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Survival Outcomes for Patients With 5+ Versus Single or 2 to 4 Brain Metastases Undergoing Stereotactic Radiosurgery (SRS)
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Volume 93 Number 3S Supplement 2015 bi-directional product (BP), volume of the post-surgical cavity including surrounding enhancement (Vol), and volume of T1+C enhanced rim (Rim) with the cavity subtracted. We first sought to determine if a 25% increase between PO and 1 or 3 month T1+C MRIs was predictive of worsened OS and PFS for each technique. If significant, we planned to determine if a 5% increase, or any increase were also predictive. Results: Median age was 61.8 years. Median OS and PFS were 18.6 and 11.7 months. A relative increase in Rim volume of 25% at 3 months was a poor prognostic factor for OS (15.2 vs 31.3 months pZ0.001) and for PFS (10.0 vs 15.5 months pZ0.011). Even at 1 month, Rim increase of 25% was a poor prognostic factor for OS and for PFS. Vol and BP change did not statistically significantly predict for OS. Rim increase of only 5% at 1 month also predicted for worse OS (15.2 vs 26.9 months pZ0.010). Further, at 1 month, any increase in Rim enhancement was associated with worse OS (15.2 vs 21.3 months pZ0.025). Conclusion: Even minor change in the relative amount of enhancement surrounding the post-surgical cavity is an early prognostic factor for OS and PFS. Changes of Vol or BP were not significant predictors of OS. These findings suggest that either a lack of early response or underappreciated progression portends a significantly worse prognosis and raises the question of whether salvage therapies should be considered earlier in these patients. Author Disclosure: J. Molitoris: None. S. Aggarwal: None. C. Gzell: None. T. Diwanji: None. M.P. Mehta: Consultant; Elekta, Novocure, Novartis. Member, Board of Directors; Pharmacyclics. Chair, Brain Tumor Committee; NRG.
2272 Hypofractionated Stereotactic Radiation Therapy/ Radiosurgery Results in Patients With Uveal Melanoma G. Yazici,1 G. Ozyigit,1 S. Yuce Sari,1 B. Tarlan,1 H. Kiratli,1 M. Cengiz,2 and F. Zorlu2; 1Hacettepe University, Ankara, Turkey, 2Hacettepe University Medical School, Ankara, Turkey Purpose/Objective(s): Evaluation of treatment results of patients who received stereotactic radiosurgery and fractionated stereotactic radiation therapy (SRS-FSRT) for uveal melanoma. Materials/Methods: We retrospectively evaluated 163 patients who received SRS-FSRT between 2007 and 2013 with the diagnosis of uveal melanoma. Treatments were applied with a frameless robotic radiosurgery system . Median age of the patients was 54 years (18-82 years). Ninety-six (59%) patients were male, and 67 (41%) patients were female. According to the Collaborative Ocular Melanoma Study (COMS), tumor size was small in 8 (5%), medium in 49 (30%), and large in 106 (65%) patients. SRS-FSRT was applied in median 3 (1-3) fractions with a total of median 54 Gy (10-60 Gy). Median maximum GTV dose was 63 Gy. Results: Median follow-up time was 16 months. Local recurrence and distant metastasis developed in 27 and 16 patients, respectively. Median local recurrence-free time was 14 months, and distant metastasis-free time was 17 months. Complete and partial response was observed in 3 and 54 patients, respectively. The lesion was stable in 55, and progressive in 49 patients. One patient was succumbed to death because of the disease, and 1 patient because of other reasons. In 36 patients, enucleation was performed after SRS-FSRT. The reason for enucleation was progression in 27, and complication in 9 patients. The rates of 2-, and 5-year overall survival (OS) were 98.3%, and 98.3%; disease-free survival (DFS) was 73.3%, and 28%; local recurrence-free survival (LRFS) was 77.5%, and 68.2%; and distant metastasis-free survival (DMFS) was 87.3%, and 29.4%. In both univariate and multivariate analyses, COMS size and SRS-FSRT dose were statistically significant prognostic factors for DFS and LRFS (Table 1, and Table 2). No statistically significant factor was detected for OS or DMFS in univariate or in multivariate analyses. When 106 patients who had COMS large tumors were analyzed separately, we found 2, and 5-year rates of OS 97%, and 97%; DFS 64%, and 24%; LRFS 70%, and 60%; DMFS 86%, and 28%, respectively. Enucleation was performed in 30 patients after SRS-FSRT.; the reason for enucleation was progression in 23, and complication in 7 patients. In this group of patients, univariate analysis revealed SRS-FSRT statistically significant for both DFS and
LRFS (pZ0.01 and pZ0.004, respectively). Similarly, in multivariate analysis SRS-FSRT dose was statistically significant for DFS (pZ0.009) and LRFS (pZ0.005). Conclusion: We detected that radiation dose applied is of great importance in uveal melanoma patients in terms of disease-free survival and local control; the best results were achieved in patients who received 45 Gy. In patients with COMS large tumors in whom enucleation is recommended in the literature, organ preservation was achieved in 72% by the help of SRSSFRT. Author Disclosure: G. Yazici: None. G. Ozyigit: None. S. Yuce Sari: None. B. Tarlan: None. H. Kiratli: None. M. Cengiz: None. F. Zorlu: None.
