Scott G. Soltys, MD

All Publications

• Long-Term Hearing Outcomes Following Stereotactic Radiosurgery in Vestibular Schwannoma Patients-A Retrospective Cohort Study. Neurosurgery Santa Maria, P. L., Shi, Y., Gurgel, R. K., Corrales, C. E., Soltys, S. G., Santa Maria, C., Murray, K., Chang, S. D., Blevins, N. H., Gibbs, I. C., Jackler, R. K. 2018

  Abstract

  BACKGROUND: An understanding of the hearing outcomes is needed for treatment counseling for patients with vestibular schwannomas (VS).OBJECTIVE: To determine long-term hearing results following stereotactic radiosurgery (SRS) for VS and identify any influential variables.METHODS: Tertiary hospital retrospective cohort.RESULTS: There were 579 tumors (576 patients) treated with SRS. Eighty-two percent (473) of tumors had ≥1 yr and 59% (344 ≥3 yr follow-up. In the 244 tumor ears, with measurable hearing before SRS who were followed ≥1 yr, 14% (31) had improved hearing, 13% (29) unchanged hearing, and 74% (158) had worsened hearing. In 175 patients with ≥3 yr follow-up and who had measurable hearing pretreatment, 6% (11 ears) improved hearing, 31% (54 ears) unchanged hearing, and 63% (110 ears) had worsened hearing. Patients with tumors with larger target volumes (P=0.040) and with neurofibromatosis type 2 (NF2; P=0.017) were associated with poorer hearing (P=0.040). Patients with word recognition scores (WRS) of 50% or poorer had tumors with a larger volume (P=0.0002), larger linear size (P=0.032), and NF2 (P=0.045). Traditionally reported hearing outcomes using the Gardner Robertson maintenance of PTA ≤50 db or WRS ≥50% were 48% at 3 yr, which overestimates hearing outcomes compared to the above reporting standards.CONCLUSION: Hearing declines over time in VS treated with SRS in a high proportion of cases. The frequency and magnitude of long-term hearing decline following SRS argues against prophylactic radiation for small tumors in hearing ears with undetermined growth behavior.

  View details for DOI 10.1093/neuros/nyy407

  View details for PubMedID 30247723

• Advance care planning needs in patients with glioblastoma undergoing radiotherapy. Journal of pain and symptom management Pollom, E., Sborov, K., Soltys, S. G., Asch, S. M., Sudore, R., Aslakson, R. A. 2018

  View details for DOI 10.1016/j.jpainsymman.2018.08.021

  View details for PubMedID 30201484

• Population description and clinical response assessment for spinal metastases: part 2 of the SPIne response assessment in Neuro-Oncology (SPINO) group report NEURO-ONCOLOGY Laufer, I., Lo, S. S., Chang, E. L., Sheehan, J., Guckenberger, M., Sohn, M., Ryu, S., Foote, M., Muacevic, A., Soltys, S. G., Chao, S., Myrehaug, S., Gerszten, P. C., Lis, E., Maralani, P., Bilsky, M., Fisher, C., Rhines, L., Verlaan, J., Schiff, D., Fehlings, M. G., Ma, L., Chang, S., Parulekar, W. R., Vogelbaum, M. A., Sahgal, A. 2018; 20 (9): 1215–24

  Abstract

  Approximately 40% of metastatic cancer patients will develop spinal metastases. The current report provides recommendations for standardization of metrics used for spinal oncology patient population description and outcome assessment beyond local control endpoints on behalf of the SPIne response assessment in Neuro-Oncology (SPINO) group.SPINO group survey was conducted in order to determine the preferences for utilization of clinician-based and patient-reported outcome measures for description of patients with spinal metastases. Subsequently, ClinicalTrials.gov registry was searched for spinal oncology clinical trials and measures for patient description and outcome reporting were identified for each trial. These two searches were used to identify currently used descriptors and instruments. A literature search was performed focusing on the measures identified in the survey and clinical trial search in order to assess their validity in the metastatic spinal tumor patient population. References for this manuscript were identified through PubMed and Medline searches.Published literature, expert survey and ongoing clinical trials were used in to synthesize recommendations for instruments for reporting of spinal stability, epidural tumor extension, neurologic and functional status and symptom severity.Accurate description of patient population and therapy effects requires a combination of clinician-based and patient reported outcome (PRO) measures. The current report provides international consensus recommendations for the systematic reporting of patient- and clinician-reported measures required to develop trials applicable to surgery for spinal metastases and post-operative spine SBRT.

  View details for DOI 10.1093/neuonc/noy047

  View details for Web of Science ID 000440947900007

  View details for PubMedID 29590465

  View details for PubMedCentralID PMC6071663

• Hippocampus-Sparing Radiation and Chemotherapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pollom, E., Soltys, S. G. 2018; 101 (3): 519–20

  View details for DOI 10.1016/j.ijrobp.2018.03.016

  View details for Web of Science ID 000433877500008

  View details for PubMedID 29893271

• CyberKnife robotic radiosurgery in the multimodal management of acromegaly patients with invasive macroadenoma: a single center's experience JOURNAL OF NEURO-ONCOLOGY Sala, E., Moore, J. M., Amorin, A., Martinez, H., Bhowmik, A. C., Lamsam, L., Chang, S., Soltys, S. G., Katznelson, L., Harsh, G. R. 2018; 138 (2): 291–98

  Abstract

  Surgery is the primary treatment for acromegaly. However, surgery may not be curative of some tumors, particularly invasive macroadenomas. Adjuvant radiation, specifically robotic stereotactic radiosurgery (rSRS), may improve the endocrine outcome. We retrospectively reviewed hormonal and radiological data of 22 acromegalic patients with invasive macroadenomas treated with rSRS at Stanford University Medical Center between 2000 and 2016. Prior to treatment, the tumor's median maximal diameter was 19 mm (2.5-50 mm). Cavernous sinus invasion occurred in 19 patients (86.3%) and compression of the optic chiasm in 2 (9.0%). At last follow up, with an average follow up of 43.2 months, all patients had a reduction in their IGF-1 levels (median IGF-1% upper limit of normal (ULN) baseline: 136% vs last follow up: 97%; p = 0.05); 9 patients (40.9%) were cured, and 4 (18.1%) others demonstrated biochemical control of acromegaly. The median time to cure was 50 months and the mean interval to cure or biochemical control was 30.3 months (± 24 months, range 6-84 months). Hypopituitarism was present in 8 patients (36.3%) and new pituitary deficits occurred in 6 patients with a median latency of 31.6 ± 14.5 months. At final radiologic follow-up, 3 tumors (13.6%) were smaller and 19 were stable in size. The mean biologically effective dose (BED) was higher in subjects cured compared to those with persistent disease, 163 Gy3 (± 47) versus 111 Gy3 (± 43), respectively (p = 0.01). No patient suffered visual deterioration. Robotic SRS is a safe and effective treatment for acromegaly: radiation-induced visual complications and hypopituitarism is rare.

  View details for DOI 10.1007/s11060-018-2793-9

  View details for Web of Science ID 000431890400008

  View details for PubMedID 29429125

• Radiation-Induced Edema After Single-Fraction or Multifraction Stereotactic Radiosurgery for Meningioma: A Critical Review INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Milano, M. T., Sharma, M., Soltys, S. G., Sahgal, A., Usuki, K. Y., Saenz, J., Grimm, J., El Naqa, I. 2018; 101 (2): 344–57

  Abstract

  Potential dosimetric and clinicopathologic predictors of radiation-induced brain edema after single-fraction or multifraction stereotactic radiosurgery (SRS) for non-base of skull (non-BOS) meningiomas are summarized based on a systematic review of the published literature.Reviewed studies (PubMed indexed from 1998 through 2017) included all or some non-BOS meningioma patients, reported risks of edema after SRS, and correlated dosimetric and/or nondosimetric measures with the magnitude of risk.Twenty-six studies reporting risks of edema after SRS for meningioma are reviewed. The treatment techniques as well as distribution of tumor locations, target dosing, and target volume varied across studies. Among 13 studies that included only non-BOS tumors or separately grouped non-BOS tumors, symptomatic edema occurred in 5% to 43% of patients and any edema occurred in 28% to 50%. The reported average time to onset of edema ranged from approximately 3 to 9 months in most studies. Factors reported to significantly correlate with increased risks of edema and/or symptomatic edema after SRS for meningioma include the following: greater tumor margin and/or maximum dose, greater tumor size and/or volume, non-BOS (particularly parasagittal) location, no prior resection for meningioma, and presence of pretreatment edema. Nevertheless, the extent and significance of these factors were inconsistent across studies. Potentially important dosimetric factors, such as volume of brain or tissue receiving single-fraction doses > 10 to 12 Gy, are not well studied.The variability in risks of edema and in factors impacting those risks is likely a result of differences across studies in the clinicopathologic characteristics of the patient populations, as well as differences in treatment modalities and SRS planning and delivery parameters. More studies on pooled populations, grouped by potential prognostic factors such as tumor location and prior therapy, are needed to better understand dosimetric and nondosimetric factors predictive of edema risk after SRS for meningioma.

  View details for DOI 10.1016/j.ijrobp.2018.03.026

  View details for Web of Science ID 000432448900023

  View details for PubMedID 29726362

• Brainstem Dose Constraints in Nonisometric Radiosurgical Treatment Planning of Trigeminal Neuralgia: A Single-Institution Experience WORLD NEUROSURGERY Zhang, M., Lamsam, L. A., Schoen, M. K., Mehta, S. S., Appelboom, G., Adler, J. K., Soltys, S. G., Chang, S. D. 2018; 113: E399–E407

  Abstract

  CyberKnife stereotactic radiosurgery (SRS) for trigeminal neuralgia (TGN) administers nonisometric, conformational high-dose radiation to the trigeminal nerve with risk of subsequent hypoesthesia.We performed a retrospective, single-institution review of 66 patients with TGN treated with CyberKnife SRS to compare outcomes from 2 distinct treatment periods: standard dosing (n = 38) and reduced dosing (n = 28). Standard and reduced dosing permitted a maximum brainstem dose of 45 Gy and 25 Gy, respectively, each with a prescription dose of 60 Gy. Primary and secondary outcomes were Barrow Neurologic Institute pain and numbness scores. Maximum brainstem dose, prepontine nerve length, and treatment history were recorded for their predictive contributions by logistic regression.After matching, patients in the standard dosing and reduced dosing groups were followed for a median of 25 months and 19.5 months, respectively. Mean trigeminal nerve length was 8.55 mm in the standard dosing group and 9.46 mm in the reduced dosing group. Baseline rates of poorly controlled pain were 97% and 88%, respectively, which improved to 23.4% and 8.3%, respectively (P < 0.001 for both). The baseline rates of bothersome numbness were null in both groups, and increased to 25% in the standard group (P = 0.006) and to 21% in the reduced group (P = 0.07). Regression analyses suggested that reduced brainstem exposure (P = 0.01), as well as a longer trigeminal nerve (P = 0.01), were predictive of durable pain control.These outcomes demonstrate that a lower maximum brainstem dose can provide excellent pain control without affecting facial numbness. Longer nerves may achieve better long-term outcomes and help optimize individual plans.

  View details for DOI 10.1016/j.wneu.2018.02.042

  View details for Web of Science ID 000432942700047

  View details for PubMedID 29454124

• CyberKnife Radiosurgery in the Multimodal Management of Patients with Cushing Disease WORLD NEUROSURGERY Moore, J. M., Sala, E., Amorin, A., Martinez, H., Bhowmik, A. C., Chang, S. D., Soltys, S. G., Harsh, G. R., Katznelson, L. 2018; 112: E425–E430

  Abstract

  Surgery is the primary treatment for Cushing disease. When surgery is unsuccessful in normalizing hypercortisolism, adjuvant radiation, such as stereotactic radiosurgery, may be useful to improve biochemical control.This retrospective study included a cohort of consecutive patients treated with CyberKnife (CK) radiosurgery for active Cushing disease at Stanford Hospital and Clinics.As first-line treatment, all patients underwent transsphenoidal surgery with histologic demonstration of an adrenocorticotropic hormone-producing pituitary adenoma. CK was performed as adjuvant therapy for persistent or recurrent disease. The median time between surgery and CK was 14 ± 34 months. Before CK, median maximal diameter of tumors was 9 mm (range, 7-32 mm), with cavernous sinus invasion in all patients (100%) and abutment of the optic chiasm in 1 patient (14.2%). With an average follow-up of 55.4 months, normalization of hypercortisolism was achieved in 4 patients (57.1%): 2 patients (28.5%) achieved normalization of the hypothalamic-pituitary-adrenal axis without glucocorticoid replacement, and 2 patients developed hypoadrenalism (28.5%). The median time to biochemical remission was 12.5 months. Hypopituitarism occurred in only 1 patient (14.2%), and no patients had visual complications. Time between surgery and radiotherapy of <14 months was associated with a significantly improved biochemical remission rate (P = 0.02).In a cohort of patients with Cushing disease, we demonstrate that CK is an effective treatment with rare complications.

  View details for DOI 10.1016/j.wneu.2018.01.057

  View details for Web of Science ID 000432932700049

  View details for PubMedID 29355797

• Survival Impact of Postoperative Radiotherapy Timing in Pediatric and Adolescent Medulloblastoma. Neuro-oncology Chin, A. L., Moding, E. J., Donaldson, S. S., Gibbs, I. C., Soltys, S. G., Hiniker, S. M., Pollom, E. L. 2018

  Abstract

  Radiation therapy (RT) remains a critical component of multimodality treatment for medulloblastoma. Traditionally, clinicians strive to start RT within 4-5 weeks of surgery, but the optimal timing after surgery remains unclear.Using the National Cancer Database, we identified pediatric and adolescent patients with medulloblastoma treated with curative-intent surgery, RT, and chemotherapy. Factors associated with early or delayed RT were identified using Pearson chi-squared tests. Overall survival (OS) differences based on RT timing were compared using the Kaplan-Meier estimator with log-rank tests. Patient, tumor, and treatment characteristics associated with OS were analyzed with univariate and multivariate Cox proportional hazard models.Among the 1338 patients analyzed, early RT (defined as initiation ≤3 weeks after surgery) was associated with younger age, M1-3 disease, and subtotal resection. Patients who initiated RT early had decreased five-year OS compared with patients who initiated RT 3.1-4, 4.1-5, or >5 weeks after surgery (72.5%, 80.5%, 79.4%, and 77.8%, respectively; p=0.019), but there was no significant difference in OS among the latter three groups (p=0.788). On multivariate analysis, early RT versus the 3.1-4-week interval was significantly associated with poorer OS (adjusted HR 1.72; 95% CI 1.19-2.48; p=0.004), while time to RT of >5 weeks but within 90 days of surgery did not adversely impact OS (p=0.563).In this large national database analysis, delaying RT within 90 days of surgery was not associated with inferior outcomes. Although clinical judgment remains paramount, postoperative RT timing should allow for healing and the development of an optimal treatment plan.

  View details for DOI 10.1093/neuonc/noy001

  View details for PubMedID 29309676

• Newly diagnosed glioblastoma: adverse socioeconomic factors correlate with delay in radiotherapy initiation and worse overall survival. Journal of radiation research Pollom, E. L., Fujimoto, D. K., Han, S. S., Harris, J. P., Tharin, S. A., Soltys, S. G. 2018

  Abstract

  The optimal time for starting radiation in patients with glioblastoma (GBM) is controversial. We aimed to evaluate postoperative radiotherapy treatment patterns and the impact of timing of radiotherapy on survival outcomes in patients with GBM using a large, national hospital-based registry in the era of Stupp chemoradiation. We performed a retrospective cohort study using the National Cancer Data Base and identified adults with GBM diagnosed between 2010 and 2013 and treated with chemoradiation. We classified time from surgery/biopsy to radiation start into the following categories: <15 days, 15-21 days, 22-28 days, 29-35 days, 36-42 days and >42 days. We assessed the relation between time to radiation start and survival using Cox proportional hazards modeling adjusting for clinically relevant variables that were selected a priori. We used multivariate logistic modeling to determine factors independently associated with receipt of delayed radiation treatment. A total of 12 738 patients met our inclusion criteria after our cohort selection process. The majority of patients underwent either gross total (n = 5270, 41%) or subtotal (n = 4700, 37%) resection, while 2768 patients (22%) underwent biopsy only. Median time from definitive surgery or biopsy to initiation of radiation was 29 days (interquartile range 24-36 days). For patients who had biopsy or subtotal resection, earlier initiation of radiation did not appear to be associated with improved survival. However, among patients who underwent gross total resection, there appeared to be improved survival with early initiation of radiation. Patients who initiated radiation within 15-21 days of gross total resection had improved survival (hazard ratio 0.82, 95% confidence interval 0.69-0.98, P = 0.03) compared with patients who had delayed (>42 days after surgery) radiation. There was also a trend (P = 0.07 to 0.12) for improved survival for patients who initiated radiation within 22-35 days of gross total resection compared with patients who had delayed radiation. Patients who were black, had Medicaid or other government insurance or were not insured, and who lived in metropolitan areas or further away from the treating facility had higher odds of receiving radiation >35 days after gross total resection. Patients who lived in higher income areas had higher odds of receiving radiation within 35 days of a gross total resection. In a large cohort of patients with GBM treated with chemoradiation, our data suggest a survival benefit in initiating radiotherapy within 35 days after gross total resection. Further research is warranted to understand barriers to timely access to optimal therapy.

