Iris C. Gibbs, MD, FACR

All Publications

• Chemoradiation impairs normal developmental cortical thinning in medulloblastoma. Journal of neuro-oncology Kundu, P., Li, M. D., Durkee, B. Y., Hiniker, S. M., Bush, K., von Eyben, R., Monje, M. L., Yeom, K. W., Donaldson, S. S., Gibbs, I. C. 2017

  Abstract

  Medulloblastoma patients are treated with surgery, radiation and chemotherapy. Radiation dose to the temporal lobe may be associated with neurocognitive sequelae. Longitudinal changes of temporal lobe cortical thickness may result from neurodevelopmental processes such as synaptic pruning. This study applies longitudinal image analysis to compare developmental change in cortical thickness in medulloblastoma (MB) patients who were treated by combined modality therapy to that of cerebellar juvenile pilocytic astrocytoma (JPA) patients who were treated by surgery alone. We hypothesized that the rates of developmental change in cortical thickness would differ between these two groups. This retrospective cohort study assessed changes in cortical thickness over time between MB and JPA patients. High-resolution magnetic resonance (MR) images of 14 MB and 7 JPA subjects were processed to measure cortical thickness of bilateral temporal lobe substructures. A linear mixed effects model was used to identify differences in substructure longitudinal changes in cortical thickness. The left temporal lobe exhibited overall increased cortical thickness in MB patients relative to JPA patients who showed overall cortical thinning (mean annual cortical thickness change: MB 0.14 mm/year versus JPA -0.018 mm/year across all substructures), particularly in the inferior temporal lobe substructures (p < 0.0001). The cortical thickness change of the right temporal lobe substructures exhibited similar, though attenuated trends (p = 0.002). MB patients exhibit overall increased cortical thickness rather than cortical thinning as seen in JPA patients and as expected in normal cortical development. These observations are possibly due to chemoradiation induced-disruption of normal neuronal mechanisms. Longitudinal image analysis may identify early biomarkers for neurocognitive function with routine imaging.

  View details for DOI 10.1007/s11060-017-2453-5

  View details for PubMedID 28534154

• 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

• 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

• Brain Perfusion and Diffusion Abnormalities in Children Treated for Posterior Fossa Brain Tumors. journal of pediatrics Li, M. D., Forkert, N. D., Kundu, P., Ambler, C., Lober, R. M., Burns, T. C., Barnes, P. D., Gibbs, I. C., Grant, G. A., Fisher, P. G., Cheshier, S. H., Campen, C. J., Monje, M., Yeom, K. W. 2017

  Abstract

  To compare cerebral perfusion and diffusion in survivors of childhood posterior fossa brain tumor with neurologically normal controls and correlate differences with cognitive dysfunction.We analyzed retrospectively arterial spin-labeled cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) in 21 patients with medulloblastoma (MB), 18 patients with pilocytic astrocytoma (PA), and 64 neurologically normal children. We generated ANCOVA models to evaluate treatment effects on the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, and cerebral white matter at time points an average of 5.7 years after original diagnosis. A retrospective review of patient charts identified 12 patients with neurocognitive data and in whom the relationship between IQ and magnetic resonance imaging variables was assessed for each brain structure.Patients with MB (all treated with surgery, chemotherapy, and radiation) had significantly lower global CBF relative to controls (10%-23% lower, varying by anatomic region, all adjusted P < .05), whereas patients with PA (all treated with surgery alone) had normal CBF. ADC was decreased specifically in the hippocampus and amygdala of patients with MB and within the amygdala of patients with PA but otherwise remained normal after therapy. In the patients with tumor previously evaluated for IQ, regional ADC, but not CBF, correlated with IQ (R(2) = 0.33-0.75).The treatment for MB, but not PA, was associated with globally reduced CBF. Treatment in both tumor types was associated with diffusion abnormalities of the mesial temporal lobe structures. Despite significant perfusion abnormalities in patients with MB, diffusion, but not perfusion, correlated with cognitive outcomes.

  View details for DOI 10.1016/j.jpeds.2017.01.019

  View details for PubMedID 28187964

• 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

• A Phase I/II Trial of 5 Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma Multiforme. International journal of radiation oncology, biology, physics Azoulay, M., Ho, C. K., Fujimoto, D. K., Modlin, L. A., Gibbs, I. C., Hancock, S. L., Li, G., Chang, S. D., Adler, J. R., Harsh, G. R., Nagpal, S., Thomas, R., Recht, L., Choi, C. Y., Soltys, S. G. 2016; 96 (2S): E131-E132

  View details for DOI 10.1016/j.ijrobp.2016.06.921

  View details for PubMedID 27673859

• 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

• 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

• 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

• 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

  View details for DOI 10.1016/j.semradonc.2015.11.010

  View details for Web of Science ID 000373242700012

• Cost-Effectiveness of Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer. Journal of clinical oncology Durkee, B. Y., Qian, Y., Pollom, E. L., King, M. T., Dudley, S. A., Shaffer, J. L., Chang, D. T., Gibbs, I. C., Goldhaber-Fiebert, J. D., Horst, K. C. 2016; 34 (9): 902-909

  Abstract

  The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab to docetaxel and trastuzumab (THP) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2) -overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of adding pertuzumab.We developed a decision-analytic Markov model to evaluate the cost effectiveness of docetaxel plus trastuzumab (TH) with or without pertuzumab in US patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost effectiveness expressed as an incremental cost-effectiveness ratio. One- and multiway deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions.Modeled median survival was 39.4 months for TH and 56.9 months for THP. The addition of pertuzumab resulted in an additional 1.82 life-years gained, or 0.64 QALYs, at a cost of $713,219 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost effectiveness at a willingness to pay of $100,000 per QALY gained.THP in patients with metastatic HER2-positive breast cancer is unlikely to be cost effective in the United States.

  View details for DOI 10.1200/JCO.2015.62.9105

  View details for PubMedID 26351332

• 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

• Treatment options for optic pathway gliomas. Current treatment options in neurology Thomas, R. P., Gibbs, I. C., Xu, L. W., Recht, L. 2015; 17 (2): 333-?

  Abstract

  Gliomas that affect the optic pathways are for the most part low-grade neoplasms that often, but not always, have good prognoses. Optimal treatment and management of optic pathway gliomas remains unclear and the decision hinges upon several factors including patient age, tumor location, and visual symptoms. We favor a treatment approach that is dependent on the location of tumor within anterior, chiasmal or posterior/hypothalamic visual pathways. In children who are minimally or not symptomatic, we recommend observation rather than early treatment intervention. Most of these patients will have neurofibromatosis type 1 (NF1) based on the natural history and their pilocytic astrocytoma histology. Serial magnetic resonance imaging studies and formal neuro-ophthalmology testing should enable close observation of these patients, with intervention being reserved for when tumor progression results in significant visual loss or proptosis. Chemotherapy is an accepted first line treatment, and a number of effective medications are available, although no agent has proven clearly superior. If progression is accompanied by the complete loss of vision, surgery can be utilized to help alleviate structural issues (ie, proptosis). Minimally symptomatic chiasmal or hypothalamic tumors that arise in the setting of NF1 can also be observed initially because of their favorable prognosis. Children with NF1 and chiasmal or posterior visual tumors who progress either on imaging or clinical grounds (ie, development of significant visual deficits) should be treated first with chemotherapy rather than radiation therapy to minimize the effects on the developing central nervous system. Individuals without NF1 presenting with a chiasmal or hypothalamic mass are candidates for biopsy to determine the underlying pathology of the lesion. Symptomatic patients with pilocytic astrocytoma should first receive chemotherapy. In contrast, other histologies including malignant optic pathway gliomas should be treated similar to other gliomas that occur in other locations with appropriate doses of radiation and chemotherapy.

  View details for DOI 10.1007/s11940-014-0333-2

  View details for PubMedID 25619537

• Treatment Options for Optic Pathway Gliomas CURRENT TREATMENT OPTIONS IN NEUROLOGY Thomas, R. P., Gibbs, I. C., Xu, L. W., Recht, L. 2015; 17 (2)

  View details for DOI 10.1007/s11940-014-0333-2

  View details for Web of Science ID 000351159000001

  View details for PubMedID 25619537

• Oncology Scan-Molecular Genotyping of Medulloblastoma: A New Treatment Era INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Terezakis, S. A., Gibbs, I. C., Haas-Kogan, D. A. 2014; 89 (2): 229-231

  View details for DOI 10.1016/j.ijrobp.2013.12.021

  View details for Web of Science ID 000335513800001

  View details for PubMedID 24837885

• 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

• The subventricular zone neural progenitor cell hypothesis in glioblastoma: epiphany, Trojan Horse, or Cheshire fact? International journal of radiation oncology, biology, physics Gibbs, I. C., Haas-Kogan, D., Terezakis, S., Kavanagh, B. D. 2013; 86 (4): 606-608

  View details for DOI 10.1016/j.ijrobp.2013.03.002

  View details for PubMedID 23773389

• A phase I trial of arsenic trioxide chemoradiotherapy for infiltrating astrocytomas of childhood. Neuro-oncology Cohen, K. J., Gibbs, I. C., Fisher, P. G., Hayashi, R. J., Macy, M. E., Gore, L. 2013; 15 (6): 783-787

  Abstract

  Background Arsenic trioxide (ATO) has demonstrated preclinical evidence of activity in the treatment of infiltrating astrocytomas. Methods We conducted a phase I trial of ATO given concomitantly with radiation therapy in children with newly diagnosed anaplastic astrocytoma, glioblastoma, or diffuse intrinsic pontine glioma. Eligible patients received a fixed daily dose of 0.15 mg/kg of ATO once a week, with each subsequent cohort of patients receiving an additional dose per week up to a planned frequency of ATO administration 5 days per week as tolerated. Twenty-four children were enrolled and 21 children were evaluable. Results ATO was well tolerated throughout the entire dose escalation, resulting in confirmation of safety when administered 5 days per week during irradiation. Conclusions The recommended dose of ATO during conventional irradiation is 0.15 mg/kg given on a daily basis with each fraction of radiation therapy administered.

  View details for DOI 10.1093/neuonc/not021

  View details for PubMedID 23460318

• 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

• Concurrent cyclophosphamide and craniospinal radiotherapy for pediatric high-risk embryonal brain tumors JOURNAL OF NEURO-ONCOLOGY Campen, C. J., Dearlove, J., Partap, S., Murphy, P., Gibbs, I. C., Dahl, G. V., Fisher, P. G. 2012; 110 (2): 287-291

  Abstract

  Embryonal tumors are an aggressive subtype of high-grade, pediatric central nervous system (CNS) tumors often with dismal survival rates. The 5-year survival for highest-risk embryonal tumors may be as low as 10 %. We report feasibility and efficacy from our experience using intravenous (IV) cyclophosphamide concurrently with craniospinal radiation (CSI) in high-risk embryonal CNS tumors of childhood. Ten consecutive children (aged: 3.5-15.5 years, median: 10.2 years, six male) with high-risk embryonal tumors, including: large cell/anaplastic medulloblastoma (6), atypical teratoid rhabdoid tumor (1), and leptomeningeal primitive neuroectodermal tumor (3), were treated with IV cyclophosphamide 1 g/M(2) on days 1 and 2 of CSI. Following a median of 36 Gy CSI plus tumor boosts, adjuvant treatment consisted of 21 doses of oral etoposide (7) and alkylator based chemotherapy from five to eight cycles in all. Of the ten patients thus treated, six remain alive with no evidence of disease and four are deceased. Median survival was 3.3 years, with a 3-year progression-free survival of 50 % (5/10). Median follow-up was: 3.3 years (range: 5 months-12.9 years) in the five patients with progression, median time-to-progression was: 1.3 years (range: 1 month-3 years). Median follow-up in the patients without progression is 8.8 years (range: 3-12.9 years). Complications due to adjuvant chemotherapy were typical and included myelosupression (10), necessitating shortened duration of chemotherapy in three, and hemorrhagic cystitis (1). In high-risk embryonal CNS tumors, cyclophosphamide given concurrently with CSI is well tolerated. Early results suggest that a phase II trial is warranted.

