Dépistage des cancers ovariens
Transcription
Dépistage des cancers ovariens
TUMEURS RARES DE L’OVAIRE et Emergence de réseaux pour la prise en charge de tumeurs rares gynécologiques Isabelle Ray-Coquard, Centre Léon Bérard Vendredi 23 Mars 2012 Paris Isabelle Ray-Coquard - 2011 Conflicts of interest 2011 • honoraria : Novartis, Sanofi, Roche, Pharmamar, Amgen, GSK, Vifor, Ratiopharma, J&J, Jansen, Schering • Advisory board :Novartis, Sanofi, Roche, Pharmamar, Amgen, GSK, J&J, Jansen, Schering, Merck, MSD • Consultant : Roche, Novartis, Pharmamar, Bipar, Sanofi, Millenium, Jansen, Vifor, Amgen, J&J, Pfizer • Research grant : Novartis, Merck, Millenium, Borinhger, MSD, Pfizer, Roche, Isabelle Ray-Coquard - 2012 Incidence & prevalence by sites Table 3. Incidence and prevalence of rare and common cancers by site in EU27 Incidence rate per 100,000 Common Rare All Common Rare All Common Rare All Common Rare All Common Rare All Common Rare All Common Rare All Common Rare All Common Rare All Digestive tract Digestive tract Digestive tract Respiratory tract Respiratory tract Respiratory tract Skin Skin Skin Breast Breast Breast Female genital tract Female genital tract Female genital tract Male genital tract Male genital tract Male genital tract Urinary system Urinary system Urinary system Haematopoietic system Haematopoietic system Haematopoietic system All sites All sites All sites 76,1 17,2 114,1 31,6 13,6 64,1 61,3 1,5 63,7 47,7 4,9 64,3 9,6 16,1 29,5 40,6 4,3 52,0 25,9 2,5 33,1 11,1 9,6 21,9 309,6 97,1 503,6 Standard error 0,1 0,1 0,1 0,1 0,0 0,1 0,1 0,0 0,1 0,1 0,0 0,1 0,0 0,0 0,1 0,1 0,0 0,1 0,1 0,0 0,1 0,0 0,0 0,1 0,2 0,1 0,3 Estimated Incidence Prevalence per incident distribution 100,000 cases in (%) EU27 380 565 67 400,3 86 143 15 50,0 570 236 100 474,6 157 903 49 56,2 68 125 21 60,2 320 391 100 130,0 306 427 96 744,6 7 487 2 14,8 318 615 100 779,7 238 471 74 522,6 24 415 8 56,9 321 429 100 700,1 47 779 32 126,7 80 669 55 176,2 147 597 100 331,7 203 224 78 279,5 21 673 8 93,0 259 868 100 399,6 129 253 78 202,2 12 693 8 18,5 165 457 100 238,7 55 273 50 59,0 48 077 44 62,5 109 721 100 123,9 1 548 036 61 2428,2 485 697 19 797,3 2 518 108 100 3565,4 Standard error 1,2 0,4 1,4 0,3 0,4 0,6 1,5 0,3 1,5 4,1 0,7 6,3 0,6 0,8 1,1 1,4 0,8 1,6 0,7 0,4 0,8 0,5 0,5 0,7 4,9 2,0 7,2 Estimated Prevalence prevalent distribution cases in (%) EU27 2 001 514 84 250 005 11 2 373 151 100 280 918 43 300 876 46 649 911 100 3 722 876 95 74 116 2 3 898 655 100 2 612 913 75 284 484 8 3 500 252 100 633 546 38 881 107 53 1 658 589 100 1 397 655 70 465 225 23 1 997 975 100 1 011 037 85 92 689 8 1 193 504 100 295 022 48 312 462 50 619 550 100 12 141 163 68 3 986 679 22 17 826 767 100 Isabelle Ray-Coquard - 2012 Incidence & survival rates by subgroups Table A. Incidence, survival and prevalence of cancers in EU27 CATEGORY AND SUBCATEGORIES EPITHELIAL TUMOURS OF CORPUS UTERI Adenocarcinoma and variants of corpus uteri Squamous cell carcinoma and variants of corpus uteri Adenoid cystic carcinoma of corpus uteri Transitional cell carcinoma of corpus uteri EPITHELIAL TUMOURS OF CERVIX UTERI Squamous cell carcinoma and variants of cervix uteri Adenocarcinoma and variants of cervix uteri Undifferentiated carcinoma of cervix uteri MIXED EPITHELIAL AND MESENCHYMAL TUMOURS OF UTERUS EPITHELIAL TUMOURS OF OVARY AND FALLOPIAN TUBE Adenocarcinoma and variants of ovary Mucinous adenocarcinoma of ovary Clear cell adenocarcinoma of ovary Adenocarcinoma and variants of fallopian tube NON EPITHELIAL TUMOURS OF OVARY Mixed epithelial mesenchymal tumors of ovary Sex cord tumours of ovary Malignant immature teratomas of ovary Germ cell tumours of ovary EPITHELIAL TUMOURS OF VULVA & VAGINA Squamous cell carcinoma and variants of vulva and