Treatment of Hodgkin lymphoma (HL) with certain radiation and chemotherapy regimens may put patients at increased risk for stomach cancer, according to a new study by scientists at the National Cancer Institute (NCI).

In the case–control study (Morton LM et al. J Clin Oncol 2013 Aug 26 [Epub ahead of print]), investigators analyzed data from 19,882 individuals who had survived for at least five years after a diagnosis of HL. The cohort included patients from the United States, Canada, Denmark, Finland, the Netherlands, Norway and Sweden. The researchers identified 89 patients who developed stomach cancer and 190 matched controls. Among the cases, the median age at diagnosis of HL was 30 years, and the median age at diagnosis of stomach cancer was 50 years.

For patients with stomach cancer, overall survival was poor: 88% of patients died, with a median survival of six months among them. The risk for stomach cancer increased with increasing radiation dose to the stomach, as well as with increasing number of chemotherapy cycles containing the alkylating agents procarbazine and dacarbazine.

“The association between procarbazine and stomach cancer risk was strikingly dependent on the radiation dose to the stomach,” the authors wrote.

Based on data from 25 cases and two controls, patients who received radiation to the stomach of 25 Gy or higher and procarbazine (≥5,600 mg/m2) had a 77.5-fold increased risk for stomach cancer (95% confidence interval [CI], 14.7-1,452). Conversely, no risk was evident among patients in any procarbazine dose category who received radiation to the stomach of less than 25 Gy.

Among patients who received procarbazine less than 5,600 mg/m2and radiation to the stomach of 25 Gy or higher, radiation-related risk for stomach cancer increased 2.8-fold (95% CI, 1.3-6.4; 23 cases, 41 controls). Additionally, dacarbazine was associated with a 5.4-fold increased risk for stomach cancer among patients who received radiation to the stomach less than 25 Gy (95% CI, 1.1-30.2; seven cases, eight controls).

“Our study adds strong support to the growing concern that stomach cancer is a rare but important adverse late effect of treatment for Hodgkin lymphoma,” said lead author Lindsay M. Morton, PhD, an investigator at the Radiation Epidemiology Branch, NCI Division of Cancer Epidemiology and Genetics, Bethesda, Md.

“Because Hodgkin lymphoma patients commonly receive treatment in their 20s and 30s, many of the stomach cancers arise before age 50, nearly 20 years earlier than is typical for newly diagnosed patients who have never had cancer,” Dr. Morton noted. “Clinicians who follow these survivors should be alert to patient complaints related to the gastrointestinal tract.”