Causes of death and effect of non-cancer-specific death on rates of overall survival in adult classic Hodgkin lymphoma: a populated-based competing risk analysis

Abstract

Background The improved prognosis of classic Hodgkin lymphoma (cHL) has been accompanied by elevated risks of non–cancer-specific death (non-CSD). The aim of this study was to verify the occurrence of non-CSD and its effect on rates of overall survival among adult patients with cHL. Methods To ensure sufficient follow-up time, we analyzed retrospective data from patients aged ≥20 years with cHL that was diagnosed between 1983 and 2005 in the Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was applied to analyze the non-CSD occurrence in relation to all factors. Using Fine-Gray’s method, we calculated the cumulative incidences of CSD and non-CSD. Stacked cumulative incidence plots and ratio of non-CSD to all causes of death were applied to evaluate the effect of non-CSD on rates of overall survival. Finally, we analyzed long-term mortality through Cox proportional hazard regression analysis and competing risk regression analysis to emphasize a more appropriate model of survival for patients with cHL. Results Among the 18,518 patients included, there were 3768 cases of CSD (20.3%) and 3217 of non-CSD (17.4%). Older age, earlier period, male sex, unmarried status, mixed cellularity (MC) and lymphocyte-depletion (LD) histological subtype, and patients received radiotherapy (RT) only were associated with more non-CSD according to binary logistic analysis. The cumulative incidence of non-CSD exceeded CSD after approximately 280 months follow-up. The most common causes of non-CSDs were cardiovascular disease, subsequent primary neoplasms, infectious diseases, accidents, and suicide. In a Cox proportional hazards model, patients who were black, unmarried, at an advanced stage or underwent chemotherapy (CT) alone were at greater risk of mortality than were white patients, who were married, at an early stage, and underwent combined modality; these populations were also found to be at greater risk for CSD in a competing risk model, but the risk of non-CSD did not differ significantly according to race and marital status, patients with early-stage disease and who underwent RT only were found to be at higher risk of non-CSD instead. Conclusions Lymphoma was the cause of death in most patients who died, but non-CSD was not unusual. Patients with cHL should be monitored closely for signs of cardiovascular disease and malignant tumors. Rates of overall survival of patients were diminished by non-CSD, and a competing risk model was more suitable for establishing the prognosis than was the Cox proportional hazards model.

Long‐term risk of cardiovascular disease mortality among classic Hodgkin lymphoma survivors

“…The CVD PMR exceeded that of cHL and other neoplasms with time. This seemed to be opposite to the previous studies that have reported that the proportion of patients who died from cardiovascular disease was lower than that from either HL or other neoplasms 4,25 . Indeed, previous studies only considered the CVD PMR for the entire population rather than analyzing the variation of PMR in different follow‐up intervals; therefore, our results clearly reflected the temporal trend of PMR of CVD among cHL survivors.…”

“…A recent study reported that the cumulative incidence of noncancer‐specific death exceeded that of cancer‐specific death in cHL patients over time. It supported our findings to some extent, although the study did not mention the cumulative incidence of CVD mortality 25 …”

“…21 Age at diagnosis, race, sex, Ann Arbor stage, and treatment are closely related to CVD in patients with Cancer September 15, 2022 cHL. 18,22,23,24,25 Several studies showed that the cumulative incidence of CVD mortality increased after long-term follow-up. 10,26,27 Few studies examined competing risks of the outcomes of patients with cHL by the risk factors mentioned previously.…”

“…The first peak period of cHL is around the age of 20 to 30 years, and the second peak is around the age of 50 to 70 years 21 . Age at diagnosis, race, sex, Ann Arbor stage, and treatment are closely related to CVD in patients with cHL 18,22,23,24,25 . Several studies showed that the cumulative incidence of CVD mortality increased after long‐term follow‐up 10,26,27 .…”

“…The development of therapeutic strategies further improves the cure rate in patients diagnosed with cHL. More recently, a study revealed that the cumulative incidence of noncancer‐specific death exceeded that of cancer mortality after approximately 280 months of follow‐up 25 . However, it remains unclear whether the incidence of CVD mortality will exceed that of cHL or other neoplasms and become the leading cause of death over time.…”