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Novel Recursive Partitioning Analysis Classification for Newly Diagnosed Glioblastoma: A Multi-institutional Study Highlighting the MGMT Promoter Methylation and IDH1 Gene Mutation Status
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Volume 99 Number 2S Supplement 2017 (nZ18) and immunotherapy (nZ3) comprised 36% of the dataset. 19 radiographic local failure events were observed with a median time to failure of 9.2 months (range, 1-40 months). A unique clinically actionable mutation was observed in 16 of 58 (29%) of brain metastases not detected in the clinically sampled primary tumor. Conclusion: Clinically actionable mutation status is associated with local control following radiation therapy for brain metastases. Prospective trials involving patients with genetically characterized brain metastases treated with targeted therapeutic strategies in combination with radiation are needed. Author Disclosure: J. Voog: None. P. Brastianos: None. J.S. Loeffler: Employee; Harvard Medical School. H.A. Shih: Employee; Dartmouth Hitchcock. Honoraria; International Journal of Radiation Oncology, UpToDate. Advisory Board; Genentech. clinical operarions director; MGH Proton Therapy Center. clinical operational leader; Massachusetts General Hospital. editor; International Journal of Radiation Oncology. hospital site residency program director; Harv. K.S. Oh: Research Grant; Elekta, Merck & Co., Inc.. Review and create questions for CME section of journal; IJROBP.
2274 Practice Patterns and Survival Outcomes of Intracranial Germinoma: An Analysis of the National Cancer Database W.G.A. Wang, H. Ye, and P. Chinnaiyan; Beaumont Health, Royal Oak, MI Purpose/Objective(s): To examine the practice pattern and survival outcome of patient with intracranial germinoma by analyzing the National Cancer Database (NCDB). Materials/Methods: Patients from the NCDB brain tumor registry between the years 2004-2014 with intracranial germinoma were extracted for analysis. The patient demographics and treatments received were examined and survival data was analyzed. Patients who had distant metastasis, received no treatments, or only surgery/chemotherapy alone were excluded from the survival analysis. An age cutoff of >21 years old was used to define the pediatric population. Patients were separated into the treatment groups of radiation therapy alone (RT) and chemotherapy followed by radiation therapy (C+RT) and survival outcome was analyzed. Results: 551 patients with intracranial germinoma meeting our inclusion criteria were identified in the NCDB. The median age was 18.4 years old and 67.2% of the patients were male. 382 patients were pediatric patients and 169 were adults. Of the adult patients, 65.7% received RT and 34.3% received C+RT, compared to the pediatric patients, where 31.8% received RT and 68.2% received C+RT. The median adult radiation dose was 4500 cGy and 3600 cGy for the pediatric patients (p<0.001). Those patients who received C+RT had a lower radiation dose compared to the RT group (p<0.001). African American patients and those with private insurance were more likely to receive RT alone. Cut point analysis showed no significant trends in the use of RT vs C+RT over the years. The 5 and 10 year overall survival (OS) for the entire cohort was 92.6% and 87.9%, respectively. Univariate analysis demonstrated improved OS with younger age, private insurance, C+RT treatment, and pediatric patients. Only age and insurance type remained significant on multivariate analysis. The 5 year OS was 92.6% (RT) vs 97.2% (C+RT) (pZ0.307) and 83.4% (RT) vs 95.4% (C+RT) (pZ0.122) in the pediatric and adult patients, respectively. Conclusion: There is a higher use of C+RT with an accompanied reduction in RT dose in the treatment of intracranial germinoma in the pediatric population. There is no difference in survival between the treatment approaches of RT or C+RT in the NCDB patient cohort. Author Disclosure: W.A. Wang: None. H. Ye: None. P. Chinnaiyan: None.
