art volumetric modulated arc therapy (VMAT) photon plans for three cases.VHEE radiotherapy treatment planning was performed by linking EGSnrc Monte Carlo (MC) dose calculations with inverse treatment planning in a research version of RayStation. In order to study the effect of VHEE treatment parameters on VHEE dose distributions, a matlab graphical user interface (GUI) for calculation of VHEE MC pencil beam doses was developed. Through the GUI, pediatric case MC simulations were run for a number of beam energies (60, 80, 100, and 120 MeV), number of beams (13, 17, and 36), pencil beam spot (0.1, 1.0, and 3.0 mm) and grid (2.0, 2.5, and 3.5 mm) sizes, and source-to-axis distance, SAD (40 and 50 cm). VHEE plans for the pediatric case calculated with the different treatment parameters were optimized and compared. Furthermore, 100 MeV VHEE plans for the pediatric case, a lung, and a prostate case were calculated and compared to the clinically delivered VMAT plans. All plans were normalized such that the 100% isodose line covered 95% of the target volume.VHEE beam energy had the largest effect on the quality of dose distributions of the pediatric case. For the same target dose, the mean doses to organs at risk (OARs) decreased by 5%-16% when planned with 100 MeV compared to 60 MeV, but there was no further improvement in the 120 MeV plan. VHEE plans calculated with 36 beams outperformed plans calculated with 13 and 17 beams, but to a more modest degree (<8%). While pencil beam spacing and SAD had a small effect on VHEE dose distributions, 0.1-3 mm pencil beam sizes resulted in identical dose distributions. For the 100 MeV VHEE pediatric plan, OAR doses were up to 70% lower and the integral dose was 33% lower for VHEE compared to 6 MV VMAT. Additionally, VHEE conformity indices (CI100 = 1.09 and CI50 = 4.07) were better than VMAT conformity indices (CI100 = 1.30 and CI50 = 6.81). The 100 MeV VHEE lung plan resulted in mean dose decrease to all OARs by up to 27% for the same target coverage compared to the clinical 6 MV flattening filter-free (FFF) VMAT plan. The 100 MeV prostate plan resulted in 3% mean dose increase to the penile bulb and the urethra, but all other OAR mean doses were lower compared to the 15 MV VMAT plan. The lung case CI100 and CI50 conformity indices were 3% and 8% lower, respectively, in the VHEE plan compared to the VMAT plan. The prostate case CI100 and CI50 conformity indices were 1% higher and 8% lower, respectively, in the VHEE plan compared to the VMAT plan.The authors have developed a treatment planning workflow for MC dose calculation of pencil beams and optimization for treatment planning of VHEE radiotherapy. The authors have demonstrated that VHEE plans resulted in similar or superior dose distributions for pediatric, lung, and prostate cases compared to clinical VMAT plans.

  View details for DOI 10.1118/1.4918923

  View details for Web of Science ID 000354776800050

  View details for PubMedID 25979053

• ACR Appropriateness Criteria (R) Induction and Adjuvant Therapy for N2 Non-small-cell Lung Cancer AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Willers, H., Stinchcombe, T. E., Barriger, R. B., Chetty, I. J., Ginsburg, M. E., Kestin, L. L., Kumar, S., Loo, B. W., Movsas, B., Rimner, A., Rosenzweig, K. E., Videtic, G. M., Chang, J. Y. 2015; 38 (2): 197-205

  Abstract

  The integration of chemotherapy, radiation therapy (RT), and surgery in the management of patients with stage IIIA (N2) non-small-cell lung carcinoma is challenging. The American College of Radiology (ACR) Appropriateness Criteria Lung Cancer Panel was charged to update management recommendations for this clinical scenario. The Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. There is limited level I evidence to guide patient selection for induction, postoperative RT (PORT), or definitive RT. Literature interpretation is complicated by inconsistent diagnostic procedures for N2 disease, disease heterogeneity, and pooled analysis with other stages. PORT is an appropriate therapy following adjuvant chemotherapy in patients with incidental pN2 disease. In patients with clinical N2 disease who are potential candidates for a lobectomy, both definitive and induction concurrent chemotherapy/RT are appropriate treatments. In N2 patients who require a pneumonectomy, definitive concurrent chemotherapy/RT is most appropriate although induction concurrent chemotherapy/RT may be considered in expert hands. Induction chemotherapy followed by surgery +/- PORT may also be an option in N2 patients. For preoperative RT and PORT, 3-dimensional conformal techniques and intensity-modulated RT are most appropriate.

  View details for DOI 10.1097/COC.0000000000000154

  View details for Web of Science ID 000351770500013

  View details for PubMedID 25803563

• To SABR or not to SABR? Indications and contraindications for stereotactic ablative radiotherapy in the treatment of early-stage, oligometastatic, or oligoprogressive non-small cell lung cancer. Seminars in radiation oncology Shultz, D. B., Diehn, M., Loo, B. W. 2015; 25 (2): 78-86

  Abstract

  Stereotactic ablative radiotherapy (SABR) is a highly effective treatment for early-stage non-small cell lung cancer. Although direct comparisons from randomized trials are not available, rates of both primary tumor control and distant metastasis are similar between SABR and surgery. Overall survival is lower after SABR compared with surgery, largely reflecting that a primary selection criterion for SABR has been medical inoperability because of decreased cardiopulmonary function and other comorbidities that lead to decreased survival independent of non-small cell lung cancer. Survival outcomes between SABR and surgery are much more similar in propensity-matched cohorts. Newer potential indications for SABR include treatment of operable patients; of oligometastatic lung cancer, in which SABR has emerged as an alternative to metastasectomy; and of oligoprogressive lung cancer, an attractive concept especially as improved personalized systemic therapies emerge, and prospective trials are currently being conducted in these settings. Although toxicity in modern series is low, SABR is clearly capable of producing fatal complications, and understanding the risk factors and approaches for mitigating them has been emerging in recent years. Thus, appropriate patient selection is a vital, evolving, and controversial topic.

  View details for DOI 10.1016/j.semradonc.2014.11.005

  View details for PubMedID 25771411

• Noninvasive pulmonary nodule elastometry by CT and deformable image registration. Radiotherapy and oncology Negahdar, M., Fasola, C. E., Yu, A. S., von Eyben, R., Yamamoto, T., Diehn, M., Fleischmann, D., Tian, L., Loo, B. W., Maxim, P. G. 2015; 115 (1): 35-40

  Abstract

  To develop a noninvasive method for determining malignant pulmonary nodule (MPN) elasticity, and compare it against expert dual-observer manual contouring.We analyzed breath-hold images at extreme tidal volumes of 23 patients with 30 MPN treated with stereotactic ablative radiotherapy. Deformable image registration (DIR) was applied to the breath-hold images to determine the volumes of the MPNs and a ring of surrounding lung tissue (ring) in each state. MPNs were also manually delineated on deep inhale and exhale images by two observers. Volumes were compared between observers and DIR by Dice similarity. Elasticity was defined as the absolute value of the volume ratio of the MPN minus one normalized to that of the ring.For all 30 tumors the Dice coefficient was 0.79±0.07 and 0.79±0.06 between DIR with observers 1 and 2, respectively, close to the inter-observer Dice value, 0.81±0.1. The elasticity of MPNs was 1.24±0.26, demonstrating that volume change of the MPN was less than that of the surrounding lung.We developed a noninvasive CT elastometry method based on DIR that measures the elasticity of biopsy-proven MPN. Our future direction would be to develop this method to distinguish malignant from benign nodules.

  View details for DOI 10.1016/j.radonc.2015.03.015

  View details for PubMedID 25824979

• Comparison of film measurements and Monte Carlo simulations of dose delivered with very high-energy electron beams in a polystyrene phantom MEDICAL PHYSICS Bazalova-Carter, M., Liu, M., Palma, B., Dunning, M., McCormick, D., Hemsing, E., Nelson, J., Jobe, K., Colby, E., Koong, A. C., Tantawi, S., Dolgashev, V., Maxim, P. G., Loo, B. W. 2015; 42 (4): 1606-1613

  Abstract

  To measure radiation dose in a water-equivalent medium from very high-energy electron (VHEE) beams and make comparisons to Monte Carlo (MC) simulation results.Dose in a polystyrene phantom delivered by an experimental VHEE beam line was measured with Gafchromic films for three 50 MeV and two 70 MeV Gaussian beams of 4.0-6.9 mm FWHM and compared to corresponding MC-simulated dose distributions. MC dose in the polystyrene phantom was calculated with the EGSnrc/BEAMnrc and DOSXYZnrc codes based on the experimental setup. Additionally, the effect of 2% beam energy measurement uncertainty and possible non-zero beam angular spread on MC dose distributions was evaluated.MC simulated percentage depth dose (PDD) curves agreed with measurements within 4% for all beam sizes at both 50 and 70 MeV VHEE beams. Central axis PDD at 8 cm depth ranged from 14% to 19% for the 5.4-6.9 mm 50 MeV beams and it ranged from 14% to 18% for the 4.0-4.5 mm 70 MeV beams. MC simulated relative beam profiles of regularly shaped Gaussian beams evaluated at depths of 0.64 to 7.46 cm agreed with measurements to within 5%. A 2% beam energy uncertainty and 0.286° beam angular spread corresponded to a maximum 3.0% and 3.8% difference in depth dose curves of the 50 and 70 MeV electron beams, respectively. Absolute dose differences between MC simulations and film measurements of regularly shaped Gaussian beams were between 10% and 42%.The authors demonstrate that relative dose distributions for VHEE beams of 50-70 MeV can be measured with Gafchromic films and modeled with Monte Carlo simulations to an accuracy of 5%. The reported absolute dose differences likely caused by imperfect beam steering and subsequent charge loss revealed the importance of accurate VHEE beam control and diagnostics.

  View details for DOI 10.1118/1.4914371

  View details for Web of Science ID 000352273200015

  View details for PubMedID 25832051

• The relationship between serial [(18)?F]PBR06 PET imaging of microglial activation and motor function following stroke in mice. Molecular imaging and biology Lartey, F. M., Ahn, G., Ali, R., Rosenblum, S., Miao, Z., Arksey, N., Shen, B., Colomer, M. V., Rafat, M., Liu, H., Alejandre-Alcazar, M. A., Chen, J. W., Palmer, T., Chin, F. T., Guzman, R., Loo, B. W., Graves, E. 2014; 16 (6): 821-829

  Abstract

  Using [(18) F]PBR06 positron emission tomography (PET) to characterize the time course of stroke-associated neuroinflammation (SAN) in mice, to evaluate whether brain microglia influences motor function after stroke, and to demonstrate the use of [(18) F]PBR06 PET as a therapeutic assessment tool.Stroke was induced by transient middle cerebral artery occlusion (MCAO) in Balb/c mice (control, stroke, and stroke with poststroke minocycline treatment). [18 F]PBR06 PET/CT imaging, rotarod tests, and immunohistochemistry (IHC) were performed 3, 11, and 22 days poststroke induction (PSI).The stroke group exhibited significantly increased microglial activation, and impaired motor function. Peak microglial activation was 11 days PSI. There was a strong association between microglial activation, motor function, and microglial protein expression on IHC. Minocycline significantly reduced microglial activation and improved motor function by day 22 PSI.[18 F]PBR06 PET imaging noninvasively characterizes the time course of SAN, and shows increased microglial activation is associated with decreased motor function.

  View details for DOI 10.1007/s11307-014-0745-0

  View details for PubMedID 24865401

• Non-Small Cell Lung Cancer, Version 1.2015 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Ettinger, D. S., Wood, D. E., Akerley, W., Bazhenova, L. A., Borghaei, H., Camidge, D. R., Cheney, R. T., Chirieac, L. R., D'Amico, T. A., Demmy, T. L., Dilling, T. J., Govindan, R., Grannis, F. W., Horn, L., Jahan, T. M., Komaki, R., Kris, M. G., Krug, L. M., Lackner, R. P., Lanuti, M., Lilenbaum, R., Lin, J., Loo, B. W., Martins, R., Otterson, G. A., Patel, J. D., Pisters, K. M., Reckamp, K., Riely, G. J., Rohren, E., Schild, S., Shapiro, T. A., Swanson, S. J., Tauer, K., Yang, S. C., Gregory, K., Hughes, M. 2014; 12 (12): 1738-1761

  Abstract

  This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) focuses on the principles of radiation therapy (RT), which include the following: (1) general principles for early-stage, locally advanced, and advanced/metastatic NSCLC; (2) target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced/palliative RT; and (3) RT simulation, planning, and delivery. Treatment recommendations should be made by a multidisciplinary team, including board-certified radiation oncologists who perform lung cancer RT as a prominent part of their practice.

  View details for Web of Science ID 000346190900012

  View details for PubMedID 25505215

• Galectin-1 mediates radiation-related lymphopenia and attenuates NSCLC radiation response. Clinical cancer research Kuo, P., Bratman, S. V., Shultz, D. B., von Eyben, R., Chan, C., Wang, Z., Say, C., Gupta, A., Loo, B. W., Giaccia, A. J., Koong, A. C., Diehn, M., Le, Q. 2014; 20 (21): 5558-5569

  Abstract

  Radiotherapy can result in lymphopenia, which has been linked to poorer survival. Here, we test the hypothesis that radiotherapy-induced lymphopenia is mediated by a tumor-secreted factor, Galectin-1 (Gal-1), which possesses T-cell proapoptotic activities.Matched Gal-1 wild-type (WT) or null mice were implanted with Lewis lung carcinoma (LLC-1) that either expressed Gal-1 or had Gal-1 stably downregulated. Tumors were irradiated locally and circulating Gal-1 and T cells were measured. Tumor growth, lung metastasis, intratumoral T-cell apoptosis, and microvessel density count were quantified. Thiodigalactoside (TDG), a Gal-1 inhibitor, was used to inhibit Gal-1 function in another group of mice to validate the observations noted with Gal-1 downregulation. Lymphocyte counts, survival, and plasma Gal-1 were analyzed in cohorts of radiotherapy-treated lung [non-small cell lung cancer (NSCLC)] and head and neck cancer patients.LLC irradiation increased Gal-1 secretion and decreased circulating T cells in mice, regardless of host Gal-1 expression. Inhibition of tumor Gal-1 with either shRNA or thiodigalactoside ablated radiotherapy-induced lymphopenia. Irradiated shGal-1 tumors showed significantly less intratumoral CD8(+) T-cell apoptosis and microvessel density, which led to marked tumor growth delay and reduced lung metastasis compared with controls. Similar observations were made after thiodigalactoside treatment. Radiotherapy-induced lymphopenia was associated with poorer overall survival in patients with NSCLC treated with hypofractionated radiotherapy. Plasma Gal-1 increased whereas T-cell decreased after radiation in another group of patients.Radiotherapy-related systemic lymphopenia appeared to be mediated by radiotherapy-induced tumor Gal-1 secretion that could lead to tumor progression through intratumoral immune suppression and enhanced angiogenesis. Clin Cancer Res; 20(21); 5558-69. ©2014 AACR.

  View details for DOI 10.1158/1078-0432.CCR-14-1138

  View details for PubMedID 25189484

• Pulmonary Ventilation Imaging Based on 4-Dimensional Computed Tomography: Comparison With Pulmonary Function Tests and SPECT Ventilation Images INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Yamamoto, T., Kabus, S., Lorenz, C., Mittra, E., Hong, J. C., Chung, M., Eclov, N., To, J., Diehn, M., Loo, B. W., Keall, P. J. 2014; 90 (2): 414-422

  Abstract

  4-dimensional computed tomography (4D-CT)-based pulmonary ventilation imaging is an emerging functional imaging modality. The purpose of this study was to investigate the physiological significance of 4D-CT ventilation imaging by comparison with pulmonary function test (PFT) measurements and single-photon emission CT (SPECT) ventilation images, which are the clinical references for global and regional lung function, respectively.In an institutional review board-approved prospective clinical trial, 4D-CT imaging and PFT and/or SPECT ventilation imaging were performed in thoracic cancer patients. Regional ventilation (V4DCT) was calculated by deformable image registration of 4D-CT images and quantitative analysis for regional volume change. V4DCT defect parameters were compared with the PFT measurements (forced expiratory volume in 1 second (FEV1; % predicted) and FEV1/forced vital capacity (FVC; %). V4DCT was also compared with SPECT ventilation (VSPECT) to (1) test whether V4DCT in VSPECT defect regions is significantly lower than in nondefect regions by using the 2-tailed t test; (2) to quantify the spatial overlap between V4DCT and VSPECT defect regions with Dice similarity coefficient (DSC); and (3) to test ventral-to-dorsal gradients by using the 2-tailed t test.Of 21 patients enrolled in the study, 18 patients for whom 4D-CT and either PFT or SPECT were acquired were included in the analysis. V4DCT defect parameters were found to have significant, moderate correlations with PFT measurements. For example, V4DCT(HU) defect volume increased significantly with decreasing FEV1/FVC (R=-0.65, P<.01). V4DCT in VSPECT defect regions was significantly lower than in nondefect regions (mean V4DCT(HU) 0.049 vs 0.076, P<.01). The average DSCs for the spatial overlap with SPECT ventilation defect regions were only moderate (V4DCT(HU)0.39 ± 0.11). Furthermore, ventral-to-dorsal gradients of V4DCT were strong (V4DCT(HU) R(2) = 0.69, P=.08), which was similar to VSPECT (R(2) = 0.96, P<.01).An 18-patient study demonstrated significant correlations between 4D-CT ventilation and PFT measurements as well as SPECT ventilation, providing evidence toward the validation of 4D-CT ventilation imaging.

  View details for DOI 10.1016/j.ijrobp.2014.06.006

  View details for Web of Science ID 000341994400026

• Stereotactic Ablative Radiotherapy for Pulmonary Oligometastases and Oligometastatic Lung Cancer JOURNAL OF THORACIC ONCOLOGY Shultz, D. B., Filippi, A. R., Thariat, J., Mornex, F., Loo, B. W., Ricardi, U. 2014; 9 (10): 1426-1433

  View details for DOI 10.1097/JTO.0000000000000317

  View details for Web of Science ID 000344368000006

• Stereotactic ablative radiotherapy for pulmonary oligometastases and oligometastatic lung cancer. Journal of thoracic oncology Shultz, D. B., Filippi, A. R., Thariat, J., Mornex, F., Loo, B. W., Ricardi, U. 2014; 9 (10): 1426-1433

  Abstract

  An increasing body of experience suggests that oligometastasis represents a minimal metastatic state with the potential for cure or prolonged survival in selected patients treated with radical local therapy to all identified sites of disease. The main clinical scenarios managed by thoracic oncology specialists are pulmonary oligometastases from primary malignancies of other anatomic sites and primary lung cancer with oligometastases to lung or other organs. Surgery has been a mainstay of treatment in these situations, with remarkably favorable outcomes following pulmonary metastasectomy in well-selected patient cohorts. As with early stage lung cancer in patients who are medically inoperable, stereotactic ablative radiotherapy is emerging as a prominent local treatment option for oligometastatic disease. We review the role and clinical experience of stereotactic ablative radiotherapy for pulmonary oligometastases and oligometastatic lung cancer.

  View details for DOI 10.1097/JTO.0000000000000317

  View details for PubMedID 25170641

• Lung Volume Reduction After Stereotactic Ablative Radiation Therapy of Lung Tumors: Potential Application to Emphysema INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Binkley, M. S., Shrager, J. B., Leung, A. N., Popat, R., Trakul, N., Atwood, T. F., Chaudhuri, A., Maxim, P. G., Diehn, M., Loo, B. W. 2014; 90 (1): 216-223

  View details for DOI 10.1016/j.ijrobp.2014.05.025

  View details for Web of Science ID 000341456500029

• ACR Appropriateness Criteria® nonsurgical treatment for locally advanced non-small-cell lung cancer: good performance status/definitive intent. Oncology (Williston Park, N.Y.) Chang, J. Y., Kestin, L. L., Barriger, R. B., Chetty, I. J., Ginsburg, M. E., Kumar, S., Loo, B. W., Movsas, B., Rimner, A., Rosenzweig, K. E., Stinchcombe, T. E., Videtic, G. M., Willers, H. 2014; 28 (8): 706-?

  Abstract

  Concurrent chemotherapy/radiotherapy has been considered the standard treatment for patients with a good performance status and inoperable stage III non-small-cell lung cancer (NSCLC). Three-dimensional chemoradiation therapy and intensity-modulated radiation therapy have been reported to reduce toxicity and allow a dose escalation to 70 Gy and beyond. However, the Radiation Therapy Oncology Group 0617 trial recently showed that dose escalation from 60 Gy to 74 Gy with concurrent chemotherapy in stage III NSCLC was associated with higher toxicity and worse survival. A "one size fits all" treatment approach may need to be changed and adapted to each patient's particular disease and unique biologic/anatomic features, as well as the most appropriate radiotherapy modalities for that patient. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application, by the panel, of a well-established consensus methodology (modified Delphi technique) to rate the appropriateness of imaging and treatment procedures. In instances in which evidence is lacking or not definitive, expert opinion may be used as the basis for recommending imaging or treatment.

  View details for PubMedID 25140629

• Circulating Tumor Microemboli Diagnostics for Patients with Non-Small-Cell Lung Cancer JOURNAL OF THORACIC ONCOLOGY Carlsson, A., Nair, V. S., Luttgen, M. S., Keu, K. V., Horng, G., Vasanawala, M., Kolatkar, A., Jamali, M., Iagaru, A. H., Kuschner, W., Loo, B. W., Shrager, J. B., Bethel, K., Hoh, C. K., Bazhenova, L., Nieva, J., Kuhn, P., Gambhir, S. S. 2014; 9 (8): 1111-1119

  Abstract

  Circulating tumor microemboli (CTM) are potentially important cancer biomarkers, but using them for cancer detection in early-stage disease has been assay limited. We examined CTM test performance using a sensitive detection platform to identify stage I non-small-cell lung cancer (NSCLC) patients undergoing imaging evaluation.First, we prospectively enrolled patients during 18F-FDG PET-CT imaging evaluation for lung cancer that underwent routine phlebotomy where CTM and circulating tumor cells (CTCs) were identified in blood using nuclear (DAPI), cytokeratin (CK), and CD45 immune-fluorescent antibodies followed by morphologic identification. Second, CTM and CTC data were integrated with patient (age, gender, smoking, and cancer history) and imaging (tumor diameter, location in lung, and maximum standard uptake value [SUVmax]) data to develop and test multiple logistic regression models using a case-control design in a training and test cohort followed by cross-validation in the entire group.We examined 104 patients with NSCLC, and the subgroup of 80 with stage I disease, and compared them to 25 patients with benign disease. Clinical and imaging data alone were moderately discriminating for all comers (Area under the Curve [AUC] = 0.77) and by stage I disease only (AUC = 0.77). However, the presence of CTM combined with clinical and imaging data was significantly discriminating for diagnostic accuracy in all NSCLC patients (AUC = 0.88, p value = 0.001) and for stage I patients alone (AUC = 0.87, p value = 0.002).CTM may add utility for lung cancer diagnosis during imaging evaluation using a sensitive detection platform.

