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Second Cancers Among Long-Term Survivors of Hodgkin’s Disease Diagnosed in Childhood and Adolescence

From the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD; The University of Iowa, Iowa City, Iowa; Cancer Care Ontario; The Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada; Department of Oncology, University Hospital, Uppsala, Sweden; Danish Cancer Society, Copenhagen, Denmark; Finnish Cancer Registry; Helsinki University Central Hospital, Helsinki, Finland; The Netherlands Cancer Institute, Amsterdam; and The Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.

Address reprint requests to Catherine Metayer, MD, PhD, National Cancer Institute, Executive Plaza South, Suite 7084, Bethesda, MD 20892.

PURPOSE: To quantify the risk of second cancers among long-term survivors of Hodgkin’s disease (HD) diagnosed before 21 years of age and to explore sex-, age-, and site-related differences.

PATIENTS AND METHODS: We analyzed data from 5,925 pediatric HD patients, including 2,646 10-year and 755 20-year survivors, who were reported to 16 population-based cancer registries in North America and Europe between 1935 and 1994.

RESULTS: A total of 157 solid tumors (observed/expected ratio [O/E] = 7.0; 95% confidence interval [CI], 5.9 to 8.2.) and 26 acute leukemias (O/E = 27.4; 95% CI, 17.9 to 40.2) were reported. Risk of solid tumors remained significantly increased among 20-year survivors (O/E = 6.6, observed [O] = 40, cumulative risk = 6.5%) and persisted for 25 years (O/E = 4.6, O = 15, cumulative risk = 11.7%). Temporal trends for cancers of thyroid, female breast, bone/connective tissue, stomach, and esophagus were consistent with the late effects of radiotherapy. Greater than 50-fold increased risks were observed for tumors of the thyroid and respiratory tract (one lung and one pleura) among children treated before age 10. At older ages (10 to 16 years), the largest number of second cancers occurred in the digestive tract (O/E = 19.3) and breast (O/E = 22.9). Risk of solid tumors increased with decreasing age at HD on a relative but not absolute scale.

CONCLUSION: Children and adolescents treated for HD experience significantly increased risks of second cancers at various sites for 2 to 3 decades. Although our results reflect the late effects of past therapeutic modalities, they underscore the importance of lifelong follow-up of pediatric HD patients given early, more aggressive treatments.

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