KEY POINTS
- The Proton Collaborative Group registry identified 104 patients with 110 lung tumors treated across 14 US proton centres. The cohort was deliberately high risk: 32.7% were ≥4 cm, 30% had prior in-field RT, and 41.8% met the SUNSET definition of ultracentral disease.
- Eligible proton regimens were either 4–5 fractions at ≥10 Gy per fraction or 8–15 fractions at ≥3.5 Gy per fraction. The most common schedules were 60 Gy/15 fractions (40%), 50 Gy/5 (17.2%), 70 Gy/10 (10%), and 60 Gy/8 (7.2%).
- Modern pencil-beam treatment predominated: 71.8% received IMPT, while 27.2% were treated with passive scattering. Median prescription dose was 60 Gy, with a median BED10 of 89.8 Gy.
- Competing-risk local control was 83.3% at one year and 77.4% at two years. Two-year local control remained 82.2% after re-irradiation, 75.8% for tumors ≥4 cm, and 75.2% for SUNSET-defined ultracentral tumors, with no significant subgroup differences.
- Target coverage mattered: increasing the proportion of internal GTV receiving ≥95% of prescription dose was associated with improved local control (HR 0.982 per percentage point, 95% CI 0.970–0.995; p=0.007). No clear association was found for BED, tumor size, re-irradiation, or ultracentral location.
- The most frequent toxicities were cough (40%), dyspnea (34.5%) and fatigue (31.8%), with no grade ≥3 toxicity reported. Re-irradiated patients had more cough (57.6% vs 32.5%; p=0.014), while tumors ≥4 cm had more pneumonitis (5.6% vs 0%; p=0.042).
- Median follow-up was only 14.5 months and median OS 12.5 months. Because many serious central-lung toxicities emerge after 12–24 months, the absence of high-grade events should not be interpreted as definitive evidence of long-term safety.
CLINICAL TAKEAWAY
Proton SBRT/HFRT appears feasible for selected lung tumors in which size, centrality, or prior RT makes ablative treatment particularly difficult, and maintaining target coverage may be important for local control. The acute safety signal is reassuring, but this registry cannot establish superiority over photons and does not yet provide mature late-toxicity data.