  View details for Web of Science ID 000340138700012

  View details for PubMedID 25157764

• Feasibility and Potential Utility of Multicomponent Exhaled Breath Analysis for Predicting Development of Radiation Pneumonitis After Stereotactic Ablative Radiotherapy JOURNAL OF THORACIC ONCOLOGY More, J. M., Eclov, N. C., Chung, M. P., Wynne, J. F., Shorter, J. H., Nelson, D. D., Hanlon, A. L., Burmeister, R., Banos, P., Maxim, P. G., Loo, B. W., Diehn, M. 2014; 9 (7): 957-964

  Abstract

  In this prospective pilot study, we evaluated the feasibility and potential utility of measuring multiple exhaled gases as biomarkers of radiation pneumonitis (RP) in patients receiving stereotactic ablative radiotherapy (SABR) for lung tumors.Breath analysis was performed for 26 patients receiving SABR for lung tumors. Concentrations of exhaled nitric oxide (eNO), carbon monoxide (eCO), nitrous oxide (eN2O), and carbon dioxide (eCO2) were measured before and immediately after each fraction using real-time, infrared laser spectroscopy. RP development (CTCAE grade ≥2) was correlated with baseline gas concentrations, acute changes in gas concentrations after each SABR fraction, and dosimetric parameters.Exhaled breath analysis was successfully completed in 77% of patients. Five of 20 evaluable patients developed RP at a mean of 5.4 months after SABR. Acute changes in eNO and eCO concentrations, defined as percent changes between each pre-fraction and post-fraction measurement, were significantly smaller in RP versus non-RP cases (p = 0.022 and 0.015, respectively). In an exploratory analysis, a combined predictor of baseline eNO greater than 24 parts per billion and acute decrease in eCO less than 5.5% strongly correlated with RP incidence (p =0.0099). Neither eN2O nor eCO2 concentrations were significantly associated with RP development. Although generally higher in patients destined to develop RP, dosimetric parameters were not significantly associated with RP development.The majority of SABR patients in this pilot study were able to complete exhaled breath analysis. Baseline concentrations and acute changes in concentrations of exhaled breath components were associated with RP development after SABR. If our findings are validated, exhaled breath analysis may become a useful approach for noninvasive identification of patients at highest risk for developing RP after SABR.

  View details for DOI 10.1097/JTO.0000000000000182

  View details for Web of Science ID 000338025600015

• Vagal and recurrent laryngeal neuropathy following stereotactic ablative radiation therapy in the chest. Practical radiation oncology Shultz, D. B., Trakul, N., Maxim, P. G., Diehn, M., Loo, B. W. 2014; 4 (4): 272-278

  Abstract

  To identify clinical and dosimetric factors associated with vagus nerve (VN) and recurrent laryngeal nerve (RecLN) injury following stereotactic ablative radiation therapy (SABR) in the chest.We examined the clinical courses and SABR plans of 67 patients treated for T1 or T2 non-small cell lung cancer of the upper right or left lung, including 2 who developed vocal cord paresis (VCP) following treatment. After developing a contouring atlas for the VN and RecLN in the thorax, dose to those structures was retrospectively determined for each patient, and we identified 12 patients whose treatment imparted significant dose to either nerve and who were assessable for more than 12 months follow-up. Biologically effective doses using linear-quadratic (LQ) and linear quadratic-linear (LQ-L) modeling were correlated with VN and RecLN toxicity.Of 12 patients, 2 developed VCP. The first underwent repeat SABR and received a cumulative single fraction equivalent dose (alpha/beta = 3; SFED3) of 37.4 or 64.5 Gy to the VN and 13.7 or 15.3 Gy to the RecLN (by LQ or LQ-L modeling, respectively). This was the highest VN dose and fifth highest RecLN dose in the cohort. The second had rheumatoid arthritis and connective tissue disease and received a SFED3 of 16 Gy to the VN and 19.5 Gy to the RecLN (by both LQ and LQ-L modeling). This was in the upper tertile of VN and RecLN doses for the cohort.Following SABR for non-small cell lung cancer, VCP was associated with high cumulative dose to the VN in 1 patient and a moderately high dose to the VN and RecLN in another patient with rheumatoid arthritis and connective tissue disease. Particularly in the setting of reirradiation or connective tissue disease, potential toxicity to the VN or RecLN should be considered.

  View details for DOI 10.1016/j.prro.2013.08.005

  View details for PubMedID 25012837

• Imaging features associated with disease progression after stereotactic ablative radiotherapy for stage I non-small-cell lung cancer. Clinical lung cancer Shultz, D. B., Trakul, N., Abelson, J. A., Murphy, J. D., Maxim, P. G., Le, Q., Loo, B. W., Diehn, M. 2014; 15 (4): 294-301 e3

  Abstract

  The aim of this study was to identify imaging-based predictors of progression in patients treated with SABR for stage I NSCLC.Between March 2003 and December 2012, 117 patients with stage I NSCLC meeting our study criteria were treated with SABR at Stanford University. Median follow-up was 17 months (range, 3-74 months) for all patients and 19 months for living patients (range, 3-74 months). Tumors were classified according to whether or not they contacted the pleura adjacent to the chest wall or mediastinum (MP), according to their maximum dimension based on computed tomography scans, and, for 102 patients who had archived pretreatment fluorine-18 fluorodeoxyglucose positron-emission tomography scans, according to SUVmax.Ten patients (9%) developed local progression, 17 (15%) developed regional progression, and 19 (16%) developed distant metastasis. Two-year freedom from local progression, freedom from regional progression, and freedom from distant metastasis (FFDM) were 88%, 83%, and 83%, respectively. Overall survival was 70% at 2 years. FFDM was significantly associated with MP contact, maximum tumor dimension, and SUVmax, and these variables could be combined into an exploratory prognostic index that identified patients at highest risk for developing metastases.In our cohort, noninvasive, imaging-based features were associated with distant progression after SABR for early stage NSCLC. If validated, our prognostic index could allow identification of patients who might benefit from systemic therapy after SABR.

  View details for DOI 10.1016/j.cllc.2013.12.011

  View details for PubMedID 24594400

• The effect of arm position on the dosimetry of thoracic stereotactic ablative radiation therapy using volumetric modulated arc therapy. Practical radiation oncology Shultz, D. B., Jang, S. S., Hanlon, A. L., Diehn, M., Loo, B. W., Maxim, P. G. 2014; 4 (3): 192-197

  Abstract

  Patient comfort and positioning stability may be improved in the arms down (AD) compared with the typical arms up (AU) position in thoracic stereotactic ablative radiation therapy (SABR). We compared plan quality for AD vs AU when using volumetric modulated arc therapy (VMAT), and evaluated the sensitivity of AD plans to arm positioning variability.We took plans of 14 patients with 17 lung tumors treated with thoracic SABR using VMAT in the AD position and simulated the same treatments in the AU position by re-optimizing after digitally removing the ipsilateral arm. To evaluate the sensitivity of AD plans to arm positioning variability, all plans were recalculated without re-optimization after assigning water density to the ipsilateral arm (AD-W) and then digitally shifting the arm 2.5 cm anterolaterally (AD-WS).Between AD and AU plans, statistically significant but clinically insignificant (all original planning constraints met) differences were found for the following parameters: mean planning target volume maximum dose, difference of 2.3% of prescription dose (P = .049); mean intermediate dose conformity index, difference of 0.27 (P = .012); median percent lung volume receiving a minimum of 10, 20, and 30 Gy (V10, V20, and V30), differences of 0.5%, 0.2%, and 0.1%, respectively (P = .040, .007, and .001); and median spinal cord maximum dose, difference of 33.5 cGy (P = .017). Similarly, between AD-W and AD-WS plans, statistically significant but clinically insignificant differences were found for median lung V20 and V30, difference of 0.0% for both (P = .034 and .016, by matched pair analysis).Our exploratory planning study suggests that when using VMAT for lung tumor SABR, AD and AU positioning achieve clinically equivalent plan quality, and AD plans are insensitive to relatively large variability in arm position.

  View details for DOI 10.1016/j.prro.2013.07.010

  View details for PubMedID 24766687

• An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nature medicine Newman, A. M., Bratman, S. V., To, J., Wynne, J. F., Eclov, N. C., Modlin, L. A., Liu, C. L., Neal, J. W., Wakelee, H. A., Merritt, R. E., Shrager, J. B., Loo, B. W., Alizadeh, A. A., Diehn, M. 2014; 20 (5): 548-554

  Abstract

  Circulating tumor DNA (ctDNA) is a promising biomarker for noninvasive assessment of cancer burden, but existing ctDNA detection methods have insufficient sensitivity or patient coverage for broad clinical applicability. Here we introduce cancer personalized profiling by deep sequencing (CAPP-Seq), an economical and ultrasensitive method for quantifying ctDNA. We implemented CAPP-Seq for non-small-cell lung cancer (NSCLC) with a design covering multiple classes of somatic alterations that identified mutations in >95% of tumors. We detected ctDNA in 100% of patients with stage II-IV NSCLC and in 50% of patients with stage I, with 96% specificity for mutant allele fractions down to ∼0.02%. Levels of ctDNA were highly correlated with tumor volume and distinguished between residual disease and treatment-related imaging changes, and measurement of ctDNA levels allowed for earlier response assessment than radiographic approaches. Finally, we evaluated biopsy-free tumor screening and genotyping with CAPP-Seq. We envision that CAPP-Seq could be routinely applied clinically to detect and monitor diverse malignancies, thus facilitating personalized cancer therapy.

  View details for DOI 10.1038/nm.3519

  View details for PubMedID 24705333

• ACR Appropriateness Criteria((R)) Early-Stage Non-Small-Cell Lung Cancer AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Videtic, G. M., Chang, J. Y., Chetty, I. J., Ginsburg, M. E., Kestin, L. L., Kong, F. (., Lally, B. E., Loo, B. W., Movsas, B., Stinchcombe, T. E., Willers, H., Rosenzweig, K. E. 2014; 37 (2): 201-207

  Abstract

  Early-stage non-small-cell lung cancer (NSCLC) is diagnosed in about 15% to 20% of lung cancer patients at presentation. In order to provide clinicians with guidance in decision making for early-stage NSCLC patients, the American College of Radiology Appropriateness Criteria Lung Cancer Panel was recently charged with a review of the current published literature to generate up-to-date management recommendations for this clinical scenario. For patients with localized, mediastinal lymph node-negative NSCLC, optimal management should be determined by an expert multidisciplinary team. For medically operable patients, surgical resection is the standard of care, with generally no role for adjuvant therapies thereafter. For patients with medical comorbidities making them at high risk for surgery, there is emerging evidence demonstrating the availability of low toxicity curative therapies, such as stereotactic body radiotherapy, for their care. As a general statement, the American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

  View details for DOI 10.1097/COC.0000000000000013

  View details for Web of Science ID 000333713100019

  View details for PubMedID 25180631

• A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer. International journal of radiation oncology, biology, physics Harris, J. P., Murphy, J. D., Hanlon, A. L., Le, Q., Loo, B. W., Diehn, M. 2014; 88 (4): 872-884

  Abstract

  Concerns have been raised about the potential for worse treatment outcomes because of dosimetric inaccuracies related to tumor motion and increased toxicity caused by the spread of low-dose radiation to normal tissues in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy (IMRT). We therefore performed a population-based comparative effectiveness analysis of IMRT, conventional 3-dimensional conformal radiation therapy (3D-CRT), and 2-dimensional radiation therapy (2D-RT) in stage III NSCLC.We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify a cohort of patients diagnosed with stage III NSCLC from 2002 to 2009 treated with IMRT, 3D-CRT, or 2D-RT. Using Cox regression and propensity score matching, we compared survival and toxicities of these treatments.The proportion of patients treated with IMRT increased from 2% in 2002 to 25% in 2009, and the use of 2D-RT decreased from 32% to 3%. In univariate analysis, IMRT was associated with improved overall survival (OS) (hazard ratio [HR] 0.90, P=.02) and cancer-specific survival (CSS) (HR 0.89, P=.02). After controlling for confounders, IMRT was associated with similar OS (HR 0.94, P=.23) and CSS (HR 0.94, P=.28) compared with 3D-CRT. Both techniques had superior OS compared with 2D-RT. IMRT was associated with similar toxicity risks on multivariate analysis compared with 3D-CRT. Propensity score matched model results were similar to those from adjusted models.In this population-based analysis, IMRT for stage III NSCLC was associated with similar OS and CSS and maintained similar toxicity risks compared with 3D-CRT.

  View details for DOI 10.1016/j.ijrobp.2013.12.010

  View details for PubMedID 24495591

• PET Imaging of Stroke-Induced Neuroinflammation in Mice Using [F-18]PBR06 MOLECULAR IMAGING AND BIOLOGY Lartey, F. M., Ahn, G., Shen, B., Cord, K., Smith, T., Chua, J. Y., Rosenblum, S., Liu, H., James, M. L., Chernikova, S., Lee, S. W., Pisani, L. J., Tirouvanziam, R., Chen, J. W., Palmer, T. D., Chin, F. T., Guzman, R., Graves, E. E., Loo, B. W. 2014; 16 (1): 109-117

  Abstract

  The purpose of this study is to evaluate the 18 kDa translocator protein (TSPO) radioligand [(18)F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([(18)F]PBR06) as a positron emission tomography (PET) imaging biomarker of stroke-induced neuroinflammation in a rodent model.Stroke was induced by transient middle cerebral artery occlusion in Balb/c mice. Dynamic PET/CT imaging with displacement and preblocking using PK111195 was performed 3 days later. PET data were correlated with immunohistochemistry (IHC) for the activated microglial markers TSPO and CD68 and with autoradiography.[(18)F]PBR06 accumulation peaked within the first 5 min postinjection, then decreased gradually, remaining significantly higher in infarct compared to noninfarct regions. Displacement or preblocking with PK11195 eliminated the difference in [(18)F]PBR06 uptake between infarct and noninfarct regions. Autoradiography and IHC correlated well spatially with uptake on PET.[(18)F]PBR06 PET specifically images TSPO in microglial neuroinflammation in a mouse model of stroke and shows promise for imaging and monitoring microglial activation/neuroinflammation in other disease models.

  View details for DOI 10.1007/s11307-013-0664-5

  View details for Web of Science ID 000329793200014

  View details for PubMedID 23836504

• Investigating the feasibility of rapid MRI for image-guided motion management in lung cancer radiotherapy. BioMed research international Sawant, A., Keall, P., Pauly, K. B., Alley, M., Vasanawala, S., Loo, B. W., Hinkle, J., Joshi, S. 2014; 2014: 485067-?

  Abstract

  Cycle-to-cycle variations in respiratory motion can cause significant geometric and dosimetric errors in the administration of lung cancer radiation therapy. A common limitation of the current strategies for motion management is that they assume a constant, reproducible respiratory cycle. In this work, we investigate the feasibility of using rapid MRI for providing long-term imaging of the thorax in order to better capture cycle-to-cycle variations. Two nonsmall-cell lung cancer patients were imaged (free-breathing, no extrinsic contrast, and 1.5 T scanner). A balanced steady-state-free-precession (b-SSFP) sequence was used to acquire cine-2D and cine-3D (4D) images. In the case of Patient 1 (right midlobe lesion, ~40 mm diameter), tumor motion was well correlated with diaphragmatic motion. In the case of Patient 2, (left upper-lobe lesion, ~60 mm diameter), tumor motion was poorly correlated with diaphragmatic motion. Furthermore, the motion of the tumor centroid was poorly correlated with the motion of individual points on the tumor boundary, indicating significant rotation and/or deformation. These studies indicate that image quality and acquisition speed of cine-2D MRI were adequate for motion monitoring. However, significant improvements are required to achieve comparable speeds for truly 4D MRI. Despite several challenges, rapid MRI offers a feasible and attractive tool for noninvasive, long-term motion monitoring.

  View details for DOI 10.1155/2014/485067

  View details for PubMedID 24524077

• Clinical implementation of intrafraction cone beam computed tomography imaging during lung tumor stereotactic ablative radiation therapy. International journal of radiation oncology, biology, physics Li, R., Han, B., Meng, B., Maxim, P. G., Xing, L., Koong, A. C., Diehn, M., Loo, B. W. 2013; 87 (5): 917-923

  Abstract

  To develop and clinically evaluate a volumetric imaging technique for assessing intrafraction geometric and dosimetric accuracy of stereotactic ablative radiation therapy (SABR).Twenty patients received SABR for lung tumors using volumetric modulated arc therapy (VMAT). At the beginning of each fraction, pretreatment cone beam computed tomography (CBCT) was used to align the soft-tissue tumor position with that in the planning CT. Concurrent with dose delivery, we acquired fluoroscopic radiograph projections during VMAT using the Varian on-board imaging system. Those kilovolt projections acquired during millivolt beam-on were automatically extracted, and intrafraction CBCT images were reconstructed using the filtered backprojection technique. We determined the time-averaged target shift during VMAT by calculating the center of mass of the tumor target in the intrafraction CBCT relative to the planning CT. To estimate the dosimetric impact of the target shift during treatment, we recalculated the dose to the GTV after shifting the entire patient anatomy according to the time-averaged target shift determined earlier.The mean target shift from intrafraction CBCT to planning CT was 1.6, 1.0, and 1.5 mm; the 95th percentile shift was 5.2, 3.1, 3.6 mm; and the maximum shift was 5.7, 3.6, and 4.9 mm along the anterior-posterior, left-right, and superior-inferior directions. Thus, the time-averaged intrafraction gross tumor volume (GTV) position was always within the planning target volume. We observed some degree of target blurring in the intrafraction CBCT, indicating imperfect breath-hold reproducibility or residual motion of the GTV during treatment. By our estimated dose recalculation, the GTV was consistently covered by the prescription dose (PD), that is, V100% above 0.97 for all patients, and minimum dose to GTV >100% PD for 18 patients and >95% PD for all patients.Intrafraction CBCT during VMAT can provide geometric and dosimetric verification of SABR valuable for quality assurance and potentially for treatment adaptation.

  View details for DOI 10.1016/j.ijrobp.2013.08.015

  View details for PubMedID 24113060

• 4D CT lung ventilation images are affected by the 4D CT sorting method. Medical physics Yamamoto, T., Kabus, S., Lorenz, C., Johnston, E., Maxim, P. G., Diehn, M., Eclov, N., Barquero, C., Loo, B. W., Keall, P. J. 2013; 40 (10): 101907-?

  Abstract

  Four-dimensional (4D) computed tomography (CT) ventilation imaging is a novel promising technique for lung functional imaging. The current standard 4D CT technique using phase-based sorting frequently results in artifacts, which may deteriorate the accuracy of ventilation imaging. The purpose of this study was to quantify the variability of 4D CT ventilation imaging due to 4D CT sorting.4D CT image sets from nine lung cancer patients were each sorted by the phase-based method and anatomic similarity-based method, designed to reduce artifacts, with corresponding ventilation images created for each method. Artifacts in the resulting 4D CT images were quantified with the artifact score which was defined based on the difference between the normalized cross correlation for CT slices within a CT data segment and that for CT slices bordering the interface between adjacent CT data segments. The ventilation variation was quantified using voxel-based Spearman rank correlation coefficients for all lung voxels, and Dice similarity coefficients (DSC) for the spatial overlap of low-functional lung volumes. Furthermore, the correlations with matching single-photon emission CT (SPECT) ventilation images (assumed ground truth) were evaluated for three patients to investigate which sorting method provides higher physiologic accuracy.Anatomic similarity-based sorting reduced 4D CT artifacts compared to phase-based sorting (artifact score, 0.45 ± 0.14 vs 0.58 ± 0.24, p = 0.10 at peak-exhale; 0.63 ± 0.19 vs 0.71 ± 0.31, p = 0.25 at peak-inhale). The voxel-based correlation between the two ventilation images was 0.69 ± 0.26 on average, ranging from 0.03 to 0.85. The DSC was 0.71 ± 0.13 on average. Anatomic similarity-based sorting yielded significantly fewer lung voxels with paradoxical negative ventilation values than phase-based sorting (5.0 ± 2.6% vs 9.7 ± 8.4%, p = 0.05), and improved the correlation with SPECT ventilation regionally.The variability of 4D CT ventilation imaging due to 4D CT sorting was moderate overall and substantial in some cases, suggesting that 4D CT artifacts are an important source of variations in 4D CT ventilation imaging. Reduction of 4D CT artifacts provided more physiologically convincing and accurate ventilation estimates. Further studies are needed to confirm this result.