  View details for DOI 10.1093/jrr/rrx103

  View details for PubMedID 29432548

• Clinical factors associated with mortality within three months after radiosurgery of asymptomatic brain metastases from non-small cell lung cancer. Journal of neuro-oncology Kakusa, B., Han, S., Aggarwal, S., Liu, B., Li, G., Soltys, S., Hayden Gephart, M. 2018

  Abstract

  Routine brain MRI surveillance frequently diagnoses small, asymptomatic brain metastases from non-small cell lung cancer (NSCLC) that are effectively treated with stereotactic radiosurgery (SRS). A subset of patients, however, may die prior to the onset of symptoms. This study identifies clinical features that distinguish neurologically-asymptomatic NSCLC brain metastases patients that die prior to routine 3 month follow-up after SRS.Retrospective chart review from 2007 to 2017 identified 18 patients with neurologically-asymptomatic NSCLC brain metastases who died < 3 months after SRS. Twenty-eight additional patients meeting criteria and surviving > 6 months after SRS were identified. Clinical factors were examined to determine characteristics correlated with survival using cox proportional hazards and nominal logistic regression models. Logistic regression models using salient factors were trained with 10-fold cross-validation and compared to the graded prognostic assessment (GPA) and score index of radiosurgery (SIR) using the AUC from receiver operant characteristic curves.The median survival following SRS was 1.4 and 9.2 months for the < 3 months and > 6 months groups, respectively. Age, number of brain metastases, and Karnofsky performance status were associated with overall survival while gender and interval between primary cancer and first brain metastasis diagnoses were associated with < 3 months and > 6 months survival, respectively. Models using GPA and SIR performed poorly compared to preliminary metrics generated in this study for prognosis of both < 3 months and > 6 months survival.Physicians require data to provide high-value, cost-conscious health care. Clinical metrics can screen patients with asymptomatic NSCLC brain metastases likely to die prior to the standard screening interval and observation could be considered.

  View details for DOI 10.1007/s11060-018-03002-0

  View details for PubMedID 30460628

• Long-Term Update of Stereotactic Radiosurgery for Benign Spinal Tumors. Neurosurgery Chin, A. L., Fujimoto, D., Kumar, K. A., Tupper, L., Mansour, S., Chang, S. D., Adler, J. R., Gibbs, I. C., Hancock, S. L., Dodd, R., Li, G., Gephart, M. H., Ratliff, J. K., Tse, V., Usoz, M., Sachdev, S., Soltys, S. G. 2018

  Abstract

  Stereotactic radiosurgery (SRS) for benign intracranial tumors is an established standard of care. The widespread implementation of SRS for benign spinal tumors has been limited by lack of long-term data.To update our institutional experience of safety and efficacy outcomes after SRS for benign spinal tumors.We performed a retrospective cohort study of 120 patients with 149 benign spinal tumors (39 meningiomas, 26 neurofibromas, and 84 schwannomas) treated with SRS between 1999 and 2016, with follow-up magnetic resonance imaging available for review. The primary endpoint was the cumulative incidence of local failure (LF), with death as a competing risk. Secondary endpoints included tumor shrinkage, symptom response, toxicity, and secondary malignancy.Median follow-up was 49 mo (interquartile range: 25-103 mo, range: 3-216 mo), including 61 courses with >5 yr and 24 courses with >10 yr of follow-up. We observed 9 LF for a cumulative incidence of LF of 2%, 5%, and 12% at 3, 5, and 10 yr, respectively. Excluding 10 tumors that were previously irradiated or that arose within a previously irradiated field, the 3-, 5-, and 10-yr cumulative incidence rates of LF were 1%, 2%, and 8%, respectively. At last follow-up, 35% of all lesions had decreased in size. With a total of 776 patient-years of follow-up, no SRS-related secondary malignancies were observed.Comparable to SRS for benign intracranial tumors, SRS provides longer term local control of benign spinal tumors and is a standard-of-care alternative to surgical resection.

  View details for DOI 10.1093/neuros/nyy442

  View details for PubMedID 30445557

• Osimertinib for EGFR-Mutant Lung Cancer with Brain Metastases: Results from a Single-Center Retrospective Study. The oncologist Xie, L., Nagpal, S., Wakelee, H. A., Li, G., Soltys, S. G., Neal, J. W. 2018

  Abstract

  Osimertinib is a third-generation tyrosine kinase inhibitor, initially approved for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) with T790M acquired resistance, and now approved in the first-line setting. However, data supporting the use of osimertinib in untreated brain metastases are limited, although it has established central nervous system (CNS) activity. Our study compares the clinical outcomes of patients experiencing progressing brain metastases treated with cranial irradiation and osimertinib with those treated with osimertinib alone.Forty patients who were treated with osimertinib at the Stanford Cancer Center from November 2015 to December 2016 were identified by searching an electronic medical record database. Eleven patients had progressing brain metastases and did not receive radiation (group A), 9 patients had progressing brain metastases and received radiation when starting osimertinib (group B), and 20 patients had stable brain metastases at the time of initiating osimertinib (group C). Patient and disease characteristics, radiographic responses, and survival outcomes were evaluated retrospectively for the three groups.The CNS response rate was 32.3%. Median time to treatment failure (TTF), overall progression-free survival (PFS), and overall survival (OS) were 10.0 months (95% confidence interval [CI], 4.5-11.8), 8.8 months (95% CI, 6.2-12.1), and 16.2 months, respectively. Median TTF was 15.1 months for group A (95% CI, 1.7-28.5), 7.7 months for group B (95% CI, 0-15.5), and 10.7 months for group C (95% CI, 9.0-12.5). The median PFS was 8.8 months for group A (95% CI, 4.3-13.4), not reached for group B, and 8.4 months for group C (95% CI, 5.6-11.1). The median OS was not reached for group A and C, and was 16.2 months for group B. There was no apparent difference in TTF, PFS, or OS between the three groups.Receiving radiation prior to starting osimertinib for patients with progressing brain metastases did not prolong TTF, PFS, or OS in our series. To minimize the risks of radiation-related toxicity, delaying radiation could be considered for some patients with EGFR-mutant NSCLC with brain metastases who initially respond to osimertinib in the second-line setting.Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor recently approved for the first-line treatment of EGFR-mutant non-small cell lung cancer. Although it appears to have central nervous system (CNS) activity, most clinical trials have excluded patients with untreated, progressing brain metastases. This study included patients with stable and progressing CNS metastases treated with osimertinib and found no apparent differences in median time to treatment failure, time to progression, and overall survival in patients who received osimertinib alone compared with those who received osimertinib and radiosurgery. This may support a clinician's decision to defer radiation for selected patients with untreated brain metastases who are candidates for osimertinib therapy.

  View details for DOI 10.1634/theoncologist.2018-0264

  View details for PubMedID 30126856

• Preoperative Vs Postoperative Radiosurgery For Resected Brain Metastases: A Review. Neurosurgery Prabhu, R. S., Patel, K. R., Press, R. H., Soltys, S. G., Brown, P. D., Mehta, M. P., Asher, A. L., Burri, S. H. 2018

  Abstract

  Patients who undergo surgical resection of brain metastases are at significant risk of cavity local recurrence without additional radiation therapy. Postoperative stereotactic radiosurgery (SRS) is a method of focal treatment to the cavity to maximize local control while minimizing the risk of neurocognitive detriment associated with whole brain radiation therapy. Recently published randomized trials have demonstrated the benefit of postoperative SRS in terms of cavity tumor control and preserving neurocognition. However, there are several potential drawbacks with postoperative SRS including a possible increase in symptomatic radiation necrosis because of the need for cavity margin expansion due to target delineation uncertainty, the variable postoperative clinical course and potential delay in administering postoperative SRS, and the theoretical risk of tumor spillage into cerebrospinal fluid at the time of surgery. Preoperative SRS is an alternative paradigm wherein SRS is delivered prior to surgical resection, which may effectively address some of these potential drawbacks. The goal of this review is to examine the rationale, technique, outcomes, evidence, and future directions for the use of SRS as an adjunct to surgical resection. This can be delivered as either preoperative or postoperative SRS with potential advantages and disadvantages to both approaches that will be discussed.

  View details for DOI 10.1093/neuros/nyy146

  View details for PubMedID 29771381

• Stereotactic Radiosurgery for Skull Base Chordomas and Chondrosarcomas CHORDOMAS AND CHONDROSARCOMAS OF THE SKULL BASE AND SPINE, 2ND EDITION Shoo, B., Soltys, S. G., White, E., Fujimoto, D. K., Gibbs, I. C., Harsh, G. R., VazGuimaraes, F. 2018: 339–46

  View details for DOI 10.1016/B978-0-12-804257-1.00031-1

  View details for Web of Science ID 000426245100033

• Correlation between small-volume spinal cord doses for spine stereotactic body radiotherapy (SBRT) JOURNAL OF RADIOSURGERY AND SBRT Ma, L., Wang, L., Lee, Y., Tseng, C., Soltys, S., Braunstein, S., Sahgal, A. 2018; 5 (3): 229–36

  View details for Web of Science ID 000435021500007

• Phase 1/2 Trial of 5-Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma: Health-Related Quality of Life Results. International journal of radiation oncology, biology, physics Pollom, E. L., Fujimoto, D., Wynne, J., Seiger, K., Modlin, L. A., Jacobs, L. R., Azoulay, M., von Eyben, R., Tupper, L., Gibbs, I. C., Hancock, S. L., Li, G., Chang, S. D., Adler, J. R., Harsh, G. R., Harraher, C., Nagpal, S., Thomas, R. P., Recht, L. D., Choi, C. Y., Soltys, S. G. 2017; 98 (1): 123-130

  Abstract

  We report a longitudinal assessment of health-related quality of life (HRQOL) in patients with glioblastoma (GBM) treated on a prospective dose escalation trial of 5-fraction stereotactic radiosurgery (25-40 Gy in 5 fractions) with concurrent and adjuvant temozolomide.HRQOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire core-30 (QLQ-C30) general, the EORTC quality of life questionnaire-brain cancer specific module (QLQ-BN20), and the M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT). Questionnaires were completed at baseline and at every follow-up visit after completion of radiosurgery. Changes from baseline for 9 predefined HRQOL measures (global quality of life, physical functioning, social functioning, emotional functioning, motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty) were calculated at every time point.With a median follow-up time of 10.4 months (range, 0.4-52 months), 139 total HRQOL questionnaires were completed by the 30 patients on trial. Compliance with HRQOL assessment was 76% at 12 months. Communication deficit significantly worsened over time, with a decline of 1.7 points per month (P=.008). No significant changes over time were detected in the other 8 scales of our primary analysis, including global quality of life. Although 8 patients (27%) experienced adverse radiation effects (ARE) on this dose escalation trial, it was not associated with a statistically significant decline in any of the primary HRQOL scales. Disease progression was associated with communication deficit, with patients experiencing an average worsening of 13.9 points per month after progression compared with 0.7 points per month before progression (P=.01).On this 5-fraction dose escalation protocol for newly diagnosed GBM, overall HRQOL remained stable and appears similar to historical controls of 30 fractions of radiation therapy. Tumor recurrence was associated with worsening communication deficit, and ARE did not correlate with a decline in HRQOL.

  View details for DOI 10.1016/j.ijrobp.2017.01.242

  View details for PubMedID 28586949

• The radiosurgery fractionation quandary: single fraction or hypofractionation? NEURO-ONCOLOGY Kirkpatrick, J. P., Soltys, S. G., Lo, S. S., Beal, K., Shrieve, D. C., Brown, P. D. 2017; 19: 38-49

  Abstract

  Stereotactic radiosurgery (SRS), typically administered in a single session, is widely employed to safely, efficiently, and effectively treat small intracranial lesions. However, for large lesions or those in close proximity to critical structures, it can be difficult to obtain an acceptable balance of tumor control while avoiding damage to normal tissue when single-fraction SRS is utilized. Treating a lesion in 2 to 5 fractions of SRS (termed "hypofractionated SRS" [HF-SRS]) potentially provides the ability to treat a lesion with a total dose of radiation that provides both adequate tumor control and acceptable toxicity. Indeed, studies of HF-SRS in large brain metastases, vestibular schwannomas, meningiomas, and gliomas suggest that a superior balance of tumor control and toxicity is observed compared with single-fraction SRS. Nonetheless, a great deal of effort remains to understand radiobiologic mechanisms for HF-SRS driving the dose-volume response relationship for tumors and normal tissues and to utilize this fundamental knowledge and the results of clinic studies to optimize HF-SRS. In particular, the application of HF-SRS in the setting of immunomodulatory cancer therapies offers special challenges and opportunities.

  View details for DOI 10.1093/neuonc/now301

  View details for Web of Science ID 000400895800005

  View details for PubMedCentralID PMC5463582

• Consensus guidelines for postoperative stereotactic body radiation therapy for spinal metastases: results of an international survey. Journal of neurosurgery. Spine Redmond, K. J., Lo, S. S., Soltys, S. G., Yamada, Y., Barani, I. J., Brown, P. D., Chang, E. L., Gerszten, P. C., Chao, S. T., Amdur, R. J., De Salles, A. A., Guckenberger, M., Teh, B. S., Sheehan, J., Kersh, C. R., Fehlings, M. G., Sohn, M., Chang, U., Ryu, S., Gibbs, I. C., Sahgal, A. 2017; 26 (3): 299-306

  Abstract

  OBJECTIVE Although postoperative stereotactic body radiation therapy (SBRT) for spinal metastases is increasingly performed, few guidelines exist for this application. The purpose of this study is to develop consensus guidelines to promote safe and effective treatment for patients with spinal metastases. METHODS Fifteen radiation oncologists and 5 neurosurgeons, representing 19 centers in 4 countries and having a collective experience of more than 1300 postoperative spine SBRT cases, completed a 19-question survey about postoperative spine SBRT practice. Responses were defined as follows: 1) consensus: selected by ≥ 75% of respondents; 2) predominant: selected by 50% of respondents or more; and 3) controversial: no single response selected by a majority of respondents. RESULTS Consensus treatment indications included: radioresistant primary, 1-2 levels of adjacent disease, and previous radiation therapy. Contraindications included: involvement of more than 3 contiguous vertebral bodies, ASIA Grade A status (complete spinal cord injury without preservation of motor or sensory function), and postoperative Bilsky Grade 3 residual (cord compression without any CSF around the cord). For treatment planning, co-registration of the preoperative MRI and postoperative T1-weighted MRI (with or without gadolinium) and delineation of the cord on the T2-weighted MRI (and/or CT myelogram in cases of significant hardware artifact) were predominant. Consensus GTV (gross tumor volume) was the postoperative residual tumor based on MRI. Predominant CTV (clinical tumor volume) practice was to include the postoperative bed defined as the entire extent of preoperative tumor, the relevant anatomical compartment and any residual disease. Consensus was achieved with respect to not including the surgical hardware and incision in the CTV. PTV (planning tumor volume) expansion was controversial, ranging from 0 to 2 mm. The spinal cord avoidance structure was predominantly the true cord. Circumferential treatment of the epidural space and margin for paraspinal extension was controversial. Prescription doses and spinal cord tolerances based on clinical scenario, neurological compromise, and prior overlapping treatments were controversial, but reasonable ranges are presented. Fifty percent of those surveyed practiced an integrated boost to areas of residual tumor and density override for hardware within the beam path. Acceptable PTV coverage was controversial, but consensus was achieved with respect to compromising coverage to meet cord constraint and fractionation to improve coverage while meeting cord constraint. CONCLUSIONS The consensus by spinal radiosurgery experts suggests that postoperative SBRT is indicated for radioresistant primary lesions, disease confined to 1-2 vertebral levels, and/or prior overlapping radiotherapy. The GTV is the postoperative residual tumor, and the CTV is the postoperative bed defined as the entire extent of preoperative tumor and anatomical compartment plus residual disease. Hardware and scar do not need to be included in CTV. While predominant agreement was reached about treatment planning and definition of organs at risk, future investigation will be critical in better understanding areas of controversy, including whether circumferential treatment of the epidural space is necessary, management of paraspinal extension, and the optimal dose fractionation schedules.

  View details for DOI 10.3171/2016.8.SPINE16121

  View details for PubMedID 27834628

• Stereotactic radiosurgery for non-vestibular cranial nerve schwanommas JOURNAL OF NEURO-ONCOLOGY D'Astous, M., Ho, A. L., Pendharkar, A., Choi, C. Y., Soltys, S. G., Gibbs, I. C., Tayag, A. T., Thompson, P. A., Adler, J. R., Chang, S. D. 2017; 131 (1): 177-183

  View details for DOI 10.1007/s11060-016-2286-7

  View details for Web of Science ID 000393065400019

• Consensus Contouring Guidelines for Postoperative Completely Resected Cavity Stereotactic Radiosurgery for Brain Metastases. International journal of radiation oncology, biology, physics Soliman, H., Ruschin, M., Angelov, L., Brown, P. D., Chiang, V. L., Kirkpatrick, J. P., Lo, S. S., Mahajan, A., Oh, K. S., Sheehan, J. P., Soltys, S. G., Sahgal, A. 2017

  Abstract

  To propose contouring guidelines based on consensus contours generated by 10 international experts for cavity stereotactic radiosurgery (SRS), an emerging treatment option after surgical resection of brain metastases. No guidelines for contouring the surgical cavity volume have been previously reported.Ten postoperative completely resected cases with varying clinical scenarios and locations within the brain were selected. For each case, 10 experts independently contoured the surgical cavity clinical target volume (CTV). All the contours were analyzed, and agreement was calculated using the simultaneous truth and performance level estimation (STAPLE) with the kappa statistic. A follow-up survey was also completed by each investigator to summarize their contouring rationale for a number of different clinical scenarios. The results from the survey and the consensus STAPLE contours were both summarized to establish contouring guidelines.A high level of agreement was found between the expert CTV contours (mean sensitivity 0.75, mean specificity 0.98), and the mean kappa was 0.65. The agreement was statistically significant at P<.001 for all cases. From these results and analyses of the survey answers, the recommendations for CTV include fusion of the preoperative magnetic resonance imaging scan to aid in volume delineation; contouring the entire surgical tract regardless of the preoperative location of the tumor; extension of the CTV 5 to 10 mm along the dura overlying the bone flap to account for microscopic disease extension in cases with preoperative dural contact; and a margin of ≤5 mm into the adjacent sinus when preoperative venous sinus contact was present.Consensus contouring guidelines for postoperative completely resected cavity SRS treatment were established using expert contours and clinical practice. However, in the absence of clinical data supporting these recommendations, these guidelines serve as a baseline for further study and refinement.

