SPECIAL DEPARTMENTS
Authors: Alan C. Aisenberg, Dianne M. Finkelstein, Flora E. van Leeuwen, Willem J. Klokman, Berthe M. P. Aleman
Journal: Journal of Clinical Oncology (2000)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.10.2186 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10811685 Alan C. AisenbergxAlan C. AisenbergSearch for articles by this author , Dianne M. FinkelsteinxDianne M. FinkelsteinSearch for articles by this author Flora E. van LeeuwenxFlora E. van LeeuwenSearch for articles by this author , Willem J. KlokmanxWillem J. KlokmanSearch for articles by this author , Berthe M. P. AlemanxBerthe M. P. AlemanSearch for articles by this author Show More Massachusetts General Hospital BostonMANetherlands Cancer Institute Amsterdamthe Netherlands https://doi.org/10.1200/JCO.2000.18.10.2186 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse10052000In Reply:We fully agree with Drs Aisenberg and Finkelstein that absolute excess risk is the most appropriate risk measure by which to judge the second cancer burden in a cohort of patients. In fact, we stated this almost literally on page 490 of our recent article.1 A high relative risk may translate into a low absolute excess risk if the second tumor concerned occurs rarely in the general population (eg, leukemia after Hodgkin’s disease [HD]). Conversely, a slightly or moderately increased relative risk may result in a high absolute excess risk if the second tumor concerned has a high incidence (eg, lung cancer after HD). Because absolute excess risks were included in our Tables 2 through 4 and were extensively discussed in our Results and Discussion sections (including the estimate of two excess cases per 100 20-year survivors per year on pages 492 and 493),1 we feel that the importance of absolute excess risk was sufficiently addressed in our article.Although treatment-related second malignancies present a major problem for long-term survivors of HD, we consider it important that the risk is not overestimated. Overestimation of second cancer risk may occur in several ways. First, incomplete follow-up may lead to overestimation of second malignancy risk if patients who remain well lose contact with clinical follow-up, whereas those with second cancer come to attention because of this. Generally, surveys with more complete follow-up have found lower relative risks of breast cancer1-3 than those in which completeness of follow-up was less satisfactory or not addressed.4,5 Second, in the 1990s, many treatment centers have introduced breast cancer screening in female survivors of HD. Because screening is expected to advance the diagnosis by at least 5 years, it is likely that this has resulted in a (transient) overestimation of breast cancer risk in these centers. Furthermore, the very high actuarial risks reported by Aisenberg et al (34% at 25 years after first treatment for women treated at ages younger than 20 years; 95% confidence interval [CI], 14% to 54%)6 and by Bhatia et al (35% at 40 years of age for those treated at ages younger than 16 years; 95% CI, 17% to 53%)5 are likely to overestimate the true risk. This may be due to losses to follow-up but also to the fact that the actuarial method is less appropriate when including events that occur at follow-up intervals later than those at which data for most of the patients were censored.7 The latter phenomenon only comes to light when actuarial curves are accompanied by the number of patients still at risk at different follow-up intervals. In our study, with (nearly) complete follow-up and 27 female patients who were diagnosed before age 20 years and were still at risk at 25 years from first treatment, the 25-year actuarial risk of breast cancer amounted to 15% (95% CI, 7% to 27%).1 Although this is still a disturbingly high risk for 40-year-old women, we think that the implications of one in six versus one in three breast cancers among long-term female HD survivors may be different. Both the survivors and their treating clinicians need to be provided with valid risk estimates. We therefore feel that, for those evaluating the treatment of HD, there is an obligation to continue reporting on second cancer risk in large series of HD patients, with long-term and complete follow-up and with the use of appropriate statistical techniques.4. van Leeuwen FE, Klokman WJ, van’t Veer MB, et al: Long-term risk of second malignancy in survivors of Hodgkin’s disease treated during adolescence or young adulthood. J Clin Oncol 18::487,2000-497, Link, Google Scholar4. Sankila R, Garwicz S, Olsen JH, et al: Risk of subsequent malignant neoplasms among 1,641 Hodgkin’s disease patients diagnosed in childhood and adolescence: A population-based cohort study in the five Nordic countries—Association of the Nordic Cancer Registries and the Nordic Society of Pediatric Hematology and Oncology. J Clin Oncol 14::1442,1996-1446, Link, Google Scholar4. Swerdlow AJ, Barber JA, Vaughan Hudson GV, et al: Risk of second malignancy after Hodgkin’s disease in a collaborative British cohort: The relation to age at treatment. J Clin Oncol 18::498,2000-509, Link, Google Scholar4. Mauch PM, Kalish LA, Marcus KC, et al: Second malignancies after treatment for laparotomy staged IA-IIIB Hodgkin’s disease: Long-term analysis of risk factors and outcome. Blood 87::3625,1996-3632, Crossref, Medline, Google Scholar4. Bhatia S, Robison LL, Oberlin O, et al: Breast cancer and other second neoplasms after childhood Hodgkin’s disease. N Engl J Med 334::745,1996-751, Crossref, Medline, Google Scholar4. Aisenberg AC, Finkelstein DM, Doppke KP, et al: High risk of breast carcinoma after irradiation of young women with Hodgkin’s disease. Cancer 79::1203,1997-1210, Crossref, Medline, Google Scholar4. Donaldson SS, Hancock SL: Second cancers after Hodgkin’s disease in childhood. N Engl J Med 334::792,1996-794, (editorial) Crossref, Medline, Google Scholar