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Recommendations for Gonadotoxicity Surveillance in Male

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Recommendations for Gonadotoxicity Surveillance in Male View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Helsingin yliopiston digitaalinen arkisto Review Recommendations for gonadotoxicity surveillance in male childhood, adolescent, and young adult cancer survivors: a report from the International Late Eff ects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium Roderick Skinner, Renee L Mulder, Leontien C Kremer, Melissa M Hudson, Louis S Constine, Edit Bardi, Annelies Boekhout, Anja Borgmann-Staudt, Morven C Brown, Richard Cohn, Uta Dirksen, Alexsander Giwercman, Hiroyuki Ishiguro, Kirsi Jahnukainen, Lisa B Kenney, Jacqueline J Loonen, Lilian Meacham, Sebastian Neggers, Stephen Nussey, Cecilia Petersen, Margarett Shnorhavorian, Marry M van den Heuvel-Eibrink, Hanneke M van Santen, William H B Wallace, Daniel M Green Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired Lancet Oncol 2017; 18: e75–90 spermatogenesis, testosterone defi ciency, and physical sexual dysfunction in male pubertal, adolescent, and young Department of Paediatric and adult cancer survivors. Guidelines for surveillance and management of potential adverse eff ects could improve cancer Adolescent Haematology/ survivors’ health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about Oncolo gy and Children’s Haemopoietic Stem Cell optimum screening practices. This clinical practice g uideline recommended by the International Late Eff ects of Transplant Unit, Great North Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed Children’s Hospital and using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male Northern Institute of Cancer childhood, adolescent, and young adult (CAYA) cancer survivors. The recommendations were developed by an Research (Prof R Skinner PhD) and Institute of Health and international multidisciplinary panel including 25 experts in relevant medical specialties, using a consistent and Society (M C Brown MSc), transparent process. Recommendations were graded according to the strength of underlying evidence and potential Newcastle University, benefi t gained by early detection and appropriate management. The aim of the recommendations is to enhance Newcastle upon Tyne, UK; evidence-based care for male CAYA cancer survivors. The guidelines reveal the paucity of high-quality evidence, Department of Pediatric Oncology, Emma Children’s highlighting the need for further targeted research. Hospital, Academic Medical Center, Amsterdam, Introduction follow-up guidelines.22 The European Union-funded Netherlands (R L Mulder PhD, Advances in the treatment of childhood, adolescent, and PanCareSurFup (PCSF) Consortium collaborated with L C Kremer PhD); Department of Oncology young adult (CAYA) cancer have led to 5-year survival IGHG to identify treatments associated with increased (Prof M M Hudson MD) and exceeding 80%.1,2 Unfortunately, many CAYA cancer risk of impaired spermatogenesis, testosterone Departments of Oncology and survivors experience long-term morb idity and mortality defi ciency, and physical sexual dysfunction in male Epidemiology and Cancer 3,4 Control (Prof D M Green MD), resulting from cancer, treatment, or both. The risk of CAYA cancer survivors, and evaluate surveillance St Jude Children’s Research treatment-induced gonadotoxicity often causes emotional strategies. This Review summarises the evidence and Hospital, Memphis, TN, USA; distress for male survivors5–10 and impaired spermato- recommendations. Treatment of impaired sperma to- Departments of Radiation genesis results in reduced or lost fertility.5,7 Testosterone genesis, testosterone defi ciency and physical sexual Oncology and Pediatrics, University of Rochester defi ciency causes delayed or arrested puberty in dysfunction by relevant specialist clinicians was not Medical Center, Rochester, NY, adolescents, and many adverse somatic and psychological included in this Review. USA (Prof L S Constine MD); consequences in adults.6,8,11,12 Sexual dysfunction can have 2nd Department of Pediatrics, both phys ical and psychosexual consequences.10,13 Aim of the study Semmeilweis University, 22 Budapest, Hungary Male survivors at risk of cancer and treatment-related IGHG’s aims and methodology have been published. (E Bardi PhD); Hungary and gonadotoxic eff ects and their health-care providers could Guideline representatives from the North American Johannes Kepler benefi t from clinical practice guidelines to facilitate Children’s Oncology Group (COG),19 Dutch Childhood Universitätsklinikum, Linz, 14–17 Austria (E Bardi); Department timely remedial or health-preserving interventions. Oncology Group (DCOG), Scottish Intercollegiate 20 of Medical Oncology, Published clinical practice guidelines developed by Guidelines Network (SIGN), United Kingdom Netherlands Cancer Institute/ 18 North American and European groups for long-term Children’s Cancer and Leukaemia Group (CCLG), PCSF Antoni van Leeuwenhoek, follow-up of CAYA cancer survivors18–21 vary in defi nitions Consortium,23 and other international paediatric onco- Amsterdam, Netherlands of at-risk populations and recommendations for logy societies developed a working group of 25 experts (A Boekhout PhD); Department of Paediatric Haematology, treatment modalities and frequency of surveillance. from nine countries, selected for their knowledge of and Oncology and Haemopoietic Because diff erences in published guidelines might publications in paediatric (four members) or adult Stem Cell Transplantation, hinder guideline implementation and provision of endocrinology (two members), andrology (one member), Charité-Universitätsmedizin, consistent clinically eff ective care, the International Late paediatric, adolescent haema tology, oncology, or Berlin, Germany (A Borgmann-Staudt MD); Eff ects of Childhood Cancer Guideline Harmonization long-term follow-up (twelve members), urology Kids Cancer Centre, Sydney Group (IGHG) was developed to critically examine (one member), radiation oncology (one member), Children’s Hospital, Sydney and the evidence and harmonise existing long-term psychology (one member), and epidemiology and UNSW Medicine, Sydney, NSW, www.thelancet.com/oncology Vol 18 February 2017 e75 Review Australia (Prof R Cohn FRACP); guideline methodology (three members). The group Papers were selected for evidence summaries if they Department of Paediatric worked together via web conferences, face-to-face reported a primary outcome. Conclusions based on Haematology and Oncology, meetings, and email correspondence. gonado trophins alone were not used to inform surveillance University Hospital Muenster, Muenster, Germany The experts looked for areas of concordance and recommendations for impaired spermatogenesis or (Prof U Dirksen MD); Department discordance across the COG, DCOG, SIGN, and CCLG testosterone defi ciency because they were not defi ned as of Translational Medicine, Lund guidelines. They devised clinical questions to address primary outcomes and patients treated with cranial University, Malmö, Sweden areas of discordance for surveillance of impaired radiotherapy might develop hypogonadotropic hypo- (Prof A Giwercman MD); Department of Pediatrics, Tokai spermatogenesis, testosterone defi ciency, and physical gonadism, and hence blunted gonadotrophin responses. University School of Medicine, limitations that lead to sexual dysfunction (subsequently Studies of surveillance modalities for impaired Isehara, Japan (H Ishiguro MD); described as physical sexual dysfunction) covering the spermatogenesis calculated the area under the curve Division of Hematology-Oncology and following key issues: who needs surveillance; which (AUC) of the receiver operating characteristics (ROC) Stem Cell Transplantation, surveillance modality should be used; how often and curves to evaluate accuracy of a diagnostic investigation. Children’s Hospital, University of for how long surveillance should be performed; and We used Tape’s criteria,24 based on the numerical value of Helsinki and Helsinki University when survivors should be referred (appendix pp 1–3). the AUC of the ROC curve, to analyse the diagnostic Hospital, Helsinki, Finland (K Jahnukainen PhD); Department value of investigations. of Pediatric Oncology, Dana- Methods In cases whereby no or only low-quality evidence was Farber/Boston Children’s Cancer We did systematic searches in the medical literature for identifi ed for the gonadotoxic eff ect (or absence) of a and Blood Disorder Center, studies of CAYA survivors (see appendix, pp 4–10, for more treatment, relevant information was extrapolated from Harvard Medical School, Boston, MA, USA (Prof L B Kenney MD); details). studies that did not meet the systematic search’s Department of Hematology, eligibility criteria, including studies published before Radboud University Medical Search strategy and selection criteria 1993. Conclusions from this supplemental search were Center, Nijmegen, Netherlands Systematic literature searches were performed between agreed upon and described as refl ecting expert opinion. (J J Loonen PhD); Department of Pediatrics, Division of January, 1993 and October, 2014 (appendix, pp 4–10). We They were categorised as probably demonstrating an Hematology/ Oncology and searched MEDLINE (through PubMed) using the search eff ect or no eff ect of the treatment, or as suggesting that Endocrinology, Emory
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