Risks for Second Cancer After Hodgkin’s Lymphoma Therapy

Published - Written by James Yeh, M.D. M.P.H.

Second Cancer Risk Up to 40 Years after Treatment for Hodgkin’s LymphomaYou are meeting Mrs. Mason in your primary care clinic for the first time today. She has a history of Hodgkin’s lymphoma and was treated with chemotherapy and radiation therapy over 25 years ago. You wonder what is her risk for additional cancers as a result of treatment for Hodgkin’s lymphoma?

While the use of radiation therapy and alkylating agents in the chemotherapy regime for Hodgkin’s lymphoma have resulted in high rates of survival, these individuals also experience higher risks of secondary solid cancers than the average population due to treatment side effects. Hodgkin’s lymphoma treatments have evolved to reduce this risk of acquiring secondary solid cancers.

In a study recently published in NEJM, the authors asked whether the kind of treatments that have been implemented since the late 1980s, with lower radiation doses, smaller radiation target fields, and less toxic chemotherapy, have had an impact on the risk of developing a second cancer.

The authors assessed a cohort of 3905 patients in the Netherlands with Hodgkin’s lymphoma who had survived for at least 5 years. This group of patients were initially treated at seven academic medical centers and hospitals between 1965 and 2000. The patients were 15 to 51 years old at the time of the treatment. The primary outcome was the incidence risk of second cancer.

About 61% of patients had received combined modality therapy with chemotherapy and radiation therapy with the remaining receiving either radiation only (27%) or chemotherapy only (12%). With a median follow-up of about 19 years, about a quarter of the cohort (n=908) developed 1,055 second cancers.

Compared to the general population, the risk of a second cancer was more than four times greater (4.6-fold, 95% CI 4.3-4.9) in patients with Hodgkin’s lymphoma. This resulted in 122 excess cancers per 10,000 person-years. Notably, the second cancer risk was not lower in patients treated in the most recent calendar period studied (1989 to 2000) compared to patients treated in earlier periods.

This risk continued to be elevated even 35 years after the initial treatment, and by 40 years, nearly 50% of the patients had a second cancer. The highest absolute excess risks were seen for cancers of the lung, breast, GI-tract, and non-Hodgkin’s lymphoma. Although lower risk of breast cancer was associated with the use of smaller radiation fields when compared to mantle field radiotherapy, breast cancer risk continues to remain elevated in the most recent period studied when less extensive radiotherapy was used.

In a NEJM editorial, Radford and Longo note that “with respect to stomach, pancreas and colorectal cancers, the authors found that the greatest risk was associated with previous infra-diaphragmatic radiotherapy and/or procarbazine containing chemotherapy for which a dose response effect was observed. Procarbazine was also implicated in the increased risk of non-Hodgkin’s lymphomas.”

What did we learn from this study? We learned that the risk of developing second cancers remain elevated despite changes over time in the treatment of Hodgkin’s lymphoma. Clinicians who take care of survivors of Hodgkin’s lymphoma should be vigilant of second cancer risks.

At the end of the visit with Mrs. Mason, you ordered screening tests for breast, lung, and colon cancers. You also look up the guidelines on surveillance care on the National Comprehensive Cancer Network and on the American Society of Clinical Oncology websites. Which cancer screening tests should be ordered for Hodgkin’s lymphoma survivors? When should these screening tests start? 

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