Quality of Life and Late treatment effects Patients with Rare Gynaecological Malignancies

1. Quality of Life and Late treatment effects Patients with Rare Gynaecological Malignancies F Joly, MD PhD, Caen, France Djihane Ahmed Lecheheb, PHD, Caen, France

2. Some rare tumors with very good prognosis 5 yrs OS 85% 80% > 80% Ray-Coquard et al Eur J Surg Oncol, 2018, Gatta et al EJC 2011

3. Context 2: Common issues • Mainly Young women, good prognosis • Conservative surgery followed by chemotherapy Quality of life and long termtreatmentssideeffects ? Survivorships issues

4. Potential long term toxicities among women treated with Chemotherapy for a rare tumor with a good prognosis The most frequent chemotherapy regimen used : BEP: Bleomycin,Etoposide, Cisplatin

5. What have we learned from testicular and childhood cancer survivors? • Some long survivors issues • Chemotherapy used in testicular cancer is the same

6. Quality of life (QoL) and Psycho-social issues • Testicular Cancer (compared to healthy population) • Long term global QoL similar to the general population • Higher level of anxiety • Higher chronic fatigue • Linked to anxiety and depression • More cognitive complaints (concentration, memory Joly JCO 2002, Mykletum JCO 2005, Skaali Psycho-oncol 2005, Liavaag JCO 2005, Spauten Ann Oncol 2015, Chovanec The Oncologist 2018, Schagen Acta Oncol 2008

7. Quality of Life and Psycho-social issues • Identification of subgroup of testicular pts with « helpless-hopless » coping style and limited social support • Implication of certain socio-economic factors • young age, • unemployment, • low educational level, alcohol problems Smith J Cancer Surv 2016, Dual JCO 2005

8. Increase of risk of psycho-social problems in young cancer survivors • Higher than general population In relation with late side-effects of the treatments Gunnes Int J Cancer 2016, Brinkman JCO 2018

9. Long term side effects after Cisplatin based chemotherapy in testicular cancer 20% of pts with high cumulative late effects in relation with chemotherapy Kerns, JCO 2018

10. Factors associated with Toxicity: testicular cancer treatd with cisplatin Chemotherapy Disability leave Older age at diagnosis Healthy : smoking and physical activity Type and nb of cycles of chemotherapy Kerns, JCO 2018

11. Second malignancy – testicular cancer • A small increase of the risk (1.5 to 2.1) • Higher if combination of Chemo and irradiation • Remain elevated even > 35 yrs after treatments • Platinum area chemotherapy : increase of leukaemia, thyroid and soft tissue cancers From Abouassaly Eur Urol 2011 Chovenec Ann Oncol 2017

12. What about women with good pronostic rare gynecological survivors? Few data

13. QoL & Late side effects – reported by the patients treated with surgery and chemotherapy Depend of age at diagnosis, type of chemotherapy, smoker, time since end of CT Matei, JCO 2009, Champion Gyn Oncol 2007

14. Fertility issues after conservative surgery and Chemotherapy • Premature menopause : 3% • Preservation of menstruel function : 71 to 95% • Median to full recovery : 5 months (range 1 to 8 months) • Initial measure of fertility reserve (AMH) • To identify the few group of pts at risk of premature menopause Reassuring data Di Tucci Crit Cancer Review, 2017, Rousset-Jablonski Bull cancer 2018

15. Reproductive and sexual concerns among women survivors Compared to women issued from the general population Greater reproductive concerns and sexual disconfort among infertile pts compared to fertile patients Gershenson JCO 2007,

16. Risk of second cancer among women with rare cancer Issued from Norway Cancer Registry, with 10 yrs of follow-up • Verylowrisk of second cancer • MainlywhenChemotherapywascombinedwith abdominal irradiation Solheim , Gyn Oncol 2013

17. Next steps : to minimize the long-term side effets

18. To better evaluate Step 2 (for patients only) Step 1 Vivrovaire Rare Tumors 160 GCT and 160 sex-Cord tumors pts ≥ 2 years after treatment Pts treated with Chemo Pts treated with surgery alone Chronic fatigue, quality of life and lateeffects of chemotherapy ? self-administeredquestionnaires Healthy CONTROL group: 70 GCT and 70 sex-Cord tumors pts Late physical effects of chemotherapy ? (Cardiovascular, respiratory, hearing, metabolic & hormonal assessments) Standardized specialized medical examination Pts treated with CT: Pts treated with surgery alone INCa French Network for Rare Malignant Ovarian Tumors (TMRO) - GINECO

19. To centralise the care of the patients • Testicular cancer • Ovarian cancer Centralisation policy for all pts in a number of North Europe countries Better Outcomes if patients treated in centers with high experiences Better Outcomes if patients treated in centers with high experiences Collette JNCI 1999, Dubois Gyn Oncol 2009, Hughet BMC health services Res 2018

20. Interventions to minimize the late treatments effects Survivorship care plan Fertility/Menopausalconcerns Promotion of healthylife

21. Survival care plan / Ex : long term follow-up testicular cancer Exemple Issued from Testicular cancer ESMO Consensus Conf, Honecker et al Ann Oncol 2018, Abouassaly Eur Urol 2011

22. Gynecological concerns • Fertility issues Fertilitypreservation • Contraception and Menopausalsymptoms In most of the cases no Contraindication Some recent guidelines Ask to your specialist! Di Tucci Crit Cancer Review, 2017, Rousset-Jablonski Bull cancer 2018

23. Interventions : promotion of healthy life in ovarian cancer patients (physical activity) Better Quality of life Less fatigue Zhou , JNCI 2017

24. Physical activity and QoL and fatigue among testicular survivors Usual care vs physical activity • Less fatigue • More vitality Adams, BJC 2018

25. Conclusions • Long term global good quality of life for a majority of the women patients • Somelatetreatmentseffects for a subgroup of pts • However few data, not reallywellknown Need of new studies • To prevent • To detect • To manage