  View details for DOI 10.1016/j.ijrobp.2017.09.047

  View details for PubMedID 29157748

• Consensus Contouring Guidelines for Postoperative Stereotactic Body Radiation Therapy for Metastatic Solid Tumor Malignancies to the Spine INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Redmond, K. J., Robertson, S., Lo, S. S., Soltys, S. G., Ryu, S., McNutt, T., Chao, S. T., Yamada, Y., Ghia, A., Chang, E. L., Sheehan, J., Sahgal, A. 2017; 97 (1): 64-74

  Abstract

  To develop consensus contouring guidelines for postoperative stereotactic body radiation therapy (SBRT) for spinal metastases.Ten spine SBRT specialists representing 10 international centers independently contoured the clinical target volume (CTV), planning target volume (PTV), spinal cord, and spinal cord planning organ at risk volume (PRV) for 10 representative clinical scenarios in postoperative spine SBRT for metastatic solid tumor malignancies. Contours were imported into the Computational Environment for Radiotherapy Research. Agreement between physicians was calculated with an expectation minimization algorithm using simultaneous truth and performance level estimation with κ statistics. Target volume definition guidelines were established by finding optimized confidence level consensus contours using histogram agreement analyses.Nine expert radiation oncologists and 1 neurosurgeon completed contours for all 10 cases. The mean sensitivity and specificity were 0.79 (range, 0.71-0.89) and 0.94 (range, 0.90-0.99) for the CTV and 0.79 (range, 0.70-0.95) and 0.92 (range, 0.87-0.99) for the PTV), respectively. Mean κ agreement, which demonstrates the probability that contours agree by chance alone, was 0.58 (range, 0.43-0.70) for CTV and 0.58 (range, 0.37-0.76) for PTV (P<.001 for all cases). Optimized consensus contours were established for all patients with 80% confidence interval. Recommendations for CTV include treatment of the entire preoperative extent of bony and epidural disease, plus immediately adjacent bony anatomic compartments at risk of microscopic disease extension. In particular, a "donut-shaped" CTV was consistently applied in cases of preoperative circumferential epidural extension, regardless of extent of residual epidural extension. Otherwise more conformal anatomic-based CTVs were determined and described. Spinal instrumentation was consistently excluded from the CTV.We provide consensus contouring guidelines for common scenarios in postoperative SBRT for spinal metastases. These consensus guidelines are subject to clinical validation.

  View details for DOI 10.1016/j.ijrobp.2016.09.014

  View details for Web of Science ID 000393293300016

  View details for PubMedID 27843035

• Imaging changes over 18 months following stereotactic radiosurgery for brain metastases: both late radiation necrosis and tumor progression can occur. Journal of neuro-oncology Fujimoto, D., von Eyben, R., Gibbs, I. C., Chang, S. D., Li, G., Harsh, G. R., Hancock, S., Fischbein, N., Soltys, S. G. 2017

  Abstract

  Following stereotactic radiosurgery (SRS) for brain metastases, the median time range to develop adverse radiation effect (ARE) or radiation necrosis is 7-11 months. Similarly, the risk of local tumor recurrence following SRS is < 5% after 18 months. With improvements in systemic therapy, patients are living longer and are at risk for both late (defined as > 18 months after SRS) tumor recurrence and late ARE, which have not previously been well described. An IRB-approved, retrospective review identified patients treated with SRS who developed new MRI contrast enhancement > 18 months following SRS. ARE was defined as stabilization/shrinkage of the lesion over time or pathologic confirmation of necrosis, without tumor. Local failure (LF) was defined as continued enlargement of the lesion over time or pathologic confirmation of tumor. We identified 16 patients, with a median follow-up of 48.2 months and median overall survival of 73.0 months, who had 19 metastases with late imaging changes occurring a median of 32.9 months (range 18.5-63.2 months) after SRS. Following SRS, 12 lesions had late ARE at a median of 33.2 months and 7 lesions had late LF occurring a median of 23.6 months. As patients with cancer live longer and as SRS is increasingly utilized for treatment of brain metastases, the incidence of these previously rare imaging changes is likely to increase. Clinicians should be aware of these late events, with ARE occurring up to 5.3 years and local failure up to 3.8 years following SRS in our cohort.

  View details for DOI 10.1007/s11060-017-2647-x

  View details for PubMedID 29098569

• New Hypofractionation Radiation Strategies for Glioblastoma. Current oncology reports Azoulay, M., Shah, J., Pollom, E., Soltys, S. G. 2017; 19 (9): 58

  Abstract

  Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, with a median survival of less than 2 years despite the standard of care treatment of 6 weeks of chemoradiotherapy. We review the data investigating hypofractionated radiotherapy (HFRT) in the treatment of newly diagnosed GBM.Investigators have explored alternative radiotherapy strategies that shorten treatment duration with the goal of similar or improved survival while minimizing toxicity. HFRT over 1-3 weeks is already a standard of care for patients with advanced age or poor performance status. For young patients with good performance status, HFRT holds the promise of radiobiologically escalating the dose and potentially improving local control while maintaining quality of life. Through the use of shorter radiotherapy fractionation regimens coupled with novel systemic agents, improved outcomes for patients with GBM may be achieved.

  View details for DOI 10.1007/s11912-017-0616-3

  View details for PubMedID 28735440

• Cost-Effectiveness of Radiation and Chemotherapy for High-Risk Low-Grade Glioma. Neuro-oncology Qian, Y., Maruyama, S., Kim, H., Pollom, E. L., Kumar, K. A., Chin, A. L., Harris, J. P., Chang, D. T., Pitt, A., Bendavid, E., Owens, D. K., Durkee, B. Y., Soltys, S. G. 2017

  Abstract

  The addition of PCV (procarbazine, lomustine, vincristine) chemotherapy to radiotherapy (RT) for patients with high-risk (≥ 40 years old or sub-totally resected) low-grade glioma (LGG) results in an absolute median survival benefit of over 5 years. We evaluated the cost-effectiveness of this treatment strategy.A decision tree with an integrated three-state Markov model was created to follow patients with high risk LGG after surgery treated with RT vs. RT+PCV. Patients existed in one of 3 health states: stable, progressive, and dead. Survival and freedom from progression were modeled to reflect the results of RTOG 9802 using time-dependent transition probabilities. Health utility values and costs of care were derived from the literature and national registry databases. Analysis was conducted from the healthcare perspective. Deterministic and probabilistic sensitivity analysis explored uncertainty in model parameters.Modeled outcomes demonstrated agreement with clinical data in expected benefit of addition of PCV to RT. The addition of PCV to RT yielded an incremental benefit of 4.77 quality-adjusted life-years (QALYs) (9.94 for RT+PCV vs. 5.17 for RT alone) at an incremental cost of $48,635 ($188,234 for RT+PCV vs. $139,598 for RT alone), resulting in an incremental cost-effectiveness ratio of $10,186 per QALY gained. Probabilistic sensitivity analysis demonstrates that within modeled distributions of parameters, RT+PCV has 99.96% probability of being cost-effectiveness at a willingness-to-pay threshold of $100,000 per QALY.The addition of PCV to RT is a cost-effective treatment strategy for patients with high-risk LGG.

  View details for DOI 10.1093/neuonc/nox121

  View details for PubMedID 28666368

• Vorinostat and Concurrent Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases: A Phase 1 Dose Escalation Trial. International journal of radiation oncology, biology, physics Choi, C. Y., Wakelee, H. A., Neal, J. W., Pinder-Schenck, M. C., Yu, H. M., Chang, S. D., Adler, J. R., Modlin, L. A., Harsh, G. R., Soltys, S. G. 2017; 99 (1): 16–21

  Abstract

  To determine the maximum tolerated dose (MTD) of vorinostat, a histone deacetylase inhibitor, given concurrently with stereotactic radiosurgery (SRS) to treat non-small cell lung cancer (NSCLC) brain metastases. Secondary objectives were to determine toxicity, local failure, distant intracranial failure, and overall survival rates.In this multicenter study, patients with 1 to 4 NSCLC brain metastases, each ≤2 cm, were enrolled in a phase 1, 3 + 3 dose escalation trial. Vorinostat dose levels were 200, 300, and 400 mg orally once daily for 14 days. Single-fraction SRS was delivered on day 3. A dose-limiting toxicity (DLT) was defined as any Common Terminology Criteria for Adverse Events version 3.0 grade 3 to 5 acute nonhematologic adverse event related to vorinostat or SRS occurring within 30 days.From 2009 to 2014, 17 patients were enrolled and 12 patients completed study treatment. Because no DLTs were observed, the MTD was established as 400 mg. Acute adverse events were reported by 10 patients (59%). Five patients discontinued vorinostat early and withdrew from the study. The most common reasons for withdrawal were dyspnea (n=2), nausea (n=1), and fatigue (n=2). With a median follow-up of 12 months (range, 1-64 months), Kaplan-Meier overall survival was 13 months. There were no local failures. One patient (8%) at the 400-mg dose level with a 2.0-cm metastasis developed histologically confirmed grade 4 radiation necrosis 2 months after SRS.The MTD of vorinostat with concurrent SRS was established as 400 mg. Although no DLTs were observed, 5 patients withdrew before completing the treatment course, a result that emphasizes the need for supportive care during vorinostat administration. There were no local failures. A larger, randomized trial may evaluate both the tolerability and potential local control benefit of vorinostat concurrent with SRS for brain metastases.

  View details for DOI 10.1016/j.ijrobp.2017.04.041

  View details for PubMedID 28816142

• Ablative Radiotherapy as a Noninvasive Alternative to Catheter Ablation for Cardiac Arrhythmias. Current cardiology reports Zei, P. C., Soltys, S. 2017; 19 (9): 79

  Abstract

  Stereotactic radioablation is a commonly utilized technology to noninvasively treat solid tumors with precision and efficacy. Using a robotic arm mounted delivery system, multiple low-dose ionizing radiation beams are delivered from multiple angles, concentrating ablative energy at the target tissue. Recently, this technology has been evaluated for treatment of cardiac arrhythmias. This review will present the basic underlying principles, proof-of-principle studies, and clinical experience with stereotactic arrhythmia radioablation.Most recently, stereotactic radioablation has been used to safely and effectively treat a limited number of patients with malignant arrhythmias, including ventricular tachycardia (VT) and atrial fibrillation (AF). Treatment protocols, outcomes, ongoing studies, and future directions will be discussed. Stereotactic radioablation is a well-established technology that has been shown to be a safe and effective therapy for patients with drug-refractory cardiac arrhythmias, including VT and AF. Further clinical evaluation to define safety and efficacy in larger populations of patients is needed.

  View details for DOI 10.1007/s11886-017-0886-2

  View details for PubMedID 28752279

  View details for PubMedCentralID PMC5532420

• Stereotactic Radiosurgery and Hypofractionated Radiotherapy for Glioblastoma. Neurosurgery Shah, J. L., Li, G., Shaffer, J. L., Azoulay, M. I., Gibbs, I. C., Nagpal, S., Soltys, S. G. 2017

  Abstract

  Glioblastoma is the most common primary brain tumor in adults. Standard therapy depends on patient age and performance status but principally involves surgical resection followed by a 6-wk course of radiation therapy given concurrently with temozolomide chemotherapy. Despite such treatment, prognosis remains poor, with a median survival of 16 mo. Challenges in achieving local control, maintaining quality of life, and limiting toxicity plague treatment strategies for this disease. Radiotherapy dose intensification through hypofractionation and stereotactic radiosurgery is a promising strategy that has been explored to meet these challenges. We review the use of hypofractionated radiotherapy and stereotactic radiosurgery for patients with newly diagnosed and recurrent glioblastoma.

  View details for DOI 10.1093/neuros/nyx115

  View details for PubMedID 28605463

• Image-guided stereotactic radiosurgery for treatment of spinal hemangioblastoma NEUROSURGICAL FOCUS Pan, J., Ho, A. L., D'Astous, M., Sussman, E. S., Thompson, P. A., Tayag, A. T., Pangilinan, L., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2017; 42 (1)

  Abstract

  OBJECTIVE Stereotactic radiosurgery (SRS) has been an attractive treatment option for hemangioblastomas, especially for lesions that are surgically inaccessible and in patients with von Hippel-Lindau (VHL) disease and multiple lesions. Although there has been a multitude of studies examining the utility of SRS in intracranial hemangioblastomas, SRS has only recently been used for spinal hemangioblastomas due to technical limitations. The purpose of this study is to provide a long-term evaluation of the effectiveness of image-guided radiosurgery in halting tumor progression and providing symptomatic relief for spinal hemangioblastomas. METHODS Between 2001 and 2011, 46 spinal hemangioblastomas in 28 patients were treated using the CyberKnife image-guided radiosurgery system at the authors' institution. Fourteen of these patients also had VHL disease. The median age at treatment was 43.5 years (range 19-85 years). The mean prescription radiation dose to the tumor periphery was 21.6 Gy (range 15-35 Gy). The median tumor volume was 0.264 cm(3) (range 0.025-70.9 cm(3)). Tumor response was evaluated on serial, contrast-enhanced CT and MR images. Clinical response was evaluated by clinical and imaging evaluation. RESULTS The mean follow-up for the cohort was 54.3 months. Radiographic follow-up was available for 19 patients with 34 tumors; 32 (94.1%) tumors were radiographically stable or displayed signs of regression. Actuarial control rates at 1, 3, and 5 years were 96.1%, 92.3%, and 92.3%, respectively. Clinical evaluation on follow-up was available for 13 patients with 16 tumors; 13 (81.2%) tumors in 10 patients had symptomatic improvement. No patient developed any complications related to radiosurgery. CONCLUSIONS Image-guided SRS is safe and effective for the primary treatment of spinal hemangioblastomas and is an attractive alternative to resection, especially for those with VHL disease.

  View details for DOI 10.3171/2016.10.FOCUS16361

  View details for Web of Science ID 000392113200012

  View details for PubMedID 28041328

• Brain Metastases From Melanoma: Therapy at the Crossroads INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Kirkpatrick, J. P., Laack, N. N., Soltys, S. G., Halasz, L. M., Breneman, J. C., Shih, H. A. 2016; 96 (4): 713-716

  View details for DOI 10.1016/j.ijrobp.2016.06.005

  View details for Web of Science ID 000385524000001

  View details for PubMedID 27788943

• The Outcome of Hypofractionated Stereotactic Radiosurgery for Large Vestibular Schwannomas. World neurosurgery Teo, M., Zhang, M., Li, A., Thompson, P. A., Tayag, A. T., Wallach, J., Gibbs, I. C., Soltys, S. G., Hancock, S. L., Chang, S. D. 2016; 93: 398-409

  Abstract

  Stereotactic radiosurgery (SRS) for large vestibular schwannomas (VS) remains controversial. We studied the tumor local control and toxicity rates after hypofractionated SRS for VS > 3 cm.A total of 587 patients with VS treated with SRS between 1998 and 2014 were reviewed retrospectively, and 30 Koos grade IV VSs were identified. There were 6 patients with neurofibromatosis 2 (NF2), 8 with cystic tumors, 22 with solid tumors, 19 who underwent primary CyberKnife (CK), and 11 with >3 cm after previous resection. Patients were treated by a median of 3 fractions at 18 Gy.After a median 97 months, the 3- and 10-year Kaplan-Meier estimates of local control were 85% and 80%, respectively, with 20% requiring salvage treatment. For patients who had previous tumor resection rather than primary CK, the estimates were 46% and 5%, respectively, with progression, and 3-year control rates of 71% and 94% (P = 0.008). Tumor control was also lower among NF2 versus non-NF2 patients (40% vs. 95%; P = 0.0014). Among patients with good clinical baselines before CK, 88% were functionally independent (modified Rankin Scale score, 0-2), 88% had good facial function (House-Brackmann grade I-II), and 38% had serviceable hearing (Gardner-Robertson grade I-II) at last follow-up. Hearing worsening was more likely among patients treated with primary CK (33% vs. 90%; P = 0.04).Overall, 80% of large VSs were adequately controlled by CK with 97 months of median follow-up. Patients with previous surgery and NF2 also appeared to have higher rates of tumor progression, and less favorable functional outcomes.

