NRG-RTOG 1106/ACRIN 6697: A phase IIR trial of standard versus adaptive (mid-treatment PET-based) chemoradiotherapy for stage III NSCLC—Results and comparison to NRG-RTOG 0617 (non-personalized RT dose escalation).

8548 Background: NRG-RTOG 0617 (R0617) found that non-personalized dose escalation of radiotherapy (RT) with concurrent chemotherapy was deleterious. NRG-RTOG 1106/ACRIN 6697 (R1106) studied adaptive chemoradiotherapy, using tumor and patient individualized RT dose intensification simultaneously with field reduction, based upon mid-treatment FDG-PET. Methods: The control arms of both studies used 60 Gy (+ weekly carboplatin/paclitaxel). The investigational arm of R0617 used 74 Gy in 37 fractions, with no field/dose adaptation, while R1106 used mid-treatment FDG-PET (after ̃40 Gy) to design an individualized dose adaptive RT plan with daily-fraction size 2.2 to 3.8 Gy (up to 80.4 Gy/30 fractions), based upon a model of isotoxic lung risk. Nearly all (93%) patients had IMRT. No patients had consolidation immunotherapy. The primary endpoint for R1106 was local-regional-progression freedom (LRPF) assessed by central review. Other endpoints reported here were survival, toxicity, and institution-defined local/regional control. Results: From 2012-2017, 127 patients were enrolled to R1106 (43 in the standard and 84 in the adaptive arms), with a median follow-up of 3.6 years. The median actual RT dose in the adaptive arm was 71 Gy (Q1-Q3 68-76 Gy). The 2-year LRPF was 59.5% versus 54.6% (p=0.66) for standard versus adaptive RT; the 3-year survival rates were 49.1% versus 47.5% (p=0.80). An exploratory analysis of 2-year in-field local primary tumor control and local-regional tumor control (institution-assessed) were 58.5% and 55.6% for standard RT, and 75.6% and 66.3% for adaptive RT, respectively. As shown in the table, there were no significant differences in cardiac or esophageal adverse events between the two arms; the adaptive RT arm had more Grade 3+ respiratory events (23.8% versus 14.3%). Conclusions: NRG-RTOG1106 did not meet its primary endpoint of demonstrating improved LRPF. Unlike R0617, there was no suggestion of a detrimental effect of adaptive dose-intensified RT on survival and cardiac events. Studies to refine personalized RT, especially in the immunotherapy era, should be considered. Outcome comparison between R0617 and R1106. Clinical trial information: NCT01507428. [Table: see text]