  View details for DOI 10.1118/1.4820538

  View details for PubMedID 24089909

• Clinical impact of dose overestimation by effective path length calculation in stereotactic ablative radiation therapy of lung tumors. Practical radiation oncology Liu, M. B., Eclov, N. C., Trakul, N., Murphy, J., Diehn, M., Le, Q., Dieterich, S., Maxim, P. G., Loo, B. W. 2013; 3 (4): 294-300

  Abstract

  To determine the clinical impact of calculated dose differences between effective path length (EPL) and Monte Carlo (MC) algorithms in stereotactic ablative radiation therapy (SABR) of lung tumors.We retrospectively analyzed the treatment plans and clinical outcomes of 77 consecutive patients treated with SABR for 82 lung tumors between 2003 and 2009 at our institution. Sixty treatments were originally planned using EPL, and 22 using MC. All plans were recalculated for the same beam specifications using MC and EPL, respectively. The doses covering 95%, 50%, and 5% (D95, D50, D5, respectively) of the target volumes were compared between EPL and MC (assumed to be the actual delivered dose), both as physical dose and biologically effective dose. Time to local recurrence was correlated with dose by Cox regression analysis. The relationship between tumor control probability (TCP) and biologically effective dose was determined via logistic regression and used to estimate the TCP decrements due to prescribing by EPL calculations.EPL overestimated dose compared with MC in all tumor dose-volume histogram parameters in all plans. The difference was >10% of the MC D95 to the planning target volume and gross tumor volume in 60 of 82 (73%) and 52 of 82 plans (63%), respectively. Local recurrence occurred in 13 of 82 tumors. Controlling for gross tumor volume, higher physical and biologically effective planning target volume D95 correlated significantly with local control (P = .007 and P = .045, respectively). Compared with MC, prescribing based on EPL translated to a median TCP decrement of 4.3% (range, 1.2%-37%) and a >5% decrement in 46% of tumors.Clinical follow-up for local lung tumor control in a sizable cohort of patients treated with SABR demonstrates that EPL overestimates dose by amounts that substantially decrease TCP in a large proportion. EPL algorithms should be avoided for lung tumor SABR.

  View details for DOI 10.1016/j.prro.2012.09.003

  View details for PubMedID 24674401

• Radiotherapy for nonadenoid cystic carcinomas of major salivary glands. American journal of otolaryngology Chung, M. P., Tang, C., Chan, C., Hara, W. Y., Loo, B. W., Kaplan, M. J., Fischbein, N., Le, Q., Chang, D. T. 2013; 34 (5): 425-430

  Abstract

  To report outcomes in patients treated with postoperative radiotherapy for nonadenoid cystic carcinomas of the major salivary glands.From 1998-2011, 37 patients with nonadenoid cystic carcinomas of the major salivary gland underwent postoperative radiotherapy. The median radiation dose was 60 Gy (range, 45-70 Gy). TNM distribution included T1-2 (n=16, 44%), T3-T4 (n=21, 56%), N0 (n=19, 51%), and N+ (n=18, 49%). Histologies included adenocarcinoma (n=13, 35%), squamous cell carcinoma (n=8, 22%), mucoepidermoid carcinoma (n=8, 22%), and other (n=8, 21%). Median follow-up was 4.7 years for all patients (range, 0.3-14.1 years) and 5.0 years for living patients (range, 1.2-12.2 years).Five-year local-regional control, overall survival (OS), and cancer-specific survival (CSS) were 97%, 76%, and 84%. On univariate analysis, OS was significantly worse for patients ≥65 years old (p=0.04). CSS was significantly worse for positive perineural invasion (p=0.02), extraparenchymal extension (p=0.04), and in patients who received no chemotherapy (p=0.02). Doses >60 Gy was significantly worse for OS (p=0.003) and CSS (p=0.003), although these patients had higher TNM (>T2, p=0.01) and trended towards a higher rate of extraparenchymal extension (p=0.08). Four patients (11%) developed ≥grade 2 toxicities; 3 patients developed early toxicities and one patient developed late toxicities.Radiotherapy for salivary gland tumors provides excellent local-regional control when combined with surgery. Distant metastasis is the predominant pattern of failure, although chemotherapy seemed to improve cancer-specific survival.

  View details for DOI 10.1016/j.amjoto.2013.03.007

  View details for PubMedID 23583094

• Toward a planning scheme for emission guided radiation therapy (EGRT): FDG based tumor tracking in a metastatic breast cancer patient MEDICAL PHYSICS Fan, Q., Nanduri, A., Yang, J., Yamamoto, T., Loo, B., Graves, E., Zhu, L., Mazin, S. 2013; 40 (8)

  Abstract

  Purpose: Emission guided radiation therapy (EGRT) is a new modality that uses PET emissions in real-time for direct tumor tracking during radiation delivery. Radiation beamlets are delivered along positron emission tomography (PET) lines of response (LORs) by a fast rotating ring therapy unit consisting of a linear accelerator (Linac) and PET detectors. The feasibility of tumor tracking and a primitive modulation method to compensate for attenuation have been demonstrated using a 4D digital phantom in our prior work. However, the essential capability of achieving dose modulation as in conventional intensity modulated radiation therapy (IMRT) treatments remains absent. In this work, the authors develop a planning scheme for EGRT to accomplish sophisticated intensity modulation based on an IMRT plan while preserving tumor tracking.Methods: The planning scheme utilizes a precomputed LOR response probability distribution to achieve desired IMRT planning modulation with effects of inhomogeneous attenuation and nonuniform background activity distribution accounted for. Evaluation studies are performed on a 4D digital patient with a simulated lung tumor and a clinical patient who has a moving breast cancer metastasis in the lung. The Linac dose delivery is simulated using a voxel-based Monte Carlo algorithm. The IMRT plan is optimized for a planning target volume (PTV) that encompasses the tumor motion using the MOSEK package and a Pinnacle(3)™ workstation (Philips Healthcare, Fitchburg, WI) for digital and clinical patients, respectively. To obtain the emission data for both patients, the Geant4 application for tomographic emission (GATE) package and a commercial PET scanner are used. As a comparison, 3D and helical IMRT treatments covering the same PTV based on the same IMRT plan are simulated.Results: 3D and helical IMRT treatments show similar dose distribution. In the digital patient case, compared with the 3D IMRT treatment, EGRT achieves a 15.1% relative increase in dose to 95% of the gross tumor volume (GTV) and a 31.8% increase to 50% of the GTV. In the patient case, EGRT yields a 15.2% relative increase in dose to 95% of the GTV and a 20.7% increase to 50% of the GTV. The organs at risk (OARs) doses are kept similar or lower for EGRT in both cases. Tumor tracking is observed in the presence of planning modulation in all EGRT treatments.Conclusions: As compared to conventional IMRT treatments, the proposed EGRT planning scheme allows an escalated target dose while keeping dose to the OARs within the same planning limits. With the capabilities of incorporating planning modulation and accurate tumor tracking, EGRT has the potential to greatly improve targeting in radiation therapy and enable a practical and effective implementation of 4D radiation therapy for planning and delivery.

  View details for DOI 10.1118/1.4812427

  View details for Web of Science ID 000322735900013

  View details for PubMedID 23927305

• Non-small cell lung cancer, version 2.2013. Journal of the National Comprehensive Cancer Network Ettinger, D. S., Akerley, W., Borghaei, H., Chang, A. C., Cheney, R. T., Chirieac, L. R., D'Amico, T. A., Demmy, T. L., Govindan, R., Grannis, F. W., Grant, S. C., Horn, L., Jahan, T. M., Komaki, R., Kong, F. S., Kris, M. G., Krug, L. M., Lackner, R. P., Lennes, I. T., Loo, B. W., Martins, R., Otterson, G. A., Patel, J. D., Pinder-Schenck, M. C., Pisters, K. M., Reckamp, K., Riely, G. J., Rohren, E., Shapiro, T. A., Swanson, S. J., Tauer, K., Wood, D. E., Yang, S. C., Gregory, K., Hughes, M. 2013; 11 (6): 645-653

  Abstract

  These NCCN Guidelines Insights focus on the diagnostic evaluation of suspected lung cancer. This topic was the subject of a major update in the 2013 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer. The NCCN Guidelines Insights focus on the major updates in the NCCN Guidelines and discuss the new updates in greater detail.

  View details for PubMedID 23744864

• Thymomas and Thymic Carcinomas Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Ettinger, D. S., Riely, G. J., Akerley, W., Borghaei, H., Chang, A. C., Cheney, R. T., Chirieac, L. R., D'Amico, T. A., Demmy, T. L., Govindan, R., Grannis, F. W., Grant, S. C., Horn, L., Jahan, T. M., Komaki, R., (Spring) Kong, F., Kris, M. G., Krug, L. M., Lackner, R. P., Lennes, I. T., Loo, B. W., Martins, R., Otterson, G. A., Patel, J. D., Pinder-Schenck, M. C., Pisters, K. M., Reckamp, K., Rohren, E., Shapiro, T. A., Swanson, S. J., Tauer, K., Wood, D. E., Yang, S. C., Gregory, K., Hughes, M. 2013; 11 (5): 562-576

  Abstract

  Masses in the anterior mediastinum can be neoplasms (eg, thymomas, thymic carcinomas, or lung metastases) or non-neoplastic conditions (eg, intrathoracic goiter). Thymomas are the most common primary tumor in the anterior mediastinum, although they are rare. Thymic carcinomas are very rare. Thymomas and thymic carcinomas originate in the thymus. Although thymomas can spread locally, they are much less invasive than thymic carcinomas. Patients with thymomas have 5-year survival rates of approximately 78%. However, 5-year survival rates for thymic carcinomas are only approximately 40%. These guidelines outline the evaluation, treatment, and management of these mediastinal tumors.

  View details for Web of Science ID 000318752600007

  View details for PubMedID 23667206

• Migration of implanted markers for image-guided lung tumor stereotactic ablative radiotherapy. Journal of applied clinical medical physics Hong, J. C., Eclov, N. C., Yu, Y., Rao, A. K., Dieterich, S., Le, Q., Diehn, M., Sze, D. Y., Loo, B. W., Kothary, N., Maxim, P. G. 2013; 14 (2): 4046-?

  Abstract

  The purpose of this study was to quantify postimplantation migration of percutaneously implanted cylindrical gold seeds ("seeds") and platinum endovascular embolization coils ("coils") for tumor tracking in pulmonary stereotactic ablative radiotherapy (SABR). We retrospectively analyzed the migration of markers in 32 consecutive patients with computed tomography scans postimplantation and at simulation. We implanted 147 markers (59 seeds, 88 coils) in or around 34 pulmonary tumors over 32 procedures, with one lesion implanted twice. Marker coordinates were rigidly aligned by minimizing fiducial registration error (FRE), the root mean square of the differences in marker locations for each tumor between scans. To also evaluate whether single markers were responsible for most migration, we aligned with and without the outlier causing the largest FRE increase per tumor. We applied the resultant transformation to all markers. We evaluated migration of individual markers and FRE of each group. Median scan interval was 8 days. Median individual marker migration was 1.28 mm (interquartile range [IQR] 0.78-2.63 mm). Median lesion FRE was 1.56 mm (IQR 0.92-2.95 mm). Outlier identification yielded 1.03 mm median migration (IQR 0.52-2.21 mm) and 1.97 mm median FRE (IQR 1.44-4.32 mm). Outliers caused a mean and median shift in the centroid of 1.22 and 0.80 mm (95th percentile 2.52 mm). Seeds and coils had no statistically significant difference. Univariate analysis suggested no correlation of migration with the number of markers, contact with the chest wall, or time elapsed. Marker migration between implantation and simulation is limited and unlikely to cause geometric miss during tracking.

  View details for DOI 10.1120/jacmp.v14i2.4046

  View details for PubMedID 23470933

• Metabolic Tumor Volume Predicts Disease Progression and Survival in Patients with Squamous Cell Carcinoma of the Anal Canal JOURNAL OF NUCLEAR MEDICINE Bazan, J. G., Koong, A. C., Kapp, D. S., Quon, A., Graves, E. E., Loo, B. W., Chang, D. T. 2013; 54 (1): 27-32

  Abstract

  PET imaging has become a useful diagnostic tool in patients with anal cancer. We evaluated the prognostic value of metabolic tumor volume (MTV) in patients with anal cancer treated with definitive chemoradiotherapy.Patients with anal cancer who underwent PET imaging for pretreatment staging or radiation therapy planning from 2003 to 2011 were included. PET parameters included MTV and maximum standardized uptake value (SUVmax). Total MTV (MTV-T) was defined as the sum of the volumes above a standardized uptake value 50% of the SUVmax within the primary tumor and involved nodes. Kaplan-Meier and Cox regression models were used to test for associations between metabolic or clinical endpoints and overall survival (OS), progression-free survival (PFS), and event-free survival (EFS). Results: Thirty-nine patients were included. Median follow-up for the cohort was 22 mo. Overall, 6 patients died and 9 patients had disease progression. The 2-y OS, PFS, and EFS for the entire cohort were 88%, 74%, and 69%, respectively. Higher MTV-T was associated with worse OS (P = 0.04), PFS (P = 0.004), and EFS (P = 0.002) on univariate analysis. Patients with an MTV greater than 26 cm(3) had worse PFS than did those with an MTV of 26 cm(3) or less (33% vs. 82%, P = 0.003). SUVmax was not prognostic for any outcome. Higher T classification (T3/T4 vs. T1/T2) was associated with worse PFS and EFS. When adjusting for T classification, MTV-T remained a significant predictor for PFS (P = 0.01) and EFS (P = 0.02).MTV-T yields prognostic information on PFS and EFS beyond that of established prognostic factors in patients with anal cancer.

  View details for DOI 10.2967/jnumed.112.109470

  View details for Web of Science ID 000313606800026

  View details for PubMedID 23236018

• An observational study of circulating tumor cells and (18)F-FDG PET uptake in patients with treatment-naive non-small cell lung cancer. PloS one Nair, V. S., Keu, K. V., Luttgen, M. S., Kolatkar, A., Vasanawala, M., Kuschner, W., Bethel, K., Iagaru, A. H., Hoh, C., Shrager, J. B., Loo, B. W., Bazhenova, L., Nieva, J., Gambhir, S. S., Kuhn, P. 2013; 8 (7)

  Abstract

  We investigated the relationship of circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) with tumor glucose metabolism as defined by (18)F-fluorodeoxyglucose (FDG) uptake since both have been associated with patient prognosis.We performed a retrospective screen of patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell Adhesion Molecule (EpCAM) independent fluid biopsy based on cell morphology for CTC detection and enumeration (defined here as High Definition CTCs or "HD-CTCs"). We then correlated HD-CTCs with quantitative FDG uptake image data calibrated across centers in a cross-sectional analysis.We assessed seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile range, IQR, 2.0-3.6) and median maximum standardized uptake value (SUVmax) was 7.2 (IQR 3.7-15.5). More than 2 HD-CTCs were detected in 63% of patients, whether across all stages (45 of 71) or in stage I disease (27 of 43). HD-CTCs were weakly correlated with partial volume corrected tumor SUVmax (r = 0.27, p-value = 0.03) and not correlated with tumor diameter (r = 0.07; p-value = 0.60). For a given partial volume corrected SUVmax or tumor diameter there was a wide range of detected HD-CTCs in circulation for both early and late stage disease.CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, in vivo tumor biology in the early stages of this deadly disease.

  View details for DOI 10.1371/journal.pone.0067733

  View details for PubMedID 23861795

• Small Cell Lung Cancer JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Kalemkerian, G. P., Akerley, W., Bogner, P., Borghaei, H., Chow, L. Q., Downey, R. J., Gandhi, L., Ganti, A. K., Govindan, R., Grecula, J. C., Hayman, J., Heist, R. S., Horn, L., Jahan, T., Koczywas, M., Loo, B. W., Merritt, R. E., Moran, C. A., Niell, H. B., O'Malley, J., Patel, J. D., Ready, N., Rudin, C. M., Williams, C. C., Gregory, K., Hughes, M. 2013; 11 (1): 78-98

  Abstract

  Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted.

  View details for Web of Science ID 000313575200011

  View details for PubMedID 23307984

• The Optimal Use of Radiotherapy in Small Cell Lung Cancer JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Shultz, D. B., Grecula, J. C., Hayman, J., Diehn, M., Loo, B. W. 2013; 11 (1): 107-114

  View details for Web of Science ID 000313575200013

• American College of Chest Physicians and Society of Thoracic Surgeons Consensus Statement for Evaluation and Management for High-Risk Patients With Stage I Non-small Cell Lung Cancer CHEST Donington, J., Ferguson, M., Mazzone, P., Handy, J., Schuchert, M., Fernando, H., Loo, B., Lanuti, M., de Hoyos, A., Detterbeck, F., Pennathur, A., Howington, J., Landreneau, R., Silvestri, G. 2012; 142 (6): 1620-1635

  Abstract

  The standard treatment of stage I non-small cell lung cancer (NSCLC) is lobectomy with systematic mediastinal lymph node evaluation. Unfortunately, up to 25% of patients with stage I NSCLC are not candidates for lobectomy because of severe medical comorbidity.A panel of experts was convened through the Thoracic Oncology Network of the American College of Chest Physicians and the Workforce on Evidence-Based Surgery of the Society of Thoracic Surgeons. Following a literature review, the panel developed 13 suggestions for evaluation and treatment through iterative discussion and debate until unanimous agreement was achieved.Pretreatment evaluation should focus primarily on measures of cardiopulmonary physiology, as respiratory failure represents the greatest interventional risk. Alternative treatment options to lobectomy for high-risk patients include sublobar resection with or without brachytherapy, stereotactic body radiation therapy, and radiofrequency ablation. Each is associated with decreased procedural morbidity and mortality but increased risk for involved lobe and regional recurrence compared with lobectomy, but direct comparisons between modalities are lacking.Therapeutic options for the treatment of high-risk patients are evolving quickly. Improved radiographic staging and the diagnosis of smaller and more indolent tumors push the risk-benefit decision toward parenchymal-sparing or nonoperative therapies in high-risk patients. Unbiased assessment of treatment options requires uniform reporting of treatment populations and outcomes in clinical series, which has been lacking to date.

  View details for DOI 10.1378/chest.12-0790

  View details for Web of Science ID 000312283800041

  View details for PubMedID 23208335

• Metabolic imaging metrics correlate with survival in early stage lung cancer treated with stereotactic ablative radiotherapy. Lung cancer Abelson, J. A., Murphy, J. D., Trakul, N., Bazan, J. G., Maxim, P. G., Graves, E. E., Quon, A., Le, Q., Diehn, M., Loo, B. W. 2012; 78 (3): 219-224

  Abstract

  To test whether (18)F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) imaging metrics correlate with outcomes in patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR).Fifty-four patients with stage I NSCLC underwent pre-SABR PET at simulation and/or post-SABR PET within 6 months. We analyzed maximum standardized uptake value (SUV(max)) and metabolic tumor volume defined using several thresholds (MTV50%, or MTV2, 4, 7, and 10). Endpoints included primary tumor control (PTC), progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS). We performed Kaplan-Meier, competing risk, and Cox proportional hazards survival analyses.Patients received 25-60 Gy in 1 to 5 fractions. Median follow-up time was 13.2 months. The 1-year estimated PTC, PFS, OS and CSS were 100, 83, 87 and 94%, respectively. Pre-treatment SUV(max) (p=0.014), MTV(7) (p=0.0077), and MTV(10) (p=0.0039) correlated significantly with OS. In the low-MTV(7)vs. high-MTV(7) sub-groups, 1-year estimated OS was 100 vs. 78% (p=0.0077) and CSS was 100 vs. 88% (p=0.082).In this hypothesis-generating study we identified multiple pre-treatment PET-CT metrics as potential predictors of OS and CSS in patients with NSCLC treated with SABR. These could aid risk-stratification and treatment individualization if validated prospectively.

  View details for DOI 10.1016/j.lungcan.2012.08.016

  View details for PubMedID 23009727

• Reproducibility of Four-dimensional Computed Tomography-based Lung Ventilation Imaging ACADEMIC RADIOLOGY Yamamoto, T., Kabus, S., von Berg, J., Lorenz, C., Chung, M. P., Hong, J. C., Loo, B. W., Keall, P. J. 2012; 19 (12): 1554-1565

  Abstract

  A novel ventilation imaging method based on four-dimensional (4D) computed tomography (CT) has been applied to the field of radiation oncology. Understanding its reproducibility is a prerequisite for clinical applications. The purpose of this study was to quantify the reproducibility of 4D CT ventilation imaging over different days and the same session.Two ventilation images were created from repeat 4D CT scans acquired over the average time frames of 15 days for 6 lung cancer patients and 5 minutes for another 6 patients. The reproducibility was quantified using the voxel-based Spearman rank correlation coefficients for all lung voxels and Dice similarity coefficients (DSC) for the spatial overlap of segmented high-, moderate-, and low-functional lung volumes. Furthermore, the relationship between the variation in abdominal motion range as a measure of the depth of breathing and variation in ventilation was evaluated using linear regression.The voxel-based correlation between the two ventilation images was moderate on average (0.50 ± 0.15). The DSCs were also moderate for the high- (0.60 ± 0.08), moderate- (0.46 ± 0.06), and low-functional lung (0.58 ± 0.09). No patients demonstrated strong correlations. The relationship between the motion range variation and ventilation variation was found to be moderate and significant.We investigated the reproducibility of 4D CT ventilation imaging over the time frames of 15 days and 5 minutes and found that it was only moderately reproducible. Respiratory variation during 4D CT scans was found to deteriorate the reproducibility. Improvement of 4D CT imaging is necessary to increase the reproducibility of 4D CT ventilation imaging.