  View details for DOI 10.1007/s11060-012-0969-2

  View details for Web of Science ID 000311208100017

  View details for PubMedID 22941430

• 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

• 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

• 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

• 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

• 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

• Stereotactic Body Radiotherapy (SBRT) Spinal Cord Tolerance: Updated Report Sahgal, A., Chang, E., Weinberg, V., Chao, S., Gibbs, I., Gerszten, P. C., Ryu, S., Wong, S., Ma, L., Larson, D. A. ELSEVIER SCIENCE INC. 2011: S132–S132

  View details for Web of Science ID 000296411700266

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

  Abstract

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

  View details for Web of Science ID 000284971100007

  View details for PubMedID 21070081

• STEREOTACTIC 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

• Cerebrovascular disease in childhood cancer survivors A Children's Oncology Group Report NEUROLOGY Morris, B., Partap, S., Yeom, K., Gibbs, I. C., Fisher, P. G., King, A. A. 2009; 73 (22): 1906-1913

  Abstract

  Curative therapy for childhood cancer has dramatically improved over past decades. Therapeutic radiation has been instrumental in this success. Unfortunately, irradiation is associated with untoward effects, including stroke and other cerebrovascular disease (CVD). The Children's Oncology Group (COG) has developed guidelines for screening survivors at risk for persistent or late sequelae of cancer therapy.This review summarizes the pathophysiology and relevant manifestations of radiation-induced CVD and outlines the specific patient groups at risk for early-onset stroke. The reader will be alerted to the availability of the COG recommendations for monitoring, and, when applicable, specific screening and treatment recommendations will be highlighted.A multidisciplinary task force critically reviewed the existing literature and scored the evidence to establish the current COG guidelines for monitoring health of survivors treated with head and neck irradiation.Previous head and neck exposure to therapeutic radiation is associated with latent CVD and increased risk for stroke in some patient groups. Common manifestations of radiation-induced CVD includes steno-occlusive disease, moyamoya, aneurysm, mineralizing microangiopathy, vascular malformations, and strokelike migraines.Risk for stroke is increased in survivors of pediatric CNS tumors, Hodgkin lymphoma, and acute lymphoblastic leukemia who received radiation to the brain and/or neck. As the population of survivors ages, vigilance for stroke and cerebrovascular disease needs to continue based on specific exposures during curative cancer therapy.

  View details for DOI 10.1212/WNL.0b013e3181c17ea8

  View details for Web of Science ID 000272205200015

  View details for PubMedID 19812380

  View details for PubMedCentralID PMC2788797

• DELAYED RADIATION-INDUCED MYELOPATHY AFTER SPINAL RADIOSURGERY NEUROSURGERY Gibbs, I. C., Patil, C., Gerszten, P. C., Adler, J. R., Burton, S. A. 2009; 64 (2): A67-A72

  Abstract

  Spinal cord injury is arguably the most feared complication in radiotherapy and has historically limited the aggressiveness of spinal tumor treatment. We report a case series of 6 patients treated with radiosurgery who developed delayed myelopathy.Between 1996 and 2005, 1075 patients with benign or malignant spinal tumors were treated by CyberKnife (Accuray, Inc., Sunnyvale, CA) robotic radiosurgery at Stanford University Medical Center and the University of Pittsburgh Medical Center. Patients were followed prospectively with clinical and radiographic assessments at 1- to 6-month intervals. A retrospective review identified patients who developed delayed radiation-induced myelopathy. Six patients (5 women, 1 man) with a mean age of 48 years (range, 25-61 years) developed delayed myelopathy at a mean of 6.3 months (range, 2-9 months) after spinal radiosurgery. Three tumors were metastatic; 3 were benign. The metastases were in the upper to midthoracic spine, whereas the benign tumors were partially in the cervical region. Three cases involved previous radiation therapy.Dose volume histograms were generated for target and critical structures. Clinical and dosimetric factors were analyzed for factors predictive of spinal cord injury. Specific dosimetric factors contributing to this complication could not be identified, but one-half of the patients with myelopathy received spinal cord biological equivalent doses exceeding 8 Gy.Delayed myelopathy after radiosurgery is uncommon with the dose schedules used in this case series. Radiation injury to the spinal cord occurred over a spectrum of dose parameters that prevented identification of specific dosimetric factors contributing to this complication. Primarily, biological equivalent dose estimates were not usable for defining spinal cord tolerance to hypofractionated dose schedules. We recommend limiting the volume of spinal cord treated above an 8-Gy equivalent dose, because half of the complications occurred beyond this level.

  View details for DOI 10.1227/01.NEU.0000341628.98141.86

  View details for Web of Science ID 000262797700014

  View details for PubMedID 19165076

• Image-guided robotic radiosurgery for spinal metastases RADIOTHERAPY AND ONCOLOGY Gibbs, I. C., Kamnerdsupaphon, P., Ryu, M., Dodd, R., Kiernan, M., Change, S. D., Adler, J. R. 2007; 82 (2): 185-190

  Abstract

  To determine the effectiveness and safety of image-guided robotic radiosurgery for spinal metastases.From 1996 to 2005, 74 patients with 102 spinal metastases were treated using the CyberKnife at Stanford University. Sixty-two (84%) patients were symptomatic. Seventy-four percent (50/68) of previously treated patients had prior radiation. Using the CyberKnife, 16-25 Gy in 1-5 fractions was delivered. Patients were followed clinically and radiographically for at least 3 months or until death.With mean follow-up of 9 months (range 0-33 months), 36 patients were alive and 38 were dead at last follow-up. No death was treatment related. Eighty-four (84%) percent of symptomatic patients experienced improvement or resolution of symptoms after treatment. Three patients developed treatment-related spinal injury. Analysis of dose-volume parameters and clinical parameters failed to identify predictors of spinal cord injury.Robotic radiosurgery is effective and generally safe for spinal metastases even in previously irradiated patients.

  View details for DOI 10.1016/j.radonc.2006.11.023

  View details for Web of Science ID 000245151400011

  View details for PubMedID 17257702

• Visual field preservation after multisession CyberKnife radiosurgery for perioptic lesions NEUROSURGERY Adler, J. R., Gibbs, I. C., Puataweepong, P., Chang, S. D. 2006; 59 (2): 244-253

  Abstract

  The restricted radiation tolerance of the anterior visual pathways represents a unique challenge for ablating adjacent lesions with single-session radiosurgery. Although preliminary studies have recently demonstrated that multisession radiosurgery for selected perioptic tumors is both safe and effective, the number of patients in these clinical series was modest and the length of follow-up limited. The current retrospective study is intended to help address these shortcomings.Forty-nine consecutive patients with meningioma (n = 27), pituitary adenoma (n = 19), craniopharyngioma (n = 2), or mixed germ cell tumor (n = 1) situated within 2 mm of a "short segment" of the optic apparatus underwent multisession image-guided radiosurgery at Stanford University Medical Center. Thirty-nine of these patients had previous subtotal surgical resection, and six had previously been treated with conventional fractionated radiotherapy (6). CyberKnife radiosurgery was delivered in two to five sessions to an average tumor volume of 7.7 cm3 and a cumulative average marginal dose of 20.3 Gy. Formal visual testing and clinical examinations were performed before treatment and at follow-up intervals beginning at 6 months.After a mean visual field follow-up of 49 months (range, 6-96 mo), vision was unchanged postradiosurgery in 38 patients, improved in eight (16%), and worse in three (6%). In each instance, visual deterioration was accompanied by tumor progression that ultimately resulted in patient death. However, one of these patients, who had a multiply recurrent adrenocorticotropic hormone-secreting pituitary adenoma, initially experienced early visual loss without significant tumor progression after both a previous course of radiotherapy and three separate sessions of radiosurgery. After a mean magnetic resonance imaging follow-up period of 46 months, tumor volume was stable or smaller in all other cases. Two patients died of unrelated nonbrain causes.Multisession radiosurgery resulted in high rates of tumor control and preservation of visual function in this group of perioptic tumors. Ninety-four percent of patients retained or improved preradiosurgical vision. This intermediate-term experience reinforces the findings from earlier studies that suggested that multisession radiosurgery can be a safe and effective alternative to either surgery or fractionated radiotherapy for selected lesions immediately adjacent to short segments of the optic apparatus.

  View details for DOI 10.1227/01.NEU.0000223512.09115.3E

  View details for Web of Science ID 000239763800017

  View details for PubMedID 16883165

• Cyberknife radiosurgery for benign intradural extramedullary spinal tumors NEUROSURGERY Dodd, R. L., Ryu, M. R., Kamnerdsupaphon, P., Gibbs, I. C., Chang, S. D., Adler, J. R. 2006; 58 (4): 674-684

  Abstract

  Microsurgical resection of benign intradural extramedullary spinal tumors is generally safe and successful, but patients with neurofibromatosis, recurrent tumors, multiple lesions, or medical problems that place them at higher surgical risk may benefit from alternatives to surgery. In this prospective study, we analyzed our preliminary experience with image-guided radiosurgical ablation of selected benign spinal neoplasms.Since 1999, CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery was used to manage 51 patients (median age, 46 yr; range, 12-86 yr) with 55 benign spinal tumors (30 schwannomas, nine neurofibromas, 16 meningiomas) at Stanford University Medical Center. Total treatment doses ranged from 1600 to 3000 cGy delivered in consecutive daily sessions (1-5) to tumor volumes that varied from 0.136 to 24.6 cm.Less than 1 year postradiosurgery, three of the 51 patients in this series (one meningioma, one schwannoma, and one neurofibroma) required surgical resection of their tumor because of persistent or worsening symptoms; only one of these lesions was larger radiographically. However, 28 of the 51 patients now have greater than 24 months clinical and radiographic follow-up. After a mean follow-up of 36 months, all of these later lesions were either stable (61%) or smaller (39%). Two patients died from unrelated causes. Radiation-induced myelopathy appeared 8 months postradiosurgery in one patient.Although more patients studied over an even longer follow-up period are needed to determine the long-term efficacy of spinal radiosurgery for benign extra-axial neoplasms, short-term clinical benefits were observed in this prospective analysis. The present study demonstrates that CyberKnife radiosurgical ablation of such tumors is technically feasible and associated with low morbidity.

  View details for DOI 10.1227/01.NEU.0000204128.84742.8F

  View details for Web of Science ID 000237047200026

  View details for PubMedID 16575331

• Staged stereotactic irradiation for acoustic neuroma NEUROSURGERY Chang, S. D., Gibbs, I. C., Sakamoto, G. T., Lee, E., Oyelese, A., Adler, J. R. 2005; 56 (6): 1254-1261

  Abstract

  Stereotactic radiosurgery has proven effective in the treatment of acoustic neuromas. Prior reports using single-stage radiosurgery consistently have shown excellent tumor control, but only up to a 50 to 73% likelihood of maintaining hearing at pretreatment levels. Staged, frame-based radiosurgery using 12-hour interfraction intervals previously has been shown by our group to achieve excellent tumor control while increasing the rate of hearing preservation at 2 years to 77%. The arrival of CyberKnife (Accuray, Inc., Sunnyvale, CA) image-guided radiosurgery now makes it more practical to treat acoustic neuroma with a staged approach. We hypothesize that such factors may further minimize injury of adjacent cranial nerves. In this retrospective study, we report our experience with staged radiosurgery for managing acoustic neuromas.Since 1999, the CyberKnife has been used to treat more than 270 patients with acoustic neuroma at Stanford University. Sixty-one of these patients have now been followed up for a minimum of 36 months and form the basis for the present clinical investigation. Among the treated patients, the mean transverse tumor diameter was 18.5 mm, whereas the total marginal dose was either 18 or 21 Gy using three 6- or 7-Gy fractions. Audiograms and magnetic resonance imaging were obtained at 6-months intervals after treatment for the first 2 years and then annually thereafter.Of the 61 patients with a minimum of 36 months of follow-up (mean, 48 mo), 74% of patients with serviceable hearing (Gardner-Robinson Class 1-2) maintained serviceable hearing at the last follow-up, and no patient with at least some hearing before treatment lost all hearing on the treated side. Only one treated tumor (2%) progressed after radiosurgery; 29 (48%) of 61 decreased in size and 31 (50%) of the 61 tumors were stable. In no patients did new trigeminal dysfunction develop, nor did any patient experience permanent injury to their facial nerve; two patients experienced transient facial twitching that resolved in 3 to 5 months.Although still preliminary, these results indicate that improved tumor dose homogeneity and a staged treatment regimen may improve hearing preservation in acoustic neuroma patients undergoing stereotactic radiosurgery.