2275 Novel Recursive Partitioning Analysis Classification for Newly Diagnosed Glioblastoma: A Multi-institutional Study Highlighting the MGMT Promoter Methylation and IDH1 Gene Mutation Status C.W. Wee,1 E. Kim,1 I.H. Kim,2 I.A. Kim,3 N. Kim,4 and C.O. Suh5; 1 Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea, Republic of (South), 2Department of Radiation
Oncology, Seoul National University Hospital, Seoul, Korea, Republic of (South), 3Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea, Republic of (South), 4 Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul, Korea, Republic of (South), 5Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea, Republic of (South) Purpose/Objective(s): To refine the recursive partitioning analysis (RPA) classification for glioblastoma incorporating the MGMT methylation and IDH1 mutation status. Materials/Methods: Three-hundred forty patients were treated with radiotherapy plus concurrent and adjuvant temozolomide in three tertiary-referral hospitals. MGMT methylation and IDH1 mutation status were available in all patients. Methylation of the MGMT (MGMTmeth) and mutation of IDH1 (IDH1mut) were observed in 42.4% and 6.2% of the patients, respectively. Results: The median follow-up for survivors and all patients were 33.2 and 20.5 months, respectively. The median survival (MS) was 23.6 months. RPA was performed on behalf of the results of the Cox proportional hazards model. MGMT methylation generated the initial partition (MGMTmeth vs. MGMTunmeth) in the RPA. Three final RPA classes were identified; class I Z MGMTmeth/IDH1mut or MGMTmeth/IDH1wt/GTR/ KPS90 (MS, 67.2 months); class II Z MGMTmeth/IDH1wt/GTR/ KPS<90, MGMTmeth/IDH1wt/residual disease, MGMTunmeth/age<50, or MGMTunmeth/age50/GTR (MS, 24.0 months); class III Z MGMTunmeth/age50/residual disease (MS, 15.2 months). Conclusion: A novel RPA classification for glioblastoma was formulated highlighting the impact of MGMTmeth and IDH1mut in the temozolomide era. This model integrating pertinent molecular information can be used effectively for the patient stratification in future clinical trials. An external validation is ongoing. Author Disclosure: C. Wee: None. E. Kim: None. I. Kim: None. I. Kim: None. N. Kim: None. C. Suh: None.
2276 Improved Survival and Intracranial Control Associated With Radiation Necrosis After Ipilimumab and Stereotactic Radiosurgery for Melanoma Brain Metastases A. Wild,1 A.P. Kiess,2 T.J. Yang,3 E.S. Weg,1 Z.A. Kohutek,1 J.D. Wolchok,1 M.A. Postow,1 V.S. Tabar,1 C.W. Brennan,1 T.A. Chan,1 Y. Yamada,3 and K. Beal1; 1Memorial Sloan Kettering Cancer Center, New York, NY, 2Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 3 MSKCC, New York, NY Purpose/Objective(s): Ipilimumab (IPI), a monoclonal antibody against CTLA-4, improves survival in patients with metastatic melanoma. However, intracranial response to IPI is modest at <25%. Thus, IPI often is combined with stereotactic radiosurgery (SRS) to optimize control of melanoma brain metastases (BM). Radiation necrosis (RN) is a common side effect following SRS. We observed an interesting clinical pattern of RN in patients treated with IPI and SRS and sought to investigate the prognostic significance of RN following SRS and IPI, postulating that RN for these patients might represent an enhanced or amplified inflammatory response. Materials/Methods: Records of patients with melanoma BM from 20052012 were reviewed to identify patients treated with both IPI and singlefraction SRS. 46 patients underwent SRS either before (41%), during (33%), or after (26%) IPI to a median dose of 21 Gy (range, 15-24 Gy). IPI was given as 3 (54%) or 10 (46%) mg/kg for a median of 4 doses (range, 1-21). Univariate Cox regression was used to assess for associations between overall survival (OS) and RN as well as established clinical prognostic factors. A multivariate proportional hazards model for OS was constructed. To avoid an immortal time bias due to time-dependence of RN, a landmark approach was used to analyze OS in which only patients surviving for longer than the median time from SRS to RN (9.0 mo) were included (nZ27). Results: Median followup was 10.0 mo (IQR, 6.0-26.1) from SRS for all patients and 21.4 mo (IQR, 13.8-65.7) for patients included in the