  View details for DOI 10.1016/j.wneu.2016.06.080

  View details for PubMedID 27368508

• CyberKnife Stereotactic Radiosurgery for Atypical and Malignant Meningiomas. World neurosurgery Zhang, M., Ho, A. L., D'Astous, M., Pendharkar, A. V., Choi, C. Y., Thompson, P. A., Tayag, A. T., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2016; 91: 574-581 e1

  Abstract

  Recurrent World Health Organization (WHO) grade II and III meningiomas have traditionally been treated by surgery alone, but early literature suggests that adjuvant stereotactic radiosurgery may greatly improve outcomes. We present the long-term tumor control and safety of a hypofractionated stereotactic radiosurgery regimen.Prospectively collected data of 44 WHO grade II and 9 WHO grade III meningiomas treated by CyberKnife for adjuvant or salvage therapy were reviewed. Patient demographics, treatment parameters, local control, regional control, locoregional control, overall survival, radiation history, and complications were documented.For WHO grade II patients, recurrence occurred in 41%, with local, regional, and locoregional failure at 60 months recorded as 49%, 58%, and 36%. For WHO grade III patients, recurrence occurred in 66%, with local, regional, and locoregional failure at 12 months recorded as 57%, 100%, and 43%. The 60-month locoregional control rates for radiation naïve and experienced patients were 48% and 0% (P = 0.14). Overall, 7 of 44 grade II patients and 8 of 9 grade III patients had died at last follow-up. The 60-month and 12-month overall survival rates for grade II and III meningiomas were 87% and 50%, respectively. Serious complications occurred in 7.5% of patients.Stereotactic radiosurgery for adjuvant and salvage treatment of WHO grade II meningioma using a hypofractionated plan is a viable treatment strategy with acceptable long-term tumor control, overall survival, and complication rates. Future studies should focus on radiation-naïve patients and local management of malignant meningioma.

  View details for DOI 10.1016/j.wneu.2016.04.019

  View details for PubMedID 27108030

• Stereotactic radiosurgery for intramedullary spinal arteriovenous malformations JOURNAL OF CLINICAL NEUROSCIENCE Kalani, M. A., Choudhri, O., Gibbs, I. C., Soltys, S. G., Adler, J. R., Thompson, P. A., Tayag, A. T., Samos, C. H., Chang, S. D. 2016; 29: 162-167

  Abstract

  Spinal cord arteriovenous malformations (AVM) are rare lesions associated with recurrent hemorrhage and progressive ischemia. Occasionally a favorable location, size or vascular anatomy may allow management with endovascular embolization and/or microsurgical resection. For most, however, there is no good treatment option. Between 1997 and 2014, we treated 37 patients (19 females, 18 males, median age 30years) at our institution diagnosed with intramedullary spinal cord AVM (19 cervical, 12 thoracic, and six conus medullaris) with CyberKnife (Accuray, Sunnyvale, CA, USA) stereotactic radiosurgery. A history of hemorrhage was present in 50% of patients. The mean AVM volume of 2.3cc was treated with a mean marginal dose of 20.5Gy in a median of two sessions. Clinical and MRI follow-up were carried out annually, and spinal angiography was repeated at 3years. We report an overall obliteration rate of 19% without any post-treatment hemorrhagic events. In those AVM that did not undergo obliteration, significant volume reduction was noted at 3years. Although the treatment paradigm for spinal cord AVM continues to evolve, radiosurgical treatment is capable of safely obliterating or significantly shrinking most intramedullary spinal cord AVM.

  View details for DOI 10.1016/j.jocn.2015.12.005

  View details for Web of Science ID 000378449800032

  View details for PubMedID 26869363

• The Parotid Gland is an Underrecognized Organ at Risk for Craniospinal Irradiation TECHNOLOGY IN CANCER RESEARCH & TREATMENT King, M. T., Modlin, L., Million, L., Donaldson, S. S., Gibbs, I. C., Choi, C. Y., Soltys, S. G. 2016; 15 (3): 472-479

  Abstract

  Current craniospinal irradiation (CSI) protocols do not include the parotid gland as an organ at risk, potentially leading to late effects of xerostomia and secondary parotid malignancies. We analyzed the effect of CSI treatment parameters on parotid dose.We retrospectively reviewed 50 consecutive patients treated with CSI to an intracranial dose >26 Gy. Parotid dose was compared to a Radiation Therapy Oncology Group (RTOG) dose constraint (at least 1 parotid with mean dose <26 Gy). The effects of CSI dose (≤24 Gy vs 24 Gy), volumetric-modulated arc therapy (VMAT) versus 3-dimensional (3D) CSI technique, boost dose (≤24 Gy vs 24 Gy), supratentorial versus infratentorial boost location, intensity-modulated radiation therapy (IMRT)-based versus 3D boost technique, supine versus prone position, and age on parotid dose were analyzed using multivariate regression analysis.The RTOG parotid dose constraint was exceeded in 22 (44%) of 50 patients. On multivariate regression analysis, lower CSI dose and VMAT CSI technique were associated with reduced parotid dose for the CSI fields. For the boost fields, lower boost dose and supratentorial boost location were associated with lower parotid dose. All 5 patients who underwent VMAT CSI met dose constraints. Furthermore, for infratentorial lesions with a total (CSI plus boost) dose prescription dose >50 Gy (n = 24), 11 of 16 patients who received low-dose CSI (18-23.4 Gy) were able to meet dose constraints, when compared to only 2 of 8 patients who received high dose CSI (36 Gy).Given the large number of patients exceeding the parotid dose constraint, the parotid gland should be considered an organ at risk. CSI dose de-escalation and IMRT-based CSI techniques may minimize the risk of xerostomia.

  View details for DOI 10.1177/1533034615583406

  View details for Web of Science ID 000375704500008

  View details for PubMedID 25948323

• Estimated Risk Level of Unified Stereotactic Body Radiation Therapy Dose Tolerance Limits for Spinal Cord. Seminars in radiation oncology Grimm, J., Sahgal, A., Soltys, S. G., Luxton, G., Patel, A., Herbert, S., Xue, J., Ma, L., Yorke, E., Adler, J. R., Gibbs, I. C. 2016; 26 (2): 165-171

  Abstract

  A literature review of more than 200 stereotactic body radiation therapy spine articles from the past 20 years found only a single article that provided dose-volume data and outcomes for each spinal cord of a clinical dataset: the Gibbs 2007 article (Gibbs et al, 2007(1)), which essentially contains the first 100 stereotactic body radiation therapy (SBRT) spine treatments from Stanford University Medical Center. The dataset is modeled and compared in detail to the rest of the literature review, which found 59 dose tolerance limits for the spinal cord in 1-5 fractions. We partitioned these limits into a unified format of high-risk and low-risk dose tolerance limits. To estimate the corresponding risk level of each limit we used the Gibbs 2007 clinical spinal cord dose-volume data for 102 spinal metastases in 74 patients treated by spinal radiosurgery. In all, 50 of the patients were previously irradiated to a median dose of 40Gy in 2-3Gy fractions and 3 patients developed treatment-related myelopathy. These dose-volume data were digitized into the dose-volume histogram (DVH) Evaluator software tool where parameters of the probit dose-response model were fitted using the maximum likelihood approach (Jackson et al, 1995(3)). Based on this limited dataset, for de novo cases the unified low-risk dose tolerance limits yielded an estimated risk of spinal cord injury of ≤1% in 1-5 fractions, and the high-risk limits yielded an estimated risk of ≤3%. The QUANTEC Dmax limits of 13Gy in a single fraction and 20Gy in 3 fractions had less than 1% risk estimated from this dataset, so we consider these among the low-risk limits. In the previously irradiated cohort, the estimated risk levels for 10 and 14Gy maximum cord dose limits in 5 fractions are 0.4% and 0.6%, respectively. Longer follow-up and more patients are required to improve the risk estimates and provide more complete validation.

  View details for DOI 10.1016/j.semradonc.2015.11.010

  View details for PubMedID 27000514

• Dose-Response Modeling of the Visual Pathway Tolerance to Single-Fraction and Hypofractionated Stereotactic Radiosurgery SEMINARS IN RADIATION ONCOLOGY Hiniker, S. M., Modlin, L. A., Choi, C. Y., Atalar, B., Seiger, K., Binkley, M. S., Harris, J. P., Liao, Y. J., Fischbein, N., Wang, L., Ho, A., Lo, A., Chang, S. D., Harsh, G. R., Gibbs, I. C., Hancock, S. L., Li, G., Adler, J. R., Soltys, S. G. 2016; 26 (2): 97-104

  Abstract

  Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using α/β = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures. Both cases were meningiomas treated with 25Gy in 5 fractions, with a 3-fraction equivalent optic nerve Dmax of 19.2 and 22.2Gy. Fitting these data to a probit dose-response model enabled risk estimates to be made for these previously unvalidated optic pathway constraints: the Dmax limits of 12Gy in 1 fraction from QUANTEC, 19.5Gy in 3 fractions from Timmerman 2008, and 25Gy in 5 fractions from AAPM Task Group 101 all had less than 1% risk. In 262 patients with perioptic tumors treated with SRS, we found a risk of optic complications of less than 1%. These data support previously unvalidated estimates as safe guidelines, which may in fact underestimate the tolerance of the optic structures, particularly in patients without prior radiation. Further investigation would refine the estimated normal tissue complication probability for SRS near the optic apparatus.

  View details for DOI 10.1016/j.semradonc.2015.11.008

  View details for Web of Science ID 000373242700003

• CyberKnife radiosurgery for brainstem metastases: Management and outcomes and a review of the literature. Journal of clinical neuroscience Liu, S., Murovic, J., Wallach, J., Cui, G., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2016; 25: 105-110

  Abstract

  To our knowledge this paper is the first to use recursive partitioning analysis (RPA) for brainstem metastasis (BSM) patient outcomes, after CyberKnife radiosurgery (CKRS; Accuray, Sunnyvale, CA, USA); nine similar previous publications used mainly Gamma Knife radiosurgery (Elekta AB, Stockholm, Sweden). Retrospective chart reviews from 2006-2013 of 949 CKRS-treated brain metastasis patients showed 54BSM patients (5.7%): 35 RPA Class II (65%) and 19 Class III (35%). There were 30 women (56%) and 24 men (44%). The median age was 59years (range 36-80) and median follow-up was 5months (range 1-52). Twenty-three patients (43%) had lung carcinoma BSM and 12 (22%) had breast cancer BSM. Fifty-four RPA Class II and III BSM patients had a median overall survival (OS) of 5months, and for each Class 8 and 2months, respectively. Of 36 RPA Class II and III patients with available symptoms (n=31) and findings (n=33), improvement/stability occurred in the majority for symptoms (86%) and findings (92%). Of 35 cases, 28 (80%) achieved BSM local control (LC); 13/14 with breast histology (93%) and 10/13 with lung histology (77%). All six RPA Class II and III patients with controlled extracranial systemic disease (ESD) experienced LC. Median tumor volume was 0.14cm(3); of 34 RPA Class II and III cases, 26 LC patients had a 0,13cm(3) median tumor volume while it was 0.27cm(3) in the eight local failures. Of 35 cases, single session equivalent dosages less than the median (n=13), at the 17.9Gy median (n=5) and greater than the median (n=17) had BSM LC in 10 (77%), four (80%) and 14 cases (82%), respectively. Univariate analysis showed Karnofsky Performance Score, RPA Class and ESD-control predicted OS. CKRS is useful for RPA Class II and III BSM patients with effective clinical and local BSM control.

  View details for DOI 10.1016/j.jocn.2015.10.013

  View details for PubMedID 26778047

• 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

• Inverse treatment planning for spinal robotic radiosurgery: an international multi-institutional benchmark trial JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS Blanck, O., Wang, L., Baus, W., Grimm, J., Lacornerie, T., Nilsson, J., Luchkovskyi, S., Palazon Cano, I., Shou, Z., Ayadi, M., Treuer, H., Viard, R., Siebert, F., Chan, M. K., Hildebrandt, G., Dunst, J., Imhoff, D., Wurster, S., Wolff, R., Romanelli, P., Lartigau, E., Semrau, R., Soltys, S. G., Schweikard, A. 2016; 17 (3): 313-330

  View details for Web of Science ID 000377678100028

• Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the SPIne response assessment in Neuro-Oncology (SPINO) group LANCET ONCOLOGY Thibault, I., Chang, E. L., Sheehan, J., Ahluwalia, M. S., Guckenberger, M., Sohn, M., Ryu, S., Foote, M., Lo, S. S., Muacevic, A., Soltys, S. G., Chao, S., Gerszten, P., Lis, E., Yu, E., Bilsky, M., Fisher, C., Schiff, D., Fehlings, M. G., Ma, L., Chang, S., Chow, E., Parelukar, W. R., Vogelbaum, M. A., Sahgal, A. 2015; 16 (16): E595-E603

  View details for Web of Science ID 000365803700029

  View details for PubMedID 26678212

• Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Shultz, D. B., Modlin, L. A., Jayachandran, P., von Eyben, R., Gibbs, I. C., Choi, C. Y., Chang, S. D., Harsh, G. R., Li, G., Adler, J. R., Hancock, S. L., Soltys, S. G. 2015; 92 (5): 993-999

  Abstract

  To report the outcomes of repeat stereotactic radiosurgery (SRS), deferring whole-brain radiation therapy (WBRT), for distant intracranial recurrences and identify factors associated with prolonged overall survival (OS).We retrospectively identified 652 metastases in 95 patients treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox regression analyzed factors predictive for OS.Patients had a median of 2 metastases (range, 1-14) treated per course, with a median of 2 courses (range, 2-14) of SRS per patient. With a median follow-up after first SRS of 15 months (range, 3-98 months), the median OS from the time of the first and second course of SRS was 18 (95% confidence interval [CI] 15-24) and 11 months (95% CI 6-17), respectively. On multivariate analysis, histology, graded prognostic assessment score, aggregate tumor volume (but not number of metastases), and performance status correlated with OS. The 1-year cumulative incidence, with death as a competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75 deaths were from neurologic causes. Nineteen patients (20%) eventually received WBRT. Adverse radiation events developed in 2% of SRS sites.Multiple courses of SRS, deferring WBRT, for distant brain metastases after initial SRS, seem to be a safe and effective approach. The graded prognostic assessment score, updated at each course, and aggregate tumor volume may help select patients in whom the deferral of WBRT might be most beneficial.

  View details for DOI 10.1016/j.ijrobp.2015.04.036

  View details for Web of Science ID 000357900600018

  View details for PubMedID 26194677

• Is Less, More? The Evolving Role of Radiation Therapy for Brain Metastases INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Soltys, S. G., Kirkpatrick, J. P., Laack, N. N., Kavanagh, B. D., Breneman, J. C., Shih, H. A. 2015; 92 (5): 963-966

  View details for DOI 10.1016/j.ijrobp.2015.03.003

  View details for Web of Science ID 000357900600012

  View details for PubMedID 26194672

• 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

• Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Atalar, B., Modlin, L. A., Choi, C. Y., Adler, J. R., Gibbs, I. C., Chang, S. D., Harsh, G. R., Li, G., Nagpal, S., Hanlon, A., Soltys, S. G. 2013; 87 (4): 713-718

  Abstract

  We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients.We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other).With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004).In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

  View details for DOI 10.1016/j.ijrobp.2013.07.034

  View details for Web of Science ID 000325763300022

  View details for PubMedID 24054875

• Cochlea radiation dose correlates with hearing loss after stereotactic radiosurgery of vestibular schwannoma. World neurosurgery Hayden Gephart, M. G., Hansasuta, A., Balise, R. R., Choi, C., Sakamoto, G. T., Venteicher, A. S., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Adler, J. R., Chang, S. D. 2013; 80 (3-4): 359-363

  Abstract

  OBJECTIVE: For multisession radiosurgery, no published data relate the volume and dose of cochlear irradiation to quantified risk of hearing loss. We conducted a retrospective, dosimetric study to evaluate the relationship between hearing loss after stereotactic radiosurgery (SRS) and the dose-volume of irradiated cochlea. METHODS: Cochlear dose data were retrospectively collected on consecutive patients who underwent SRS (18 Gy in 3 sessions) for vestibular schwanoma between 1999 and 2005 at Stanford University Hospital. Inclusion criteria included Gardner-Robertson (GR) grade I or II hearing prior to radiosurgical treatment, complete audiograms, and magnetic resonance imaging (MRI) follow-up. A cochlea dose-volume histogram was generated for each of the 94 patients who qualified for this study. RESULTS: GR grade I-II hearing posttreatment was maintained in 74% of patients (70/94). Median time to last follow-up audiogram was 2.4 years (range 0.4-8.9) and to last MRI was 3.6 years (range 0.5-9.4). Each higher level of cochlear irradiation was associated with increased risk of hearing loss. Larger cochlear volume was associated with lower risk of hearing loss. Controlling for differences in cochlear volume among subjects, each additional mm(3) of cochlea receiving 10 to 16 Gy (single session equivalent doses of 6.6-10.1 Gy3) significantly increased the odds of hearing loss by approximately 5%. CONCLUSIONS: Larger cochlear volume is associated with lower risk of hearing loss following trisession SRS for vestibular schwannoma. Controlling for this phenomenon, higher radiation dose and larger irradiated cochlear volume are significantly associated with higher risk of hearing loss. This study confirms and quantifies the risk of hearing loss following trisession SRS for vestibular schwannoma.