  View details for DOI 10.1016/j.acra.2012.07.006

  View details for Web of Science ID 000311654800016

  View details for PubMedID 22975070

• Cell-free DNA as a Biomarker of Residual Disease Following Radiation Therapy for Non-small Cell Lung Cancer 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Bratman, S. V., Eclov, N. C., Modlin, L. A., Neal, J., Loo, B. W., Wu, G., Richardson, K., Newman, A. M., Alizadeh, A., Diehn, M. ELSEVIER SCIENCE INC. 2012: S713–S713

  View details for Web of Science ID 000310542902315

• Is Recontouring Organs-at-Risk (OAR) for Adaptive Radiation Therapy Plans for Locally Advanced Lung Cancer Necessary? A Preactivation Analysis From Radiation Therapy Oncology Group (RTOG) 1106 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Chen, W., Cui, Y., Kong, F., Machtay, M., Videtic, G., Loo, B., Gore, E., Galvin, J., Yu, Y., Xiao, Y. ELSEVIER SCIENCE INC. 2012: S602–S602

  View details for Web of Science ID 000310542902020

• Quantitative Evaluation of Impact Upon Tumor Control Probability (TCP) From Quality Assurance Criteria for Non-small Cell Lung Cancer From RTOG 1106 Study 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Chen, W., Cui, Y., Kong, F., Machtay, M., Videtic, G., Loo, B., Gore, E., Galvin, J., Yan, Y., Xiao, Y. ELSEVIER SCIENCE INC. 2012: S601–S601

  View details for Web of Science ID 000310542902018

• Acute Changes in Composition of Exhaled Breath Predict Radiation Pneumonitis Following Stereotactic Ablative Radiation Therapy 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) More, J. M., Eclov, N. C., Chung, M., Shorter, J. H., BURMEISTER, R., BANOS, P., Maxim, P., Loo, B. W., Diehn, M. ELSEVIER SCIENCE INC. 2012: S155–S156

  View details for Web of Science ID 000310542900386

• Feasibility of Pulmonary Interstitial Lymphography-guided Targeting in Stereotactic Ablative Radiation Therapy of Lung Tumors 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Abelson, J. A., Kothary, N., Fleischmann, D., Hofmann, L., Kielar, K., Maxim, P., Le, Q., Diehn, M., Loo, B. W. ELSEVIER SCIENCE INC. 2012: S173–S173

  View details for Web of Science ID 000310542900432

• Non-Small Cell Lung Cancer JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Ettinger, D. S., Akerley, W., Borghaei, H., Chang, A. C., Cheney, R. T., Chirieac, L. R., D'Amico, T. A., Demmy, T. L., Ganti, A. K., Govindan, R., Grannis, F. W., Horn, L., Jahan, T. M., Jahanzeb, M., Kessinger, A., Komaki, R., Kong, F. (., Kris, M. G., Krug, L. M., Lennes, I. T., Loo, B. W., Martins, R., O'Malley, J., Osarogiagbon, R. U., Otterson, G. A., Patel, J. D., Pinder-Schenck, M. C., Pisters, K. M., Reckamp, K., Riely, G. J., Rohren, E., Swanson, S. J., Wood, D. E., Yang, S. C., Hughes, M., Gregory, K. M. 2012; 10 (10): 1236-1271

  Abstract

  Most patients with non-small cell lung cancer (NSCLC) are diagnosed with advanced cancer. These guidelines only include information about stage IV NSCLC. Patients with widespread metastatic disease (stage IV) are candidates for systemic therapy, clinical trials, and/or palliative treatment. The goal is to identify patients with metastatic disease before initiating aggressive treatment, thus sparing these patients from unnecessary futile treatment. If metastatic disease is discovered during surgery, then extensive surgery is often aborted. Decisions about treatment should be based on multidisciplinary discussion.

  View details for Web of Science ID 000309901900007

  View details for PubMedID 23054877

• Postchemoradiotherapy Positron Emission Tomography Predicts Pathologic Response and Survival in Patients With Esophageal Cancer 53rd Annual Meeting of the American-Society-of-Radiation-Oncology (ASTRO) Jayachandran, P., Pai, R. K., Quon, A., Graves, E., Krakow, T. E., La, T., Loo, B. W., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2012: 471–77

  Abstract

  To correlate the prechemoradiotherapy (CRT) and post-CRT metabolic tumor volume (MTV) on positron emission tomography (PET) scanning with the pathologic response and survival in patients receiving preoperative CRT for esophageal cancer.The medical records of 37 patients with histologically confirmed Stage I-IVA esophageal cancer treated with CRT with or without surgical resection were reviewed. Of the 37 patients, 21 received preoperative CRT (57%) and 16 received definitive CRT (43%). All patients had a pre-CRT and 32 had a post-CRT PET scan. The MTV was measured on the pre-CRT PET and post-CRT PET scan, respectively, using a minimum standardized uptake value (SUV) threshold x, where x = 2, 2.5, 3, or the SUV maximum × 50%. The total glycolytic activity (TGA(x)) was defined as the mean SUV × MTV(x). The MTV ratio was defined as the pre-CRT PET MTV/post-CRT MTV. The SUV ratio was defined similarly. A single pathologist scored the pathologic response using a tumor regression grade (TRG) scale.The median follow-up was 1.5 years (range, 0.4-4.9). No significant correlation was found between any parameters on the pre-CRT PET scan and the TRG or overall survival (OS). Multiple post-CRT MTV values and post-TGA values correlated with the TRG and OS; however, the MTV(2.5(Post)) and TGA(2.5(Post)) had the greatest correlation. The MTV(2) ratio correlated with OS. The maximum SUV on either the pre-CRT and post-CRT PET scans or the maximum SUV ratio did not correlate with the TRG or OS. Patients treated preoperatively had survival similar compared with those treated definitively with a good PET response (p = 0.97) and significantly better than that of patients treated definitively with a poor PET response (p < 0.0001).The maximum SUV was not a predictive or prognostic parameter. The MTV(2.5) and TGA(2.5) were useful markers for predicting the response and survival on the post-CRT PET scan. The MTV(2) ratio also correlated with survival. Post-CRT PET can potentially guide therapy after CRT.

  View details for DOI 10.1016/j.ijrobp.2011.12.029

  View details for Web of Science ID 000308062700055

  View details for PubMedID 22381904

• Esophageal tolerance to high-dose stereotactic ablative radiotherapy DISEASES OF THE ESOPHAGUS Abelson, J. A., Murphy, J. D., Loo, B. W., Chang, D. T., Daly, M. E., Wiegner, E. A., Hancock, S., Chang, S. D., Le, Q., Soltys, S. G., Gibbs, I. C. 2012; 25 (7): 623-629

  Abstract

  Dose-volume parameters are needed to guide the safe administration of stereotactic ablative radiotherapy (SABR). We report on esophageal tolerance to high-dose hypofractionated radiation in patients treated with SABR. Thirty-one patients with spine or lung tumors received single- or multiple-fraction SABR to targets less than 1 cm from the esophagus. End points evaluated include D(5cc) (minimum dose in Gy to 5 cm(3) of the esophagus receiving the highest dose), D(2cc) , D(1cc) , and D(max) (maximum dose to 0.01 cm(3) ). Multiple-fraction treatments were correlated using the linear quadratic and linear quadratic-linear/universal survival models. Three esophageal toxicity events occurred, including esophagitis (grade 2), tracheoesophageal fistula (grade 4-5), and esophageal perforation (grade 4-5). Chemotherapy was a cofactor in the high-grade events. The median time to development of esophageal toxicity was 4.1 months (range 0.6-6.1 months). Two of the three events occurred below a published D(5cc) threshold, all three were below a D(2cc) threshold, and one was below a D(max) threshold. We report a dosimetric analysis of incidental dose to the esophagus from SABR. High-dose hypofractionated radiotherapy led to a number of high-grade esophageal adverse events, suggesting that conservative parameters to protect the esophagus are necessary when SABR is used, especially in the setting of chemotherapy or prior radiotherapy.

  View details for DOI 10.1111/j.1442-2050.2011.01295.x

  View details for Web of Science ID 000308712300008

  View details for PubMedID 22168251

• Stereotactic Ablative Radiotherapy for Reirradiation of Locally Recurrent Lung Tumors JOURNAL OF THORACIC ONCOLOGY Trakul, N., Harris, J. P., Le, Q., Hara, W. Y., Maxim, P. G., Loo, B. W., Diehn, M. 2012; 7 (9): 1462-1465

  Abstract

  Patients with thoracic tumors that recur after irradiation currently have limited therapeutic options. Retreatment using stereotactic ablative radiotherapy (SABR) is appealing for these patients because of its high conformity but has not been studied extensively. Here we report our experience with SABR for lung tumors in previously irradiated regions.We conducted a retrospective study of patients with primary lung cancer or metastatic lung tumors treated with SABR. We identified 17 such tumors in 15 patients and compared their outcomes with those of a cohort of 135 previously unirradiated lung tumors treated with SABR during the same time period.Twelve-month local control (LC) for retreated tumors was 65.5%, compared with 92.1% for tumors receiving SABR as initial treatment. Twelve-month LC was significantly worse for reirradiated tumors in which the time interval between treatments was 16 months or less (46.7%), compared with those with longer intertreatment intervals (87.5%). SABR reirradiation did not lead to significant increases in treatment-related toxicity.SABR for locally recurrent lung tumors arising in previously irradiated fields seems to be feasible and safe for appropriately selected patients. LC of retreated lesions was significantly lower, likely owing to the lower doses used for retreatment. Shorter time to retreatment was associated with increased risk of local failure, suggesting that these tumors may be particularly radioresistant. Our findings suggest that dose escalation may improve LC while maintaining acceptable levels of toxicity for these patients.

  View details for DOI 10.1097/JTO.0b013e31825f22ce

  View details for Web of Science ID 000308073300024

  View details for PubMedID 22895143

• Tumor Volume-Adapted Dosing in Stereotactic Ablative Radiotherapy of Lung Tumors INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Trakul, N., Chang, C. N., Harris, J., Chapman, C., Rao, A., Shen, J., Quinlan-Davidson, S., Filion, E. J., Wakelee, H. A., Colevas, A. D., Whyte, R. I., Dieterich, S., Maxim, P. G., Hristov, D., Tran, P., Quynh-Thu Le, Q. T., Loo, B. W., Diehn, M. 2012; 84 (1): 231-237

  Abstract

  Current stereotactic ablative radiotherapy (SABR) protocols for lung tumors prescribe a uniform dose regimen irrespective of tumor size. We report the outcomes of a lung tumor volume-adapted SABR dosing strategy.We retrospectively reviewed the outcomes in 111 patients with a total of 138 primary or metastatic lung tumors treated by SABR, including local control, regional control, distant metastasis, overall survival, and treatment toxicity. We also performed subset analysis on 83 patients with 97 tumors treated with a volume-adapted dosing strategy in which small tumors (gross tumor volume <12 mL) received single-fraction regimens with biologically effective doses (BED) <100 Gy (total dose, 18-25 Gy) (Group 1), and larger tumors (gross tumor volume ≥12 mL) received multifraction regimens with BED ≥100 Gy (total dose, 50-60 Gy in three to four fractions) (Group 2).The median follow-up time was 13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases), local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control, freedom from distant metastasis, and overall survival did not differ significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities developed in Group 2 (p = 0.02).A volume-adapted dosing approach for SABR of lung tumors seems to provide excellent local control for both small- and large-volume tumors and may reduce toxicity.

  View details for DOI 10.1016/j.ijrobp.2011.10.071

  View details for Web of Science ID 000308061900060

  View details for PubMedID 22381907

• Prognostic Value of Metabolic Tumor Volume and Velocity in Predicting Head-and-Neck Cancer Outcomes INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Chu, K. P., Murphy, J. D., La, T. H., Krakow, T. E., Iagaru, A., Graves, E. E., Hsu, A., Maxim, P. G., Loo, B., Chang, D. T., Quynh-Thu Le, Q. T. 2012; 83 (5): 1521-1527

  Abstract

  We previously showed that metabolic tumor volume (MTV) on positron emission tomography-computed tomography (PET-CT) predicts for disease recurrence and death in head-and-neck cancer (HNC). We hypothesized that increases in MTV over time would correlate with tumor growth and biology, and would predict outcome. We sought to examine tumor growth over time in serial pretreatment PET-CT scans.From 2006 to 2009, 51 patients had two PET-CT scans before receiving HNC treatment. MTV was defined as the tumor volume ≥ 50% of maximum SUV (SUV(max)). MTV was calculated for the primary tumor, nodal disease, and composite (primary tumor + nodes). MTV and SUV velocity were defined as the change in MTV or SUV(max) over time, respectively. Cox regression analyses were used to examine correlations between SUV, MTV velocity, and outcome (disease progression and overall survival).The median follow-up time was 17.5 months. The median time between PET-CT scans was 3 weeks. Unexpectedly, 51% of cases demonstrated a decrease in SUV(max) (average, -0.1 cc/week) and MTV (average, -0.3 cc/week) over time. Despite the variability in MTV, primary tumor MTV velocity predicted disease progression (hazard ratio 2.94; p = 0.01) and overall survival (hazard ratio 1.85; p = 0.03).Primary tumor MTV velocity appears to be a better prognostic indicator of disease progression and survival in comparison to nodal MTV velocity. However, substantial variability was found in PET-CT biomarkers between serial scans. Caution should be used when PET-CT biomarkers are integrated into clinical protocols for HNC.

  View details for DOI 10.1016/j.ijrobp.2011.10.022

  View details for Web of Science ID 000306128100047

  View details for PubMedID 22270168

• Intrafraction Verification of Gated RapidArc by Using Beam-Level Kilovoltage X-Ray Images INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Li, R., Mok, E., Chang, D. T., Daly, M., Loo, B. W., Diehn, M., Quynh-Thu Le, Q. T., Koong, A., Xing, L. 2012; 83 (5): E709-E715

  Abstract

  To verify the geometric accuracy of gated RapidArc treatment using kV images acquired during dose delivery.Twenty patients were treated using the gated RapidArc technique with a Varian TrueBeam STx linear accelerator. One to 7 metallic fiducial markers were implanted inside or near the tumor target before treatment simulation. For patient setup and treatment verification purposes, the internal target volume (ITV) was created, corresponding to each implanted marker. The gating signal was generated from the Real-time Position Management (RPM) system. At the beginning of each fraction, individualized respiratory gating amplitude thresholds were set based on fluoroscopic image guidance. During the treatment, we acquired kV images immediately before MV beam-on at every breathing cycle, using the on-board imaging system. After the treatment, all implanted markers were detected, and their 3-dimensional (3D) positions in the patient were estimated using software developed in-house. The distance from the marker to the corresponding ITV was calculated for each patient by averaging over all markers and all fractions.The average 3D distance between the markers and their ITVs was 0.8 ± 0.5 mm (range, 0-1.7 mm) and was 2.1 ± 1.2 mm at the 95th percentile (range, 0-3.8 mm). On average, a left-right margin of 0.6 mm, an anterior-posterior margin of 0.8 mm, and a superior-inferior margin of 1.5 mm is required to account for 95% of the intrafraction uncertainty in RPM-based RapidArc gating.To our knowledge, this is the first clinical report of intrafraction verification of respiration-gated RapidArc treatment in stereotactic ablative radiation therapy. For some patients, the markers deviated significantly from the ITV by more than 2 mm at the beginning of the MV beam-on. This emphasizes the need for gating techniques with beam-on/-off controlled directly by the actual position of the tumor target instead of external surrogates such as RPM.

  View details for DOI 10.1016/j.ijrobp.2012.03.006

  View details for Web of Science ID 000306128100022

  View details for PubMedID 22554582

  View details for PubMedCentralID PMC4476315

• Validation that metabolic tumor volume predicts outcome in head-and-neck cancer. International journal of radiation oncology, biology, physics Tang, C., Murphy, J. D., Khong, B., La, T. H., Kong, C., Fischbein, N. J., Colevas, A. D., Iagaru, A. H., Graves, E. E., Loo, B. W., Le, Q. 2012; 83 (5): 1514-1520

  Abstract

  We have previously reported that metabolic tumor volume (MTV) obtained from pretreatment (18)F-fluorodeoxydeglucose positron emission tomography (FDG PET)/ computed tomography (CT) predicted outcome in patients with head-and-neck cancer (HNC). The purpose of this study was to validate these results on an independent dataset, determine whether the primary tumor or nodal MTV drives this correlation, and explore the interaction with p16(INK4a) status as a surrogate marker for human papillomavirus (HPV).The validation dataset in this study included 83 patients with squamous cell HNC who had a FDG PET/CT scan before receiving definitive radiotherapy. MTV and maximum standardized uptake value (SUV(max)) were calculated for the primary tumor, the involved nodes, and the combination of both. The primary endpoint was to validate that MTV predicted progression-free survival and overall survival. Secondary analyses included determining the prognostic utility of primary tumor vs. nodal MTV.Similarly to our prior findings, an increase in total MTV of 17 cm(3) (difference between the 75th and 25th percentiles) was associated with a 2.1-fold increase in the risk of disease progression (p = 0.0002) and a 2.0-fold increase in the risk of death (p = 0.0048). SUV(max) was not associated with either outcome. Primary tumor MTV predicted progression-free (hazard ratio [HR] = 1.94; p < 0.0001) and overall (HR = 1.57; p < 0.0001) survival, whereas nodal MTV did not. In addition, MTV predicted progression-free (HR = 4.23; p < 0.0001) and overall (HR = 3.21; p = 0.0029) survival in patients with p16(INK4a)-positive oropharyngeal cancer.This study validates our previous findings that MTV independently predicts outcomes in HNC. MTV should be considered as a potential risk-stratifying biomarker in future studies of HNC.

  View details for DOI 10.1016/j.ijrobp.2011.10.023

  View details for PubMedID 22270174

• 4D-CT Lung Ventilation Images Vary with 4D-CT Sorting Techniques 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) Yamamoto, T., Kabus, S., Lorenz, C., Johnston, E., Maxim, P., Loo, B., Keall, P. AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS. 2012: 3614–14

  View details for Web of Science ID 000308905804076

• The Management of Patients With Stage IIIA Non-Small Cell Lung Cancer With N2 Mediastinal Node Involvement JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Martins, R. G., D'Amico, T. A., Loo, B. W., Pinder-Schenck, M., Borghaei, H., Chaft, J. E., Ganti, A. K., Kong, F. (., Kris, M. G., Lennes, I. T., Wood, D. E. 2012; 10 (5): 599-613

  Abstract

  Patients with stage IIIA non-small cell lung cancer, determined based on involvement of ipsilateral mediastinal lymph nodes, represent the most challenging management problem in this disease. Patients with this stage disease may have very different degrees of lymph node involvement. The pathologic confirmation of this involvement is a key step in the therapeutic decision. The difference in the degree of lymph node compromise has prognostic and treatment implications. Based on multiple considerations, patients can be treated with induction chemotherapy, chemoradiotherapy followed by surgery, or definitive chemoradiotherapy without surgery. Data derived from clinical trials have provided incomplete guidance for physicians and their patients. The best therapeutic plan is achieved through the multidisciplinary cooperation of a team specialized in lung cancer.

  View details for Web of Science ID 000303557700006

  View details for PubMedID 22570291

• Interim-treatment quantitative PET parameters predict progression and death among patients with hodgkin's disease RADIATION ONCOLOGY Tseng, D., Rachakonda, L. P., Su, Z., Advani, R., Horning, S., Hoppe, R. T., Quon, A., Graves, E. E., Loo, B. W., Tran, P. T. 2012; 7

  Abstract

  We hypothesized that quantitative PET parameters may have predictive value beyond that of traditional clinical factors such as the International Prognostic Score (IPS) among Hodgkin's disease (HD) patients.Thirty HD patients treated at presentation or relapse had staging and interim-treatment PET-CT scans. The majority of patients (53%) had stage III-IV disease and 67% had IPS ≥ 2. Interim-treatment scans were performed at a median of 55 days from the staging PET-CT. Chemotherapy regimens used: Stanford V (67%), ABVD (17%), VAMP (10%), or BEACOPP (7%). Hypermetabolic tumor regions were segmented semiautomatically and the metabolic tumor volume (MTV), mean standardized uptake value (SUV mean), maximum SUV (SUV max) and integrated SUV (iSUV) were recorded. We analyzed whether IPS, absolute value PET parameters or the calculated ratio of interim- to pre-treatment PET parameters were associated with progression free survival (PFS) or overall survival (OS).Median follow-up of the study group was 50 months. Six of the 30 patients progressed clinically. Absolute value PET parameters from pre-treatment scans were not significant. Absolute value SUV max from interim-treatment scans was associated with OS as determined by univariate analysis (p < 0.01). All four calculated PET parameters (interim/pre-treatment values) were associated with OS: MTV int/pre (p < 0.01), SUV mean int/pre (p < 0.05), SUV max int/pre (p = 0.01), and iSUV int/pre (p < 0.01). Absolute value SUV max from interim-treatment scans was associated with PFS (p = 0.01). Three calculated PET parameters (int/pre-treatment values) were associated with PFS: MTV int/pre (p = 0.01), SUV max int/pre (p = 0.02) and iSUV int/pre (p = 0.01). IPS was associated with PFS (p < 0.05) and OS (p < 0.01).Calculated PET metrics may provide predictive information beyond that of traditional clinical factors and may identify patients at high risk of treatment failure early for treatment intensification.

  View details for DOI 10.1186/1748-717X-7-5

  View details for Web of Science ID 000301710700001

  View details for PubMedID 22260710

• Metabolic Tumor Volume is an Independent Prognostic Factor in Patients Treated Definitively for Non-Small-Cell Lung Cancer CLINICAL LUNG CANCER Lee, P., Bazan, J. G., Lavori, P. W., Weerasuriya, D. K., Quon, A., Quynh-Thu Le, Q. T., Wakelee, H. A., Graves, E. E., Loo, B. W. 2012; 13 (1): 52-58

  Abstract

  Fluorine-18 flurodeoxyglucose positron emission tomography (FDG-PET) imaging has rapidly become the standard of care for staging patients with lung cancer. We evaluated the prognostic value of metabolic tumor volume (MTV), a measure of tumor burden on FDG-PET imaging, in patients with non-small-cell lung cancer (NSCLC) treated definitively.A retrospective review identified 61 patients with NSCLC who underwent FDG-PET imaging for pretreatment staging. Metabolically active tumor regions were segmented on the PET scans semiautomatically to calculate the total body MTV. We determined the relationship of overall survival (OS) and progression-free survival (PFS) with MTV in the entire cohort, and in the subgroup treated definitively.The estimated median PFS and OS for the entire cohort were 11.1 months and 18.9 months. Higher MTV was significantly associated with worse OS (P = 0.00075) and PFS (P = 0.00077). For definitively treated patients, when MTV was analyzed as a binary value above or below the median value, 2-year PFS was 60% versus 39.7% (median PFS 34.9 vs. 11.9 months) and 2-year OS was 79.7% versus 33.3% (median OS 41.9 vs. 18.9 months), respectively (log-rank P = 0.12 for PFS and P = 0.066 for OS). When MTV was analyzed as a continuous variable, multivariate Cox proportional hazards analysis demonstrated a trend to worse PFS (hazard ratio [HR] = 1.31; P = 0.12) and significantly worse OS (HR = 1.53; P = 0.018) with increasing MTV after controlling for known prognostic variables.Tumor burden as assessed by MTV yields prognostic information on survival beyond that of established prognostic factors in patients with NSCLC treated definitively.