Volume 99 Number 2S Supplement 2017 (nZ18) and immunotherapy (nZ3) comprised 36% of the dataset. 19 radiographic local failure events were observed with a median time to failure of 9.2 months (range, 1-40 months). A unique clinically actionable mutation was observed in 16 of 58 (29%) of brain metastases not detected in the clinically sampled primary tumor. Conclusion: Clinically actionable mutation status is associated with local control following radiation therapy for brain metastases. Prospective trials involving patients with genetically characterized brain metastases treated with targeted therapeutic strategies in combination with radiation are needed. Author Disclosure: J. Voog: None. P. Brastianos: None. J.S. Loeffler: Employee; Harvard Medical School. H.A. Shih: Employee; Dartmouth Hitchcock. Honoraria; International Journal of Radiation Oncology, UpToDate. Advisory Board; Genentech. clinical operarions director; MGH Proton Therapy Center. clinical operational leader; Massachusetts General Hospital. editor; International Journal of Radiation Oncology. hospital site residency program director; Harv. K.S. Oh: Research Grant; Elekta, Merck & Co., Inc.. Review and create questions for CME section of journal; IJROBP.
2274 Practice Patterns and Survival Outcomes of Intracranial Germinoma: An Analysis of the National Cancer Database W.G.A. Wang, H. Ye, and P. Chinnaiyan; Beaumont Health, Royal Oak, MI Purpose/Objective(s): To examine the practice pattern and survival outcome of patient with intracranial germinoma by analyzing the National Cancer Database (NCDB). Materials/Methods: Patients from the NCDB brain tumor registry between the years 2004-2014 with intracranial germinoma were extracted for analysis. The patient demographics and treatments received were examined and survival data was analyzed. Patients who had distant metastasis, received no treatments, or only surgery/chemotherapy alone were excluded from the survival analysis. An age cutoff of >21 years old was used to define the pediatric population. Patients were separated into the treatment groups of radiation therapy alone (RT) and chemotherapy followed by radiation therapy (C+RT) and survival outcome was analyzed. Results: 551 patients with intracranial germinoma meeting our inclusion criteria were identified in the NCDB. The median age was 18.4 years old and 67.2% of the patients were male. 382 patients were pediatric patients and 169 were adults. Of the adult patients, 65.7% received RT and 34.3% received C+RT, compared to the pediatric patients, where 31.8% received RT and 68.2% received C+RT. The median adult radiation dose was 4500 cGy and 3600 cGy for the pediatric patients (p<0.001). Those patients who received C+RT had a lower radiation dose compared to the RT group (p<0.001). African American patients and those with private insurance were more likely to receive RT alone. Cut point analysis showed no significant trends in the use of RT vs C+RT over the years. The 5 and 10 year overall survival (OS) for the entire cohort was 92.6% and 87.9%, respectively. Univariate analysis demonstrated improved OS with younger age, private insurance, C+RT treatment, and pediatric patients. Only age and insurance type remained significant on multivariate analysis. The 5 year OS was 92.6% (RT) vs 97.2% (C+RT) (pZ0.307) and 83.4% (RT) vs 95.4% (C+RT) (pZ0.122) in the pediatric and adult patients, respectively. Conclusion: There is a higher use of C+RT with an accompanied reduction in RT dose in the treatment of intracranial germinoma in the pediatric population. There is no difference in survival between the treatment approaches of RT or C+RT in the NCDB patient cohort. Author Disclosure: W.A. Wang: None. H. Ye: None. P. Chinnaiyan: None.