  View details for DOI 10.1016/j.wneu.2012.04.001

  View details for PubMedID 22484770

• CyberKnife radiosurgery for the management of skull base and spinal chondrosarcomas. Journal of neuro-oncology Jiang, B., Veeravagu, A., Feroze, A. H., Lee, M., Harsh, G. R., Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D. 2013; 114 (2): 209-218

  Abstract

  The use of CyberKnife (CK) stereotactic radiosurgery (SRS) for the management of central nervous system chondrosarcomas has not been previously reported. To evaluate outcomes of primary, recurrent, and metastatic chondrosarcomas of the skull base and spine treated with CK SRS, a retrospective observational study of 16 patients treated between 1996 and 2011 with CK SRS was performed using an IRB-approved database at Stanford University Medical Center. Twenty lesions (12 cranial, 8 spinal) across six males and ten females were analyzed. The median age at SRS was 51 years and median follow-up was 33 months. Median tumor volume was 11.0 cm³ and median marginal dosages were 22, 24, 26, 27, and 30 Gy for one to five fractionations, respectively. Overall Kaplan-Meier survival rates were 88, 88, 80, and 66 % at 1, 3, 5, and 10 years after initial presentation. Survival rates at 1, 3, and 5 years after CK were 81, 67, and 55 %, respectively. Actuarial tumor control was 41 ± 13 % at 60 months. At 36 months follow-up, tumor control was 80 % in primary lesions, 50 % in recurrent lesions, and 0.0 % in metastatic disease (p = 0.07). Tumor control was 58 % in cranial lesions and 38 % in spinal lesions. Radiation injury was reported in one patient. CK SRS appears to be a safe adjuvant therapy and offers moderate control for primary cranial chondrosarcoma lesions. There appears to be a clinically, albeit not statistically, significant trend towards poorer outcomes in similarly treated metastatic, recurrent, and spinal chondrosarcomas (p = 0.07). Lesions not candidates for single fraction SRS may be treated with hypofractionated SRS without increased risk for radiation necrosis.

  View details for DOI 10.1007/s11060-013-1172-9

  View details for PubMedID 23748573

• Cavity Volume Dynamics After Resection of Brain Metastases and Timing of Postresection Cavity Stereotactic Radiosurgery NEUROSURGERY Atalar, B., Choi, C. Y., Harsh, G. R., Chang, S. D., Gibbs, I. C., Adler, J. R., Soltys, S. G. 2013; 72 (2): 180-185

  Abstract

  An alternative treatment option to whole-brain irradiation after surgical resection of brain metastases is resection cavity stereotactic radiosurgery (SRS).To review the dynamics of cavity volume change after surgical resection with the goal of determining the optimal timing for cavity SRS.Preresection tumor, postresection/pre-SRS cavity, and post-SRS cavity volumes were measured for 68 cavities in 63 patients treated with surgery and postresection cavity SRS. Percent differences between volumes were calculated and correlation analyses were performed to assess volume changes before and after SRS.For the majority of tumors, the postresection cavity volume was smaller than the preresection tumor volume by a median percent volume change of -29% (range, -82% to 1258%), with larger preresection tumors resulting in greater cavity shrinkage (P < .001). To determine the optimal timing for cavity SRS, we examined cavity volume dynamics by comparing the early postresection (postoperative days 0-3) and treatment planning magnetic resonance imaging scans (median time to magnetic resonance imaging, 20 days; range, 9-33 days) and found no association between the postresection day number and volume change (P = .75). The volume decrease resulting from tumor resection was offset by the addition of a 2-mm clinical target volume margin, which is our current technique.The greatest volume change occurs immediately after surgery (postoperative days 0-3) with no statistically significant volume change occurring up to 33 days after surgery for most patients. Therefore, there is no benefit of cavity shrinkage in waiting longer than the first 1 to 2 weeks to perform cavity SRS.

  View details for DOI 10.1227/NEU.0b013e31827b99f3

  View details for Web of Science ID 000313734400028

  View details for PubMedID 23149969

• Probabilities of Radiation Myelopathy Specific to Stereotactic Body Radiation Therapy to Guide Safe Practice INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Sahgal, A., Weinberg, V., Ma, L., Chang, E., Chao, S., Muacevic, A., Gorgulho, A., Soltys, S., Gerszten, P. C., Ryu, S., Angelov, L., Gibbs, I., Wong, C. S., Larson, D. A. 2013; 85 (2): 341-347

  Abstract

  Dose-volume histogram (DVH) results for 9 cases of post spine stereotactic body radiation therapy (SBRT) radiation myelopathy (RM) are reported and compared with a cohort of 66 spine SBRT patients without RM.DVH data were centrally analyzed according to the thecal sac point maximum (Pmax) volume, 0.1- to 1-cc volumes in increments of 0.1 cc, and to the 2 cc volume. 2-Gy biologically equivalent doses (nBED) were calculated using an α/β = 2 Gy (units = Gy(2/2)). For the 2 cohorts, the nBED means and distributions were compared using the t test and Mann-Whitney test, respectively. Significance (P<.05) was defined as concordance of both tests at each specified volume. A logistic regression model was developed to estimate the probability of RM using the dose distribution for a given volume.Significant differences in both the means and distributions at the Pmax and up to the 0.8-cc volume were observed. Concordant significance was greatest for the Pmax volume. At the Pmax volume the fit of the logistic regression model, summarized by the area under the curve, was 0.87. A risk of RM of 5% or less was observed when limiting the thecal sac Pmax volume doses to 12.4 Gy in a single fraction, 17.0 Gy in 2 fractions, 20.3 Gy in 3 fractions, 23.0 Gy in 4 fractions, and 25.3 Gy in 5 fractions.We report the first logistic regression model yielding estimates for the probability of human RM specific to SBRT.

  View details for DOI 10.1016/j.ijrobp.2012.05.007

  View details for Web of Science ID 000313642000020

  View details for PubMedID 22713832

• What Is the Optimal Treatment of Large Brain Metastases? An Argument for a Multidisciplinary Approach INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Choi, C. Y., Chang, S. D., Gibbs, I. C., Adler, J. R., Harsh, G. R., Atalar, B., Lieberson, R. E., Soltys, S. G. 2012; 84 (3): 688-693

  Abstract

  Single-modality treatment of large brain metastases (>2 cm) with whole-brain irradiation, stereotactic radiosurgery (SRS) alone, or surgery alone is not effective, with local failure (LF) rates of 50% to 90%. Our goal was to improve local control (LC) by using multimodality therapy of surgery and adjuvant SRS targeting the resection cavity.We retrospectively evaluated 97 patients with brain metastases >2 cm in diameter treated with surgery and cavity SRS. Local and distant brain failure (DF) rates were analyzed with competing risk analysis, with death as a competing risk. The overall survival rate was calculated by the Kaplain-Meier product-limit method.The median imaging follow-up duration for all patients was 10 months (range, 1-80 months). The 12-month cumulative incidence rates of LF, with death as a competing risk, were 9.3% (95% confidence interval [CI], 4.5%-16.1%), and the median time to LF was 6 months (range, 3-17 months). The 12-month cumulative incidence rate of DF, with death as a competing risk, was 53% (95% CI, 43%-63%). The median survival time for all patients was 15.6 months. The median survival times for recursive partitioning analysis classes 1, 2, and 3 were 33.8, 13.7, and 9.0 months, respectively (p = 0.022). On multivariate analysis, Karnofsky Performance Status (≥80 vs. <80; hazard ratio 0.54; 95% CI 0.31-0.94; p = 0.029) and maximum preoperative tumor diameter (hazard ratio 1.41; 95% CI 1.08-1.85; p = 0.013) were associated with survival. Five patients (5%) required intervention for Common Terminology Criteria for Adverse Events v4.02 grade 2 and 3 toxicity.Surgery and adjuvant resection cavity SRS yields excellent LC of large brain metastases. Compared with other multimodality treatment options, this approach allows patients to avoid or delay whole-brain irradiation without compromising LC.

  View details for DOI 10.1016/j.ijrobp.2012.01.028

  View details for Web of Science ID 000309560600051

  View details for PubMedID 22445007

• Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Choi, C. Y., Chang, S. D., Gibbs, I. C., Adler, J. R., Harsh, G. R., Lieberson, R. E., Soltys, S. G. 2012; 84 (2): 336-342

  Abstract

  Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity.We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competing risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests.The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients.Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.

  View details for DOI 10.1016/j.ijrobp.2011.12.009

  View details for Web of Science ID 000308062700035

  View details for PubMedID 22652105

• CyberKnife stereotactic radiosurgery for the treatment of intramedullary spinal cord metastases JOURNAL OF CLINICAL NEUROSCIENCE Veeravagu, A., Lieberson, R. E., Mener, A., Chen, Y., Soltys, S. G., Gibbs, I. C., Adler, J. R., Tian, A. G., Chang, S. D. 2012; 19 (9): 1273-1277

  Abstract

  Spinal cord intramedullary metastases are uncommon and treatment options are limited. We reviewed our experience treating these lesions with radiosurgery to assess safety and efficacy, and to define preliminary treatment recommendations. With Institutional Review Board approval, we identified nine patients with 11 metastases treated with radiosurgery at Stanford University Hospital, between 2000 and 2010. We also reviewed all available published series discussing the treatment of spinal cord metastases. Our patients ranged in age from 33 years to 77 years (median 63 years) and included seven women and two men. Tumors ranged in size from 0.12 cm(3) to 6.4 cm(3) (median 0.48 cm(3)). Five were from breast cancer, two were non-small cell lung cancers, one was a cystic adenocarcinoma, and one was from an epithelioid hemangioepithelioma. All patients had neurologic deficits and multiple other metastases. We delivered 14 Gy to 27 Gy (median 21 Gy) in one to five (median 3) fractions. Complete follow-up was available for all nine patients. One patient remains alive 14 months after therapy. Of the eight deceased patients, survival ranged from one month and two days to nine months and six days (median four months and four days). There were no local recurrences or worsened neurological deficits. To our knowledge this is the largest reported series of spinal cord intramedullary metastases treated with radiosurgery. Survival was poor due to systemic disease, but radiosurgery appears to be safe and prevented local recurrences. With fewer sessions than conventional radiation and less morbidity than surgery, we feel radiosurgery is appropriate for the palliative treatment of these lesions.

  View details for DOI 10.1016/j.jocn.2012.02.002

  View details for Web of Science ID 000308730900014

  View details for PubMedID 22766103

• 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

• International Spine Radiosurgery Consortium Consensus Guidelines for Target Volume Definition in Spinal Stereotactic Radiosurgery INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Cox, B. W., Spratt, D. E., Lovelock, M., Bilsky, M. H., Lis, E., Ryu, S., Sheehan, J., Gerszten, P. C., Chang, E., Gibbs, I., Soltys, S., Sahgal, A., Deasy, J., Flickinger, J., Quader, M., Mindea, S., Yamada, Y. 2012; 83 (5): E597-E605

  Abstract

  Spinal stereotactic radiosurgery (SRS) is increasingly used to manage spinal metastases. However, target volume definition varies considerably and no consensus target volume guidelines exist. This study proposes consensus target volume definitions using common scenarios in metastatic spine radiosurgery.Seven radiation oncologists and 3 neurological surgeons with spinal radiosurgery expertise independently contoured target and critical normal structures for 10 cases representing common scenarios in metastatic spine radiosurgery. Each set of volumes was imported into the Computational Environment for Radiotherapy Research. Quantitative analysis was performed using an expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE) with kappa statistics calculating agreement between physicians. Optimized confidence level consensus contours were identified using histogram agreement analysis and characterized to create target volume definition guidelines.Mean STAPLE agreement sensitivity and specificity was 0.76 (range, 0.67-0.84) and 0.97 (range, 0.94-0.99), respectively, for gross tumor volume (GTV) and 0.79 (range, 0.66-0.91) and 0.96 (range, 0.92-0.98), respectively, for clinical target volume (CTV). Mean kappa agreement was 0.65 (range, 0.54-0.79) for GTV and 0.64 (range, 0.54-0.82) for CTV (P<.01 for GTV and CTV in all cases). STAPLE histogram agreement analysis identified optimal consensus contours (80% confidence limit). Consensus recommendations include that the CTV should include abnormal marrow signal suspicious for microscopic invasion and an adjacent normal bony expansion to account for subclinical tumor spread in the marrow space. No epidural CTV expansion is recommended without epidural disease, and circumferential CTVs encircling the cord should be used only when the vertebral body, bilateral pedicles/lamina, and spinous process are all involved or there is extensive metastatic disease along the circumference of the epidural space.This report provides consensus guidelines for target volume definition for spinal metastases receiving upfront SRS in common clinical situations.

  View details for DOI 10.1016/j.ijrobp.2012.03.009

  View details for Web of Science ID 000306128100006

  View details for PubMedID 22608954

• Management of intracranial and extracranial chordomas with CyberKnife stereotactic radiosurgery JOURNAL OF CLINICAL NEUROSCIENCE Jiang, B., Veeravagu, A., Lee, M., Harsh, G. R., Lieberson, R. E., Bhatti, I., Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D. 2012; 19 (8): 1101-1106

  Abstract

  Chordomas are rare, malignant bone tumors of the axial skeleton, occurring particularly at the cranial base or in the sacro-coccygeal region. Although slow growing, chordomas are locally aggressive and challenging to treat. We evaluate the outcomes of skull base and spinal chordomas in 20 patients treated with CyberKnife (CK) stereotactic radiosurgery (SRS) (Accuray, Sunnyvale, CA, USA) between 1994 and 2010 at Stanford Hospital. There were 12 males and eight females (10-78 years; median age: 51.5 years). Eleven patients received CK as primary adjuvant therapy and nine patients received CK for multiple recurrences. The average tumor volume treated was 16.1cm(3) (2.4-45.9 cm(3)), with a mean marginal dose of 32.5 Gy (18-50 Gy). Median follow-up was 34 months (2-131 months). Overall, tumor control was achieved in 11 patients (55%), with eight patients showing tumor size reduction. However, nine patients showed progression and eventually succumbed to the disease (mean time from CK to death was 26.3 months). Of the patients treated with CK as the primary adjuvant therapy, 81.8% had stable or improved outcomes. Only 28.6% of those treated with CK for recurrences had stable or improved outcomes. The overall Kaplan-Meyer survival at five years from the first CK treatment was 52.5%. Moderate tumor control rates can be achieved with few complications with CK SRS. Poor control is associated with complex multiple surgical resections, long delay between initial resection and CK therapy, and recurrently aggressive disease uncontrolled by prior radiation.

  View details for DOI 10.1016/j.jocn.2012.01.005

  View details for Web of Science ID 000306500400009

  View details for PubMedID 22727205

• A Planned Neck Dissection Is Not Necessary in All Patients With N2-3 Head-and-Neck Cancer After Sequential Chemoradiotherapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Soltys, S. G., Choi, C. Y., Fee, W. E., Pinto, H. A., Le, Q. 2012; 83 (3): 994-999

  Abstract

  To assess the role of a planned neck dissection (PND) after sequential chemoradiotherapy for patients with head-and-neck cancer with N2-N3 nodal disease.We reviewed 90 patients with N2-N3 head-and-neck squamous cell carcinoma treated between 1991 and 2001 on two sequential chemoradiotherapy protocols. All patients received induction and concurrent chemotherapy with cisplatin and 5-fluorocuracil, with or without tirapazamine. Patients with less than a clinical complete response (cCR) in the neck proceeded to a PND after chemoradiation. The primary endpoint was nodal response. Clinical outcomes and patterns of failure were analyzed.The median follow-up durations for living and all patients were 8.3 years (range, 1.5-16.3 year) and 5.4 years (range, 0.6-16.3 years), respectively. Of the 48 patients with nodal cCR whose necks were observed, 5 patients had neck failures as a component of their recurrence [neck and primary (n = 2); neck, primary, and distant (n = 1); neck only (n = 1); neck and distant (n = 1)]. Therefore, PND may have benefited only 2 patients (4%) [neck only failure (n = 1); neck and distant failure (n = 1)]. The pathologic complete response (pCR) rate for those with a clinical partial response (cPR) undergoing PND (n = 30) was 53%. The 5-year neck control rates after cCR, cPR→pCR, and cPR→pPR were 90%, 93%, and 78%, respectively (p = 0.36). The 5-year disease-free survival rates for the cCR, cPR→pCR, and cPR→pPR groups were 53%, 75%, and 42%, respectively (p = 0.04).In our series, patients with N2-N3 neck disease achieving a cCR in the neck, PND would have benefited only 4% and, therefore, is not recommended. Patients with a cPR should be treated with PND. Residual tumor in the PND specimens was associated with poor outcomes; therefore, aggressive therapy is recommended. Studies using novel imaging modalities are needed to better assess treatment response.

