Two sites of Paris Cancer Institute CARPEM have a strong activity in gynaecological oncology: Cochin Hospital (CCH) and European Georges Pompidou Hospital (HEGP). The gynaecological cancers program involves 5 departments of APHP.Centre Université de Paris (Women, mother, and child; Imaging and Pathology; Oncology; Geriatrics and Biology and Genomic Medicine) working together. It is the most important centre dedicated to gynaecological oncology in the Great Paris area (with an ESGO: European Society Gynæcological Oncology accreditation).

Twenty-eight physicians, surgeons and biologists are mainly dedicated to gynaecological patients care and altogether 17 beds are dedicated to gynaecological oncology.  This program took care of 1160 new cases of gynaecological cancers in 2018 (ovarian and endometrial cancers). Both sites (HEGP and CCH) have medical and surgical strengths and 1078 new cases of gynaecological tumours have been surgically removed in 2018, 728 patients were treated by chemotherapy (for detail annex 1).

All these activities are structured around 2 weekly cancer multidisciplinary team meetings including members of the gynaecological programs (Thursday and Wednesday), and 2 sarcoma multidisciplinary meeting (monthly in HEGP, weekly in CCH). These meetings follow the APHP guidelines, INCA national guidelines, and ESMO guidelines. Rare gynaecological cancers are discussed in the monthly national rare gynaecological tumours multidisciplinary meeting (INCa) at CCH. 

A remarkable feature of these 2 sites is that they are able to provide not only all possible modalities of therapeutic care from surgery (supraradical surgery of advanced or recurrent ovarian cancer, mini-invasive laparoscopic and robot-assisted surgery of early uterine cancer, sentinel lymph node biopsy) to fertility preservation, targeted therapies, stereotaxic radiotherapy and “after cancer cares” (sporting activities, hormone replacement therapies, etc.) but also all diagnostic procedures. Molecular biology platform enables us to quickly diagnose somatic or constitutional mutations, namely in ovarian and endometrial cancers (Breast and Ovary syndrome, Lynch syndrome), and improve treatment and prevention of these patients. We take part in the “Women at Risk” and PREDIF networks dedicated to the screening of familial ovarian and endometrial cancers. Furthermore, we developed a multidisciplinary clinic for patients with HPV related cancers to offer screening in all sites at risk for HPV related cancers (gynaecological, anal and ORL).

Physicians, surgeons and biologists of this program are strongly involved in clinical and translational research. One of specificity of the clinical research conducted in this program is the involvement of surgeons. They dedicate their efforts, in cervical cancers to demonstrate the clinical use of detection of sentinel lymph node and in ovarian cancers to demonstrate the benefit of upfront surgery in resectable advanced ovarian cancer.

Clinical research

Several clinical trials (29, 13 phases I/II and 15 phase III)) are ongoing providing access to innovation in most of clinical situations encountered by the women with gynaecological cancer (see annex 2).

The surgical teams are particularly involved in Sentinel Lymph Node (SLN) biopsy in early cervical cancers and conducted two previous prospective and randomized trials and one ongoing international randomized trial to compare SLN biopsy and full pelvic lymphadenectomy (SENTICOL trials). A prospective randomized trial is also ongoing in high risk endometrial cancers to compare SLN biopsy and pelvic plus paraaortic lymphadenectomy (SENTIRAD).  An international randomized trial is ongoing to assess the interest of radical surgery in early cervical cancer (SHAPE). Research in robotic surgery in uterine cancers has also been developed in both sites.  

In the field of ovarian cancers, several trials have been conducted in upfront and interval surgery and three ongoing randomized trials assess the benefit of upfront surgery in resectable advanced ovarian cancer (TRUST, international trial), the number of cycles of chemotherapy in interval debulking (CHRONO), and the benefit of lymph node dissection in patients without suspicious nodes. Surgery and HIPEC has also been investigated in two randomized trials (DESKTOP III and CHIPOR).

