Background Hodgkin lymphoma (HL) survivors are at increased risk to develop late treatment-related complications, including second malignant neoplasms (SMNs) and cardiovascular disease (CVD). Research to date has focused on separate risk estimates for these outcomes. We aimed to examine the combined risk of SMN and CVD, providing more insight into the total burden of morbidity from these severe late effects.
Methods Our multicenter cohort comprised 2,908 5-year HL survivors, treated before age 51 between 1965 and 2000. CVD endpoints (coronary heart disease, cardiomyopathy and congestive heart failure, and valvular heart disease) were assessed through general practitioners. Data on SMNs were obtained from linkage with the Netherlands Cancer Registry, including all invasive cancers except basal cell carcinomas. Cumulative incidences of SMN and/or CVD were calculated with death from other causes as competing risk. Treatment-specific risks of developing SMN and/or CVD were quantified using Cox regression analysis. The mean cumulative count (MCC) will be calculated as the average number of events per individual in our cohort over a given follow-up period (results will be available in October 2016).
Results After a median follow-up of 22 years, we identified 874 SMNs and 1044 CVDs. 1249 patients developed ≥1 major event; of those 240 developed both an SMN and CVD. After a follow-up of 40 years, at a median attained age of 60 years, the cumulative incidence of SMN or CVD was 67.4% (95%CI: 64.6-70.0), with 22.5% (95%CI: 19.8-25.3) of patients being diagnosed with both events. Both supradiaphragmatic RT (Hazard Ratio [HR]: 2.5, 95%CI: 2.1-3.1) and anthracycline-containing CT (HR: 1.2, 95%CI: 1.0-1.4) independently increased the risk of SMN or CVD. Supradiaphragmatic RT was associated with a 4.1-fold increased (95%CI: 2.3-7.3) risk of developing both SMN and CVD.
Conclusions HL survivors experience a high disease burden from SMN and/or CVD during follow-up. The cumulative incidence of SMN and/or CVD in our HL population treated between 1965 and 2000 amounted to 67% after 40 years from initial treatment. Supradiaphragmatic RT most strongly increased the risk developing SMN and/or CVD.