2273 Survival Outcomes for Patients With 5+ Versus Single or 2 to 4 Brain Metastases Undergoing Stereotactic Radiosurgery (SRS) D.M. Routman, S.X. Bian, L. Ji, S. Groshen, M.L.J. Apuzzo, C. Yu, and E.L. Chang; University of Southern California, Keck School of Medicine, Los Angeles, CA Purpose/Objective(s): Recent studies have suggested equivalent SRS outcomes for patients with 5+ brain metastases (mets) compared to single or 2-4 brain mets, and that total intracranial volume is the more important prognostic factor. Our study evaluated survival in patients with 5 or more brain mets treated with SRS, in comparison to patients with single versus 2-4 lesions. We also investigated the association between total intracranial tumor volume and overall survival (OS). Materials/Methods: This retrospective analysis included all patients at our institution from 1994 to 2012 treated with SRS for mets to the brain, totaling 1017 patients, of which survival data from the cancer registry was available for 843 (83%). Of the 843 patients, the most common primary malignancies were melanoma, lung, and breast, for 388, 173, and 96 patients, respectively. Patients were grouped according to number of metastases: 1 (n Z 428), 2-4 (n Z 358), and 5 or more (n Z 57). Total treatment volume was categorized as <5, 5-10, 10-20, and >20 cc’s. OS was calculated from the day SRS was performed to the date of last followup or date of death. Analysis included Kaplan-Meier curves and Cox proportional hazard models investigating the association between OS and number of lesions, total treatment volume, age, and primary histology. Results: Median OS was 8.3 months for all 843 patients (95% CI, [7.7 9.2]). Median OS was significantly different for the 1, 2-4, and 5 or more groups at 10.4 months (95% CI [ 8.9 - 9.9]), 7.3 months (95% CI [6.4 to 8.2] and 6.2 months (95% CI [3.8-7.8], respectively (p<0.001, test for trend). Median follow-up was 36.9 months for patients alive at time of analysis. On multivariable trend analysis, lesion number, total treatment volume, and age of patient had a significant association with OS (p0.001). Using Akaike’s information criteria, lesion number is a stronger risk factor for OS than total volume or age: patients with 5 or more lesions had a HR of 1.96 for death, compared to patients with 1 lesion; the HR was 1.48 for patients with 2-4 lesions. A marginally significant association was found between primary malignancy and OS (pZ0.065), with melanoma histology showing worse survival than patients with other histology on multivariable analysis. Conclusion: Our study suggests that brain metastasis lesion number has prognostic significance for OS. Furthermore, our data suggests lesion number is a greater risk factor for worse OS than total intracranial tumor volume. Patients with 5 or more brain metastases had the largest HR of 1.96 when compared to the patient characteristic of a single brain metastasis. Author Disclosure: D.M. Routman: None. S.X. Bian: None. L. Ji: None. S. Groshen: None. M.L. Apuzzo: None. C. Yu: None. E.L. Chang: None.
