297 - Planning, Delivery and Safety of Dose-Escalated Radiation in GRECO2: Secondary Analysis of a Large International Randomized Trial for Localized Pancreatic Cancer
Presenter(s)
R. A. Kuehnle1, T. A. Aguilera1, J. M. Frakes2, J. A. Dorth3, J. M. Caster4, M. Ghaly5, E. B. Ludmir6, S. K. Seung Jr7, K. W. Merrell8, G. Khan9, S. Al Mutar10, B. Zaki11, G. V. Walker12, R. Ramjeesingh13, S. Apisarnthanarax14, S. Zhang15, J. M. M. Sorensen16, J. M. Herman17, S. Hoffe2, and P. J. Parikh18; 1Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX, 2H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, 3Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, 4Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, IA, 5Northwell, New Hyde Park, NY, 6Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 7The Oregon Clinic, Portland, OR, United States, 8Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 9Department of Medical Oncology, Henry Ford Cancer Institute, Detroit, MI, 10Department of Internal Medicine, Division of Hematology/Oncology, UT Southwestern Medical Center, Dallas, TX, 11Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 12Banner MD Anderson Cancer Center, Gilbert, AZ, 13Nova Scotia Health Authority, Halifax, NS, Canada, 14Department of Radiation Oncology, University of Washington, Seattle, WA, 15UT Southwestern Medical Center, Dallas, TX, 16Galera Therapeutics, Malvern, PA, 17Department of Radiation Medicine, Northwell, New Hyde Park, NY, 18Department of Radiation Oncology, Henry Ford Health, Detroit, MI
Purpose/Objective(s):
We evaluated whether protocol-defined dose-escalated stereotactic ablative radiation (SAbR) for localized pancreatic ductal adenocarcinoma (PDAC) can be delivered across international institutions with consistent plan quality, target coverage, organ-at-risk (OAR) sparing, and low early toxicity under a robust radiation therapy quality assurance (RTQA) framework.Materials/Methods:
In this double-blind placebo controlled randomized trial, patients with locally advanced or borderline resectable PDAC were assigned to SAbR with or without a dismutase mimetic after induction chemotherapy. For this prespecified secondary analysis, we reviewed plans that underwent centralized review per a prospectively defined RTQA manual and independent third-party assessment with steering committee adjudication as needed. Target coverage, OAR constraints, platform type (MR- vs CT-guided), adaptive capability, and grade =3 toxicity were evaluated. Acute toxicity via 30-day events was reported to the FDA upon trial closure.Results:
Among 177 enrolled patients, 139 from 30 institutions in North America and Europe had evaluable plans. On initial review, 71.9% of cases met acceptability criteria, increasing to 97.8% after modification or secondary review. The most common deviation was coverage of the GTV. GTV coverage criteria of 95% at 50 Gy was met in 36.0% of plans, and 50% coverage of the GTV at 50 Gy was achieved in 98.6%. High priority OAR constraints (stomach, duodenum, and small bowel) were met in 91.4%, and all constraints in 50.4% of plans; deviations most commonly involved low-priority portal vein and spleen constraints. Dose-escalated SAbR was delivered across 63 MR- and 76 CT-based platforms (C-arm, coplanar/helical, robotic) without differences in coverage or OAR dosimetry. Adaptive systems were hypothesized to improve GTV coverage, but there was no statistical difference with a p-value of 0.056. At 30 days, grade =3 acute toxicity occurred in 18.5% of patients, with no treatment-related deaths. There were 9 occurrences of GI related toxicity among 168 patients. Toxicity did not differ with the addition of dismutase mimetic.Conclusion:
Protocol-defined dose-escalated SAbR for PDAC is reproducible, deliverable, and safe across diverse international platforms within a centralized RTQA framework. These findings validate the feasibility of multi-institutional pancreatic dose escalation at phase II scale and establish a technical and safety benchmark that enables intensified, adaptive, and biologically integrated radiotherapy strategies in future cooperative group trials.