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Second Primary Gastrointestinal Cancers

DCEG investigators are leading a multi-center international study of second primary gastrointestinal (GI) cancers among survivors of Hodgkin lymphoma and cancers of the testis, breast, and cervix. This is the first study to comprehensively investigate the radiation-dose response relation for upper GI cancers following fractionated, higher dose radiation exposures.  It is also one of the few studies to investigate the role of chemotherapy in risk of secondary, non-hematologic malignancies.

The primary aim of the study is to provide new information on the relation between radiation dose and cancer risk for three GI organs (stomach, esophagus, and pancreas), for which few quantitative data exist. In addition, new data will be generated on site-specific age and temporal patterns of radiation-related GI cancers, and the possible influence of chemotherapy and other factors. These efforts involve analyses of both cohort and case-control studies.

Four international population-based cohorts including over 900,000 1-year survivors of Hodgkin lymphoma and cancers of the testis, breast, and cervix were assembled. The purpose of these cohorts was to evaluate site-specific second cancer incidence and trends in cause-specific mortality. Analyses of these cohorts have newly quantified the age and temporal patterns of risk for subsequent cancer and non-cancer outcomes, and highlighted that many of the excess risks often persist for over 25 years following the first cancer diagnosis. Survivors of testicular cancer were demonstrated to have increased risk of mortality from infections, digestive diseases, and circulatory diseases when compared with the general population. Survivors of both breast and cervical cancers experience excess risks of subsequent cancer at least 25 years after diagnosis, particularly for women diagnosed for these two cancers at young ages. In addition, breast cancer survivors have a higher risk of suicide than women in the general population. Finally, risk of solid cancers following Hodgkin lymphoma are strongly related to both young age at diagnosis and attained age, but do not appear to have changed over calendar time. In contrast, risk of acute myeloid leukemia following Hodgkin lymphoma has decreased over time, likely due to changes in chemotherapy.

Given the extensive nature of data collection required for a detailed evaluation of dose-response relations for radiotherapy and chemotherapy, a nested-case control design was chosen to address this aim, resulting in a total of seven case-control studies: Hodgkin lymphoma followed by stomach, pancreas, and esophagus cancers; testis cancer followed by stomach and pancreas cancers; breast cancer followed by esophagus cancer; and cervical cancer followed by stomach cancer. Initial analyses demonstrated that esophageal cancer risk following radiotherapy for breast cancer increased linearly with increasing radiation dose to the specific site of the esophageal tumor (P<0.001), and analyses of other case-control studies are ongoing.

For more information, contact Lindsay Morton.