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Originally published as JCO Early Release 10.1200/JCO.2009.23.5895 on August 17 2009 © 2009 American Society of Clinical Oncology.
Reply to B. Mispelaere et alDivision of Cancer Medicine and Radiotherapy, Department of Clinical Cancer Research, Rikshospitalet University Hospital, Oslo, Norway
Department of Mathematics, University of Oslo, Oslo, Norway
Division of Cancer Medicine and Radiotherapy, Department of Clinical Cancer Research, Rikshospitalet University Hospital; and Faculty Division, Norwegian Radium Hospital, University of Oslo, Oslo, Norway The comments by Mispelaere et al1 on female cancer survivors are well taken. We agree that our study2 would have been more clinically relevant had we had information concerning our patients' desire to become pregnant after therapy. This shortcoming was also mentioned as a limitation in our article under Discussion. However, Mispelaere et al have to bear in mind that our 10-year reproduction rates were determined on the basis of a population-based registry that records established pregnancies. One principal aim was to compare reproduction rates in patients with cancer with those in the normal population. Our group has already published results of other studies, in which we investigated long-term post-treatment fertility rates in patients who had expressed their desires regarding parenthood.3,4
In our study,2 it was assumed that survivors who were childless at diagnosis would be more likely to want to have at least one child, similar to those who were childless in the general population (childless survivors were compared with those in the general population who were also childless at date of diagnosis or other assigned date). Therefore, all analyses were stratified by parenthood before cancer (childless v In our study,2 the rates were computed using survival analysis methods, taking length of follow-up into consideration. Our cumulative rates refer to 10 years after date of diagnosis, whereas Mispelaere et al1 report that their questionnaire was sent to patients 2 to 8 years after end of treatment. If the rates presented by Mispelaere et al were computed as proportions, ignoring the time aspect, they should be lower than our rates. In addition, women who answered the questionnaire only 2 years after their treatment may have wanted to wait some time before possible pregnancy—or may even have been advised to postpone it. Furthermore, Mispelaere et al report their results without any CIs. Bearing in mind that their estimates were computed from rather small numbers (only nine women wanted to become pregnant), there is considerable uncertainty connected to the estimates, and the CIs would have been broad and would likely have included our cumulative rate estimates. We computed a 95% CI (3.5% to 14.9%) using a binomial distribution—it demonstrated that this interval covers our estimates. Mispelaere et al1 claim that all their patients received cytotoxic treatment, but they do not describe any radiation treatment, which must have been given to some of their patients with malignant lymphoma and breast cancer. Furthermore, it remains unclear whether any of the patients with breast cancer had received hormone treatment, which would certainly have influenced post-treatment fertility. Because we did not have information on individual treatment, we described only treatment strategies (Table 1 of our report).2 Also, it seems problematic to combine survivors of breast cancer with those of malignant lymphoma, because they are administered completely different therapies. Another problem with the study by Mispelaere et al is the age distribution of survivors, which was considerably different between the two diagnoses. Breast cancer, but not malignant lymphoma, is extremely rare before the age of 25 years, an important cutoff age for preservation of gonadal function after chemotherapy.5 In conclusion, we agree that it is clinically relevant to include information about patients' desires concerning future parenthood in postcancer fertility studies. Mispelaere et al1 are to be congratulated on having such information in a limited patient cohort. Their results are by no means contrary to our findings; rather, they are limitedly complementary. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. ACKNOWLEDGMENT We thank the Lance Armstrong Foundation for financial support and the Medical Birth Registry of Norway, which provided data and helped with management; we particularly thank Stein Emil Vollset. REFERENCES
1. Mispelaere B, Van de Werf E, D'Hooghe T, et al: Reproduction rates after cytotoxic therapy. J Clin Oncol 27:e118–e119, 2009. 2. Cvancarova M, Samuelsen SO, Magelssen H, et al: Reproduction rates after cancer treatment: Experience from the Norwegian Radium Hospital. J Clin Oncol 27:334–343, 2009. 3. Brydøy M, Fosså SD, Klepp O, et al: Paternity following treatment for testicular cancer. J Natl Cancer Inst 97:1580–1588, 2005. 4. Kiserud CE, Fosså A, Holte H, et al: Post-treatment parenthood in Hodgkin's lymphoma survivors. Br J Cancer 96:1442–1449, 2007.[Medline] 5. Haukvik UK, Dieset I, Bjøro T, et al: Treatment-related premature ovarian failure as a long-term complication after Hodgkin's lymphoma. Ann Oncol 17:1428–1433, 2006.
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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one child before treatment). In population-based analysis, information concerning family planning was not available, so we had to establish fertility rates stratified by parity, although we admit this was an unproven assumption. Mispelaere et al
