Sequential immune checkpoint inhibition after palliative radiotherapy in patients with advanced head and neck squamous cell carcinoma: A retrospective cohort study

Head and neck squamous cell carcinoma (HNSCC) frequently presents at an advanced stage, where curative options are often not feasible. Palliative radiotherapy (RT) can relieve symptoms and improve performance status, potentially enabling systemic therapy. Immune checkpoint inhibitors (ICIs) have a survival benefit in recurrent and metastatic HNSCC; however, the optimal sequencing of RT and ICIs remains to be elucidated. The present study aimed to evaluate the clinical outcomes of ICI therapy administered after palliative RT in patients with advanced HNSCC. Consecutive patients with advanced HNSCC treated at The University of Tokyo Hospital (Tokyo, Japan) between January 2017 and December 2024 were retrospectively reviewed. Eligible patients received initial palliative RT, with or without subsequent ICIs within 6 months (RT‑ICI vs. RT groups). Clinical data, including demographics, RT parameters, treatment regimens and outcomes, were collected. Overall survival (OS) and progression‑free survival (PFS) analyses were performed using the Kaplan‑Meier method and Cox proportional hazards models. Among 74 patients (median age, 75 years; 82% male), 17 received ICIs following RT. The RT‑ICI group achieved a 2‑year OS rate of 55.8% compared with 5.7% in the RT group (P<0.001). Median PFS time in the RT‑ICI group was 12.7 months, with a 2‑year PFS rate of 20.9%. Multivariate analysis confirmed RT‑ICI treatment [hazard ratio (HR) 0.22, 95% confidence interval (CI) 0.09‑0.55; P=0.001], higher biologically effective dose (≥39 Gy; HR 0.46, 95% CI 0.24‑0.91; P=0.025) and preserved performance status (HR 1.99, 95% CI 1.02‑3.88; P=0.043) as independent predictors of OS. Grade 3 or higher immune‑related adverse events occurred in three patients (17.6%). In conclusion, sequential ICI therapy after palliative RT was revealed to be associated with improved survival outcomes in patients with advanced HNSCC. Higher RT dose was also associated with a better survival; however, no causal or mechanistic conclusions can be drawn from this observation. Further prospective studies are warranted to confirm these findings, and to clarify the optimal sequencing and dosing strategies.