RARE GYNECOLOGICAL CANCERS Isabelle Ray-Coquard MD, PhD Centre Léon Bérard Lyon, France Stresa, March 2011
Rare Gynecological cancer: <ul><li>Ovarian site </li></ul><ul><li>Fallopian tube </li></ul><ul><li>Uterine site </li></ul>...
Rare ovarian cancers  <ul><li>Mostly: </li></ul><ul><ul><li>Germ cell tumors and sex cords tumors   </li></ul></ul><ul><li...
Rare endometrial cancers  <ul><li>Mostly : </li></ul><ul><ul><li>Uterine sarcoma / mesenchymal tumor </li></ul></ul><ul><u...
Rare Cervix cancers  <ul><li>Mostly: </li></ul><ul><ul><li>Some subtype of Squamous cell carcinomas </li></ul></ul><ul><ul...
Rare vulva & vagina cancers  (10% of all gyneco cancers) <ul><li>Mostly: </li></ul><ul><ul><li>Squamous cell carcinomas (9...
Gestational trophoblastic diseases:  0.57 to 1/100 000 pregnancies; <1% <ul><li>Hydatiform mole  </li></ul><ul><ul><li>(co...
Incidence & prevalence by sites
Survival rate by sites
Incidence & survival rates by subgroups
Specificity of rare gynecologic cancer <ul><li>Extreme variability of the Population  </li></ul><ul><ul><li>Different loca...
Definition of rare gynecologic cancer ? <ul><li>Rare due to the localization : vulva & vagina </li></ul><ul><li>Rare due t...
1) Example of uterine sarcoma…. Ducimetière F, et al PLoSOne 2011 3 to 5% of all invasive uterine cancers 3% of all STS or...
<ul><li>Histological subtypes: </li></ul><ul><ul><li>Leiomyosarcoma  (+++) HR+, WT1 & PDGFRα +,  5yrs - OS  50 to 0%; rela...
Uterine sarcoma Treatment Algorithm 1st line 3rd line 2nd line *if doxorubicin or ifosfamide not recommended Localised sta...
Endometrial stromal sarcoma biology & IHC <ul><li>3 specific fusion transcript:  </li></ul><ul><li>t(7;17) (p15;q21)    J...
Endometrial stromal sarcoma Treatment Algorithm F Amant, Lancet 2009
Endometrial stromal sarcoma  Hormonal therapy options F Amant, Lancet 10 & Fayette et al, ASCO 06
2) Rare ovarian cancers <ul><li>Mostly Sex cords and germ cell   </li></ul><ul><ul><li>Few data from literature </li></ul>...
PRINCIPLE OF INITIAL SURGERY <ul><li>Surgery must delineated :  </li></ul><ul><li>The diagnosis  </li></ul><ul><li>The sta...
<ul><li>At least  :   </li></ul><ul><ul><li>unilateral annexectomy </li></ul></ul><ul><ul><li>Complete exploration (pelvis...
GERM CELL TUMOURS <ul><li>Platinum based chemotherapy   (Williams 1987) especially since 1987 3 or 4 cycles of BEP (Gershe...
SEX CORD AND STROMA TUMOURS <ul><li>Ovarian stromal tumours </li></ul><ul><ul><li>Granulosa cell tumours </li></ul></ul><u...
SEX CORD AND STROMA TUMOURS  <ul><li>8% of ovarian tumours </li></ul><ul><li>Most of them are secretories : synthesis of p...
Relapse risk for GCT <ul><li>AUTHORS Nb cases Nb rec.  % </li></ul><ul><li>Schwartz 37 6 16 </li></ul><ul><li>Stenwig 118 ...
Survival after relapse <ul><li>AUTHORS Interval Survival </li></ul><ul><li>Schwartz 1-9 yrs 19% </li></ul><ul><li>Panckrat...
Clinical Prognostic Factors in SCT <ul><li>Stage </li></ul><ul><li>Age </li></ul><ul><li>Tumor Size </li></ul><ul><li>Bila...
Preop rupture:  3/12 pts received CT Intraop rupture: 4/9 pts received CT TUMOR RUPTURE Schneider et al, JCO vol 22, n10, ...
HISTOLOGIC PROGNOSTIC FACTORS IN GCT <ul><li>Histologic pattern </li></ul><ul><li>Degree of cellular atypia </li></ul><ul>...
<ul><li>SEER database of 326 pts (01/1992 to 12/2001) </li></ul><ul><li>134 young patients (<50 years) with stage I  </li>...
