- Ipilimumab

- Ipilimumab

I. J. Radiation Oncology d Biology d Physics S302 Volume 81, Number 2, Supplement, 2011 Materials/Methods: A retrospective review from a prospectiv...

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I. J. Radiation Oncology d Biology d Physics

S302

Volume 81, Number 2, Supplement, 2011

Materials/Methods: A retrospective review from a prospective database of 46 patients with 52 surgical cavities undergoing radiosurgical treatment to the resection cavity after surgery for brain metastases. All patients underwent treatment to the 50% isodose line. Magnetic resonance (MR)-imaging studies were reviewed immediate post-operatively (within 48 hours), at the time of radiosurgery (Mean of 26.6 days post-surgery; Median 21 days), and at 3 months post-operatively to determine the presence of a discernable radiosurgical target, the target volume, and the safe allowable dose to the tumor margin. At final follow-up, MRimaging studies were also used to assess for local recurrence and radiation induced complications. Results: Immediately post-operatively, the median volumes of the resection cavity were 11.5 cm3 and a radiosurgical target was identified in all patients. The mean anticipated allowable dose to the tumor margin was 16 Gy (Range, 15- 22 Gy). At the time of radiosurgical treatment (Mean, 26.6 days post operatively, median 21 days, Range of 5-145 days post-operatively, the radiosurgical target was identified in all patients, and the median volume of the target was 9.2 cm3. The mean dose prescribed to the tumor margin at this time-point was 17.4 Gy (Range, 15-22 Gy). At final follow-up (Mean, 9.6 months, Range 2-31 months) the median cavity volume 4.8 cm3 with a mean anticipated allowable radiation dose of 42 Gy. Two patients suffered from local radiation necrosis and one from tumor recurrence at the radiosurgical site. Conclusions: Radiosurgery to the resection cavity appears highly effective in preventing local recurrence. Optimal timing to treatment appears to be approximately 2-4 weeks post resection. Extremely early treatment may result in suboptimal dosing due to large target volume, while the surgical cavity often collapses late post-operatively, inhibiting visualization of the target and requiring a higher dose of radiation resulting in increased likelihood of radiation dependant side effects to tumor free areas. Author Disclosure: F.H. Delly: None. S. Mittal: None. A. Ransom: None. D. Hulsebus: None. H. Kim: None. M. Guthikonda: None. J. Jagannathan: None.

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Outcomes for Gamma Knife Radiosurgery for Brainstem Metastases

J. M. Kilburn, T. L. Ellis, J. J. Urbanic, J. D. Bourland, M. T. Munley, A. F. deGuzman, K. P. McMullen, E. G. Shaw, S. B. Tatter, M. D. Chan Wake Forest University School of Medicine, Winston-Salem, NC Purpose/Objective(s): Brainstem metastases represent a clinical dilemma because of the catastrophic sequela of either local failure or treatment-related edema. Gamma Knife Radiosurgery (GKRS) has been reported in the successful treatment of brainstem metastases, though toxicity thresholds remain mostly undefined. Materials/Methods: Between 2/00 and 12/10, a total of 52 brainstem metastases in 44 patients were treated with GKRS. Median Karnofsky performance status was 80 (range, 60-90). A median dose of 18 Gy (range, 10-22Gy) was prescribed to the tumor margin. Locations included 28 pontine, 9 midbrain, 4 medullary, and 3 spanning the midbrain and pons. Primary tumor site included 17 lung, 15 breast, 4 renal cell, 4 melanoma, 2 ovarian, 1 colon, and 1 unknown. 25 patients had undergone previous whole brain radiation therapy. Patients were followed with serial imaging and clinically. Electronic medical records were used to assess for clinical and imaging outcomes. Toxicity was graded by the SOMA/LENT scale. Neurologic death, as defined by Patchell et al., included patients with progressive neurologic dysfunction with controlled extracranial disease, or patients with severe neurologic dysfunction who died of intercurrent illness. Results: Median follow-up was 6 months. Multiple brain metastases were treated in 75% of patients. The median number of additional lesions treated was 2 (range, 0-39). Median size of brainstem metastasis was 0.134 cc, (range, 0.013-6.600 cc). Overall survival rate at 1 year was 32% (95% CI 51.0 to 20.1%) for the entire population with a median survival time of 6 months (95% CI 5.0 to 16.5). Local control rate at 6 months and 1 year was 81% (95% CI 67 to 99) and 64% (95% CI 45 to 89). Cause of death was neurologic in 14 patients, non-neurologic in 16 patients, and unknown in four. Four patients experienced toxicities related to their brainstem metastasis. Of these, one patient had grade II toxicity and three patients had grade III toxicities. No toxic deaths occurred. Univariate analysis of tumor volume revealed that volume greater than 1.2 cc predicted for toxicity (Fisher Exact Test, p\ 0.001). One of the patients with grade III toxicity was treated with bevacizumab several months after symptom onset, and subsequently had near-complete resolution of symptoms. Conclusions: A strategy of using lower marginal doses with GKRS to brain stem metastases appears to lead to a lower local control rate than seen with lesions treated within the standard dose range. Tumor size greater than 1.2 cc predicted for treatment-related toxicity, even with lower marginal doses. Author Disclosure: J.M. Kilburn: None. T.L. Ellis: None. J.J. Urbanic: None. J.D. Bourland: None. M.T. Munley: None. A.F. deGuzman: None. K.P. McMullen: None. E.G. Shaw: None. S.B. Tatter: None. M.D. Chan: None.

