Survival after Hodgkin lymphoma: causes of death and excess mortality in patients treated in 8 consecutive trials.

Background: The objective of this study was to analyze cause-specific excess mortality in adult patients with Hodgkin lymphoma (HL) with respect to treatment modality.

Methods: The study population consisted of 4401 Belgian, Dutch, and French patients aged 15 to 69, in all stages of disease, who were treated between 1964 and 2000. Excess mortality was expressed by using a standardized mortality ratio (SMR) and calculating the absolute excess risk (AER). Relative survival was calculated and analyzed using a previously described regression model.

Results: At a median follow-up of 7.8 years, 725 of 4401 patients (16.5%) had died, 51% of HL, 10% of treatment-related toxicity, 18% of second cancer, 5% of cardiovascular diseases, 2% of infections, 8% of other causes, and 6% of an unspecified cause. Overall, the SMR was 7.4 (95% confidence limits [CL], 6.9-8.0), and the AER was 182.8 (95% CL, 167.7-198.8). These indicators were 3.8 (95% CL, 3.2-4.5) and 27.9, respectively, for deaths from a second cancer and 4.0 (95% CL, 2.3-6.7) and 3.3, respectively for deaths from infection. After 15 years, the observed survival rate was 75%, and the relative survival rate was 80%. In patients with early-stage disease, the overall excess mortality was associated with age > or =40 years (P = .007), men (P < .001), unfavorable prognosis features (P < .001), and 2 treatments: combined nonstandard nonalkylating chemotherapy plus involved-field radiotherapy (P = .002) and mantle-field irradiation alone (P = .003). With follow-up censored at the first recurrence, no treatment modalities were associated with excess mortality.

Conclusions: Progressive disease remained the primary cause of death in patients with HL in the first decades after treatment. Excess mortality in patients with early-stage disease was linked significantly to treatment modalities that were associated with poor treatment failure-free survival.