<ul><li>Author CT N. RR   </li></ul><ul><li>Gersherson 1987 CAP 8 63% </li></ul><ul><li>Pectasides 1992 CAP 10 60% </li></...
Vorinostat  in Stage IV GGCT  Histone Deacetylase (HDAC) Inhibitor  Response  after 11 months of treatment. Prior treatmen...
Summary for rare ovarian cancers <ul><li>What we support with some evidence: </li></ul><ul><ul><li>Surgery is the cornerst...
<ul><li>http://ovaire-rare.org   </li></ul><ul><li>Display on-line </li></ul><ul><li>STEERING COMMITTEE : Pierre Biron, He...
RATIONAL for a dedicated Website <ul><li>With health care professionals: </li></ul><ul><ul><li>To homogeneously manage tre...
METHODS <ul><li>The website on rare malignant tumours of the ovary elaborated by the GINECO group can be visited on intern...
Clinical study inclusion
2008 RESULTS <ul><li>In 2008, 172 patients with GCT or SCT were included in the prospective study. </li></ul>Observed inlu...
<ul><li>Total agreement 42 (63%) </li></ul><ul><li>Partial  a g r e e m e n t   17 (25%) </li></ul><ul><ul><li>Difference ...
CONCLUSIONS   <ul><li>After 4 years, the use of the website is effective and enables to recruit patients.  </li></ul><ul><...
<ul><li>Controversial results & Some improvement trails… </li></ul><ul><ul><li>Complete concordance of pathological diagno...
2009,  2 nd  step  : National rare Gynecologic cancer network <ul><li>Optimizing the recruitment with systematic expert pa...
Ministère de la Santé  et des sports  Call for proposal 2010 INCa – DHOS Approval for national referent cancer center dedi...
Objectives for gynecological projet - care  <ul><li>To increase the number of patients with rare gynecological disease whe...
Objectives - research <ul><li>To increase the number of included patients in dedicated clinical trials  </li></ul><ul><ul>...
New strategies & new targets Today, more than 250 tumors samples and clinical data for GCT & SCT are available & dedicated...
List of regional experts centers  CHU Hôpital Civil Institut Bergonié Centre Jean Perrin Centre Georges François Leclerc C...
Approval  and Financial support by INCA  2010
Example of dedicated CPG’s for mucinous ovarian cancer
 
3) Management & improvements for gestational trophoblastic disease
French Trophoblastic Disease Reference Center Lyon Sud University Hospital <ul><li>Hydatidiform moles </li></ul><ul><li>Ge...
Registration of patients to the  trophoblastic disease reference center francois.golfier@chu-lyon.fr, touria.hajri@chu-lyo...
Conclusions <ul><li>Rare Gynecologic cancers = same problematic than all other rare cancers: </li></ul><ul><ul><li>Absence...
 
Specificity of rare gynecological cancers <ul><li>Σ of rare cancers > to Σ of frequent cancers ? </li></ul><ul><li>All vul...
Sex cords ovarian cancers <ul><li>Most frequent rare ovarian cancers </li></ul><ul><li>Fertility sparing surgery is mandat...
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Rare Solid Cancers: An Introduction - Slide 8 - I. Ray-Coquard - Rare female genital cancers

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  • 8% de tumerus ovariennes derivent de cordons sexuels et du mésenchyme de la gonade embryonnaire
  • Several known oncogenes have been investigated as candidates for a role in the pathogenesis of GCT King found no association of c-myc, .. Immunochemistery and prognosis in a panel of 40 GCTs Kalfa et al., found that the extinction of FOXL2 in 26 pts with JGCT was prognosis of relapse vs no for pts with normal expression
  • Re Page d’accueil …. Annonce du site à tous les membres de TMRO avec login et ancien mot de passe, changeable après à la connexion. Transfert des données des patientes incluses dans TMRO dans cette nouvelle base, avec nouvelle politique … à définir.
