The NRG Oncology and the American College of Radiology Network (ACRIN) multicenter, phase II trial, NRG-RTOG 1106/ACRIN 6697, is the first randomized trial to demonstrate the feasibility and safety of performing adaptive radiotherapy (RT) escalation in patients with locally advanced non-small cell lung cancer (NSCLC). The improvement of in-field tumor control appeared similar to the level (1% improvement with 1Gy dose escalation) of the single institutional study of adaptive radiotherapy performed at University of Michigan, and different from that of RTOG617 with non-adaptive high dose radiation in stage III NSCLC. The results were presented at the virtual edition of the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer, Singapore.
The NRG Oncology randomized phase III trial NRG-RTOG 0617 offered the insight that a higher dose of radiotherapy delivered with chemoradiotherapy actually worsened tumor control and survival for this patient population. NRG-RTOG 1106/ACRIN 6697 was designed to bridge this treatment gap by testing adaptive radiotherapy dose escalation with chemotherapy to see if this treatment could enhance two-year local-regional tumor control compared to the 60 Gy standard dose of radiotherapy this patient population typically receives. The use of fluorodeoxyglucose-positron emission tomography (FDG-PET/CT) imaging would help identify resistant aggressive tumor identified mid-treatment and adapt personalized treatment plans per each individual’s tolerance.
Patients with Stage III NSCLC were randomly assigned in a 2:1 ratio to receive either the standard radiotherapy at 60 Gy (Standard Arm) or the adaptive radiotherapy treatment that resulted in a median dose escalation of 11 Gy (Adaptive Arm). Patients on both treatment arms received FDG-PET/CT imaging at mid-treatment for radiation. The Standard Arm included 43 eligible patients whereas the Adaptive Arm included 84 eligible patients. The Standard Arm had a median follow up of 3.7 years for surviving patients with acceptable overall radiotherapy compliance rates (92.9% and 50% per protocol). The 2-year overall local-regional progression free rate was 59.5% (95% CI: 37.9, 75.7). Median local-regional progression free time was 27.5 months (95% CI: 14.3, not reached) in the Standard Arm. The Adaptive Arm had a median follow up of 3.4 years for surviving patients with acceptable overall radiotherapy compliance rates (95.8% for the initial course of treatment and 32.4% for adaptive course per protocol) and 2-year overall local-regional progression free rates were 54.6% (95% CI: 39.9, 67.0). Median local-regional progression free time was 28.4 months (95% CI: 19.1, not reached) in the Adaptive Arm. There were no significant differences in grade 3 or worse toxicity of lung, esophagus, and heart or overall survival, progression-free survival, and lung cancer specific survival between treatment arms. Adaptive radiotherapy did increase in-field local-regional tumor control by 11% and in-field primary tumor control by 17% during the trial.
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