Sex-stratified risk of second malignancies in Hodgkin lymphoma survivors: A retrospective study.

Abstract

e19041 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), we identified patients diagnosed with HL as a first primary malignancy. 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, the overall SIR for second malignancies was elevated across both sexes, with variation by cancer type and latency. Notably, Non-Hodgkin lymphoma exhibited persistently elevated and statistically significant observed-to-expected (O/E) ratios in both sexes across all latency periods, with particularly high risk within the first year post-Hodgkin lymphoma (M: 21.98, F: 26.51). Respiratory system cancers also showed consistently elevated risks (e.g., M: 2.44, F: 6.26 at & <1 year), remaining significant across all latency intervals. Thyroid cancer demonstrated striking early excess risk, especially among males (M: 15.67, F: 9.75 at <1 year), which sharply declined over time. Acute myeloid leukemia followed a similar latency-driven pattern, with the highest risk observed in early latency (M: 14.94, F: 15.67 at 1–5 years) and a gradual decline thereafter. Breast cancer, as a female-specific malignancy, showed a latency-dependent increase, with significant elevation only at >10 years (F: 1.80). Sex-specific differences were evident in several cancers, including urinary system, melanoma, and thyroid, where females generally exhibited higher O/E ratios. These findings highlight the importance of both latency and sex in tailoring surveillance strategies for Hodgkin lymphoma 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.