Re-irradiation with concurrent and maintenance nivolumab in locally recurrent and inoperable squamous cell carcinoma of the head and neck: A single-center cohort study

Background: The rate of loco-regional recurrences for locally advanced head and neck squamous cell carcinoma (HNSCC) following standard treatment reaches up to 50%, accompanied by a probability of 20% to develop a second primary tumor in the head and neck region. Methods: Ten patients with inoperable, in-field recurrence of HNSCC following previous primary or adjuvant radiotherapy (RT) in combination with concurrent platinum-based chemotherapy were reirradiated with 60 Gray in 30 fractions between December 2017 and January 2020 with concurrent and maintenance nivolumab administration. Data were retrospectively collected and compared with patients who underwent re-irradiation (ReRT) with concurrent cisplatin following propensity score matching (PSM). Local progression-free survival (LPFS) and overall survival (OS) were visualized using Kaplan-Meier method (log-rank test). Results: All patients completed ReRT. Median number of applied courses of nivolumab was 12 (range, 3-38). OS rate was 50% at 12 months and the median OS was 11 (range, 2-23) months. Six and 12 month LPFS rates were 60% and 30%, respectively. Median LPFS was 8 (range, 2-19) months. OS and LPFS rates were not inferior to those of patients treated with concurrent cisplatin. No unexpected radiation-related toxicity occurred. A total of four patients developed any-grade immune-related adverse events of which two presented with grade 3 toxicities. One patient died within 3 weeks after ReRT. Higher blood levels of CRP (p = 0.004), lower levels of hemoglobin (p = 0.029) and higher neutrophil/lymphocyte ratio (p = 0.004) were associated with impaired LPFS. Higher recursive portioning analysis (RPA) class was associated with impaired LPFS (p = 0.022) and OS (p = 0.024). Conclusion: The combination of ReRT and nivolumab for locally recurrent HNSCC was feasible without occurrence of unexpected toxicities. Combined radioimmunotherapy might offer an effective treatment option for carefully selected pre-irradiated patients ineligible for salvage surgery. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.