Does previous neck dissection or irradiation mitigate the response to immunotherapy in advanced/metastatic head and neck squamous cell carcinoma?

Immunotherapy has brought new hope to patients with locally advanced, recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). This study aimed to evaluate the outcomes at our institution, focusing on the response to immunotherapy in patients whose draining lymph nodes were previously dissected and/or irradiated. A retrospective study on patients treated with immunotherapy, indicated for unresectable or R/M HNSCC between 2014 and 2024, was conducted. Treatment response and survival outcomes were analysed. Eighty-four patients were identified, including 26 patients (31%) who were treated with immunotherapy without any previous therapy to the draining lymph nodes and 58 patients who had been treated with neck dissection or radiotherapy (ND/RT) before immunotherapy. The latter were significantly younger (63 vs 71 years; P = 0.037) with fewer distant metastases upon initiation of immunotherapy (7% vs 31%; P = 0.007). Combined positive score <1 was the only factor significantly associated with disease progression, adjusted for age, previous ND/RT, and metastatic disease (P = 0.038). When ND/RT preceded immunotherapy, higher rates of disease progression were noted in comparison to naive necks, but the difference did not reach statistical significance (54% vs 33%, respectively; P = 0.134). Overall, previous dissection or radiotherapy to draining lymph nodes did not negatively affect the response to immunotherapy nor the survival outcomes in advanced or R/M HNSCC.