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Long-Term Outcomes of Adult Medulloblastoma Patients Treated With Radiation Therapy
Volume 99 Number 2S Supplement 2017 (RT) in the treatment of resected atypical meningiomas (AM) has been controversial. We sought to examine the role of RT for AM in the adjuvant and salvage setting at the University of California at Los Angeles (UCLA). Materials/Methods: 43 patients diagnosed with AM treated with RT at UCLA from 1999-2015 were identified and retrospectively analyzed. We noted that the definition of grade II AM changed in 2007. Patients were selected based on the grading system during the year they were diagnosed. Data on age, race, gender, surgical type, radiation dose and modality were investigated. Estimates of relapse-free survival (RFS) and overall survival (OS) were performed using the Kaplan-Meier method. Results: 30 patients received adjuvant radiation therapy (ART) after surgery at the initial diagnosis. Of those, 14 had gross total resection (GTR), 16 had subtotal resection (STR). 13 received salvage radiation therapy (SaRT) for recurrent AM following previous surgery. Of those, 9 received GTR at initial diagnosis, 4 underwent STR. The median age at diagnosis was 59, range 38-79. There were 31 Caucasian, 7 Asian, 3 African American, and 2 Hispanic. There were 21 females and 22 males. The median follow up was 32.5 months, range 1.5-108. In the ART group, 1 patient received stereotactic radiosurgery (SRS) and 29 patients received fractionated external beam radiotherapy (EBRT). The median dose was 55.8 Gy (range 48.6-59.4). The single SRS dose was 12 Gy, which is noted to be unusually low for SRS to AM. In the SaRT group, 4 patients received SRS and 9 patients received fractionated EBRT. The median dose was 54 Gy (range 50.4-60); the median SRS dose was 14 Gy (range 14-16). In the ART group, the RFS at 3 and 5 year was 90% and 78%, respectively; the OS at 3 and 5 year was 95%. In the SaRT group, the RFS at 3 and 5 year was 62.5%; the OS at 3 and 5 year was 100%. Compared to historic controls reporting ART for AM, the RFS and OS at 5 years range from 5092% and 67-84%, respectively. We performed an analysis using the Surveillance, Epidemiology, and End Results Program (SEER) database evaluating patients with grade II AM who underwent GTR without ART between 2004-2010. The 3 and 5 year OS were 89% and 84%, respectively. Conclusion: ART for AM at our institution provides similar RFS and OS compared to historical controls published in the literature. With further data collection, we plan to evaluate the outcomes of these patients based on surgical resection, STR vs GTR, to determine the role of ART in AM. Patients from the SEER database with GTR had high 3 and 5 year OS. SaRT for resected AM that recurred also provided excellent OS, although RFS was not as high in the adjuvant setting. The role of ART in AM after GTR remains controversial. However, there appears to be a benefit to ART vs SaRT for local control and further studies are necessary to evaluate this potential benefit. Author Disclosure: A.T. Dang: None. C. Wang: None. T.B. Kaprealian: Honoraria; UCLA Medical Education Program Melanoma Management.
2162 Radiomic Features Extracted from Magnetic Resonance Imaging (MRI) Are Associated with Clinical Outcomes in Low-Grade Glioma S.E. Day,1 M.B. Spraker,2 L. Wootton,2 D.S. Hippe,2 W.A. Chaovalitwongse,2 M. Hoff,3 L.M. Halasz,2 and M. Nyflot4; 1 University of Washington, Department of Radiation Oncology, Seattle, WA, 2University of Washington, Seattle, WA, 3University of Washington, Department of Radiology, Seattle, WA, 4University of Washington Radiation Oncology, Seattle, WA Purpose/Objective(s): Low grade gliomas (LGG) are typically slowgrowing, but have a variable pace of progression, so selection of optimal treatment can be difficult. Radiomics seeks to quantify complex features of clinical imaging data that are related to underlying tumor biology. This technique has been used for classification and prognostication in glioblastoma, but the utility of radiomic features for LGG remains unknown. This study tested hypothesis that clinical features and radiomic features extracted from T2-weighted MRI are associated with overall survival (OS) in patients with LGG. Materials/Methods: Preoperative T2-weighted MR images were collected from 40 patients with WHO grade II LGG, 18 years or older, and with at least one year of follow-up. Clinical data were collected from the medical record.