vagina Adenocarcinoma and variants of vulva and vagina Paget disease of vulva and vagina Undifferentiated carcinoma of vulva and vagina Incidence rate New cases Observed 5-yr survival Relative 5-yr survival Complete prevalence Prevalent Cases 10,42 52 102 69,5 79,5 133,11 665 573 9,54 47 721 71,7 81,3 126,65 633 271 0,12 583 46,1 53,4 0,95 4 745 0,00 7 70,0 74,5 0,29 1 453 0,00 1 0,0 0,0 0,01 31 6,07 30 373 61,9 66,6 106,46 532 319 4,28 21 398 62,8 67,3 76,24 381 213 1,01 5 055 62,2 66,7 15,59 77 945 0,03 125 30,0 34,1 0,32 1 597 0,45 2 228 31,6 37,4 2,59 12 954 9,41 47 036 33,0 37,7 59,78 298 918 5,97 29 849 33,1 37,0 39,13 195 664 0,84 4 225 52,4 58,0 9,56 47 779 0,32 1 617 49,9 53,9 2,55 12 756 0,27 1 337 42,6 47,8 1,98 9 917 0,43 2 166 57,8 62,5 6,69 33 457 0,16 783 15,9 18,2 0,49 2 474 0,13 671 76,1 82,7 1,85 9 271 0,07 338 80,4 83,2 1,50 7 519 0,07 374 83,7 84,5 2,24 11 185 1,91 9 571 47,0 60,9 15,34 76 689 1,50 7 514 46,4 59,6 12,42 62 107 0,08 388 35,3 42,9 0,52 2 623 0,05 255 78,0 98,0 0,47 2 350 0,01 40 26,3 31,5 0,05 236 0,02 118 89,6 90,0 0,86 4 297 0,02 118 89,6 90,0 0,78 3 906 TROPHOBLASTIC TUMOURS OF PLACENTA Choriocarcinoma of placenta * ICD-O3 code not available Isabelle Ray-Coquard - 2012 Rare ovarian cancer Germ cell tumors Sex cords stromal tumors But also: borderline (serous, mucinous, papillary) Epithelial: mucinous & clear cell Sarcoma (angiosarcoma, leiomyosarcoma, SSE, fibrosarcoma) carcinosarcoma Small cell carcinoma (< 0,5%) Metastasis from carcinoma (uterus, breast, colon, Krukenberg) NHL & leukemia Germ cell tumors (1) Specificities : curable with chemotherapy Similar results than testicular lesion = similar disease? Abnormalities of isochromosome 12 [i(12p)] Rapid development Chemotherapy efficient allow conservative surgery LES TUMEURS GERMINALES (2) Différents groupes histologiques : Les dysgerminomes (45%). Les tumeurs non dysgerminomateuses: – les tumeurs du sac endodermiques (20%) – les tératomes (grade de maturité) (20%) – les carcinomes embryonnaires purs (5%) – les choriocarcinomes purs rares (<5%) – les tumeurs composites (10%). LES TUMEURS GERMINALES (3) Les marqueurs tumoraux : Type de tumeur FP hCG LDH Dysgerminome - + Tumeur sinus endodermique + - Tératome immature - - Carcinome embryonnaire + + Choriocarcinome - + Tumeur mixte Bonne spécificité mais sensibilité médiocre Doivent toujours être dosés avant chirurgie d’une masse pelvienne chez une patiente jeune. Autres marqueurs: CA 125, CA 19-9, NSE, Angiotensine, MCSF LES TUMEURS GERMINALES (4) facteurs pronostiques Les facteurs décrits – la taille tumorale > 10 cm – le type histologique:sinus endodermique, choriocarcinome – le grade histologique (tératomes immatures) – l ’âge > 22 ans – le PS – Le stade élevé, et la rupture tumorale taux de survie à 5 ans <30% CARE PROCESS RATIONAL Rare ovarian followed: tumour treatment is established as – Surgery is conformed to the ovarian carcinoma surgery with possibility of conservative approach – Chemotherapy supported by the evidence based on testicular germ cell tumors. – Surgery, chemotherapy and a eventual second look surgery are strongly interlinked. The surgical act, which remains essential can rely on the chemotherapy efficiency and had to salvage the reproductive function LES TUMEURS GERMINALES (5) chirurgie • Conservatrice l’immense majorité des cas • 3 objectifs : - thérapeutique (ablation de la tumeur) - diagnostique (histologie) - détermination du stade d’extension • Femme jeune + marqueurs non dosés (contexte d’urgence) + examen extemporané impossible: annexectomie unilatérale (ré intervention rapide si adénocarcinome) ==> évite des chirurgies mutilantes inutiles si T germinale. LES TUMEURS GERMINALES (6) chirurgie • Au minimum : – annexectomie