  View details for DOI 10.1016/j.cllc.2011.05.001

  View details for Web of Science ID 000299270900008

  View details for PubMedID 21703935

• Evaluation of a metal artifact reduction technique in tonsillar cancer delineation. Practical radiation oncology Abelson, J. A., Murphy, J. D., Wiegner, E. A., Abelson, D., Sandman, D. N., Boas, F. E., Hristov, D., Fleischmann, D., Daly, M. E., Chang, D. T., Loo, B. W., Hara, W., Le, Q. 2012; 2 (1): 27-34

  Abstract

  Metal artifacts can degrade computed tomographic (CT) simulation imaging and impair accurate delineation of tumors for radiation treatment planning purposes. We investigated a Digital Imaging and Communications in Medicine-based metal artifact reduction technique in tonsillar cancer delineation.Eight patients with significant artifact and tonsil cancer were evaluated. Each patient had a positron emission tomography (PET)-CT and a contrast-enhanced CT obtained at the same setting during radiotherapy simulation. The CTs were corrected for artifact using the metal deletion technique (MDT). Two radiation oncologists independently delineated primary gross tumor volumes (GTVs) for each patient on native (CTnonMDT), metal corrected (CTMDT), and reference standard (CTPET/nonMDT) imaging, 1 week apart. Mixed effects models were used to determine if differences among GTVs were statistically significant. Two diagnostic radiologists and 2 radiation oncologists independently qualitatively evaluated CTs for each patient. Ratings were on an ordinal scale from -3 to +3, denoting that CTMDT was markedly, moderately, or slightly worse or better than CTnonMDT. Scores were compared with a Wilcoxon signed-rank test.The GTVPET/nonMDT were significantly smaller than GTVnonMDT (P = .004) and trended to be smaller than GTVMDT (P = .084). The GTVnonMDT and GTVMDT were not significantly different (P = .93). There was no significant difference in the extent to which GTVnonMDT or GTVMDT encompassed GTVPET/nonMDT (P = .33). In the subjective assessment of image quality, CTMDT did not significantly outperform CTnonMDT. In the majority of cases, the observer rated the CTMDT equivalent to (53%) or slightly superior (41%) to the corresponding CTnonMDT.The MTD modified images did not produce GTVMDT that more closely reproduced GTVPET/nonMDT than did GTVnonMDT. Moreover, the MTD modified images were not judged to be significantly superior when compared to the uncorrected images in terms of subjective ability to visualize the tonsilar tumors. This study failed to demonstrate value of the adjunctive use of a CT corrected for artifacts in the tumor delineation process. Artifacts do make tumor delineation challenging, and further investigation of other body sites is warranted.

  View details for DOI 10.1016/j.prro.2011.06.004

  View details for PubMedID 24674033

• An automated method for comparing motion artifacts in cine four-dimensional computed tomography images. Journal of applied clinical medical physics Cui, G., Jew, B., Hong, J. C., Johnston, E. W., Loo, B. W., Maxim, P. G. 2012; 13 (6): 3838-?

  Abstract

  The aim of this study is to develop an automated method to objectively compare motion artifacts in two four-dimensional computed tomography (4D CT) image sets, and identify the one that would appear to human observers with fewer or smaller artifacts. Our proposed method is based on the difference of the normalized correlation coefficients between edge slices at couch transitions, which we hypothesize may be a suitable metric to identify motion artifacts. We evaluated our method using ten pairs of 4D CT image sets that showed subtle differences in artifacts between images in a pair, which were identifiable by human observers. One set of 4D CT images was sorted using breathing traces in which our clinically implemented 4D CT sorting software miscalculated the respiratory phase, which expectedly led to artifacts in the images. The other set of images consisted of the same images; however, these were sorted using the same breathing traces but with corrected phases. Next we calculated the normalized correlation coefficients between edge slices at all couch transitions for all respiratory phases in both image sets to evaluate for motion artifacts. For nine image set pairs, our method identified the 4D CT sets sorted using the breathing traces with the corrected respiratory phase to result in images with fewer or smaller artifacts, whereas for one image pair, no difference was noted. Two observers independently assessed the accuracy of our method. Both observers identified 9 image sets that were sorted using the breathing traces with corrected respiratory phase as having fewer or smaller artifacts. In summary, using the 4D CT data of ten pairs of 4D CT image sets, we have demonstrated proof of principle that our method is able to replicate the results of two human observers in identifying the image set with fewer or smaller artifacts.

  View details for DOI 10.1120/jacmp.v13i6.3838

  View details for PubMedID 23149777

• Malignant Pleural Mesothelioma JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Ettinger, D. S., Akerley, W., Borghaei, H., Chang, A., Cheney, R. T., Chirieac, L. R., D'Amico, T. A., Demmy, T. L., Ganti, A. K., Govindan, R., Grannis, F. W., Horn, L., Jahan, T. M., Jahanzeb, M., Kessinger, A., Komaki, R., Kong, F. (., Kris, M. G., Krug, L. M., Lennes, I. T., Loo, B. W., Martins, R., O'Malley, J., Osarogiagbon, R. U., Otterson, G. A., Patel, J. D., Pinder-Schenck, M., Pisters, K. M., Reckamp, K., Riely, G. J., Rohren, E., Swanson, S. J., Wood, D. E., Yang, S. C. 2012; 10 (1): 26-41

  View details for Web of Science ID 000299007500006

  View details for PubMedID 22223867

• Correlation between metabolic tumor volume and pathologic tumor volume in squamous cell carcinoma of the oral cavity RADIOTHERAPY AND ONCOLOGY Murphy, J. D., Chisholm, K. M., Daly, M. E., Wiegner, E. A., Truong, D., Iagaru, A., Maxim, P. G., Loo, B. W., Graves, E. E., Kaplan, M. J., Kong, C., Le, Q. 2011; 101 (3): 356-361

  Abstract

  To explore the relationship between pathologic tumor volume and volume estimated from different tumor segmentation techniques on (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in oral cavity cancer.Twenty-three patients with squamous cell carcinoma of the oral tongue had PET-CT scans before definitive surgery. Pathologic tumor volume was estimated from surgical specimens. Metabolic tumor volume (MTV) was defined from PET-CT scans as the volume of tumor above a given SUV threshold. Multiple SUV thresholds were explored including absolute SUV thresholds, relative SUV thresholds, and gradient-based techniques.Multiple MTV's were associated with pathologic tumor volume; however the correlation was poor (R(2) range 0.29-0.58). The ideal SUV threshold, defined as the SUV that generates an MTV equal to pathologic tumor volume, was independently associated with maximum SUV (p=0.0005) and tumor grade (p=0.024). MTV defined as a function of maximum SUV and tumor grade improved the prediction of pathologic tumor volume (R(2)=0.63).Common SUV thresholds fail to predict pathologic tumor volume in head and neck cancer. The optimal technique that allows for integration of PET-CT with radiation treatment planning remains to be defined. Future investigation should incorporate biomarkers such as tumor grade into definitions of MTV.

  View details for DOI 10.1016/j.radonc.2011.05.040

  View details for Web of Science ID 000298894700003

  View details for PubMedID 21665308

  View details for PubMedCentralID PMC3178721

• ON-BOARD IMAGING VALIDATION OF OPTICALLY GUIDED STEREOTACTIC RADIOSURGERY POSITIONING SYSTEM FOR CONVENTIONALLY FRACTIONATED RADIOTHERAPY FOR PARANASAL SINUS AND SKULL BASE CANCER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Maxim, P. G., Loo, B. W., Murphy, J. D., Chu, K. P., Hsu, A., Quynh-Thu Le, Q. T. 2011; 81 (4): 1153-1159

  Abstract

  To evaluate the positioning accuracy of an optical positioning system for stereotactic radiosurgery in a pilot experience of optically guided, conventionally fractionated, radiotherapy for paranasal sinus and skull base tumors.Before each daily radiotherapy session, the positioning of 28 patients was set up using an optical positioning system. After this initial setup, the patients underwent standard on-board imaging that included daily orthogonal kilovoltage images and weekly cone beam computed tomography scans. Daily translational shifts were made after comparing the on-board images with the treatment planning computed tomography scans. These daily translational shifts represented the daily positional error in the optical tracking system and were recorded during the treatment course. For 13 patients treated with smaller fields, a three-degree of freedom (3DOF) head positioner was used for more accurate setup.The mean positional error for the optically guided system in patients with and without the 3DOF head positioner was 1.4 ± 1.1 mm and 3.9 ± 1.6 mm, respectively (p <.0001). The mean positional error drifted 0.11 mm/wk upward during the treatment course for patients using the 3DOF head positioner (p = .057). No positional drift was observed in the patients without the 3DOF head positioner.Our initial clinical experience with optically guided head-and-neck fractionated radiotherapy was promising and demonstrated clinical feasibility. The optically guided setup was especially useful when used in conjunction with the 3DOF head positioner and when it was recalibrated to the shifts using the weekly portal images.

  View details for DOI 10.1016/j.ijrobp.2010.08.049

  View details for Web of Science ID 000296823600035

  View details for PubMedID 21543166

• What the Diagnostic Radiologist Needs to Know about Radiation Oncology RADIOLOGY Terezakis, S. A., Heron, D. E., Lavigne, R. F., Diehn, M., Loo, B. W. 2011; 261 (1): 30-44

  Abstract

  Substantial technologic advances in radiation treatment planning and delivery have made possible exquisite tailoring of three-dimensional radiation dose distributions that conform to the tumor treatment volume while avoiding adjacent normal tissues. Although such highly precise treatment can increase the therapeutic ratio, it also introduces the potential that tumor extension outside the target is missed because it is unrecognized at the time of radiation treatment planning. As a result, accurate targeting of the tumor with radiation is of utmost importance to the radiation oncologist. Communication between diagnostic radiologists and radiation oncologists is essential, particularly given the subtleties that accompany image interpretation, to optimize the care of the cancer patient.

  View details for DOI 10.1148/radiol.11101688

  View details for Web of Science ID 000295039000006

  View details for PubMedID 21931140

• Molecular Imaging with C-11-PD153035 PET/CT Predicts Survival in Non-Small Cell Lung Cancer Treated with EGFR-TKI: A Pilot Study JOURNAL OF NUCLEAR MEDICINE Meng, X., Loo, B. W., Ma, L., Murphy, J. D., Sun, X., Yu, J. 2011; 52 (10): 1573-1579

  Abstract

  Outcomes are suboptimal when molecularly targeted therapies are used in patient populations unselected for the molecular target. This pilot study examines the correlation of PET using (11)C-labeled 4-N-(3-bromoanilino)-6,7-dimethoxyquinazoline ((11)C-PD153035), an imaging biomarker of epidermal growth factor receptor (EGFR), with outcomes in patients with non-small cell lung cancer (NSCLC) treated with the EGFR tyrosine kinase inhibitor erlotinib.Patients with advanced chemotherapy-refractory NSCLC were prospectively enrolled on a trial of erlotinib at a dose of 150 mg daily and imaged by (11)C-PD153035 PET/CT at baseline, after 1-2 wk, and after 6 wk from the start of treatment. Overall survival and progression-free survival (OS and PFS, respectively) times were correlated with the (11)C-PD153035 standardized uptake value (SUV) at each of the imaging times.Twenty-one patients were enrolled. Follow-up to progression was complete in all patients and to death in 18 of 21. By Cox regression analysis, baseline maximum SUV correlated strongly with OS and PFS (hazard ratio = 0.40, P = 0.002, and hazard ratio = 0.044, P < 0.001, respectively) independent of histology. Patients with higher maximum SUV (≥median) survived more than twice as long as patients with lower maximum SUV (median OS = 11.4 vs. 4.6 mo, P = 0.002; PFS = 4.4 vs. 1.8 mo, P < 0.001). However, (11)C-PD153035 uptake on follow-up scans was less well correlated with survival.Our preliminary results suggest (11)C-PD153035 PET/CT may be a noninvasive and rapid method for identifying patients with refractory advanced NSCLC of adenocarcinoma or squamous histology likely to respond to the EGFR tyrosine kinase inhibitor but not for monitoring treatment response.

  View details for DOI 10.2967/jnumed.111.092874

  View details for Web of Science ID 000295537800016

  View details for PubMedID 21903741

• Stereotactic ablative radiotherapy (SABR) for lung cancer: What does the future hold? Journal of thoracic disease Loo, B. W. 2011; 3 (3): 150-152

  View details for DOI 10.3978/j.issn.2072-1439.2011.06.08

  View details for PubMedID 22263081

• Results from a Single Institution Phase II Trial of Concurrent Docetaxel/Carboplatin/Radiotherapy Followed by Surgical Resection and Consolidation Docetaxel/Carboplatin in Stage III Non-Small-Cell Lung Cancer CLINICAL LUNG CANCER Das, M., Donington, J. S., Murphy, J., Kozak, M., Eclov, N., Whyte, R. I., Hoang, C. D., Zhou, L., Le, Q., Loo, B. W., Wakelee, H. 2011; 12 (5): 280-285

  Abstract

  The optimal treatment of locally advanced non-small-cell lung cancer (NSCLC) remains controversial. We hypothesized that using a trimodality approach in selected patients with stage IIIA/IIIB disease would be both feasible and efficacious with reasonable toxicity.We enrolled 13 patients with resectable stage III NSCLC on a prospective phase II trial of trimodality therapy. Induction treatment consisted of weekly docetaxel 20 mg/m(2) and weekly carboplatin at an area under curve (AUC) of 2 concurrent with 45 Gy thoracic radiotherapy. Resection was performed unless felt to be unsafe or if patients had progressive disease. Postoperative consolidation consisted of docetaxel 75 mg/m(2) and carboplatin at an AUC of 6 every 3 weeks for 3 cycles with growth factor support.All patients responded to induction chemoradiotherapy as measured by total gross tumor volume reductions of 43% on average (range, 27%-64%). Twelve patients underwent resection of the tumor and involved nodes, yielding a resectability rate of 92%. The primary endpoint of 2-year overall survival (OS) was 72% (95% confidence interval [CI], 36%-90%), and 2-year progression-free survival (PFS) was 36% (95% CI, 9%-64%). The maximal toxicity observed per patient was grade II in 5 patients (38%); grade III in 7 patients (54%); grade IV in 1 patient (8%); and grade V in none.This trimodality approach resulted in promising outcomes with reasonable toxicity in carefully selected patients with stage III NSCLC at a single institution.

  View details for DOI 10.1016/j.cllc.2011.06.003

  View details for Web of Science ID 000294600800003

  View details for PubMedID 21752720

• HIGH RETENTION AND SAFETY OF PERCUTANEOUSLY IMPLANTED ENDOVASCULAR EMBOLIZATION COILS AS FIDUCIAL MARKERS FOR IMAGE-GUIDED STEREOTACTIC ABLATIVE RADIOTHERAPY OF PULMONARY TUMORS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hong, J. C., Yu, Y., Rao, A. K., Ditererich, S., Maxim, P. G., Le, Q., Diehn, M., Sze, D. Y., Kothary, N., Loo, B. W. 2011; 81 (1): 85-90

  Abstract

  To compare the retention rates of two types of implanted fiducial markers for stereotactic ablative radiotherapy (SABR) of pulmonary tumors, smooth cylindrical gold "seed" markers ("seeds") and platinum endovascular embolization coils ("coils"), and to compare the complication rates associated with the respective implantation procedures.We retrospectively analyzed the retention of percutaneously implanted markers in 54 consecutive patients between January 2004 and June 2009. A total of 270 markers (129 seeds, 141 coils) were implanted in or around 60 pulmonary tumors over 59 procedures. Markers were implanted using a percutaneous approach under computed tomography (CT) guidance. Postimplantation and follow-up imaging studies were analyzed to score marker retention relative to the number of markers implanted. Markers remaining near the tumor were scored as retained. Markers in a distant location (e.g., pleural space) were scored as lost. CT imaging artifacts near markers were quantified on radiation therapy planning scans.Immediately after implantation, 140 of 141 coils (99.3%) were retained, compared to 110 of 129 seeds (85.3%); the difference was highly significant (p<0.0001). Of the total number of lost markers, 45% were reported lost during implantation, but 55% were lost immediately afterwards. No additional markers were lost on longer-term follow-up. Implanted lesions were peripherally located for both seeds (mean distance, 0.33 cm from pleural surface) and coils (0.34 cm) (p=0.96). Incidences of all pneumothorax (including asymptomatic) and pneumothorax requiring chest tube placement were lower in implantation of coils (23% and 3%, respectively) vs. seeds (54% and 29%, respectively; p=0.02 and 0.01). The degree of CT artifact was similar between marker types.Retention of CT-guided percutaneously implanted coils is significantly better than that of seed markers. Furthermore, implanting coils is at least as safe as implanting seeds. Using coils should permit implantation of fewer markers and require fewer repeat implantation procedures owing to lost markers.

  View details for DOI 10.1016/j.ijrobp.2010.04.037

  View details for Web of Science ID 000294093300012

  View details for PubMedID 20675070

• INTENSITY-MODULATED RADIOTHERAPY FOR ORAL CAVITY SQUAMOUS CELL CARCINOMA: PATTERNS OF FAILURE AND PREDICTORS OF LOCAL CONTROL INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Quynh-Thu Le, Q. T., Kozak, M. M., Maxim, P. G., Murphy, J. D., Hsu, A., Loo, B. W., Kaplan, M. J., Fischbein, N. J., Chang, D. T. 2011; 80 (5): 1412-1422

  Abstract

  Few studies have evaluated the use of intensity-modulated radiotherapy (IMRT) for squamous cell carcinoma (SCC) of the oral cavity (OC). We report clinical outcomes and failure patterns for these patients.Between October 2002 and June 2009, 37 patients with newly diagnosed SCC of the OC underwent postoperative (30) or definitive (7) IMRT. Twenty-five patients (66%) received systemic therapy. The median follow-up was 38 months (range, 10-87 months). The median interval from surgery to RT was 5.9 weeks (range, 2.1-10.7 weeks).Thirteen patients experienced local-regional failure at a median of 8.1 months (range, 2.4-31.9 months), and 2 additional patients experienced local recurrence between surgery and RT. Seven local failures occurred in-field (one with simultaneous nodal and distant disease) and two at the margin. Four regional failures occurred, two in-field and two out-of-field, one with synchronous metastases. Six patients experienced distant failure. The 3-year actuarial estimates of local control, local-regional control, freedom from distant metastasis, and overall survival were 67%, 53%, 81%, and 60% among postoperative patients, respectively, and 60%, 60%, 71%, and 57% among definitive patients. Four patients developed Grade ≥ 2 chronic toxicity. Increased surgery to RT interval predicted for decreased LRC (p = 0.04).Local-regional control for SCC of the OC treated with IMRT with or without surgery remains unsatisfactory. Definitive and postoperative IMRT have favorable toxicity profiles. A surgery-to-RT interval of < 6 weeks improves local-regional control. The predominant failure pattern was local, suggesting that both improvements in target delineation and radiosensitization and/or dose escalation are needed.

  View details for DOI 10.1016/j.ijrobp.2010.04.031

  View details for Web of Science ID 000293207600020

  View details for PubMedID 20675073

• IN REGARD TO BROWN ET AL. (INT J RADIAT ONCOL BIOL PHYS 2010;78:323-327) REPLY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Brown, J. M., Loo, B. W., Diehn, M., Carlson, D. J. 2011; 80 (5): 1605-1605

  View details for DOI 10.1016/j.ijrobp.2011.03.032

  View details for Web of Science ID 000293207600049

• POSTRADIATION METABOLIC TUMOR VOLUME PREDICTS OUTCOME IN HEAD-AND-NECK CANCER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Murphy, J. D., La, T. H., Chu, K., Quon, A., Fischbein, N. J., Maxim, P. G., Graves, E. E., Loo, B. W., Le, Q. 2011; 80 (2): 514-521

  Abstract

  To explore the prognostic value of metabolic tumor volume measured on postradiation (18)F-fluorodeoxyglucose positron emission tomography (PET) imaging in patients with head-and-neck cancer.Forty-seven patients with head-and-neck cancer who received pretreatment and posttreatment PET/computed tomography (CT) imaging along with definitive chemoradiotherapy were included in this study. The PET/CT parameters evaluated include the maximum standardized uptake value, metabolic tumor volume (MTV(2.0)-MTV(4.0); where MTV(2.0) refers to the volume above a standardized uptake value threshold of 2.0), and integrated tumor volume. Kaplan-Meier and Cox regression models were used to test for association between PET endpoints and disease-free survival and overall survival.Multiple postradiation PET endpoints correlated significantly with outcome; however, the most robust predictor of disease progression and death was MTV(2.0). An increase in MTV(2.0) of 21 cm(3) (difference between 75th and 25th percentiles) was associated with an increased risk of disease progression (hazard ratio [HR] = 2.5, p = 0.0001) and death (HR = 2.0, p = 0.003). In patients with nonnasopharyngeal carcinoma histology (n = 34), MTV(2.0) <18 cm(3) and MTV(2.0) ≥18 cm(3) yielded 2-year disease-free survival rates of 100% and 63%, respectively (p = 0.006) and 2-year overall survival rates of 100% and 81%, respectively (p = 0.009). There was no correlation between MTV(2.0) and disease-free survival or overall survival with nasopharyngeal carcinoma histology (n = 13). On multivariate analysis, only postradiation MTV(2.0) was predictive of disease-free survival (HR = 2.47, p = 0.0001) and overall survival (HR = 1.98, p = 0.003).Postradiation metabolic tumor volume is an adverse prognostic factor in head-and-neck cancer. Biomarkers such as MTV are important for risk stratification and will be valuable in the future with risk-adapted therapies.