The surgical and medical teams are also involved in Lynch Syndrome with several publications in screening, prophylactic surgery and characterization of Lynch Syndrome-related endometrial cancers. Several projects are ongoing, such as the psychological features of patients (APPLE) and breast cancer and Lynch Syndrome.

Regarding medical oncology, the participation of each centre to therapeutic trials is the result of a coordinated policy in order to optimize the number of inclusions and offer the largest panel of therapeutic options, especially for patients with advanced refractory disease or rare tumour. Thus, large phase III trials are generally opened in both centres, while trials focusing on a rare situation (defined on clinical, histological or molecular criteria) are opened in one centre with no concurrent trial in the other. 

Translational research

Translational research involves 10 senior researchers and mainly 2 Inserm research Team located to the Cordeliers research centre and the PARCC. These research teams are led by Pierre Laurent-Puig and Eric Tartour and investigates new biomarkers in gynaecological cancer (ovarian and endometrial, and cervical cancers).

The main translational research fields are about cell-free DNA (cfDNA) in ovarian and endometrial cancers and HPV in cervical cancer.

• An ongoing research project deals with the prognostic and predictive value of circulating tumour DNA (ctDNA) in advanced ovarian cancer (Projet BIOVAIRE; A-S. Bats). Ovarian cancer is the leading cause of death in gynaecological tumours after breast cancer with more than 3,000 estimated deaths in France in 2008. It is necessary to develop method for early detection of this cancer and to predict prognosis, recurrences or treatment failures in patients with ovarian cancer. This project targets: (i) the development and validation of new assays and strategies for cfDNA analysis in ovarian cancer; (ii) a clinical validation aspect aiming at demonstrating the pertinence of cfDNA follow-up for ovarian cancer patients’ management. Plasma samples from 125 patients with advanced ovarian cancer will be collected at time of diagnosis and then at each cycle of chemotherapy, and during the time of patient follow-up (up to 2 years), to assess the levels of CA-125 and cfDNA. Pelvic ultrasound and thoraco-abdomino-pelvic Computed Tomography (CT) will also be performed at base line and during follow-up for morphological analysis and malignancy evaluation of ovarian masses.

Concerning endometrial cancer, a cohort of endometrial cancer (EC) was built, bringing together clinical data, tumour tissue, tumour DNA and RNA (the MICE cohort). We showed that the molecular characterization of the CE could provide prognostic information independent of the stage and histological characteristics of the tumour (Beinse et al. submitted). In a parallel work, we explored the molecular alterations associated with NRF2 activation, a player of redox regulation and also in EC chemoresistance (Beinse et al. Plos one 2019). Using this cohort, we plan to characterize tumour DNA methylation profiles in endometrial carcinoma and assess their prognostic value. This project will be enlarged to the detection of ctDNA and could also have several clinical applications in EC: molecular characterization, prognostic evaluation, monitoring of treatment effectiveness and early detection of relapse. To detect ctDNA, we are developing a new highly sensitive approach using droplet digital PCR and characterization of a DNA methylation profile, which is specific of endometrial carcinoma. This project will be conducted by a fellow during his PhD. G Beinse has received a grant from the French National Cancer Institute.

• Concerning cervical cancers, we set up a project aiming to identify molecular HPV related biomarkers associated with recurrence in cervical cancer patients without nodal invasion N- (TRANSLACOL H Péré). project aims at identifying molecular HPV related biomarkers associated with recurrence in cervical cancer patients without nodal invasion (N-) (IP: H. Péré, INSERM UMR-S, ARCAGY-GINECO TRANSLACOL). Since the quasi-totality of cervical cancers are related to previous HPV infection, we propose to identify molecular parameters linked to the HPV infection that correlates with an increased risk of recurrence in patients with “good prognosis” early cervical cancer as determined by classical clinical and histological parameters. These molecular biomarkers are based on HPV capture technic performed on tumour samples (HPV whole genome sequencing / HPV status: integrated or episomal / integration site in the virus and human genome) and HPV ctDNA detection in lymph nodes by droplet-based digital PCR.