  View details for DOI 10.1227/01.NEU.0000159650.79833.2B

  View details for Web of Science ID 000229690300018

  View details for PubMedID 15918941

• 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

• 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. 2016: -?

  Abstract

  Non-vestibular cranial nerve schwannomas (NVCNS) are rare lesions, representing <10 % of cranial nerve schwannomas. The optimal treatment for NVCNS is often derived from vestibular schwannomas experience. Surgical resection has been referred to as the first line treatment for those benign tumors, but significant complication rates are reported. Stereotactic radiosurgery (SRS) has arisen as a mainstay of treatment for many benign tumors, including schwanommas. We retrospectively reviewed the outcomes of NVCNS treated by SRS to characterize tumor control, symptom relief, toxicity, and the role of hypo-fractionation of SRS dose. Eighty-eight (88) patients, with ninety-five (95) NVCNS were treated with either single or multi-session SRS from 2001 to 2014. Local control was achieved in 94 % of patients treated (median follow-up of 33 months, range 1-155). Complications were seen in 7.4 % of cases treated with SRS. At 1-year, 57 % of patients had improvement or resolution of their symptoms, while 35 % were stable and 8 % had worsening or increased symptoms. While 42 % received only one session, results on local control were similar for one or multiple sessions (p = 0.424). SRS for NVCNS is a treatment modality that provides excellent local control with minimal complication risk compared to traditional neurosurgical techniques. Tumor control obtained with a multi-session treatment was not significantly different from single session treatment. Safety profile was also comparable for uni or multi-session treatments. We concluded that, as seen in VS treated with CK SRS, radiosurgery treatment can be safely delivered in cases of NVCNS.

  View details for PubMedID 27752881

• The Role of Stereotactic Radiosurgery in the Reirradiation of Metastatic Spinal Tumors. International journal of radiation oncology, biology, physics Ho, C. K., Kumar, K. A., White, E. C., Azoulay, M., Fujimoto, D. K., Aggarwal, S., Gensheimer, M. F., Gibbs, I. C., Adler, J. R., Chang, S. D., Hancock, S. L., Choi, C. Y., Soltys, S. G. 2016; 96 (2S): E131-?

  View details for DOI 10.1016/j.ijrobp.2016.06.920

  View details for PubMedID 27673858

• 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

• 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

• 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

• Clinical characteristics and pituitary dysfunction in patients with metastatic cancer to the sella. Endocrine practice Ariel, D., Sung, H., Coghlan, N., Dodd, R., Gibbs, I. C., Katznelson, L. 2013; 19 (6): 914-919

  Abstract

  Objective: Metastatic disease to the sella is uncommon and there are limited available data regarding the clinical aspects of this disease. We sought to characterize the clinical demographics of sellar metastases.Methods: Retrospective chart review of adults at Stanford University Medical Center from 1980 to 2011 with metastatic disease to the sella.Results: 13 subjects were identified (9 F). The mean age at diagnosis was 55 years (range: 25-73 y). 6 (46%) had breast carcinoma, 3 (23%) had renal cell carcinoma, 2 (15%) had squamous cell carcinoma of the head and neck, 1 had bronchoalveolar carcinoma of the lung, and 1 had nodular sclerosing Hodgkin's lymphoma. The most common presenting signs and symptoms were headache (58%), followed by fatigue (50%), polyuria (50%), visual field defects (42%), and ophthalmoplegia (42%). 75% presented with at least one pituitary hormone insufficiency, including 6 (50%) with diabetes insipidus (DI). 8 (67%) subjects had secondary hypothyroidism, and 5 (45%) had secondary adrenal insufficiency. Of the patients with stalk involvement, 86% had DI. All patients had a prior diagnosis of malignancy for a mean duration of 95 months.Conclusion: In this retrospective review, the most common neoplastic sources to the sella were breast and renal cell carcinoma. Secondary hypothyroidism was the most common endocrine abnormality, followed by DI, and adrenal insufficiency. New onset central hypothyroidism and diabetes insipidus along with known malignancy in a patient with a sellar lesion should raise the suspicion of a metastatic source.

  View details for DOI 10.4158/EP12407.OR

  View details for PubMedID 23757610

• 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

• 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

• Volumetric Analysis of Intracranial Arteriovenous Malformations Contoured for CyberKnife Radiosurgery With 3-Dimensional Rotational Angiography vs Computed Tomography/Magnetic Resonance Imaging. Neurosurgery Veeravagu, A., Hansasuta, A., Jiang, B., Karim, A. S., Gibbs, I. C., Chang, S. D. 2013; 73 (2): 262-270

  Abstract

  BACKGROUND:: Accurate target delineation has significant impact on brain arteriovenous malformations (AVMs) obliteration, treatment success, and potential complications of stereotactic radiosurgery. OBJECTIVE:: We compare the nidal contouring of AVMs using fused images of contrasted computerized tomography (CT) and magnetic resonance (MRI) with matched images of three-dimensional (3-D) cerebral angiography for Cyberknife radiosurgery (CKRS) treatment planning. METHODS:: Between May 2009 and April 2012, 3-D cerebral angiography was integrated into CKRS target planning for thirty consecutive patients. The AVM nidal target volumes were delineated using fused CT and MRI scans versus fused CT, MRI, and 3-D cerebral angiography for each patient. RESULTS:: The mean volume of the AVM nidus contoured with the addition of 3-D cerebral angiography to the CT/MRI fusion (9.09 cm, 95% CI 5.39-12.8 cm) was statistically smaller than the mean volume contoured with CT/ MRI fused scans alone (14.1 cm, 95% CI 9.16-19.1 cm), with a mean volume difference of δ=5.01 cm (p=0.001). Diffuse AVM nidus was associated with larger mean volume differences in comparison to a compact nidus (δ=6.51 vs. 2.11 cm, p=0.02). The mean volume difference was not statistically associated with the patient's gender (male δ=5.61, female δ=5.06, p=0.84), prior hemorrhage status (yes δ=5.69, no δ=5.23, p=0.86), or prior embolization status (yes δ=6.80, no δ=5.95, p=0.11). CONCLUSION:: For brain AVMs treated with CKRS, the addition of 3-D cerebral angiography to CT/MRI fusions for diagnostic accuracy results in a statistically significant reduction in contoured nidal volume as compared to standard CT/MRI fusion-based contouring.

  View details for DOI 10.1227/01.neu.0000430285.00928.30

  View details for PubMedID 23615081

• Pituitary stalk Langerhans cell histiocytosis treated with CyberKnife radiosurgery. Clinical neurology and neurosurgery Hong, W., Murovic, J. A., Gibbs, I., Vogel, H., Chang, S. D. 2013; 115 (5): 573-577

  Abstract

  Langerhans cell histiocytosis (LCH) is a rare idiopathic disease that is characterized by clonal proliferation of Langerhans histiocytes in various parts of the body. These atypical cells have been found to infiltrate single or multiple organs, including bone, lungs, liver, spleen, lymph nodes, and skin. Central nervous system invasion in LCH patients has rarely been reported, especially in the adult population.We describe three histopathologically confirmed cases of adult LCH that involves both the pituitary stalk and hypothalamus, and report our limited experience of such cases in this location that has been treated with CyberKnife radio surgery.The treatment goal of controlling lesion growth is achieved by CyberKnife radiosurgery in this case series. All patients tolerated the treatment well without obvious complications.

  View details for DOI 10.1016/j.clineuro.2012.07.004

  View details for PubMedID 22835714

• 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 for the Treatment of Spinal Metastases: Analysis of Tumor Control and Patterns of Failure 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D., Modlin, L. A., Choi, C. Y. ELSEVIER SCIENCE INC. 2012: S195–S195

  View details for Web of Science ID 000310542900488

• Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Modlin, L. A., Atalar, B., Choi, C. Y., Gibbs, I. C., Chang, S. D., Harsh, G. R., Adler, J. R., Soltys, S. G. ELSEVIER SCIENCE INC. 2012: S116–S117

  View details for Web of Science ID 000310542900291

• 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

• 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

• 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

• Extravascular Papillary Endothelial Hyperplasia Mimicking Neoplasm After Radiosurgery: Case Report NEUROSURGERY Karamchandani, J., Vogel, H., Fischbein, N., Gibbs, I., Edwards, M. S., Harsh, G. 2012; 70 (4): E1043-E1048

  Abstract

  Papillary endothelial hyperplasia (PEH) is a rare form of exuberant reactive endothelial proliferation that can mimic neoplasm. We report the largest series of patients with histologically confirmed intracranial extravascular PEH developing in the field of previous treatment with stereotactic radiosurgery.We collected the clinical, radiological, surgical, and pathological findings from 4 patients in whom intracranial extravascular PEH developed after treatment with stereotactic radiosurgery. In all patients, the development of an enlarging hemorrhagic mass lesion at the site of previous radiotherapy on magnetic resonance imaging was radiographically suspicious for neoplasm and prompted biopsy or resection. All 4 patients elected to undergo biopsy or surgical resection. Histological examination of the biopsy and resection specimens in all patients demonstrated the classic features of PEH.The interval to the development of PEH ranged from 5 months to 6 years, 10 months. Clinical follow-up was available for 3 of the 4 patients. None of these 3 patients have demonstrated evidence of recurrence during a mean follow-up period of 22 months (range, 15-30 months). These patients share common radiological features, potentially allowing preoperative diagnosis and improved guidance of clinical management. These cases suggest a link between radiosurgery and the development of PEH. These findings also suggest that PEH should be considered in the differential diagnosis for patients treated with radiosurgery in whom a hemorrhagic mass lesion subsequently develops at or near the site of previous treatment. We think that complete surgical excision is the best treatment for intracranial PEH.

  View details for DOI 10.1227/NEU.0b013e31822e81f9

  View details for Web of Science ID 000301934000010

  View details for PubMedID 22426048

• 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

• 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

• TECHNIQUE FOR TARGETING ARTERIOVENOUS MALFORMATIONS USING FRAMELESS IMAGE-GUIDED ROBOTIC RADIOSURGERY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hristov, D., Liu, L., Adler, J. R., Gibbs, I. C., Moore, T., Sarmiento, M., Chang, S. D., Dodd, R., Marks, M., Do, H. M. 2011; 79 (4): 1232-1240

  Abstract

  To integrate three-dimensional (3D) digital rotation angiography (DRA) and two-dimensional (2D) digital subtraction angiography (DSA) imaging into a targeting methodology enabling comprehensive image-guided robotic radiosurgery of arteriovenous malformations (AVMs).DRA geometric integrity was evaluated by imaging a phantom with embedded markers. Dedicated DSA acquisition modes with preset C-arm positions were configured. The geometric reproducibility of the presets was determined, and its impact on localization accuracy was evaluated. An imaging protocol composed of anterior-posterior and lateral DSA series in combination with a DRA run without couch displacement between acquisitions was introduced. Software was developed for registration of DSA and DRA (2D-3D) images to correct for: (a) small misalignments of the C-arm with respect to the estimated geometry of the set positions and (b) potential patient motion between image series. Within the software, correlated navigation of registered DRA and DSA images was incorporated to localize AVMs within a 3D image coordinate space. Subsequent treatment planning and delivery followed a standard image-guided robotic radiosurgery process.DRA spatial distortions were typically smaller than 0.3 mm throughout a 145-mm × 145-mm × 145-mm volume. With 2D-3D image registration, localization uncertainties resulting from the achievable reproducibility of the C-arm set positions could be reduced to about 0.2 mm. Overall system-related localization uncertainty within the DRA coordinate space was 0.4 mm. Image-guided frameless robotic radiosurgical treatments with this technique were initiated.The integration of DRA and DSA into the process of nidus localization increases the confidence with which radiosurgical ablation of AVMs can be performed when using only an image-guided technique. Such an approach can increase patient comfort, decrease time pressure on clinical and technical staff, and possibly reduce the number of cerebral angiograms needed for a particular patient.

