Secondary cancer is the leading cause of death 15 years or more after diagnosis of early‐stage Hodgkin lymphoma

Introduction: Classical Hodgkin lymphoma (cHL) often occurs in early adulthood and disease control is achieved by several treatment strategies, including radiotherapy (RT) added to chemotherapy in early stage disease. Long-term treatment-related toxicity is therefore an important issue, in particular with regard to toxicity from RT. Even if the latter seems to be reduced as methods of delivery are being refined, repeated investigations of long-term results are warranted. Methods: A Swedish population-based cohort, n = 215, of stage I-IIA cHL treated with 2–4 cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) and 30 Gy limited field RT, between 1999 and 2005 is followed by linkage to health registries. Limited field being a modification of involved field, with a reduction of the target volume. In a first report (Br J Haematol. 2020) no excess mortality was detected. In a later report (J Clin Oncol. 2022) excess morbidity in secondary cancer and diseases of the circulatory system was seen when comparing with matched comparators. Relative survival rate (RSR) is now updated using the Ederer II method for all patients, patients with and without early progression (<5 years from diagnosis), and for comparators. Mortality is analyzed by years of life lost to secondary cancer and to diseases of the circulatory system, according to cause of death. Years of life lost are calculated in relation to expected survival, from the time of death, derived from life tables. Results: Median age at time of diagnosis is 34 years (range 18–77). Median follow-up for survival is 20 years (range 16–23) with 34 deaths occurring among patients of which 14 are seen more than 15 years after diagnosis. RSR for all patients is 0.97 (95% CI: 0.90–1.02) at 20 years. RSR at 20 years for patients with and without early progression is 0.76 (95% CI: 0.47–0.93) and 0.99 (95% CI: 0.92–1.04), respectively (Figure 1). Analyzing the impact on the whole cohort of deaths later than 15 years from diagnosis, years of life lost to secondary cancer are 0.22 years per patient and 0.07 per comparator (p < 0.001). In the same period years of life lost to diseases of the circulatory system are 0.14/patient and 0.20/comparator (p < 0.001). Conclusions: In this cHL cohort treated with chemotherapy and RT, survival is very good 20 years after diagnosis. A trend towards excess mortality can be seen, starting 15 years after diagnosis. The small group with early progression has significant excess mortality with an impact on RSR for the whole cohort. The excess mortality is correlated in time with a significantly higher risk for death from a secondary cancer. Thus, the appearance of excess secondary cancers among patients seems to impact survival. There is, so far, no signs of a comparable effect from the excess morbidity in diseases of the circulatory system. The research was funded by: Cancerfonden and Stiftelsen onkologiska klinikens i Uppsala forskningsfond. Keyword: Late Effects in Lymphoma Survivors No conflicts of interests pertinent to the abstract.