Risk of heart failure in survivors of Hodgkin lymphoma: effects of cardiac exposure to radiation and anthracyclines

Abstract

Key Points• Risk of HF increases following cardiac radiation doses above 20 Gy.• Anthracyclines increase HF rate by threefold independently of radiation.Hodgkin lymphoma (HL) survivors treated with radiotherapy and/or chemotherapy are known to have increased risks of heart failure (HF), but a radiation dose-response relationship has not previously been derived. A case-control study, nested in a cohort of 2617 five-year survivors of HL diagnosed before age 51 years during 1965 to 1995, was conducted. Cases (n 5 91) had moderate or severe HF as their first cardiovascular diagnosis. Controls (n 5 278) were matched to cases on age, sex, and HL diagnosis date. Treatment and follow-up information were abstracted from medical records. Mean heart doses and mean left ventricular doses (MLVD) were estimated by reconstruction of individual treatments on representative computed tomography datasets. Average MLVD was 16.7 Gy for cases and 13.8 Gy for controls (P difference 5 .003). HF rate increased with MLVD: relative to 0 Gy, HF rates following MVLD of 1-15, 16-20, 21-25, and ‡26 Gy were 1.27, 1.65, 3.84, and 4.39, respectively (P trend < .001). Anthracyclinecontaining chemotherapy increased HF rate by a factor of 2.83 (95% CI: 1.43-5.59), and there was no significant interaction with MLVD (P interaction 5 .09). Twenty-five-year cumulative risks of HF following MLVDs of 0-15 Gy, 16-20 Gy, and ‡21 Gy were 4.4%, 6.2%, and 13.3%, respectively, in patients treated without anthracycline-containing chemotherapy, and 11.2%, 15.9%, and 32.9%, respectively, in patients treated with anthracyclines. We have derived quantitative estimates of HF risk in patients treated for HL following radiotherapy with or without anthracycline-containing chemotherapy. Our results enable estimation of HF risk for patients before treatment, during radiotherapy planning, and during follow-up. (Blood. 2017;129(16):2257-2265 Medscape Continuing

Cumulative anthracycline exposure and risk of cardiotoxicity; a Danish nationwide cohort study of 2440 lymphoma patients treated with or without anthracyclines

“…Whether higher cumulative anthracycline dose in those patients would have increased risk of cardiotoxicity is unknown. Our database also lacks information on radiotherapy site, which has been associated with CHF in Hodgkin lymphoma survivors if radiation doses to the myocardium exceeded 20 Gy (van Nimwegen et al , ). We did not see any association between radiotherapy and cardiotoxicity in our study, potentially reflecting the fact that mediastinal irradiation is uncommon in DLBCL.…”

Adolescent and young adult Hodgkin lymphoma: Raising the bar through collaborative science and multidisciplinary care

“…In one study, 20–25 Gy was associated with 5%–6% cumulative incidence, while 36 Gy was associated with 21% cumulative incidence of cardiovascular disease. By age 50 years, the cumulative incidence of HL survivors experiencing at least one grade 3–5 toxicity was 45.5% versus 15.7% in controls . Recent efforts to reduce RT doses and narrow radiation fields are at the forefront of research.…”

Temporal trends in treatment‐related incidence of diseases of the circulatory system among Hodgkin lymphoma patients

“…While the refinement of treatment options for HL has significantly improved the prognosis for affected patients, including patients diagnosed in advanced stage, late effects (encompassing also cerebrovascular conditions) from treatment toxicity remain a concern. Results from existing literature have contributed to an enhanced understanding of the timing and magnitude of very late treatment effects, especially in relation to RT, but are primarily based on patients treated with outdated therapy (including extensive field RT) . Furthermore, several previous studies have reported increased cumulative probabilities of cardiac late effects among HL patients, such as heart failure, coronary heart disease and valvular heart disease, showing an up to 50% risk of being diagnosed with cardiovascular disease within 40 years after diagnosis (taking the competing risk of death into account) .…”

“…However, while approximately 90% of young HL patients today will be cured from their lymphoma, treatment toxicity remains a concern . Morbidity from diseases of the circulatory system (DCS) among patients treated for HL includes, e.g., coronary heart disease, congestive heart failure, valvular heart disease and stroke . Furthermore, the 40‐year cumulative incidence of cardiovascular disease has been shown to be above 50% among HL survivors .…”