unilatérale – exploration complète (pelvis + toute la cavité abdominale) – lavage péritonéal et/ou prélèvement de toute ascite – biopsies péritonéales multiples systématiques (y compris au niveau de l’épiploon) – prélèvement de tout élément suspect • Pas de consensus sur 3 points : ganglions, ovaire controlatéral, réduction tumorale. LES TUMEURS GERMINALES (7) Prise en charge initiale chimio? Chimiothérapie à base de platine (Williams 1987) plus particulièrement depuis 1987 3 ou 4 cycles BEP (Gershenson 1990) Selon les stades tumoraux/résidus post op: – stades II et III : 3 ou 4 cycles de BEP (résidu tumoral) – stades IV: 4 cycles de BEP – stades I (70%): * dysgerminome pur Ia et Ib * tératomes immatures Ia Ib de grade 1 pas de traitement complémentaire ap Xie tous les autres chimiothérapie ? Radiothérapie adjuvante: a priori plus d’indication GERM CELL TUMOURS post therapeutic follow-up: INTENSIVE (every 2 months the first year) – Clinical – Biologic – CT scans – Measure of the toxicities due to the chemotherapy – Assessment of the fertility potential GERM CELL TUMOURS Care process of the relapse Relapse after treatment without CT: – Chemotherapy through platinium salts – +/- supplementary surgical act. Additional treatment after CT failure: – Debulking surgery yes if teratomas – chemotherapy: protocole depending on the sensibility to platinium (6 months) – HD chemotherapies (therapeutic trials or individualy decision) – VP 16 oral; VAC; ifosfamide, phase I, targeted th? …. LES TUMEURS DE CORDONS SEXUELS ET DU STROMA Tumeurs stromales ovariennes – tumeurs de la granulosa (90%) forme adulte forme juvénile – tumeurs du groupe fibro-thécome (1- 4 %) Les tumeurs stromales de Sertoli et Leydig (2%) (androblastomes) Les tumeurs des cordons sexuels avec tubules annelés (<1%) Gynandroblastomes (<1%) Les tumeurs à cellules stéroïdiennes (<1%) LES TUMEURS DE CORDONS SEXUELS ET DU STROMA 7% de tumeurs ovariennes La plupart sont fonctionnelles : synthèse de progestérone, oestrogènes, androgènes, corticostéroïdes Problématique particulière – diagnostic différentiel? – critères histologiques de malignité? – Chirurgie conservatrice ? – pronostic? Indication de traitement adjuvant? Mutation of FOXL2 in Granulosa-Cell Tumors of the ovary. Sohrab P.Shah et al NEJM 2009 Clinical Prognostic Factors in SCT • • • • • Stage Age Tumor Size Bilaterality Rupture TUMOR RUPTURE Preop rupture: 3/12 pts received CT Intraop rupture: 4/9 pts received CT Schneider et al, JCO vol 22, n10, 2004 HISTOLOGIC PROGNOSTIC FACTORS IN GCT • • • Histologic pattern Degree of cellular atypia Mitotic activity Ki 67 over expression Mutation of chromosome 6, 12, 22 ? Controversial c-myc, p21-ras, c-erB2 and p53 no FOXL2 not expressed or underexpressed in juvenile aggressive GCT yes? PRINCIPE DE LA CHIRURGIE INITIALE • Surgery as Primary Treatment: Total abdominal hysterectomy and bilateral salpingo-oophorectomy + complete Surgical Staging • Complete exploration of the cavity • Cytologic evaluation • Omentectomy • Peritoneal biopsies Place of Fertility-Sparing Surgery? Lymph nodes dissection? Chirurgie conservatrice ? • SEER database of 326 pts (01/1992 to 12/2001) • 134 young patients (<50 years) with stage I • 97% and 94% survival at 5 and 10 years • 71 pts (54%) had conservative uterine-sparing surgery • No outcome difference between women undergoing standard vs. conservative surgery (97% vs. 98%) Zhang et al. Gynecol Oncol, 2007 Place du curage ganglionnaire RISQUE DE RECHUTE TCG AUTHORS Nb cases Nb rec. % Schwartz 37 6 16 Stenwig 118 24 21.2 Evans 118 22 18.6 34 3 8.6 Kim Chan 83 20 24 Ray-Coquard 70 19 27 460 94 20 Total SURVIE APRES RECHUTE AUTHORS Schwartz Interval Survival 1-9 yrs 19% Panckratz 13% Stenwig 1-22 yrs 