Phase 2 SBRT “hot spot” dose-painting radiotherapy to intensify tumor hotspots in early NSCLC.

Roswell Park Cancer Institute is running PRESTO, a randomized Phase 2 trial testing whether intentionally creating higher-dose “hot spots” inside the tumor during stereotactic ablative radiotherapy (SABR/SBRT)—a physical, DNA-damaging ionizing radiation modality—improves local tumor control versus standard SBRT planning. Patients with early-stage, node-negative NSCLC (AJCC v8 stage I–II; T1–3N0) who are candidates for SABR are randomized to standard SBRT vs hot-spot SBRT, delivered in 1–5 fractions over ~1–11 days, with imaging (CT ± FDG PET/CT), biospecimen collection, and optional lymph node sampling. Key endpoints include local control, progression-free survival, overall survival, and grade 3+ toxicity burden; exploratory work tracks immune marker changes after SBRT and includes analyses around beta-blocker use, stress, and quality of life. Today’s care for medically inoperable early-stage NSCLC is SBRT alone (or surgery if operable), so the angle here is a purely planning-based intensification strategy that could raise control rates without adding a new systemic drug—while carefully quantifying any added toxicity risk.