Cardiovascular Risk May Increase With Radiotherapy Use During Treatment of Early-Stage Hodgkin Lymphoma

PET-negative patients who are treated with radiotherapy had a slightly increased absolute cardiovascular disease risk, although magnitude of these effects varied widely.

Although a majority of patients with early-stage Hodgkin lymphoma experience reduced relapse risk with advanced radiotherapy techniques, the long-term risk of increased cardiovascular disease should be monitored, according to a study published in the Journal of Clinical Oncology.

Investigators found that the average 30-year radiation-related absolute excess overall cardiovascular mortality was 0.56% (range, 0.01%-6.79%). More specifically, mortality was less than 0.5% in 67% of patients and greater than 1% in 15%. The 30-year excess incidence was 6.24% (range, 0.31%-31.09%), with 58% of patients at less than 5% and 24% at greater than 10%.

Patients treated with involved-field radiation therapy (IFRT) on the RAPID trial (NCT00943423) were examined in this analysis. Data from those who were PET-negative (n = 426), defined as having a Deauville score of 1 or 2, following initial chemotherapy were used to predict 30-year radiation-related cardiovascular risk.

There were 183 PET-negative patients who received IFRT, but sufficient data were only available for 144. There were 129 PET-positive patients who received IFRT, but sufficient data were only available for 103.

The mean heart dose (MHD) for PET-negative patients was 4.0 Gy, 0.3 for those without and 7.8 Gy with mediastinal involvement. For almost all patients without mediastinal involvement (72 out of 73; 98.6%), the MHD was 1 Gy, whereas in those with mediastinal involvement, the MHD ranged widely (range, 0.8-24.0 Gy). Patients who received the mean radiation dose to the common carotid arteries received over 20 Gy on average, but wide variations were noted in those receiving unilateral and bilateral neck irradiation. Those who were PET-positive and received IFRT had similar dose distributions as those who were PET-negative.

PET-negative patients who received IFRT after doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) had an average predicted 30-year cardiovascular mortality risk of 5.02% (range, 0.30%-19.37%), comprised of expected risk from the general population (3.52%), absolute risk due to anthracycline use (0.94%), and risk brought on by IFRT (0.56%). The absolute excess risk from IFRT was specifically related to ischemic heart disease (0.36%) and stroke (0.14%). Investigators estimated that if IFRT was given selectively to 50% of PET-negative patients with the lowest risk, then the 30-year absolute radiation related risk would be 0.11%.

The average predicted 30-year absolute excess risk of radiation-related mortality from heart disease for PET-negative patients receiving less than 0.5 Gy MHD was 0.03% versus 2.20% in those receiving 10 Gy or more. The average risk was 0.42%, at 0.79% for those with mediastinal involvement and 0.05% for those without. Women had a higher MHD at 5.4 Gy versus 2.7 Gy in men, attributable to a higher rate of mediastinal involvement (59% vs 41%, respectively). However, the 30-year absolute excess mortality risk in treatment-related heart disease was higher in men (1.5%) than women (1.2%).

Additionally, the predicted 30-year average absolute excess radiation-related risk of mortality from stroke for those receiving less than 10 Gy was 0.05% versus 0.24% in those receiving 30 Gy or more; the average for all patients was 0.14%.

Patients receiving IFRT after receiving ABVD had a 35.8% average predicted 30-year risk of developing cardiovascular disease, comprised of expected risk from general population (22.9%), absolute excess risk because of anthracycline chemotherapy (6.7%), and risk from IFRT (6.2%). The absolute excess risk because of IFRT included the risk of ischemic heart disease (3.28%) and stoke (2.31%). The 30-year predicted absolute radiation-related risk was less than 5% in 58% of patients and the mean individual risk was 3.61%. The individual risk was greater than 10% in 24% of patients. Investigators predicted if IFRT was given to 50% of the population, the 30-year excess risk would be 1.79%.

The predicted 30-year absolute excess risk of developing radiation-related heart disease for those receiving less than 0.5 Gy was 0.21% and 16.33% for those receiving 10 or more Gy. The average radiation-related risk for individuals was 3.93%, at 7.66% for those with mediastinal involvement and 0.31% for those without.

Patients who were receiving less than 10 Gy had a predicted 30-year absolute excess risk of incident stroke of 0.66% versus 3.42% for 30 Gy. The median radiation-related risk for individuals was 2.31%.

“Our study gives a representative picture of cardiovascular risk from IFRT for all patients in the RAPID trial who were PET- negative after initial chemotherapy. Previous dosimetry studies have concentrated largely on patients with more extensive mediastinal involvement and reported techniques to reduce cardiac exposure. In this study, radiotherapy did not include the mediastinum for more than half the patients and we confirm previous findings that the level of mediastinal involvement is a critical determinant of cardiac dose, largely independent of the radiation techniques used,” concluded investigators.


Cutter DJ, Ramroth J, Diez P, et al. Predicted risks of cardiovascular disease following chemotherapy and radiotherapy in the UK NCRI RAPID trial of positron emission tomography-directed therapy for early-stage Hodgkin lymphoma. Published Online August 13. 2021. J Clin Oncol. doi:10.1200/JCO.21.00408

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