Radiotherapy in Addition to Immunotherapy-Based Systemic Therapy Delays Progression and Prolongs Survival in Recurrent Head and Neck Cancer

KEYNOTE 048 study established the milestone of immunotherapy in recurrent/metastatic head and neck cancer (HNSCC). However, subgroup analysis revealed there was no survival benefit from immunotherapy over EXTREME regimen for the specific setting with recurrence only. This study aimed to investigate whether local radiotherapy (RT) in addition to immunotherapy could delay progression and prolong survival outcomes in recurrent only HNSCC. This is a single-center retrospective study. From January 2019 to November 2023, HNSCC patients who were treated with immunotherapy based systemic therapy plus local/regional radiotherapy in our institution were primarily selected. Among these patients, only those with locoregional recurrence alone and receiving radiotherapy and immunotherapy as first-line treatment after the diagnosis of recurrence were included into final analysis. Overall survival (OS), progression free survival (PFS), local-regional progression free survival (LRPFS) and distant metastasis free survival (DMFS) were analyzed. Treatment related adverse events were collected according to the medical reports. A total of 23 patients with recurrent HNSCC met the inclusion criteria and were finally analyzed. The median recurrent age was 55 years, and the majority was male (82.6%). The median time of progression from the initial course of treatment was 9.3 months. Nineteen patients (82.6%) harbored stage rIV disease according to AJCC 8th edition. The predominant site of primary lesion was oral cavity (69.6%). All immunotherapy agents were PD1 inhibitors and pembrolizumab was most commonly administered (43.5%). The combination pattern of immunotherapy and RT consisted of induction immunotherapy in 15 patients (65.2%), concurrent immunotherapy with RT in 10 patients (43.5%) and consolidation immunotherapy in 6 patients (26.1%). Median RT dose was 66.0 Gy (range = 57.24 Gy to 76.42 Gy) with conventional dose fractionation. Among 17 patients with available CPS, 11 with CPS ≥ 20, 5 with CPS 1-19 and only 1 patient with CPS <1. The median follow-up time was 16.4 months. For overall cohort, the median PFS was 17.0 months while the median OS, LRFS and DMFS were not reached. The 1-year OS, PFS, LRFS and DMFS were 100%, 81.6%, 87.4% and 100%, respectively. As compared with those with CPS < 20 or unknown, patients with CPS ≥ 20 presented superior PFS (1-y PFS: 100% vs 52.5%, P = 0.033). Dermatitis (17.4%), thyroid disfunction (13%) and hepatitis (8.7%) were the most frequent immune-related AE, among which 2 patients discontinued immunotherapy (8.7%). This study presented promising survival results in recurrent lonely HNSCC, supporting the use of RT with intermediate to radical dose as the first-line treatment in addition to immunotherapy-based systemic therapy, in particular for patients with CPS ≥ 20.