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Abstract 2162; Table 1 Variable Tumor 1p/19qstatus Wild type 1p Deleted 19q Deleted Unknown Histology - WHO II Oligodendroglioma Oligoastrocytoma Astrocytoma
n (%) 11 (27.5) 25 (62.5) 26 (65) 3 (7.5) 32 (80) 6 (15) 2 (5)
MRIs were evaluated by a radiation oncologist, who segmented each tumor volume. Clinical variables included sex, age, tumor 1p status, tumor 19q status, extent of surgery, and radiation versus chemotherapy. Radiomics extracted 45 different radiomic features in four groups: intensity histograms, co-occurence matrices, neighborhood difference matrices, and zone size matrices. Tumor diameter was treated as a radiomic feature for analysis. Univariate Cox regression was used to test for clinical and radiomic features with significant association to OS. Hazard ratios (HRs) were standardized to show the change in risk per 1-SD increase in the feature. Results: Sixty-two percent of patients were male, with median age of 47.6 years (range: 24-72y). Median follow up was 69.7 months (range 28.8201.2 months). Forty-three percent had gross-total resection and 40% had subtotal resection. Histologic characteristics are shown in Table 1. Median OS was 147 months, with 8 deaths observed over follow up. In univariate analysis, ten radiomic features were significantly associated with OS (p<0.05). Two features had p<0.01. The top features included kurtosis (HR 2.4, pZ0.004), tumor diameter (HR 2.8, pZ0.010), skewness (HR 0.2, pZ0.011), and contrast (HR 0.3, pZ0.025). Tumor size was the only clinical feature significantly (p<0.05) associated with survival. Conclusion: This preliminary study found that some radiomics features extracted from preoperative MRIs may have the potential to predict OS outcomes for patients with LGG. These results suggest that models incorporating radiomic features may be useful for patient stratification. Future work will expand the size of the cohort and evaluate optimized models of clinical and radiomic features. Author Disclosure: S.E. Day: None. M.B. Spraker: None. L. Wootton: None. D.S. Hippe: Research Grant; GE healthcare, Philips healthcare. W.A. Chaovalitwongse: None. M. Hoff: None. L.M. Halasz: Research Grant; Fred Hutch/Univ of Washington Cancer Consortium. M. Nyflot: Research Grant; Radiological society of North America.
2163 Long-Term Outcomes of Adult Medulloblastoma Patients Treated With Radiation Therapy B. De, K. De Braganca, K. Beal, M. Souweidane, S. Patel, and S.L. Wolden; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): Medulloblastoma (MB) is rare in adults and consequently treatment guidelines are not well-established. While survival and prognostic factors are commonly reported, few series include information on patient presentations and treatment effects. We examined patient presentation and long-term outcomes of adult MB patients at one institution. Materials/Methods: The records of 24 consecutive patients (14 male, 10 female) aged 18 years who received radiotherapy (RT) for primary MB from 1990-2016 at a single institution were reviewed. Median age at diagnosis was 28 years (range, 18-72 years). Results: Symptom duration before initial presentation was a median of 3.3 months (range, 0.1-36 months). Most common presenting symptoms were headache (nZ21), nausea/vomiting (nZ17), dizziness/vertigo (nZ11), and ataxia (nZ10). Tumor location was midline in 13 patients. Fourteen patients were standard risk and 10 were high risk. Eighteen patients had gross total resection, 5 patients had subtotal resection, and 1 had biopsy only. Median craniospinal RT and boost doses were 36 Gy (range, 23.4-39.6 Gy) and 55.8 Gy (range, 54-59.4 Gy), respectively. Five patients had adjuvant treatment with RT only. Of the remaining 19 patients, 15 patients received concurrent + adjuvant
