- Email: [email protected]
RTOG 9802 and 9813
6
International Journal of Radiation Oncology Biology Physics
status 0 to 1 (84%). Most cancers were T1 (65%) and squamous cell (45%). Median follow-up was 26.6 months. There were 5 DLTs seen; the table details the protocol prespecified DLTs and the worst treatmentrelated adverse events. MTD is 12.0 Gy/fr; DLT on this arm was 7.2% (95% CI 2.8%-14.4%). Conclusion: The novel statistical design used in RTOG 0813 allowed for seamless uninterrupted accrual of pts onto successive dose-escalated cohorts, with a large number of pts contributing to DLT data. The rates of toxicity prespecified as DLT were relatively low. The highest dose level allowed by the protocol was associated with a 7.2% rate of DLT; however, there still is considerable toxicity associated with this level. A decision regarding the optimal dose to be used for centrally located cancers needs to await the efficacy analysis of the phase 2 portion of this study.
(RTOG Specimen Bank), U24CA196067 (NRG Specimen Bank), R01CA108633 (to AC), 1R01CA169368 (to AC), 1RC2CA148190 (to AC), U10CA180850-01 (to AC) from the National Cancer Institute (NCI), Brain Tumor Funders Collaborative Grant (to AC), The Ohio State University Comprehensive Cancer Center (to AC), and the Merck & Co. Trial Information: NCT00003375 (9802); NCT00004259 (9813).
LBA 11 Treatment Responses and Survival in IDH1-Mutant Grade II and III Gliomas in NRG Oncology/RTOG 9802 and 9813 E.H. Bell,1 P. Zhang,2 J.C. Buckner,3 S.M. Chang,4 A.L. Salavaggione,1 D. Brachman,5 R.J. Lee,6 A.D. Murtha,7 P.D. Brown,8 C.J. Schultz,9 S. Malone,10 M.P. Mehta,11 S.L. Pugh,2 and A. Chakravarti1; 1The Ohio State University Wexner Medical Center, Columbus, OH, 2NRG Oncology Statistics and Data Management Center, Philadelphia, PA, 3Mayo Clinic, Rochester, MN, 4UCSF Medical Center, San Francisco, CA, 5St. Joseph’s Hospital and Medical Center accruals for Arizona Oncology Services Foundation, Phoenix, AZ, 6Intermountain Medical Center, Murray, UT, 7 Cross Cancer Institute, Edmonton, AB, Canada, 8Mayo Clinic accruals for Rochester Methodist Hospital, Rochester, MN, 9Medical College of Wisconsin, Department of Radiation Oncology, Milwaukee, WI, 10The Ottawa Hospital Regional Cancer Centre, Ottawa, ON, Canada, 11 University of Maryland School of Medicine, Baltimore, MD Purpose/Objective(s): WHO grade II and III gliomas are heterogeneous both genotypically and phenotypically. Patients harboring mutant IDH gliomas have increased survival times, and multiple studies have confirmed the prognostic significance of IDH mutations. However, what has yet to be fully evaluated are the treatment effects of radiation and chemotherapy for both grade II and III gliomas that contain IDH mutations. This study sought to examine the treatment differences between adjuvant radiation therapy (RT) and adjuvant chemoradiation strategies in IDH1-mutant grade II and III gliomas. Materials/Methods: Grade II and III glioma specimens with IDH1 mutations were analyzed from Radiation Therapy Oncology Group (RTOG) 9802, a phase 3 study of RT versus RT+procarbazine, CCNU, and vincristine (PCV) in grade II gliomas and RTOG 9813, a phase 3 study of RT+temozolomide (TMZ) versus RT+nitrosourea (NU) in grade III gliomas. Mutation status was confirmed by immunohistochemistry (IDH1R132H-specific antibody). