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Repeat Stereotactic Radiosurgery (SRS) for Brain Metastases Locally Recurrent Following Initial SRS
S320
International Journal of Radiation Oncology Biology Physics
linear quadratic model is known to be inaccurate at high fractional doses, the clinical outcomes reported supports the dose schedules employed. Necrosis rates were lower with F-SRS but not statistically different. Further investigation of F-SRS as a method for improving the therapeutic ratio for large tumors or those located near eloquent regions is warranted. Author Disclosure: G. Savir: None. D.K. Ebner: None. J. Chan: None. P. Rava: None. D. Cielo: None. T. Kinsella: None. T.A. DiPetrillo: None. D. Wazer: None. J.T. Hepel: None.
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2259 Improving Patient Selection for Stereotactic Radiosurgery as the Initial Radiation Therapy Approach for Brain Metastases D. Gorovets,1,2 D.K. Ebner,2 P. Rava,3 D. Tybor,1 D. Cielo,2 Y. Puthawala,2 T.J. Kinsella,2 T.A. DiPetrillo,1,2 D.E. Wazer,1,2 and J.T. Hepel1,2; 1Tufts Medical Center, Boston, MA, 2Brown Alpert Medical School, Providence, RI, 3University of Massachusetts Memorial Medical Center, Worcester, MA Purpose/Objective(s): Patients with brain metastases are a heterogeneous group of cancer patients. Recent ASTRO clinical practice guidelines suggest that stereotactic radiosurgery (SRS) alone can be effectively used as the initial radiotherapeutic approach for limited brain metastases measuring 4cm in patients with good expected prognoses (3 months). The primary advantage of SRS compared to whole brain radiation therapy (WBRT) is the ability to spare normal brain tissue and preserve neurocognition. The aim of the present study was to identify predictors for extended survival free from salvage WBRT in patients with newly diagnosed brain metastases treated with SRS. Materials/Methods: From 2001-2012, over 500 patients with brain metastases were treated with SRS at our institution. For this study, we included only patients with a Karnofsky Performance Status (KPS) 70%, without prior or concurrent WBRT, and with adequate follow-up. Two cohorts of patients were identified: those with 1 year survival free from WBRT, and those who required salvage WBRT or died within 3 months of radiosurgery. We evaluated patient, tumor, and treatment variables and performed univariate (Fisher’s exact test) and multivariate analyses (binary logistic regression) assessing the differences between these two cohorts. A p-value of <0.05 was considered statistically significant. Results: Three hundred and eight patients with a median follow-up of 9.4 months were evaluated. Fifty six patients (18%) had WBRT-free survival 3 months while 104 patients (34%) survived beyond 1 year without the need for salvage WBRT. Patients with 1 year WBRT-free survival were significantly more likely to have the following characteristics on univariate analysis: age <65 years old (64 % vs 45%), RTOG Recursive Partitioning Analysis (RPA) class I (39% vs 11%), breast primary (14% vs 5%), controlled primary (83% vs 63%), asymptomatic presentation (28% vs 13%), surgical resection of a brain metastasis (29% vs 11%), single brain metastasis (62% vs 29%), supratentorial or infratentorial involvement (not both) (83% vs 63%), absence of extracranial metastases (64% vs 20%), and oligometastatic disease burden (5 total metastases) (77% vs 32%). On multivariate analysis asymptomatic presentation, absence of extracranial metastases, and oligometastatic disease burden continued to be statistically significant. Conclusions: Patient selection for SRS alone as the initial radiation therapy strategy for brain metastases should incorporate symptoms at presentation and extent of extracranial metastatic disease. A more comprehensive approach taking these variables into account will allow for more appropriate utilization of this technology and for the prediction of patients who benefit the most from withholding WBRT. Author Disclosure: D. Gorovets: None. D.K. Ebner: None. P. Rava: None. D. Tybor: None. D. Cielo: None. Y. Puthawala: None. T.J. Kinsella: None. T.A. DiPetrillo: None. D.E. Wazer: None. J.T. Hepel: None.