13% Evans 1-23 yrs 27% Chimiotherapie Advanced /Recurrent Sex-cord Stromal Tumors Author CT N. RR Gersherson 1987 CAP 8 63% Pectasides 1992 CAP 10 60% Uygun 2003 CAP 9 44% Colombo 1986 PVB 11 82% Zambetti 1990 PVB 7 66% Pecorelli 1999 PVB 38 61% Gersherson 1996 BEP 6 83% Homsley 1999 BEP 57 61% Sex cords TUMORS Care process of the relapse Relapse after treatment without CT: – Supplementary surgical act. – Chemotherapy with platinium salts Additional treatment after CT failure: – Debulking surgery – chemotherapy: protocole depending on the sensibility to platinium (6 months) – VP 16 oral, VAC, Docetaxel – GEM, phase I, targeted th? …. Vorinostat in Stage IV GCT 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 Bevacizumab & TSC Ovarian small cell carcinoma • Very underestimated tumors • Histogenesis? Classification? • High calcium level (para endocrine) – Young adult (median age 24 years) – hypercalcemia in 2/3 of pts – stage > Ia for more 50% of patients – Poor prognostic (60% of Ia relapsed and died) – Prognostic factors : age > 30 y, calcium level, size < 10 cm, only small cells • Pulmonary form – As SCPC – Oldest patients • Treatment: complete surgery, HD chemotherapy & pelvic radiation Mucinous ovarian carcinoma • • • • • • Rare epithelial tumor: < 5% Young patients (median age 58 y) From borderline mucinous tumor Low grade, localized disease (75%) Ras mutation (50%) Specificities: – Advanced disease rare – Differential diagnosis – Standard chemotherapy very disapointing CLINICAL PRESENTATION AND SENSITIVITY TO PLATIN-BASED CHEMOTHERAPY (CT) OF MUCINOUS ADVANCED EPITHELIAL OVARIAN CARCINOMA: THE GINECOGROUP EXPERIENCE Response rate (% of evaluable patients) Serous Mucinous (N=342) (N=51) Response (complete + partial) 277 (81%) 20 (67%) Stable disease 36 (10%) 1 (3%) Progression 29 (9%) 9 (30%) p 0.0001 Progressive disease during chemotherapy was observed in 40% of pts with stage IV mucinous EOC. J Alexandre for the GINECO-Group, France. Progression-Free Survival Overall Survival Fonction de survie cum ulée Fonction de survie cum ulée 1 1 Serous Mucinous 0,8 0,8 0,6 0,6 0,4 0,4 0,2 0,2 0 0 12 24 36 48 60 72 0 84 0 Mucinous 36 serous mucinous Progression Free Survival Serous 24 48 60 overall survival (months) months Progressionmonths Free Survival (months) serous 12 mucinous Overall survival Median (CI95%) Log rank Median (CI95%) Log rank 17.5 (16.2-19.1) 0.002 47.2 (43.1-52.2) <0.0001 11.4 (6.9-14.2) 21.6 (13.5-32.1) 72 84 A GCIG Intergroup multicentre trial of open label carboplatin and paclitaxel +/bevacizumab compared with oxaliplatin and capecitabine +/- bevacizumab as first line chemotherapy in patients with mucinous Epithelial Ovarian Cancer (mEOC) The mEOC Study is a multi-national collaboration with the Gynecologic Oncology Group (GOG), USA. RATIONALE FACTORIAL TRIAL DESIGN (332 patients) mEOC FIGO stages II–IV OR recurrent stage I No previous chemotherapy; >18yrs; PS=0-2 Patients with mucinous epithelial ovarian cancer (mEOC) are currently treated with carboplatin + paclitaxel chemotherapy. However this treatment is not as effective in treating mEOC, as it is in treating other forms of ovarian cancer. Because mEOC shares molecular similarities with mucinous tumours of the gastrointestinal (GI) tract, it is thought that the chemotherapy agents (oxaliplatin + capecitabine) used to treat these GI tumours may be effective in treating mEOC. A trial evaluating bevacizumab in ovarian cancer is already underway (ICON-7 & GOG 218), so it is appropriate to examine this therapy specifically in patients with mucinous tumours. Furthermore the results of chemotherapy and bevacizumab have been positive in mucinous large bowel tumours. It is reasonable to incorporate anti-VEGF therapy in