GERM CELL OVARIAN TUMORS: AN ITALIAN EXPERIENCE I.R.C.C.S SAN RAFFAELE HOSPITAL-MILAN 11/06/2010 Dott.ssa Giorgia Mangili Gynecology and Obstetric Department, IRCCS San Raffaele Hospital – Milan.
GERM CELL OVARIAN TUMORS: AN ITALIAN EXPERIENCE
I.R.C.C.S SAN RAFFAELE HOSPITAL-MILAN
11/06/2010
Dott.ssa Giorgia Mangili
Gynecology and Obstetric Department,IRCCS San Raffaele Hospital – Milan.
PATIENTS CHARACTERISTICS
N = 123 patients
Duration of symptoms
Emergency 4,9% < 30 days 39,8% >30 days 26%No symptoms 15,4%
Unknown 13,8%
Mean Age (range)
27.7(11-76)
PresentingSign/symptom
Pelvic pain 52,8%
Abdominal enlargement
53,7%
Abdomino-pelvic mass
53,7%
Menstrual irregularities
11,4%
Amoenorrea 3,2%
Ascites 5,7%
Fever 2%
Hyrsutism 0,9%
HISTOLOGY AND STAGE
Histology N (%)
Dysgerminoma49(39,8%)
Immature Teratoma
35(28,5%)
Endodermal Sinus
26(21,1%)
Mixed12(9,8%)
Embrional Carcinoma
1(0,8%)
47,15%(58)
1,63%(2)
21,95%(27)
0,81%(1)
1,63%(2)
2,44%(3)
1,63%(2)
19,51%(24)
3,25%(4)
0
0,1
0,2
0,3
0,4
0,5
0,6
Frequenza
IA IB IC IIA IIB IIIA IIIB IIIC IV
Stadio
Stage
SURGICAL TREATMENT
MITO center 65,9%
Elsewhere 34,1%
Laparoscopy 17,9%
Laparotomy 82,1%
Fertility Sparing 74,8%
Radical 25,2%
24,7
36,7
Age and type of Surgery
T-test (p<0.05)
Fertility Sparing
Radical
Stage I 81,6% 18,4%
Stage II-III.IV 58,3% 41,7%
POSTOPERATIVE TREATMENT
Schedule N . (%)
PEB 70 (87,6)
PVB 8 (9,8)
EP 1 (1,2)
TAX-CARBO 1 (1,2)
CARBO 1 (1,2)
Chemoterapy in 66%
Histology N. (%)
Dysgerminoma 28 (57,1)
Immature Teratoma 15 (42,8)
Endodermal Sinus 26 (100)
Mixed 11 (91,7)
Embrional Carcinoma 1 (100)
REPRODUCTIVE FUNCTIONResume mestrual function
96,6%
Premature ovarian failure
3,4% Attempting conception 15
Failures 3
Conceving patients 12
Adjuvant chemotherpy 7
Conceptions 16
Normal pregnancy 10
Miscarriages 4
Terminations 2
Conceiving patients 12
Stage IA 7
Stage IC 3
Stage IIIC 2
Dysgerminoma 8
Teratoma immature 2
Endodermal Sinus 1
Mixed 1
2 patients with XY gonadal disgenesis delivered healty infants, with donor oocyte IVF
Miscarriage Rate= 25%
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%
RISK FACTORS FOR RECURRENCEFACTOR N. RECURRENCE RATE P (χ-square)
Primary Surgery in MITO center
Primary Surgery elsewhere
81
42
11,1%
30,9%0.006
Age < 45 years
Age>45 years
10
113
50%
15%0.027
Peritoneal Washing positive
Peritoneal Washing: negative
15
65
33,3%
10,8%0.006
Dysgerminoma
Non-dysgerminoma
49
74
10,2%
23%0.07
Stage I
Stage II-III-IV
87
36
13,8%
27,7%0.06
Conservative Surgery
Radical Surgery
92
31
17,4%
19,3%NS
OUTCOME
5 YEARS OVERALL SURVIVAL= 88,8%
MEDIAN FOLLOW UP TIME= 61 MONTHS
PROGNOSTIC FACTORS
FACTOR P value - RR
Non dysgerminoma histology 0.033 - 9,235
