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Table of Contents
Year : 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

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

Date of Submission13-Nov-2021
Date of Decision21-Nov-2021
Date of Acceptance22-Nov-2021
Date of Web Publication29-Dec-2021

Correspondence Address:
Suvir Singh
Department of Clinical Hematology and Stem Cell Transplantation, Dayanand Medical College and Hospital, Ludhiana - 141 001, Punjab
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/crst.crst_282_21

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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;4:807-8

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 Aug 20];4:807-8. Available from: https://www.crstonline.com/text.asp?2021/4/4/807/334220

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.

  References Top

Cutter DJ, Ramroth J, Diez P, Buckle A, Ntentas G, Popova B, 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. J Clin Oncol 2021;39:3591-601.  Back to cited text no. 1
George J, Rapsomaniki E, Pujades-Rodriguez M, Shah AD, Denaxas S, Herrett E, et al. How does cardiovascular disease first present in women and men? Incidence of 12 cardiovascular diseases in a contemporary cohort of 1,937,360 people. Circulation 2015;132:1320-8.  Back to cited text no. 2
Shanbhag S, Ambinder RF. Hodgkin lymphoma: A review and update on recent progress. CA Cancer J Clin 2018;68:116-32.  Back to cited text no. 3
Follows GA, Ardeshna KM, Barrington SF, Culligan DJ, Hoskin PJ, Linch D, et al. Guidelines for the first line management of classical Hodgkin lymphoma. Br J Haematol 2014;166:34-49.  Back to cited text no. 4
van Nimwegen FA, Schaapveld M, Janus CP, Krol AD, Petersen EJ, Raemaekers JM, et al. Cardiovascular disease after Hodgkin lymphoma treatment: 40-year disease risk. JAMA Intern Med 2015;175:1007-17.  Back to cited text no. 5
van Nimwegen FA, Schaapveld M, Cutter DJ, Janus CP, Krol AD, Hauptmann M, et al. Radiation dose-response relationship for risk of coronary heart disease in survivors of Hodgkin lymphoma. J Clin Oncol 2016;34:235-43.  Back to cited text no. 6
Jones LW, Liu Q, Armstrong GT, Ness KK, Yasui Y, Devine K, et al. Exercise and risk of major cardiovascular events in adult survivors of childhood hodgkin lymphoma: A report from the childhood cancer survivor study. J Clin Oncol 2014;32:3643-50.  Back to cited text no. 7
van Leeuwen-Segarceanu EM, Bos WJ, Dorresteijn LD, Rensing BJ, der Heyden JA, Vogels OJ, et al. Screening Hodgkin lymphoma survivors for radiotherapy induced cardiovascular disease. Cancer Treat Rev 2011;37:391-403.  Back to cited text no. 8
Mulrooney DA, Nunnery SE, Armstrong GT, Ness KK, Srivastava D, Donovan FD, et al. Coronary artery disease detected by coronary computed tomography angiography in adult survivors of childhood Hodgkin lymphoma. Cancer 2014;120:3536-44.  Back to cited text no. 9
Dora TK, Deshmukh J, Chatterjee A, Goel A, Bose S, Singh A, et al. Conformal radiation therapy versus volumetric arc therapy in high dose concurrent chemoradiotherapy for carcinoma esophagus: A retrospective analysis. Cancer Res Stat Treat 2021;4:456-65.  Back to cited text no. 10
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Petersen PM, Aznar MC, Berthelsen AK, Loft A, Schut DA, Maraldo M, et al. Prospective phase II trial of image-guided radiotherapy in Hodgkin lymphoma: Benefit of deep inspiration breath-hold. Acta Oncol 2015;54:60-6.  Back to cited text no. 11
De Sanctis V, Bolzan C, D'Arienzo M, Bracci S, Fanelli A, Cox MC, et al. Intensity modulated radiotherapy in early stage Hodgkin lymphoma patients: Is it better than three dimensional conformal radiotherapy? Radiat Oncol 2012;7:129.  Back to cited text no. 12
Higby C, Khafaga Y, Al-Shabanah M, Mousa A, Ilyas M, Nazer G, et al. Volumetric-modulated arc therapy (VMAT) versus 3D-conformal radiation therapy in supra-diaphragmatic Hodgkin's lymphoma with mediastinal involvement: A dosimetric comparison. J Egypt Natl Canc Inst 2016;28:163-8.  Back to cited text no. 13
Engert A, Plütschow A, Eich HT, Lohri A, Dörken B, Borchmann P, et al. Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med 2010;363:640-52.  Back to cited text no. 14
Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, et al. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med 2011;366:399-408.  Back to cited text no. 15


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