Investigation of Relation of Radiation Therapy Quality With Toxicity and Survival in LAP07 Phase 3 Trial for Locally Advanced Pancreatic Carcinoma.

Abstract Purpose The XXXXX multicenter randomized study assessed whether chemoradiotherapy (CRT) increases overall survival (OS) versus continuation chemotherapy in patients whose locally advanced pancreatic cancer (LAPC) was controlled after 4 months of induction chemotherapy. This analysis investigated whether failure to adhere to radiation therapy (RT) guidelines influenced survival and toxicity. Methods and Materials This is a planned analysis of secondary objectives in the framework of a randomized international phase III trial. The protocol included detailed written RT guidelines. All participating institutions undertook an initial benchmark case to check adherence to protocol guidelines. Centers with major deviation were not allowed to include patients until they achieved a significant improvement and rigorously followed the guidelines. On-trial RT quality assurance (RTQA) consisted of a central review of treatment plan with dose-volume histograms for each patient. Adherence to guidelines was graded as per protocol (PP), minor deviation (MiD), or major deviation (MaD). Results Fifty-seven benchmark cases were evaluated, 26% were classified as PP, 60% MiD, and 14% MaD. Among the 442 included patients, 133 patients were randomized in the CRT arm and 117 were assessable for RT quality analysis. RT quality was graded as PP in 38.5% of patients, MiD in 43.6% of patients, and MaD in 17.9% of patients. Most frequent protocol violations were dose distribution heterogeneities. Median overall survival was 17 months with PP and MiD versus 13.4 months with MaD (HR 1.63; [95% CI, 0.99-2.71]; P=.055). There was no difference in terms of progression free survival (HR: 1.09 [95% CI ; 0.66-1.8] p=0.72). Patients with MaD had more nausea than patients treated PP or with MiD (P=0.0045). Conclusions MaD was associated with a trend for worst survival. There was no difference in terms of progression free survival. Due to the low rate of major deviations, their impact on the XXX trial results may be negligeable.