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Carcinoma endometriale:Carcinoma endometriale:
la la terapia adiuvanteterapia adiuvante
Quale e QuandoQuale e Quando
Carcinoma endometriale:Carcinoma endometriale:
la la terapia adiuvanteterapia adiuvante
Quale e QuandoQuale e Quando
Vincenzo Scotto di PalumboVincenzo Scotto di Palumbo
Ospedale Santo Spirito in SassiaOspedale Santo Spirito in Sassia
RomaRoma
La stadiazione FIGO 1988La stadiazione FIGO 1988
Grading e sopravvivenzaGrading e sopravvivenza
Invasione miometriale e sopravvivenzaInvasione miometriale e sopravvivenza
Il problema linfonodaleIl problema linfonodale
Fattori di prognosi e sopravvivenzaFattori di prognosi e sopravvivenza
Terapia adiuvanteTerapia adiuvante
ormonoterapia
radioterapia
chemioterapia
combinazioni
OrmonoterapiaOrmonoterapia
Martin-Hirsch P L, Jarvis G, Kitchener H, Lilford R. Progestagens for endometrial cancer (Cochrane Review). The Cochrane Library, Issue 1, 2008
•Cochrane Gynecological Cancer Group:
“Progestagens for endometrial cancer”
•Metanalysis of 6 clinical trials (4351 patients)–Only 3 trials with Stage I patients –In 3 trials also patients with advanced disease
Cochrane review: adjuvant progestagens
Cochrane review: adjuvant progestagens
Radioterapia adjuvanteRadioterapia adjuvante
Fasci esterni
Brachiterapia
Combinazione delle due modalità
Locoregional recurrenceLocoregional recurrenceAll stage I patients: External beam radiotherapy vs No external beam radiotherapy
Distant recurrenceDistant recurrenceAll stage I patients: External beam radiotherapy vs No external beam radiotherapy
Adjuvant radiotherapy for stage I endometrial cancer; systematic review and meta-analysis (Cochrane Review). In: Annals of Oncology 22, 1596-1604, 2007
Endometrial cancer related deathsEndometrial cancer related deathsSubgroup analysis of patients at least Subgroup analysis of patients at least 1 high risk factor1 high risk factor, Ic or grade 3, Ic or grade 3
Endometrial cancer related deathsEndometrial cancer related deathsSubgroup analysis of patients at least Subgroup analysis of patients at least 2 high risk factor2 high risk factor, Ic or grade 3, Ic or grade 3
Adjuvant radiotherapy for stage I endometrial cancer; systematic review and meta-analysis (Cochrane Review). In: Annals of Oncology 22, 1596-1604, 2007
Inclusion criteria
• Stage 1A grade 3• Stage 1B grade 3• Stage 1C grade 1-3• Serous or clear-cell cancers
Adjuvant external beam radiotherapy (EBRT) in the treatment of endometrial cancer: results of the randomized MRC ASTEC and NCIC CTC EN.5 trials
EN.5 started July 1996; ASTEC July 1998905 patients randomizedJ Orton. ASCO 2007
Overall Survival Recurrence-free Survival
Isolated Vaginal or Pelvic Initial Recurrence
J Orton. ASCO 2007
ResultsResults
Metanalisi su overall survivalMetanalisi su overall survival
0.2 % difference in 5-year OS (87.8% in EBRT and 88% in no EBRT)95% CI of difference = -2.0% to 3.0%
J Orton. ASCO 2007
Maggi R, BJC 95: 266-271, 2006Maggi R, BJC 95: 266-271, 2006
Inclusions criteria
• Stage IC grade 3 • Stage IIA-IIB grade 3 with myometrial invasion > 50%• Stage III
Caratteristiche dello studioCaratteristiche dello studio
Maggi R, BJC 95: 266-271, 2006Maggi R, BJC 95: 266-271, 2006
Sopravvivenza libera da malattiaSopravvivenza libera da malattia
Maggi R, BJC 95: 266-271, 2006Maggi R, BJC 95: 266-271, 2006
Sopravvivenza totaleSopravvivenza totale
Maggi R, BJC 95: 266-271, 2006Maggi R, BJC 95: 266-271, 2006