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chemotherapy and 4 received adjuvant CTX only. Most common adjuvant agents used were platinum-based (nZ14), vincristine (nZ12), and lomustine (nZ11). At a median follow-up of 9.7 years (range, 1.0-20.5 years), 4 patients recurred in the posterior fossa, and 1 also recurred above the tentorium. All 4 received salvage chemotherapy, 1 with stem cell rescue, 2 had surgery, and 1 had tumor bed re-RT. Of 5 patients who expired, 2 died of disease progression, 2 died of other causes with no evidence of disease, and 1 died after treatment complications. At last follow-up, 17 patients are alive with no evidence of disease. Of living patients, 12 were able to live without assistance. Of 15 patients employed before treatment, only 9 remained able to work in a similar capacity. Among patients with available data, common long-term effects include executive dysfunction (nZ15), weakness/ataxia (nZ14), and depression/anxiety (nZ9). Kaplan-Meier estimates of 10-year overall survival (OS) and progression-free survival (PFS) are 80% (95% confidence interval [CI], 54%-95%) and 79% (CI, 53%-92%), respectively. Conclusion: Despite encouraging disease control in this cohort of adult MB patients, long-term effects related to therapy, including neuropsychological problems, may limit quality of life. Multimodality pediatric treatment regimens using lower RT doses may be considered to reduce treatment-related morbidity. Future studies may focus on treatment stratification based on molecular subtyping. Author Disclosure: B. De: None. K. De Braganca: None. K. Beal: Stock; Magnolia Medical Technology (MMT). M. Souweidane: Honoraria; Aesculap. S. Patel: None. S.L. Wolden: None.
Results: Baseline patient and treatment characteristics, including age, performance status, prior therapies, number of brain metastases, tumor volume, and SRS dose did not differ significantly between the groups. Acute and late toxicities are summarized in Table 1. 24 of 154 (15.6%) SRS treatments resulted in acute toxicities. Only 4 (2.6%) were grade 3-4. Of these, 2 patients developed cerebral hemorrhage, 1 cerebral edema, and 1 paresis. 14 of 91 patients (15.4%) developed late toxicities. Only 5 (5.5%) were grade 3-4, all of which were pathologically confirmed radiation necrosis. Neither acute toxicities nor late toxicities demonstrated association with ipilimumab or timing of its administration (p<0.819 and p<0.231, respectively). Conclusion: Ipilimumab was well tolerated in patients with melanoma brain metastases receiving SRS, regardless of timing of administration. We report 2.6% and 5.5% incidence of clinically significant acute and late toxicities, respectively. The combination appears to be safe for use in clinical practice. Author Disclosure: K. Diao: Employee; Loma Linda University. Research Grant; Harvard Medical School. S.X. Bian: Employee; Stanford School of Medicine. L. Ji: None. S. Groshen: None. D.M. Routman: None. C. Yu: None. N.A. Wagle: None. G. Zada: None. E.L. Chang: Honoraria; AbbVie, Elekta, Brainlab; ASCO.