  • Right answer are 1 2
  • Right answers are 1 3 5
  • Rare Solid Cancers: An Introduction - Slide 8 - I. Ray-Coquard - Rare female genital cancers

    1. 1. RARE GYNECOLOGICAL CANCERS Isabelle Ray-Coquard MD, PhD Centre Léon Bérard Lyon, France Stresa, March 2011
    2. 2. Rare Gynecological cancer: <ul><li>Ovarian site </li></ul><ul><li>Fallopian tube </li></ul><ul><li>Uterine site </li></ul><ul><li>Cervix site </li></ul><ul><li>Vulva and vagina </li></ul><ul><li>Gestational </li></ul><ul><li>trophopbalstic disease </li></ul>There are six potential sites for gynecologic cancer, each with a distinctive anatomy and histology. The cancer can be traced to a derivative cell. Ovary epithelial neoplasms include the common varieties of adenocarcinomas and also give rise to a rich variety of germ cell neoplasms. The uterine wall undergoes dramatic proliferative change monthly in its glandular epithelium during the menstrual cycle, gives rise to adenocarcinomas. The cervix has a simple columnar epithelium and changes to a stratified squamous epithelium, which gives rise to squamous cell cancers. The fallopian tube is lined by ciliated columnar epithelium and tends to give rise mainly to serous adenocarcinomas. Syncytiotrophoblast gives rise to choriocarcinoma, gestational trophoblast tumors.
    3. 3. Rare ovarian cancers <ul><li>Mostly: </li></ul><ul><ul><li>Germ cell tumors and sex cords tumors </li></ul></ul><ul><li>But also: </li></ul><ul><ul><li>Invasive Border line tumors (serous, mucinous, papillary) </li></ul></ul><ul><ul><li>Mucinous and clear cell carcinoma </li></ul></ul><ul><ul><li>Sarcoma (angiosarcoma, leiomyosarcoma, fibrosarcoma) </li></ul></ul><ul><ul><li>carcinosarcoma </li></ul></ul><ul><ul><li>Small cell tumors </li></ul></ul><ul><ul><li>metastasis (endometrial, breast, digestive) </li></ul></ul><ul><ul><li>NHML (primary or metastasis) & leukemia </li></ul></ul>
    4. 4. Rare endometrial cancers <ul><li>Mostly : </li></ul><ul><ul><li>Uterine sarcoma / mesenchymal tumor </li></ul></ul><ul><ul><ul><li>Leiomyosarcoma </li></ul></ul></ul><ul><ul><ul><li>Endometrial stromal sarcoma </li></ul></ul></ul><ul><ul><ul><li>Adenosarcoma </li></ul></ul></ul><ul><ul><ul><li>Very rare: hemangiopericytoma, leiomyoblastoma, leiomyomatosis, angiosarcoma, GIST, liposarcoma…. </li></ul></ul></ul><ul><li>But also: </li></ul><ul><ul><li>Carcinosarcoma +++ </li></ul></ul><ul><ul><li>Uterine papillary serous carcinoma </li></ul></ul><ul><ul><li>Clear cell carcinoma </li></ul></ul><ul><ul><li>NHML (primary or metastasis) & leukemia </li></ul></ul>
    5. 5. Rare Cervix cancers <ul><li>Mostly: </li></ul><ul><ul><li>Some subtype of Squamous cell carcinomas </li></ul></ul><ul><ul><ul><li>Verrucous, condylomatous, papillary squamotransitional carcinoma, sarcomatoid carcinoma </li></ul></ul></ul><ul><ul><li>Glandular tumors: </li></ul></ul><ul><ul><ul><li>Adenocarcinoma, mucinous carcinoma, endometroid, papillary </li></ul></ul></ul><ul><ul><ul><li>Clear cell adenocarcinoma, seours papillary, transitional, </li></ul></ul></ul><ul><ul><ul><li>Adenoid cystic carcinoma, adenoid basal carcinoma </li></ul></ul></ul><ul><li>But also: </li></ul><ul><ul><li>Small cell carcinoma +++ </li></ul></ul><ul><ul><li>Carcinoid tumors </li></ul></ul><ul><ul><li>Sarcomas (RMS, granulocytic, leiomyosarcoma, PNET) </li></ul></ul>
    6. 6. Rare vulva & vagina cancers (10% of all gyneco cancers) <ul><li>Mostly: </li></ul><ul><ul><li>Squamous cell carcinomas (90%) </li></ul></ul><ul><ul><li>Melanoma </li></ul></ul><ul><li>But also: </li></ul><ul><ul><li>Basal cell carcinoma (2 – 4%) </li></ul></ul><ul><ul><li>Sarcomas (leiomyosarcoma, MFH, epitheloid) </li></ul></ul><ul><ul><li>Kaposi, metastatic disease, Merckel cell carcinoma) </li></ul></ul>
