TY - JOUR
T1 - Safety and efficacy of a five-fraction stereotactic body radiotherapy schedule for centrally located non–small-cell lung cancer
T2 - NRG Oncology/RTOG 0813 trial
AU - Bezjak, Andrea
AU - Paulus, Rebecca
AU - Gaspar, Laurie E.
AU - Timmerman, Robert D.
AU - Straube, William L.
AU - Ryan, William F.
AU - Garces, Yolanda I.
AU - Pu, Anthony T.
AU - Singh, Anurag K.
AU - Videtic, Gregory M.
AU - McGarry, Ronald C.
AU - Iyengar, Puneeth
AU - Pantarotto, Jason R.
AU - Urbanic, James J.
AU - Sun, Alexander Y.
AU - Daly, Megan E.
AU - Grills, Inga S.
AU - Sperduto, Paul
AU - Normolle, Daniel P.
AU - Bradley, Jeffrey D.
AU - Choy, Hak
N1 - Funding Information:
Supported by National Cancer Institute grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology Statistics and Data Management Center), UG1CA189867 (National Cancer Institute Community Oncology Research Program), U24CA180803 (Imaging and Radiation Oncology Core), P30CA047904 (University of Pittsburgh Medical Center Hillman Cancer Center).
Publisher Copyright:
Copyright © 2019 American Society of Clinical Oncology. All rights reserved.
PY - 2019/5/20
Y1 - 2019/5/20
N2 - PURPOSE Patients with centrally located early-stage non–small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC. MATERIALS AND METHODS Medically inoperable patients with biopsy-proven, positron emission tomography–staged T1 to 2 (# 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it. RESULTS One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively. CONCLUSION The MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.
AB - PURPOSE Patients with centrally located early-stage non–small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC. MATERIALS AND METHODS Medically inoperable patients with biopsy-proven, positron emission tomography–staged T1 to 2 (# 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it. RESULTS One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively. CONCLUSION The MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.
UR - http://www.scopus.com/inward/record.url?scp=85066163705&partnerID=8YFLogxK
U2 - 10.1200/JCO.18.00622
DO - 10.1200/JCO.18.00622
M3 - Article
C2 - 30943123
AN - SCOPUS:85066163705
SN - 0732-183X
VL - 37
SP - 1316
EP - 1325
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 15
ER -