2165 Radiographic Response and Edema Trajectory Following Treatment of Melanoma Brain Metastases with Stereotactic Radiosurgery and Ipilimumab Immunotherapy K. Diao,1,2 S.X. Bian,2 L. Ji,2 S. Groshen,2 D.M. Routman,3 C. Yu,2 P.E. Kim,2 N.A. Wagle,2 G. Zada,2 and E.L. Chang2; 1Harvard Medical School, Boston, MA, 2University of Southern California Keck School of Medicine, Los Angeles, CA, 3Department of Radiation Oncology, Mayo Clinic, Rochester, MN
2164 Acute and Late Toxicities in the Setting of Combination Stereotactic Radiosurgery and Ipilimumab for Patients With Melanoma Brain Metastases K. Diao,1,2 S.X. Bian,2 L. Ji,2 S. Groshen,2 D.M. Routman,3 C. Yu,2 N.A. Wagle,2 G. Zada,2 and E.L. Chang2; 1Harvard Medical School, Boston, MA, 2University of Southern California Keck School of Medicine, Los Angeles, CA, 3Department of Radiation Oncology, Mayo Clinic, Rochester, MN
Purpose/Objective(s): The trajectory of brain metastases and peritumoral edema following treatment with combination stereotactic radiosurgery (SRS) and immunotherapy is not well described. Better understanding of tumor and edema trajectory will improve clinicians’ ability to assess tumor response in this patient population. We reported imaging findings on post-Gadolinium T1weighted (post-Gd T1) and T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences after SRS in patients with melanoma brain metastases treated with or without ipilimumab. Materials/Methods: We retrospectively analyzed 56 patients with 209 brain metastases treated with SRS at our institution from 2007 to 2015. We divided lesions into three groups of ipilimumab administration: >4 weeks prior to SRS, within +/- 4 weeks of SRS, and >4 weeks after SRS or did not receive ipilimumab. The maximum diameter of each lesion and its edema was measured in post-Gd T1 and FLAIR MRI in three orthogonal planes. Volume was estimated using the validated formula: volume Z (length x width x height)/2. Tumor and edema volumes at 1.5 months, 3 months, and 6 months after SRS were compared to baseline and the percent change calculated. Statistical significance was calculated using mixed effect analysis of variance with patient effect as a random effect. Pvalues were based on permutation tests. Results: Tumor and edema trajectories following SRS are summarized in Table 1. There was a significant difference in median tumor volume change at
Purpose/Objective(s): The central nervous system (CNS) toxicity profile of combination treatment with stereotactic radiosurgery (SRS) and ipilimumab is not well defined. We compared acute and late CNS toxicities in patients receiving SRS and ipilimumab versus SRS alone with an emphasis on timing of administration of ipilimumab relative to SRS. Materials/Methods: We retrospectively reviewed 91 analyzable patients with melanoma brain metastases treated with 154 SRS procedures at our institution from 2007 to 2015. 51 patients received ipilimumab and 40 did not. The median follow-up time was 7.11 months. We divided patients into three groups of ipilimumab administration: >4 weeks prior to SRS, within +/- 4 weeks of SRS, and >4 weeks after SRS or no ipilimumab. Neurological symptoms were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03. We defined clinically significant as grade 3-4. Time to events were calculated from the date of first SRS treatment. Acute toxicities were defined as having occurred within 3 months of each SRS procedure and late toxicities were defined as having occurred after 3 months of initial SRS procedure. Significance was calculated with the Pearson chi-square test.
Abstract 2164; Table 1
Acute and Late Toxicities by Timing of Ipilimumab Maximum Grade of Toxicity
Timing of Ipilimumab Acute Toxicity >4 weeks before SRS Within 4 weeks of SRS None or >4 weeks after SRS Late Toxicity >4 weeks before SRS Within 4 weeks of SRS None or >4 weeks after SRS
1
2
3
Toxicity 4
Yes
No
Total
4 (6%) 3 (11%) 5 (8%)
4 (6%) 1 (4%) 3 (5%)
0 (0%) 1 (4%) 1 (2%)
1 (2%) 0 (0%) 1 (2%)
9 5 10
54 22 54
63 27 64
2 (9%) 0 (0%) 1 (2%)
0 (0%) 2 (8%) 4 (9%)
1 (5%) 1 (4%) 2 (4%)
0 (0%) 1 (4%) 0 (0%)
3 4 7
19 20 38
22 24 45
p-value p<0.819
p<0.231
2162 Radiomic Features Extracted from Magnetic Resonance Imaging (MRI) Are Associated with Clinical Outcomes in Low-Grade Glioma S.E. Day,1 M.B. Spraker,2 L. Wootton,2 D.S. Hippe,2 W.A. Chaovalitwongse,2 M. Hoff,3 L.M. Halasz,2 and M. Nyflot4; 1 University of Washington, Department of Radiation Oncology, Seattle, WA, 2University of Washington, Seattle, WA, 3University of Washington, Department of Radiology, Seattle, WA, 4University of Washington Radiation Oncology, Seattle, WA Purpose/Objective(s): Low grade gliomas (LGG) are typically slowgrowing, but have a variable pace of progression, so selection of optimal treatment can be difficult. Radiomics seeks to quantify complex features of clinical imaging data that are related to underlying tumor biology. This technique has been used for classification and prognostication in glioblastoma, but the utility of radiomic features for LGG remains unknown. This study tested hypothesis that clinical features and radiomic features extracted from T2-weighted MRI are associated with overall survival (OS) in patients with LGG. Materials/Methods: Preoperative T2-weighted MR images were collected from 40 patients with WHO grade II LGG, 18 years or older, and with at least one year of follow-up. Clinical data were collected from the medical record.