Repeat Stereotactic Radiosurgery (SRS) for Brain Metastases Locally Recurrent Following Initial SRS P. Jayachandran, D. Shultz, L. Modlin, R. Von Eyben, I.C. Gibbs, S. Chang, G. Harsh, G. Li, J. Adler, S.L. Hancock, and S.G. Soltys; Stanford University, Stanford, CA Purpose/Objectives: Local failure (LF) of brain metastases (BM) after initial stereotactic radiosurgery (SRS) may be treated with whole brain radiation therapy (WBRT). We report the outcomes for patients treated by repeat SRS after LF of BM, deferring WBRT. Materials/Methods: In a retrospective review of SRS for BM from 2006 - 2013, we identified a cohort of 19 patients with 27 lesions treated with repeat SRS after LF following initial SRS (15 had SRS only and 12 had resection followed by SRS cavity boost). Among these 19 patients there were 60 courses of SRS for 139 BM (112 as primary treatment and 27 with repeat SRS). SRS was delivered in 1-5 fractions; dose was converted to SFED (single fraction equivalent dose with alpha/beta Z 10). Kaplan-Meier rates of overall survival (OS), the cumulative incidence of LF, with death as a competing risk, and crude incidence of radiation necrosis (RN) were calculated for both cohorts. For tumors re-treated with SRS, LF was calculated from the time of the salvage SRS course. Cox proportional hazards analyzed factors predictive (p <0.05) for LF and OS. Results: The median clinical follow-up was 12.3 months (0 - 48 months). For the 27 recurrent metastases, initial SRS targeted a median tumor volume of 1.29 cc (range 0.04 - 11.8 cc) to a median SFED of 22 Gy10 (16 - 24 Gy10). Median volume was 6.6 cc (0.11 - 31.4 cc) at the second course to a median SFED of 17.3 Gy10 (14.5 - 24 Gy10). At retreatment, 12 metastases were treated in 1 fraction (median 20 Gy, range 16-24 Gy), 1 in 2 fractions (22 Gy), 10 in 3 fractions (median 24 Gy, range 21-27 Gy), and 4 in 5 fractions (median 27.5 Gy, range 25-30 Gy). For all metastases, LF at 1 year and 2 years was 17% and 25%, respectively. LF at 1 year for the 27 re-treated metastases was 25% versus 17% (p Z 0.5) for the 112 metastases. On overall univariate analysis, LF was not significantly correlated with SFED, volume, fractionation, age, GPA, KPS, or histology. Four of 19 patients (21%) developed RN at 6 sites, 4 of which were retreatments. The rate of RN at 1 year was 15% and 2% (p Z 0.01) for metastases re-treated and primarily treated, respectively. Two sites of RN were asymptomatic, 2 were resected and 2 received hyperbaric oxygen. Median time to RN for the re-treated lesions was 9 months (6-12 months) following the second course. Neurologic death occurred in 3 (16%) patients. Two patients were eventually treated with WBRT, none within the first 22 months. Median OS was 36 months (16-55 months). Median OS from the time of repeat SRS was 26 months (0-34 months). KPS, sum of lesions, and dose were significantly correlated with OS (p Z 0.0005, <0.0001, and 0.0490, respectively). Conclusions: For BM locally recurrent following initial SRS, repeat SRS with deferral of WBRT is a treatment option with acceptable rates of local control and toxicity. Author Disclosure: P. Jayachandran: None. D. Shultz: None. L. Modlin: None. R. von Eyben: None. I.C. Gibbs: None. S. Chang: None. G. Harsh: None. G. Li: None. J. Adler: None. S.L. Hancock: None. S.G. Soltys: None.
2261 Lower-Dose Stereotactic Radiosurgery for Small Brain Metastases: Local Control and Toxicity J. Burkeen, B.M. Alexander, M.C. Horvath, L.W. Christianson, M.A. Dyer, I.F. Dunn, A.J. Golby, M.D. Johnson, E.B. Claus, E.A. Chiocca, E.Q. Lee, N.U. Lin, K.J. Marcus, S. Friesen, E.G. Mannarino, M. Wagar, F.L. Hacker, and N.D. Arvold; Dana-Farber/Brigham & Women’s Cancer Center, Boston, MA Purpose/Objective(s): RTOG 9005 reported a maximum tolerated dose of 24 Gy for single dose stereotactic radiosurgery (SRS) treatment of brain metastases 20 mm. While this dose is used at many centers, it is not
International Journal of Radiation Oncology Biology Physics
linear quadratic model is known to be inaccurate at high fractional doses, the clinical outcomes reported supports the dose schedules employed. Necrosis rates were lower with F-SRS but not statistically different. Further investigation of F-SRS as a method for improving the therapeutic ratio for large tumors or those located near eloquent regions is warranted. Author Disclosure: G. Savir: None. D.K. Ebner: None. J. Chan: None. P. Rava: None. D. Cielo: None. T. Kinsella: None. T.A. DiPetrillo: None. D. Wazer: None. J.T. Hepel: None.