  View details for DOI 10.1016/j.ijrobp.2010.01.057

  View details for Web of Science ID 000290837100028

  View details for PubMedID 20646870

• Tumor Volume as a Potential Imaging-Based Risk-Stratification Factor in Trimodality Therapy for Locally Advanced Non-small Cell Lung Cancer JOURNAL OF THORACIC ONCOLOGY Kozak, M. M., Murphy, J. D., Schipper, M. L., Donington, J. S., Zhou, L., Whyte, R. I., Shrager, J. B., Hoang, C. D., Bazan, J., Maxim, P. G., Graves, E. E., Diehn, M., Hara, W. Y., Quon, A., Quynh-Thu Le, Q. T., Wakelee, H. A., Loo, B. W. 2011; 6 (5): 920-926

  Abstract

  The role of trimodality therapy for locally advanced non-small cell lung cancer (NSCLC) continues to be defined. We hypothesized that imaging parameters on pre- and postradiation positron emission tomography (PET)-computed tomography (CT) imaging are prognostic for outcome after preoperative chemoradiotherapy (CRT)/resection/consolidation chemotherapy and could help risk-stratify patients in clinical trials.We enrolled 13 patients on a prospective clinical trial of trimodality therapy for resectable locally advanced NSCLC. PET-CT was acquired for radiation planning and after 45 Gy. Gross tumor volume (GTV) and standardized uptake value were measured at pre- and post-CRT time points and correlated with nodal pathologic complete response, loco-regional and/or distant progression, and overall survival. In addition, we evaluated the performance of automatic deformable image registration (ADIR) software for volumetric response assessment.All patients responded with average total GTV reductions after 45 Gy of 43% (range: 27-64%). Pre- and post-CRT GTVs were highly correlated (R² = 0.9), and their respective median values divided the patients into the same two groups. ADIR measurements agreed closely with manually segmented post-CRT GTVs. Patients with GTV ≥ median (137 ml pre-CRT and 67 ml post-CRT) had 3-year progression-free survival (PFS) of 14% versus 75% for GTV less than median, a significant difference (p = 0.049). Pre- and post-CRT PET-standardized uptake value did not correlate significantly with pathologic complete response, PFS, or overall survival.Preoperative CRT with carboplatin/docetaxel/45 Gy resulted in excellent response rates. In this exploratory analysis, pre- and post-CRT GTV predicted PFS in trimodality therapy, consistent with our earlier studies in a broader cohort of NSCLC. ADIR seems robust enough for volumetric response assessment in clinical trials.

  View details for DOI 10.1097/JTO.0b013e31821517db

  View details for Web of Science ID 000289554100012

  View details for PubMedID 21774104

• Reducing 4D CT artifacts using optimized sorting based on anatomic similarity MEDICAL PHYSICS Johnston, E., Diehn, M., Murphy, J. D., Loo, B. W., Maxim, P. G. 2011; 38 (5): 2424-2429

  Abstract

  Four-dimensional (4D) computed tomography (CT) has been widely used as a tool to characterize respiratory motion in radiotherapy. The two most commonly used 4D CT algorithms sort images by the associated respiratory phase or displacement into a predefined number of bins, and are prone to image artifacts at transitions between bed positions. The purpose of this work is to demonstrate a method of reducing motion artifacts in 4D CT by incorporating anatomic similarity into phase or displacement based sorting protocols.Ten patient datasets were retrospectively sorted using both the displacement and phase based sorting algorithms. Conventional sorting methods allow selection of only the nearest-neighbor image in time or displacement within each bin. In our method, for each bed position either the displacement or the phase defines the center of a bin range about which several candidate images are selected. The two dimensional correlation coefficients between slices bordering the interface between adjacent couch positions are then calculated for all candidate pairings. Two slices have a high correlation if they are anatomically similar. Candidates from each bin are then selected to maximize the slice correlation over the entire data set using the Dijkstra's shortest path algorithm. To assess the reduction of artifacts, two thoracic radiation oncologists independently compared the resorted 4D datasets pairwise with conventionally sorted datasets, blinded to the sorting method, to choose which had the least motion artifacts. Agreement between reviewers was evaluated using the weighted kappa score.Anatomically based image selection resulted in 4D CT datasets with significantly reduced motion artifacts with both displacement (P = 0.0063) and phase sorting (P = 0.00022). There was good agreement between the two reviewers, with complete agreement 34 times and complete disagreement 6 times.Optimized sorting using anatomic similarity significantly reduces 4D CT motion artifacts compared to conventional phase or displacement based sorting. This improved sorting algorithm is a straightforward extension of the two most common 4D CT sorting algorithms.

  View details for DOI 10.1118/1.3577601

  View details for Web of Science ID 000290625700016

  View details for PubMedID 21776777

• Investigation of four-dimensional computed tomography-based pulmonary ventilation imaging in patients with emphysematous lung regions PHYSICS IN MEDICINE AND BIOLOGY Yamamoto, T., Kabus, S., Klinder, T., Lorenz, C., von Berg, J., Blaffert, T., Loo, B. W., Keall, P. J. 2011; 56 (7): 2279-2298

  Abstract

  A pulmonary ventilation imaging technique based on four-dimensional (4D) computed tomography (CT) has advantages over existing techniques. However, physiologically accurate 4D-CT ventilation imaging has not been achieved in patients. The purpose of this study was to evaluate 4D-CT ventilation imaging by correlating ventilation with emphysema. Emphysematous lung regions are less ventilated and can be used as surrogates for low ventilation. We tested the hypothesis: 4D-CT ventilation in emphysematous lung regions is significantly lower than in non-emphysematous regions. Four-dimensional CT ventilation images were created for 12 patients with emphysematous lung regions as observed on CT, using a total of four combinations of two deformable image registration (DIR) algorithms: surface-based (DIR(sur)) and volumetric (DIR(vol)), and two metrics: Hounsfield unit (HU) change (V(HU)) and Jacobian determinant of deformation (V(Jac)), yielding four ventilation image sets per patient. Emphysematous lung regions were detected by density masking. We tested our hypothesis using the one-tailed t-test. Visually, different DIR algorithms and metrics yielded spatially variant 4D-CT ventilation images. The mean ventilation values in emphysematous lung regions were consistently lower than in non-emphysematous regions for all the combinations of DIR algorithms and metrics. V(HU) resulted in statistically significant differences for both DIR(sur) (0.14 ± 0.14 versus 0.29 ± 0.16, p = 0.01) and DIR(vol) (0.13 ± 0.13 versus 0.27 ± 0.15, p < 0.01). However, V(Jac) resulted in non-significant differences for both DIR(sur) (0.15 ± 0.07 versus 0.17 ± 0.08, p = 0.20) and DIR(vol) (0.17 ± 0.08 versus 0.19 ± 0.09, p = 0.30). This study demonstrated the strong correlation between the HU-based 4D-CT ventilation and emphysema, which indicates the potential for HU-based 4D-CT ventilation imaging to achieve high physiologic accuracy. A further study is needed to confirm these results.

  View details for DOI 10.1088/0031-9155/56/7/023

  View details for Web of Science ID 000288506600026

  View details for PubMedID 21411868

• HYPOFRACTIONATION RESULTS IN REDUCED TUMOR CELL KILL COMPARED TO CONVENTIONAL FRACTIONATION FOR TUMORS WITH REGIONS OF HYPOXIA INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Carlson, D. J., Keall, P. J., Loo, B. W., Chen, Z. J., Brown, J. M. 2011; 79 (4): 1188-1195

  Abstract

  Tumor hypoxia has been observed in many human cancers and is associated with treatment failure in radiation therapy. The purpose of this study is to quantify the effect of different radiation fractionation schemes on tumor cell killing, assuming a realistic distribution of tumor oxygenation.A probability density function for the partial pressure of oxygen in a tumor cell population is quantified as a function of radial distance from the capillary wall. Corresponding hypoxia reduction factors for cell killing are determined. The surviving fraction of a tumor consisting of maximally resistant cells, cells at intermediate levels of hypoxia, and normoxic cells is calculated as a function of dose per fraction for an equivalent tumor biological effective dose under normoxic conditions.Increasing hypoxia as a function of distance from blood vessels results in a decrease in tumor cell killing for a typical radiotherapy fractionation scheme by a factor of 10(5) over a distance of 130 μm. For head-and-neck cancer and prostate cancer, the fraction of tumor clonogens killed over a full treatment course decreases by up to a factor of ∼10(3) as the dose per fraction is increased from 2 to 24 Gy and from 2 to 18 Gy, respectively.Hypofractionation of a radiotherapy regimen can result in a significant decrease in tumor cell killing compared to standard fractionation as a result of tumor hypoxia. There is a potential for large errors when calculating alternate fractionations using formalisms that do not account for tumor hypoxia.

  View details for DOI 10.1016/j.ijrobp.2010.10.007

  View details for Web of Science ID 000288471500031

  View details for PubMedID 21183291

• Four-dimensional computed tomography pulmonary ventilation images vary with deformable image registration algorithms and metrics MEDICAL PHYSICS Yamamoto, T., Kabus, S., Klinder, T., von Berg, J., Lorenz, C., Loo, B. W., Keall, P. J. 2011; 38 (3): 1348-1358

  Abstract

  A novel pulmonary ventilation imaging technique based on four-dimensional (4D) CT has advantages over existing techniques and could be used for functional avoidance in radiotherapy. There are various deformable image registration (DIR) algorithms and two classes of ventilation metric that can be used for 4D-CT ventilation imaging, each yielding different images. The purpose of this study was to quantify the variability of the 4D-CT ventilation to DIR algorithms and metrics.4D-CT ventilation images were created for 12 patients using different combinations of two DIR algorithms, volumetric (DIR(vol)) and surface-based (DIR(sur)), yielding two displacement vector fields (DVFs) per patient (DVF(voI) and DVF(sur)), and two metrics, Hounsfield unit (HU) change (V(HU)) and Jacobian determinant of deformation (V(Jac)), yielding four ventilation image sets (V(HU)(vol), V(HU)(sur), V(Jac)(voI), and V(Jac)(sur). First DVF(vol) and DVF(sur) were compared visually and quantitatively to the length of 3D displacement vector difference. Second, four ventilation images were compared based on voxel-based Spearman's rank correlation coefficients and coefficients of variation as a measure of spatial heterogeneity. V(HU)(vol) was chosen as the reference for the comparison.The mean length of 3D vector difference between DVF(vol) and DVF(sur) was 2.0 +/- 1.1 mm on average, which was smaller than the voxel dimension of the image set and the variations. Visually, the reference V(HU)(vol) demonstrated similar regional distributions with V(HU)(sur); the reference, however, was markedly different from V(Jac)(vol) and V((Jac)(sur). The correlation coefficients of V(HU)(vol) with V(HU)(sur), V(Jac)(vol) and V(Jac)(sur) were 0.77 +/- 0.06, 0.25 +/- 0.06 and 0.15 +/- 0.07, respectively, indicating that the metric introduced larger variations in the ventilation images than the DIR algorithm. The spatial heterogeneities for V(HU)(vol), 'V(HU)(sur), V(Jac)(vol), and V(Jac)(sur) were 1.8 +/- 1.6, 1.8 +/- 1.5 (p = 0. 85), 0.6 +/- 0.2 (p = 0.02), and 0.7 +/- 0.2 (p = 0.03), respectively, also demonstrating that the metric introduced larger variations.4D-CT pulmonary ventilation images vary widely with DIR algorithms and metrics. Careful physiologic validation to determine the appropriate DIR algorithm and metric is needed prior to its applications.

  View details for DOI 10.1118/1.3547719

  View details for Web of Science ID 000287879400022

  View details for PubMedID 21520845

• Stereotactic ablative radiotherapy: what's in a name? Practical Radiation Oncology BW Loo Jr, JY Chang, LA Dawson, BD Kavanagh, AC Koong, S Senan, RD Timmerman 2011; 1 (1): 38-39
• Volume Doubling Times and Outcomes in Stereotactic Ablative Radiotherapy of Early-stage Non-small Cell Lung Cancer Chung, M. P., Trakul, N., Le, Q., Hara, W. Y., Dieterich, S., Maxim, P. G., Diehn, M., Loo, B. W. ELSEVIER SCIENCE INC. 2011: S592–S592

  View details for Web of Science ID 000296411701294

• Analysis of Migration of Implanted Markers for Image-Guided Lung Tumor Stereotactic Ablative Radiotherapy Hong, J. C., Eclov, N. C., Yu, Y., Rao, A. K., Dieterich, S., Maxim, P. G., Le, Q., Diehn, M., Kothary, N., Loo, B. W. ELSEVIER SCIENCE INC. 2011: S580–S581

  View details for Web of Science ID 000296411701270

• Stereotactic Ablative Radiotherapy for Previously Irradiated Lung Tumors Trakul, N., Harris, J. P., Le, Q., Hara, W. Y., Maxim, P. G., Loo, B. W., Diehn, M. ELSEVIER SCIENCE INC. 2011: S605–S605

  View details for Web of Science ID 000296411701321

• Targeting Lung Tumors in Image-Guided Stereotactic Ablative Radiotherapy using Pulmonary Interstitial Lymphography Abelson, J. A., Kothary, N., Fleischmann, D., Hofmann, L., Kielar, K. N., Maxim, P. G., Le, Q., Hara, W. Y., Diehn, M., Loo, B. W. ELSEVIER SCIENCE INC. 2011: S601–S601

  View details for Web of Science ID 000296411701313

• Changes in FDG-PET/CT Parameters on Serial Pre-radiotherapy Scans Predict Disease Progression and Survival in Patients with Non-small Cell Lung Cancer Bazan, J. G., Chung, M. P., Eastham, D. V., Wakelee, H., Hara, W. Y., Maxim, P. G., Graves, E., Le, Q. T., Diehn, M., Loo, B. W. ELSEVIER SCIENCE INC. 2011: S579–S580

  View details for Web of Science ID 000296411701268

• PET imaging of cerebral ischemia-induced neuroinflammation in mice using F-18-PBR06 Lartey, F. M., Ahn, G., Shen, B., Cord, K., Smith, T., Chua, J. Y., Rosenblum, S., Tirouvanziam, R., Palmer, T., Guzman, R., Chin, F. T., Graves, E., Loo, B. W. WILEY-BLACKWELL. 2011: S319–S319

  View details for Web of Science ID 000295901600319

• Motion Management and Image Guidance for Thoracic Tumor Radiotherapy: Clinical Treatment Programs IMRT IGRT SBRT- ADVANCES IN THE TREATMENT PLANNING AND DELIVERY OF RADIOTHERAPY Loo, B. W., Kavanagh, B. D., Meyer, J. L. 2011; 43: 271-291

  Abstract

  Managing target motion first requires understanding the nature of the motion characteristic of the tumor in the individual patient. It is important to have effective immobilization and patient training strategies to help reduce motion, and then to design appropriate margins and compensation for the residual motion that is quantified. Especially when considering complex, technically demanding treatments that require a degree of patient cooperation, careful patient selection is needed to ensure that the potential benefits of the treatment design are actually realized. Finally, accurate treatment hinges critically on verification - of overall positioning, of target and organ motion at the time of treatment, and of the performance of the selected treatment strategy. Properly selected imaging methods are central to this verification process. This discussion will present practical solutions for motion management and image guidance of radiotherapy for thoracic tumors, and most of these concepts are widely applicable to treatment of other tumor sites as well.

  View details for Web of Science ID 000292117400013

  View details for PubMedID 21625158

• INTENSITY-MODULATED RADIOTHERAPY FOR LOCALLY ADVANCED CANCERS OF THE LARYNX AND HYPOPHARYNX HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Daly, M. E., Le, Q., Jain, A. K., Maxim, P. G., Hsu, A., Loo, B. W., Kaplan, M. J., Fischbein, N. J., Colevas, A. D., Pinto, H., Chang, D. T. 2011; 33 (1): 103-111

  Abstract

  Limited data evaluate intensity-modulated radiotherapy (IMRT) for cancers of the hypopharynx and larynx. We report clinical outcomes and failure patterns for these patients.Between September 2001 and December 2007, 42 patients with squamous cell carcinoma (SCC) of the hypopharynx (n = 23) and larynx (n = 19) underwent IMRT, 11 postoperatively and 31 definitively. Thirty-six received systemic therapy. Median follow-up was 30 months among surviving patients.Three local failures occurred within the high-dose region and 3 occurred in regional nodes. Seven patients developed distant metastasis as the initial failure. Three-year actuarial estimates of locoregional control, freedom from distant metastasis, and overall survival rates were, respectively, 80%, 72%, and 46%.IMRT provides good locoregional control for SCC of the hypopharynx and larynx compared with historical controls. Locoregional relapses occurred in the high-dose volumes, suggesting adequate target volume delineation. Hypopharyngeal tumors, which fare worse than laryngeal tumors, warrant investigation of more aggressive treatment.

  View details for DOI 10.1002/hed.21406

  View details for Web of Science ID 000286290400017

  View details for PubMedID 20848427

• CyberKnife Stereotactic Ablative Radiotherapy for Lung Tumors TECHNOLOGY IN CANCER RESEARCH & TREATMENT Gibbs, I. C., Loo, B. W. 2010; 9 (6): 589-596

  Abstract

  Stereotactic ablative radiotherapy (SABR) has emerged as a promising treatment for early stage non-small cell lung cancer, particularly for patients unable to tolerate surgical resection. High rates of local tumor control have been demonstrated with acceptable toxicity and the practical advantage of a short course of treatment. The CyberKnife image-guided robotic radiosurgery system has unique technical characteristics that make it well suited for SABR of tumors that move with breathing, including lung tumors. We review the qualities of the CyberKnife platform for lung tumor SABR, and provide a summary of clinical data using this system specifically.

  View details for Web of Science ID 000284971100007

  View details for PubMedID 21070081

• STEREOTACTIC ABLATIVE RADIOTHERAPY SHOULD BE COMBINED WITH A HYPOXIC CELL RADIOSENSITIZER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Brown, J. M., Diehn, M., Loo, B. W. 2010; 78 (2): 323-327

  Abstract

  To evaluate the effect of tumor hypoxia on the expected level of cell killing by regimens of stereotactic ablative radiotherapy (SABR) and to determine the extent to which the negative effect of hypoxia could be prevented using a clinically available hypoxic cell radiosensitizer.We have calculated the expected level of tumor cell killing from regimens of SABR, both with and without the assumption that 20% of the tumor cells are hypoxic, using the standard linear quadratic model and the universal survival curve modification. We compare the results obtained with our own clinical data for lung tumors of different sizes and with published data from other studies. We also have calculated the expected effect on cell survival of adding the hypoxic cell sensitizer etanidazole at clinically achievable drug concentrations. Modeling tumor cell killing with any of the currently used regimens of SABR produces results that are inconsistent with the majority of clinical findings if tumor hypoxia is not considered. However, with the assumption of tumor hypoxia, the expected level of cell killing is consistent with clinical data. For only some of the smallest tumors are the clinical data consistent with no tumor hypoxia, but there could be other reasons for the sensitivity of these tumors. The addition of etanidazole at clinically achievable tumor concentrations produces a large increase in the expected level of tumor cell killing from the large radiation doses used in SABR.The presence of tumor hypoxia is a major negative factor in limiting the curability of tumors by SABR at radiation doses that are tolerable to surrounding normal tissues. However, this negative effect of hypoxia could be overcome by the addition of clinically tolerable doses of the hypoxic cell radiosensitizer etanidazole.

  View details for DOI 10.1016/j.ijrobp.2010.04.070

  View details for Web of Science ID 000282147000002

  View details for PubMedID 20832663

• Alternatives to Surgery for Early Stage Non-Small Cell Lung Cancer-Ready for Prime Time? CURRENT TREATMENT OPTIONS IN ONCOLOGY Das, M., Abdelmaksoud, M. H., Loo, B. W., Kothary, N. 2010; 11 (1-2): 24-35

  Abstract

  Surgery is the standard of care for early stage non-small cell lung cancer (NSCLC), with lobectomy being the most oncologically sound resection. Medically inoperable patients and high-risk surgical candidates require effective alternatives to surgery; even operable patients may opt for less invasive options if they are proven to achieve similar outcomes to surgery. Minimally invasive local treatment modalities including dose-intensified conformal radiation therapy, most notably stereotactic ablative radiotherapy (SABR; also known as stereotactic body radiation therapy), and thermal ablation methods such as radiofrequency ablation (RFA) and microwave ablation (MWA) are emerging as promising treatment options whose roles in the treatment of early stage lung cancer are being defined. Early clinical experience and a rapidly growing body of prospective clinical trials, primarily in medically inoperable patients, are demonstrating encouraging effectiveness and safety outcomes in some cases approaching historical results with surgery. Given the very poor prognosis of the medically inoperable patient population, these alternatives to surgery, particularly SABR, are starting to be considered appropriate first-line therapy in properly selected patients, and prospective cooperative group trials to evaluate and optimize RFA and SABR in specific patient subsets are being conducted. For operable patients, prospective multi-center and cooperative groups trials of SABR are ongoing or completed, and international randomized trials of SABR vs. surgery have been initiated. Thus, promising alternatives to surgery for early stage NSCLC are ready for prime time evaluation in the setting of clinical trials, and participation in ongoing trials for both operable and medically inoperable patients is strongly encouraged.

  View details for DOI 10.1007/s11864-010-0119-z

  View details for Web of Science ID 000281247200003

  View details for PubMedID 20577833

• Stereotactic body radiation therapy (stereotactic ablative radiotherapy) for stage I non-small cell lung cancer--updates of radiobiology, techniques, and clinical outcomes. Discovery medicine Hadziahmetovic, M., Loo, B. W., Timmerman, R. D., Mayr, N. A., Wang, J. Z., Huang, Z., Grecula, J. C., Lo, S. S. 2010; 9 (48): 411-417

  Abstract

  Stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), has emerged as one of the standard treatment options for stage I non-small cell lung cancer (NSCLC), mainly in medically inoperable patients. Its use has also been explored in operable patients. A large body of experience, either from retrospective studies or clinical trials, has been accumulated over the years and more is known about the radiobiology, cancer biology, technical aspects, clinical outcomes, and toxicities of SBRT. This article provides updates of these aspects of SBRT for stage I NSCLC.

