Excess Cardiovascular Disease Risk in Patients With Early-Stage Lymphoma: Personalizing Radiotherapy Delivery

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As reported in the Journal of Clinical Oncology by Cutter et al, an analysis from the UK NCRI RAPID trial of positron-emission tomography (PET)-directed therapy in patients with early-stage Hodgkin lymphoma indicated that the use of involved-field radiotherapy in PET-negative patients who had received anthracycline-containing chemotherapy was associated with average 30-year excess risks of 6.24% for cardiovascular disease and 0.5% for cardiovascular disease mortality.

As stated by the investigators, “The contemporary management of early-stage Hodgkin lymphoma involves balancing the risk of late adverse effects of radiotherapy against the increased risk of relapse if radiotherapy is omitted. This study provides information on the risk of radiation-related cardiovascular disease to help personalize the delivery of radiotherapy in early-stage Hodgkin lymphoma.”

Study Details

The analysis included data from 144 patients who were PET-negative after three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy and received involved-field radiotherapy. Cardiac and carotid radiation doses and chemotherapy exposure were combined with established dose-response relationships and population-based cardiovascular disease incidence and mortality rates to analyze cardiovascular disease risk. Risk ranges reflect anthracycline and radiotherapy doses and involved structures. 

Key Findings

The average mean heart radiation dose was 4.0 Gy (range = 0.1–24.0 Gy) and the average bilateral common carotid artery dose was 21.5 Gy (range 0.6–38.1 Gy).

The average predicted 30-year risk of developing cardiovascular disease was 35.8% (range = 7.7%–86.8%), comprising 22.9% expected risk from general population rates, 6.7% absolute excess associated with anthracycline use, and 6.2% absolute excess risk associated with involved-field radiotherapy. Involved-field radiotherapy–associated risk included 3.28% risk for ischemic heart disease and 2.31% risk for stroke. The predicted absolute excess risk was < 5% in 58% of patients and > 10% in 24%, with a range of 0.31% to 31.09% across patients.

The average predicted 30-year cardiovascular disease mortality risk was 5.02% (range = 0.30%–19.37%), comprising 3.52% expected risk from general population, 0.94% absolute excess risk associated with anthracycline use, and 0.56% absolute excess risk associated with involved-field radiotherapy. Involved-field radiotherapy risk included 0.36% risk of death due to ischemic heart disease and 0.14% due to stroke; for overall heart disease, excess risk was 0.42%, including 0.79% vs 0.05% with vs without mediastinal involvement. The predicted absolute excess risk was < 0.5% in 67% of patients and > 1% in 15%, with a range of 0.01% to 6.79% across patients.

The investigators concluded, “Predicted excess cardiovascular risk is small for most patients, so radiotherapy may provide net benefit. However, for a minority of patients receiving high doses of radiation to cardiovascular structures, it may be preferable to consider advanced radiotherapy techniques to reduce doses or to omit radiotherapy and accept the increased relapse risk. Individual assessment of cardiovascular and other risks before treatment would allow personalized decision making about radiotherapy in early-stage Hodgkin lymphoma.”

David J. Cutter, MD, DPhil, of the Nuffield Department of Population Health, University of Oxford, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Cancer Research UK and British Heart Foundation Centre for Research Excellence. For full disclosures of the study authors, visit

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