2260
2259 Improving Patient Selection for Stereotactic Radiosurgery as the Initial Radiation Therapy Approach for Brain Metastases D. Gorovets,1,2 D.K. Ebner,2 P. Rava,3 D. Tybor,1 D. Cielo,2 Y. Puthawala,2 T.J. Kinsella,2 T.A. DiPetrillo,1,2 D.E. Wazer,1,2 and J.T. Hepel1,2; 1Tufts Medical Center, Boston, MA, 2Brown Alpert Medical School, Providence, RI, 3University of Massachusetts Memorial Medical Center, Worcester, MA Purpose/Objective(s): Patients with brain metastases are a heterogeneous group of cancer patients. Recent ASTRO clinical practice guidelines suggest that stereotactic radiosurgery (SRS) alone can be effectively used as the initial radiotherapeutic approach for limited brain metastases measuring 4cm in patients with good expected prognoses (3 months). The primary advantage of SRS compared to whole brain radiation therapy (WBRT) is the ability to spare normal brain tissue and preserve neurocognition. The aim of the present study was to identify predictors for extended survival free from salvage WBRT in patients with newly diagnosed brain metastases treated with SRS. Materials/Methods: From 2001-2012, over 500 patients with brain metastases were treated with SRS at our institution. For this study, we included only patients with a Karnofsky Performance Status (KPS) 70%, without prior or concurrent WBRT, and with adequate follow-up. Two cohorts of patients were identified: those with 1 year survival free from WBRT, and those who required salvage WBRT or died within 3 months of radiosurgery. We evaluated patient, tumor, and treatment variables and performed univariate (Fisher’s exact test) and multivariate analyses (binary logistic regression) assessing the differences between these two cohorts. A p-value of <0.05 was considered statistically significant. Results: Three hundred and eight patients with a median follow-up of 9.4 months were evaluated. Fifty six patients (18%) had WBRT-free survival 3 months while 104 patients (34%) survived beyond 1 year without the need for salvage WBRT. Patients with 1 year WBRT-free survival were significantly more likely to have the following characteristics on univariate analysis: age <65 years old (64 % vs 45%), RTOG Recursive Partitioning Analysis (RPA) class I (39% vs 11%), breast primary (14% vs 5%), controlled primary (83% vs 63%), asymptomatic presentation (28% vs 13%), surgical resection of a brain metastasis (29% vs 11%), single brain metastasis (62% vs 29%), supratentorial or infratentorial involvement (not both) (83% vs 63%), absence of extracranial metastases (64% vs 20%), and oligometastatic disease burden (5 total metastases) (77% vs 32%). On multivariate analysis asymptomatic presentation, absence of extracranial metastases, and oligometastatic disease burden continued to be statistically significant. Conclusions: Patient selection for SRS alone as the initial radiation therapy strategy for brain metastases should incorporate symptoms at presentation and extent of extracranial metastatic disease. A more comprehensive approach taking these variables into account will allow for more appropriate utilization of this technology and for the prediction of patients who benefit the most from withholding WBRT. Author Disclosure: D. Gorovets: None. D.K. Ebner: None. P. Rava: None. D. Tybor: None. D. Cielo: None. Y. Puthawala: None. T.J. Kinsella: None. T.A. DiPetrillo: None. D.E. Wazer: None. J.T. Hepel: None.
