Development of second primary malignancies (SPMs) in head and neck cancer survivors stratified by receipt of radiation therapy (RT) and chemotherapy (CT).

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11055 Background: Head and neck cancers (HNC) often require multimodality management for curative intent with surgery, radiation therapy (RT) with or without chemotherapy (CT), resulting in significant impairment of nutrition, speech and quality of life. Survivors are also at risk for future cancers from field cancerization. We aim to study the incidence and characteristics of SPMs in HNC survivors. Methods: We performed a retrospective analysis of the Surveillance, Epidemiology and End Results (SEER) 17 registries database to identify the cases diagnosed with cancer of the oral cavity, pharynx or larynx as primary malignancy between the years 2000 to 2021. The data was stratified by receipt of RT and CT. Standardized incidence ratios (SIR) for the development of SPMs were calculated using the SEER Stat software. Results: A total of 206144 HNC survivors were identified, of which 78055 received CT + RT (CRT group) while 57898 patients received RT with no/unknown CT (RT group). The CRT group had a lower risk than the RT group for several local SPMs with SIRs (p<0.05): lip (5.13, 5.71), salivary gland (4.11, 5.21), floor of mouth (18.47, 19.7), gum/other mouth (20.18, 25.04), tonsil (4.54, 5.47) and larynx (5.18, 6.79). However, the CRT group had higher SIRs (p<0.05) than the RT group for tongue SPMs (15.91, 13.03) and all pharyngeal SPMs: nasopharynx (9.65, 8.51), oropharynx (13.21, 12.11), hypopharynx (20.47, 16.44), other oral cavity/pharynx (31.08, 24.69). The CRT group had higher SIRs (p<0.05) than RT recipients for most gastrointestinal SPMs: esophagus (6.44, 4.53), stomach (1.49, 1.27), colorectal (1.34, 1.23). The RT group had higher SIRs (p<0.05) than CRT recipients for hepatobiliary SPMs (1.48, 1.29) and anus/anal canal /anorectum SPMs (1.87, 1.73). CRT group had higher risk than RT group for nose/nasal cavity/middle ear, lung/ bronchus, bone/joint, soft tissue and kidney SPMs but lower risk for trachea, eye/orbit non - melanoma, and thyroid SPMs (Table). CRT group had a lower risk for nodal Hodgkin Lymphoma (SIR 0.3) and myeloma (SIR 0.76) than the general population (p<0.05). Both groups had lower risk for Chronic Lymphocytic Leukemia SPMs, with SIRs: RT 0.71, CRT 0.59 (p<0.05). Understandably, CRT recipients had a higher risk for Acute Myeloid Leukemia (SIR 2.24, p<0.05). Conclusions: HNC survivors demonstrate varying risks for SPMs in RT and CRT recipients. This necessitates close monitoring during survivorship care, with a comprehensive approach to screening and preventive measures to improve long-term outcomes and quality of life. SPMs in HNC survivors. SPM RTSIR (p<0.05) CRTSIR (p<0.05) Nose, nasal cavity, middle ear 6.25 8.33 Lung, bronchus 4.01 4.69 Trachea 55.08 38.19 Bones, joints 4.62 6.15 Soft tissue including heart 1.67 2.21 Urinary bladder 1.27 1.24 Kidney 1.29 1.42 Eye, orbit – Non-melanoma 6.18 5.19 Thyroid 2.93 2.77

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