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and tested using the log-rank test. Results: Seventy-one and 49 IDH1R132H-mutant patients were analyzed for treatment differences from RTOG 9802 and 9813, respectively. In each study, the 2 treatment arms were balanced on sample size and were similar with respect to patient baseline characteristics. Most patients in both studies were <50 years old, male, with a KPS of 90 to 100, and with minor or no neurologic symptoms. For RTOG 9802, patients treated with RT+PCV demonstrated increased PFS and OS relative to patients treated with RT alone (HRZ0.32, P<.001 [PFS]; HRZ 0.42, PZ.02 [OS]). For RTOG 9813, patients treated with RT+TMZ had increased PFS times and trended toward better OS than patients treated with RT+NU (HRZ0.37, PZ.004 [PFS]; HRZ0.55, PZ.11 [OS]). Conclusion: Taken together, study results highlight the radiation and chemosensitivity of IDH1-mutant grade II and III gliomas and strongly suggests that both adjuvant radiation and chemotherapy prolong survival times in this subpopulation of glioma patients. Further research into treatment effects in molecular subgroups of grade II and III gliomas is warranted. Acknowledgment(s): This project was supported by grants U10CA21661 (RTOG-Ops-Stat), U10CA180868 (NRG Oncology Operations), U10CA 180822 (NRG Oncology SDMC), U10CA37422 (CCOP), U24CA114734
LBA 12 A Prognostic Analysis on Using the Combination of Tumor Volume and Epstein-Barr Virus DNA in Patients With Nasopharyngeal Carcinoma Treated With IMRT L. Lu,1 J. Li,2 W. Jia,3 C. Zhao,4 and T. Lu5; 1651 Dongfeng road east, Guangzhou, China, 2Sun Yat-sen University, the first affiliated hospital, guangzhou, China, 3Sun Yat-sen University, Cancer Center, Guangzhou, China, 4Sun Yat-Sen University Cancer Center, Guangzhou, China, 5Sun Yat-Sen University Cancer Center, Guang Dong Province, United States Purpose/Objective(s): To evaluate the prognostic effect of combining the assessment of tumor volume with that of Epstein-Barr virus DNA (EBV DNA) level and their impacts in the prognosis analysis in nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT). Materials/Methods: A total of 180 consecutive NPC patients who underwent IMRT were enrolled from 2006 to 2010. Pretreatment plasma EBV DNA level was quantified by a polymerase chain reaction assay. The tumor volume was delineated by IMRT planning system. Survival rates of different groups of patients segregated by tumor volume and EBV DNA level alone or by the combination of the tumor volume and EBV DNA level were compared cross-over. Results: Increased tumor volume and elevated EBV DNA levels were significantly correlated with poor disease-free, distant, and overall survival in the patients. The 5-year survival rates in patients with GTVnx (gross tumor volume of the nasopharynx) 20 cm3 and >20 cm3 were 95.1% and 70.6% (PZ.001), while in patients with GTVnd (gross tumor volume of the lymph nodes) 10 cm3 and >10 cm3 were 86.0% and 75.8% (PZ.051), respectively. The same 5-year survival in patients with EBV DNA <10,000 copies/ mL and 10,000 copies/mL were 98.6% and 67.2% (P<.001), respectively. The patients were segregated into 4 groups by combination of tumor volume and pretreatment EBV DNA level. The patients with a lower EBV DNA level showed significantly better prognosis than those with a higher EBV DNA level in same GTVnx or GTVnd groups. The results demonstrate that the accuracy of prognostic evaluation was further improved. Conclusion: Our study has, for the first time in the studies of NPC, implemented a prognostic analysis on NPC patients by using the combined variable of tumor volume and pretreatment plasma EBV DNA concentration. Patients with small tumor volume or a low plasma EBV DNA level demonstrated a better prognosis. The cross-grouping analysis in the combination of 2 factors revealed that the combination of tumor volume and EBV DNA had a better prognosis predictive value for NPC patients. It is recommended that the 2 indicators representing the tumor load can be incorporated into clinical staging of NPC so as to better guide the prognosis of patients. Late Breaking Abstract #12 Overall survival of patient subgroups with combination of tumor volume and pretreatment EBV DNA Level.