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Abstract 2162; Table 1 Variable Tumor 1p/19qstatus Wild type 1p Deleted 19q Deleted Unknown Histology - WHO II Oligodendroglioma Oligoastrocytoma Astrocytoma
n (%) 11 (27.5) 25 (62.5) 26 (65) 3 (7.5) 32 (80) 6 (15) 2 (5)
MRIs were evaluated by a radiation oncologist, who segmented each tumor volume. Clinical variables included sex, age, tumor 1p status, tumor 19q status, extent of surgery, and radiation versus chemotherapy. Radiomics extracted 45 different radiomic features in four groups: intensity histograms, co-occurence matrices, neighborhood difference matrices, and zone size matrices. Tumor diameter was treated as a radiomic feature for analysis. Univariate Cox regression was used to test for clinical and radiomic features with significant association to OS. Hazard ratios (HRs) were standardized to show the change in risk per 1-SD increase in the feature. Results: Sixty-two percent of patients were male, with median age of 47.6 years (range: 24-72y). Median follow up was 69.7 months (range 28.8201.2 months). Forty-three percent had gross-total resection and 40% had subtotal resection. Histologic characteristics are shown in Table 1. Median OS was 147 months, with 8 deaths observed over follow up. In univariate analysis, ten radiomic features were significantly associated with OS (p<0.05). Two features had p<0.01. The top features included kurtosis (HR 2.4, pZ0.004), tumor diameter (HR 2.8, pZ0.010), skewness (HR 0.2, pZ0.011), and contrast (HR 0.3, pZ0.025). Tumor size was the only clinical feature significantly (p<0.05) associated with survival. Conclusion: This preliminary study found that some radiomics features extracted from preoperative MRIs may have the potential to predict OS outcomes for patients with LGG. These results suggest that models incorporating radiomic features may be useful for patient stratification. Future work will expand the size of the cohort and evaluate optimized models of clinical and radiomic features. Author Disclosure: S.E. Day: None. M.B. Spraker: None. L. Wootton: None. D.S. Hippe: Research Grant; GE healthcare, Philips healthcare. W.A. Chaovalitwongse: None. M. Hoff: None. L.M. Halasz: Research Grant; Fred Hutch/Univ of Washington Cancer Consortium. M. Nyflot: Research Grant; Radiological society of North America.