2275 Novel Recursive Partitioning Analysis Classification for Newly Diagnosed Glioblastoma: A Multi-institutional Study Highlighting the MGMT Promoter Methylation and IDH1 Gene Mutation Status C.W. Wee,1 E. Kim,1 I.H. Kim,2 I.A. Kim,3 N. Kim,4 and C.O. Suh5; 1 Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea, Republic of (South), 2Department of Radiation
Oncology, Seoul National University Hospital, Seoul, Korea, Republic of (South), 3Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea, Republic of (South), 4 Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul, Korea, Republic of (South), 5Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea, Republic of (South) Purpose/Objective(s): To refine the recursive partitioning analysis (RPA) classification for glioblastoma incorporating the MGMT methylation and IDH1 mutation status. Materials/Methods: Three-hundred forty patients were treated with radiotherapy plus concurrent and adjuvant temozolomide in three tertiary-referral hospitals. MGMT methylation and IDH1 mutation status were available in all patients. Methylation of the MGMT (MGMTmeth) and mutation of IDH1 (IDH1mut) were observed in 42.4% and 6.2% of the patients, respectively. Results: The median follow-up for survivors and all patients were 33.2 and 20.5 months, respectively. The median survival (MS) was 23.6 months. RPA was performed on behalf of the results of the Cox proportional hazards model. MGMT methylation generated the initial partition (MGMTmeth vs. MGMTunmeth) in the RPA. Three final RPA classes were identified; class I Z MGMTmeth/IDH1mut or MGMTmeth/IDH1wt/GTR/ KPS90 (MS, 67.2 months); class II Z MGMTmeth/IDH1wt/GTR/ KPS<90, MGMTmeth/IDH1wt/residual disease, MGMTunmeth/age<50, or MGMTunmeth/age50/GTR (MS, 24.0 months); class III Z MGMTunmeth/age50/residual disease (MS, 15.2 months). Conclusion: A novel RPA classification for glioblastoma was formulated highlighting the impact of MGMTmeth and IDH1mut in the temozolomide era. This model integrating pertinent molecular information can be used effectively for the patient stratification in future clinical trials. An external validation is ongoing. Author Disclosure: C. Wee: None. E. Kim: None. I. Kim: None. I. Kim: None. N. Kim: None. C. Suh: None.
2276 Improved Survival and Intracranial Control Associated With Radiation Necrosis After Ipilimumab and Stereotactic Radiosurgery for Melanoma Brain Metastases A. Wild,1 A.P. Kiess,2 T.J. Yang,3 E.S. Weg,1 Z.A. Kohutek,1 J.D. Wolchok,1 M.A. Postow,1 V.S. Tabar,1 C.W. Brennan,1 T.A. Chan,1 Y. Yamada,3 and K. Beal1; 1Memorial Sloan Kettering Cancer Center, New York, NY, 2Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 3 MSKCC, New York, NY Purpose/Objective(s): Ipilimumab (IPI), a monoclonal antibody against CTLA-4, improves survival in patients with metastatic melanoma. However, intracranial response to IPI is modest at <25%. Thus, IPI often is combined with stereotactic radiosurgery (SRS) to optimize control of melanoma brain metastases (BM). Radiation necrosis (RN) is a common side effect following SRS. We observed an interesting clinical pattern of RN in patients treated with IPI and SRS and sought to investigate the prognostic significance of RN following SRS and IPI, postulating that RN for these patients might represent an enhanced or amplified inflammatory response. Materials/Methods: Records of patients with melanoma BM from 20052012 were reviewed to identify patients treated with both IPI and singlefraction SRS. 46 patients underwent SRS either before (41%), during (33%), or after (26%) IPI to a median dose of 21 Gy (range, 15-24 Gy). IPI was given as 3 (54%) or 10 (46%) mg/kg for a median of 4 doses (range, 1-21). Univariate Cox regression was used to assess for associations between overall survival (OS) and RN as well as established clinical prognostic factors. A multivariate proportional hazards model for OS was constructed. To avoid an immortal time bias due to time-dependence of RN, a landmark approach was used to analyze OS in which only patients surviving for longer than the median time from SRS to RN (9.0 mo) were included (nZ27). Results: Median followup was 10.0 mo (IQR, 6.0-26.1) from SRS for all patients and 21.4 mo (IQR, 13.8-65.7) for patients included in the