  View details for DOI 10.1016/j.ijrobp.2011.07.042

  View details for Web of Science ID 000305256000055

  View details for PubMedID 22137026

• Stereotactic Radiosurgery as the Primary Treatment for New and Recurrent Paragangliomas: Is Open Surgical Resection Still the Treatment of Choice? WORLD NEUROSURGERY Lieberson, R. E., Adler, J. R., Soltys, S. G., Choi, C., Gibbs, I. C., Chang, S. D. 2012; 77 (5-6): 745-761

  Abstract

  Paragangliomas (PGs) or glomus tumors are rare, and publications comparing treatment alternatives are few. We sought to analyze our experience with stereotactic radiosurgery (SRS), review the literature, and develop treatment guidelines.We retrospectively examined the outcomes of 41 PGs in 36 patients treated with SRS at Stanford. Our data from medical records, telephone interviews, and imaging studies were combined with previously reported SRS data and compared to results following other treatments.With a median clinical follow-up of 4.8 years (3.9 years radiographic), local control was 100%. Complications included increase in preexistent vertigo in one patient and transient cranial neuropathies in two patients. Published surgical series describe a lower local control rate as well as more frequent and severe complications. Published radiation therapy (RT) series document a slightly lower local control rate than SRS, but SRS can be delivered more quickly and conveniently. Open surgery and other combinations of treatments appear to be required for several subpopulations of PG patients.We feel that SRS should be the primary treatment for most new and recurrent PGs. Even some very large PGs are appropriate for SRS. RT remains an appropriate option in some centers, especially those where SRS is not available. PGs occurring in the youngest patients, catecholamine secreting PGs, and PGs causing rapidly progressing neurologic deficits may be more appropriate for open resection. Metastatic PGs may benefit from combinations of chemotherapy and SRS or RT. Treatment guidelines are proposed.

  View details for DOI 10.1016/j.wneu.2011.03.026

  View details for Web of Science ID 000307523800038

  View details for PubMedID 22818172

• NORMAL TISSUE COMPLICATION PROBABILITY ESTIMATION BY THE LYMAN-KUTCHER-BURMAN METHOD DOES NOT ACCURATELY PREDICT SPINAL CORD TOLERANCE TO STEREOTACTIC RADIOSURGERY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Luxton, G., Choi, C. Y., Gibbs, I. C., Chang, S. D., Adler, J. R., Soltys, S. G. 2012; 82 (5): 2025-2032

  Abstract

  To determine whether normal tissue complication probability (NTCP) analyses of the human spinal cord by use of the Lyman-Kutcher-Burman (LKB) model, supplemented by linear-quadratic modeling to account for the effect of fractionation, predict the risk of myelopathy from stereotactic radiosurgery (SRS).From November 2001 to July 2008, 24 spinal hemangioblastomas in 17 patients were treated with SRS. Of the tumors, 17 received 1 fraction with a median dose of 20 Gy (range, 18-30 Gy) and 7 received 20 to 25 Gy in 2 or 3 sessions, with cord maximum doses of 22.7 Gy (range, 17.8-30.9 Gy) and 22.0 Gy (range, 20.2-26.6 Gy), respectively. By use of conventional values for α/β, volume parameter n, 50% complication probability dose TD(50), and inverse slope parameter m, a computationally simplified implementation of the LKB model was used to calculate the biologically equivalent uniform dose and NTCP for each treatment. Exploratory calculations were performed with alternate values of α/β and n.In this study 1 case (4%) of myelopathy occurred. The LKB model using radiobiological parameters from Emami and the logistic model with parameters from Schultheiss overestimated complication rates, predicting 13 complications (54%) and 18 complications (75%), respectively. An increase in the volume parameter (n), to assume greater parallel organization, improved the predictive value of the models. Maximum-likelihood LKB fitting of α/β and n yielded better predictions (0.7 complications), with n = 0.023 and α/β = 17.8 Gy.The spinal cord tolerance to the dosimetry of SRS is higher than predicted by the LKB model using any set of accepted parameters. Only a high α/β value in the LKB model and only a large volume effect in the logistic model with Schultheiss data could explain the low number of complications observed. This finding emphasizes that radiobiological models traditionally used to estimate spinal cord NTCP may not apply to the dosimetry of SRS. Further research with additional NTCP models is needed.

  View details for DOI 10.1016/j.ijrobp.2011.03.004

  View details for Web of Science ID 000301891300082

  View details for PubMedID 21531516

• Trigeminal neuralgia treatment dosimetry of the Cyberknife MEDICAL DOSIMETRY Ho, A., Lo, A. T., Dieterich, S., Soltys, S. G., Gibbs, I. C., Chang, S. G., Adler, J. R. 2012; 37 (1): 42-46

  Abstract

  There are 2 Cyberknife units at Stanford University. The robot of 1 Cyberknife is positioned on the patient's right, whereas the second is on the patient's left. The present study examines whether there is any difference in dosimetry when we are treating patients with trigeminal neuralgia when the target is on the right side or the left side of the patient. In addition, we also study whether Monte Carlo dose calculation has any effect on the dosimetry. We concluded that the clinical and dosimetric outcomes of CyberKnife treatment for trigeminal neuralgia are independent of the robot position. Monte Carlo calculation algorithm may be useful in deriving the dose necessary for trigeminal neuralgia treatments.

  View details for DOI 10.1016/j.meddos.2010.12.012

  View details for Web of Science ID 000301035000009

  View details for PubMedID 21723113

• Impact of Dose Hot Spots on Spinal Cord Tolerance Following Stereotactic Body Radiotherapy: A Generalized Biological Effective Dose Analysis TECHNOLOGY IN CANCER RESEARCH & TREATMENT Sahgal, A., Ma, L., Fowler, J., Weinberg, V., Gibbs, I., Gerszten, P. C., Ryu, S., Soltys, S., Chang, E., Wong, C. S., Larson, D. A. 2012; 11 (1): 35-40

  Abstract

  The purpose of this study was to investigate the effects of high-dose inhomogeneous irradiation to small volumes of spinal cord with a new generalized biological effective dose (gBED) analysis for spine stereotactic body radiotherapy (SBRT). The gBED was applied to spinal cord dosimetric data (contoured per the thecal sac) at specified volumes for a cohort of five patients with radiation-induced myelopathy (RM) and compared to nineteen patients without RM post-SBRT. The spinal cord gBED was calculated and normalized to a conventional 2-Gy equivalent dose fraction scheme (α/β = 2 Gy for late toxicity). Differences between the conventional BED and those gBED calculations by accounting for small-volume dosing within the spinal cord was observed. Statistically significant differences in the mean gBED between the RM group and the non-RM group was observed both at the maximum point volume (gBED of 66 Gy vs. 37 Gy (p = 0.01), respectively) and at the 0.1 cm(3) volume (gBED of 53 Gy vs. 28 Gy (p = 0.01), respectively). No significant difference at the 0.1 cm(3) volume was observed based on the mean BED comparisons. No significant differences were observed at the larger 1 cm(3), 2 cm(3) or 5 cm(3) volumes for either BED or gBED comparisons. We conclude that differences in dose hot spots characteristics within small inhomogenously irradiated volumes of spinal cord can affect spinal cord tolerance following SBRT treatments.

  View details for Web of Science ID 000298867500005

  View details for PubMedID 22181329

• REIRRADIATION HUMAN SPINAL CORD TOLERANCE FOR STEREOTACTIC BODY RADIOTHERAPY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Sahgal, A., Ma, L., Weinberg, V., Gibbs, I. C., Chao, S., Chang, U., Werner-Wasik, M., Angelov, L., Chang, E. L., Sohn, M., Soltys, S. G., Letourneau, D., Ryu, S., Gerszten, P. C., Fowler, J., Wong, C. S., Larson, D. A. 2012; 82 (1): 107-116

  Abstract

  We reviewed the treatment for patients with spine metastases who initially received conventional external beam radiation (EBRT) and were reirradiated with 1-5 fractions of stereotactic body radiotherapy (SBRT) who did or did not subsequently develop radiation myelopathy (RM).Spinal cord dose-volume histograms (DVHs) for 5 RM patients (5 spinal segments) and 14 no-RM patients (16 spine segments) were based on thecal sac contours at retreatment. Dose to a point within the thecal sac that receives the maximum dose (P(max)), and doses to 0.1-, 1.0-, and 2.0-cc volumes within the thecal sac were reviewed. The biologically effective doses (BED) using α/β = 2 Gy for late spinal cord toxicity were calculated and normalized to a 2-Gy equivalent dose (nBED = Gy(2/2)).The initial conventional radiotherapy nBED ranged from ~30 to 50 Gy(2/2) (median ~40 Gy(2/2)). The SBRT reirradiation thecal sac mean P(max) nBED in the no-RM group was 20.0 Gy(2/2) (95% confidence interval [CI], 10.8-29.2), which was significantly lower than the corresponding 67.4 Gy(2/2) (95% CI, 51.0-83.9) in the RM group. The mean total P(max) nBED in the no-RM group was 62.3 Gy(2/2) (95% CI, 50.3-74.3), which was significantly lower than the corresponding 105.8 Gy(2/2) (95% CI, 84.3-127.4) in the RM group. The fraction of the total P(max) nBED accounted for by the SBRT P(max) nBED for the RM patients ranged from 0.54 to 0.78 and that for the no-RM patients ranged from 0.04 to 0.53.SBRT given at least 5 months after conventional palliative radiotherapy with a reirradiation thecal sac P(max) nBED of 20-25 Gy(2/2) appears to be safe provided the total P(max) nBED does not exceed approximately 70 Gy(2/2), and the SBRT thecal sac P(max) nBED comprises no more than approximately 50% of the total nBED.

  View details for DOI 10.1016/j.ijrobp.2010.08.021

  View details for Web of Science ID 000298526100018

  View details for PubMedID 20951503

• Multisession Stereotactic Radiosurgery for Vestibular Schwannomas: Single-Institution Experience With 383 Cases NEUROSURGERY Hansasuta, A., Choi, C. Y., Gibbs, I. C., Soltys, S. G., Tse, V. C., Lieberson, R. E., Hayden, M. G., Sakamoto, G. T., Harsh, G. R., Adler, J. R., Chang, S. D. 2011; 69 (6): 1200-1209

  Abstract

  Single-session stereotactic radiosurgery (SRS) treatment of vestibular schwannomas results in excellent tumor control. It is not known whether functional outcomes can be improved by fractionating the treatment over multiple sessions.To examine tumor control and complication rates after multisession SRS.Three hundred eighty-three patients treated with SRS from 1999 to 2007 at Stanford University Medical Center were retrospectively reviewed. Ninety percent were treated with 18 Gy in 3 sessions, targeting a median tumor volume of 1.1 cm3 (range, 0.02-19.8 cm3).During a median follow-up duration of 3.6 years (range, 1-10 years), 10 tumors required additional treatment, resulting in 3- and 5-year Kaplan-Meier tumor control rates of 99% and 96%, respectively. Five-year tumor control rate was 98% for tumors < 3.4 cm3. Neurofibromatosis type 2-associated tumors were associated with worse tumor control (P = .02). Of the 200 evaluable patients with pre-SRS serviceable hearing (Gardner-Robertson grade 1 and 2), the crude rate of serviceable hearing preservation was 76%. Smaller tumor volume was associated with hearing preservation (P = .001). There was no case of post-SRS facial weakness. Eight patients (2%) developed trigeminal dysfunction, half of which was transient.Multisession SRS treatment of vestibular schwannomas results in an excellent rate of tumor control. The hearing, trigeminal nerve, and facial nerve function preservation rates reported here are promising.

  View details for DOI 10.1227/NEU.0b013e318222e451

  View details for Web of Science ID 000296794500024

  View details for PubMedID 21558974

• Stereotactic Radiosurgery Yields Long-term Control for Benign Intradural, Extramedullary Spinal Tumors NEUROSURGERY Sachdev, S., Dodd, R. L., Chang, S. D., Soltys, S. G., Adler, J. R., Luxton, G., Choi, C. Y., Tupper, L., Gibbs, I. C. 2011; 69 (3): 533-539

  Abstract

  The role of stereotactic radiosurgery in the treatment of benign intracranial lesions is well established. Although a growing body of evidence supports its role in the treatment of malignant spinal lesions, a much less extensive dataset exists for treatment of benign spinal tumors.To examine the safety and efficacy of stereotactic radiosurgery for treatment of benign, intradural extramedullary spinal tumors.From 1999 to 2008, 87 patients with 103 benign intradural extramedullary spinal tumors (32 meningiomas, 24 neurofibromas, and 47 schwannomas) were treated with stereotactic radiosurgery at Stanford University Medical Center. Forty-three males and 44 females had a median age of 53 years (range, 12-86). Twenty-five patients had neurofibromatosis. Treatment was delivered in 1 to 5 sessions (median, 2) with a mean prescription dose of 19.4 Gy (range, 14-30 Gy) to an average tumor volume of 5.24 cm (range, 0.049-54.52 cm).After a mean radiographic follow-up period of 33 months (range, 6-87), including 21 lesions followed for ≥ 48 months, 59% were stable, 40% decreased in size, and a single tumor (1%) increased in size. Clinically, 91%, 67%, and 86% of meningiomas, neurofibromas, and schwannomas, respectively, were symptomatically stable to improved at last follow-up. One patient with a meningioma developed a new, transient myelopathy at 9 months, although the tumor was smaller at last follow-up.As a viable alternative to microsurgical resection, stereotactic radiosurgery provides safe and efficacious long-term control of benign intradural, extramedullary spinal tumors with a low rate of complication.

  View details for DOI 10.1227/NEU.0b013e318218db23

  View details for Web of Science ID 000293586200003

  View details for PubMedID 21832967

• CyberKnife Stereotactic Radiosurgery for Recurrent, Metastatic, and Residual Hemangiopericytomas JOURNAL OF HEMATOLOGY & ONCOLOGY Veeravagu, A., Jiang, B., Patil, C. G., Lee, M., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2011; 4

  Abstract

  Hemangiopericytoma is a rare and aggressive meningeal tumor. Although surgical resection is the standard treatment, hemangiopericytomas often recur with high incidences of metastasis. The purpose of this study was to evaluate the role of CyberKnife stereotactic radiosurgery (CK) in the management of recurrent, metastatic, and residual hemangiopericytomas.In a review of the Stanford radiosurgery database between 2002 and 2009, the authors found 14 patients who underwent CK therapy for recurrent, metastatic, and residual hemangiopericytomas. A total of 24 tumors were treated and the median patient age was 52 years (range 29-70 years) at the time of initial CK therapy. The median follow-up period was 37 months (10-73 months) and all patients had been previously treated with surgical resection. Mean tumor volume was 9.16 cm3 and the mean marginal and maximum radiosurgical doses to the tumors were 21.2 Gy and 26.8 Gy, respectively.Of the 24 tumors treated, 22 have clinical follow-up data at this time. Of those 22 tumors, 12 decreased in size (54.5%), 6 remained unchanged (27.3%), and 4 showed recurrence (18.2%) after CK therapy. Progression-free survival rate was 95%, 71.5%, and 71.5% at 1, 3, and 5 years after multiple CK treatments. The 5-year survival rate after CK was 81%.CK is an effective and safe management option for hemangiopericytomas. The current series demonstrates a tumor control of 81.8%. Other institutions have demonstrated similar outcomes with stereotactic radiosurgery, with tumor control ranging from 46.4% to 100%.

  View details for DOI 10.1186/1756-8722-4-26

  View details for Web of Science ID 000291817100001

  View details for PubMedID 21645367

  View details for PubMedCentralID PMC3118387

• Stereotactic Radiosurgery of Cranial Nonvestibular Schwannomas: Results of Single- and Multisession Radiosurgery NEUROSURGERY Choi, C. Y., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Sakamoto, G. T., Patel, D. A., Lieberson, R. E., Chang, S. D., Adler, J. R. 2011; 68 (5): 1200-1208

  Abstract

  Surgical resection of nonvestibular cranial schwannomas carries a considerable risk of postoperative complications. Stereotactic radiosurgery (SRS) offers a non-invasive treatment alternative. The efficacy and safety of multi-session SRS of nonvestibular cranial schwannomas has not been well studied.To analyze the results of single- and multi-session SRS of nonvestibular cranial schwannomas.From 2001 to 2007, 42 lesions in 40 patients were treated with SRS at Stanford University Medical Center, targeting schwannomas of cranial nerves IV (n = 1), V (n = 18), VII (n = 6), X (n = 5), XII (n = 2), jugular foramen (n = 8), and cavernous sinus (n = 2). SRS was delivered to a median marginal dose of 18 Gy (range, 15-33 Gy) in 1 to 3 sessions, targeting a median tumor volume of 3.2 cm (range, 0.1-23.7 cm). The median doses for treatments in 1 (n = 18), 2 (n = 9), and 3 (n = 15) sessions were 17.5, 20, and 18 Gy, respectively.With a median follow-up of 29 months (range, 6-84 months), tumor control was achieved in 41 of the 42 lesions. Eighteen of 42 lesions (43%) decreased in size; 23 tumors (55%) remained stable. There were 2 cases of new or worsening cranial nerve deficits in patients treated in single session; no patient treated with multi-session SRS experienced any cranial nerve toxicity (P = 0.18).SRS of nonvestibular cranial schwannomas provides excellent tumor control with minimal risk of complications. There was a trend towards decreased complications with multi-session SRS.