Our research teams are also involved in immunotherapy in ovarian cancer. These research areas are developed in the program 1 and 2 of the SIRIC CARPEM.

The Gynaecological cancer Program integrates 8 interns each year and 5 fellows.

Medical and surgical teams are widely involved in the university teaching of gynaecological pathologies in Paris Descartes University and in several national teaching degrees/master’s degrees in the field of oncology:

• DES in Obstetrics and Gynaecology
• DES in Medical Gynaecology
• DES in Oncology
• Targeted therapies module DESC in oncology (F Goldwasser and J Alexandre)
• DIU in Gynaecological and Breast Oncology
• DIU of Gynaecological robotic surgery including an oncological module (AS. Bats)
• DIU in Menopause
• DIU in Oncogeriatrics
• DIU in Clinical Psycho-oncology Psychiatry

The Gynaecological cancers program propose several clinical and research perspectives.

From a clinical point of view, we would like to:

• Develop robotic surgery
• Develop Day surgery
• Develop a Fast-track surgery program
• Implement a rehabilitation program for patients with gynaecological cancers, supporting quality of life of patients (psychological and sexual aspects, sport activities…)
• Develop screening and prophylactic surgery of patients at risk for gynaecological cancers
• From the clinical research point of view, we have planned to:
• Increase our inclusion rate in therapeutic trials with complementary trials
• Develop of a prospective database of gynaecological cancers
• Finally, translational research will be developed, particularly in the field of biomarkers (cfDNA, HPV…)

The selected publications highlight the strength of these research fields and the strong collaboration between physicians and researchers in the gynaecological cancers program:

1. Balaya V, Mathevet P, Magaud L, Bonsang-Kitzis H, Delomenie M, Montero Macias R, Ngô C, Bats AS, Lécuru F. Predictive factors of unexpected lymphatic drainage pathways in early-stage cervical cancer. Gynecol Oncol. 2019 Jul;154(1):102-109.
2. Balaya V, Lécuru F, Magaud L, Ngô C, Huchon C, Bats AS, Mathevet P. Perioperative morbidity of radical trachelectomy with lymphadenectomy in early-stage cervical cancer: a French prospective multicentric cohort. J Gynecol Oncol. 2019 May;30(3):e34.
3. Bretagne M, Jouinot A, Durand JP, Huillard O, Boudou Rouquette P, Tlemsani C, Arrondeau J, Sarfati G, Goldwasser F, Alexandre J. Estimation of glomerular filtration rate in cancer patients with abnormal body composition and relation with carboplatin toxicity. Cancer Chemother Pharmacol. 2017 Jul;80(1):45-53.
4. Rossi L, Le Frere-Belda MA, Laurent-Puig P, Buecher B, De Pauw A, Stoppa-Lyonnet D, Canlorbe G, Caron O, Borghese B, Colas C, Delhomelle H, Chabbert-Buffet N, Grandjouan S, Lecuru F, Bats AS. Clinicopathologic Characteristics of Endometrial Cancer in Lynch Syndrome: A French Multicenter Study. Int J Gynecol Cancer. 2017 Jun;27(5):953-960.
5. Poveda A, Del Campo JM, Ray-Coquard I, Alexandre J, Provansal M, Guerra Alía EM, Casado A, Gonzalez-Martin A, Fernández C, Rodriguez I, Soto A, Kahatt C, Fernandez Teruel C, Galmarini CM, Pérez de la Haza A, Bohan P, Berton-Rigaud D. Phase II randomized study of PM01183 versus topotecan in patients with platinum-resistant/refractory advanced ovarian cancer. Ann Oncol. 2017 Jun;28(6):1280-1287.
6. Ngô C, Cornou C, Rossi L, Bats AS, Bensaid C, Frati A, Nos C, Lécuru F. Evidence for the use of robotically assisted surgery in gynecologic cancers. Curr Opin Oncol. 2016 Sep;28(5):398-403.
7. Dessapt AL, Huchon C, Ngo C, Bats AS, Bensaid C, Lecuru F. Is complete cytoreductive surgery feasible in this patient with ovarian cancer? Surg Oncol. 2016 Sep;25(3):326-31.
8. Beinse G, Emile G, Cessot A, Boudou-Rouquette P, Huillard O, Saidu NE, Borghese B, Goldwasser F, Pujade Lauraine E, Alexandre J. A Real-Life Experience of Bevacizumab in Elderly Women With Advanced Ovarian Carcinoma. J. Int J Gynecol Cancer. 2016 Sep; 26(7):1196-200.
9. Sugiyama T, Okamoto A, Enomoto T, Hamano T, Aotani E, Terao Y, Suzuki N, Mikami M, Yaegashi N, Kato K, Yoshikawa H, Yokoyama Y, Tanabe H, Nishino K, Nomura H, Kim JW, Kim BG, Pignata S, Alexandre J, Green J, Isonishi S, Terauchi F, Fujiwara K, Aoki D. Randomized Phase III Trial of Irinotecan Plus Cisplatin Compared With Paclitaxel Plus Carboplatin As First-Line Chemotherapy for Ovarian Clear Cell Carcinoma: JGOG3017/GCIG Trial. J Clin Oncol. 2016 Aug;34(24):2881-7.
10. Péré H, Pavie J, Pernot S, Veyer D, Bertaud D, Hurel S, Bélec L, Hans S, Ménard M, Cochand-Priollet B, Weiss L, Bats AS, Badoual C; AP-HP CoMPap (Consultation Multidisciplinaire Papillomavirus) group. Comment on “Increased risk of second cancers at sites associated with HPV after a prior HPV-associated malignancy, a systematic review and meta-analysis”. Br J Cancer. 2019 Apr;120(9):952-953. doi: 10.1038/s41416-019-0439-0.