  View details for DOI 10.1016/j.ijrobp.2010.05.015

  View details for Web of Science ID 000288471500036

  View details for PubMedID 20801584

• Extravascular Papillary Endothelial Hyperplasia Mimicking Neoplasm Following Radiosurgery. Neurosurgery Karamchandani, J., Vogel, H., Fischbein, N., Gibbs, I., Edwards, M. S., Harsh, G. 2011

  Abstract

  BACKGROUND AND IMPORTANCE:: Papillary endothelial hyperplasia (PEH) is a rare form of exuberant reactive endothelial proliferation that can mimic neoplasm. We report the largest series of patients with histologically confirmed intracranial extravascular PEH developing in the field of prior treatment with stereotactic radiosurgery. CLINICAL PRESENTATION:: We collected the clinical, radiological, surgical, and pathologic findings in four cases of patients who developed intracranial extravascular PEH following treatment with stereotactic radiosurgery. In all cases the development of an enlarging hemorrhagic mass lesion in the site of prior radiotherapy on MRI was radiographically suspicious for neoplasm and prompted biopsy or resection. In all four cases the patients elected to undergo biopsy or surgical resection. Histologic examination of the biopsy and resection specimens in all cases demonstrated the classic features of PEH. CONCLUSION:: The interval to the development of PEH ranged from five months to six years and ten months. Clinical follow up was available for three of the four patients. None of these three patients has demonstrated evidence of recurrence during a mean follow-up period of 22 months (15-30 months). These cases share common radiological features, potentially allowing for pre-operative diagnosis and improved guidance of clinical management. These cases suggest a link between radiosurgery and the development of PEH. These findings also suggest that PEH should be considered in the differential diagnosis for patients treated with radiosurgery who subsequently develop a hemorrhagic mass lesion at or near the site of prior treatment. We think that complete surgical excision is the best treatment for intracranial PEH.

  View details for DOI 10.1227/NEU.0b013e31822e81f9

  View details for PubMedID 21937944

• The CyberKnife in Clinical Use: Current Roles, Future Expectations IMRT IGRT SBRT- ADVANCES IN THE TREATMENT PLANNING AND DELIVERY OF RADIOTHERAPY Dieterich, S., Gibbs, I. C. 2011; 43: 181-194

  Abstract

  The CyberKnife system deploys a linac mounted on an agile robot and directed under image guidance for stereotactic radiotherapy using nonisocentric beam delivery. A design advantage of the CyberKnife system is its method of active image guidance during treatment delivery. Recent developments in the hardware and software of the system have significantly enhanced its functionality: (a) an optimized path traversal process significantly reduces the robot motion time, resulting in reductions of overall treatment times of at least 5-10 min; (b) to optimize the accuracy of dose calculation in CyberKnife planning/delivery, Monte Carlo algorithms have been introduced; (c) the new IRIS collimator reduces the monitor units required, increases treatment speed and improves conformality and homogeneity of treatment plans; (d) XSight lung tracking, an algorithm for fiducial-less lung tracking, has been developed for peripheral, radio-dense lung tumors with diameters >15 mm; and (e) a sequential optimization planning process incorporates a more flexible approach to optimize the multiple, complex treatment planning criteria used today. The clinical efficacy of CyberKnife radiosurgery for brain/head lesions such as metastases, arteriovenous malformations, acoustic neuromas and meningiomas is well established. Since there is no need for skeletal fixation with the CyberKnife, radiosurgery can be applied to targets beyond the brain, and the technology has been extensively used for stereotactic body radiotherapy, treating targets in many anatomic sites. Currently, clinical studies have been completed or are ongoing for common malignancies including tumors involving the spine, lung, pancreas, liver and prostate.

  View details for Web of Science ID 000292117400009

  View details for PubMedID 21625154

• 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

• DOSE-ESCALATION STUDY OF SINGLE-FRACTION STEREOTACTIC BODY RADIOTHERAPY FOR LIVER MALIGNANCIES INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Goodman, K. A., Wiegner, E. A., Maturen, K. E., Zhang, Z., Mo, Q., Yang, G., Gibbs, I. C., Fisher, G. A., Koong, A. C. 2010; 78 (2): 486-493

  Abstract

  We performed a Phase I dose-escalation study to explore the feasibility and safety of treating primary and metastatic liver tumors with single-fraction stereotactic body radiotherapy (SBRT).Between February 2004 and February 2008, 26 patients were treated for 40 identifiable lesions. Nineteen patients had hepatic metastases, 5 had intrahepatic cholangiocarcinomas, and 2 had recurrent hepatocellular carcinomas. The prescribed radiation dose was escalated from 18 to 30 Gy at 4-Gy increments with a planned maximum dose of 30 Gy. Cumulative incidence functions accounted for competing risks to estimate local failure (LF) incidence over time under the competing risk of death.All patients tolerated the single-fraction SBRT well without developing a dose-limiting toxicity. Nine acute Grade 1 toxicities, one acute Grade 2 toxicity, and two late Grade 2 gastrointestinal toxicities were observed. After a median of 17 months follow-up (range, 2-55 months), the cumulative risk of LF at 12 months was 23%. Fifteen patients have died: 11 treated for liver metastases and 4 with primary liver tumors died. The median survival was 28.6 months, and the 2-year actuarial overall survival was 50.4%.It is feasible and safe to deliver single-fraction, high-dose SBRT to primary or metastatic liver malignancies measuring ≤5 cm. Moreover, single-fraction SBRT for liver lesions demonstrated promising local tumor control with minimal acute and long-term toxicity. Single-fraction SBRT appears to be a viable nonsurgical option, but further studies are warranted to evaluate both control rates and impact on quality of life.

  View details for DOI 10.1016/j.ijrobp.2009.08.020

  View details for Web of Science ID 000282147000026

  View details for PubMedID 20350791

• Frameless image guided robotic radiosurgery of arteriovenous malformation localized on spatially correlated digital subtraction and C-arm CT angiography images JOURNAL OF NEUROINTERVENTIONAL SURGERY Hristov, D., Adler, J. R., Gibbs, I. C., Dodd, R., Marks, M., Chang, S. D., Do, H. M. 2010; 2 (3): 252-254

  Abstract

  A case is reported of frameless image guided robotic radiosurgery for an arteriovenous malformation (AVM). C-arm CT (CACT) and concurrent digital subtraction angiography images were used for AVM localization within the CACT volume. Treatment planning was performed on CT images registered with the CACT dataset. During delivery, a robotic linear accelerator tracked the target based on localization with frequent stereoscopic x-ray imaging. This case demonstrates that a frameless approach to AVM radiosurgery is possible.

  View details for DOI 10.1136/jnis.2009.001941

  View details for Web of Science ID 000281357900019

  View details for PubMedID 21990637

• 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

• Stereotactic Radiosurgery of the Post-operative Resection Cavity for Brain Metastases: Optimization of the Treatment Technique 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Soltys, S. G., Gibbs, I. C., Chang, S. D., Adler, J. R., Harsh, G. R., LIEBERSON, R. E., Choi, C. Y. ELSEVIER SCIENCE INC. 2010: S7–S7

  View details for Web of Science ID 000288775700015

• Human Spinal Cord Re-irradiation Guidelines for Stereotactic Body Radiotherapy 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Sahgal, A., Ma, L., Weinberg, V., Gibbs, I., Chao, S., Chang, U., Werner-Wasik, M., Fowler, J., Wong, S., Larson, D. A. ELSEVIER SCIENCE INC. 2010: S285–S285

  View details for Web of Science ID 000288775700616

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

  View details for DOI 10.1016/j.radonc.2009.08.024

  View details for Web of Science ID 000272762900048

  View details for PubMedID 19748142

• 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

• Cyberknife Radiotherapy for Vestibular Schwannoma OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA Sakamoto, G. T., Blevins, N., Gibbs, I. C. 2009; 42 (4): 665-?

  Abstract

  Stereotactic radiosurgery is a well-established treatment modality for vestibular schwannoma. Initial reports using single-stage radiosurgery have demonstrated excellent tumor control rates. Many patients now elect to undergo radiosurgery given the potential for tumor control while avoiding the morbidity associated with microsurgical resection. In attempt to improve hearing preservation rates of single-state radiosurgery, staged frame-based radiotherapy using a 12-hour interfraction interval was used at the authors' institution and has shown a hearing preservation rate of 77% at 2 years of follow-up. With the arrival of the Cyberknife, a frameless, image-guided radiotherapy system, staged stereotactic radiotherapy for vestibular schwannoma became more practical. This article outlines the rationale and treatment protocols developed at Stanford University (California) and reports the authors' initial experience using the Cyberknife to treat vestibular schwannoma.

  View details for DOI 10.1016/j.otc.2009.04.006

  View details for Web of Science ID 000270502100007

  View details for PubMedID 19751871

• 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

• 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

• 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

• FORAMINAL NERVE SHEATH TUMORS: INTERMEDIATE FOLLOW-UP AFTER CYBERKNIFE RADIOSURGERY NEUROSURGERY Murovic, J. A., Gibbs, I. C., Chang, S. D., Mobley, B. C., Park, J., Adler, J. R. 2009; 64 (2): A33-A43

  Abstract

  To conduct a retrospective review of outcomes in 15 patients with 18 foraminal tumors, including 17 benign peripheral nerve sheath tumors and 1 malignant peripheral nerve sheath tumor, who underwent CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery at Stanford University Medical Center from 1999 to 2006.Symptoms and findings, neurofibromatosis (NF) association, previous radiation, imaging, dosimetry, tumor volume, central necrosis, and the relation of these factors to outcomes were evaluated.Before treatment, 1 asymptomatic patient had radiculopathic findings, 3 patients experienced local pain with intact neurological examinations, and 7 patients had radiculopathic complaints with intact (1 patient), radiculopathic (4 patients), or radiculomyelopathic examinations (2 patients). Five patients had myelopathic complaints and findings. Three patients had NF1-associated neurofibromas, 1 patient with NF2 had a schwannoma, and 1 patient had a schwannomatosis-related lesion. Two likely radiation-induced lesions, a neurofibroma and a malignant peripheral nerve sheath tumor, were observed. Prescribed doses ranging from 16 to 24 Gy, delivered in 1 to 3 fractions of 6 to 20 Gy, resulted in maximum tumor doses ranging from 20.9 to 30 Gy. Target volumes ranged from 1.36 to 16.9 mL. After radiosurgery, the asymptomatic case remained asymptomatic, and neurological findings improved. Thirteen of 15 symptomatic patients with (12 patients) or without (3 patients) neurological findings improved (3 cases after resection) or remained stable, and 2 patients worsened. Symptoms and examinations remained stable or improved in 8 (80%) of 10 patients with schwannomas and 3 (60%) of 5 patients with neurofibromas. Tumor volumes decreased in 12 (67%) of 18 tumors and increased in 3 tumors. Tumor volumes decreased in 8 of 10 schwannomas and 3 of 7 neurofibromas. Central necrosis developed in 8 (44%) of 18 tumors.CyberKnife radiosurgery resulted in pain relief and functional preservation in selected foraminal peripheral nerve sheath tumors and a malignant peripheral nerve sheath tumor. Symptomatic and neurological improvements were more noticeable with schwannomas. Myelopathic symptoms may necessitate surgical debulking before radiosurgery.

