Hypofractionated and stereotactic body proton radiotherapy for a high-risk lung cancer cohort: A multi-institutional experience from the proton collaborative group prospective registry.

Introduction: Lung cancer is commonly treated with stereotactic body radiotherapy (SBRT) and hypofractionated RT (HFRT). Delivering these ablative regimens with proton beam therapy (PBT) may yield dosimetric and clinical advantages, particularly for high-risk cases. We evaluated safety and efficacy of SBRT/HFRT PBT for lung tumors, including unfavorable subgroups. Methods: Adults with lung tumors treated with PBT ≤15 fractions were identified from a prospective, multi-institutional registry. Eligible regimens included 4-5 fractions at ≥10Gy/fraction (≥48Gy total) or 8-15 fractions at ≥3.5Gy/fraction (≥52.5Gy total). Local control (LC) was estimated using cumulative incidence with death as a competing risk, and Fine-Gray models were used for subgroup comparisons. Results: 104 patients with 110 tumors (83.6% non-small cell lung cancer) were included: 32.7% ≥4 cm, 41.8% ultracentral, and 30% re-irradiated. Most common regimens were 60Gy/15 fractions (40%) and 50Gy/5 fractions (17.2%); 71.8% received intensity-modulated PBT. 1-and 2-year LC rates were 83.1% and 77.4%, with no difference by tumor size, ultracentral location, or re-irradiation. Internal gross tumor volume receiving 95% of dose was associated with improved LC ( Conclusions: In the largest prospectively enrolled report of SBRT/HFRT via intensity-modulated PBT for a high-risk lung tumor cohort, 1- and 2-year LC rates were 83.1% and 77.4%, with no grade ≥ 3 toxicities. LC was similar among high-risk subgroups. However, short survival and follow-up durations limited assessment of the findings. Despite the prospective registry, reliable long-term follow-up data remained limited for many patients, somewhat restricting result interpretation.