    7. 7. Gestational trophoblastic diseases: 0.57 to 1/100 000 pregnancies; <1% <ul><li>Hydatiform mole </li></ul><ul><ul><li>(complet or partial) </li></ul></ul><ul><li>Invasive mole </li></ul><ul><li>Choriocarcinoma </li></ul><ul><li>Placental site </li></ul><ul><li>Trophoblastic tumor </li></ul>
    8. 8. Incidence & prevalence by sites
    9. 9. Survival rate by sites
    10. 10. Incidence & survival rates by subgroups
    11. 11. Specificity of rare gynecologic cancer <ul><li>Extreme variability of the Population </li></ul><ul><ul><li>Different localizations </li></ul></ul><ul><ul><li>Age (young versus elderly) </li></ul></ul><ul><ul><li>Risk factors (hormonal, …) </li></ul></ul><ul><ul><li>Environmental factors versus genetic predisposition </li></ul></ul><ul><ul><li>Various histology (epithelial, mesenchymatous, melanoma…) </li></ul></ul><ul><ul><ul><li>extreme variability of treatment strategies </li></ul></ul></ul>
    12. 12. Definition of rare gynecologic cancer ? <ul><li>Rare due to the localization : vulva & vagina </li></ul><ul><li>Rare due to the age class: ovarian high grade serous carcinoma for adolescent patient </li></ul><ul><li>Rare due to histology or histological subtype in such localization: vulvar melanoma </li></ul><ul><li>Rare for all : trophoblastic diseases, ESS, ovarian Sex Cords tumors </li></ul>
    13. 13. 1) Example of uterine sarcoma…. Ducimetière F, et al PLoSOne 2011 3 to 5% of all invasive uterine cancers 3% of all STS or visceral sarcoma
    14. 14. <ul><li>Histological subtypes: </li></ul><ul><ul><li>Leiomyosarcoma (+++) HR+, WT1 & PDGFRα +, 5yrs - OS 50 to 0%; relapse rate 50 to 75% Prognostic factors: tumor size and grade </li></ul></ul><ul><ul><li>STUMP (uncertain malignancy) </li></ul></ul><ul><ul><li>Endometrial stromal sarcoma (low & high grade) t(7;17) HR+++ 5yrs – OS 98 to 55%; Prognostic factors: size, stage, no undifferientated component </li></ul></ul><ul><ul><li>Rare : Undifferentiated sarcoma (high grade) </li></ul></ul><ul><ul><li>Adenosarcoma (low grade +++) </li></ul></ul><ul><ul><li>Very rare : angiosarcoma, hemangio pericytoma, pleomorphic, liposarcoma, desmoplastic, GIST … </li></ul></ul>Uterine Sarcoma: Epidemiology
    15. 15. Uterine sarcoma Treatment Algorithm 1st line 3rd line 2nd line *if doxorubicin or ifosfamide not recommended Localised stage Hysterectomy with oophorectomy +/- RT Cure (40–50%) Metastases (50–70%) Surgery (15% ) Doxorubicin Ifosfamide Yondelis Yondelis* Ifosfamide Doxorubicin Yondelis Yondelis Combination ? ? OS 10–12 months PFS 5–8 months ?
    16. 16. Endometrial stromal sarcoma biology & IHC <ul><li>3 specific fusion transcript: </li></ul><ul><li>t(7;17) (p15;q21)  JAZF1 & SUZ12; PHF1 & JAZF1 or PHF1 & EPC1 </li></ul><ul><li>All members of polycomb group (PCb) of genes inolved in the histones methylation </li></ul>
    17. 17. Endometrial stromal sarcoma Treatment Algorithm F Amant, Lancet 2009
    18. 18. Endometrial stromal sarcoma Hormonal therapy options F Amant, Lancet 10 & Fayette et al, ASCO 06
    19. 19. 2) Rare ovarian cancers <ul><li>Mostly Sex cords and germ cell </li></ul><ul><ul><li>Few data from literature </li></ul></ul><ul><ul><li>Only retrospective studies </li></ul></ul><ul><ul><li>The most important series : 200 patients over 15 years </li></ul></ul><ul><ul><li>Information come from data concerning other localizations, clinical situations or hystology: </li></ul></ul><ul><ul><li>TESTICULAR GERM CELL TUMOURS </li></ul></ul><ul><ul><li>NO DEFINITE NOR CONSENSUAL DATA </li></ul></ul>