2274 Evolution of Small Cerebral Metastases Treated With Either Hypofractionated Stereotactic Radiation Therapy (hfSRT) or Radiosurgery (RS) R. Tanguy,1 C. Malet,1 P. Pommier,1 C. Carrie,1 L. Claude,1 S. Racadot,1 M.L. Isabelle,2 and M.P. Sunyach1; 1Centre Leon Berard, Lyon, France, 2 Centre Leon Berard, Lyon, France
Volume 93 Number 3S Supplement 2015 bi-directional product (BP), volume of the post-surgical cavity including surrounding enhancement (Vol), and volume of T1+C enhanced rim (Rim) with the cavity subtracted. We first sought to determine if a 25% increase between PO and 1 or 3 month T1+C MRIs was predictive of worsened OS and PFS for each technique. If significant, we planned to determine if a 5% increase, or any increase were also predictive. Results: Median age was 61.8 years. Median OS and PFS were 18.6 and 11.7 months. A relative increase in Rim volume of 25% at 3 months was a poor prognostic factor for OS (15.2 vs 31.3 months pZ0.001) and for PFS (10.0 vs 15.5 months pZ0.011). Even at 1 month, Rim increase of 25% was a poor prognostic factor for OS and for PFS. Vol and BP change did not statistically significantly predict for OS. Rim increase of only 5% at 1 month also predicted for worse OS (15.2 vs 26.9 months pZ0.010). Further, at 1 month, any increase in Rim enhancement was associated with worse OS (15.2 vs 21.3 months pZ0.025). Conclusion: Even minor change in the relative amount of enhancement surrounding the post-surgical cavity is an early prognostic factor for OS and PFS. Changes of Vol or BP were not significant predictors of OS. These findings suggest that either a lack of early response or underappreciated progression portends a significantly worse prognosis and raises the question of whether salvage therapies should be considered earlier in these patients. Author Disclosure: J. Molitoris: None. S. Aggarwal: None. C. Gzell: None. T. Diwanji: None. M.P. Mehta: Consultant; Elekta, Novocure, Novartis. Member, Board of Directors; Pharmacyclics. Chair, Brain Tumor Committee; NRG.
2272 Hypofractionated Stereotactic Radiation Therapy/ Radiosurgery Results in Patients With Uveal Melanoma G. Yazici,1 G. Ozyigit,1 S. Yuce Sari,1 B. Tarlan,1 H. Kiratli,1 M. Cengiz,2 and F. Zorlu2; 1Hacettepe University, Ankara, Turkey, 2Hacettepe University Medical School, Ankara, Turkey Purpose/Objective(s): Evaluation of treatment results of patients who received stereotactic radiosurgery and fractionated stereotactic radiation therapy (SRS-FSRT) for uveal melanoma. Materials/Methods: We retrospectively evaluated 163 patients who received SRS-FSRT between 2007 and 2013 with the diagnosis of uveal melanoma. Treatments were applied with a frameless robotic radiosurgery system . Median age of the patients was 54 years (18-82 years). Ninety-six (59%) patients were male, and 67 (41%) patients were female. According to the Collaborative Ocular Melanoma Study (COMS), tumor size was small in 8 (5%), medium in 49 (30%), and large in 106 (65%) patients. SRS-FSRT was applied in median 3 (1-3) fractions with a total of median 54 Gy (10-60 Gy). Median maximum GTV dose was 63 Gy. Results: Median follow-up time was 16 months. Local recurrence and distant metastasis developed in 27 and 16 patients, respectively. Median local recurrence-free time was 14 months, and distant metastasis-free time was 17 months. Complete and partial response was observed in 3 and 54 patients, respectively. The lesion was stable in 55, and progressive in 49 patients. One patient was succumbed to death because of the disease, and 1 patient because of other reasons. In 36 patients, enucleation was performed after SRS-FSRT. The reason for enucleation was progression in 27, and complication in 9 patients. The rates of 2-, and 5-year overall survival (OS) were 98.3%, and 98.3%; disease-free survival (DFS) was 73.3%, and 28%; local recurrence-free survival (LRFS) was 77.5%, and 68.2%; and distant metastasis-free survival (DMFS) was 87.3%, and 29.4%. In both univariate and multivariate analyses, COMS size and SRS-FSRT dose were statistically significant prognostic factors for DFS and LRFS (Table 1, and Table 2). No statistically significant factor was detected for OS or DMFS in univariate or in multivariate analyses. When 106 patients who had COMS large tumors were analyzed separately, we found 2, and 5-year rates of OS 97%, and 97%; DFS 64%, and 24%; LRFS 70%, and 60%; DMFS 86%, and 28%, respectively. Enucleation was performed in 30 patients after SRS-FSRT.; the reason for enucleation was progression in 23, and complication in 7 patients. In this group of patients, univariate analysis revealed SRS-FSRT statistically significant for both DFS and
LRFS (pZ0.01 and pZ0.004, respectively). Similarly, in multivariate analysis SRS-FSRT dose was statistically significant for DFS (pZ0.009) and LRFS (pZ0.005). Conclusion: We detected that radiation dose applied is of great importance in uveal melanoma patients in terms of disease-free survival and local control; the best results were achieved in patients who received 45 Gy. In patients with COMS large tumors in whom enucleation is recommended in the literature, organ preservation was achieved in 72% by the help of SRSSFRT. Author Disclosure: G. Yazici: None. G. Ozyigit: None. S. Yuce Sari: None. B. Tarlan: None. H. Kiratli: None. M. Cengiz: None. F. Zorlu: None.