  View details for DOI 10.1227/01.NEU.0000341632.39692.9E

  View details for Web of Science ID 000262797700010

  View details for PubMedID 19165072

• Spinal Stereotactic Radiosurgery for Metastatic Tumor Recurrence within a Prior External Beam Irradiation Field 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D., Jackson, P. S., LIEBERSON, R. E., Choi, C. Y. ELSEVIER SCIENCE INC. 2009: S126–S126

  View details for Web of Science ID 000270573600270

• Re-treatment Spinal Cord Tolerance for Spine Stereotactic Body Radiotherapy 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Sahgal, A., Ma, L., Gibbs, I., Chao, S., Chang, U., Weinberg, V., Soltys, S., Fowler, J., Wong, S., Larson, D. ELSEVIER SCIENCE INC. 2009: S239–S239

  View details for Web of Science ID 000270573600512

• Stereotactic Radiosurgery Yields Long-term Control for Benign Intradural, Extramedullary Spine Tumors 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Sachdev, S., Dodd, R. L., Chang, S. D., Soltys, S. G., Adler, J. R., Luxton, G., Choi, C. Y., Tupper, L. A., Gibbs, I. C. ELSEVIER SCIENCE INC. 2009: S101–S101

  View details for Web of Science ID 000270573600216

• 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

• Radiation therapy and CyberKnife radiosurgery in the management of craniopharyngiomas NEUROSURGICAL FOCUS Lee, M., Kalani, M. Y., Cheshier, S., Gibbs, I. C., Adler, J. R., Chang, S. D. 2008; 24 (5)

  Abstract

  Many benign intracranial tumors are amenable to radiotherapy treatment including meningiomas, schwannomas, pituitary tumors, and craniopharyngiomas. The authors present their experience in the treatment of craniopharyngiomas in 16 patients using frameless CyberKnife stereotactic radiosurgery (SRS). The authors discuss the role of radiation therapy in the management of these tumors, and more specifically, the role of CyberKnife SRS.Sixteen patients were treated for residual or recurrent craniopharyngioma between 2000 and 2007 with CyberKnife SRS at Stanford University Medical Center. All patients underwent magnetic resonance imaging and visual and neuroendocrine evaluations before and at regular intervals after SRS. A multisession treatment regimen and a nonisocentric treatment plan for each patient were used with a mean marginal dose of 21.6 Gy and a mean maximal dose of 29.9 Gy.There were adequate clinical data to assess outcomes in 11 of 16 patients. Evaluation of patients between 13 and 71 years of age (mean 34.5 years) with a mean follow-up period of 15.4 months revealed no deterioration in visual or neuroendocrine function. Tumor shrinkage was achieved in 7 of these 11 patients, and tumor control in another 3. One patient had cystic enlargement of the residual tumor.The authors' early experience with the application of CyberKnife SRS to residual or recurrent craniopharyngiomas has been positive; control or shrinkage of the tumor was achieved in 91% of patients, with no visual or neuroendocrine complications. Longer-term follow-up with a larger group of patients is required to fully evaluate the safety and effectiveness of this treatment modality.

  View details for DOI 10.3171/FOC/2008/24/5/E4

  View details for Web of Science ID 000256374300004

  View details for PubMedID 18447743

• The use of TLD and Gafchromic film to assure submillimeter accuracy for image-guided radiosurgery MEDICAL DOSIMETRY Ho, A. K., Gibbs, I. C., Chang, S. D., Main, B., Adler, J. R. 2008; 33 (1): 36-41

  Abstract

  The Cyberknife is an image-guided radiosurgical system. It uses a compact X-band 6-MV linear accelerator mounted on a robotic arm to deliver radiosurgical doses. While routine quality assurance (QA) is essential for any radiosurgery system, QA plays an even more vital role for the Cyberknife system, due to the complexity of the system and the wide range of applications. This paper presents a technique for performing quality assurance using thermoluminescence detectors (TLDs) and Gafchromic films that is intended to be specific for the Cyberknife. However, with minor modification, the proposed method can also be used for QA of other radiosurgery systems. Our initial QA procedure for the CyberKnife utilized a 30 x 30 x 11-cm solid water phantom containing a planar array of slots for 1x 1 x 1-mm TLDs on a 2-mm grid. With the objective of significantly simplifying CyberKnife QA, a new procedure for verification was developed, which uses much fewer TLDs than the prior solid water phantom technique. This new method requires only that the system target dose to the center of a cluster of 7 TLDs. In a prior study with Gafchromic films, conducted at 3 different Cyberknife facilities, the mean clinically relevant error was demonstrated to be 0.7 mm. A similar Gafchromic film analysis replicated these error measurements as part of the present investigation. It cannot be emphasized enough the importance of implementing routine QA to verify the accuracy of any radiosurgery system. Our quality assurance procedure tests the treatment planning system, as well as the entire treatment delivery including the image targeting system and the robot system. Either TLDs or Gafchromic films may be used for QA test of a radiosurgery system. Using both methods for measurement has the advantage independently verifying the accuracy of the system. This approach, which is routinely in used at our institution, has repeatedly confirmed the submillimeter targeting accuracy of our Cyberknife.

  View details for DOI 10.1016/j.meddos.2007.04.009

  View details for Web of Science ID 000253610200006

  View details for PubMedID 18262121

• Visual field preservation after multisession cyberknife radiosurgery for perioptic lesions. Neurosurgery Adler, J. R., Gibbs, I. C., Puataweepong, P., Chang, S. D. 2008; 62: 733-743

  Abstract

  The restricted radiation tolerance of the anterior visual pathways represents a unique challenge for ablating adjacent lesions with single-session radiosurgery. Although preliminary studies have recently demonstrated that multisession radiosurgery for selected perioptic tumors is both safe and effective, the number of patients in these clinical series was modest and the length of follow-up limited. The current retrospective study is intended to help address these shortcomings.Forty-nine consecutive patients with meningioma (n = 27), pituitary adenoma (n = 19), craniopharyngioma (n = 2), or mixed germ cell tumor (n = 1) situated within 2 mm of a "short segment" of the optic apparatus underwent multisession image-guided radiosurgery at Stanford University Medical Center. Thirty-nine of these patients had previous subtotal surgical resection, and six had previously been treated with conventional fractionated radiotherapy (6). CyberKnife radiosurgery was delivered in two to five sessions to an average tumor volume of 7.7 cm3 and a cumulative average marginal dose of 20.3 Gy. Formal visual testing and clinical examinations were performed before treatment and at follow-up intervals beginning at 6 months.After a mean visual field follow-up of 49 months (range, 6-96 mo), vision was unchanged postradiosurgery in 38 patients, improved in eight (16%), and worse in three (6%). In each instance, visual deterioration was accompanied by tumor progression that ultimately resulted in patient death. However, one of these patients, who had a multiply recurrent adrenocorticotropic hormone-secreting pituitary adenoma, initially experienced early visual loss without significant tumor progression after both a previous course of radiotherapy and three separate sessions of radiosurgery. After a mean magnetic resonance imaging follow-up period of 46 months, tumor volume was stable or smaller in all other cases. Two patients died of unrelated nonbrain causes.Multisession radiosurgery resulted in high rates of tumor control and preservation of visual function in this group of perioptic tumors. Ninety-four percent of patients retained or improved preradiosurgical vision. This intermediate-term experience reinforces the findings from earlier studies that suggested that multisession radiosurgery can be a safe and effective alternative to either surgery or fractionated radiotherapy for selected lesions immediately adjacent to short segments of the optic apparatus.

  View details for DOI 10.1227/01.neu.0000316277.14748.63

  View details for PubMedID 18596432

• 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

• Preliminary guidelines for avoidance of radiation-induced myelopathy following spine stereotactic body radiosurgery (SBRS) 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Sahgal, A., Gibbs, I., Ryu, S., Ma, L., Gerszten, P., Soltys, S., Weinberg, V., Fowler, J., Chang, E., Larson, D. ELSEVIER SCIENCE INC. 2008: S220–S220

  View details for Web of Science ID 000258805300490

• 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

• Primary paraspinal leiomyosarcoma invading the cervical spinal canal successfully treated with surgery, radiotherapy, and chemotherapy - Case report JOURNAL OF NEUROSURGERY-SPINE Lehman, N. L., Jacobs, C. D., Holsten, P. A., Jaikumar, S., Lehman, T. D., Gibbs, I. C., Shuer, L. M. 2007; 6 (5): 441-446

  Abstract

  A primary paraspinal leiomyosarcoma invading the spine is an exceedingly rare neoplasm that may clinically mimic a schwannoma. The authors report a case involving a 45-year-old man with a primary leiomyosarcoma of the cervical paraspinal musculature that invaded the spinal canal at C1-2 and subsequently metastasized to the lungs and pancreas. Aggressive treatment consisting of resection of the primary tumor, adjunctive radiation therapy and chemotherapy, and surgical debulking of metastatic disease resulted in local tumor control at the primary site and long-term survival of the patient.

  View details for Web of Science ID 000246048100011

  View details for PubMedID 17542511

• Cyberknife targeting the pterygopalatine ganglion for the treatment of chronic cluster headaches. Neurosurgery Lad, S. P., Lipani, J. D., Gibbs, I. C., Chang, S. D., Adler, J. R., Henderson, J. M. 2007; 60 (3): E580-?

  Abstract

  Cluster headache (CH) is a severe unilateral and periorbital facial pain syndrome that is often associated with autonomic symptoms, including ipsilateral lacrimation, nasal congestion, conjunctival injection, miosis, ptosis, and eyelid edema. We evaluated the treatment of medically refractory CH with CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery targeting the pterygopalatine ganglion.A 56-year-old man presented with a 20-year history of medically refractory CH. His symptoms were described as left-sided, severe, stabbing, burning, and often being associated with tearing and rhinorrhea. These headaches occurred virtually every morning and interfered with sleep, lifestyle, and work performance.The patient underwent two pterygopalatine nerve block trials, both of which resulted in the complete relief of headaches for a 24-hour period. Contrast-enhanced computed axial tomography and magnetic resonance imaging scans were fused for target identification and treatment planning. The target volume measured 0.296 cm3 and a single fraction of 45.50 Gy was delivered to the 78% isodose line with a maximum dose of 65 Gy. The patient kept a detailed diary of his headaches and was followed for 12 months after treatment.Results of CyberKnife targeting of the pterygopalatine ganglion in a patient with medically intractable CHs have revealed a significant decrease in the severity and frequency of headaches after a 12-month follow-up period. In addition, the patient has been able to reduce his medication intake, allowing for a significant decrease in medication-related side effects. Longer follow-up periods and additional studies are required to determine the long-term efficacy and late side effects of this treatment strategy.

