The Feasibility of Quality Assurance in the TOPGEAR International Phase III Clinical Trial of Neoadjuvant Chemoradiotherapy for Gastric Cancer (An Intergroup Trial of the AGITG/TROG/EORTC/CCTG).

Abstract

The TOPGEAR (Trial of Preoperative Therapy for Gastric and Esophagogastric Junction Adenocarcinoma) international phase III trial hypothesized that adding preoperative chemoradiation (CRT) to perioperative chemotherapy will improve survival in patients (pts) with gastric cancer. Owing to the complexity of gastric irradiation, a comprehensive radiation therapy quality assurance (RTQA) program was implemented. The objective of this report is to describe the RTQA methods and outcomes. RTQA was undertaken in 'real time' prior to treatment for the first 5 pts randomized to CRT from each center. Once acceptable quality was achieved, RTQA was completed for one third of subsequent cases. RTQA consisted of evaluating the following parameters: 1) clinical target volume (CTV) and organ-at-risk (OAR) contouring; 2) RT planning parameters (CT simulation, dose prescription/planning technique, per-protocol planning constraints). Protocol violations between high- (defined as 20+ pts enrolled) and low-volume centers were compared using Fisher's exact test. As of December 2020, 554 pts from 70 centers were enrolled. In total, 277 were randomized to receive RT and 196 (71%) were included for RTQA; of these, 57 (29%) and 139 (71%) were from high- and low-volume centers, respectively. The initial RTQA pass rate was 72% (n = 141). There was no significant difference in the initial pass rate between the high- and low-volume centers (79% vs 69%; P = 0.22) For the 55 cases requiring resubmission, detailed feedback was provided, and most cases had multiple protocol violations. At least one aspect of the CTV had to be adjusted in 49/55 (89%) cases with inadequate coverage of the duodenum down to the 3rd part most commonly seen (n = 28/55, 51%). Table 1 summarizes CTV contouring protocol violations. OARs were generally appropriately contoured with five (9%) cases requiring adjustment. Two cases failed RTQA due to treatment planning violations (kidney dose, lung dose) in absence of contouring (CTV, OAR) concerns. Following resubmission, 192 (98%) passed RTQA and four (2%) required a second resubmission. In a large multicenter trial RTQA is feasible and effective in achieving high quality RT treatment plans. Ongoing education and audits should be performed to ensure consistent quality of treatment plans over the study period.