the mEOC study. Randomise 83 patients Carboplatin AUC 5/6* Paclitaxel 175mg/m2 6 x 21-day cycles 83 patients Oxaliplatin 130 mg/m2 Capecitabine 850mg/m2 bd 6 x 21-day cycles Clinical assessment every 6 weeks for 36 weeks Telephone call at week 3 between every 6-week visit PRIMARY OBJECTIVE The primary aim of this trial is to determine whether chemotherapy with oxaliplatin + capecitabine improves the survival of patients with mucinous ovarian cancer, compared to standard chemotherapy with carboplatin + paclitaxel. In addition, we aim to determine whether Bevacizumab improves overall survival of patients with mucinous epithelial ovarian cancer. SECONDARY OBJECTIVES Progression free survival Response rate Toxicity Quality of life measured by FACT-O TOI, FACT/GOG-NTX Subscale and EQ-5D QoL questionnaires Translational research CURRENT STATUS Interest from sites in UK, Denmark, Finland, Sweden, Norway, France, Italy & Germany. MHRA & MREC approved in UK, NCRI approved trial. 8 Sites open in the UK mEOC Flyer – June 2010 83 patients 83 patients Carboplatin AUC 5/6* Paclitaxel 175mg/m2 6 x 21-day cycles Oxaliplatin 130 mg/m2 Capecitabine 850mg/m2 bd 6 x 21-day cycles Bevacizumab 15mg/kg given every 3 weeks for 5 or 6 cycles Bevacizumab 15mg/kg given every 3 weeks for 5 or 6 cycles ELIGIBILITY CRITERIASummarised Inclusion Criteria: • Histological diagnosis of mucinous ovarian carcinoma • FIGO stage II-IV • Aged 18 or above • Life expectancy >3 months • No previous chemotherapy or radiotherapy • Recurrent stage I • ECOG performance status 0, 1 and 2 • Adequate haematological, renal and hepatic function • Adequate neurological function (sensory & motor grade 1) • Urine dipstick for proteinuria <2+ • Adequate coagulation parameters Exclusion Criteria: • Histological diagnosis of non-mucinous ovarian carcinoma • Previous history of malignancy except cervical carcinoma in situ, and basal cell carcinoma of the skin • Concurrent uncontrolled medical condition • Previous chemotherapy, radiotherapy or any investigational treatment for ovarian or rectal cancer. • Symptoms or history of peripheral neuropathy • Previous history of malabsorption or other conditions preventing oral treatment • Clinically significant cardiac disease, including M.I. in last 12 months • Previous CVA, TIA or SAH in last 6 months • Non healing wound, ulcer or bone fracture • Surgery or significant traumatic injury within 4 weeks of first planned dose of bevacizumab • Uncontrolled hypertension • History/evidence of thrombotic/haemorrhagic disorders Bevacizumab 15mg/kg given every 3 weeks for 12 cycles Clinical assessment every 6 weeks for 36 weeks CONTACT: Rachel Slade, Trial Coordinator [email protected] +44 (0) 20 7679 9857 CT scans are carried out post cycle 3 of chemo, 1 month after completion of cycle 6, then 3 monthly for Year 1 Follow up: 3 monthly years 1-2, 6 monthly years 3-5 *The carboplatin dose depends on the method used to obtain GFR. If GFR has been estimated, AUC=6, if GFR has been measured, AUC=5 Chief Investigator- Prof Martin Gore Royal Marsden Hospital, London Conducted by the Cancer Research UK & UCL Cancer Trials Centre RÉSUMÉ Ce que nous savons: – Tumeurs curables même à la rechute pour certaines – Sujets jeunes, fonction ovarienne à respecter – Efficacité de la chimiothérapie en fonction histo++++ – Prise en charge initiale svt inadéquat (trop/pas assez) Ce que nous ne savons pas: – Facteurs pronostiques & biologie moléculaire – Diagnostic différentiel – Geste chirurgical agressif pour qui? – Chimiothérapie adjuvante pour qui? – Alternatives thérapeutiques ? OBSERVATOIRE NATIONAL DES TUMEURS MALIGNES RARES DE L’OVAIRE : http://ovaire-rare.org Clinical study inclusion 01/07/2008 01/03/2008 01/11/2007 