  View details for PubMedID 17327771

• CyberKnife targeting the pterygopalatine ganglion for the treatment of chronic cluster headaches NEUROSURGERY Lad, S. P., Lipani, J. D., Gibbs, I. C., Chang, S. D., Adler, J. R., Henderson, J. M. 2007; 60 (3): 580-581

  View details for DOI 10.1227/01.NEU.0000255348.33582.DE

  View details for Web of Science ID 000244797000041

• A study of the accuracy of CyberKnife spinal radiosurgery using skeletal structure tracking NEUROSURGERY Ho, A. K., Fu, D., Cotrutz, C., Hancock, S. L., Chang, S. D., Gibbs, I. C., Maurer, C. R., Adler, J. R. 2007; 60 (2): 147-156

  View details for DOI 10.1227/01.NEU.0000249248.55923.EC

  View details for Web of Science ID 000244230600037

• A study of the accuracy of cyberknife spinal radiosurgery using skeletal structure tracking. Neurosurgery Ho, A. K., Fu, D., Cotrutz, C., Hancock, S. L., Chang, S. D., Gibbs, I. C., Maurer, C. R., Adler, J. R. 2007; 60 (2): ONS147-56

  Abstract

  New technology has enabled the increasing use of radiosurgery to ablate spinal lesions. The first generation of the CyberKnife (Accuray, Inc., Sunnyvale, CA) image-guided radiosurgery system required implanted radiopaque markers (fiducials) to localize spinal targets. A recently developed and now commercially available spine tracking technology called Xsight (Accuray, Inc.) tracks skeletal structures and eliminates the need for implanted fiducials. The Xsight system localizes spinal targets by direct reference to the adjacent vertebral elements. This study sought to measure the accuracy of Xsight spine tracking and provide a qualitative assessment of overall system performance.Total system error, which is defined as the distance between the centroids of the planned and delivered dose distributions and represents all possible treatment planning and delivery errors, was measured using a realistic, anthropomorphic head-and-neck phantom. The Xsight tracking system error component of total system error was also computed by retrospectively analyzing image data obtained from eleven patients with a total of 44 implanted fiducials who underwent CyberKnife spinal radiosurgery.The total system error of the Xsight targeting technology was measured to be 0.61 mm. The tracking system error component was found to be 0.49 mm.The Xsight spine tracking system is practically important because it is accurate and eliminates the use of implanted fiducials. Experience has shown this technology to be robust under a wide range of clinical circumstances.

  View details for PubMedID 17297377

• Spinal and paraspinal lesions: The role of stereotactic body radiotherapy 38th San Francisco Radiation Oncology Conference Gibbs, I. C. KARGER. 2007: 407–414

  Abstract

  Stanford University has a long legacy of contributions to the field of radiation therapy. The Cyberknife image-guided robotic radiosurgery is the latest in a series of radiation advancements that allows for improved treatment of tumors. Here we present a decade of experience in using robotic radiosurgery to treat 295 spinal and paraspinal lesions including spinal metastases, benign intradural tumors, and arteriovenous malformations. Our analysis of clinical outcomes confirms the promise of this technology in terms of efficacy and safety.

  View details for Web of Science ID 000248596600025

  View details for PubMedID 17641523

• 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

• Isolated Langerhans cell histiocytosis in an adult with central diabetes insipidus: case report and review of literature. Endocrine practice Ouyang, D. L., Roberts, B. K., Gibbs, I. C., Katznelson, L. 2006; 12 (6): 660-663

  Abstract

  To report a case of ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) in a patient with two distinct neuroendocrine tumors and to highlight the difficulties of establishing the differential diagnosis of EAS.We describe the clinical presentation of the current case, discuss its management, and report the results of molecular studies undertaken to determine whether the two tumors had a common origin.A 52-year-old woman presented with obvious features of Cushing's syndrome. Findings on hormonal evaluation were consistent with EAS. Pituitary magnetic resonance imaging revealed normal findings. Computed tomographic imaging disclosed two masses, one in the lung and one in the pancreas. Somatostatin receptor scintigraphy showed uptake only in the pancreatic mass, which was surgically removed. It was a well-differentiated neuroendocrine tumor, with negative immunostaining for ACTH. Hypercortisolemia did not resolve after removal of the pancreatic tumor. The lung mass was subsequently excised, and pathology examination showed a carcinoid tumor with immunostaining for ACTH. Thereafter, plasma ACTH became immeasurable. The two tumors had similar patterns of X-chromosome inactivation; thus, whether they arose independently could be neither confirmed nor excluded.This case demonstrates that, in the presence of more than one neuroendocrine tumor, somatostatin receptor scintigraphy may misguide the decision regarding the appropriate surgical course in patients with EAS, and it highlights the need for accurate studies to determine the source of ACTH in patients with EAS.

  View details for PubMedID 17229663

• Robotic radiosurgery for the treatment of radioresistant brain metastases 7th Congress of the European-Association-for-Neuro-Oncology (EANO) Hara, W., Li, G., Puataweepong, P., Adler, J., Chang, S., Gibbs, I. C. OXFORD UNIV PRESS INC. 2006: 486–86

  View details for Web of Science ID 000240877301365

• Frameless image-guided intracranial and extracranial radiosurgery using the Cyberknife robotic system. Cancer radiothérapie : journal de la Société française de radiothérapie oncologique Gibbs, I. C. 2006; 10 (5): 283-287

  Abstract

  The Cyberknife is an image-guided robotic radiosurgery system. The image guidance system includes a kilovoltage X-ray imaging source and amorphous silica detectors. The radiation delivery device is a mobile X-band linear accelerator mounted onto a robotic arm. Through a highly complex interplay between the image guidance system, an automated couch, and the high-speed linear accelerator, near real-time tracking of the target is achieved. The Cyberknife gained Federal Drug Administration clearance in the United States in 2001 for treatment of tumors "anywhere in the body where radiation treatment is indicated." Because the Cyberknife system does not rely on rigid fixation of a stereotactic frame, tumors outside of the intracranial compartment, even those tumors that move with respiration can be treated with a similar degree of ease as intracranial targets. A description of the Cyberknife technology and a review of some of the current intracranial and extracranial applications are detailed herein.

  View details for PubMedID 16859948

• Multisession cyberknife radiosurgery for intramedullary spinal cord arteriovenous malformations NEUROSURGERY Sinclair, J., Chang, S. D., Gibbs, I. C., Adler, J. R. 2006; 58 (6): 1081-1088

  Abstract

  Intramedullary spinal cord arteriovenous malformations (AVMs) have an unfavorable natural history that characteristically involves myelopathy secondary to progressive ischemia and/or recurrent hemorrhage. Although some lesions can be managed successfully with embolization and surgery, AVM size, location, and angioarchitecture precludes treatment in many circumstances. Given the poor outlook for such patients, and building on the successful experience with radiosurgical ablation of cerebral AVMs, our group at Stanford University has used CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) to treat selected spinal cord AVMs since 1997. In this article, we retrospectively analyze our preliminary experience with this technique.Fifteen patients with intramedullary spinal cord AVMs (nine cervical, three thoracic, and three conus medullaris) were treated by image-guided SRS between 1997 and 2005. SRS was delivered in two to five sessions with an average marginal dose of 20.5 Gy. The biologically effective dose used in individual patients was escalated gradually over the course of this study. Clinical and magnetic resonance imaging follow-up were carried out annually, and spinal angiography was repeated at 3 years.After a mean follow-up period of 27.9 months (range, 3-59 mo), six of the seven patients who were more than 3 years from SRS had significant reductions in AVM volumes on interim magnetic resonance imaging examinations. In four of the five patients who underwent postoperative spinal angiography, persistent AVM was confirmed, albeit reduced in size. One patient demonstrated complete angiographic obliteration of a conus medullaris AVM 26 months after radiosurgery. There was no evidence of further hemorrhage after CyberKnife treatment or neurological deterioration attributable to SRS.This description of CyberKnife radiosurgical ablation demonstrates its feasibility and apparent safety for selected intramedullary spinal cord AVMs. Additional experience is necessary to ascertain the optimal radiosurgical dose and ultimate efficacy of this technique.

  View details for DOI 10.1227/01.NEU.0000215891.25153.BA

  View details for Web of Science ID 000237785900023

  View details for PubMedID 16723887

• Role of radiation therapy in pediatric cancer HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA Gibbs, I. C., Tuamokumo, N., Yock, T. I. 2006; 20 (2): 455-?

  Abstract

  Whether in its preventive role of CNS prophylaxis for high-risk ALL, its central role in brain tumors, its adjunct role combined with chemotherapy for disease such as Hodgkin's lymphoma, Ewing's sarcoma, and rhabdomyosarcoma, or its palliative role for metastatic disease, radiation remains an important therapy for pediatric cancers.

  View details for DOI 10.1016/j.hoc.2006.01.015

  View details for Web of Science ID 000238365200010

  View details for PubMedID 16730302

• Stereotactic radiosurgery using CT cisternography and non-isocentric planning for the treatment of trigeminal neuralgia. Computer aided surgery Lim, M., Cotrutz, C., Romanelli, P., Schaal, D., Gibbs, I., Chang, S. D., Adler, J. R. 2006; 11 (1): 11-20

  Abstract

  Frame-based radiosurgical rhizotomy has been shown in clinical studies to be effective for managing trigeminal neuralgia (TN). To date, however, only a small pilot study has been published for the frameless, image-guided CyberKnife system. We present our preliminary experience with 29 trigeminal neuralgia patients treated with the frameless CyberKnife using X-ray image-guided targeting, a novel CT method for target definition, and non-isocentric planning.All 29 patients failed previous medical therapy and 14 had undergone prior surgical procedures. CT iohexal cisternography was used to identify the 6- to 8-mm segment of nerve to be lesioned. The marginal dose ranged from 60 to 70 Gy (median 66.4 Gy) as defined at an average 79th percentile. The corresponding Dmax varied from 71.4 to 86.4 Gy (median 77.91 Gy).After a median 10-month follow-up, 26 of 29 (90%) patients rated their pain control as excellent and 3 (10%) reported no improvement. Median time to improvement was 6 days. No or only minor progression in numbness was reported by 22 of 29 (76%) patients, 4 of 29 (14%) patients reported worsening, and 3 of 29 (10%) reported the onset of severe ipsilateral facial numbness. Two patients whose target volume inadvertently included the semi-lunar ganglion developed painful dysethesias in the distribution of their numbness.Although the optimal dose and length of nerve to be lesioned are still being refined, this preliminary experience suggests that image-guided robotic radiosurgery can effectively lesion the trigeminal nerve. Further follow-up is needed to determine whether our method has advantages over the more commonly used procedure for radiosurgical trigeminal rhizotomy.

  View details for PubMedID 16531338

• Profile of daily life in children with brain tumors: An assessment of health-related quality of life 39th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Bhat, S. R., Goodwin, T. L., Burwinkle, T. M., Lansdale, M. F., Dahl, G. V., Huhn, S. L., Gibbs, I. C., Donaldson, S. S., Rosenblum, R. K., Varni, J. W., Fisher, P. G. AMER SOC CLINICAL ONCOLOGY. 2005: 5493–5500

  Abstract

  The survival of children with CNS tumors approaches 70%, yet health-related quality of life (HRQOL) has not been investigated rigorously in this population. We aimed to show that universal assessment of HRQOL could be obtained easily by using the PedsQL 4.0 and to provide a composite profile of their daily lives.The PedsQL was administered to all patients seen in the neuro-oncology clinic at Lucile Packard Children's Hospital (Palo Alto, CA) from December 2001, to September 2002. Patients were compared with healthy controls by using two-sided t tests to evaluate statistically significant differences.One hundred thirty-four patients (73 male; mean age +/- standard deviation, 11.8 +/- 5.4 years; 55 had low-grade glioma, 32 had medulloblastoma/primitive neuroectodermal tumor/embryonal tumor, 17 had malignant astrocytoma, nine had germ-cell tumor, and 21 had other types of tumors) were assessed, each in less than 20 minutes. Scores on both child and parent-proxy reports for the total HRQOL, psychosocial, physical, emotional, social, and school-functioning scales were all significantly lower than controls (P < .01). Patients with low-grade glioma were reported to have the highest total HRQOL. Children receiving radiation therapy (XRT) but no chemotherapy had significantly lower total, psychosocial, emotional, and social functioning than those receiving other treatments, including XRT plus chemotherapy.The PedsQL can be used to assess HRQOL rapidly and easily in children with CNS tumors, who have significantly worse HRQOL than healthy children. Children receiving XRT fare worse overall; chemotherapy added to XRT does not seem to worsen HRQOL. Assessment of HRQOL should be included as an outcome in future clinical trials.

