Stomach cancer risk after treatment for hodgkin lymphoma

Abstract

Purpose: 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.

Patients and methods: 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.

Results: 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.

Conclusion: 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.

Fig 1.

Mean radiation dose to stomach from specific radiotherapy fields for Hodgkin lymphoma with at least some subdiaphragmatic exposure, by stomach site. All radiotherapy fields with exclusively supradiaphragmatic exposure gave mean dose to all stomach sites < 2 Gy, including mantle with lower border at diaphragm (51% cases, 55% controls; mean total stomach dose, 1.3 Gy), mediastinum (21% cases, 24% controls; mean, 0.8 Gy), supraclavicular (10% cases, 7% controls; mean, 0.1 Gy), axilla (17% cases, 16% controls; mean, 0.5 Gy), neck with or without head (37% cases, 27% controls; mean, 0.2 Gy), and other neck/chest (9% cases, 7% controls; mean, 0.4 Gy). (*) Percentages were calculated among patients who received radiotherapy (82 cases, 164 controls). Patients may have received multiple treatment fields.

Fig 2.

Risk of stomach cancer after Hodgkin lymphoma in relation to radiation dose to stomach and procarbazine dose. OR, odds ratio. (*) Radiation dose was estimated to stomach tumor location (matched location for controls). (†) Assuming procarbazine dose of 1,400 mg/m² per cycle (14 days × 100 mg/m² per day), categories correspond to zero, one to three, four to five, and ≥ six cycles of MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) or MOPP-like regimens. Other protocols (eg, MOPP-ABV [MOPP–doxorubicin, bleomycin, and vinblastine], BEACOPP [bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone]) include procarbazine dose of 700 mg/m² per cycle. (‡) ORs and 95% CIs were adjusted for receipt of any dacarbazine and unknown radiation dose.