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Journal of Clinical Oncology, Vol 20, Issue 16 (August), 2002: 3484-3494
© 2002 American Society for Clinical Oncology

Second Malignant Neoplasms Among Long-Term Survivors of Hodgkin’s Disease: A Population-Based Evaluation Over 25 Years

By Graça M. Dores, Catherine Metayer, Rochelle E. Curtis, Charles F. Lynch, E. Aileen Clarke, Bengt Glimelius, Hans Storm, Eero Pukkala, Flora E. van Leeuwen, Eric J. Holowaty, Michael Andersson, Tom Wiklund, Timo Joensuu, Mars B. van’t Veer, Marilyn Stovall, Mary Gospodarowicz, Lois B. Travis

From the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD; The University of Iowa, Iowa City, IA; Cancer Care Ontario and The Princess Margaret Hospital, University of Toronto, Ontario, Canada; Department of Oncology, University Hospital, Uppsala, Sweden; Danish Cancer Society, Copenhagen, Denmark; Department of Oncology, Helsinki University Hospital, Helsinki, Finland; the Netherlands Cancer Institute, Amsterdam; The Dr Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; and Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, Houston TX.

Address reprint requests to Graça M. Dores, MD, MPH, National Cancer Institute, Executive Plaza South, Suite 7039, Bethesda, MD 20892; email: doresg{at}mail.nih.gov

PURPOSE: To quantify the relative and absolute excess risks (AER) of site-specific second cancers, in particular solid tumors, among long-term survivors of Hodgkin’s disease (HD) and to assess risks according to age at HD diagnosis, attained age, and time since initial treatment.

PATIENTS AND METHODS: Data from 32,591 HD patients (1,111 25-year survivors) reported to 16 population-based cancer registries in North America and Europe (1935 to 1994) were analyzed.

RESULTS: Two thousand one hundred fifty-three second cancers (observed-to-expected ratio [O/E] = 2.3; 95% confidence interval [CI] = 2.2 to 2.4), including 1,726 solid tumors (O/E = 2.0; 95% CI, 1.9 to 2.0) were reported. Cancers of the lung (observed [Obs] = 377; O/E = 2.9), digestive tract (Obs = 376; O/E = 1.7), and female breast (Obs = 234; O/E = 2.0) accounted for the largest number of subsequent malignancies. Twenty-five years after HD diagnosis, the actuarial risk of developing a solid tumor was 21.9%. The relative risk of solid neoplasms decreased with increasing age at HD diagnosis, however, patients aged 51 to 60 years at HD diagnosis sustained the highest cancer burden (AER = 79.2/10,000 patients/year). After a progressive rise in relative risk and AER of all solid tumors over time, there was an apparent downturn in risk at 25 years. Temporal trends and treatment group distribution for cancers of the esophagus, stomach, rectum, female breast, bladder, thyroid, and bone/connective tissue were suggestive of a radiogenic effect.

CONCLUSION: Significantly increased risks of second cancers were observed in all HD age groups. Although significantly elevated risks of stomach, female breast, and uterine cervix cancers persisted for 25 years, an apparent decrease in relative risk and AER of solid tumors at other sites is suggested.




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