  View details for DOI 10.1200/JCO.2005.10.190

  View details for Web of Science ID 000231371700020

  View details for PubMedID 16110009

• Phase I dose escalation study of CyberKnife stereotactic radiosurgery for liver malignancies 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Lieskovsky, Y. C., Koong, A., Fisher, G., Yang, G., Ho, A., Nguyen, M., Gibbs, I., Goodman, K. ELSEVIER SCIENCE INC. 2005: S283–S283

  View details for Web of Science ID 000232083301001

• Efficacy and safety of stereotactic radiosurgery for glomus jugulare tumors. Neurosurgical focus Lim, M., Gibbs, I. C., Adler, J. R., Chang, S. D. 2004; 17 (2): E11-?

  Abstract

  Since the mid-1990s the use of radiosurgery for glomus jugulare tumors has grown in popularity. Despite its increased use, follow-up periods for radiosurgery are short and the numbers of patients reported are small. To add to the available information, the authors report their experience with the application of linear accelerator (LINAC) or CyberKnife modalities in 13 patients with 16 tumors.All patients were treated with frame-based LINAC or CyberKnife radiosurgery, with doses ranging from 1400 to 2700 cGy. Patients were retrospectively assessed for posttreatment side effects, which included hearing loss, tongue weakness, and vocal hoarseness. The patients' most recent magnetic resonance (MR) images were also assessed for changes in tumor size. The median follow-up duration was 41 months and the mean follow-up period was 60 months. All tumors remained stable or decreased in size on follow-up MR images. All patients had stable neurological symptoms, and one experienced transient ipsilateral tongue weakness and hearing loss, both of which subsequently resolved. One patient experienced transient ipsilateral vocal cord paresis; however, this individual had received previous external-beam radiation therapy.The authors' findings continue to support radiosurgery as an effective and safe method of treatment for glomus jugulare tumors that results in low rates of morbidity.

  View details for PubMedID 15329026

• Preliminary visual field preservation after staged CyberKnife radiosurgery for perioptic lesions NEUROSURGERY Pham, C. J., Chang, S. D., Gibbs, I. C., Jones, P., Heilbrun, M. P., Adler, J. R. 2004; 54 (4): 799-810

  Abstract

  The limited radiation tolerance of the optic nerves and the optic chiasm makes it a challenge to treat immediately adjacent lesions with radiosurgery. Staged or hypofractionated radiosurgery has the virtue of combining the accuracy and conformality of radiosurgery with the normal tissue-sparing benefits of fractionation. We describe a consecutive series of patients with meningiomas and pituitary adenomas abutting the anterior visual pathways who were treated with staged, image-guided radiosurgery.Thirty-four patients with either meningiomas (20 patients) or pituitary adenomas (14 patients) within 2 mm of the optic apparatus were treated. Several patients had previously been treated with conventional fractionated radiotherapy (5 patients) or subtotal surgical resection (23 patients). Radiosurgery was delivered in two to five stages to a cumulative average marginal dose of 20.0 Gy. Visual testing and clinical examinations were performed before treatment and at follow-up intervals beginning at 6 months after treatment.The mean follow-up period was 29 months (range, 15-62 mo). Pre- and posttreatment vision was unchanged in 20 patients, improved in 10, and worse in 3. One patient died during follow-up as a result of an unrelated cardiac event. Visual loss was accompanied by tumor progression in two cases. In a third patient with a multiply recurrent adrenocorticotropic hormone-secreting pituitary adenoma, injury to one optic nerve occurred after both a prior course of radiotherapy and three separate sessions of radiosurgery.Staged radiosurgery resulted in high rates of tumor control and preservation of visual function. Ninety-one percent of patients retained their presurgical vision. Staged radiosurgery may be a safe and effective alternative to either surgery or fractionated radiotherapy for selected lesions adjacent to the optic apparatus.

  View details for DOI 10.1227/01.NEU.0000114261.18723.6A

  View details for Web of Science ID 000220769100004

  View details for PubMedID 15046645

• Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Koong, A. C., Le, Q. T., Ho, A., Fong, B., Fisher, G., Cho, C., Ford, J., Poen, J., Gibbs, I. C., Mehta, V. K., Kee, S., Trueblood, W., Yang, G., Bastidas, J. A. 2004; 58 (4): 1017-1021

  Abstract

  To determine the feasibility and toxicity of delivering stereotactic radiosurgery to patients with locally advanced pancreatic cancer.Patients with Eastern Cooperative Oncology Group performance status < or=2 and locally advanced pancreatic cancer were enrolled on this Phase I dose escalation study. Patients received a single fraction of radiosurgery consisting of either 15 Gy, 20 Gy, or 25 Gy to the primary tumor. Acute gastrointestinal toxicity was scored according to the Radiation Therapy Oncology Group criteria. Response to treatment was determined by serial high-resolution computed tomography scanning.Fifteen patients were treated at 3 dose levels (3 patients received 15 Gy, 5 patients received 20 Gy, and 7 patients received 25 Gy). At these doses, no Grade 3 or higher acute gastrointestinal toxicity was observed. This trial was stopped before any dose-limiting toxicity was reached, because the clinical objective of local control was achieved in all 6 evaluable patients treated at 25 Gy.It is feasible to deliver stereotactic radiosurgery to patients with locally advanced pancreatic cancer. The recommended dose to achieve local control without significant acute gastrointestinal toxicity is 25 Gy.

  View details for DOI 10.1016/j.ijrobp.2003.11.004

  View details for Web of Science ID 000220084200001

  View details for PubMedID 15001240

• Radiation tolerance of the spinal cord to staged radiosurgery 6th Meeting of the International-Stereotactic-Radiosurgery-Society Gibbs, I. C., Chang, S. D., Pham, C., Adler, J. R. KARGER. 2004: 22–28

  View details for Web of Science ID 000221523300003

• Temporal pattern of pain relief using cyberknife radiosurgery for trigeminal neuralgia: A preliminary report 6th Meeting of the International-Stereotactic-Radiosurgery-Society Romanelli, P., Chang, S., Gibbs, I. C., Heit, G., Adler, J. R. KARGER. 2004: 181–189

  View details for Web of Science ID 000221523300021

• Quality assurance of the cyberknife fiducial and skull tracking systems 6th Meeting of the International-Stereotactic-Radiosurgery-Society Ho, A., Cotrutz, C., Chang, S. D., Adler, J. R., Gibbs, I. C. KARGER. 2004: 255–259

  View details for Web of Science ID 000221523300028

• Radiation-induced cyclooxygenase 2 up-regulation is dependent on redox status in prostate cancer cells RADIATION RESEARCH Li, L. Y., Steinauer, K. K., Dirks, A. J., Husbeck, B., Gibbs, I., Knox, S. J. 2003; 160 (6): 617-621

  Abstract

  Cyclooxygenase 2 (COX2) is the inducible isozyme of COX, a key enzyme in arachidonate metabolism and the conversion of arachidonic acid (AA) to prostaglandins (PGs) and other eicosanoids. Previous studies have demonstrated that the COX2 protein is up-regulated in prostate cancer cells after irradiation and that this results in elevated levels of PGE(2). In the present study, we further investigated whether radiation-induced COX2 up-regulation is dependent on the redox status of cells from the prostate cancer cell line PC-3. l-Buthionine sulfoximine (BSO), which inhibits gamma glutamyl cysteine synthetase (gammaGCS), and the antioxidants alpha-lipoic acid and N-acetyl-l-cysteine (NAC) were used to modulate the cellular redox status. BSO decreased the cellular GSH level and increased cellular reactive oxygen species (ROS) in PC-3 cells, whereas alpha-lipoic acid and NAC increased the GSH level and decreased cellular ROS. Both radiation and the oxidant H(2)O(2) had similar effects on COX2 up-regulation and PGE(2) production in PC-3 cells, suggesting that radiation-induced COX2 up-regulation is secondary to the production of ROS. The relative increases in COX2 expression and PGE(2) production induced by radiation and H(2)O(2) were even greater when PC-3 cells were pretreated with BSO. When the cells were pretreated with alpha-lipoic acid or NAC for 24 h, both radiation- and H(2)O(2)-induced COX2 up-regulation and PGE(2) production were markedly inhibited. These results demonstrate that radiation-induced COX2 up-regulation in prostate cancer cells is modulated by the cellular redox status. Radiation-induced increases in ROS levels contribute to the adaptive response of PC-3 cells, resulting in elevated levels of COX2.

  View details for Web of Science ID 000187079200001

  View details for PubMedID 14640786

• Long-term outcomes after external beam irradiation and brachytherapy boost for base-of-tongue cancers INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Gibbs, I. C., Le, Q. T., Shah, R. D., Terris, D. J., Fee, W. E., Goffinet, D. R. 2003; 57 (2): 489-494

  Abstract

  To assess long-term efficacy and toxicity associated with external beam irradiation (EBRT) and interstitial (192)Ir implantation for the treatment of squamous carcinoma of the base of tongue.Between April 1975 and December 1993, 41 patients with base-of-tongue carcinomas were treated with (192)Ir interstitial implants after EBRT at Stanford University. One patient had Stage I, 6 had Stage II, 7 had Stage III, and 27 had Stage IV tumors. Twenty-eight patients had cervical lymph node involvement at diagnosis. All received EBRT to a median dose of 50 Gy (range 48.9-68 Gy) to the primary tumor and regional lymph nodes before brachytherapy. Interstitial implant was performed 2-4 weeks after EBRT. Intraoperatively, nylon catheters were placed via steel trocars into the base of tongue, glossotonsillar groove, and pharyngo-epiglottic fold using a catheter looping technique. Twenty-three of 28 node-positive patients also underwent simultaneous neck dissections. Postoperatively, the (192)Ir seeds were inserted and allowed to remain in place for approximately 35 h to achieve a median tumor dose of 26 Gy (range 20-34 Gy) to a median volume of 73 cc. Survival, local control, and complications were assessed.With a median follow-up of 62 months (range 9-215) for all patients and 90 months for alive patients, the 5-year Kaplan-Meier survival estimate was 66%. The 5-year local control rate was 82%, with 7 patients recurring locally, 2 of whom were salvaged with surgery. Nodal control was achieved in 93% of patients with either EBRT alone or in combination with neck dissection. The 5-year freedom from distant metastasis rate was 83%. Acute complications included transient bleeding (5%) and infection (8%). Late complication included soft-tissue necrosis/ulceration (7%), osteoradionecrosis (5%), and xerostomia.Base-of-tongue carcinoma can be effectively treated with EBRT and (192)Ir implant boost. Local control is excellent and complication rates are acceptable.

  View details for DOI 10.1016/S0360-3016(03)00597-2

  View details for Web of Science ID 000185315200023

  View details for PubMedID 12957261

• Radiosurgery and radiotherapy for sacral tumors. Neurosurgical focus Gibbs, I. C., Chang, S. D. 2003; 15 (2): E8-?

  Abstract

  Sacral tumors represent a small subset of spinal lesions and typically include chordomas, metastases, other primary bone tumors, and benign schwannomas. Resection is the standard treatment for many sacral tumors, but many types of sacral lesions have the potential for recurrence after excision. In these cases, adjuvant radiotherapy is often beneficial. Although conventional radiotherapy plays an important role in the management of spinal lesions, the radiation doses required for adequate local control of many sacral lesions generally exceed the tolerance doses of normal tissues, thus limiting its definitive role in the management of sacral tumors. Recent advances in the field of stereotactic radiosurgery have allowed precise targeting of the sacrum. In this report the authors review the use of these two forms of radiation treatment and their role in managing sacral tumors.