Subgroup Combination of GTVnx & EBV DNA GTVnx20 cm3, low EBV DNA GTVnx20 cm3, high EBV DNA GTVnx>20 cm3, low EBV DNA GTVnx>20 cm3, high EBV DNA Combination of GTVnd & EBV DNA GTVnd10 cm3, low EBV DNA GTVnd10 cm3, high EBV DNA GTVnd>10 cm3, low EBV DNA GTVnd>10 cm3, high EBV DNA
5-Year P No. of survival (%) 95% CI (%) value patients <.001 54 29 26 71
97.1 86.1 91.8 61.6
94.2 to 100 79.6 to 92.6 86.2 to 97.4 55.1 to 68.1
65 50 15 50
98.4 68.8 100 66.1
96.8 to 100 61.4 to 76.2 — 58.8 to 73.4
<.001
International Journal of Radiation Oncology Biology Physics
status 0 to 1 (84%). Most cancers were T1 (65%) and squamous cell (45%). Median follow-up was 26.6 months. There were 5 DLTs seen; the table details the protocol prespecified DLTs and the worst treatmentrelated adverse events. MTD is 12.0 Gy/fr; DLT on this arm was 7.2% (95% CI 2.8%-14.4%). Conclusion: The novel statistical design used in RTOG 0813 allowed for seamless uninterrupted accrual of pts onto successive dose-escalated cohorts, with a large number of pts contributing to DLT data. The rates of toxicity prespecified as DLT were relatively low. The highest dose level allowed by the protocol was associated with a 7.2% rate of DLT; however, there still is considerable toxicity associated with this level. A decision regarding the optimal dose to be used for centrally located cancers needs to await the efficacy analysis of the phase 2 portion of this study.
(RTOG Specimen Bank), U24CA196067 (NRG Specimen Bank), R01CA108633 (to AC), 1R01CA169368 (to AC), 1RC2CA148190 (to AC), U10CA180850-01 (to AC) from the National Cancer Institute (NCI), Brain Tumor Funders Collaborative Grant (to AC), The Ohio State University Comprehensive Cancer Center (to AC), and the Merck & Co. Trial Information: NCT00003375 (9802); NCT00004259 (9813).
LBA 11 Treatment Responses and Survival in IDH1-Mutant Grade II and III Gliomas in NRG Oncology/RTOG 9802 and 9813 E.H. Bell,1 P. Zhang,2 J.C. Buckner,3 S.M. Chang,4 A.L. Salavaggione,1 D. Brachman,5 R.J. Lee,6 A.D. Murtha,7 P.D. Brown,8 C.J. Schultz,9 S. Malone,10 M.P. Mehta,11 S.L. Pugh,2 and A. Chakravarti1; 1The Ohio State University Wexner Medical Center, Columbus, OH, 2NRG Oncology Statistics and Data Management Center, Philadelphia, PA, 3Mayo Clinic, Rochester, MN, 4UCSF Medical Center, San Francisco, CA, 5St. Joseph’s Hospital and Medical Center accruals for Arizona Oncology Services Foundation, Phoenix, AZ, 6Intermountain Medical Center, Murray, UT, 7 Cross Cancer Institute, Edmonton, AB, Canada, 8Mayo Clinic accruals for Rochester Methodist Hospital, Rochester, MN, 9Medical College of Wisconsin, Department of Radiation Oncology, Milwaukee, WI, 10The Ottawa Hospital Regional Cancer Centre, Ottawa, ON, Canada, 11 University of Maryland School of Medicine, Baltimore, MD Purpose/Objective(s): WHO grade II and III gliomas are heterogeneous both genotypically and phenotypically. Patients harboring mutant IDH gliomas have increased survival times, and multiple studies have confirmed the prognostic significance of IDH mutations. However, what has yet to be fully evaluated are the treatment effects of radiation and chemotherapy for both grade II and III gliomas that contain IDH mutations. This study sought to examine the treatment differences between adjuvant radiation therapy (RT) and adjuvant chemoradiation strategies in IDH1-mutant grade II and III gliomas. Materials/Methods: Grade II and III glioma specimens with IDH1 mutations were analyzed from Radiation Therapy Oncology Group (RTOG) 9802, a phase 3 study of RT versus RT+procarbazine, CCNU, and vincristine (PCV) in grade II gliomas and RTOG 9813, a phase 3 study of RT+temozolomide (TMZ) versus RT+nitrosourea (NU) in grade III gliomas. Mutation status was confirmed by immunohistochemistry (IDH1R132H-specific antibody). