Second cancer risk in female survivors of Hodgkin lymphoma across treatment eras in England and Wales

Subsequent primary malignancies (SPMs) are the leading cause of long-term treatment-related mortality in Hodgkin lymphoma (HL). A population-based cohort study in England and Wales analyzed SPM risks in a large female cohort of childhood and adult patients with HL treated over a 60-year period. The study included 7428 women diagnosed with HL before age 36 years from 1954, with follow-up through 2018. During a median follow-up of 20.2 years, 1200 women developed 1467 invasive cancers (SIR 3.3; 95% CI 3.1-3.5), most commonly breast, lung, and thyroid cancers. Solid tumor risks were highest following radiotherapy, with a strong dose-dependent response. Alkylator use with radiotherapy was associated with reduced risks of breast cancer but increased risk of GI cancers. In treatment period 2000-2010 solid cancer risk was 25% lower than in 1954-1989. This decrease was attenuated and nonsignificant after adjustment for radiotherapy use but not affected by adjustment for chemotherapy use. No decline was observed for hematologic malignancies. Cumulative incidence of SPMs reached 36% at 50 years. The authors conclude that female patients treated in more recent eras have a substantially lower long-term risk of solid SPM. Nevertheless, persistently elevated risks remained beyond 50 years of follow-up, underscoring the need for lifelong surveillance and targeted screening of survivors.