Spatially fractionated induction radiotherapy to widen the therapeutic window in locally advanced non-small cell lung cancer (SPARROW): study protocol of a multicenter, randomized, open-label seamless phase I/II trial

作者：Sebastian Regnery, Markus Ehle, David Neugebauer, Lukas Gerke, Rasmus Schindehütte, Lukas Bauer, Stephan Mende, Marietta Kirchner, Alexandra Balzer, Aoife Gahlawat, Amir Abdollahi, Daniel Kazdal, Albrecht Stenzinger, Juliane Hörner‐Rieber, Matthias Uhl, Kynann P. Aninditha, Marc De Munter, Thomas Welzel, Jürgen Debus, Fabian Weykamp · 发表于：Clinical Lung Cancer · 年份：2026 · DOI：10.1016/j.cllc.2026.07.008 · 研究领域：Lung Cancer Diagnosis and Treatment、Hepatocellular Carcinoma Treatment and Prognosis、Effects of Radiation Exposure

Background Inoperable, locally advanced non-small cell lung cancer (LA-NSCLC) remains associated with high rates of locoregional failure despite concurrent chemoradiotherapy and consolidation immunotherapy. Uniform dose escalation has failed to improve outcomes. We propose to address intra- and interindividual tumor heterogeneity by spatially fractionated radiotherapy (SFRT) and stereotactic body radiotherapy (SBRT). Patients & Methods SPARROW is a prospective, multicenter, open-label seamless phase I/II randomized clinical trial. In phase I, up to 32 patients with inoperable LA-NSCLC receive induction SFRT (Lattice or central boost, 1 × 18 Gy), followed by a 4-week interval and adaptive consolidation radiotherapy (25 × 2.4 Gy). Tumor volume reduction (primary endpoint), safety, and feasibility guide selection of the optimal SFRT approach. A "backup arm" allows SBRT of small primary tumors with mediastinal fractionated radiotherapy (25 × 2.4 Gy). In phase II, 100 patients are randomized (1:1) to this personalized treatment (induction SFRT or SBRT of the primary) versus standard fractionated radiotherapy (30–35 × 2 Gy). Both treatment arms employ intensity-modulated and adaptive radiation techniques. The primary endpoint is progression-free survival (PFS). Secondary and translational endpoints include overall survival, locoregional control, patient-reported outcomes, circulating tumor DNA and immune profiling. Discussion SPARROW investigates whether personalized and novel radi...