2273 Survival Outcomes for Patients With 5+ Versus Single or 2 to 4 Brain Metastases Undergoing Stereotactic Radiosurgery (SRS) D.M. Routman, S.X. Bian, L. Ji, S. Groshen, M.L.J. Apuzzo, C. Yu, and E.L. Chang; University of Southern California, Keck School of Medicine, Los Angeles, CA Purpose/Objective(s): Recent studies have suggested equivalent SRS outcomes for patients with 5+ brain metastases (mets) compared to single or 2-4 brain mets, and that total intracranial volume is the more important prognostic factor. Our study evaluated survival in patients with 5 or more brain mets treated with SRS, in comparison to patients with single versus 2-4 lesions. We also investigated the association between total intracranial tumor volume and overall survival (OS). Materials/Methods: This retrospective analysis included all patients at our institution from 1994 to 2012 treated with SRS for mets to the brain, totaling 1017 patients, of which survival data from the cancer registry was available for 843 (83%). Of the 843 patients, the most common primary malignancies were melanoma, lung, and breast, for 388, 173, and 96 patients, respectively. Patients were grouped according to number of metastases: 1 (n Z 428), 2-4 (n Z 358), and 5 or more (n Z 57). Total treatment volume was categorized as <5, 5-10, 10-20, and >20 cc’s. OS was calculated from the day SRS was performed to the date of last followup or date of death. Analysis included Kaplan-Meier curves and Cox proportional hazard models investigating the association between OS and number of lesions, total treatment volume, age, and primary histology. Results: Median OS was 8.3 months for all 843 patients (95% CI, [7.7 9.2]). Median OS was significantly different for the 1, 2-4, and 5 or more groups at 10.4 months (95% CI [ 8.9 - 9.9]), 7.3 months (95% CI [6.4 to 8.2] and 6.2 months (95% CI [3.8-7.8], respectively (p<0.001, test for trend). Median follow-up was 36.9 months for patients alive at time of analysis. On multivariable trend analysis, lesion number, total treatment volume, and age of patient had a significant association with OS (p0.001). Using Akaike’s information criteria, lesion number is a stronger risk factor for OS than total volume or age: patients with 5 or more lesions had a HR of 1.96 for death, compared to patients with 1 lesion; the HR was 1.48 for patients with 2-4 lesions. A marginally significant association was found between primary malignancy and OS (pZ0.065), with melanoma histology showing worse survival than patients with other histology on multivariable analysis. Conclusion: Our study suggests that brain metastasis lesion number has prognostic significance for OS. Furthermore, our data suggests lesion number is a greater risk factor for worse OS than total intracranial tumor volume. Patients with 5 or more brain metastases had the largest HR of 1.96 when compared to the patient characteristic of a single brain metastasis. Author Disclosure: D.M. Routman: None. S.X. Bian: None. L. Ji: None. S. Groshen: None. M.L. Apuzzo: None. C. Yu: None. E.L. Chang: None.
2274 Evolution of Small Cerebral Metastases Treated With Either Hypofractionated Stereotactic Radiation Therapy (hfSRT) or Radiosurgery (RS) R. Tanguy,1 C. Malet,1 P. Pommier,1 C. Carrie,1 L. Claude,1 S. Racadot,1 M.L. Isabelle,2 and M.P. Sunyach1; 1Centre Leon Berard, Lyon, France, 2 Centre Leon Berard, Lyon, France