Long-Term Cause-Specific Mortality in Hodgkin Lymphoma Patients

Simone de Vries, Michael Schaapveld, Cécile P.M. Janus, Laurien A. Daniëls, Eefke J. Petersen, Richard W.M. van der Maazen, Josée M. Zijlstra, Max Beijert, Marten R. Nijziel, Karijn M.S. Verschueren, Leontien C.M. Kremer, Anna M. van Eggermond, Pieternella J. Lugtenburg, Augustinus D.G. Krol, Judith M. Roesink, Wouter J. Plattel, Dick Johan van Spronsen, Gustaaf W. van Imhoff, Jan Paul de Boer, Berthe M.P. AlemanFlora E. van Leeuwen

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BACKGROUND: Few studies have examined the impact of treatment-related morbidity on long-term, cause-specific mortality in Hodgkin lymphoma (HL) patients.

METHODS: This multicenter cohort included 4919 HL patients, treated before age 51 years between 1965 and 2000, with a median follow-up of 20.2 years. Standardized mortality ratios, absolute excess mortality (AEM) per 10 000 person-years, and cause-specific cumulative mortality by stage and primary treatment, accounting for competing risks, were calculated.

RESULTS: HL patients experienced a 5.1-fold (AEM = 123 excess deaths per 10 000 person-years) higher risk of death due to causes other than HL. This risk remained increased in 40-year survivors (standardized mortality ratio = 5.2, 95% confidence interval [CI] = 4.2 to 6.5, AEM = 619). At age 54 years, HL survivors experienced similar cumulative mortality (20.0%) from causes other than HL to 71-year-old individuals from the general population. Whereas HL mortality statistically significantly decreased over the calendar period (P < .001), solid tumor mortality did not change in the most recent treatment era. Patients treated in 1989-2000 had lower 25-year cardiovascular disease mortality than patients treated in 1965-1976 (4.3% vs 5.7%; subdistribution hazard ratio = 0.65, 95% CI = 0.46 to 0.93). Infectious disease mortality was not only increased after splenectomy but also after spleen irradiation (hazard ratio = 2.81, 95% CI = 1.55 to 5.07). For stage I-II, primary treatment with chemotherapy (CT) alone was associated with statistically significantly higher HL mortality (P < .001 for CT vs radiotherapy [RT]; P = .04 for CT vs RT+CT) but lower 30-year mortality from causes other than HL (15.8%, 95% CI = 9.7% to 23.3%) compared with RT alone (36.9%, 95% CI = 34.0% to 39.8%, P = .001) and RT and CT combined (29.8%, 95% CI = 26.8% to 32.9%, P = .02).

CONCLUSIONS: Compared with the general population, HL survivors have a substantially reduced life expectancy. Optimal selection of patients for primary CT is crucial, weighing risks of HL relapse and long-term toxicity.

Original languageEnglish
Pages (from-to)760-769
Number of pages10
JournalJournal of the National Cancer Institute
Issue number6
Publication statusPublished - 1-Jun-2021

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