    20. 20. PRINCIPLE OF INITIAL SURGERY <ul><li>Surgery must delineated : </li></ul><ul><li>The diagnosis </li></ul><ul><li>The staging of the disease </li></ul><ul><li>The initial therapeutic act. </li></ul><ul><li>Specific issues : </li></ul><ul><ul><li>The first step is often done by non oncologist specialists </li></ul></ul><ul><ul><li>The place of fertility-sparing surgery </li></ul></ul><ul><ul><li>The role for re staging </li></ul></ul><ul><ul><li>The benefit from systematic lymph node dissection </li></ul></ul>
    21. 21. <ul><li>At least : </li></ul><ul><ul><li>unilateral annexectomy </li></ul></ul><ul><ul><li>Complete exploration (pelvis + abdominal cavity) </li></ul></ul><ul><ul><li>Peritoneal waching +/- cytology </li></ul></ul><ul><ul><li>Systematic peritoneal biopsy (omentum) </li></ul></ul><ul><ul><li>Resection of all suspect events </li></ul></ul><ul><ul><li>Major point is fertility sparing surgery </li></ul></ul><ul><li>No consensus on 3 points : </li></ul><ul><ul><li>nodes, contrrolateral ovary, debulking surgery. </li></ul></ul>GERM CELL TUMOURS
    22. 22. GERM CELL TUMOURS <ul><li>Platinum based chemotherapy (Williams 1987) especially since 1987 3 or 4 cycles of BEP (Gershenson 1990) </li></ul><ul><li>Depending on the tumour stages/postoperative residue: </li></ul><ul><ul><li>stages II and III : 3 or 4 cycles BEP (residual tumor) </li></ul></ul><ul><ul><li>stage IV: 4 cycles BEP </li></ul></ul><ul><ul><li>stades I (70%): * pure dysgerminoma Ia and Ib </li></ul></ul><ul><ul><li> * immature teratomas Ia Ib grade 1 </li></ul></ul><ul><ul><li>no supplementary treatment after surgery </li></ul></ul><ul><li>Adjuvant radiotherapy : in general no more indication </li></ul>
    23. 23. SEX CORD AND STROMA TUMOURS <ul><li>Ovarian stromal tumours </li></ul><ul><ul><li>Granulosa cell tumours </li></ul></ul><ul><ul><ul><li>Adult form </li></ul></ul></ul><ul><ul><ul><li>Juvenile form </li></ul></ul></ul><ul><ul><li>Tumours of the fibro-thecoma group </li></ul></ul><ul><li>Sertoli and Leydig Stromal tumours (androblastomas) </li></ul><ul><li>Gynandroblastomas </li></ul><ul><li>Steroid cell tumours </li></ul>
    24. 24. SEX CORD AND STROMA TUMOURS <ul><li>8% of ovarian tumours </li></ul><ul><li>Most of them are secretories : synthesis of progesterone, oestrogens, androgens, corticosteroids …. </li></ul><ul><li>Special issue </li></ul><ul><ul><li>Differential diagnosis ? </li></ul></ul><ul><ul><li>Malignancy histologic criterias? </li></ul></ul><ul><ul><li>Prognosis? And so indication of adjuvant treatment </li></ul></ul>
    25. 25. Relapse risk for GCT <ul><li>AUTHORS Nb cases Nb rec. % </li></ul><ul><li>Schwartz 37 6 16 </li></ul><ul><li>Stenwig 118 24 21.2 </li></ul><ul><li>Evans 118 22 18.6 </li></ul><ul><li>Kim 34 3 8.6 </li></ul><ul><li>Chan 83 20 24 </li></ul><ul><li>Ray-Coquard 70 19 27 </li></ul><ul><li>Total 460 94 25% </li></ul>
    26. 26. Survival after relapse <ul><li>AUTHORS Interval Survival </li></ul><ul><li>Schwartz 1-9 yrs 19% </li></ul><ul><li>Panckratz 13% </li></ul><ul><li>Stenwig 1-22 yrs 13% </li></ul><ul><li>Evans 1-23 yrs 27% </li></ul>
    27. 27. Clinical Prognostic Factors in SCT <ul><li>Stage </li></ul><ul><li>Age </li></ul><ul><li>Tumor Size </li></ul><ul><li>Bilaterality </li></ul><ul><li>Rupture </li></ul>
    28. 28. Preop rupture: 3/12 pts received CT Intraop rupture: 4/9 pts received CT TUMOR RUPTURE Schneider et al, JCO vol 22, n10, 2004
    29. 29. HISTOLOGIC PROGNOSTIC FACTORS IN GCT <ul><li>Histologic pattern </li></ul><ul><li>Degree of cellular atypia </li></ul><ul><li>Mitotic activity </li></ul><ul><li>Ki 67 exp </li></ul><ul><li>Mutation of chromosome 6, 12, 22 ? </li></ul><ul><li>c-myc, p21-ras, c-erB2 and p53 </li></ul><ul><li>FOXL2 not expressed or under- expressed in juvenile aggressive GCT </li></ul>Controversial no yes?
