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NCI Study Links Hodgkin Lymphoma Treatment to Risk of Stomach Cancer

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Key Points

  • Hodgkin lymphoma survivors who received subdiaphragmatic radiotherapy and chemotherapy regimens containing high doses of the alkylating agent procarbazine were at an increased risk of developing stomach cancer.
  • Secondary malignancies, such as breast, lung, and stomach cancers are a leading cause of morbidity and mortality in survivors of Hodgkin lymphoma.
  • Expanded screening for second cancers in the highest-risk patients may be warranted, along with expanded research of carcinogenic risks with other drugs commonly used today in treating cancer.

Hodgkin lymphoma survivors who received subdiaphragmatic radiotherapy and chemotherapy regimens containing high doses of the alkylating agent procarbazine (Matulane) were at an increased risk of developing stomach cancer, according to a large study by scientists at the National Cancer Institute (NCI). The study is reported in the Journal of Clinical Oncology.

While major advances in the treatment of Hodgkin lymphoma, including new types of chemotherapy and more-targeted radiotherapy, have led to dramatic improvements in 5-year survival rates—88% today vs 72% in the 1970s, according to data from the NCI’s Surveillance, Epidemiology and End Results Program—secondary malignancies, such as breast, lung, and stomach cancers are a leading cause of morbidity and mortality. Emerging evidence suggests that the development of secondary gastrointestinal malignancies is a major concern as survivors of Hodgkin lymphoma age and that treatments for Hodgkin lymphoma may play a critical role in the development of these malignancies, wrote the study researchers.

To better understand the link between Hodgkin lymphoma treatments and subsequent stomach cancer risk, Lindsay M. Morton, PhD, NCI Division of Cancer Epidemiology and Genetics, and her colleagues analyzed data from the Netherlands, Denmark, Finland, Norway, Sweden, the United States, and Canada. Their analysis included a cohort of nearly 20,000 survivors of Hodgkin lymphoma who were diagnosed between 1953 and 2003. Of 17,477 cases examined, the researchers identified 89 survivors who later developed stomach cancer. Detailed information about their treatments was obtained from patient medical records, which the scientists used to estimate radiation doses to the stomach and calculate the doses and types of chemotherapy used.

Determining a Link to Stomach Cancer

By comparing the treatments received by the survivors of Hodgkin lymphoma who developed stomach cancer with the treatments received by survivors who did not, the researchers were able to determine the risks of developing stomach cancer from Hodgkin lymphoma treatment. Their analysis found that the risk of stomach cancer increased with increasing doses of radiation to the stomach. Patients who received the highest radiation doses had a risk of developing stomach cancer nearly threefold greater than patients who received the lowest doses. In addition, the risks associated with radiation were even higher for survivors who also received procarbazine.

The NCI study also suggested an increased stomach cancer risk in patients who received a similar alkylating agent dacarbazine, a component of the chemotherapy regimen ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), which, according to the authors, is the most commonly used first-line therapy for Hodgkin lymphoma in the United States today. More research on this outcome is needed, however, since few patients in the study received dacarbazine, said the researchers.

Screening for Secondary Cancers May Be Warranted

“Our study adds strong evidence to the growing concern that GI malignancies represent an important adverse late effect of treatment for patients with Hodgkin lymphoma and other patients receiving comparable treatments. For current patients, risks and benefits of exposure to both procarbazine and subdiaphragmatic radiotherapy should be weighed carefully,” wrote the researchers. “Consideration of expanded screening of [Hodgkin lymphoma] survivors for second cancers in the highest-risk patients may be warranted, along with expanded research of carcinogenic risks with other drugs that are commonly used today, including dacarbazine and platinum agents.” 

This research was supported by the Intramural Research Program of the NCI as well as through NCI-issued contracts. The authors reported no potential conflicts of interest. 

 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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