Rationale: Immune checkpoint inhibitors (ICIs) have revolutionized the management of head and neck squamous cell carcinoma, particularly in the recurrent/metastatic setting. Although the combination of ICIs and radiotherapy (RT) in locally advanced disease has not yet demonstrated clear survival benefits, the strong biological rationale for their synergistic action continues to support investigation, especially in frail or elderly patients unfit for standard chemoradiotherapy. Patient concerns: An 83-year-old male presented with odynophagia, dysphagia, significant weight loss, and right cervical swelling, all impairing oral intake and quality of life. Diagnoses: Moderately differentiated squamous cell carcinoma (G2) of the oropharynx (right base of tongue), human papillomavirus-negative, programmed death-ligand 1 combined positive score = 30. The tumor was staged as cT4a cN3b M1. Interventions: The patient underwent hypofractionated RT (50 Gy in 20 fractions) delivering only to the primary lesion, followed by pembrolizumab 200 mg every 3 weeks. One pulmonary oligoprogressive lesion was treated with stereotactic body RT (60 Gy in 8 fractions). After 29 cycles of pembrolizumab, treatment was discontinued due to the onset of immune-related grade 3 hepatotoxicity. Two additional pulmonary oligoprogressive lesions were treated with stereotactic body radiotherapy, 55 Gy in 5 fractions. Outcomes: A complete response was achieved and maintained at both the primary tumor and nodal sites. Following immunotherapy discontinuation, liver biopsy confirmed immune-related cholangitis. Despite persistent elevation of cholestatic markers, disease control on T and N was preserved. A new pulmonary oligoprogression is currently under active surveillance. Lessons: This case supports the hypothesis of synergism between RT and immunotherapy in an elderly and frail patient with advanced head and neck squamous cell carcinoma. Hypofractionated RT on the primary tumor alone, combined with ICIs, may lead to sustained locoregional control. Immune-related hepatic toxicity, while clinically significant, did not preclude stable disease.
Zoboli et al. (2026) studied this question.