    30. 30. <ul><li>SEER database of 326 pts (01/1992 to 12/2001) </li></ul><ul><li>134 young patients (<50 years) with stage I </li></ul><ul><li>97% and 94% survival at 5 and 10 years </li></ul><ul><li>71 pts (54%) had conservative uterine-sparing surgery </li></ul><ul><li>No outcome difference between women undergoing standard vs. conservative surgery (97% vs. 98%) </li></ul><ul><ul><ul><ul><ul><li>Zhang et al. Gynecol Oncol, 2007 </li></ul></ul></ul></ul></ul>Fertility sparing surgery ?
    31. 31. <ul><li>Author CT N. RR </li></ul><ul><li>Gersherson 1987 CAP 8 63% </li></ul><ul><li>Pectasides 1992 CAP 10 60% </li></ul><ul><li>Uygun 2003 CAP 9 44% </li></ul><ul><li>Colombo 1986 PVB 11 82% </li></ul><ul><li>Zambetti 1990 PVB 7 66% </li></ul><ul><li>Pecorelli 1999 PVB 38 61% </li></ul><ul><li>Gersherson 1996 BEP 6 83% </li></ul><ul><li>Homsley 1999 BEP 57 61% </li></ul><ul><li>Brown 2008 CbT 11 81% </li></ul>Chemotherapy in advanced /recurrent sex-cord stromal tumors
    32. 32. Vorinostat in Stage IV GGCT Histone Deacetylase (HDAC) Inhibitor Response after 11 months of treatment. Prior treatment included BEP, doxorubicin, tamoxifen, carboplatin, leuprolide, topotecan, paclitaxel, …. Rubin et al, Clin Cancer Res December 1, 2006
    33. 33. Summary for rare ovarian cancers <ul><li>What we support with some evidence: </li></ul><ul><ul><li>Surgery is the cornerstone of treatment: consider fertility-preserving surgery in young pts </li></ul></ul><ul><ul><li>Postoperative chemotherapy for stage II-IV , recurrences, </li></ul></ul><ul><ul><li>Repeat surgical resections, whenever feasible, for recurrent diseases </li></ul></ul><ul><li>What we would like to know: </li></ul><ul><ul><li>Differential histological diagnosis </li></ul></ul><ul><ul><li>Prognostic factors </li></ul></ul><ul><ul><li>Radical or conservative surgery, and adjuvant treatment for which patients? </li></ul></ul><ul><ul><li>Biological search for new targeted treatment but for which targets? </li></ul></ul>
    34. 34. <ul><li>http://ovaire-rare.org </li></ul><ul><li>Display on-line </li></ul><ul><li>STEERING COMMITTEE : Pierre Biron, Hervé Curé, Jean-Pierre Droz, Pierre Duvillard, Jean Paul Guastalla, Jean-Pierre Lotz, Pierre Méeus, Laurent Mignot, Eric Pujade Lauraine, Isabelle Ray-Coquard, Daniel Raudrant, Véronique Trillet Lenoir, Isabelle Treilleux, Chistophe Tournigand. </li></ul>2002: Ovarian rare malignant tumours national website observatory Private access Public access
    35. 35. RATIONAL for a dedicated Website <ul><li>With health care professionals: </li></ul><ul><ul><li>To homogeneously manage treatment of adult ovarian rare tumour </li></ul></ul><ul><ul><li>To put the different expert knowledge at the physicians disposal (on-line expert advice). </li></ul></ul><ul><ul><li>To include patients with germ cell or sex cords tumors on the prospective databasis </li></ul></ul><ul><ul><li>To systematically confirm the histological diagnosis with centralized expert review </li></ul></ul><ul><ul><li>To perform molecular analysis of these rare ovarian cancer with all available tumor samples </li></ul></ul><ul><li>For the public: </li></ul><ul><ul><li>To keep inform the public with the available scientific data </li></ul></ul><ul><ul><li>To inform patients about new therapeutic options </li></ul></ul>
    36. 36. METHODS <ul><li>The website on rare malignant tumours of the ovary elaborated by the GINECO group can be visited on internet: http://www.ovaire-rare.org </li></ul><ul><li>Shortly, each physician, identified by his registration number at the national Medical Association, will register online, then be given a confidential password for connecting to the database . </li></ul><ul><li>He will then be able to include patients with germ cell or sex cords tumors and/or enter information concerning his patients on the on-line expert advice forum. </li></ul><ul><li>The physician will then have access to on-line expert advice through the website. </li></ul>
    37. 37. Clinical study inclusion
    38. 38. 2008 RESULTS <ul><li>In 2008, 172 patients with GCT or SCT were included in the prospective study. </li></ul>Observed inlusions Observed inclusions Expected inclusions