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Outcomes of Melanoma Brain Metastasis Management with Gamma Knife Radiosurgery +/- Ipilimumab

J. Knisely1, V. L. S. Chiang2, H. M. Kluger2, J. C. Flanigan2, M. Sznol3, J. B. Yu2 1 Hofstra North Shore-LIJ School of Medicine, Manhasset, NY, 2Yale University School of Medicine & Yale Cancer Center, New Haven, CT, 3Yale University School of Medicine & Yale Cancer Center, New Haven, CT

Purpose/Objective(s): To evaluate survival in patients treated with definitive stereotactic radiosurgery (SRS) for melanoma brain metastases during a period in which ipilimumab therapy was introduced. Materials/Methods: Seventy-seven patients with brain metastases from melanoma treated with definitive SRS between 11/2002 and 11/2010 were identified through an IRB-approved medical record review. For every patient, all visualized metastases were treated. Survival from the date of the first SRS treatment was assessed in relation to age, gender, craniotomy status, use of whole brain radiation therapy (WBRT), use of ipilimumab, numbers of brain metastases (stratified as 1, 2-3, or .3), performance status, and the calculated Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) score for melanoma. Results: Median survival was 8.8 months (95% CI 4.93-18.4). 27/77 patients received ipilimumab. Ipilimumab recipients’ median survival was 21.3 months (95% CI 6.43-26.7) and was 4.9 months (95% CI 3.3-10.4) in those not getting ipilimumab. Overall 2 year survival was 29.3% [95% CI 18.2-41.2%]. For patients who did not get ipilimumab, 2 year survival was 19.7% [95% CI

Proceedings of the 53rd Annual ASTRO Meeting 9.0%-33.5%], whereas for patients who got ipilimumab, 2 year survival was 47.2% [95% CI 24.8-66.8%]. Factors associated with getting ipilimumab were a higher DS-GPA and younger age. More patients having DS-GPAs of 0, 1, or 2 did not get ipilimumab as compared to patients with a DS-GPA of 3-4 (chi-square p = 0.05). Uni- and multivariate Cox proportional hazards analysis for survival showed DS-GPA was the most significant predictor of overall survival and was superior to performance status alone. In the final multivariate model, ipilimumab use was not associated with a statistically significant improvement in the hazard of death (HR 0.61 [95% CI 0.33-1.10. p = .12], whereas DS-GPAs of 2, 3 and 4 had a reduced hazard of death compared to DS-GPAs of 0 or 1 (p\.001 for each). A uni- and multivariate Cox proportional hazards analysis with data censored at 24 months was run to analyze the benefit of ipilimumab within this time frame. This showed ipilumumab improved the hazard for death (HR 0.48 [95% CI 0.24-0.93], p = .03). DS-GPA still significantly reduced the hazard of death. Conclusions: The survival of melanoma brain metastasis patients when managed with ipilimumab and SRS can exceed the expected 4-6 months. Adding ipilimumab to definitive SRS raised median survival in our retrospective cohort from 9 to 21 months, and 47% of those who got ipilimumab were alive at 2 years. This association remained significant even after adjustment for performance status. Ipilimumab appears to contribute to protracted survivals for patients with metastatic melanoma whose brain metastases are managed with SRS. Author Disclosure: J. Knisely: None. V.L.S. Chiang: None. H.M. Kluger: None. J.C. Flanigan: None. M. Sznol: F. Consultant/ Advisory Board; Bristol Meyers Squibb. J.B. Yu: None.

