Salvage Re-Irradiation with Proton Beam Therapy for New or Locoregionally Recurrent Non-Small Cell Lung Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Outcomes have improved for Stage III non-small cell lung cancer (NSCLC) patients, but up to 25% can experience isolated locoregional recurrence after definitive chemo-RT. Salvage re-irradiation represents a high-risk but potentially definitive option for these cases, and advancements in particle therapy may enhance the feasibility of re-treatment. <h3>Materials/Methods</h3> This retrospective study evaluates 66 patients who underwent salvage re-irradiation with proton beam therapy at our cancer center for new or recurrent NSCLC within or adjacent to a prior definitive RT field. All patients underwent multidisciplinary evaluation and full restaging work-up prior to re-treatment. Toxicity was scored via CTCAE v5.0, and outcomes were estimated using Kaplan-Meier. Associations were analyzed via Cox proportional hazards and logistic regression. <h3>Results</h3> Patients received IMPT (32%) or passive scatter (68%) to a median re-RT dose of 60-CGE in 30-fractions for new (8%) or recurrent (92%) non-small cell lung cancer (NSCLC), at a median time of 2-years (range: 1-3) from prior thoracic RT (with 23% previously receiving ≥2 courses). More than half (55%) received chemotherapy with proton re-RT: 32 (48%) concurrently, 4 induction (pre-RT), and 1 both. At a follow-up of 13.5 months, the median OS and PFS were 15-months (95% CI 13-17) and 12-months (95% CI 9.5-15), respectively. Actuarial OS at 1-year and 2-years was 61% and 32%, corresponding to PFS of 54% and 24%. Age >70 was associated with greater mortality (HR 2.23, p=0.011), while concurrent chemotherapy was associated with improved PFS (HR 0.53, p=0.022). Altogether, 30 patients (45%) ultimately demonstrated progression, including isolated locoregional recurrence among 16 (24%), isolated distant progression among 8 (12%), and combined site as first presentation among 6 (9%). The incidence of any Grade 2+ toxicity was 26% (including 8 pulmonary and 13 esophageal) and associated with RT dose >60CGE (OR 3.78, p=0.025) and age >70 (OR 0.29, p=0.036). Grade 3 events among 4 patients (6%) included: bronchial stenosis with hemoptysis (following Dmax >140 Gy to PBT), esophageal strictures (occurring at Dmax 77-88 Gy), and pneumonitis (despite meeting standard constraints). There were no cardiac, neurologic, or vascular toxicities. No grade 4 or 5 events. <h3>Conclusion</h3> Reirradiation with proton beam therapy can be safe with minimal toxicity and promising outcomes (which may be further enhanced by concurrent chemotherapy). However, older patients may be at greater risk, and adverse events can still occur despite meeting literature-supported constraints.