Weight gain after lymphoma treatment: fat or fiction?

The evolution of lymphoma therapy over the last several decades stands as one of the great success stories of medical oncology. More than 80% of patients with Hodgkin lymphoma can now expect to live 5 years beyond diagnosis, and 5-year survival for many non-Hodgkin lymphomas exceeds 60% [1]. But the story does not end when the cancer is controlled, and one consequence of our success is the need to further evolve our thinking from cancer survival to cancer survivorship more broadly. Continuing to improve outcomes after a lymphoma diagnosis will just as surely require a better understanding of the long-term and late effects of lymphoma treatment as innovations in treatment itself.

In solid tumor oncology, where survivorship studies are more mature, the metabolic consequences of cancer treatment, particularly obesity, have attracted much recent attention [2]. For instance, data are relatively consistent in supporting an association between adjuvant chemotherapy for breast cancer and subsequent weight gain, which may influence not only breast cancer-specific survival but also health status in general [3]. To date obesity has been explored for its causal association with lymphoma incidence and its potential impact on lymphoma survival, but obesity as a consequence of lymphoma treatment has not yet been systematically investigated [4].

The study by Lynce et al. represents a first step in that direction [5]. Noting that survivors of childhood blood cancers appear more likely to gain weight than age-matched controls, they seek to determine whether similar weight gain is observed among adult patients receiving chemotherapy for lymphoma. They assembled a cohort of patients treated at their institution for a heterogeneous group of Hodgkin and non-Hodgkin lymphomas and retrospectively followed them for 18 months beyond their initial treatment, to characterize changes in weight and body mass. While the study's findings are necessarily limited by the lack of a control population and relatively short follow-up, they are nevertheless telling. Sixty-one percent of patients gained an average 10.4 pounds (6.4% above baseline) during the observation period. And even among the group of patients without B-symptoms at diagnosis (used here as a proxy for pre-morbid weight loss), the average weight gain from baseline approached 4%. As the authors point out in their discussion, this represents a near doubling of the rate (0.6% body weight/year) observed among otherwise healthy adults in a recent US population-based study [6]. These observations should be confirmed through subsequent study and, if so, prompt more rigorous investigation to understand the etiology of this process.

Perhaps the most concerning finding presented here, however, is quite nearly self-evident. At the time of diagnosis, 34.7% of the patients were overweight and 30.6% were obese, which proportions increased to 37.3% and 35.9%, respectively, at the 18-month follow-up. No matter the time course or cause for the weight gain, these patients represent a population at markedly increased risk for obesity-related morbidity, particularly cardiovascular disease. Doxorubicin and other anthracyclines remain key components of much lymphoma chemotherapy, and their association with cardiomyopathy has been well characterized. Yet even after controlling for age, gender, cumulative dose and mediastinal radiation, obesity remains an independent risk factor for myocardial dysfunction among doxorubicin-treated patients with lymphoma [7]. Helping obese patients with lymphoma lose weight, and preventing overweight patients from becoming obese, could thus potentially reduce the long-term morbidity associated with anthracycline chemotherapy. National guidelines for Hodgkin disease already recommended interventions to decrease the likelihood of adverse cardiovascular outcomes, and similar attention to modifiable cardiovascular risk factors would seem reasonable for most patients with non-Hodgkin lymphoma as well [8].

Studies like the one by Lynce et al. help to open a new chapter in lymphoma research. While work continues to improve the efficacy and limit the toxicity of future therapy, physicians must necessarily contend with the unintended consequences of past and present treatments. To achieve a satisfying ending for survivors of lymphoma will require far greater attention to what unfortunately does not always follow happily after.

Potential conflict of interest:

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