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J Clin Oncol. 2013 Sep 20;31(27):3369-77. doi: 10.1200/JCO.2013.50.6832. Epub 2013 Aug 26.

Stomach cancer risk after treatment for hodgkin lymphoma.

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Lindsay M. Morton, Graça M. Dores, Rochelle E. Curtis, Ethel S. Gilbert, Ruth A. Kleinerman, and Joseph F. Fraumeni Jr, National Cancer Institute, Bethesda, MD; Graça M. Dores, Department of Veterans Affairs Medical Center, Oklahoma City, OK; Charles F. Lynch, University of Iowa, Iowa City, IA; Marilyn Stovall, Susan A. Smith, and Rita E. Weathers, University of Texas MD Anderson Cancer Center, Houston, TX; Per Hall and Magnus Kaijser, Karolinska Institute, Stockholm, Sweden; David C. Hodgson and Eric J. Holowaty, University of Toronto, Toronto, Ontario, Canada; Hans H. Storm, Danish Cancer Society; Michael Andersson, Copenhagen University Hospital, Copenhagen, Denmark; Tom Børge Johannesen and Frøydis Langmark, Cancer Registry of Norway; Sophie D. Fossa, Oslo University Hospital and University of Oslo, Oslo, Norway; Michael Hauptmann, Alexandra W. Van den Belt-Dusebout, Berthe M. Aleman, and Flora E. van Leeuwen, Netherlands Cancer Institute, Amsterdam, the Netherlands; Heikki Joensuu and Leila Vaalavirta, Helsinki University Central Hospital; Eero Pukkala, Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland; Lois B. Travis, University of Rochester Medical Center, Rochester, NY.



Treatment-related stomach cancer is an important cause of morbidity and mortality among the growing number of Hodgkin lymphoma (HL) survivors, but risks associated with specific HL treatments are unclear.


We conducted an international case-control study of stomach cancer nested in a cohort of 19,882 HL survivors diagnosed from 1953 to 2003, including 89 cases and 190 matched controls. For each patient, we quantified cumulative doses of specific alkylating agents (AAs) and reconstructed radiation dose to the stomach tumor location.


Stomach cancer risk increased with increasing radiation dose to the stomach (Ptrend < .001) and with increasing number of AA-containing chemotherapy cycles (Ptrend = .02). Patients who received both radiation to the stomach ≥ 25 Gy and high-dose procarbazine (≥ 5,600 mg/m(2)) had strikingly elevated stomach cancer risk (25 cases, two controls; odds ratio [OR], 77.5; 95% CI, 14.7 to 1452) compared with those who received radiation < 25 Gy and procarbazine < 5,600 mg/m(2) (Pinteraction < .001). Risk was also elevated (OR, 2.8; 95% CI, 1.3 to 6.4) among patients who received radiation to the stomach ≥ 25 Gy but procarbazine < 5,600 mg/m(2); however, no procarbazine-related risk was evident with radiation < 25 Gy. Treatment with dacarbazine also increased stomach cancer risk (12 cases, nine controls; OR, 8.8; 95% CI, 2.1 to 46.6), after adjustment for radiation and procarbazine doses.


Patients with HL who received subdiaphragmatic radiotherapy had dose-dependent increased risk of stomach cancer, with marked risks for patients who also received chemotherapy containing high-dose procarbazine. For current patients, risks and benefits of exposure to both procarbazine and subdiaphragmatic radiotherapy should be weighed carefully. For patients treated previously, GI symptoms should be evaluated promptly.

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