  View details for DOI 10.1227/NEU.0b013e31820c0474

  View details for Web of Science ID 000289230300033

  View details for PubMedID 21273918

• TOLERANCE OF THE SPINAL CORD TO STEREOTACTIC RADIOSURGERY: INSIGHTS FROM HEMANGIOBLASTOMAS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Choi, C. Y., Gibbs, I. C., Adler, J. R., Chang, S. D., Lieberson, R. E., Soltys, S. G. 2011; 80 (1): 213-220

  Abstract

  To evaluate spinal cord dose-volume effects, we present a retrospective review of stereotactic radiosurgery (SRS) treatments for spinal cord hemangioblastomas.From November 2001 to July 2008, 27 spinal hemangioblastomas were treated in 19 patients with SRS. Seventeen tumors received a single fraction with a median dose of 20 Gy (range, 18-30 Gy). Ten lesions were treated using 18-25 Gy in two to three sessions. Cord volumes receiving 8, 10, 12, 14, 16, 18, 20, 22, and 24 Gy and dose to 10, 100, 250, 500, 1000, and 2000 mm(3) of cord were determined. Multisession treatments were converted to single-fraction biologically effective dose (SFBED).Single-fraction median cord D(max) was 22.7 Gy (range, 17.8-30.9 Gy). Median V10 was 454 mm(3) (range, 226-3543 mm(3)). Median dose to 500 mm(3) cord was 9.5 Gy (range, 5.3-22.5 Gy). Fractionated median SFBED(3) cord D(max) was 14.1 Gy(3) (range, 12.3-19.4 Gy(3)). Potential toxicities included a Grade 2 unilateral foot drop 5 months after SRS and 2 cases of Grade 1 sensory deficits. The actuarial 3-year local tumor control estimate was 86%.Despite exceeding commonly cited spinal cord dose constraints, SRS for spinal hemangioblastomas is safe and effective. Consistent with animal experiments, these data support a partial-volume tolerance model for the human spinal cord. Because irradiated cord volumes were generally small, application of these data to other clinical scenarios should be made cautiously. Further prospective studies of spinal radiosurgery are needed.

  View details for DOI 10.1016/j.ijrobp.2010.01.040

  View details for Web of Science ID 000290006300031

  View details for PubMedID 21481724

• CyberKnife radiosurgery can control recurrent epidermoid cysts of the central nervous system. Journal of radiosurgery and SBRT Lieberson, R. E., Mener, A., Choi, C., Kalani, M. A., Soltys, S. G., Gibbs, I. C., Heit, G., Adler, J. R., Chang, S. D. 2011; 1 (3): 247–52

  Abstract

  Epidermoid cysts of the central nervous system may be difficult to resect and recurrent lesions may be impossible to control with open surgery. We identified three patients with recurrent epidermoids treated with radiosurgery at Stanford. One patient with a middle fossa lesion that had been resected twice in six years, presented with a 4.5 cubic centimeter recurrence and was treated with radiosurgery. Follow-up scans over three years showed no additional growth. Two patients had spinal lesions. One had undergone numerous, unsuccessful procedures in the three years before the radiosurgical treatment and subsequent open resection of a 3.8 cubic centimeter recurrence. His scans remain unremarkable eight years after treatment. The other, with acaudaequina mass, had required five open resections in 11 years. Following the last resection, the residual was treated radiosurgically. The lesion eventually increased in size, but became symptomatic only after seven years. A second course of radiosurgery was delivered. We believe that stereotactic radiosurgery can be safe for some epidermoid cysts of the central nervous system, decreases their growth rate, and may facilitate subsequent open surgery. It should be considered for select individuals with recurrent or unresectable lesions.

  View details for PubMedID 29296323

  View details for PubMedCentralID PMC5725322

• Cyberknife Stereotactic Radiosurgery for Treatment of Atypical (Who Grade II) Cranial Meningiomas NEUROSURGERY Choi, C. Y., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Jackson, P. S., Lieberson, R. E., Chang, S. D., Adler, J. R. 2010; 67 (5): 1180-1188

  Abstract

  The optimal management of subtotally resected atypical meningiomas is unknown.To perform a retrospective review of patients with residual or recurrent atypical meningiomas treated with stereotactic radiosurgery (SRS).Twenty-five patients were treated, either immediately after surgery (n = 15) or at the time of radiographic progression or treatment failure (n = 10). SRS was delivered to with a median marginal dose of 22 Gy (range, 16-30) in 1 to 4 fractions (median, 1), targeting a median tumor volume of 5.3 cm³ (range, 0.3-26.0).With a median follow-up time of 28 months (range, 3-67), the 12-, 24-, and 36-month actuarial local and regional control rates for all patients were 94%, 94%, 74%, and 90%, 90%, 62%, respectively. There were 2 cases of radiation toxicity. On univariate analysis, the number of recurrences before SRS (P = .046), late SRS (ie, waiting until tumor progression to initiate treatment) (P = .03), and age at treatment ≥ 60 years (P = .01) were significant predictors of recurrence. Of the 20 radiation-naïve patients, 2 patients failed with the targeted lesion and 3 elsewhere in the resection bed, resulting in 12-, 24- and 36-month actuarial local and regional control rates of 100%, 100%, 73% and 93%, 93%, 75%, respectively. The overall locoregional control rates at 12, 24, and 36 months were 93%, 93%, and 54%, respectively.Irradiation of the entire postoperative tumor bed may not be necessary for the majority of patients with subtotally resected atypical meningiomas. Patients in this series achieved outcomes comparable to that of historical control rates for larger volume, conventionally fractionated radiotherapy.

  View details for DOI 10.1227/NEU.0b013e3181f2f427

  View details for Web of Science ID 000283479500003

  View details for PubMedID 20871435

• STEREOTACTIC RADIOSURGERY FOR TREATMENT OF SPINAL METASTASES RECURRING IN CLOSE PROXIMITY TO PREVIOUSLY IRRADIATED SPINAL CORD INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Choi, C. Y., Adler, J. R., Gibbs, I. C., Chang, S. D., Jackson, P. S., Minn, A. Y., Lieberson, R. E., Soltys, S. G. 2010; 78 (2): 499-506

  Abstract

  As the spinal cord tolerance often precludes reirradiation with conventional techniques, local recurrence within a previously irradiated field presents a treatment challenge.We retrospectively reviewed 51 lesions in 42 patients treated from 2002 to 2008 whose spinal metastases recurred in a previous radiation field (median previous spinal cord dose of 40 Gy) and were subsequently treated with stereotactic radiosurgery (SRS).SRS was delivered to a median marginal dose of 20 Gy (range, 10-30 Gy) in 1-5 fractions (median, 2), targeting a median tumor volume of 10.3 cm(3) (range, 0.2-128.6 cm(3)). Converting the SRS regimens with the linear quadratic model (α/β = 3), the median spinal cord maximum single-session equivalent dose (SSED) was 12.1 Gy(3) (range, 4.7-19.3 Gy(3)). With a median follow-up of 7 months (range, 2-47 months), the Kaplan-Meier local control and overall survival rates at 6/12 months were 87%/73% and 81%/68%, respectively. A time to retreatment of ≤12 months and the combination of time to retreatment of ≤12 months with an SSED of <15 Gy(10) were significant predictors of local failure on univariate and multivariate analyses. In patients with a retreatment interval of <12 months, 6/12 month local control rates were 88%/58%, with a SSED of >15 Gy(10), compared to 45%/0% with <15 Gy(10), respectively. One patient (2%) experienced Grade 4 neurotoxicity.SRS is safe and effective in the treatment of spinal metastases recurring in previously irradiated fields. Tumor recurrence within 12 months may correlate with biologic aggressiveness and require higher SRS doses (SSED >15 Gy(10)). Further research is needed to define the partial volume retreatment tolerance of the spinal cord and the optimal target dose.

  View details for DOI 10.1016/j.ijrobp.2009.07.1727

  View details for Web of Science ID 000282147000028

  View details for PubMedID 20133079

• SPINAL CORD TOLERANCE FOR STEREOTACTIC BODY RADIOTHERAPY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Sahgal, A., Ma, L., Gibbs, I., Gerszten, P. C., Ryu, S., Soltys, S., Weinberg, V., Wong, S., Chang, E., Fowler, J., Larson, D. A. 2010; 77 (2): 548-553

  Abstract

  Dosimetric data are reported for five cases of radiation-induced myelopathy after stereotactic body radiotherapy (SBRT) to spinal tumors. Analysis per the biologically effective dose (BED) model was performed.Five patients with radiation myelopathy were compared to a subset of 19 patients with no radiation myelopathy post-SBRT. In all patients, the thecal sac was contoured to represent the spinal cord, and doses to the maximum point, 0.1-, 1-, 2-, and 5-cc volumes, were analyzed. The mean normalized 2-Gy-equivalent BEDs (nBEDs), calculated using an alpha/beta value of 2 for late toxicity with units Gy 2/2, were compared using the t test and analysis of variance test.Radiation myelopathy was observed at the maximum point with doses of 25.6 Gy in two fractions, 30.9 Gy in three fractions, and 14.8, 13.1, and 10.6 Gy in one fraction. Overall, there was a significant interaction between patient subsets and volume based on the nBED (p = 0.0003). Given individual volumes, a significant difference was observed for the mean maximum point nBED (p = 0.01).The maximum point dose should be respected for spine SBRT. For single-fraction SBRT 10 Gy to a maximum point is safe, and up to five fractions an nBED of 30 to 35 Gy 2/2 to the thecal sac also poses a low risk of radiation myelopathy.

  View details for DOI 10.1016/j.ijrobp.2009.05.023

  View details for Web of Science ID 000278167500033

  View details for PubMedID 19765914

• MULTISESSION CYBERKNIFE STEREOTACTIC RADIOSURGERY OF LARGE, BENIGN CRANIAL BASE TUMORS: PRELIMINARY STUDY NEUROSURGERY Tuniz, F., Soltys, S. G., Choi, C. Y., Chang, S. D., Gibbs, I. C., Fischbein, N. J., Adler, J. R. 2009; 65 (5): 898-907

  Abstract

  Although radiosurgery plays an important role in managing benign cranial base lesions, the potential for increased toxicity with single-session treatment of large tumors is a concern. In this retrospective study, we report the intermediate-term rate of local control, morbidity, and clinical outcomes of patients with large cranial base tumors treated with multisession stereotactic radiosurgery with the CyberKnife (Accuray, Inc., Sunnyvale, CA).Between 1999 and 2008, 34 consecutive patients with large (>15 cm), benign cranial base tumors (21 meningiomas, 9 schwannomas, 4 glomus jugulare tumors) underwent primary or postoperative radiosurgical treatment using a multisession approach at Stanford University and were considered in this retrospective study. Forty-four percent of these patients had undergone previous subtotal surgical resection or radiotherapy. CyberKnife radiosurgery was delivered in 2 to 5 sessions (median, 3 sessions) to a median tumor volume of 19.3 cm (range, 15.8-69.3 cm). The median marginal dose was 24 Gy (range, 18-25 Gy) prescribed to a median 78% isodose line.After a median clinical follow-up of 31 months (range, 12-77 months), 21% of patients experienced clinical improvement of neurological symptoms, whereas neurological status remained unchanged among the rest. Four patients experienced prolonged use of glucocorticoids owing to transient neurological worsening and radiographic signs of radiation injury. No permanent neurotoxicity was seen. To date, all tumors remain locally controlled.Over our modest length of follow-up, multisession radiosurgery appears to be a safe and effective option for selected large, benign brain and cranial base lesions.

  View details for DOI 10.1227/01.NEU.0000359316.34041.A8

  View details for Web of Science ID 000270876100013

  View details for PubMedID 19834402

• STEREOTACTIC RADIOSURGICAL TREATMENT OF CRANIAL AND SPINAL HEMANGIOBLASTOMAS NEUROSURGERY Moss, J. M., Choi, C. Y., Adler, J. R., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2009; 65 (1): 79-85

  Abstract

  Stereotactic radiosurgery has been used for nearly 2 decades to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. There is a paucity of long-term published radiosurgical treatment outcomes, particularly for spinal lesions, in a large patient population. The purpose of this study was to provide a long-term retrospective evaluation of radiosurgical hemangioblastoma treatment effectiveness, with a special emphasis on the relatively recent use of frameless, image-guided radiosurgery in the treatment of spinal lesions.From 1991 to 2007, 92 hemangioblastomas in 31 patients, 26 with von Hippel-Lindau disease, were treated with radiosurgery (27 tumors treated with frame-based linear accelerator radiosurgery, and 67 tumors were treated with CyberKnife radiosurgery). The mean patient age was 41 years (range, 18-81 years). The radiation dose to the tumor periphery averaged 23.4 Gy (range, 12-40 Gy). The mean tumor volume was 1.8 cm (range, 0.058-65.4 cm). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic, and magnetic resonance imaging scans.Clinical and radiographic follow-up data were available for 82 hemangioblastoma tumors. Only 13 (16%) of the treated hemangioblastomas progressed, whereas 18 tumors (22%) showed radiographic regression, and 51 tumors (62%) remained unchanged in size. With median follow-up of 69 months (range, 5-164 months), the actuarial local control rates at 36 and 60 months were 85% and 82%, respectively. Radiosurgery improved lesion-associated symptoms in 36 of 41 tumors. During the follow-up period, 9 patients died of causes unrelated to the progression of their treated hemangioblastomas, and 5 patients developed radiation necrosis.Stereotactic radiosurgery is safe and effective in the treatment of hemangioblastomas and is an attractive alternative to surgery for patients, including those with von Hippel-Lindau disease.

  View details for DOI 10.1227/01.NEU.0000348015.51685.D2

  View details for Web of Science ID 000268265600010

  View details for PubMedID 19574828

• CYBERKNIFE FOR BRAIN METASTASES OF MALIGNANT MELANOMA AND RENAL CELL CARCINOMA NEUROSURGERY Hara, W., Tran, P., Li, G., Su, Z., Puataweepong, P., Adler, J. R., Soltys, S. G., Chang, S. D., Gibbs, I. C. 2009; 64 (2): A26-A32

  Abstract

  To evaluate the efficacy of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) for patients with brain metastases of malignant melanoma and renal cell carcinoma.We conducted a retrospective review of all patients treated by image-guided radiosurgery at our institution between March 1999 and December 2005. Sixty-two patients with 145 brain metastases of renal cell carcinoma or melanoma were identified.The median follow-up period was 10.5 months. Forty-four patients had malignant melanoma, and 18 patients had renal cell carcinoma. The median age was 57 years, and patients were classified as recursive partitioning analysis Class 1 (6 patients), 2 (52 patients) or 3 (4 patients). Thirty-three patients had been treated systemically with either chemotherapy or immunotherapy, and 33 patients were taking corticosteroids at the time of treatment. The mean tumor volume was 1.47 mL (range, 0.02-35.7 mL), and the mean prescribed dose was 20 Gy (range, 14-24 Gy). The median survival after SRS was 8.3 months. Actuarial survival at 6 and 12 months was 57 and 37%, respectively. On multivariate analysis, Karnofsky Performance Scale score (P < 0.01) and previous immunotherapy/clinical trial (P = 0.01) significantly affected overall survival. One-year intracranial progression-free survival was 38%, and local control was 87%. Intracranial control was impacted by whole-brain radiotherapy (P = 0.01), previous chemotherapy (P = 0.01), and control of the primary at the time of SRS (P = 0.02). Surgical resection had no effect on intracranial or local control. Radiographic evidence of radiation necrosis developed in 4 patients (6%).CyberKnife radiosurgery provided excellent local control with acceptable toxicity in patients with melanoma or renal cell brain metastases. Initial SRS alone appeared to be a reasonable option, as survival was dictated by systemic disease.

  View details for DOI 10.1227/01.NEU.0000339118.55334.EA

  View details for Web of Science ID 000262797700009

  View details for PubMedID 19165071

• NONISOCENTRIC RADIOSURGICAL RHIZOTOMY FOR TRIGEMINAL NEURALGIA NEUROSURGERY Adler, J. R., Bower, R., Gupta, G., Lim, M., Efron, A., Gibbs, I. C., Chang, S. D., Soltys, S. G. 2009; 64 (2): A84-A90

  Abstract

  Although stereotactic radiosurgery is an established procedure for treating trigeminal neuralgia (TN), the likelihood of a prompt and durable complete response is not assured. Moreover, the incidence of facial numbness remains a challenge. To address these limitations, a new, more anatomic radiosurgical procedure was developed that uses the CyberKnife (Accuray, Inc., Sunnyvale, CA) to lesion an elongated segment of the retrogasserian cisternal portion of the trigeminal sensory root. Because the initial experience with this approach resulted in an unacceptably high incidence of facial numbness, a gradual dose and volume de-escalation was performed over several years. In this single-institution prospective study, we evaluated clinical outcomes in a group of TN patients who underwent lesioning with seemingly optimized nonisocentric radiosurgical parameters.Forty-six patients with intractable idiopathic TN were treated between January 2005 and June 2007. Eligible patients were either poor surgical candidates or had failed previous microvascular decompression or destructive procedures. During a single radiosurgical session, a 6-mm segment of the affected nerve was treated with a mean marginal prescription dose of 58.3 Gy and a mean maximal dose of 73.5 Gy. Monthly neurosurgical follow-up was performed until the patient became pain-free. Longer-term follow-up was performed both in the clinic and over the telephone. Outcomes were graded as excellent (pain-free and off medication), good (>90% improvement while still on medication), fair (50-90% improvement), or poor (no change or worse). Facial numbness was assessed using the Barrow Neurological Institute Facial Numbness Scale score.Symptoms disappeared completely in 39 patients (85%) after a mean latency of 5.2 weeks. In most of these patients, pain relief began within the first week. TN recurred in a single patient after a pain-free interval of 7 months; all symptoms abated after a second radiosurgical procedure. Four additional patients underwent a repeat rhizotomy after failing to respond adequately to the first operation. After a mean follow-up period of 14.7 months, patient-reported outcomes were excellent in 33 patients (72%), good in 11 patients (24%), and poor/no improvement in 2 patients (4%). Significant ipsilateral facial numbness (Grade III on the Barrow Neurological Institute Scale) was reported in 7 patients (15%).Optimized nonisocentric CyberKnife parameters for TN treatment resulted in high rates of pain relief and a more acceptable incidence of facial numbness than reported previously. Longer follow-up periods will be required to establish whether or not the durability of symptom relief after lesioning an elongated segment of the trigeminal root is superior to isocentric radiosurgical rhizotomy.