  View details for PubMedID 20515609

• INTENSITY-MODULATED RADIOTHERAPY IN THE TREATMENT OF OROPHARYNGEAL CANCER: CLINICAL OUTCOMES AND PATTERNS OF FAILURE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Le, Q., Maxim, P. G., Loo, B. W., Kaplan, M. J., Fischbein, N. J., Pinto, H., Chang, D. T. 2010; 76 (5): 1339-1346

  Abstract

  To report outcomes, failures, and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for squamous cell carcinoma of the oropharynx.Between Aug 2001 and Oct 2007, 107 patients were treated with IMRT with curative intent at Stanford University. Twenty-two patients were treated postoperatively, and 85 were treated definitively. Concurrent platinum-based chemotherapy was administered to 86 patients (80%) and cetuximab to 8 patients (7%). The prescribed dose was 66 Gy at 2.2 Gy/fraction for definitively treated cases and 60 Gy at 2 Gy/fraction for postoperative cases. Median follow-up was 29 months among surviving patients (range, 4-105 months).Eight patients had persistent disease or local-regional failure at a median of 6.5 months (range, 0-9.9 months). Six local failures occurred entirely within the high-risk clinical target volume (CTV) (one with simultaneous distant metastasis). One patient relapsed within the high- and intermediate-risk CTV. One patient had a recurrence at the junction between the IMRT and low-neck fields. Seven patients developed distant metastasis as the first site of failure. The 3-year local-regional control (LRC), freedom from distant metastasis, overall survival, and disease-free survival rates were 92%, 92%, 83%, and 81%, respectively. T stage (T4 vs. T1-T3) was predictive of poorer LRC (p = 0.001), overall survival (p = 0.001), and disease-free survival (p < 0.001) rates. Acute toxicity consisted of 58% grade 3 mucosal and 5% grade 3 skin reactions. Six patients (6%) developed grade >or=3 late complications.IMRT provides excellent LRC for oropharyngeal squamous cell carcinoma. Distant metastases are a major failure pattern. No marginal failures were observed.

  View details for DOI 10.1016/j.ijrobp.2009.04.006

  View details for Web of Science ID 000276675300012

  View details for PubMedID 19540068

• High Retention and Safety of Percutaneously Implanted Endovascular Embolization Coils as Fiducial Markers for Image-guided Stereotactic Ablative Radiotherapy of Pulmonary Tumors 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Hong, J. C., Yu, Y., Rao, A. K., Dieterich, S., Maxim, P. G., Le, Q. T., Diehn, M., Sze, D. Y., Kothary, N., Loo, B. W. ELSEVIER SCIENCE INC. 2010: S518–S519

  View details for Web of Science ID 000288775701202

• Mid-treatment Metabolic Tumor Volume Predicts Progression and Death among Patients with Hodgkin's Disease 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Tseng, D., Rachakonda, L. P., Su, Z., Advani, R., Horning, S., Rosenberg, S. A., Hoppe, R. T., Quon, A., Graves, E. E., Loo, B. W., Tran, P. T. ELSEVIER SCIENCE INC. 2010: S546–S547

  View details for Web of Science ID 000288775701265

• Prognostic Value of Metabolic Tumor Volume and Velocity in Predicting Head and Neck Cancer Outcomes 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Chu, K. P., Murphy, J., La, T. H., Loo, B. W., Krakow, T. E., Hsu, A., Maxim, P. G., Graves, E., Chang, D., Le, Q. ELSEVIER SCIENCE INC. 2010: S460–S460

  View details for Web of Science ID 000288775701074

• Clinical Management of Patients with Temporal Lobe Necrosis 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Krakow, T. E., Hara, W., Yun, S., Soltys, S., Chang, S., Fischbein, N., Loo, B., Le, Q. ELSEVIER SCIENCE INC. 2010: S455–S455

  View details for Web of Science ID 000288775701063

• Definitive Radiotherapy for New Primary Tumors in the Lung: The Benefit of the Doubt 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Jones, J. C., Trakul, N., Hara, W., Abelson, J. A., Maxim, P., Dieterich, S., Le, Q., Diehn, M., Loo, B. W. ELSEVIER SCIENCE INC. 2010: S500–S500

  View details for Web of Science ID 000288775701162

• Volume Adapted Dosing in Stereotactic Ablative Radiotherapy of Lung Tumors 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Trakul, N., Harris, J., Dieterich, S., Maxim, P., Le, Q., Loo, B. W., Diehn, M. ELSEVIER SCIENCE INC. 2010: S179–S179

  View details for Web of Science ID 000288775700383

• Can Temporal Lobe Necrosis be Prevented in Patients with Nasopharyngeal/Skull Base Tumors Undergoing a Stereotactic Radiosurgery Boost? A Dose Volume Analysis 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Hara, W., Yun, S., Hsu, A., Soltys, S., Adler, J., Le, Q., Loo, B. W. ELSEVIER SCIENCE INC. 2010: S431–S431

  View details for Web of Science ID 000288775701011

• Marked Tumor Response and Fatal Hemoptysis During Radiation for Lung Cancer in a Human Immunodeficiency Virus-Positive Patient Taking Nelfinavir JOURNAL OF THORACIC ONCOLOGY Chapman, C. H., Shen, J., Filion, E. J., Tran, P. T., Hara, W., Asuncion, A., Marko, D., Wakelee, H., Berry, G. J., Dimmick, K. W., Loo, B. W., Green, J. 2009; 4 (12): 1587-1589

  View details for Web of Science ID 000272095500025

  View details for PubMedID 20009915

• Re: "The safety and efficacy of robotic image-guided radiosurgery system treatment for intra- and extracranial lesions: A systematic review of the literature" [Radiotherapy and Oncology 89 (2009) 245-253] RADIOTHERAPY AND ONCOLOGY Gibbs, I. C., Levendag, P. C., Fariselli, L., Bondiau, P., Lartigau, E., Loo, B. W., Gagnon, G. J., Koong, A. 2009; 93 (3): 656-657

  View details for DOI 10.1016/j.radonc.2009.08.024

  View details for Web of Science ID 000272762900048

  View details for PubMedID 19748142

• Cooperative Group Research Efforts in Thoracic Malignancies 2009: A Review From the 10th Annual International Lung Cancer Congress CLINICAL LUNG CANCER Wakelee, H., Loo, B. W., Kernstine, K. H., Putnam, J. B., Edelman, M. J., Vokes, E. E., Schiller, J. H., Baas, P., Saijo, N., Adjei, A., Goss, G., Choy, H., Gandara, D. R. 2009; 10 (6): 395-404

  Abstract

  Critical advances in the treatment of patients with lung cancer have occurred in the past few years. The cooperative groups in North America and internationally have played crucial roles in these advances. The leaders of the groups meet on a regular basis to review the progress of their trials. However, they rarely have a chance to discuss all ongoing and planned trials, except at the annual Lung Cancer Congress held each June. This article captures this exchange from the 10th Annual Lung Cancer Congress held in June 2009. Exciting efforts are ongoing for all stages of non-small-cell lung cancer, small-cell lung cancer, and mesothelioma. A major focus of the groups at this time is a push toward more personalized medicine, as reflected in the selection criteria for many of the trials, along with planned correlates to better define populations most likely to benefit. Agents targeting the vascular endothelial growth factor (VEGF) pathway, including many tyrosine kinase inhibitors against the VEGF receptor, and those targeting the epidermal growth factor receptor pathway, are under extensive development with many combination trials ongoing.

  View details for DOI 10.3816/CLC.2009.n.075

  View details for Web of Science ID 000271378500002

  View details for PubMedID 19900856

• Quantification of pre-treatment metabolic tumor growth rate in lung cancer Eastham, D., Chapman, C. H., Rao, A. K., Balasubramanian, N., Quon, A., Vasanawala, M. S., Wakelee, H., Le, Q., Colevas, D. A., Maxim, P. A., Graves, E., Loo, B. W. LIPPINCOTT WILLIAMS & WILKINS. 2009: S733–S733

  View details for Web of Science ID 000269496002262

• Mid-treatment PET predicts progression in hypofractionated accelerated radiation therapy for lung tumors Chang, C. N., Fillion, E., Chapman, C., Rao, A., Wakelee, H., Ganjoo, K., Le, Q., Maxim, P., Quon, A., Graves, E. E., Loo, B. W. LIPPINCOTT WILLIAMS & WILKINS. 2009: S939–S939

  View details for Web of Science ID 000269496002721

• Excellent early local control with tumor volume adapted dosing of stereotactic body radiation therapy for pulmonary tumors Chang, C. N., Zhou, L. Y., MacFarlane, G., Tran, P., Rao, A., Chapman, C., Le, Q., Wakelee, H., Colevas, A. D., Whyte, R., Hristov, D., Dieterich, S., Maxim, P., Loo, B. W. LIPPINCOTT WILLIAMS & WILKINS. 2009: S938–S939

  View details for Web of Science ID 000269496002720

• METABOLIC TUMOR VOLUME PREDICTS FOR RECURRENCE AND DEATH IN HEAD-AND-NECK CANCER 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) La, T. H., Filion, E. J., Turnbull, B. B., Chu, J. N., Lee, P., Nguyen, K., Maxim, P., Quon, A., Graves, E. E., Loo, B. W., Le, Q. ELSEVIER SCIENCE INC. 2009: 1335–41

  Abstract

  To evaluate the prognostic value of metabolic tumor volume measured on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and other clinical factors in patients treated for locally advanced head-and-neck cancer (HNC) at a single institution.Between March 2003 and August 2007, 85 patients received positron emission tomography (PET)/computed tomography-guided chemoradiotherapy for HNC. Metabolically active tumor regions were delineated on pretreatment PET scans semiautomatically using custom software. We evaluated the relationship of (18)F-fluorodeoxyglucose-PET maximum standardized uptake value (SUV) and total metabolic tumor volume (MTV) with disease-free survival (DFS) and overall survival (OS).Mean follow-up for surviving patients was 20.4 months. The estimated 2-year locoregional control, DFS, and OS for the group were 88.0%, 69.5%, and 78.4%, respectively. The median time to first failure was 9.8 months among the 16 patients with relapse. An increase in MTV of 17.4 mL (difference between the 75th and 25th percentiles) was significantly associated with an increased hazard of first event (recurrence or death) (1.9-fold, p < 0.001), even after controlling for Karnofsky performance status (KPS) (1.8-fold, p = 0.001), and of death (2.1-fold, p < 0.001). We did not find a significant relationship of maximum SUV, stage, or other clinical factors with DFS or OS.Metabolic tumor volume is an adverse prognostic factor for disease recurrence and death in HNC. MTV retained significance after controlling for KPS, the only other significant adverse prognostic factor found in this cohort. MTV is a direct measure of tumor burden and is a potentially valuable tool for risk stratification and guiding treatment in future studies.

  View details for DOI 10.1016/j.ijrobp.2008.10.060

  View details for Web of Science ID 000268346100006

  View details for PubMedID 19289263

• Safety and Efficacy of Percutaneous Fiducial Marker Implantation for Image-guided Radiation Therapy JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Kothary, N., Heit, J. J., Louie, J. D., Kuo, W. T., Loo, B. W., Koong, A., Chang, D. T., Hovsepian, D., Sze, D. Y., Hofmann, L. V. 2009; 20 (2): 235-239

  Abstract

  To evaluate the safety and technical success rate of percutaneous fiducial marker implantation in preparation for image-guided radiation therapy.From January 2003 to January 2008, we retrospectively reviewed 139 percutaneous fiducial marker implantations in 132 patients. Of the 139 implantations, 44 were in the lung, 61 were in the pancreas, and 34 were in the liver. Procedure-related major and minor complications were documented. Technical success was defined as implantation enabling adequate treatment planning and computed tomographic simulation.The major and minor complication rates were 5% and 17.3%, respectively. Pneumothorax after lung implantation was the most common complication. Pneumothoraces were seen in 20 of the 44 lung implantations (45%); a chest tube was required in only seven of the 44 lung transplantations (16%). Of the 139 implantations, 133 were successful; in six implantations (4.3%) the fiducial markers migrated and required additional procedures or alternate methods of implantation.Percutaneous implantation of fiducial marker is a safe and effective procedure with risks that are similar to those of conventional percutaneous organ biopsy.

  View details for DOI 10.1016/j.jvir.2008.09.026

  View details for Web of Science ID 000263075000012

  View details for PubMedID 19019700

• Stereotactic body radiotherapy for primary and oligometastatic cancers Community Oncology MT Spiotto, BW Loo Jr, DT Chang 2009; 6 (10): 456-462
• Does Pre-treatment Metabolic Tumor Growth Rate (MTGR) Predict Progression in Lung Cancer? 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Eastham, D. V., Chapman, C. H., Rao, A. K., Narasimhan, B., Quon, A., Vasanawala, M. S., Wakelee, H., Le, Q., Colevas, A. D., Loo, B. W. ELSEVIER SCIENCE INC. 2009: S446–S446

  View details for Web of Science ID 000270573601456

• Post-Operative Radiation Therapy (PORT) in Completely Resected Non-Small-Cell Lung Cancer CURRENT TREATMENT OPTIONS IN ONCOLOGY Krupitskaya, Y., Loo, B. W. 2008; 9 (4-6): 343-356

  Abstract

  High-level evidence to guide the optimal postoperative management of patients with completely resected non-small-cell lung cancer (NSCLC) is lacking. Large randomized controlled trials have established postoperative chemotherapy as the standard of care for patients with pathologically involved lymph nodes. Recent retrospective and non-randomized studies provide evidence of the benefit of post-operative radiation therapy (PORT) in patients with mediastinal nodal involvement (N2 stage). A large multi-institutional randomized trial of PORT in this patient population is now underway. Based on currently available data, PORT may be considered for fit patients with completely resected NSCLC with N2 nodal involvement, preferably after completion of adjuvant chemotherapy. At this point, PORT is not recommended for patients with less than N2 nodal stage. Ideally, modern three-dimensional conformal radiation technique should be used, with attention to normal organ sparing, particularly lung and heart. Appropriate image guidance tools are encouraged to individualize treatment margins, account for breathing-induced motion, and minimize irradiation of normal tissues. The target volume should include at a minimum the bronchial stump, ipsilateral hilum, and involved nodal stations, and covering adjacent mediastinal nodal stations is recommended. A total dose of 50-54 Gy in 1.8-2 Gy fractions is appropriate.

  View details for DOI 10.1007/s11864-009-0090-8

  View details for Web of Science ID 000267146600010

  View details for PubMedID 19387842

• RETROSPECTIVE ANALYSIS OF ARTIFACTS IN FOUR-DIMENSIONAL CT IMAGES OF 50 ABDOMINAL AND THORACIC RADIOTHERAPY PATIENTS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Yamamoto, T., Langner, U., Loo, B. W., Shen, J., Keall, P. J. 2008; 72 (4): 1250-1258

  Abstract

  To quantify the type, frequency, and magnitude of artifacts in four-dimensional (4D) CT images acquired using a multislice cine method.Fifty consecutive patients who underwent 4D-CT scanning and radiotherapy for thoracic or abdominal cancers were included in this study. All the 4D-CT scans were performed on the GE multislice PET/CT scanner with the Varian Real-time Position Management system in cine mode. The GE Advantage 4D software was used to create 4D-CT data sets. The artifacts were then visually and quantitatively analyzed. We performed statistical analyses to evaluate the relationships between patient- or breathing-pattern-related parameters and the occurrence as well as magnitude of artifacts.It was found that 45 of 50 patients (90%) had at least one artifact (other than blurring) with a mean magnitude of 11.6 mm (range, 4.4-56.0 mm) in the diaphragm or heart. We also observed at least one artifact in 6 of 20 lung or mediastinal tumors (30%). Statistical analysis revealed that there were significant differences between several breathing-pattern-related parameters, including abdominal displacement (p < 0.01), for the subgroups of patients with and without artifacts. The magnitude of an artifact was found to be significantly but weakly correlated with the abdominal displacement difference between two adjacent couch positions (R = 0.34, p < 0.01).This study has identified that the frequency and magnitude of artifacts in 4D-CT is alarmingly high. Significant improvement is needed in 4D-CT imaging.

  View details for DOI 10.1016/j.ijrobp.2008.06.1937

  View details for Web of Science ID 000260592600040

  View details for PubMedID 18823717

• Excellent local control with stereotactic radiotherapy boost after external beam radiotherapy in patients with nasopharyngeal carcinoma 87th Annual Meeting of the American-Radium-Society Hara, W., Loo, B. W., Goffinet, D. R., Chang, S. D., Adler, J. R., Pinto, H. A., Fee, W. E., Kaplan, M. J., Fischbein, N. J., Le, Q. ELSEVIER SCIENCE INC. 2008: 393–400

  Abstract

  To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC).Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy.At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors.Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.

  View details for DOI 10.1016/j.ijrobp.2007.10.027

  View details for Web of Science ID 000255971100013

  View details for PubMedID 18164839

• Complications of ablative therapies in lung cancer CLINICAL LUNG CANCER Padda, S., Kothary, N., Donington, J., Cannon, W., Loo, B. W., Kee, S., Wakelee, H. 2008; 9 (2): 122-126

  Abstract

  Two cases of complications secondary to the use of microwave ablation (MWA) in non-small-cell lung cancer (NSCLC) are discussed herein. The first case involves a 62-year-old man with stage IB NSCLC who declined surgery and pursued MWA. Within 7 months, he had residual disease at the MWA treatment site, and surgery was performed. The patient was found to have pleural and chest wall involvement, making complete resection impossible. The second case involves an 86-year-old woman with a second local recurrence of NSCLC and previous treatment including surgery and chemoradiation therapy. She was initially a surgical candidate but declined surgery and pursued MWA. Within 6 months, she had residual disease at the MWA treatment site. A second MWA was performed, and she developed a large cavitary abscess at the MWA site and had subsequent clinical decline. Less invasive ablation therapies and stereotactic radiosurgery are being developed for patients with inoperable lung cancer. Because these modalities have recently been developed, trials that clearly show efficacy and survival benefit are yet to be completed. Ablation procedures can result in complications, including residual disease and cavitary lesions susceptible to infection. These cases highlight the caution that should still be observed when recommending lung ablation strategies and the importance of selecting appropriate patients.

  View details for Web of Science ID 000255039000010

  View details for PubMedID 18501100

• Initial evaluation of F-18-fluorothymidine (FLT) PET/CT scanning for primary pancreatic cancer EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Quon, A., Chang, S. T., Chin, F., Kamaya, A., Dick, D. W., Loo, B. W., Gambhir, S. S., Koong, A. C. 2008; 35 (3): 527-531

  Abstract

  The aim of this study was to evaluate the potential of (18)F-fluorothymidine (FLT) PET/CT for imaging pancreatic adenocarcinoma.This was a pilot study of five patients (four males, one female) with newly diagnosed and previously untreated pancreatic adenocarcinoma. Patients underwent FLT PET/CT, (18)F-fluorodeoxyglucose (FDG) PET/CT, and contrast-enhanced CT scanning before treatment. The presence of cancer was confirmed by histopathological analysis at the time of scanning in all five patients. The degree of FLT and FDG uptake at the primary tumor site was assessed using visual interpretation and semi-quantitative SUV analyses.The primary tumor size ranged from 2.5 x 2.8 cm to 3.5 x 7.0 cm. The SUV of FLT uptake within the primary tumor ranged from 2.1 to 3.1. Using visual interpretation, the primary cancer could be detected from background activity in two of five patients (40%) on FLT PET/CT. By comparison, FDG uptake was higher in each patient with a SUV range of 3.4 to 10.8, and the primary cancer could be detected from background in all five patients (100%).In this pilot study of five patients with primary pancreatic adenocarcinoma, FLT PET/CT scanning showed poor lesion detectability and relatively low levels of radiotracer uptake in the primary tumor.

  View details for DOI 10.1007/s00259-007-0630-z

  View details for Web of Science ID 000254402800010

  View details for PubMedID 17960376

• Metabolic tumor volume predicts for recurrence and death in head and neck cancer 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) La, T. H., Filion, E. J., Turnbull, B. B., CHU, J. N., Lee, P., Nguyen, K., Maxim, P., Loo, B. W., Graves, E. E., Le, Q. ELSEVIER SCIENCE INC. 2008: S159–S160

  View details for Web of Science ID 000258805300356

• Dose escalation feasible due to gating in lung cancer patients 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Luxion, G., Antony, J., Loo, B. W., Carlson, D., Maxim, P. G., Xing, L. ELSEVIER SCIENCE INC. 2008: S625–S625

  View details for Web of Science ID 000258805302301

• Tumor size is a critical determinant of local control in single fraction stereotactic radiotherapy of pulmonary tumors 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Loo, B. W., Shen, J., Quinlan-Davidson, S., Filion, E., Dieterich, S., Maxim, P. G., Wakelee, H. A., Whyte, R. I., Le, Q. ELSEVIER SCIENCE INC. 2008: S467–S468

  View details for Web of Science ID 000258805301520

• Quantification of motion of different thoracic locations using four-dimensional computed tomography: Implications for radiotherapy planning 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Maxim, P. G., Loo, B. W., Shirazi, H., Thorndyke, B., Luxton, G., Le, Q. ELSEVIER SCIENCE INC. 2007: 1395–1401

  Abstract

  To assess the respiratory motion of different thoracic nodal locations and its dependence on the presence of enlarged nodes; to assess the respiratory motion of different parenchymal tumor locations; and to determine the appropriate margins to cover the respiratory motion of targets at these locations.We reviewed the four-dimensional computed tomography scans of 20 patients with thoracic tumors treated at our institution. The motion of four central thoracic locations (aortic arch, carina, and bilateral hila), parenchymal tumor locations (upper vs. lower, and anterior vs. middle vs. posterior thorax), and bilateral diaphragmatic domes was measured.For the central thoracic locations, the largest motion was in the superoinferior (SI) dimension (>5 mm for bilateral hila and carina, but <4 mm for aortic arch). No significant difference was found in the motion of these locations in the absence or presence of enlarged nodes. For parenchymal tumors, upper tumors exhibited smaller SI motion than did lower tumors (3.7 vs. 10.4 mm, p = 0.029). Similarly, anterior tumors exhibited smaller motion than did posterior tumors in both the SI (4.0 vs. 8.0 mm, p = 0.013) and lateral (2.8 vs. 4.6 mm, p = 0.045) directions. The margins that would be needed to encompass the respiratory motion of each of the evaluated locations in 95% of patients were tabulated and range from 3.4 to 37.2 mm, depending on the location and direction.The results of our study have provided data for appropriate site-specific internal target volume expansion that could be useful in the absence of four-dimensional computed tomography-based treatment planning. However, generalizing the results from a small patient population requires discretion.

