A D Wagner1, S Oertelt-Prigione2, A Adjei3, T Buclin4, V Cristina5, C Csajka6, G Coukos7, U Dafni8, G-P Dotto9, M Ducreux10, J Fellay11, J Haanen12, A Hocquelet13, I Klinge14, V Lemmens15, A Letsch16, M Mauer17, M Moehler18, S Peters5, B C Özdemir19. 1. Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. Electronic address: Dorothea.wagner@chuv.ch. 2. Department of Primary and Community Care, Radboud Institute of Health Sciences (RIHS), Radboud University Medical Center, Nijmegen, The Netherlands. 3. Department of Oncology, Mayo Clinic, Rochester, USA. 4. Service of Clinical Pharmacology, Lausanne University, Lausanne. 5. Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. 6. Service of Clinical Pharmacology, Lausanne University, Lausanne; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Lausanne. 7. Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Ludwig Lausanne Branch and Swiss Cancer Center, Lausanne, Switzerland. 8. Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; National and Kapodistrian University of Athens, Athens, Greece. 9. Department of Biochemistry, Lausanne University, Lausanne, Switzerland; Massachusetts General Hospital, Boston, USA; International Cancer Prevention Institute, Epalinges, Switzerland. 10. Gastrointestinal Cancer Unit, Gustave Roussy, Paris Saclay University, Villejuif, France. 11. Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne; EPFL School of Life Sciences, Lausanne, Switzerland. 12. Division of Medical Oncology and Immunology, Department of Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 13. Department of Radiodiagnostic and Interventional Radiology, Lausanne University Hospital, Lausanne, Switzerland. 14. Dutch Society for Gender and Health. 15. Department of Research and Development, Comprehensive Cancer Organisation the Netherlands, Utrecht; Department of Public Health, Erasmus Medical Centre University, Rotterdam, The Netherlands. 16. Department of Hematology and Oncology, Charity CBF, Berlin; Charity Comprehensive Cancer Center CCCC, Berlin; Palliative Care Unit, Campus Benjamin Franklin, Berlin, Germany. 17. EORTC, Brussels, Belgium. 18. Department of Internal Medicine 1/Gastrointestinal Oncology, Johannes-Gutenberg-University Clinic, Mainz, Germany. 19. Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; International Cancer Prevention Institute, Epalinges, Switzerland.
Abstract
BACKGROUND: The importance of sex and gender as modulators of disease biology and treatment outcomes is well known in other disciplines of medicine, such as cardiology, but remains an undervalued issue in oncology. Considering the increasing evidence for their relevance, European Society for Medical Oncology decided to address this topic and organized a multidisciplinary workshop in Lausanne, Switzerland, on 30 November and 1 December 2018. DESIGN: Twenty invited faculty members and 40 selected physicians/scientists participated. Relevant content was presented by faculty members on the basis of a literature review conducted by each speaker. Following a moderated consensus session, the final consensus statements are reported here. RESULTS: Clinically relevant sex differences include tumour biology, immune system activity, body composition and drug disposition and effects. The main differences between male and female cells are sex chromosomes and the level of sexual hormones they are exposed to. They influence both local and systemic determinants of carcinogenesis. Their effect on carcinogenesis in non-reproductive organs is largely unknown. Recent evidence also suggests differences in tumour biology and molecular markers. Regarding body composition, the difference in metabolically active, fat-free body mass is one of the most prominent: in a man and a woman of equal weight and height, it accounts for 80% of the man's and 65% of the woman's body mass, and is not taken into account in body-surface area based dosing of chemotherapy. CONCLUSION: Sex differences in cancer biology and treatment deserve more attention and systematic investigation. Interventional clinical trials evaluating sex-specific dosing regimens are necessary to improve the balance between efficacy and toxicity for drugs with significant pharmacokinetic differences. Especially in diseases or disease subgroups with significant differences in epidemiology or outcomes, men and women with non-sex-related cancers should be considered as biologically distinct groups of patients, for whom specific treatment approaches merit consideration.
BACKGROUND: The importance of sex and gender as modulators of disease biology and treatment outcomes is well known in other disciplines of medicine, such as cardiology, but remains an undervalued issue in oncology. Considering the increasing evidence for their relevance, European Society for Medical Oncology decided to address this topic and organized a multidisciplinary workshop in Lausanne, Switzerland, on 30 November and 1 December 2018. DESIGN: Twenty invited faculty members and 40 selected physicians/scientists participated. Relevant content was presented by faculty members on the basis of a literature review conducted by each speaker. Following a moderated consensus session, the final consensus statements are reported here. RESULTS: Clinically relevant sex differences include tumour biology, immune system activity, body composition and drug disposition and effects. The main differences between male and female cells are sex chromosomes and the level of sexual hormones they are exposed to. They influence both local and systemic determinants of carcinogenesis. Their effect on carcinogenesis in non-reproductive organs is largely unknown. Recent evidence also suggests differences in tumour biology and molecular markers. Regarding body composition, the difference in metabolically active, fat-free body mass is one of the most prominent: in a man and a woman of equal weight and height, it accounts for 80% of the man's and 65% of the woman's body mass, and is not taken into account in body-surface area based dosing of chemotherapy. CONCLUSION: Sex differences in cancer biology and treatment deserve more attention and systematic investigation. Interventional clinical trials evaluating sex-specific dosing regimens are necessary to improve the balance between efficacy and toxicity for drugs with significant pharmacokinetic differences. Especially in diseases or disease subgroups with significant differences in epidemiology or outcomes, men and women with non-sex-related cancers should be considered as biologically distinct groups of patients, for whom specific treatment approaches merit consideration.
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