Sex-stratified risk of second malignancies in Hodgkin lymphoma survivors: A SEER-based analysis of latency and cancer type.

547 Background: Hodgkin lymphoma (HL) survivors are at increased risk of second primary malignancies (SPMs), often related to treatment exposures such as radiation and chemotherapy. Understanding sex specific and time dependent patterns of SPMs is essential to guide survivorship care and improve long term outcomes. Methods: Using SEER 12 Registries (1992–2021), patients diagnosed with HL as a primary malignancy were identified. We applied SEER*Stat multiple primary–standardized incidence ratio (MP-SIR) sessions to calculate expected and observed cases of second malignancies. Outcomes were stratified by cancer type (solid vs hematologic), sex, and latency interval (<1 year, 1–5 years, 5–10 years, >10 years). We reported standardized incidence ratios (SIRs, O/E) with statistical significance determined by 95% confidence intervals. Results: Among HL survivors, overall SIRs for second malignancies were elevated across both sexes, with variation by cancer type and latency. Non Hodgkin lymphoma showed persistently elevated O/E ratios in both sexes across all latency periods, with especially high risk within the first year post HL (M: 21.98, F: 26.51). Respiratory system cancers demonstrated consistently elevated risks (e.g., M: 2.44, F: 6.26 at <1 year), remaining significant over time. Thyroid cancer showed marked early risk, particularly among males (M: 15.67, F: 9.75 at <1 year), which declined over time. Acute myeloid leukemia followed a similar latency-driven trend, with peak risk at 1–5 years (M: 14.94, F: 15.67) and decreasing thereafter. Breast cancer displayed a latency-dependent increase, with significant elevation only at >10 years (F: 1.80). Sex-specific differences were notable in several cancers, including urinary tract, melanoma, and thyroid, where females generally had higher O/E ratios. These findings underscore the importance of latency and sex in guiding tailored surveillance for HL survivors. Conclusions: This analysis highlights the importance of sex and latency specific surveillance strategies in HL survivorship care. Early vigilance for hematologic malignancies and long term screening for radiation-associated solid tumors is warranted. These findings support risk-adapted follow-up and inform guideline development for survivorship clinics. Summary table of select cancers. Cancer Type <1 year M <1 year F 1-5 years M 1-5 years F 5-10 years M 5-10 years F >10 years M >10 years F Total M Total F Colon and Rectum 1.4 1.5 0.9 0.9 1 1.1 1.2 1.6 1.1 1.4 Respiratory System 2.4 6.3 1.6 1.2 1.9 2.6 2.3 2.5 2.0 2.4 Thyroid 15.7 9.8 0.8 2.6 1.6 1.6 2.7 2.8 2.7 2.7 Breast 0 0.8 0 0.6 2.5 1.2 0 1.8 0.6 1.4 Melanoma of the Skin 1.4 0.8 1.1 2.3 1.4 1.6 1.7 1.4 1.5 1.6