01/07/2007 250 01/03/2007 01/11/2006 50 01/07/2006 01/03/2006 100 01/11/2005 01/07/2005 01/03/2005 01/11/2004 01/07/2004 01/03/2004 01/11/2003 01/07/2003 01/03/2003 01/11/2002 01/07/2002 01/03/2002 2008 RESULTS Expected inclusions 200 150 Série1 Observed inlusions Série2 Observed inclusions 0 • In 2008, 172 patients with GCT or SCT were included in the prospective study. • Controversial results & Some improvement trails… – Complete concordance of pathological diagnosis between initial and second opinion : 67% – Initial surgery not always optimal, sometime « exotic » – Non exhaustivity of all french cases 2009, 2nd step : National rare gynecologic cancer network • Optimizing the recruitment with systematic expert pathological review on real time (< 10 days) to help initial pathologist and oncologists. • Extention with other French institutions to other rare gynecological tumors (borderline, carcinosarcoma, mucinous, clear cell, small cell carcinoma…) • Elaboration of a cancer network organisation with all French expert centers for these rare gynecological tumors to organize the patient management at the national level (financial support by French NCI, 2010) Ministère de la Santé et des sports APPEL A PROJETS 2010 INCa – DHOS Labellisation de Centres experts nationaux pour cancers rares de l’adulte Dossier de candidature Mesure 23 plan cancer: Labéliser centres de référence pour cancer rare (vocation nationale + équipe de recherche reconnue) réseau régional et filière de soins Soutenir démarche qualité de la prof anatomo pathologique Tumeurs concernées • 1) Les tumeurs malignes du stroma et des cordons sexuels et les tumeurs malignes germinales • 2) Les tumeurs épithéliales rares malignes (mucineuses, à cellules claires) et borderline avec implants ou bien posant des problèmes d’interprétation au gynéco pathologiste du centre de référence régional. • 3) les cancers à petites cellules avec hypercalcémie et les tumeurs endocrines sur strume ovarienne • 4) Les autres catégories de tumeurs rares, comme les tumeurs mixtes malignes müllériennes. Objectifs – soins Augmentation du nombre de patientes dont la prise en charge s’effectue via les RCP de recours dédiées lors de la prise en charge initiale, post opératoire ou lors de la prise en charge secondaire Augmentation du nombre de patientes bénéficiant d’une double lecture Mise à disposition du diagnostic moléculaire dans les centres experts nationaux. Organisation de la formation des soignants pour la prise en charge des tumeurs rares de l’ovaire. Organisation de l’information des patients et leur famille, via le site Internet dédié et la création du comité de patientes mise en place 2011 Mise à jour et suivi des référentiels de bonne pratiques médicales Objectifs - recherche Augmentation du nombre de patients inclus dans les études de recherche clinique par an, Développement de chimiothérapies et thérapies ciblées guidées par la pharmaco génomique et les altérations génétiques de la tumeur. Suivi de la prise en charge des patientes atteintes de tumeurs rares de l’ovaire et suivi des pratiques médicales en conformité avec les recommandations de pratiques cliniques et les avis proposés par les RCP de recours regionales ou nationale. Surveillance épidémiologique (dans le cadre du site internet dédié) et suivi de ces cancers rares. agreement and Financial support by INCA 2010 Coordonator : I Ray-Coquard List of regional experts centers AP - HOPITAUX DE PARIS E Pujade-Lauraine / MC Vacher-Lavenu A Cortez C Genestie MA Le Frère-Belda F Walker INSTITUT GUSTAVE ROUSSY Centre Oscar Lambret E Leblanc / I Farré P Pautier / P Duvillard Centre Henri Becquerel H Sevestre (CHU) M Baron / JC Sabourin (CHU) Institut Jean Godinot H Curé / C Garbar Centre Alexis