    39. 39. <ul><li>Total agreement 42 (63%) </li></ul><ul><li>Partial a g r e e m e n t 17 (25%) </li></ul><ul><ul><li>Difference for </li></ul></ul><ul><ul><ul><li>Histologic grade (5) </li></ul></ul></ul><ul><ul><ul><li>Mitotic activity (2) </li></ul></ul></ul><ul><ul><ul><li>Same subgroup but not subtype (10) </li></ul></ul></ul><ul><li>Total disagreement 8 (12%) </li></ul><ul><ul><li>Granulosa cell tumor  small cell carcinoma, clear cell carc </li></ul></ul><ul><ul><li>Sertoli Leydig  Fibrotecoma (begnin T) </li></ul></ul><ul><ul><li>Juvenile granulosa  Dysgerminoma </li></ul></ul><ul><ul><li>Unclassified sex cord T.  Synovialosarcoma (with translocation) </li></ul></ul><ul><ul><li>Teratoma  Carcinosarcoma </li></ul></ul><ul><ul><li>Dysgerminoma  indifferentied Carcinoma </li></ul></ul><ul><ul><li>Teratoma  malignant neurectodermic tumor NOW </li></ul></ul>37% non agreement Centralized review diagnosis (n=67) Ray-Coquard et al, ESMO 2008
    40. 40. CONCLUSIONS <ul><li>After 4 years, the use of the website is effective and enables to recruit patients. </li></ul><ul><li>Histological discrepancies between initial diagnosis and second opinion suggest that this tool is useful for including patients in the clinical trial. </li></ul><ul><li>The website provides very interesting data for a better knowledge of these rare tumors and will possibly help improve medical practice. </li></ul>
    41. 41. <ul><li>Controversial results & Some improvement trails… </li></ul><ul><ul><li>Complete concordance of pathological diagnosis between initial and second opinion : 67% </li></ul></ul><ul><ul><li>Initial surgery not always optimal, sometime « exotic » </li></ul></ul><ul><ul><li>Non all French cases are reported </li></ul></ul>
    42. 42. 2009, 2 nd step : National rare Gynecologic cancer network <ul><li>Optimizing the recruitment with systematic expert pathological review on real time ( < 10 days) to help initial pathologist and oncologists. </li></ul><ul><li>Extension with other French institutions to other rare gynaecological tumors (borderline, mucinous, clear cell, small cell carcinoma…) </li></ul><ul><li>Elaboration of a cancer network organisation with all French expert centres for these rare gynaecological tumors to organize the patient management at the national level (financial support by French NCI, 2010) </li></ul>
    43. 43. Ministère de la Santé et des sports Call for proposal 2010 INCa – DHOS Approval for national referent cancer center dedicated to rare cancers <ul><li>Measure 23 of national cancer plan : </li></ul><ul><ul><li>Approval for referent cancer rare centers </li></ul></ul><ul><ul><li> Regional network and organized care management </li></ul></ul><ul><ul><li> pathologists and experts review </li></ul></ul>
    44. 44. Objectives for gynecological projet - care <ul><li>To increase the number of patients with rare gynecological disease where medical strategy of care is decided in dedicated regional multidisplinary staff at the time of the initial and first relapse management </li></ul><ul><li>To increase the number of tumor samples with systematic second opinion by expert pathologists </li></ul><ul><li>Availability of molecular diagnosis for all patients (ex: FOXL2 mutational status for SCT). </li></ul><ul><li>To delineate and to implement standardized pathological report. </li></ul><ul><li>To delineate a national & specific multidisciplinary staff dedicated to exceptional situations or used of specific drugs (via the website). </li></ul><ul><li>To organize national dedicated workshops and continuing medical education. </li></ul><ul><li>To organize and diffuse information for patients, families, with support of patients advocacy groups </li></ul><ul><li>To elaborate, diffuse and maintain clinical practices guidelines dedicated to rare gynecologic cancers </li></ul>
    45. 45. Objectives - research <ul><li>To increase the number of included patients in dedicated clinical trials </li></ul><ul><ul><li>International (MEoc trial (GCIG-MRC)) or national (beva & SCT) </li></ul></ul><ul><li>To develop tumor banking for all these patients (all included patients signed an informed consent) to delineate specific biologic research. </li></ul><ul><li>To develop treatment strategies and targeted treatments based on pharmaco genomic and tumoral genetic alterations. </li></ul><ul><li>Epidemiological survey of such diseases. </li></ul><ul><li>Evaluation of medical practices concerning rare cancer with comparison of such practices to clinical guidelines and experts advices. </li></ul>
    46. 46. New strategies & new targets Today, more than 250 tumors samples and clinical data for GCT & SCT are available & dedicated to determine new targets ….