2163 Long-Term Outcomes of Adult Medulloblastoma Patients Treated With Radiation Therapy B. De, K. De Braganca, K. Beal, M. Souweidane, S. Patel, and S.L. Wolden; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): Medulloblastoma (MB) is rare in adults and consequently treatment guidelines are not well-established. While survival and prognostic factors are commonly reported, few series include information on patient presentations and treatment effects. We examined patient presentation and long-term outcomes of adult MB patients at one institution. Materials/Methods: The records of 24 consecutive patients (14 male, 10 female) aged 18 years who received radiotherapy (RT) for primary MB from 1990-2016 at a single institution were reviewed. Median age at diagnosis was 28 years (range, 18-72 years). Results: Symptom duration before initial presentation was a median of 3.3 months (range, 0.1-36 months). Most common presenting symptoms were headache (nZ21), nausea/vomiting (nZ17), dizziness/vertigo (nZ11), and ataxia (nZ10). Tumor location was midline in 13 patients. Fourteen patients were standard risk and 10 were high risk. Eighteen patients had gross total resection, 5 patients had subtotal resection, and 1 had biopsy only. Median craniospinal RT and boost doses were 36 Gy (range, 23.4-39.6 Gy) and 55.8 Gy (range, 54-59.4 Gy), respectively. Five patients had adjuvant treatment with RT only. Of the remaining 19 patients, 15 patients received concurrent + adjuvant
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International Journal of Radiation Oncology Biology Physics
chemotherapy and 4 received adjuvant CTX only. Most common adjuvant agents used were platinum-based (nZ14), vincristine (nZ12), and lomustine (nZ11). At a median follow-up of 9.7 years (range, 1.0-20.5 years), 4 patients recurred in the posterior fossa, and 1 also recurred above the tentorium. All 4 received salvage chemotherapy, 1 with stem cell rescue, 2 had surgery, and 1 had tumor bed re-RT. Of 5 patients who expired, 2 died of disease progression, 2 died of other causes with no evidence of disease, and 1 died after treatment complications. At last follow-up, 17 patients are alive with no evidence of disease. Of living patients, 12 were able to live without assistance. Of 15 patients employed before treatment, only 9 remained able to work in a similar capacity. Among patients with available data, common long-term effects include executive dysfunction (nZ15), weakness/ataxia (nZ14), and depression/anxiety (nZ9). Kaplan-Meier estimates of 10-year overall survival (OS) and progression-free survival (PFS) are 80% (95% confidence interval [CI], 54%-95%) and 79% (CI, 53%-92%), respectively. Conclusion: Despite encouraging disease control in this cohort of adult MB patients, long-term effects related to therapy, including neuropsychological problems, may limit quality of life. Multimodality pediatric treatment regimens using lower RT doses may be considered to reduce treatment-related morbidity. Future studies may focus on treatment stratification based on molecular subtyping. Author Disclosure: B. De: None. K. De Braganca: None. K. Beal: Stock; Magnolia Medical Technology (MMT). M. Souweidane: Honoraria; Aesculap. S. Patel: None. S.L. Wolden: None.
Results: Baseline patient and treatment characteristics, including age, performance status, prior therapies, number of brain metastases, tumor volume, and SRS dose did not differ significantly between the groups. Acute and late toxicities are summarized in Table 1. 24 of 154 (15.6%) SRS treatments resulted in acute toxicities. Only 4 (2.6%) were grade 3-4. Of these, 2 patients developed cerebral hemorrhage, 1 cerebral edema, and 1 paresis. 14 of 91 patients (15.4%) developed late toxicities. Only 5 (5.5%) were grade 3-4, all of which were pathologically confirmed radiation necrosis. Neither acute toxicities nor late toxicities demonstrated association with ipilimumab or timing of its administration (p<0.819 and p<0.231, respectively). Conclusion: Ipilimumab was well tolerated in patients with melanoma brain metastases receiving SRS, regardless of timing of administration. We report 2.6% and 5.5% incidence of clinically significant acute and late toxicities, respectively. The combination appears to be safe for use in clinical practice. Author Disclosure: K. Diao: Employee; Loma Linda University. Research Grant; Harvard Medical School. S.X. Bian: Employee; Stanford School of Medicine. L. Ji: None. S. Groshen: None. D.M. Routman: None. C. Yu: None. N.A. Wagle: None. G. Zada: None. E.L. Chang: Honoraria; AbbVie, Elekta, Brainlab; ASCO.