Vautrin B Weber / A Leroux Centre François Baclesse F Joly / C Blanc-Fournier Clinique Armoricaine de Radiologie AC Hardy-Bessard CHU Hôpital Civil JE Kurtz / G Averous Centre Eugène Marquis / CHU Rennes J Leveque / S Henno Centre Georges François Leclerc L Favier / L Arnould CHR La Source J Meunier / C Bonneau Centre Catherine de Sienne A Lortholary / A Dubois (IHP) CHU Hôpital Jean Minjoz E Kalbacher / MP Algros CHU de Poitiers C Nadeau / O Renaud CHU Lyon -La Croix Rousse M Devouassoux CENTRE LEON BERARD I Ray-Coquard / I Treilleux CHU Dupuytren S Lavau-Denes / V Fermeaux Centre Jean Perrin C Pomel / F Penault-Llorca Institut Bergonié A Floquet / G Mac Grogan Groupe Hospitalier Sud Réunion M Boukerrou CHU Hôpital Michalon F Sergent Centre Val d'Aurelle M Fabbro/ MC Chateau Centre Claudius Regaud D Querleu / E Mery Institut Paoli Calmettes M Provensal / E Charafe-Jauffret C Charpin (CHU) Example of dedicated CPG’s for mucinous ovarian cancer ALIENOR : A multi-centre, randomized, open label, phase II trial of Bevacizumab plus weekly Paclitaxel then Bevacizumab monotherapy in maintenance versus observation in patients with relapsed ovarian sexcord stromal tumours • INCLUSION CRITERIA: Histological diagnosis of ovarian SCST previously treated with platinum-based chemotherapy. • PRIMARY ENDPOINT: The non-progression rate after 6 months of combination or standard chemotherapy. • SECONDARY ENDPOINTS: – Progression free survival – Overall Survival – Objective Response Rate and duration of response – Safety profiles of the association of Paclitaxel and Bevacizumab and the safety profile of Bevacizumab monotherapy. • ANCILLARY STUDY: – Plasma biomarkers, circulating endothelial cells , functional MRI • STATISTICAL CONSIDERATIONS: – A maximum sample size of 60 patients (30/ arm) will be included – A Bayesian approach will be used with 2 interim analyses planned after the inclusion of 6 and 8 patients per arm. • LENGTH STUDY: – Patients will be enrolled over 24 month period – duration of patient follow-up will 18 months from start of treatment SCT after at least one line of chemotherapy randomisation W Paclitaxel + Bevacizumab until progression or intolerance W Paclitaxel alone until progression or intolerance Progression Bevacizumab Since 2011, activity from French Ovarian cancer network • 661 registered centers (private, public), & 26 outside French territory • > 317 pathologists • 24 regional referent centers & 3 national centers • 28 referents pathologists organized in network • 676 patients since 2002 • 291 new patients en 2011 – 227 for initial management, 64 in relapse 2011 – multidiciplinary decision from Experts Régional centers (CER) or National centers (CEN) Multidiscipli N of cases nary staff discussed in CER 291 81 N of cases discussed in CER & CEN N of cases discussed only in CEN No MS 120 76 14 2011 – second opinion by Experts pathologist from regional or national expert centers 2011 TOTAL Second opinion No SO ND total 291 155 80 56 From CER From national 90 201 29 126 49 31 12 44 2011 – second opinion asked by initial pathologists And not by the regional or national centers total total Rhônes-Alpes, IDF*, Aquitaine, PACA, Pays de la Loire 447 path-init SO by Path not SO by is expert other one ref expert path 125 112 204 204 ND SO by expert path 118 118 conclusions • Tumeurs ovaires/gynécologiques rares = même problématique que tous les autres cancers rares: – Rares, svt curables, peu alternatives thérapeutiques … – Bons arguments pour travailler ensemble : • Organisation du diagnostic • Organisation des soins • Organisation des connaissances & de l’information • Organisation de la recherche clinique et fondamentale – Niveau international indispensable : GCIG?, world gyneco network?