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Single-fraction versus Multi-fraction Radiosurgery for Large Brain Metastases: The UCSF Experience

Z. A. Seymour, N. Kased, C. Chuang, D. A. Larson, M. W. McDermott, P. K. Sneed UCSF, San Francisco, CA Purpose/Objective(s): Our institution began Gamma Knife (GK) radiosurgery (RS) in 1991 and added CyberKnife (CK) RS in April 2003, continuing GK for small or numerous targets while using CK for unreachable tumors or when fractionation was deemed desirable, such as for tumors .3 cm, .1 cm in brainstem, or adjacent to chiasm. We hypothesized that fractionation would provide equivalent or better local control and less risk of necrosis for these subsets. This study retrospectively evaluates the usage, efficacy, and radiation necrosis risk for multi-fraction CK vs. single-fraction GK RS for brain metastases (BM) .3 cm. Materials/Methods: All patients with BM treated with CK RS were reviewed. Actuarial survival, local freedom from progression (LFFP), and risk of necrosis were evaluated using the Kaplan-Meier method, censoring controlled lesions at the time of last imaging follow-up for LFFP analysis. Delay from planning MRI to CK treatment was investigated as a possible risk factor for poorer survival time and LFFP. Results will be compared with those of single-fraction GK RS for BM .3 cm treated 1/00-3/03 (preCK) and 4/03-12/09. Results: Seventy four patients with 124 BM underwent 78 CK RS courses; 7 BM had postoperative CK after gross total resection (GTR) and 5 patients had postoperative CK after GTR of a single BM. Small lesions in ‘‘safe’’ locations were treated with a single dose (16-20 Gy) and other lesions had fractionated CK RS, commonly 25-30 Gy in 5 fractions. The overall median survival time was 9.2 months. Forty-nine BM (40%) were .3 cm in 49 patients with a median target volume of 16.7 ml and median survival of 10.0 mo. No resection cavities treated post-GTR failed. Excluding these targets, CK RS for BM .3 cm yielded 6-month and 1-year LFFP of 88% and 40% with median survival of 7.7 months. For all targets .3 cm, 1- and 2-year risk of necrosis was 16% and 37% by lesion and by patient vs. 10% at 1- and 2-year for BM #3 cm. Among 70 CK patients with documented planning MRI, longer interval from MRI to start of CK (e.g. .2 vs. #2 weeks) was associated with poorer survival (median 11.5 vs. 5.6 months; p = 0.038) and LFFP by patient (median 22.8 vs. 7.7 months; p = 0.020). PreCK vs. during the CK era, 73 of 1315 and 81 of 2680 BM treated with GK were .3 cm (5.6% vs 3.0%), with a median target volume of 11-13 ml, treated volume 14-16.5 ml, and prescribed dose 16 Gy. Results of GK for BM .3 cm will be presented. Conclusions: Fractionated CK RS appears to yield mediocre local control and necrosis risk for BM .3 cm, with improved results using planning MRI obtained within 2 weeks of CK treatment. Results will be compared with those of GK RS. Author Disclosure: Z.A. Seymour: None. N. Kased: None. C. Chuang: None. D.A. Larson: None. M.W. McDermott: None. P.K. Sneed: None.

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Outcomes and Toxicities following Gamma Knife Radiosurgery with or without Surgical Resection for Glomus Tumors

M. S. Jawad, I. S. Grills, I. Naumann, D. Bojrab, K. Marvin, P. Y. Chen, J. M. Kartush, D. R. Pieper William Beaumont Hospital, Royal Oak, MI Purpose/Objective(s): To evaluate outcomes and toxicities following Gamma Knife (GK) radiosurgery with or without surgery in patients with glomus tumors. Materials/Methods: 21 patients underwent GK for glomus jugulare (GJ) (n = 16) or glomus tympanicum (n = 5) tumors. 16 patients (76%) had surgery; of these, 69% had multiple resections, 75% (n = 12) underwent pre-operative embolization with 11 in GJ tumors, and 88% (n = 14) had ipsilateral neck dissections. 6 patients received GK for residual disease, 10 for recurrence, and 5 for definitive therapy. Median age was 61 years with 5 men and 16 women. The median marginal GK dose was 14 Gy (range 11-17 Gy) to the 48% isodose line (range 40-50%). Median tumor volume was 7.3 cc (range 0.41-32.3cc) with a median conformality index of 1.67 (range 1.2-2.1). All tumors were reachable with the Leksell frame appropriately placed. House-Brackmann (HB) grading was used for facial nerve deficits, and pure tone average and speech discrimination scores were recorded and classified according to AAO and Gardner-Robertson scales for hearing. Results: Overall median follow-up was 1.04 years. In patients who underwent surgery with residual tumor, median follow-up time from most recent surgical procedure was 2.2 years (range 1.4-4.0) and from GK was 1.5 years (range 0.1-3.0). For

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