GERM CELL OVARIAN TUMORS: AN ITALIAN EXPERIENCE

Transcription

1 I.R.C.C.S SAN RAFFAELE HOSPITAL-MILAN GERM CELL OVARIAN TUMORS: AN ITALIAN EXPERIENCE Dott.ssa Giorgia Mangili Gynecology and Obstetric Department, IRCCS San Raffaele Hospital Milan. 11/06/2010

2 PATIENTS CHARACTERISTICS N = 123 patients Mean Age (range) 27.7 (1176) Duration of symptoms Emergency < 30 days >30 days No symptoms 4,9% 39,8% 26% 15,4% Unknown 13,8% Presenting Sign/symptom Pelvic pain 52,8% Abdominal enlargement Abdominopelvic mass Menstrual irregularities 53,7% Amoenorrea 3,2% Ascites 5,7% Fever 2% Hyrsutism 0,9% 53,7% 11,4%

3 HISTOLOGY AND STAGE Dysgerminoma N (%) 49(39,8%) Immature Teratoma 35(28,5%) Endodermal Sinus 26(21,1%) Mixed Embrional Carcinoma Stage 12(9,8%) 0,6 0,5 1(0,8%) Frequenza Histology 47,15% (58) 0,4 21,95% (27) 0,3 19,51% (24) 0,2 0 0,81% 1,63% 2,44% 1,63% (1) (2) (3) (2) 1,63% (2) 0,1 IA IB IC IIA IIB Stadio IIIA IIIB 3,25% (4) IIIC IV

4 SURGICAL TREATMENT MITO center 65,9% Elsewhere 34,1% Laparoscopy 17,9% Laparotomy 82,1% Fertility Sparing 74,8% Radical 25,2% Age and type of Surgery Fertility Sparing Radical Stage I 81,6% 18,4% Stage II-III.IV 58,3% 41,7% 36,7 24,7 T-test (p<0.05)

5 POSTOPERATIVE TREATMENT Chemoterapy in 66% Schedule N. (%) Histology N. (%) PEB 70 (87,6) Dysgerminoma 28 (57,1) PVB 8 (9,8) Immature Teratoma 15 (42,8) EP 1 (1,2) Endodermal Sinus 26 (100) TAX-CARBO 1 (1,2) Mixed 11 (91,7) CARBO 1 (1,2) Embrional Carcinoma 1 (100)

6 REPRODUCTIVE FUNCTION Resume mestrual function Premature ovarian failure 96,6% 3,4% Attempting conception 15 Failures 3 Conceving patients 12 Miscarriage Rate= 25% Adjuvant chemotherpy 7 Conceptions 16 Normal pregnancy 10 Miscarriages 4 Terminations 2 2 patients with XY gonadal disgenesis delivered healty infants, with donor oocyte IVF Conceiving patients 12 Stage IA 7 Stage IC 3 Stage IIIC 2 Dysgerminoma 8 Teratoma immature 2 Endodermal Sinus 1 Mixed 1

7 RECURRENCES OVERALL RECURRENCE RATE= 17,8% MEDIAN TIME TO RECURRENCE= 9 MONTHS 1. Immature teratoma: 25,7% 2. Endodermal Sinus Tumor: 19,2% 3. Mixed tumor: 16,6% 4. Dysgerminoma: 10,2%

8 RISK FACTORS FOR RECURRENCE FACTOR N. RECURRENCE RATE Primary Surgery in MITO center 81 11,1% Primary Surgery elsewhere 42 30,9% Age < 45 years 10 50% Age>45 years % Peritoneal Washing positive 15 33,3% Peritoneal Washing: negative 65 10,8% Dysgerminoma 49 10,2% Non-dysgerminoma 74 23% Stage I 87 13,8% Stage II-III-IV 36 27,7% Conservative Surgery 92 17,4% Radical Surgery 31 19,3% P (χ-square) NS

