Neoadjuvant immunochemotherapy followed by definitive radiotherapy in locally advanced head and neck squamous cell carcinoma: two-year survival outcomes

PURPOSE: To evaluate the clinical response, survival outcomes, and organ-preservation potential in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients treated with neoadjuvant immunochemotherapy (NIC) followed by definitive radiotherapy (DRT). METHODS: We retrospectively reviewed patients with stage III-IVb HNSCC treated with NIC followed by DRT between 2021 and 2023. Tumor response was assessed after NIC and after completion of DRT according to RECIST 1.1. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Toxicities were graded according to CTCAE 5.0 criteria. RESULTS: A total of 74 patients were included, with hypopharyngeal tumors accounting for 47.3%. All patients completed at least two cycles of NIC. After NIC, the objective response rate was 89.2%, with clinical complete response (cCR) and clinical partial response (cPR) rates of 1.4% and 87.8%, respectively. After DRT, the corresponding rates shifted to 17.6% and 77.0%, respectively. With a median follow-up of 24 months (range: 5-38 months), the estimated 2-year OS and PFS rates were 83.2% and 61.7%. Among patients with laryngeal or hypopharyngeal carcinoma, the larynx-preservation rate was 95.2% and the 2-year larynx-preservation OS reached 73.6%. NIC-related adverse events were predominantly grades 1-3 (90.0%). CONCLUSION: NIC followed by DRT was associated with high response rates, encouraging survival outcomes, and manageable toxicities in this retrospective cohort. While organ-preservation rates are promising, the modest PFS highlights the need for further investigation in larger or selective cohorts.