Primary Results of NRG-RTOG1106/ECOG-ACRIN 6697: A Randomized Phase II Trial of Individualized Adaptive (chemo)Radiotherapy Using Midtreatment ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Stage III Non-Small Cell Lung Cancer.

Abstract

NRG-RTOG0617 demonstrated a detrimental effect of uniform high-dose radiation in stage III non-small cell lung cancer. NRG-RTOG1106/ECOG-ACRIN6697 (ClinicalTrials.gov identifier: NCT01507428), a randomized phase II trial, studied whether midtreatment ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can guide individualized/adaptive dose-intensified radiotherapy (RT) to improve and predict outcomes in patients with this disease. Patients fit for concurrent chemoradiation were randomly assigned (1:2) to standard (60 Gy/30 fractions) or FDG-PET-guided adaptive treatment, stratified by substage, primary tumor size, and histology. All patients had midtreatment FDG-PET/CT; adaptive arm patients had an individualized, intensified boost RT dose to residual metabolically active areas. The primary therapeutic end point was 2-year centrally reviewed freedom from local-regional progression (FFLP), defined as no progression in or near the planning target volume and/or regional nodes. FFLP was analyzed on a modified intent-to-treat population at a one-sided <i>Z</i>-test significance level of 0.15. The primary imaging end point was centrally reviewed change in SUV_peak from baseline to midtreatment; its association with FFLP was assessed using the two-sided Wald test on the basis of Cox regression. Of 138 patients enrolled, 127 were eligible. Adaptive-arm patients received a mean 71 Gy in 30 fractions, with mean lung dose 17.9 Gy. There was no significant difference in centrally reviewed 2-year FFLP (59.5% and 54.6% in standard and adaptive arms; <i>P</i> = .66). There were no significant differences in protocol-specified grade 3 toxicities, survival, or progression-free survival (<i>P</i> > .4). Median SUV_peak and metabolic tumor volume (MTV) in the adaptive arm decreased 49% and 54%, from pre-RT to mid-RT PET. However, ΔSUV_peak and ΔMTV were not associated with FFLP (hazard ratios, 0.997; <i>P</i> = .395 and .461). Midtreatment PET-adapted RT dose escalation as given in this study was safe and feasible but did not improve efficacy outcomes.