Radiation-Induced Malignancies of the Head and Neck: A Single-Center Population Study and Survival Outcomes

Background: Radiation-induced malignancies (RIMs) of the head and neck are rare but serious long-term complications of radiotherapy. With increasing cancer survival rates, their incidence is rising. This study reports the clinicopathological features, treatment approaches, and survival outcomes of patients with head and neck RIMs managed at the National Cancer Institute (Istituto Nazionale dei Tumori—INT) in Milan, Italy. Methods: A retrospective analysis was conducted on patients diagnosed with head and neck RIMs between 2003 and 2024 at the Istituto Nazionale dei Tumori, Milan. Inclusion criteria comprised tumor development within the irradiated field, histological distinction from the primary neoplasm, latency exceeding three years, and absence of alternative etiologic factors. Clinical data were obtained from institutional records. Overall survival (OS) was estimated using the Kaplan–Meier method, with significance set at p < 0.05. Results: Fifty patients fulfilled the inclusion criteria (52% male; median age at primary diagnosis, 40 years). The mean latency between primary and secondary tumors was 20.8 years. The most frequent RIM site was the oral cavity, with squamous cell carcinoma as the predominant histology (66%). Surgery was performed in 66% of cases, achieving R0 resection in 67%. The 2- and 5-year OS rates were 67.4% and 39.3%, respectively, with significantly superior survival after surgery. Conclusions: Head and neck RIMs present substantial diagnostic and therapeutic challenges. Radical surgery remains the most effective treatment, while long-term surveillance and multicenter research are essential to optimize management and mitigate secondary tumor risk.