Ultra-Hypofractionated Re-Irradiation with Anti-PD-1 Immunotherapy for Locoregionally Recurrent (after Radical Chemo-Radiotherapy) Non-Small Cell Lung Cancer

SIMPLE SUMMARY: Concurrent administration of anti-PD-1 immunotherapy with one or two fractions of ultra-hypofractionated (8 Gy/fraction) radiotherapy for patients with locoregionally recurrent non-small cell lung cancer (NSCLC) after radical chemo-radiotherapy was examined in a cohort of 11 patients. This immuno-radiotherapy scheme was safe and provided 81.8% objective response rates. The complete response rate was 27.2%, while tumor regression by 80–100% of initial dimensions was noted in 63.5% of patients. The 22-month locoregional relapse-free rate was 54.5%, while the projected 2-year disease-specific overall survival was 62%. These encouraging results provide the basis to pursue immuno-radiotherapy trials with ultra-hypofractionated radiotherapy schemes in this ill-fated group of NSCLC patients. ABSTRACT: Large fractions of radiotherapy of 8 Gy (ultra-hypofractionated RT, ultra-hypoRT) promote anti-tumor immune responses that have been clinically substantiated in combination trials with immune checkpoint inhibitors (ICIs). In the current study, we postulated that ultra-hypoRT in combination with ICIs may enhance tumor clearance in NSCLC patients with locoregional relapse after radical chemo-RT. Between 2019 and 2021, eleven patients received re-irradiation with one or two fractions of 8 Gy concurrently with anti-PD1 immunotherapy (nivolumab or pembrolizumab). RT-related toxicities were negligible, while immune-related adverse events enforced immunotherapy interruption in 36% of patients. The overall response rate was 81.8%. Tumor reduction between 80 and 100% was noted in 63.5% of patients. Within a median follow-up of 22 months, the locoregional relapse-free rate was 54.5%, while the projected 2-year disease-specific overall survival was 62%. The results were independent of PD-L1 status. The current report provides encouraging evidence that a relatively low biological dose of RT delivered with 8 Gy fractions is feasible and can be safely combined with anti-PD-1 immunotherapy. Despite the low number of patients, the significant tumor regression achieved and the long-lasting locoregional control and overall progression-free intervals provide a basis to pursue immuno-RT trials with U-hypoRT schemes in this group of NSCLC patients of poor prognosis.