The need for gender medicine in oncology: ‘unexploited potential for individualised treatment’
n oncology, not much attention has been paid to the role of gender and sex. This is a missed opportunity to learn and individualise treatment, according to dr. Anna Dorothea Wagner, medical oncologist in the Centre Hospitalier Universitaire Vaudois in Lausanne and chair of the ESMO Gender Medicine Task Force. ‘Gender has so far rarely been included as an influencing factor in cancer research, although for instance in the field of cardiology it is clear that sex and gender play a role in the development and progression of disease.’ Wagner is working with researchers at IKNL to investigate the role of gender in non-sex related cancers, using data from the Netherlands Cancer Registry (NCR).
‘I saw that women in my clinic, especially young women, often suffer more side-effects from anti-cancer medication, for no obvious reason. It made me wonder if it could have something to do with the fact that they were women,’ says Wagner about how she got involved in the topic of gender medicine. ‘I went to the literature: cardiologists have known for 20 years that there are gender differences in treatment effects.’ She continues: ‘In the last decades, we’ve made significant progress in oncology by individualising treatment on the basis of tumour characteristics, which is very important,’ says Wagner, ‘but there is also definitely progress to be made on the basis of host characteristics. The potential there has not yet been exploited.’
The ESMO Gender Medicine Task Force’s mission is ‘to raise awareness of the presence of potential sex and gender differences in the biology and treatment outcomes of non-sex related cancers’. It is doing this by developing material for ESMO’s educational programmes; encouraging oncology professionals to consider sex and gender aspects in their education, research and practice; and developing educational resources to help oncologists understand sex and gender differences in the biology and the impact on the treatment outcomes of non-sex related cancers.
Founding the Task Force
The ESMO Gender Medicine Task Force was launched in 2019 after a very successful workshop on gender medicine in oncology, explains Wagner, which highlighted the need for such a task force. ‘We had faculty members from many different fields of oncology. IKNL-board member Valery Lemmens was also present, even though he is a very busy man. We also did our best to encourage young oncologists to participate in the workshop.’ Wagner: ‘Although gender medicine is not a very popular subject, it attracted the people that are really interested and who think this is an important subject.’
It was after the workshop that dr. Rob Verhoeven, epidemiologist at IKNL, became part of the ESMO Gender Medicine Task Force. He currently works with Wagner on investigating the role of gender in cancer. ‘Gender or sex is always used as a variable, but there is not a lot of thought going into the purpose of the variable,’ he says. ‘We “correct” for gender, and that’s usually it. I always wondered if there was more behind the variable.’ Valery Lemmens, after attending the workshop, put Verhoeven on the path of gender medicine. ‘When we talked about it, it made me realise we could do so much more with our cancer registry data. Then I learned the Task Force was still looking for an epidemiologist, so I went for it.’
Education and awareness
The Task Force has developed educational materials on gender medicine in oncology like factsheets (which can be found on their website behind a login) and they are currently developing an e-learning module on the impact of sex and gender on cancer. ‘There are and will be educational events during ESMO congresses, including ESMO Asia this year,’ says Wagner. Verhoeven: ‘We organise sessions at these conferences dedicated to the topic of gender medicine, specifically to raise awareness among oncologists about the existence and importance of sex and gender differences.’
Men and women are not just subgroups
’In the past, differences in efficacy and toxicity of treatments were attributed to statistical errors, because men and women were considered as subgroups,’ says Wagner. ‘The point is, however, as we wrote in the paper about the first workshop, that men and women with non sex-related cancers are biologically distinct groups of patients. Therefore, the risks and benefits of any intervention in oncology – from prevention to screening to treatment to quality-of-life assessment – should be analysed separately in men and women.’ Wagner continues: ‘An important project we’re working on is a systematic review of sex differences in pharmacokinetics, body composition and physiology with impact on drug metabolism.’
Role of sex and gender in non-sex related cancers
Currently, Wagner is working with Verhoeven and others at IKNL, using NCR data to investigate the role of gender and sex for the top 5 non-sex related cancers in terms of mortality. Wagner: ‘What we’re doing is looking at differences in patient characteristics, tumour characteristics, treatment allocation and survival.’ Verhoeven: ‘I think what’s important is that we’re especially trying to have a comprehensive point of view; so not only studying differences in variables like tumour characteristics and treatment allocation, but create a comprehensive overview of differences in incidence, disease characteristics, treatment allocation and survival.’
