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Review
. 2016 Dec 2;2016(1):323-330.
doi: 10.1182/asheducation-2016.1.323.

Long-term risk of second malignancy and cardiovascular disease after Hodgkin lymphoma treatment

Flora E van Leeuwen  1 , Andrea K Ng  2
Affiliations
Review

Long-term risk of second malignancy and cardiovascular disease after Hodgkin lymphoma treatment

Flora E van Leeuwen et al. Hematology Am Soc Hematol Educ Program. .

Abstract

Long-term survivors of Hodgkin lymphoma (HL) experience several late adverse effects of treatment, with second malignant neoplasms (SMNs) and cardiovascular diseases (CVDs) being the leading causes of death in these patients. Other late effects have also been identified, such as pulmonary dysfunction, endocrinopathies (thyroid dysfunction, infertility), neck muscle atrophy, and persistent fatigue. HL survivors have two- to fourfold increased risks to develop SMNs and CVD compared with the general population. With respect to SMNs, radiotherapy is associated with 1.5- to 15-fold increased risk of solid malignancies. The relative risk (RR) of solid tumors increases steadily with increasing follow-up time from 5 to 15 years since radiotherapy, and remains elevated for at least 40 years. The RR of solid SMNs increases strongly with younger age at first treatment. Risks of lung, breast, and gastrointestinal (GI) cancers increase with higher radiation dose. Alkylating agent chemotherapy, especially procarbazine, does not only increase risk of leukemia but also of solid malignancies, in particular, cancers of the lung and GI tract. In contrast, gonadotoxic chemotherapy decreases the risk of radiation-associated breast cancer, through induction of premature menopause. Smoking appears to multiply the radiation- and chemotherapy-associated risks of lung cancer. Both radiotherapy and chemotherapy for HL may cause cardiovascular toxicity. Radiotherapy increases the risk of coronary heart disease, valvular heart disease, congestive heart failure (HF), and pericarditis, whereas anthracycline-containing chemotherapy increases the risks of HF and valvular heart disease. Cardiovascular toxicity following radiotherapy is usually observed from 5 to at least 35 years after therapy, whereas anthracycline-related toxicity is already observed during treatment, up to at least 25 years. The joint effects of anthracyclines, radiotherapy, and conventional cardiovascular risk factors (eg, hypertension, smoking, and physical inactivity) appear to be additive rather than multiplicative. HL survivors need lifelong risk-based screening for selected SMNs and CVDs. Furthermore, preventive strategies should include lifestyle and drug-based interventions to minimize exposure to conventional risk factors for cancer and CVD.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Risk (SIR and AER) of new malignancies after HL according to follow-up interval. CI, confidence interval; yrs, years.
Figure 2.
Figure 2.
Cumulative incidence of solid malignancy after HL according to calendar period of treatment. Solid lines represent the observed incidence; and dashed lines the expected incidence in the general population.
Figure 3.
Figure 3.
Cumulative incidence of CVDs after HL according to treatment, with death from any cause as a competing risk.
See this image and copyright information in PMC

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