  View details for Web of Science ID 000251561100008

  View details for PubMedID 17869025

• Metabolic tumor burden predicts for disease progression and death in lung cancer 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Lee, P., Weerasuriya, D. K., Lavori, P. W., Quon, A., Hara, W., Maxim, P. G., Le, Q., Wakelee, H. A., Donington, J. S., Graves, E. E., Loo, B. W. ELSEVIER SCIENCE INC. 2007: 328–33

  Abstract

  In lung cancer, stage is an important prognostic factor for disease progression and survival. However, stage may be simply a surrogate for underlying tumor burden. Our purpose was to assess the prognostic value of tumor burden measured by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging.We identified 19 patients with lung cancer who had staging PET-CT scans before any therapy, and adequate follow-up (complete to time of progression for 18, and death for 15 of 19). Metabolically active tumor regions were segmented on pretreatment PET scans semi-automatically using custom software. We determined the relationship between times to progression (TTP) and death (OS) and two PET parameters: total metabolic tumor volume (MTV), and standardized uptake value (SUV).The estimated median TTP and OS for the cohort were 9.3 months and 14.8 months. On multivariate Cox proportional hazards regression analysis, an increase in MTV of 25 ml (difference between the 75th and 25th percentiles) was associated with increased hazard of progression and of death (5.4-fold and 7.6-fold), statistically significant (p = 0.0014 and p = 0.001) after controlling for stage, treatment intent (definitive or palliative), age, Karnofsky performance status, and weight loss. We did not find a significant relationship between SUV and TTP or OS.In this study, high tumor burden assessed by PET MTV is an independent poor prognostic feature in lung cancer, promising for stratifying patients in randomized trials and ultimately for selecting risk-adapted therapies. These results will need to be validated in larger cohorts with longer follow-up, and evaluated prospectively.

  View details for DOI 10.1016/j.ijrobp.2007.04.036

  View details for Web of Science ID 000249796100002

  View details for PubMedID 17869659

• RT_Image: An open-source tool for investigating PET in radiation oncology TECHNOLOGY IN CANCER RESEARCH & TREATMENT Graves, E. E., Quon, A., Loo, B. W. 2007; 6 (2): 111-121

  Abstract

  Positron emission tomography (PET) has emerged as a valuable imaging modality for the diagnosis and staging of cancer. However, despite evidence that PET may be useful for defining target volumes for radiation therapy, no standardized methodology for accomplishing this task exists. To facilitate the investigation of the utility of PET imaging in radiotherapy treatment planning and accelerate its integration into clinical radiation oncology, we have developed software for exploratory analysis and segmentation of functional imaging datasets. The application, RT_Image, allows display of multiple imaging datasets and associated three-dimensional regions-of-interest (ROIs) at arbitrary view angles and fields of view. It also includes semi-automated image segmentation tools for defining metabolically active tumor volumes that may aid creation of target volumes for treatment planning. RT_Image is DICOM compliant, permitting the transfer of imaging data and DICOM-RT structure sets between the application and treatment planning software. RT_Image has been used by radiation oncologists, nuclear medicine physicians, and radiation physicists to analyze over 200 PET datasets. Novel segmentation techniques have been implemented within this programming framework for therapy planning and for evaluation of molecular imaging-derived parameters as prognostic indicators. RT_Image represents a freely-available software base on which further investigations of the utlity of PET and molecular imaging in radiation oncology may be built. The development of tools such as this is critical in order to realize the potential of molecular imaging-guided radiation therapy.

  View details for Web of Science ID 000245969900007

  View details for PubMedID 17375973

• Impact of integrated PET/CT on variability of target volume delineation in rectal cancer TECHNOLOGY IN CANCER RESEARCH & TREATMENT Patel, D. A., Chang, S. T., Goodman, K. A., Quon, A., Thorndyke, B., Gambhir, S. S., McMillan, A., Loo, B. W., Koong, A. C. 2007; 6 (1): 31-36

  Abstract

  Several studies have demonstrated substantial variability among individual radiation oncologists in defining target volumes using computed tomography (CT). The objective of this study was to determine the impact of combined positron emission tomography and computed tomography (PET/CT) on inter-observer variability of target volume delineation in rectal cancer. We also compared the relative concordance of two PET imaging tracers, 18F-fluorodeoxyglucose (FDG) and 18F-fluorodeoxythymidine (FLT), against conventional computed tomography (CT). Six consecutive patients with locally advanced rectal cancer were enrolled onto an institutional protocol involving preoperative chemoradiotherapy and correlative studies including FDG- and FLT-PET scans acquired in the treatment position. Using these image data sets, four radiation oncologists independently delineated primary and nodal gross tumor volumes (GTVp and GTVn) for a hypothetical boost treatment. Contours were first defined based on CT alone with observers blinded to the PET images, then based on combined PET/CT. An inter-observer similarity index (SI), ranging from a value of 0 for complete disagreement to 1 for complete agreement of contoured voxels, was calculated for each set of volumes. For primary gross tumor volume (GTVp), the difference in estimated SI between CT and FDG was modest (CT SI = 0.77 vs. FDG SI = 0.81), but statistically significant (p = 0.013). The SI difference between CT and FLT for GTVp was also slight (FLT SI = 0.80) and marginally non-significant (p < 0.082). For nodal gross tumor volume, (GTVn), SI was significantly lower for CT based volumes with an estimated SI of 0.22 compared to an estimated SI of 0.70 for FDG-PET/CT (p < 0.0001) and an estimated SI of 0.70 for FLT-PET/CT (p < 0.0001). Boost target volumes in rectal cancer based on combined PET/CT results in lower inter-observer variability compared with CT alone, particularly for nodal disease. The use of FDG and FLT did not appear to be different from this perspective.

  View details for Web of Science ID 000244732600005

  View details for PubMedID 17241098

• Clinical role of F-18-FDG PET/CT in the management of squamous cell carcinoma of the head and neck and thyroid carcinoma JOURNAL OF NUCLEAR MEDICINE Quon, A., Fischbein, N. J., McDougall, I. R., Le, Q., Loo, B. W., Pinto, H., Kaplan, M. J. 2007; 48: 58S-67S

  Abstract

  18F-FDG PET/CT has rapidly become a widely used imaging modality for evaluating a variety of malignancies, including squamous cell carcinoma of the head and neck and thyroid cancer. Using both published data and the multidisciplinary experience at our institution, we provide a practical set of guidelines and algorithms for the use of 18F-FDG PET/CT in the evaluation and management of head and neck cancer and thyroid cancer.

  View details for Web of Science ID 000243420900008

  View details for PubMedID 17204721

• Results of a phase I dose-escalation study using single-fraction stereotactic radiotherapy for lung tumors 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Le, Q., Loo, B. W., Ho, A., Cotrutz, C., Koong, A. C., Wakelee, H., Kee, S. T., Constantinescu, D., Whyte, R. I., Donington, J. LIPPINCOTT WILLIAMS & WILKINS. 2006: 802–9

  Abstract

  The purpose of this study was to report initial results of a phase I study using single-fraction stereotactic radiotherapy (RT) in patients with inoperable lung tumors.Eligible patients included those with inoperable T1-2N0 non-small cell lung cancer (NSCLC) or solitary lung metastases. Treatments were delivered by means of the CyberKnife. All patients underwent computed tomography-guided metallic fiducial placement in the tumor for image-guided targeting. Nine to 20 patients were treated per dose cohort starting at 15 Gy/fraction followed by dose escalation of 5 to 10 Gy to a maximal dose of 30 Gy/fraction. A minimal 3-month period was required between each dose level to monitor toxicity.Thirty-two patients (21 NSCLC and 11 metastatic tumors) were enrolled. At 25 Gy, pulmonary toxicity was noted in patients with prior pulmonary RT and treatment volumes greater than 50 cc; therefore, dose escalation to 30 Gy was applied only to unirradiated patients and treatment volume less than 50 cc. Ten patients received doses less than 20 Gy, 20 received 25 Gy, and two received 30 Gy. RT-related complications were noted for doses greater than 25 Gy and included four cases of grade 2 to 3 pneumonitis, one pleural effusion, and three possible treatment-related deaths. The 1-year freedom from local progression was 91% for dose greater than 20 Gy and 54% for dose less than 20 Gy in NSCLC (p = 0.03). NSCLC patients had significantly better freedom from relapse (p = 0.003) and borderline higher survival than those with metastatic tumors (p = 0.07).Single-fraction stereotactic RT is feasible for selected patients with lung tumors. For those with prior thoracic RT, 25 Gy may be too toxic. Higher dose was associated with improved local control. Longer follow-up is necessary to determine the treatment efficacy and toxicity.

  View details for Web of Science ID 000241649300008

  View details for PubMedID 17409963

• Indirect MR lymphangiography of the head and neck using conventional gadolinium contrast: A pilot study in humans 45th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Loo, B. W., Draney, M. T., Sivanandan, R., Ruehm, S. G., Pawlicki, T., Xing, L., Herfkens, R. J., Le, Q. ELSEVIER SCIENCE INC. 2006: 462–68

  Abstract

  To evaluate indirect magnetic resonance lymphangiography (MR-LAG) using interstitial injection of conventional gadolinium contrast (gadoteridol and gadopentetate dimeglumine) for delineating the primary lymphatic drainage of head-and-neck sites.We performed head-and-neck MR-LAG in 5 healthy volunteers, with injection of dermal and mucosal sites. We evaluated the safety of the procedure, the patterns of enhancement categorized by injection site and nodal level, the time course of enhancement, the optimal concentration and volume of contrast, and the optimal imaging sequence.The worst side effects of interstitial contrast injection were brief, mild pain and swelling at the injected sites that were self-limited. MR-LAG resulted in consistent visualization of the primary lymphatic drainage pattern specific to each injected site, which was reproducible on repeated examinations. The best enhancement was obtained with injection of small volumes (0.3-0.5 mL) of either agent diluted, imaging within 5-15 min of injection, and a three-dimensional fast spoiled gradient echo sequence with magnetization transfer.We found head-and-neck MR-LAG to be a safe, convenient imaging method that provides functional information about the lymphatic drainage of injected sites. Applied to head-and-neck cancer, it has the potential to identify sites at highest risk of occult metastatic spread for radiotherapy or surgical planning, and possibly to visualize micrometastases.

  View details for DOI 10.1016/j.ijrobp.2006.05.045

  View details for Web of Science ID 000240699500024

  View details for PubMedID 16965993

• Four-dimensional cone-beam computed tomography using an on-board imager MEDICAL PHYSICS Li, T., Xing, L., Munro, P., McGuinness, C., Chao, M., Yang, Y., Loo, B., Koong, A. 2006; 33 (10): 3825-3833

  Abstract

  On-board cone-beam computed tomography (CBCT) has recently become available to provide volumetric information of a patient in the treatment position, and holds promises for improved target localization and irradiation dose verification. The design of currently available on-board CBCT, however, is far from optimal. Its quality is adversely influenced by many factors, such as scatter, beam hardening, and intra-scanning organ motion. In this work we quantitatively study the influence of organ motion on CBCT imaging and investigate a strategy to acquire high quality phase-resolved [four-dimensional (4D)] CBCT images based on phase binning of the CBCT projection data. An efficient and robust method for binning CBCT data according to the patient's respiratory phase derived in the projection space was developed. The phase-binned projections were reconstructed using the conventional Feldkamp algorithm to yield 4D CBCT images. Both phantom and patient studies were carried out to validate the technique and to optimize the 4D CBCT data acquisition protocol. Several factors that are important to the clinical implementation of the technique, such as the image quality, scanning time, number of projections, and radiation dose, were analyzed for various scanning schemes. The general references drawn from this study are: (i) reliable phase binning of CBCT projections is accomplishable with the aid of external or internal marker and simple analysis of its trace in the projection space, and (ii) artifact-free 4D CBCT images can be obtained without increasing the patient radiation dose as compared to the current 3D CBCT scan.

  View details for DOI 10.1118/1.2349692

  View details for Web of Science ID 000241424100024

  View details for PubMedID 17089847

• 4D cone-beam CT (CBCT) using an on-board imager 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine Li, T., Xing, L., Munro, P., Yang, Y., Loo, B., Koong, A. AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS. 2006: 2234–34

  View details for Web of Science ID 000238688502246

• Dosimetric impact by temporal changes of the PTV in head in neck cancers 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Maxim, P. G., Tran, P., Hsu, A., Daly, M., Loo, B. W., Wu, R., Pawlicki, T., Le, Q. ELSEVIER SCIENCE INC. 2006: S638–S639

  View details for Web of Science ID 000241221602277

• Integrated analysis of pancreatic tumor motion using multiple image-guided modalities 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Cox, B., Ho, T., Thorndyke, B., Pawlicki, T., Loo, B., Xing, L., Goodman, K., Koong, A. ELSEVIER SCIENCE INC. 2006: S53–S54

  View details for Web of Science ID 000241221600091

• Optical detection of tumors in vivo by visible light tissue oximetry TECHNOLOGY IN CANCER RESEARCH & TREATMENT Maxim, P. G., Carson, J. J., Benaron, D. A., Loo, B. W., Xing, L., Boyer, A. L., Friedland, S. 2005; 4 (3): 227-234

  Abstract

  Endoscopy is a standard procedure for identifying tumors in patients suspected of having gastrointestinal (G.I.) cancer. The early detection of G.I. neoplasms during endoscopy is currently made by a subjective visual inspection that relies to a high degree on the experience of the examiner. This process can be difficult and unreliable, as tumor lesions may be visually indistinguishable from benign inflammatory conditions and the surrounding mucosa. In this study, we evaluated the ability of local ischemia detection using visible light spectroscopy (VLS) to differentiate neoplastic from normal tissue based on capillary tissue oxygenation during endoscopy. Real-time data were collected (i) from human subjects (N = 34) monitored at various sites during endoscopy (enteric mucosa, malignant, and abnormal tissue such as polyps) and (ii) murine animal subjects with human tumor xenografts. Tissue oximetry in human subjects during endoscopy revealed a tissue oxygenation (StO2%, mean +/- SD) of 46 +/- 22% in tumors, which was significantly lower than for normal mucosal oxygenation (72 +/- 4%; P < or = 0.0001). No difference in tissue oxygenation was observed between normal and non-tumor abnormal tissues (P = N.S.). Similarly, VLS tissue oximetry for murine tumors revealed a mean local tumor oxygenation of 45% in LNCaP, 50% in M21, and 24% in SCCVII tumors, all significantly lower than normal muscle tissue (74%, P < 0.001). These results were further substantiated by positive controls, where a rapid real-time drop in tumor oxygenation was measured during local ischemia induced by clamping or epinephrine. We conclude that VLS tissue oximetry can distinguish neoplastic tissue from normal tissue with a high specificity (though a low sensitivity), potentially aiding the endoscopic detection of gastrointestinal tumors.

  View details for Web of Science ID 000229787600001

  View details for PubMedID 15896077

• Enhancing 4D PET through retrospective stacking 47th Annual Meeting of the American-Association-of-Physicists-in-Medicine Thorndyke, B., Schreibmann, E., Maxim, P., Loo, B., Boyer, A., Koong, A., Xing, L. AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS. 2005: 2096–96

  View details for Web of Science ID 000229908601310

• Effect of respiratory cycle irregularities on image quality in four-dimensional computed tomography 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Thorndyke, B., Xing, L., Graves, E., Loo, B. W. ELSEVIER SCIENCE INC. 2005: S506–S506

  View details for Web of Science ID 000232083301373

• Determining margin for target deformation and rotation in respiratory motion-tracked stereotactic radiosurgery of pancreatic cancer 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Loo, B. W., Thorndyke, B. R., Maxim, P. G., Ho, A., Goodman, K. A., Xing, L., Yang, G. P., Koong, A. C. ELSEVIER SCIENCE INC. 2005: S31–S31

  View details for Web of Science ID 000232083300056

• Results of a phase I dose escalation study using single fraction stereotactic radiosurgery (SFSR) for lung tumors 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Le, Q. X., Ho, A., Cotrutz, C., Loo, B., Petrik, D., Wakelee, H., Kee, S. T., Whyte, R. I., Donington, J. S. ELSEVIER SCIENCE INC. 2005: S226–S226

  View details for Web of Science ID 000232083300377

• A method of target definition in PET-based radiotherapy planning 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Loo, B. W., Quon, A., Vasanawala, M. S., Le, Q., Graves, E. E. ELSEVIER SCIENCE INC. 2004: S602–S602

  View details for Web of Science ID 000223854700784

• Plasmablastic lymphoma presenting in a human immunodeficiency virus-negative patient: a case report ANNALS OF HEMATOLOGY Nguyen, D. D., Loo, B. W., Tillman, G., Natkunam, Y., Cao, T. M., Vaughan, W., Dorfman, R. F., Goffinet, D. R., Jacobs, C. D., Advani, R. H. 2003; 82 (8): 521-525

  Abstract

  Plasmablastic lymphoma (PBL), an aggressive non-Hodgkin's lymphoma that carries a poor prognosis, previously has been identified almost exclusively in patients infected with the human immunodeficiency virus (HIV). We present a case of a 42-year-old HIV-negative patient presenting with an isolated nasal cavity mass, the typical presentation for PBL. The patient was given systemic chemotherapy, central nervous system prophylaxis, and consolidative locoregional radiotherapy and achieved a complete clinical response. This case suggests PBL should be considered in HIV-negative patients with characteristic findings.

  View details for DOI 10.1007/s00277-003-0684-3

  View details for Web of Science ID 000184757100013

  View details for PubMedID 12783213

• A new sample preparation method for biological soft X-ray microscopy: nitrogen-based contrast and radiation tolerance properties of glycol methacrylate-embedded and sectioned tissue JOURNAL OF MICROSCOPY-OXFORD Loo, B. W., Sauerwald, I. M., Hitchcock, A. P., Rothman, S. S. 2001; 204: 69-86

  Abstract

  We describe the preparation of a biological tissue for imaging in a transmission soft X-ray microscope. Sections of exocrine pancreas embedded in glycol methacrylate polymer, an embedding medium widely used in visible light and electron microscopy, were examined. Contrast was based primarily on the nitrogen content of the tissue, and dual-wavelength imaging at the nitrogen K-shell absorption edge was used to map the distribution and provide quantitative densitometry of both the protein and embedding matrix components of the sample. The measurements were calibrated by obtaining the absorption spectrum of protein near the nitrogen edge. The contrast was consistent and reproducible, making possible the first large-scale X-ray microscopic study on sections of plastic-embedded soft tissue. At radiation doses of up to 10(8) Gray, much more than required for routine imaging, no distortion and little mass loss were observed. This sample preparation method should permit routine imaging of tissues in X-ray microscopes, previously a difficult task, as well as multimodal imaging (using visible light, X-ray, electron, and scanned probe microscopies) on the same sample.

  View details for Web of Science ID 000171285700009

  View details for PubMedID 11580815

• Automatic image acquisition, calibration and montage assembly for biological X-ray microscopy JOURNAL OF MICROSCOPY-OXFORD Loo, B. W., Meyer-Ilse, W., Rothman, S. S. 2000; 197: 185-201

  Abstract

  We describe a system for the automatic acquisition and processing of digital images in a high-resolution X-ray microscope, including the formation of large-field high-resolution image montages. A computer-controlled sample positioning stage provides approximate coordinates for each high-resolution subimage. Individual subimages are corrected to compensate for time-varying, non-uniform illumination and CCD-related artefacts. They are then automatically assembled into a montage. The montage assembly algorithm is designed to use the overlap between each subimage and multiple neighbours to improve the performance of the registration step and the fidelity of the result. This is accomplished by explicit use of recorded stage positions, optimized ordering of subimage insertion, and registration of subimages to the developing montage. Using this procedure registration errors are below the resolution limit of the microscope (43 nm). The image produced is a seamless, large-field montage at full resolution, assembled automatically without human intervention. Beyond this, it is also an accurate X-ray transmission map that allows the quantitative measurement of anatomical and chemical features of the sample. Applying these tools to a biological problem, we have conducted the largest X-ray microscopical study to date.

  View details for Web of Science ID 000085459300007

  View details for PubMedID 10652011

• Two- and three-dimensional segmentation for measurement of particles in the analysis of microscopic digital images of biological samples Conference on Three-Dimensional Microscopy - Image Acquisition and Processing III Loo, B. W., Parvin, B., Rothman, S. S. SPIE - INT SOC OPTICAL ENGINEERING. 1996: 209–215

  View details for Web of Science ID A1996BF46V00026

• High resolution microscopic imaging with x-rays: Technology and application to the biological sciences Wescon/95 - Microelectronics, Communications Technology, Producing Quality Products, Mobile and Portable Power, Emerging Technologies Loo, B. W., Rothman, S. S. I E E E. 1995: 668–672

  View details for Web of Science ID A1995BE64P00119

• X-RAY MICROTOMOGRAPHY - 3-DIMENSIONAL RECONSTRUCTION METHODS FOR X-RAY MICROSCOPY OF BIOLOGICAL SAMPLES 3-Dimensional Microscopy - Image Acquisition and Processing II Conference Loo, B. W., Brown, J. K., Rothman, S. S. SPIE - INT SOC OPTICAL ENGINEERING. 1995: 196–209

  View details for Web of Science ID A1995BC95B00024

• AN ENVIRONMENTAL SAMPLE CHAMBER FOR X-RAY MICROSCOPY JOURNAL OF MICROSCOPY-OXFORD Goncz, K. K., Batson, P., CIARLO, D., Loo, B. W., Rothman, S. S. 1992; 168: 101-110

  View details for Web of Science ID A1992JV21500010

• X-RAY STEREOMICROSCOPY - HIGH-RESOLUTION 3-D IMAGING OF HUMAN SPERMATOZOA IN AQUEOUS SUSPENSION WITH NATURAL CONTRAST JOURNAL OF MICROSCOPY-OXFORD Loo, B. W., Williams, S., Meizel, S., Rothman, S. S. 1992; 166: RP5-RP6

  View details for Web of Science ID A1992HW41100010

  View details for PubMedID 1625335

• An environmental sample chamber for x-ray microscopy J Microsc Goncz KK, Batson P, Ciarlo D, Loo BW Jr, Rothman SS 1992; 168: 101-110