Repeat Stereotactic Radiosurgery (SRS) for Brain Metastases Locally Recurrent Following Initial SRS P. Jayachandran, D. Shultz, L. Modlin, R. Von Eyben, I.C. Gibbs, S. Chang, G. Harsh, G. Li, J. Adler, S.L. Hancock, and S.G. Soltys; Stanford University, Stanford, CA Purpose/Objectives: Local failure (LF) of brain metastases (BM) after initial stereotactic radiosurgery (SRS) may be treated with whole brain radiation therapy (WBRT). We report the outcomes for patients treated by repeat SRS after LF of BM, deferring WBRT. Materials/Methods: In a retrospective review of SRS for BM from 2006 - 2013, we identified a cohort of 19 patients with 27 lesions treated with repeat SRS after LF following initial SRS (15 had SRS only and 12 had resection followed by SRS cavity boost). Among these 19 patients there were 60 courses of SRS for 139 BM (112 as primary treatment and 27 with repeat SRS). SRS was delivered in 1-5 fractions; dose was converted to SFED (single fraction equivalent dose with alpha/beta Z 10). Kaplan-Meier rates of overall survival (OS), the cumulative incidence of LF, with death as a competing risk, and crude incidence of radiation necrosis (RN) were calculated for both cohorts. For tumors re-treated with SRS, LF was calculated from the time of the salvage SRS course. Cox proportional hazards analyzed factors predictive (p <0.05) for LF and OS. Results: The median clinical follow-up was 12.3 months (0 - 48 months). For the 27 recurrent metastases, initial SRS targeted a median tumor volume of 1.29 cc (range 0.04 - 11.8 cc) to a median SFED of 22 Gy10 (16 - 24 Gy10). Median volume was 6.6 cc (0.11 - 31.4 cc) at the second course to a median SFED of 17.3 Gy10 (14.5 - 24 Gy10). At retreatment, 12 metastases were treated in 1 fraction (median 20 Gy, range 16-24 Gy), 1 in 2 fractions (22 Gy), 10 in 3 fractions (median 24 Gy, range 21-27 Gy), and 4 in 5 fractions (median 27.5 Gy, range 25-30 Gy). For all metastases, LF at 1 year and 2 years was 17% and 25%, respectively. LF at 1 year for the 27 re-treated metastases was 25% versus 17% (p Z 0.5) for the 112 metastases. On overall univariate analysis, LF was not significantly correlated with SFED, volume, fractionation, age, GPA, KPS, or histology. Four of 19 patients (21%) developed RN at 6 sites, 4 of which were retreatments. The rate of RN at 1 year was 15% and 2% (p Z 0.01) for metastases re-treated and primarily treated, respectively. Two sites of RN were asymptomatic, 2 were resected and 2 received hyperbaric oxygen. Median time to RN for the re-treated lesions was 9 months (6-12 months) following the second course. Neurologic death occurred in 3 (16%) patients. Two patients were eventually treated with WBRT, none within the first 22 months. Median OS was 36 months (16-55 months). Median OS from the time of repeat SRS was 26 months (0-34 months). KPS, sum of lesions, and dose were significantly correlated with OS (p Z 0.0005, <0.0001, and 0.0490, respectively). Conclusions: For BM locally recurrent following initial SRS, repeat SRS with deferral of WBRT is a treatment option with acceptable rates of local control and toxicity. Author Disclosure: P. Jayachandran: None. D. Shultz: None. L. Modlin: None. R. von Eyben: None. I.C. Gibbs: None. S. Chang: None. G. Harsh: None. G. Li: None. J. Adler: None. S.L. Hancock: None. S.G. Soltys: None.
2261 Lower-Dose Stereotactic Radiosurgery for Small Brain Metastases: Local Control and Toxicity J. Burkeen, B.M. Alexander, M.C. Horvath, L.W. Christianson, M.A. Dyer, I.F. Dunn, A.J. Golby, M.D. Johnson, E.B. Claus, E.A. Chiocca, E.Q. Lee, N.U. Lin, K.J. Marcus, S. Friesen, E.G. Mannarino, M. Wagar, F.L. Hacker, and N.D. Arvold; Dana-Farber/Brigham & Women’s Cancer Center, Boston, MA Purpose/Objective(s): RTOG 9005 reported a maximum tolerated dose of 24 Gy for single dose stereotactic radiosurgery (SRS) treatment of brain metastases 20 mm. While this dose is used at many centers, it is not