  View details for DOI 10.1227/01.NEU.0000341631.49154.62

  View details for Web of Science ID 000262797700016

  View details for PubMedID 19165079

• Stereotactic radiosurgery for a cardiac sarcoma: A case report TECHNOLOGY IN CANCER RESEARCH & TREATMENT Soltys, S. G., Kalani, M. Y., Cheshier, S. H., Szabo, K. A., Lo, A., Chang, S. D. 2008; 7 (5): 363-367

  Abstract

  Pulmonary artery intimal sarcoma is an uncommon tumor with a poor prognosis. We report a case of a 75-year-old man with a pulmonary artery sarcoma, recurrent following surgical resection. To palliate symptoms of this recurrence, he underwent CyberKnife stereotactic radiosurgery with a clinical and radiographic response of his treated disease. No acute or sub-acute toxicity was seen until the patient's death due to metastatic disease 10 weeks following treatment. The feasibility and short-term safety of this technique are reviewed, with emphasis on the stereotactic planning considerations, such as mediastinal organ movement and radiation tolerance.

  View details for Web of Science ID 000259799000003

  View details for PubMedID 18783285

• Predictors of peritumoral edema after stereotactic radiosurgery of supratentorial meningiomas NEUROSURGERY Patil, C. G., Hoang, S., Borchers, D. J., Sakamoto, G., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Chang, S. D., Adler, J. R. 2008; 63 (3): 435-440

  Abstract

  Anecdotal evidence suggests that radiosurgical ablation of parasagittal meningiomas may be associated with increased risk of subsequent edema. Potential predictors of postradiosurgical peritumoral edema, including parasagittal tumor location, tumor size, and treatment dose, were evaluated.We retrospectively reviewed records of 102 patients with 111 supratentorial meningiomas treated with CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS). A median marginal dose of 18.0 Gy (range, 11.3-25.0 Gy) was delivered in 1 to 5 sessions (fractions). Potential predictors of posttreatment symptomatic edema were evaluated using Fisher's exact test.Of the 102 patients followed for a mean of 20.9 months (range, 6-77 mo), 15 (14.7%) developed symptomatic edema after SRS. Nine of 31 with parasagittal meningiomas (29.0%) and 6 of 80 with nonparasagittal supratentorial meningiomas (7.5%) developed symptomatic edema (P = 0.0053). Compared with patients with meningiomas in nonmidline supratentorial locations, patients with parasagittal meningiomas were more than 4 times as likely to develop symptomatic edema after SRS (odds ratio, 4.1; 95% confidence interval, 1.5-11.5). The 6-, 12-, and 18-month actuarial rates of symptomatic edema development were significantly greater for patients with parasagittal meningiomas than for patients with nonparasagittal meningiomas (17.8 versus 1.3%, 25.4 versus 5.8%, and 35.2 versus 7.8%, respectively).Patients with parasagittal meningiomas are at greater risk of developing peritumoral symptomatic edema after SRS. Close follow-up after SRS may be particularly important in such patients. These results highlight the need to pursue strategies that could decrease the incidence of postradiosurgical edema in patients with parasagittal meningioma.

  View details for Web of Science ID 000259625600010

  View details for PubMedID 18812954

• Survival following CyberKnife radiosurgery and hypofractionated radiotherapy for newly diagnosed glioblastoma multiforme TECHNOLOGY IN CANCER RESEARCH & TREATMENT Lipani, J. D., Jackson, P. S., Soltys, S. G., Sato, K., Adler, J. R. 2008; 7 (3): 249-255

  Abstract

  Current therapeutic goals for treatment of Glioblastoma Multiforme (GBM) involve gross total resection followed by multifractionated focal external beam radiation therapy (EBRT). Patients treated with optimal therapy have a median survival of approximately 12-15 months. In the present study, we sought to determine whether a hypofractionated dosing schedule using CyberKnife is at least as effective as multifractionated focal EBRT. A retrospective analysis was conducted on 20 histopathologically confirmed GBM patients treated with CyberKnife at Okayama Kyokuto Hospital in Japan after gross total resection (n=11), subtotal resection (n=8), or biopsy (n=1). Eight patients also received adjuvant ACNU and Vincrisitine chemotherapy according to local protocol; however, no patient received any other form of radiation besides post surgical/biopsy CyberKnife treatment. The treated tumor volumes ranged from 9.62 cm(3)-185.81 cm(3) (mean: 86.08 cm(3)). The marginal dose (D90) ranged from 19.99 Gy-41.47 Gy (mean: 34.58 Gy) with a maximum mean dose of 43.99 Gy (range: 23.33 Gy-56.89 Gy). The prescribed isodose line ranged from 50.38%-85.68% with a mean of 79.25%. Treatment was delivered in 1-8 fractions (mean: 5.65). Patients were followed from 2-36 months (mean: 16.45 months). Overall median survival was 16 months with 55% of patients alive at 12 months and 34% of patients alive at 24 months. Median survival of patients in Recursive Partitioning Analysis (RPA) classes III or IV was 32 months versus 12 months for those in RPA class V. Median survival for patients who received gross total resection was 36 months versus 8 months for those who underwent subtotal resection or biopsy. The results of this study using CyberKnife stereotactic radiosurgery (SRS) and hypofractionated radiotherapy compared favorably to historic data using focal EBRT in newly diagnosed post surgical GBM patients. A larger prospective analysis that compares CyberKnife SRS and hypofractionated radiotherapy to focal EBRT is warranted.

  View details for Web of Science ID 000256746700011

  View details for PubMedID 18473497

• Stereotactic radiosurgery of the postoperative resection cavity for brain metastases INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Soltys, S. G., Adler, J. R., Lipani, J. D., Jackson, P. S., Choi, C. Y., Puataweepong, P., White, S., Gibbs, I. C., Chang, S. D. 2008; 70 (1): 187-193

  Abstract

  The purpose of this study was to analyze results of adjuvant stereotactic radiosurgery (SRS) targeted at resection cavities of brain metastases without whole-brain irradiation (WBI).Patients who underwent SRS to the tumor bed, deferring WBI after resection of a brain metastasis, were retrospectively identified.Seventy-two patients with 76 cavities treated from 1998 to 2006 met inclusion criteria. The SRS was delivered to a median marginal dose of 18.6 Gy (range, 15-30 Gy) targeting an average tumor volume of 9.8 cm(3) (range, 0.1-66.8 cm(3)). With a median follow-up of 8.1 months (range, 0.1-80.5 months), 65 patients had follow-up imaging assessable for control analyses. Actuarial local control rates at 6 and 12 months were 88% and 79%, respectively. On univariate analysis, increasing values of conformality indices were the only treatment variables that correlated significantly with improved local control; local control was 100% for the least conformal quartile compared with 63% for the remaining quartiles. Target volume, dose, and number of sessions were not statistically significant.In this retrospective series, SRS administered to the resection cavity of brain metastases resulted in a 79% local control rate at 12 months. This value compares favorably with historic results with observation alone (54%) and postoperative WBI (80-90%). Given the improved local control seen with less conformal plans, we recommend inclusion of a 2-mm margin around the resection cavity when using this technique.

  View details for DOI 10.1016/j.ijrobp.2007.06.068

  View details for Web of Science ID 000251867700026

  View details for PubMedID 17881139

• CyberKnife (R) robotic radiosurgery system for tumor treatment EXPERT REVIEW OF ANTICANCER THERAPY Hara, W., Soltys, S. G., Gibbs, I. C. 2007; 7 (11): 1507-1515

  Abstract

  Defined by its high level of accuracy and rapid radiation dose fall-off, radiosurgery has emerged as an effective radiation technique over the past few decades. Although it was once limited to conditions of the brain, head and neck regions, technological advances in computing and imaging have allowed the application of radiosurgery to conditions throughout the entire body. Using advanced imaging and robotics, the CyberKnife (Accuray, Inc., Sunnyvale, CA, USA) is one of few systems capable of delivering radiosurgery with exquisite accuracy to tumors, cancers and other conditions throughout the body. This review focuses on the development, technology, clinical efficacy and future directions of the CyberKnife.

  View details for DOI 10.1586/14737140.7-11.1507

  View details for Web of Science ID 000251444300009

  View details for PubMedID 18020920

• CyberKnife rhizotomy for facetogenic back pain: a pilot study. Neurosurgical focus Li, G., Patil, C., Adler, J. R., Lad, S. P., Soltys, S. G., Gibbs, I. C., Tupper, L., Boakye, M. 2007; 23 (6): E2-?

  Abstract

  By targeting the medial branches of the dorsal rami, radiofrequency ablation and facet joint injections can provide temporary amelioration of facet joint-producing (or facetogenic) back pain. The authors used CyberKnife radiosurgery to denervate affected facet joints with the goal of obtaining a less invasive yet more thorough and durable antinociceptive rhizotomy.Patients with refractory low-back pain, in whom symptoms are temporarily resolved by facet joint injections, were eligible. The patients were required to exhibit positron emission tomography-positive findings at the affected levels. Radiosurgical rhizotomy, targeting the facet joint, was performed in a single session with a marginal prescription dose of 40 Gy and a maximal dose of 60 Gy.Seven facet joints in 5 patients with presumptive facetogenic back pain underwent CyberKnife lesioning. The median follow-up was 9.8 months (range 3-16 months). The mean planning target volume was 1.7 cm(3) (range 0.9-2.7 cm(3)). A dose of 40 Gy was prescribed to a mean isodose line of 79% (range 75-80%). Within 1 month of radiosurgery, improvement in pain was observed in 3 of the 5 patients with durable responses at 16, 12, and 6 months, respectively, of follow-up. Two patients, after 12 and 3 months of follow-up, have neither improved nor worsened. No patient has experienced acute or late-onset toxicity.These preliminary results suggest that CyberKnife radiosurgery could be a safe, effective, and non-invasive alternative to radiofrequency ablation for managing facetogenic back pain. No patient suffered recurrent symptoms after radiosurgery. It is not yet known whether pain relief due to such lesions will be more durable than that produced by alternative procedures. A larger series of patients with long-term follow-up is ongoing.

  View details for PubMedID 18081475

• Efficacy and safety of CyberKnife radiosurgery for acromegaly. Pituitary Roberts, B. K., Ouyang, D. L., Lad, S. P., Chang, S. D., Harsh, G. R., Adler, J. R., Soltys, S. G., Gibbs, I. C., Remedios, L., Katznelson, L. 2007; 10 (1): 19-25

  Abstract

  Acromegaly is a disease characterized by GH hypersecretion, and is typically caused by a pituitary somatotroph adenoma. The primary mode of therapy is surgery, and radiotherapy is utilized as an adjuvant strategy to treat persistent disease. The aim of this study was to determine the efficacy and tolerability of CyberKnife stereotactic radiosurgery in acromegaly.A retrospective review of biochemical and imaging data for subjects with acromegaly treated with CyberKnife stereotactic radiosurgery between 1998 and 2005 at Stanford University Hospital.Nine patients with active acromegaly were treated with radiosurgery using the CyberKnife (CK).Biochemical response based on serum insulin-like growth factor-1 (IGF-1), anterior pituitary hormone function, and tumor size with MRI scans were analyzed.After a mean follow up of 25.4 months (range, 6-53 months), CK radiosurgery resulted in complete biochemical remission in 4 (44.4%) subjects, and in biochemical control with the concomitant use of a somatostatin analog in an additional subject. Smaller tumor size was predictive of treatment success: baseline tumor volume was 1.28 cc (+/- 0.81, SD) vs. 3.93 cc (+/- 1.54) in subjects with a normal IGF-1 vs. those with persistent, active disease, respectively (P = 0.02). The mean biologically effective dose (BED) was higher in subjects who achieved a normal IGF-1 vs. those with persistent, active disease, 172 Gy(3) (+/-28) vs. 94 Gy(3) (+/-17), respectively (P < 0.01). At least one new anterior pituitary hormone deficiency was observed after CK in 3 (33%) patients: two developed hypogonadism, and one developed panhypopituitarism.CK radiosurgery may be a valuable adjuvant therapy for the management of acromegaly.

  View details for PubMedID 17273921

• Sample classification from protein mass spectrometry, by 'peak probability contrasts' BIOINFORMATICS Tibshirani, R., Hastie, T., Narasimhan, B., Soltys, S., Shi, G. Y., Koong, A., Le, Q. T. 2004; 20 (17): 3034-3044

  Abstract

  Early cancer detection has always been a major research focus in solid tumor oncology. Early tumor detection can theoretically result in lower stage tumors, more treatable diseases and ultimately higher cure rates with less treatment-related morbidities. Protein mass spectrometry is a potentially powerful tool for early cancer detection. We propose a novel method for sample classification from protein mass spectrometry data. When applied to spectra from both diseased and healthy patients, the 'peak probability contrast' technique provides a list of all common peaks among the spectra, their statistical significance and their relative importance in discriminating between the two groups. We illustrate the method on matrix-assisted laser desorption and ionization mass spectrometry data from a study of ovarian cancers.Compared to other statistical approaches for class prediction, the peak probability contrast method performs as well or better than several methods that require the full spectra, rather than just labelled peaks. It is also much more interpretable biologically. The peak probability contrast method is a potentially useful tool for sample classification from protein mass spectrometry data.

  View details for DOI 10.1093/bioinformatics/bth357

  View details for Web of Science ID 000225361400017

  View details for PubMedID 15226172

• The use of plasma surface-enhanced laser desorption/ionization time-of-flight mass spectrometry proteomic patterns for detection of head and neck squamous cell cancers 45th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Soltys, S. G., Le, Q. T., Shi, G. Y., Tibshirani, R., Giaccia, A. J., Koong, A. C. AMER ASSOC CANCER RESEARCH. 2004: 4806–12

  Abstract

  Our study was undertaken to determine the utility of plasma proteomic profiling using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry for the detection of head and neck squamous cell carcinomas (HNSCCs).Pretreatment plasma samples from HNSCC patients or controls without known neoplastic disease were analyzed on the Protein Biology System IIc SELDI-TOF mass spectrometer (Ciphergen Biosystems, Fremont, CA). Proteomic spectra of mass:charge ratio (m/z) were generated by the application of plasma to immobilized metal-affinity-capture (IMAC) ProteinChip arrays activated with copper. A total of 37356 data points were generated for each sample. A training set of spectra from 56 cancer patients and 52 controls were applied to the "Lasso" technique to identify protein profiles that can distinguish cancer from noncancer, and cross-validation was used to determine test errors in this training set. The discovery pattern was then used to classify a separate masked test set of 57 cancer and 52 controls. In total, we analyzed the proteomic spectra of 113 cancer patients and 104 controls.The Lasso approach identified 65 significant data points for the discrimination of normal from cancer profiles. The discriminatory pattern correctly identified 39 of 57 HNSCC patients and 40 of 52 noncancer controls in the masked test set. These results yielded a sensitivity of 68% and specificity of 73%. Subgroup analyses in the test set of four different demographic factors (age, gender, and cigarette and alcohol use) that can potentially confound the interpretation of the results suggest that this model tended to overpredict cancer in control smokers.Plasma proteomic profiling with SELDI-TOF mass spectrometry provides moderate sensitivity and specificity in discriminating HNSCC. Further improvement and validation of this approach is needed to determine its usefulness in screening for this disease.

  View details for Web of Science ID 000222840700027

  View details for PubMedID 15269156

• Human papillomavirus and p53 mutational status as prognostic factors in head and neck carcinoma HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Sisk, E. A., Soltys, S. G., ZHU, S. B., Fisher, S. G., Carey, T. E., Bradford, C. R. 2002; 24 (9): 841-849

  Abstract

  Mutations of the p53 tumor-suppressor gene are common in squamous cell carcinoma of the head and neck (SCCHN) and may portend a worse prognosis. Human papillomavirus (HPV) represents another potential prognostic factor for SCCHN. The oncogenic potential of HPV may be due to the ability of its E6 oncoprotein to promote degradation of wild-type p53 protein. We wish to determine whether there is a lower incidence of p53 mutations in HPV-positive versus HPV-negative tumors, and if HPV and/or p53 status has an impact on survival.Thirty-two SCCHN specimens were analyzed for mutations of the p53 gene using single-strand conformational polymorphism (SSCP) analysis followed by DNA sequencing. The HPV status of all specimens was evaluated by use of polymerase chain reaction with HPV consensus primers and Southern blot hybridization. Pertinent clinical information was obtained from chart review.Nonsilent p53 mutations were present in 2 of 15 (13%) of HPV-positive tumors compared with 6 of 17 (35%) of HPV-negative tumors (p =.229; Fisher's exact test, odds ratio.28). A survival advantage was found between HPV-positive compared with HPV-negative specimens (p =.0264) and between p53 wild type compared with p53 mutant specimens (p =.01) by univariate log rank analysis. When stratified according to both HPV and p53 status, a statistically significant survival difference was observed largely because of a 100% survival for the HPV-positive/p53 wild-type group (p =.003).This preliminary study supports the notion that the presence of HPV confers a survival advantage among HNSCC patients, particularly when p53 is wild type.

  View details for DOI 10.1002/hed.10146

  View details for Web of Science ID 000177651400003

  View details for PubMedID 12211048