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Journal of Clinical Oncology, Vol 18, Issue 3 (February), 2000: 498
© 2000 American Society for Clinical Oncology

Risk of Second Malignancy After Hodgkin’s Disease in a Collaborative British Cohort: The Relation to Age at Treatment

By A. J. Swerdlow, J. A. Barber, G. Vaughan Hudson, D. Cunningham, R. K. Gupta, B. W. Hancock, A. Horwich, T. A. Lister, D. C. Linch

From the Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine; the Department of Medical Statistics and Evaluation, Imperial College School of Medicine; the British National Lymphoma Investigation, University College Hospital; and the Imperial Cancer Research Fund Medical Oncology Unit, St Bartholomew’s Hospital, London; the Lymphoma Unit and the Academic Unit of Radiotherapy and Oncology, The Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey; and the Department of Clinical Oncology, Weston Park Hospital, Sheffield, United Kingdom.

Address reprint requests to A.J. Swerdlow, DM, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, United Kingdom; email a.swerdlow{at}lshtm.ac.uk

PURPOSE: To assess long-term site-specific risks of second malignancy after Hodgkin’s disease in relation to age at treatment and other factors.

PATIENTS AND METHODS: A cohort of 5,519 British patients with Hodgkin’s disease treated during 1963 through 1993 was assembled and followed-up for second malignancy and mortality. Follow-up was 97% complete.

RESULTS: Three hundred twenty-two second malignancies occurred. Relative risks of gastrointestinal, lung, breast, and bone and soft tissue cancers, and of leukemia, increased significantly with younger age at first treatment. Absolute excess risks and cumulative risks of solid cancers and leukemia, however, were greater at older ages than at younger ages. Gastrointestinal cancer risk was greatest after mixed-modality treatment (relative risk [RR] = 3.3; 95% confidence interval [CI], 2.1 to 4.8); lung cancer risks were significantly increased after chemotherapy (RR = 3.3; 95% CI, 2.4 to 4.7), mixed-modality treatment (RR = 4.3; 95% CI, 2.9 to 6.2), and radiotherapy (RR = 2.9; 95% CI, 1.9 to 4.1); breast cancer risk was increased only after radiotherapy without chemotherapy (RR = 2.5; 95% CI, 1.4 to 4.0); and leukemia risk was significantly increased after chemotherapy (RR = 31.6; 95% CI, 19.7 to 47.6) and mixed-modality treatment (RR = 38.1; 95% CI, 24.6 to 55.9). These risks were generally greater after treatment at younger ages: for patients treated at ages younger than 25 years, there were RRs of 18.7 (95% CI, 5.8 to 43.5) for gastrointestinal cancer after mixed-modality treatment, 14.4 (95% CI, 5.7 to 29.3) for breast cancer after radiotherapy, and 85.2 (95% CI, 45.3 to 145.7) for leukemia after chemotherapy (with or without radiotherapy).

CONCLUSION: Age at treatment has a major effect on risk of second malignancy after Hodgkin’s disease. Although absolute excess risks are greater for older patients, RRs of several important malignancies are much greater for patients who are treated when young. The increased risk of gastrointestinal cancers may relate particularly to mixed-modality treatment, and that of lung cancer to chemotherapy as well as radiotherapy; there are also well-known increased risks of breast cancer from radiotherapy and leukemia from chemotherapy. The roles of specific chemotherapeutic agents in the etiology of solid cancers after Hodgkin’s disease require detailed investigation.




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