Cancer Research, Statistics, and Treatment

: 2021  |  Volume : 4  |  Issue : 4  |  Page : 807--808

Risk of cardiovascular events after combined modality therapy for early-stage favorable Hodgkin's lymphoma: Low but not zero

Kaveri Joshi1, Suvir Singh2,  
1 Department of Immunohematology and Blood Transfusion, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Clinical Hematology and Stem Cell Transplantation, Dayanand Medical College and Hospital, Ludhiana, Punjab, India

Correspondence Address:
Suvir Singh
Department of Clinical Hematology and Stem Cell Transplantation, Dayanand Medical College and Hospital, Ludhiana - 141 001, Punjab

How to cite this article:
Joshi K, Singh S. Risk of cardiovascular events after combined modality therapy for early-stage favorable Hodgkin's lymphoma: Low but not zero.Cancer Res Stat Treat 2021;4:807-808

How to cite this URL:
Joshi K, Singh S. Risk of cardiovascular events after combined modality therapy for early-stage favorable Hodgkin's lymphoma: Low but not zero. Cancer Res Stat Treat [serial online] 2021 [cited 2022 May 28 ];4:807-808
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Full Text

Cutter et al. recently published data describing 600 patients with early-stage Hodgkin's lymphoma treated with combined modality therapy and the long-term cardiovascular risks in this cohort.[1] Based on the radiotherapy doses received by various cardiac structures and major intrathoracic vessels, an estimate of long-term cardiovascular risk was derived. Data from a large, published trial from the United Kingdom were used to estimate the cardiovascular risk and mortality per unit radiation received.[2] The average cardiac dose received was 4 Gy (range, 0.1–24), with more than 50% of the patients receiving <1 Gy. Based on the predictive model for long-term risk, overall excess incidence of 6.24% and excess cardiovascular mortality of 0.56% were predicted.

The results of this study are illustrative and clinically relevant for several reasons. Treatment of Hodgkin's lymphoma has evolved over the past four decades, with 5-year survival ranging from 80% to 90% in early-stage disease.[3] In order to reduce the toxicity in this group of patients, attempts have been made to abbreviate chemotherapy regimens to reduce long-term toxicity. As a result, two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 20 Gy involved-field radiotherapy have become standard compared to more intensive regimens.[4]

With more emerging data on long-term cardiovascular risks, the role of radiotherapy as part of combined modality therapy for early-stage disease continues to be an active topic for discussion. Long-term cardiovascular risk in survivors of Hodgkin's lymphoma was assessed in a large study including 2524 patients with a median follow-up of 20 years. Lymphoma survivors were noted to have a 4–6 fold higher cardiovascular risk compared to age-matched controls, with a 50% cumulative incidence of cardiovascular disease.[5] The risk was higher among patients receiving mediastinal radiation and anthracyclines as part of the treatment. Therefore, though the cardiovascular risk with combined modality therapy appears variable, it is definitely significant and provides opportunities for risk reduction over the long term.

First, although the absolute risk in several datasets appears low, various factors including radiation exposure to cardiac tissue and major vessels determine the long-term incidence of cardiovascular disease. It is also clear from several studies that other cardiovascular risk factors have an additive effect on the absolute cardiovascular risk for an individual. For instance, cardiovascular risk is heightened in patients who have a history of smoking, physical inactivity, or systemic hypertension.[6],[7] This provides a potential avenue for modifying long-term risk in these patients.

Therefore, objective assessment of baseline cardiovascular risk is recommended for all patients, with the potential omission of mediastinal radiation for the highest-risk patients.[8] Post treatment, screening for coronary artery disease can be performed non-invasively by computed tomography (CT) coronary angiography, which has acceptable sensitivity to be used as a screening tool.[9] CT coronary angiography is recommended starting 10 years after the completion of therapy. As noted above, management of other cardiovascular risk factors is paramount, and management of smoking, lifestyle, and hypertension can modulate long-term cardiovascular risk.

Advances in radiation techniques also enable the reduction of exposure to cardiovascular structures.[10] Deep inspiration breath hold has been shown to reduce cardiac and pulmonary exposure without reducing the treatment efficacy.[11] In addition, planning and dose calculation using intensity-modulated arc therapy/volumetric modulated arc therapy has been shown to enable better sparing of cardiovascular structures.[12],[13]

Further studies to evaluate the effect of reducing radiation doses must be planned. The pivotal HD10 trial displayed non-inferiority of 20 Gy versus 30 Gy as part of combined modality therapy, which provides a basis for studying the further reduction of radiation dosage.[14] The overall trade-off after omission of radiation therapy appears to be a lower progression-free survival, but there was no significant difference in the overall survival. The Canadian HD6 trial omitted radiation completely in early-stage Hodgkin's lymphoma, which showed non-inferiority by adding two more cycles of ABVD (total of 4 ABVD cycles) in a completely radiation-free regimen.[15] Although the trial received a lot of criticism, a radiation-free approach for young or female patients may be worth evaluating in a randomized trial.

At present, the role of radiation therapy as part of combined modality therapy appears essential, but the long-term risk of cardiovascular events, especially with mediastinal exposure, is not negligible. The approaches listed above will enable us to identify high-risk patients and attempt to further reduce the long-term risk in lymphoma survivors.

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Conflicts of interest

There are no conflicts of interest.


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