Elizabeth M Gore1, Chen Hu2, Alexander Y Sun3, Daniel F Grimm4, Suresh S Ramalingam5, Neal E Dunlap6, Kristin A Higgins5, Maria Werner-Wasik7, Aaron M Allen8, Puneeth Iyengar9, Gregory M M Videtic10, Russell K Hales11, Ronald C McGarry12, James J Urbanic13, Anthony T Pu14, Candice A Johnstone15, Volker W Stieber16, Rebecca Paulus17, Jeffrey D Bradley18. 1. Froedtert and the Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: egore@mcw.edu. 2. NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania; Johns Hopkins University, Baltimore, Maryland. 3. University Health Network-Princess Margaret Hospital, Toronto, Ontario, Canada. 4. Zablocki Veterans Administration Medical Center, Milwaukee, Wisconsin. 5. Emory University/Winship Cancer Institute, Atlanta, Georgia. 6. James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky. 7. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. 8. Rabin Medical Center, Petah Tikva, Israel. 9. University of Texas Southwestern Medical Center, Dallas, Texas. 10. Cleveland Clinic Foundation, Cleveland, Ohio. 11. Johns Hopkins University, Baltimore, Maryland. 12. University of Kentucky, Lexington, Kentucky. 13. University of California San Diego Moores Cancer Center, La Jolla, California. 14. Sutter Cancer Research Consortium, Sacramento, California. 15. Froedtert and the Medical College of Wisconsin, Milwaukee, Wisconsin. 16. Novant Health Forsyth Medical Center Accruals for Southeast Clinical Oncology Research Consortium NCI Community Oncology Research Program, Goldsboro, North Carolina. 17. NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania. 18. Washington University, St. Louis, Missouri.
Abstract
INTRODUCTION: NRG Oncology RTOG 0937 is a randomized phase II trial evaluating 1-year overall survival (OS) with prophylactic cranial irradiation (PCI) or PCI plus consolidative radiation therapy (PCI+cRT) to intrathoracic disease and extracranial metastases for extensive-disease SCLC. METHODS:Patients with one to four extracranial metastases were eligible after a complete response or partial response to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included partial response versus complete response after chemotherapy and one versus two to four metastases; age younger than 65 years versus 65 years or older was added after an observed imbalance. PCI consisted of 25 Gy in 10 fractions. cRT consisted of 45 Gy in 15 fractions. To detect an improvement in OS from 30% to 45% with a 34% hazard reduction (hazard ratio = 0.66) under a 0.1 type 1 error (one sided) and 80% power, 154 patients were required. RESULTS: A total of 97 patients were randomized between March 2010 and February 2015. Eleven patients were ineligible (nine in the PCI group and two in the PCI+cRT group), leaving 42 randomized to receivePCI and 44 to receive PCI+cRT. At planned interim analysis, the study crossed the futility boundary for OS and was closed before meeting the accrual target. Median follow-up was 9 months. The 1-year OS was not different between the groups: 60.1% (95% confidence interval [CI]: 41.2-74.7) for PCI and 50.8% (95% CI: 34.0-65.3) for PCI+cRT (p = 0.21). The 3- and 12-month rates of progression were 53.3% and 79.6% for PCI and 14.5% and 75% for PCI+cRT, respectively. Time to progression favored PCI+cRT (hazard ratio = 0.53, 95% CI: 0.32-0.87, p = 0.01). One patient in each arm had grade 4 therapy-related toxicity and one had grade 5 therapy-related pneumonitis with PCI+cRT. CONCLUSIONS: OS exceeded predictions for both arms. cRT delayed progression but did not improve 1-year OS. Published by Elsevier Inc.
RCT Entities:
INTRODUCTION: NRG Oncology RTOG 0937 is a randomized phase II trial evaluating 1-year overall survival (OS) with prophylactic cranial irradiation (PCI) or PCI plus consolidative radiation therapy (PCI+cRT) to intrathoracic disease and extracranial metastases for extensive-disease SCLC. METHODS:Patients with one to four extracranial metastases were eligible after a complete response or partial response to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included partial response versus complete response after chemotherapy and one versus two to four metastases; age younger than 65 years versus 65 years or older was added after an observed imbalance. PCI consisted of 25 Gy in 10 fractions. cRT consisted of 45 Gy in 15 fractions. To detect an improvement in OS from 30% to 45% with a 34% hazard reduction (hazard ratio = 0.66) under a 0.1 type 1 error (one sided) and 80% power, 154 patients were required. RESULTS: A total of 97 patients were randomized between March 2010 and February 2015. Eleven patients were ineligible (nine in the PCI group and two in the PCI+cRT group), leaving 42 randomized to receive PCI and 44 to receive PCI+cRT. At planned interim analysis, the study crossed the futility boundary for OS and was closed before meeting the accrual target. Median follow-up was 9 months. The 1-year OS was not different between the groups: 60.1% (95% confidence interval [CI]: 41.2-74.7) for PCI and 50.8% (95% CI: 34.0-65.3) for PCI+cRT (p = 0.21). The 3- and 12-month rates of progression were 53.3% and 79.6% for PCI and 14.5% and 75% for PCI+cRT, respectively. Time to progression favored PCI+cRT (hazard ratio = 0.53, 95% CI: 0.32-0.87, p = 0.01). One patient in each arm had grade 4 therapy-related toxicity and one had grade 5 therapy-related pneumonitis with PCI+cRT. CONCLUSIONS:OS exceeded predictions for both arms. cRT delayed progression but did not improve 1-year OS. Published by Elsevier Inc.
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