Radiation Therapy Quality Assurance Analysis of Alliance A021501: Preoperative mFOLFIRINOX or mFOLFIRINOX Plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Pancreas

Abstract

Purpose: Alliance A021501 is the first randomized trial to evaluate stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemotherapy. In this post hoc study, we reviewed the quality of radiation therapy (RT) delivered.

Methods and materials: SBRT (6.6 Gy × 5) was intended but hypofractionated RT (5 Gy × 5) was permitted if SBRT specifications could not be met. Institutional credentialing through the National Cancer Institute-funded Imaging and Radiation Oncology Core (IROC) was required. Rigorous RT quality assurance (RT QA) was mandated, including pretreatment review by a radiation oncologist. Revisions were required for unacceptable deviations. Additionally, we performed a post hoc RT QA analysis in which contours and plans were reviewed by 3 radiation oncologists and assigned a score (1, 2, or 3) based on adequacy. A score of 1 indicated no deviation, 2 indicated minor deviation, and 3 indicated a major deviation that could be clinically significant. Clinical outcomes were compared by treatment modality and by case score.

Results: Forty patients were registered to receive RT (1 planned but not treated) at 27 centers (18 academic and 9 community). Twenty-three centers were appropriately credentialed for moving lung/liver targets and 4 for static head and neck only. Thirty-two of 39 patients (82.1%) were treated with SBRT and 7 (17.9%) with hypofractionated RT. Five cases (13%) required revision before treatment. On post hoc review, 23 patients (59.0%) were noted to have suboptimal contours or plan coverage, 12 (30.8%) were scored a 2, and 11 (28.2%) were scored a 3. There were no apparent differences in failure patterns or surgical outcomes based on treatment technique or post hoc case score. Details related to on-treatment imaging were not recorded.

Conclusions: Despite rigorous QA, we encountered variability in simulation, contouring, plan coverage, and dose on trial. Although clinical outcomes did not appear to have been affected, findings from this analysis serve to inform subsequent PDAC SBRT trial designs and QA requirements.

Figure 1:

Alliance A021501 Trial Schema Abbreviations: BLR, borderline resectable; PDAC, pancreatic ductal adenocarcinoma; IROC, Imaging and Radiation Oncology Core; FOLFIRINOX, leucovorin, fluorouracil, irinotecan, oxaliplatin; RT, radiation therapy

Figure 2:

Example of each case score for target contours. Panel 2A depicts a case scored as 1 due to appropriate inclusion of the SMV within the tumor-vessel interface contour. Panel 2B depicts a case scored as 2 due to partial omission of the SMV posteriorly. Panel 2C depicts a case scored as 3 due to exclusion of the SMA from the TVI despite abutment of the SMA by gross disease. Blue contour: PTV 36 Gy (iTVI plus 3mm); Green contour: 33 Gy PTV (25 Gy PTV minus the PRVgi); Yellow contour: 25 Gy PTV [(iGTV + iTVI) plus 3mm]. Abbreviations: iGTV, gross target volume accounting for motion; SMV, superior mesenteric vein; SMA, superior mesenteric artery; iTVI, tumor-vessel interface accounting for motion; PTV, planning target volume; PRVgi, gastrointestinal planning risk volume.