Hodgkin’s lymphoma survivors who undergo both radiotherapy and chemotherapy face an increased risk of subsequent pancreatic cancer, an intervention case-control study demonstrated. In fact, the risk was 18-fold among those who received subdiaphragmatic radiation delivered at 10 Gy or higher in addition to six or more cycles of chemotherapy that contained an alkylating agent.

"Several studies have reported significantly increased risks of pancreatic cancer among long-term HL [Hodgkin’s Lymphoma] survivors, but no prior study of HL survivors has assessed the risk of pancreatic cancer in relation to radiation dose or specific chemotherapeutic agents," researchers led by Dr. Graca M. Dores wrote in the July 25, 2014 issue of the Annals of Oncology. "In the general U.S. population, pancreatic cancer is the fourth most common cause of cancer death, with an overall 5-year relative survival of 5.8%," they noted.

A new study says that Hodgkin's lymphoma survivors who undergo both radiotherapy and chemotherapy face an increased risk of subsequent pancreatic cancer.

In what the investigators characterized as the first analysis of its kind, Dr. Dores of the division of cancer epidemiology and genetics at the National Cancer Institute and associates drew from six population-based registries and data from main hospitals in the Netherlands to locate HL survivors who received a diagnosis of HL as their primary cancer between 1953 and 2003 and who had survived at least 5 years beyond the initial diagnosis. The cohort was comprised of 19,882 HL survivors, including 36 cases of pancreatic cancer and 70 matched controls. The researchers used logistic regression to estimate odds ratios for pancreatic cancer by comparing the histories of case patients to those of matched controls (Ann. Oncol. July 25 [doi:10.1093/annonc/mdu287]).

The median age at HL diagnosis was 47 years, and 73% had stage I or II disease. Among the 36 patients who developed pancreatic cancer, the median age of pancreatic cancer onset among cases was 61 years, a median of 19 years following the initial HL diagnosis. Dr. Dores and associates found that the risk of pancreatic cancer increased with increasing radiation dose to the location of the pancreatic tumor (P = .005) and increasing number of chemotherapy cycles that contained alkylating agents (P = .008). The risk of prostate cancer was 18-fold higher among those who received subdiaphragmatic radiation delivered at 10 Gy or higher in addition to six or more cycles of chemotherapy that contained an alkylating agent. "This risk was significantly greater than the OR of 3.8 predicted by an additive model (P = .041) and nonsignificantly greater than the OR of 5.4 predicted by a multiplicative model (P = 0.29)," the researchers wrote. "Analyses based on continuous variables yielded similar results."

In discussing the implications of the findings, Dr. Dores and associates acknowledged that treatment approaches for HL "have changed considerably over the past several decades in an effort to maximize efficacy and minimize toxicity. Although radiotherapy remains an important therapeutic modality, radiation volumes and doses have decreased considerably over time, and subdiaphragmatic radiotherapy is infrequently indicated. While the first-line therapy for many HL patients today includes doxorubicin and dacarbazine, procarbazine and cyclophosphamide continue to be used, although often with lower cumulative doses than used in the past. Our findings for topoisomerase II inhibitors are equivocal, but warrant further investigation."

They went on to note that the study extends the range of solid cancers associated with chemotherapy "and adds to the evidence that the combination of chemotherapy and radiotherapy can increase risks beyond those predicted by a multiplicative model. For HL patients, radiation dose-response relationships have now been demonstrated for second cancers of the lung, female breast, stomach, and pancreas and, with the exception of breast cancer, increased risks of these cancers have been observed after receipt of AA [alkylating agent]-containing therapy. Changes in HL therapy over time should reduce second cancer risks compared to those observed with past treatments. In the interim, health care providers caring for long-term HL survivors should be alert to this treatment sequela and encourage a healthy lifestyle to minimize additional cancer risk factors."

The study was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and National Cancer Institute contracts to Cancer Care Ontario, Toronto; Danish Cancer Society, Copenhagen; Finnish Cancer Registry, Helsinki; Information Management Services, Inc., Silver Spring, Md.; Karolinska Institute, Stockholm; University of Iowa; The University of Texas MD Anderson Cancer Center; and Westat, Inc., Rockville, Md. The Dutch study also was supported by the Lance Armstrong Foundation and the Dutch Cancer Society.

dbrunk@frontlinemedcom.com

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Radiotherapy plus chemotherapy drive risk of pancreatic cancer in HL patients