    47. 47. List of regional experts centers CHU Hôpital Civil Institut Bergonié Centre Jean Perrin Centre Georges François Leclerc Centre Eugène Marquis Clinique Armoricaine de Radiologie CHU La Source Institut Jean Godinot CHU Hôpital Jean Minjoz AP-HP Hôpitaux de Paris Institut Gustave Roussy CRLC Val d'Aurelle CHU Dupuytren Centre Alexis Vautrin Centre Claudius Regaud Centre Henri Becquerel Centre François Baclesse Centre Catherine de Sienne CHU de Poitiers Institut Paoli Calmettes Groupe Hospitalier Sud Réunion CHU Hôpital Michalon CHU La Croix Rousse Centre Léon Bérard
    48. 48. Approval and Financial support by INCA 2010
    49. 49. Example of dedicated CPG’s for mucinous ovarian cancer
    50. 51. 3) Management & improvements for gestational trophoblastic disease
    51. 52. French Trophoblastic Disease Reference Center Lyon Sud University Hospital <ul><li>Hydatidiform moles </li></ul><ul><li>Gestational Trophoblastic Neoplasia: </li></ul><ul><li>invasive moles and choriocarcinomas </li></ul><ul><li>National Cancer Institute (INCa) funding </li></ul><ul><li>Coordinating center in Lyon </li></ul><ul><li>Regional centers in each of the 22 french regions </li></ul><ul><li>Network of 8 reference pathologists </li></ul><ul><li>INCa – HAS validated guidelines </li></ul><ul><li>ObGyn and Medical Oncologists collaboration </li></ul>Prof. François GOLFIER, MD, PhD – French Trophoblastic Disease Reference Center
    52. 53. Registration of patients to the trophoblastic disease reference center francois.golfier@chu-lyon.fr, touria.hajri@chu-lyon.fr [email_address] Internet (mole-chorio.com) Prof. François GOLFIER, MD, PhD – French Trophoblastic Disease Reference Center
    53. 54. Conclusions <ul><li>Rare Gynecologic cancers = same problematic than all other rare cancers: </li></ul><ul><ul><li>Absence of knowledge, curability, few therapeutic options, no dedicated clinical trials…. </li></ul></ul><ul><ul><li>Sufficient arguments to work all together : </li></ul></ul><ul><ul><ul><li>For diagnosis and molecular tools </li></ul></ul></ul><ul><ul><ul><li>Strategy of management </li></ul></ul></ul><ul><ul><ul><li>Exchanges on local experiences concerning organization of care </li></ul></ul></ul><ul><ul><ul><li>Organization and delineation of research (clinical and biologic) </li></ul></ul></ul><ul><ul><li>International cooperation need : Europe - GCIG </li></ul></ul>
    54. 56. Specificity of rare gynecological cancers <ul><li>Σ of rare cancers > to Σ of frequent cancers ? </li></ul><ul><li>All vulvar cancers are to be considered as rare cancers? </li></ul><ul><li>Gestational diseases represented more than 5% of rare gynecological cancers? </li></ul><ul><li>Survival data are better for all rare gynecological cancer than frequent tumors ? </li></ul><ul><li>Low grade endometrial stromal cancer were really sensible to chemotherapy ? </li></ul>
    55. 57. Sex cords ovarian cancers <ul><li>Most frequent rare ovarian cancers </li></ul><ul><li>Fertility sparing surgery is mandatory for all localized stage </li></ul><ul><li>Standard chemotherapy is BEP regimen </li></ul><ul><li>Histological diagnosis and prognosis are relatively easy to be define for such cancers </li></ul><ul><li>Evidence for the use of targeted treatment for such cancers </li></ul>

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