Many studies include gender or sex in their analyses, explains Verhoeven, ‘but they often don’t connect the dots between gender and/or sex and the other variables, like treatment allocation or survival.’ Verhoeven, Wagner and colleagues already published work that point out sex and gender differences in oesophageal, gastric and pancreatic cancer. ‘I think the NCR is an excellent source of data for this project,’ says Wagner, ‘since it is comprehensive and representative for Europe. And because of your health care system, where everybody can receive treatment regardless of their means, we know that things like treatment differences are not due to gender-based social-economic differences.’ Wagner continues: ‘And the people at IKNL are also motivated and enthusiastic collaborators. It is really a pleasure to collaborate with them.’
Contact Rob Verhoeven, senior researcher, or read published works:
- First workshop report: Wagner AD, Oertelt-Prigione S, Adjei A, Buclin T, Cristina V, Csajka C, Coukos G, Dafni U, Dotto GP, Ducreux M, Fellay J, Haanen J, Hocquelet A, Klinge I, Lemmens V, Letsch A, Mauer M, Moehler M, Peters S, Özdemir BC. Gender medicine and oncology: report and consensus of an ESMO workshop. Ann Oncol. 2019 Dec 1;30(12):1914-1924. doi: 10.1093/annonc/mdz414. PMID: 31613312.
- Recent editorial: Özdemir BC, Oertelt-Prigione S, Adjei AA, Borchmann S, Haanen JB, Letsch A, Mir O, Quaas A, Verhoeven RHA, Wagner AD. Investigation of sex and gender differences in oncology gains momentum: ESMO announces the launch of a Gender Medicine Task Force. Ann Oncol. 2022 Feb;33(2):126-128. doi: 10.1016/j.annonc.2021.11.011. Epub 2022 Jan 17. PMID: 35058112.
- Work with NCR data:
- Dijksterhuis WPM, Kalff MC, Wagner AD, Verhoeven RHA, Lemmens VEPP, van Oijen MGH, Gisbertz SS, van Berge Henegouwen MI, van Laarhoven HWM. Gender Differences in Treatment Allocation and Survival of Advanced Gastroesophageal Cancer: A Population-Based Study. J Natl Cancer Inst. 2021 Nov 2;113(11):1551-1560. doi: 10.1093/jnci/djab075. PMID: 33837791; PMCID: PMC8562959.
- Pijnappel EN, Schuurman M, Wagner AD, de Vos-Geelen J, van der Geest LGM, de Groot JB, Koerkamp BG, de Hingh IHJT, Homs MYV, Creemers GJ, Cirkel GA, van Santvoort HC, Busch OR, Besselink MG, van Eijck CHJ, Wilmink JW, van Laarhoven HWM. Sex, Gender and Age Differences in Treatment Allocation and Survival of Patients With Metastatic Pancreatic Cancer: A Nationwide Study. Front Oncol. 2022 Mar 24;12:839779. doi: 10.3389/fonc.2022.839779. PMID: 35402271; PMCID: PMC8987273.
- Kalff MC, Wagner AD, Verhoeven RHA, Lemmens VEPP, van Laarhoven HWM, Gisbertz SS, van Berge Henegouwen MI; Dutch Upper GI Cancer Audit group. Sex differences in tumor characteristics, treatment, and outcomes of gastric and esophageal cancer surgery: nationwide cohort data from the Dutch Upper GI Cancer Audit. Gastric Cancer. 2022 Jan;25(1):22-32. doi: 10.1007/s10120-021-01225-1. Epub 2021 Aug 7. PMID: 34365540; PMCID: PMC8732809.
- Özdemir BC, Csajka C, Dotto GP, Wagner AD. Sex Differences in Efficacy and Toxicity of Systemic Treatments: An Undervalued Issue in the Era of Precision Oncology. J Clin Oncol. 2018 Sep 10;36(26):2680-2683. doi: 10.1200/JCO.2018.78.3290. Epub 2018 Jul 13. PMID: 30004815.
- Wagner AD, Grothey A, Andre T, Dixon JG, Wolmark N, Haller DG, Allegra CJ, de Gramont A, VanCutsem E, Alberts SR, George TJ, O'Connell MJ, Twelves C, Taieb J, Saltz LB, Blanke CD, Francini E, Kerr R, Yothers G, Seitz JF, Marsoni S, Goldberg RM, Shi Q. Sex and Adverse Events of Adjuvant Chemotherapy in Colon Cancer: An Analysis of 34 640 Patients in the ACCENT Database. J Natl Cancer Inst. 2021 Apr 6;113(4):400-407. doi: 10.1093/jnci/djaa124. PMID: 32835356; PMCID: PMC8023830.