Elevated βHCG and αFP 0.043 - 4.05
Endodermal Sinus Tumor 0.001 - 6,31
Stage > I 0.004 - 5,576
Age >45 0.003 - 6,124
Residual disease 0.018 - 4,206
Capsular rupture 0.02 - 5,874
Tumor on serosal surface 0.015 - 4,95
Positive Peritoneal cytology 0.024 - 3,94
Cox Regression Univariate Analysis
FACTOR P value - RR
Endodermal Sinus Tumor 0.001 - 6,94
Stage > I 0.003 - 6,94
Cox Regression Multivariate Analysis
SURVIVAL ANALYSIS
Endodermal Sinus Tumor Other hystologies
Log rank p value=0.001
Endodermal Sinus versus Other hystologies
Other hystologies
Stage II-III-IV
Stage I
Log rank p value< 0.001
Stage I versus Stage II-III-IV
5y-OS Endodermal Sinus=69,6%5y-OS Other histologies= 94,2%
5y-OS stage I= 95,6%5y-OS advanced stages= 73,2%
PROGNOSTIC PREDICTORS IN RELAPSE PATIENTS
Factors P value-RR
Endodermal Sinus 8,69 - 0.004
Endodermal Sinus versus Other hystologies Debulking Surgery versus No surgery
Other hystologies
Endodermal Sinus
Debulking Surgery
No Surgery
Factors P value-RR
No debulking surgery 9,74 - 0.002
Log rank p value< 0.001Log rank p value< 0.001
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
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
• Questions ?
• Is it warrented adiuvant chemotherapy in stage I T
• How to manage “clinical stage I A “dysgerminoma?
IS ADJUVANT CHEMOTHERAPY INDI CATED IN STAGE I PURE IMMATURE OVARIAN TERATOMA? IS ADJUVANT CHEMOTHERAPY INDI CATED IN STAGE I PURE IMMATURE OVARIAN TERATOMA?
Stage I Immature teratoma: 28 patients
Grade 1: 9 patients
Grade 2:12 patients
Grade 3: 7 patients
IA: 8 patients
IC: 1 patients
Surgery in 9 patients
No Relapse
IA: 5 patients
IB: 2 patients
IC:5 patients
IA: 6 patients
IC: 1 patients
Surgery in 8 patients
Surgery+ PEB in 4 patients
3 Relapse: IC
Surgery in 2 patients
Surgery+ PEB in 5 patients
3 Relapse: IA
Surgery in 3 :Mature teratoma
Surgeryin 1:
Mature teratoma
Surgery+ PEB in 2:
Immature teratoma
STAGE IA DYSGERMINOMA
Median Age (range) 22,5 (11-59)
Fertility Sparing Radical Surgery
65,4%34,6%
Surgical Staging
•Complete
•Lymph node dissection
• Peritoneal biopsies and/or omentectomy
• Peritoneal washing
19,2%
38,5%
46,2%
65,4%
Adjuvant Chemotherapy 27%
N =26 patients
STAGE IA DYSGERMINOMA
Surgical
treatmentSite of Relapse
Relapse
treatmentOutcome
TAH+BSO Pelvic Surgery+PEB NED
USO+
Washing
Abdomino-pelvic,
lymph-nodal PEB NED
USO+
peritoneal
biopsies
Abdomino-pelvic,
lymp-nodal,
controlateral ovarySurgery+PVB NED
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
Grazie a tutte le persone che in questi anni hanno lavorato con meUn 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 OttolinaUn saluto al Professor Ferrari e un augurio di buon lavoro al Prof Candiani