3673 - SFRT with iOAR Sparing Combined with Concurrent Chemoradiotherapy for Unresectable Stage III NSCLC: A Randomized Phase II/III Trial
Presenter(s)
W. Gong1, J. Yang2,3, L. F. Han1, Y. Li4, L. Du5, J. Wang6, T. Wang7, M. Zhao8, and W. Yan9,10; 1Junxin Oncology Institute, Foshan Fosun Chancheng Hospital, Foshan, Guangdong, China, 2Junxin Oncology Institute, Foshan, Guangdong, China, 3Azure Research Institute, Richmond, KY, 4Foshan Fosun Chancheng Hospital, Foshan, Guangdong, China, 5Department of Radiation Oncology, The First Medical Center of the PLA General Hospital, Beijing, Beijing, China, 6Department of Radiation Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China, 7Department of Radiotherapy, Liaoning Cancer Hospital, Cancer Hospital of Dalian University of Technology, Shenyang, Liaoning, China, 8The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China, 9College of Medicine, University of Kentucky, Lexington, KY, 10Azure Reserach Institute, Richmond, KY
Purpose/Objective(s): Concurrent chemoradiotherapy (CCRT) followed by immunotherapy is standard of care for unresectable stage III non-small cell lung cancer (NSCLC); however, primary tumor failure and radiation-induced lymphopenia (RIL) remain major barriers to long-term survival. This multicenter randomized phase II trial evaluates whether integrating stereotactic body radiotherapy (SBRT) or spatially fractionated radiotherapy (SFRT) for primary tumor dose intensification, combined with hypofractionated mediastinal chemoradiotherapy and immune-organ-at-risk (iOAR) sparing, improves local control and preserves immune function compared to standard CCRT.
Materials/Methods: This national, multicenter, prospective, open-label, randomized phase II trial enrolls 132 patients with unresectable stage III NSCLC randomized 1:1 to standard CCRT (60 Gy/30 fractions) or an experimental arm integrating SBRT or SFRT to the primary tumor with hypofractionated mediastinal chemoradiotherapy. The experimental arm is stratified into three cohorts by tumor size and location: peripheral tumors =5 cm (SBRT), central or residual tumors =5 cm (SBRT boost), and large or central tumors >5 cm (SFRT). All experimental plans incorporate iOAR sparing with mandatory dose constraints to the sinoatrial node and left coronary artery origin. Consolidation immunotherapy or targeted therapy is administered per molecular status. The primary endpoint is objective response rate (ORR) per RECIST 1.1. Secondary endpoints include progression-free survival, local control, overall survival, treatment-related toxicity, quality of life, and incidence of grade 3-4 lymphopenia. Exploratory endpoints include FDG-PET metabolic response and distant metastasis-free survival.
Results: This trial is actively enrolling. Preliminary data including enrollment accrual, treatment compliance, acute toxicity profiles, and early response assessments will be presented at the meeting.
Conclusion: This randomized phase II trial will provide critical prospective evidence on the efficacy, safety, and immunologic impact of SBRT/SFRT-based dose intensification with iOAR-sparing strategies in locally advanced NSCLC. By integrating hypofractionation, spatial dose modulation, and cardiac substructure sparing, this biologically informed paradigm aims to enhance local control and immunotherapy synergy without increasing toxicity, potentially redefining radiotherapy standards in the immunotherapy era.