9 OUTCOME 5 YEARS OVERALL SURVIVAL= 88,8% MEDIAN FOLLOW UP TIME= 61 MONTHS

10 PROGNOSTIC FACTORS Cox Regression Univariate Analysis FACTOR P value - RR Non dysgerminoma histology ,235 Elevated βhcg and αfp Endodermal Sinus Tumor ,31 Stage > I ,576 Age > ,124 Residual disease ,206 Capsular rupture ,874 Tumor on serosal surface ,95 Positive Peritoneal cytology ,94 Cox Regression Multivariate Analysis FACTOR P value - RR Endodermal Sinus Tumor ,94 Stage > I ,94

11 SURVIVAL ANALYSIS Endodermal Sinus versus Other hystologies Other hystologies Endodermal Sinus Tumor Log rank p value= y-OS Endodermal Sinus=69,6% 5y-OS Other histologies= 94,2% Stage I versus Stage II-III-IV Stage I Other hystologies Stage II-III-IV Log rank p value< y-OS stage I= 95,6% 5y-OS advanced stages= 73,2%

12 PROGNOSTIC PREDICTORS IN RELAPSE PATIENTS Endodermal Sinus versus Other hystologies Debulking Surgery versus No surgery Other hystologies Debulking Surgery Endodermal Sinus No Surgery Log rank p value< Log rank p value< Factors P value-rr Factors P value-rr Endodermal Sinus 8, No debulking surgery 9,

13 GERM CELL OVARIAN TUMORS: MITO-9 Prognosis of MOGT is excellent Older age, first treatment not in a MITO center are the main risk factors for recurrence Endodermal sinus histology and stage are indipendent predictors of survival Endodermal sinus histology and debulking surgery are predictor of survival at relapse

14 ROLE OF MULTICENTRIC RETROSPECTIVE STUDIES Compare different terapeutic approaches when there are not established guidelines Define guidelines in rare tumors as is not possible to performe prospective randomized studies

15 Questions? Is it warrented adiuvant chemotherapy in stage I T How to manage clinical stage I A dysgerminoma?

16 IS IS ADJUVANT ADJUVANTCHEMOTHERAPY CHEMOTHERAPY INDI INDI CATED CATED IN IN STAGE STAGE II PURE PURE IMMATURE IMMATUREOVARIAN OVARIAN TERATOMA? TERATOMA? Stage I Immature teratoma: 28 patients Grade 1: 9 patients IA: 8 patients IC: 1 patients Surgery in 9 patients No Relapse Grade 2: 12 patients IA: 5 patients IB: 2 patients Surgery in 8 patients IC:5 patients Surgery+ PEB in 4 patients 3 Relapse: IC Surgery in 3 : Mature teratoma Grade 3: 7 patients IA: 6 patients Surgery in 2 patients IC: 1 patients Surgery+ PEB in 5 patients 3 Relapse: IA Surgery+ PEB in 2: Immature teratoma Surgery in 1: Mature teratoma

17 STAGE IA DYSGERMINOMA N =26 patients Median Age (range) Fertility Sparing Radical Surgery 22,5 (11-59) 65,4% 34,6% Surgical Staging Complete 19,2% Lymph node dissection 38,5% Peritoneal biopsies and/or omentectomy 46,2% Peritoneal washing 65,4% Adjuvant Chemotherapy 27%

18 STAGE IA DYSGERMINOMA Surgical treatment Site of Relapse TAH+BSO Pelvic USO+ Abdomino-pelvic, Washing USO+ peritoneal biopsies lymph-nodal Relapse treatment Outcome Surgery+PEB NED PEB NED Surgery+PVB NED Abdomino-pelvic, lymp-nodal, controlateral ovary

19 STAGE IA DYSGERMINOMA After a median follow up of 100 months all patients are NED Conservative surgery with a complete surgical staging is the gold standard Patients with incomplete staging could undergo surgical restaging Chemotherapy should be reserved to relapse

20 Grazie a tutte le persone che in questi anni hanno lavorato con me Un ringraziamento particolare a Cristina Sigismondi per l aiuto profuso nel preparare tutte le relazioni in cui sono stati presentati i dati del MITO e a Jessica Ottolina Un saluto al Professor Ferrari e un augurio di buon lavoro al Prof Candiani