Hodgkin lymphoma: Late effects of treatment and guidelines for surveillance

https://doi.org/10.1053/j.seminhematol.2016.05.008Get rights and content

Abstract

Long-term survivors of Hodgkin lymphoma (HL) are at risk for a range of late effects, with second malignant neoplasm and cardiovascular diseases being the leading causes of death in these patients. The excess risks remain significantly elevated decades after treatment, and are clearly associated with extent of treatment exposures. Other late effects have also been identified, such as pulmonary dysfunction, endocrinopathies, muscle atrophy, and persistent fatigue. Systemic documentation of late effects and recognition of treatment- and patient-related risk factors are important, as they inform optimal surveillance and risk-reduction strategies, as well as guide therapeutic modifications in newly diagnosed patients to minimize treatment-related complications. As HL therapy evolves over time, with adoption of novel agents and contemporary treatment techniques, late effect risks and follow-up recommendations need to be continuously updated.

Introduction

After the introduction of modern radiotherapy (RT) and combination chemotherapy (CT) in the 1960s, Hodgkin lymphoma (HL) has become the prototype of a curable malignancy [1]. However, over the past decades it has been clearly demonstrated that both RT and CT can increase the risk of second malignant neoplasms (SMNs), cardiovascular disease (CVD), and other treatment complications [1], [2], [3], [4]. Excess mortality from SMNs and CVD has been demonstrated to substantially reduce the life expectancy of HL survivors [5], [6].

Section snippets

Risk of second malignancy

Increased risks of solid tumors in irradiated HL patients and of leukemia in CT-treated patients have been reported consistently in the literature [4], [7]. In a recent study that included HL patients treated from 1965 to 2000 [8], the excess risk of second malignancy remains significantly increased beyond 35 years after HL treatment (Fig. 1), with a 40-year cumulative incidence of second cancer estimated at 43.6% (Fig. 2). The largest standardized incidence ratios (SIRs) are observed for

Risk of cardiovascular disease

Both RT involving the heart and anthracycline-containing CT can increase the risk of CVD in HL survivors. Radiation-induced CVD includes coronary heart disease (CHD), valvular heart disease (VHD), myocardial dysfunction, electrical conduction abnormalities, and pericardial disease [2], [24]. Anthracyclines can, depending on the cumulative dose, lead to both acute cardiomyopathy and chronic cardiac complications (especially HF) [25], [26], [27]. RT- and anthracycline-associated cardiac damage

Pulmonary dysfunction

Both mediastinal RT and bleomycin are associated with acute lung toxicity, but can also lead to persistently reduced pulmonary function and long-term pulmonary fibrosis. Several studies have documented decline in pulmonary function in HL patient after adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy and mediastinal irradiation, with persistently reduced function up to 3 years post-treatment. In a study on HL survivors beyond 5 years after treatment [46], almost 30% of the

Current guidelines for surveillance

Several organizations offer surveillance guidelines for HL survivors, with special attention to key late effects such as second malignancy and cardiovascular disease. The National Comprehensive Cancer Network (NCCN) provides guidelines for monitoring for late effects specifically for HL survivors 5 years after initial treatment, including types of testing and their timing [70]. The long-term follow-guidelines from Children’s Oncology Group (COG) present detailed recommendation according to

Conclusions and future directions

Decades of successful HL therapy has allowed the elucidation of an array of long-term complications among the survivors. The study of late effects is critical as it guides patient counseling and development of follow up strategies for survivors, and motivates development of new treatments aimed to mitigate the side effects. However, late effects of treatment and the surveillance guidelines are moving targets. As new agents and novel techniques are introduced for HL, additional time is needed

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