2165 Radiographic Response and Edema Trajectory Following Treatment of Melanoma Brain Metastases with Stereotactic Radiosurgery and Ipilimumab Immunotherapy K. Diao,1,2 S.X. Bian,2 L. Ji,2 S. Groshen,2 D.M. Routman,3 C. Yu,2 P.E. Kim,2 N.A. Wagle,2 G. Zada,2 and E.L. Chang2; 1Harvard Medical School, Boston, MA, 2University of Southern California Keck School of Medicine, Los Angeles, CA, 3Department of Radiation Oncology, Mayo Clinic, Rochester, MN
2164 Acute and Late Toxicities in the Setting of Combination Stereotactic Radiosurgery and Ipilimumab for Patients With Melanoma Brain Metastases K. Diao,1,2 S.X. Bian,2 L. Ji,2 S. Groshen,2 D.M. Routman,3 C. Yu,2 N.A. Wagle,2 G. Zada,2 and E.L. Chang2; 1Harvard Medical School, Boston, MA, 2University of Southern California Keck School of Medicine, Los Angeles, CA, 3Department of Radiation Oncology, Mayo Clinic, Rochester, MN
Purpose/Objective(s): The trajectory of brain metastases and peritumoral edema following treatment with combination stereotactic radiosurgery (SRS) and immunotherapy is not well described. Better understanding of tumor and edema trajectory will improve clinicians’ ability to assess tumor response in this patient population. We reported imaging findings on post-Gadolinium T1weighted (post-Gd T1) and T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences after SRS in patients with melanoma brain metastases treated with or without ipilimumab. Materials/Methods: We retrospectively analyzed 56 patients with 209 brain metastases treated with SRS at our institution from 2007 to 2015. We divided lesions into three groups of ipilimumab administration: >4 weeks prior to SRS, within +/- 4 weeks of SRS, and >4 weeks after SRS or did not receive ipilimumab. The maximum diameter of each lesion and its edema was measured in post-Gd T1 and FLAIR MRI in three orthogonal planes. Volume was estimated using the validated formula: volume Z (length x width x height)/2. Tumor and edema volumes at 1.5 months, 3 months, and 6 months after SRS were compared to baseline and the percent change calculated. Statistical significance was calculated using mixed effect analysis of variance with patient effect as a random effect. Pvalues were based on permutation tests. Results: Tumor and edema trajectories following SRS are summarized in Table 1. There was a significant difference in median tumor volume change at
Purpose/Objective(s): The central nervous system (CNS) toxicity profile of combination treatment with stereotactic radiosurgery (SRS) and ipilimumab is not well defined. We compared acute and late CNS toxicities in patients receiving SRS and ipilimumab versus SRS alone with an emphasis on timing of administration of ipilimumab relative to SRS. Materials/Methods: We retrospectively reviewed 91 analyzable patients with melanoma brain metastases treated with 154 SRS procedures at our institution from 2007 to 2015. 51 patients received ipilimumab and 40 did not. The median follow-up time was 7.11 months. We divided patients into three groups of ipilimumab administration: >4 weeks prior to SRS, within +/- 4 weeks of SRS, and >4 weeks after SRS or no ipilimumab. Neurological symptoms were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03. We defined clinically significant as grade 3-4. Time to events were calculated from the date of first SRS treatment. Acute toxicities were defined as having occurred within 3 months of each SRS procedure and late toxicities were defined as having occurred after 3 months of initial SRS procedure. Significance was calculated with the Pearson chi-square test.
Abstract 2164; Table 1
Acute and Late Toxicities by Timing of Ipilimumab Maximum Grade of Toxicity
Timing of Ipilimumab Acute Toxicity >4 weeks before SRS Within 4 weeks of SRS None or >4 weeks after SRS Late Toxicity >4 weeks before SRS Within 4 weeks of SRS None or >4 weeks after SRS
1
2
3
Toxicity 4
Yes
No
Total
4 (6%) 3 (11%) 5 (8%)
4 (6%) 1 (4%) 3 (5%)
0 (0%) 1 (4%) 1 (2%)
1 (2%) 0 (0%) 1 (2%)
9 5 10
54 22 54
63 27 64
2 (9%) 0 (0%) 1 (2%)
0 (0%) 2 (8%) 4 (9%)
1 (5%) 1 (4%) 2 (4%)
0 (0%) 1 (4%) 0 (0%)
3 4 7
19 20 38
22 24 45
p-value p<0.819
p<0.231