11. Beinse G, Just PA, Rance B, Izac B, Letourneur F, Saidu NEB, Chouzenoux S, Nicco C, Goldwasser F, Pasmant E, Batteux F, Borghese B, Alexandre J, Leroy K. The NRF2 transcriptional target NQO1 has low mRNA levels in TP53-mutated endometrial carcinomas. PLoS One. 2019 Mar;14(3):e021441
12. Zonta E, Garlan F, Pécuchet N, Perez-Toralla K, Caen O, Milbury C, Didelot A, Fabre E, Blons H, Laurent-Puig P, Taly V. Multiplex Detection of Rare Mutations by Picoliter Droplet Based Digital PCR: Sensitivity and Specificity Considerations. PLoS One. 2016 Jul 14;11(7):e0159094.
13. Karaki S, Pere H, Badoual C, Tartour E. Hope in the Long Road Toward the Development of a Therapeutic Human Papillomavirus Vaccine. Clin Cancer Res. 2016 May 15;22(10):2317-9.
14. Perez-Toralla K, Pekin D, Bartolo JF, Garlan F, Nizard P, Laurent-Puig P, Baret JC, Taly V. [Digital PCR compartmentalization I. Single-molecule detection of rare mutations]. Med Sci (Paris). 2015 Jan;31(1):84-92.
15. Beinse G, Rance B, Just PA, Izac B, Letourneur F, Bennett Saidu NE, Chouzenoux S, Nicco C, Goldwasser F, Batteux F, Durdux C, Chapron C, Pasmant E, Leroy K, Alexandre J, Borghese B. Identification of TP53 mutated group using a Molecular and Immunohistochemical Classification of Endometrial carcinoma (MICE) to improve prognostic evaluation for adjuvant treatments

Annex 1:  Main indicators of clinical activities

Annex 2:  Ongoing Clinical Trials

If you are interested by this program and want to candidate to a PhD, post doctoral position, contact the leader

Pr Anne-Sophie Bats