  View details for PubMedID 15350039

• Improved local control with stereotactic radiosurgical boost in patients with nasopharyngeal carcinoma 44th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Le, Q. T., Tate, D., Koong, A., Gibbs, I. C., Chang, S. D., Adler, J. R., Pinto, H. A., Terris, D. J., Fee, W. E., Goffinet, D. R. ELSEVIER SCIENCE INC. 2003: 1046–54

  Abstract

  Treatment of nasopharyngeal carcinoma using conventional external beam radiotherapy (EBRT) alone is associated with a significant risk of local recurrence. Stereotactic radiosurgery (STR) was used to boost the tumor site after EBRT to improve local control.Forty-five nasopharyngeal carcinoma patients received a STR boost after EBRT at Stanford University. Seven had T1, 16 had T2, 4 had T3, and 18 had T4 tumors (1997 American Joint Commission on Cancer staging). Ten had Stage II, 8 had Stage III, and 27 had Stage IV neoplasms. Most patients received 66 Gy of EBRT delivered at 2 Gy/fraction. Thirty-six received concurrent cisplatin-based chemotherapy. STR was delivered to the primary site 4-6 weeks after EBRT in one fraction of 7-15 Gy.At a medium follow-up of 31 months, no local failures had occurred. The 3-year local control rate was 100%, the freedom from distant metastasis rate was 69%, the progression-free survival rate was 71%, and the overall survival rate was 75%. Univariate and multivariate analyses revealed N stage (favoring N0-N1, p = 0.02, hazard ratio HR 4.2) and World Health Organization histologic type (favoring type III, p = 0.002, HR 13) as significant factors for freedom from distant metastasis. World Health Organization histologic type (p = 0.004, HR 10.5) and age (p = 0.01, HR 1.07/y) were significant factors for survival. Late toxicity included transient cranial nerve weakness in 4, radiation-related retinopathy in 1, and asymptomatic temporal lobe necrosis in 3 patients who originally had intracranial tumor extension.STR boost after EBRT provided excellent local control in nasopharyngeal carcinoma patients. The incidence of late toxicity was acceptable. More effective systemic treatment is needed to achieve improved survival.

  View details for DOI 10.1016/S0360-3016(03)00117-2

  View details for Web of Science ID 000183937500018

  View details for PubMedID 12829140

• The efficacy of linear accelerator stereotactic radiosurgery in treating glomus jugulare tumors TECHNOLOGY IN CANCER RESEARCH & TREATMENT Lim, M., Gibbs, I. C., Adler, J. R., Martin, D. P., Chang, S. D. 2003; 2 (3): 261-265

  Abstract

  Treatment of glomus jugulare tumors with radiosurgery has grown in acceptance since the first reported treatment in 1995, but only a few centers have reported their experiences with limited follow up time. We report our experience with stereotactic radiosurgery in nine patients with ten glomus tumors. All patients were treated either with frame based LINAC or Cyberknife with doses ranging from 1600 cGy to 2500 cGy. Three patients received no previous therapy and one patient received additional external beam radiation for concomitant treatment of carotid body tumors. Patients were then followed for post treatment side effects in addition to change in tumor size by MRI evaluation. The median clinical follow-up time was 26 months (mean 54 months), median radiographic follow-up was 21.5 months (mean 46 months), with a range from 3 to 126 months. The results from our center demonstrated nine of ten tumors to be stable in size by MRI exam, and one tumor which regressed in size. Nine patients had stable neurological symptoms, and one patient experienced transient ipsilateral tongue weakness and hearing loss, both of which subsequently resolved. Our results continue to support radiosurgery as a suitable form of treatment for glomus jugulare tumors as evidenced by results from this four and a half year follow-up.

  View details for Web of Science ID 000183918300008

  View details for PubMedID 12779355

• Patterns of patient movement during frameless image-guided radiosurgery INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Murphy, M. J., Chang, S. D., Gibbs, I. C., Le, Q. T., Hai, J., Kim, D., Martin, D. P., Adler, J. R. 2003; 55 (5): 1400-1408

  Abstract

  Image-guided radiosurgery aligns the treatment beam to the target site by using a radiographic imaging system to locate anatomic landmarks associated with the treatment target. Because the procedure is performed without a rigid frame, the precision of dose alignment can be affected by patient movement. Movement is limited by noninvasive restraints and compensated by remeasuring the target position at short intervals throughout treatment and then realigning the beam. Frameless image-guided radiosurgery has been used at our institution to treat 250 cranial, 23 spinal, 9 lung, and 3 pancreas cases involving malignant and benign tumors as well as vascular malformations. We have analyzed the target position records for all of these cases to assess the frequency, magnitude, and case-by-case patterns of patient movement.The position of the treatment site during image-guided radiosurgery was measured at approximately 1-2-min intervals, on average, using orthogonal amorphous silicon X-ray cameras and an image registration process that determined all six degrees of freedom in the target's position. The change in position from one measurement to the next was indicative of patient movement.The treatment site position along each axis of translation was observed to vary by an average of 0.45 mm for the cranium, 0.53 mm for the cervical spine, 0.53 mm for the lumbar and thoracic spine, 1.06 mm for the lung, and 1.50 mm for the pancreas. Half of all cranial cases showed systematic drifting of the target away from the initial setup position.Using noninvasive restraints and supports, short-term movement of the head and spine during image-guided radiosurgery was limited to a radius of 0.8 mm, which satisfies the prevailing standard for radiosurgical dose alignment precision, but maintaining this margin of error throughout a treatment fraction requires regular monitoring of the target site's position.

  View details for DOI 10.1016/S0360-3016(02)04597-2

  View details for Web of Science ID 000181803500035

  View details for PubMedID 12654453

• An analysis of the accuracy of the Cyberknife: A robotic nameless stereotactic radiosurgical system NEUROSURGERY Chang, S. D., Main, W., Martin, D. P., Gibbs, I. C., Heilbrun, M. P. 2003; 52 (1): 140-146

  Abstract

  The use of stereotactic radiosurgical systems to treat intracranial and extracranial tumors and other lesions requires a high degree of accuracy in target identification and localization. The purpose of this study was to evaluate the total system accuracy of the CyberKnife (Accuray, Inc., Sunnyvale, CA), a frameless, image-guided, stereotactic radiosurgery system.Clinically relevant accuracy or application accuracy of the CyberKnife radiosurgery system is based on 1) the beam delivery accuracy, which combines the robot and the camera image tracking system, and 2) target localization accuracy, which combines computed tomographic (CT) imaging and treatment planning. Clinically relevant accuracy can be measured by delivering a radiation dose to phantoms, in which the target is defined on a set of CT images using all components of the CyberKnife system, including the treatment planning software, the robot, the camera tracking system, and the linear accelerator. Clinically relevant accuracy was measured in head phantoms loaded with packs of radiochromic film. The accuracy measured is the displacement of the dose contours from the treatment plan to that measured in the radiosurgically exposed phantom.Measurements of mean errors of the second-generation CyberKnife system at Stanford University Medical Center, installed in 2001, ranged from 0.7 mm for a CT slice thickness of 0.625 mm to 1.97 mm for a CT slice thickness of 3.75 mm.The frameless, image-guided, second-generation CyberKnife radiosurgery system has a clinically relevant accuracy of 1.1 +/- 0.3 mm when CT slice thicknesses of 1.25 mm are used. CyberKnife precision is comparable to published localization errors in current frame-based radiosurgical systems.

  View details for DOI 10.1227/01.NEU.0000039162.72141.18

  View details for Web of Science ID 000180195800031

  View details for PubMedID 12493111

• Image-guided radiosurgery in the treatment of spinal metastases. Neurosurgical focus MURPHY, M. J., Chang, S., Gibbs, I., Le, Q. T., Martin, D., Kim, D. 2001; 11 (6)

  Abstract

  The authors describe a new method for treating metastatic spinal tumors in which noninvasive, image-guided, frameless stereotactic radiosurgery is performed. Stereotactic radiosurgery delivers a high dose of radiation in a single or limited number of fractions to a lesion while maintaining delivery of a low dose to adjacent normal structures.Image-guided radiosurgery was developed by coupling an orthogonal pair of real-time x-ray cameras to a dynamically manipulated robot-mounted linear accelerator that guides the radiation beam to treatment sites associated with radiographic landmarks. This procedure can be conducted in an outpatient setting without the use of framebased skeletal fixation. The system relies on skeletal landmarks or implanted fiducial markers to locate treatment targets. Four patients with spinal metastases underwent radiosurgery with total prescription doses of 1000 to 1600 cGy in one or two fractions. Alignment of the treatment dose with the target volume was accurate to within 1.5 mm. During the course of each treatment fraction, patient movement was less than 0.5 mm on average. Dosimetry was highly conformal, with a demonstrated ability to deliver 1600 cGy to the perimeter of an irregular target volume while keeping exposure to the cord itself below 800 cGy.These experiences indicate that frameless radiosurgery is a viable therapeutic option for metastatic spine disease.

  View details for PubMedID 16463998

• Image-guided extracranial radiosurgery 7th International Meeting on Progress in Radio-Oncology (ICRO/OGRO 7) Sattah, M., Guerrero, T., Chang, S., Martin, D., Le, Q. T., Gibbs, I., Adler, J. MEDIMOND S R L. 2001: 153–162

  View details for Web of Science ID 000176997100020

• Radiation induces upregulation of cyclooxygenase-2 (COX-2) protein in PC-3 cells INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Steinauer, K. K., Gibbs, I., Ning, S. C., French, J. N., Armstrong, J., Knox, S. J. 2000; 48 (2): 325-328

  Abstract

  To investigate the impact of gamma-irradiation on cyclooxygenase-2 (COX-2) expression and its enzymatic activity in PC-3 cells. Cell cycle redistribution, viability, and apoptosis were quantitated in control and irradiated cells with or without the COX-2 inhibitor NS-398.Western blot analysis was used to assess COX-2 protein expression. Prostaglandin (PGE(2)) was measured after addition of arachidonic acid (AA) using a Monoclonal Immunoassay Kit. Cell cycle and apoptosis were assessed using flow cytometry.We observed a dose-dependent increase in COX-2 of 37.0%, 79.7%, and 97.5% following irradiation with 5, 10, and 15 Gy, respectively. The PGE(2) level of irradiated cells was higher than in controls (1512 +/- 157.5 vs. 973.7 +/- 54.2 rhog PGE(2)/mL; p < 0.005, n = 4) while cells irradiated in the presence of NS-398 had reduced PGE(2) levels (218.8 +/- 80.1 rhog PGE(2)/mL; p < 0.005; n = 4). We found no differences in cell cycle distribution or apoptosis between cells irradiated in the presence or absence of NS-398.COX-2 protein is upregulated and enzymatically active after irradiation, resulting in elevated levels of PGE(2). This effect can be suppressed by NS-398, which has clinical implications for therapies combining COX-2 inhibitors with radiation therapy.

  View details for Web of Science ID 000089069100004

  View details for PubMedID 10974444

• Treatment of cutaneous T-Cell lymphoma with chimeric anti-CD4 monoclonal antibody BLOOD Knox, S., Hoppe, R. T., Maloney, D., Gibbs, I., Fowler, S., Marquez, C., Cornbleet, P. J., Levy, R. 1996; 87 (3): 893-899

  Abstract

  Chimeric anti-CD4 monoclonal antibody was administered intravenously as a single dose to eight patients with mycosis fungoides. The dose was escalated throughout the study between patients groups, and individual patients received 50, 100, or 200 mg per dose. Seven of eight patients responded to treatment with an average freedom from progression of 25 weeks (range, 6 to 52 weeks). The treatment was well tolerated, and there was no clinical evidence of immunosuppression. Following treatment, there was significant suppression of peripheral blood CD4 counts in all patients for 1 to 22+ weeks. Only one patient made a very low titer human antichimeric antibody response. All but two patients made primary antibody and T-cell proliferative responses to a foreign antigen administered 24 hours after antibody infusion. However, there was generally marked, but temporary suppression of T-cell proliferative responses in vitro to phytohemagglutinin (PHA), tetanus toxoid, and normal donor lymphocytes. We conclude that at the dose levels studied, this antibody (1) had clinical efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4) decreased T-cell proliferative responses in vitro, and (5) did not induce tolerance to a foreign antigen.

  View details for Web of Science ID A1996TT48400008

  View details for PubMedID 8562959