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

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.

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“…A growing number of alternatives that have an effect on tumour development are being observed. These new pathways can have their effect on different processes and locations, such as signalling cascades that regulate the redox state, as in the case of aprepitant [6]; in nanocompounds, such as naringin-dextrin, which increases apoptosis and suppresses oxidative stress and inflammation [7]; or by combination of new doses of different treatments, like radiotherapy and immunotherapy, helping tumour regression [8]. Early diagnosis systems and improved treatments help to increase the survival rate in this population [9].…”