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and tested using the log-rank test. Results: Seventy-one and 49 IDH1R132H-mutant patients were analyzed for treatment differences from RTOG 9802 and 9813, respectively. In each study, the 2 treatment arms were balanced on sample size and were similar with respect to patient baseline characteristics. Most patients in both studies were <50 years old, male, with a KPS of 90 to 100, and with minor or no neurologic symptoms. For RTOG 9802, patients treated with RT+PCV demonstrated increased PFS and OS relative to patients treated with RT alone (HRZ0.32, P<.001 [PFS]; HRZ 0.42, PZ.02 [OS]). For RTOG 9813, patients treated with RT+TMZ had increased PFS times and trended toward better OS than patients treated with RT+NU (HRZ0.37, PZ.004 [PFS]; HRZ0.55, PZ.11 [OS]). Conclusion: Taken together, study results highlight the radiation and chemosensitivity of IDH1-mutant grade II and III gliomas and strongly suggests that both adjuvant radiation and chemotherapy prolong survival times in this subpopulation of glioma patients. Further research into treatment effects in molecular subgroups of grade II and III gliomas is warranted. Acknowledgment(s): This project was supported by grants U10CA21661 (RTOG-Ops-Stat), U10CA180868 (NRG Oncology Operations), U10CA 180822 (NRG Oncology SDMC), U10CA37422 (CCOP), U24CA114734
LBA 12 A Prognostic Analysis on Using the Combination of Tumor Volume and Epstein-Barr Virus DNA in Patients With Nasopharyngeal Carcinoma Treated With IMRT L. Lu,1 J. Li,2 W. Jia,3 C. Zhao,4 and T. Lu5; 1651 Dongfeng road east, Guangzhou, China, 2Sun Yat-sen University, the first affiliated hospital, guangzhou, China, 3Sun Yat-sen University, Cancer Center, Guangzhou, China, 4Sun Yat-Sen University Cancer Center, Guangzhou, China, 5Sun Yat-Sen University Cancer Center, Guang Dong Province, United States Purpose/Objective(s): To evaluate the prognostic effect of combining the assessment of tumor volume with that of Epstein-Barr virus DNA (EBV DNA) level and their impacts in the prognosis analysis in nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT). Materials/Methods: A total of 180 consecutive NPC patients who underwent IMRT were enrolled from 2006 to 2010. Pretreatment plasma EBV DNA level was quantified by a polymerase chain reaction assay. The tumor volume was delineated by IMRT planning system. Survival rates of different groups of patients segregated by tumor volume and EBV DNA level alone or by the combination of the tumor volume and EBV DNA level were compared cross-over. Results: Increased tumor volume and elevated EBV DNA levels were significantly correlated with poor disease-free, distant, and overall survival in the patients. The 5-year survival rates in patients with GTVnx (gross tumor volume of the nasopharynx) 20 cm3 and >20 cm3 were 95.1% and 70.6% (PZ.001), while in patients with GTVnd (gross tumor volume of the lymph nodes) 10 cm3 and >10 cm3 were 86.0% and 75.8% (PZ.051), respectively. The same 5-year survival in patients with EBV DNA <10,000 copies/ mL and 10,000 copies/mL were 98.6% and 67.2% (P<.001), respectively. The patients were segregated into 4 groups by combination of tumor volume and pretreatment EBV DNA level. The patients with a lower EBV DNA level showed significantly better prognosis than those with a higher EBV DNA level in same GTVnx or GTVnd groups. The results demonstrate that the accuracy of prognostic evaluation was further improved. Conclusion: Our study has, for the first time in the studies of NPC, implemented a prognostic analysis on NPC patients by using the combined variable of tumor volume and pretreatment plasma EBV DNA concentration. Patients with small tumor volume or a low plasma EBV DNA level demonstrated a better prognosis. The cross-grouping analysis in the combination of 2 factors revealed that the combination of tumor volume and EBV DNA had a better prognosis predictive value for NPC patients. It is recommended that the 2 indicators representing the tumor load can be incorporated into clinical staging of NPC so as to better guide the prognosis of patients. Late Breaking Abstract #12 Overall survival of patient subgroups with combination of tumor volume and pretreatment EBV DNA Level.
Subgroup Combination of GTVnx & EBV DNA GTVnx20 cm3, low EBV DNA GTVnx20 cm3, high EBV DNA GTVnx>20 cm3, low EBV DNA GTVnx>20 cm3, high EBV DNA Combination of GTVnd & EBV DNA GTVnd10 cm3, low EBV DNA GTVnd10 cm3, high EBV DNA GTVnd>10 cm3, low EBV DNA GTVnd>10 cm3, high EBV DNA
5-Year P No. of survival (%) 95% CI (%) value patients <.001 54 29 26 71
97.1 86.1 91.8 61.6
94.2 to 100 79.6 to 92.6 86.2 to 97.4 55.1 to 68.1
65 50 15 50
98.4 68.8 100 66.1
96.8 to 100 61.4 to 76.2 — 58.8 to 73.4
<.001