Stage III or IV “low volume” - Any histologyResidual tumour less than 2 cm after
surgery424 pts
Stage III or IV “low volume” - Any histologyResidual tumour less than 2 cm after
surgery424 pts
Whole abdominal radiotherapy (WAI) 30 Gy in 20 daily fractions Boost to the pelvis or to an extended field
encompassing pelvic and para-aortic lymph nodes
Chemotherapy Doxorubicin 60 mg/m2
Cisplatin 50 mg/m2
Every 3 weeks, for 8 cycles (only Cisplatin was to be infused during the 8°cycle)
Randall ME, J Clin Oncol 24: 36-44, 2006
Sopravvivenza libera da malattiaSopravvivenza libera da malattia
Randall ME, J Clin Oncol 24: 36-44, 2006
HR 0.71 (95%CI 0.55-0.91, p<0.01)
Sopravvivenza totaleSopravvivenza totale
Randall ME, J Clin Oncol 24: 36-44, 2006
HR 0.68 (95%0.52-0.89, p<0.01)
55%
42%
ConclusionsConclusions
Randall ME, J Clin Oncol 24: 36-44, 2006
A randomized phase III study on adjuvant treatment A randomized phase III study on adjuvant treatment with radiation (RT) +/- chemotherapy (CT)with radiation (RT) +/- chemotherapy (CT)in early stage high-risk endometrial cancer in early stage high-risk endometrial cancer
(NSGO-EC-9501/EORTC 55991)(NSGO-EC-9501/EORTC 55991)
NSGO EORTC
Thomas Hogberg, ASCO. 2007
Inclusion criteria
• Stage IC, II or III cancer plus grade 3 histology• Serous or clear-cell cancers• Aneuploid tumors plus grade 3 histology• Aneuploid tumors plus stage IC, II or III cancer
A randomized phase III study on adjuvant treatment A randomized phase III study on adjuvant treatment with radiation (RT) +/- chemotherapy (CT)with radiation (RT) +/- chemotherapy (CT)in early stage high-risk endometrial cancer in early stage high-risk endometrial cancer
(NSGO-EC-9501/EORTC 55991)(NSGO-EC-9501/EORTC 55991)
NSGO EORTC
RANDOMIZATION
Thomas Hogberg, ASCO. 2007
HR 0.62 (CI 0.40-0.97) p=0.03; estimated difference in 5-yr PFS 7% from 72% to 79%
Sopravivenza libera da malattiaSopravivenza libera da malattia
Sopravivenza totaleSopravivenza totale
HR 0.65 (CI 0.40-1.06) p=0.08; estimated difference in 5-yr OS 8% from 74% to 82%
Considerazioni degli autoriConsiderazioni degli autori
HR 0.35 (CI 0.16-0.77) p=0.009; estimated difference in 5-yr PFS 14% from 73% to 87%
ConclusionsConclusions
Despite that 27% of patients randomized to CT+RT received no, or only party of the
prescribed CT, CT+RT was better than RT alone as adjuvant therapy for patients with early
endometrial cancer at high risk for micrometastases
GOG 184GOG 184
Endometrial carcinoma
• Surgical stage III
• Hysterectomy and BSO
• <2 cm Residual disease
• Optimal Lymph Node Sampling
Endometrial carcinoma
• Surgical stage III
• Hysterectomy and BSO
• <2 cm Residual disease
• Optimal Lymph Node Sampling
Pelvic+/-
Para-AorticIrradiation
+/-Intravaginal
Brachytherapy
Pelvic+/-
Para-AorticIrradiation
+/-Intravaginal
Brachytherapy
RANDOMIZED
RANDOMIZED
Regimen I*
Doxorubicin**45mg/mqCisplatin50mg/mqG-CSF***
5mcg/kg 2-11
Regimen I*
Doxorubicin**45mg/mqCisplatin50mg/mqG-CSF***
5mcg/kg 2-11
Regimen II*
Doxorubicin**45mg/mq day 1
Cisplatin50mg/mq day 1
Paclitaxel160mg/mq day 2
G-CSF***5mcg/kg 3-12
Regimen II*
Doxorubicin**45mg/mq day 1
Cisplatin50mg/mq day 1
Paclitaxel160mg/mq day 2
G-CSF***5mcg/kg 3-12
*q weeks 3 x 6 courses**Maximum total doxorubicin dose is 270 mg/mq for both regimen
Register
Laparotomia Laparoscopia
Età media 75 64
BMI medio 23.7 19.3
Stadio: Ia 6 1
Ib 7 3
Ic 7 1
IIa 1 0
IIb 2 1
IIIa 4 1
IIIc 1 1
IVb 1 0
Istotipo: Adenocarcinomi 29 7
Sieropapilliferi 1 1
Adenosquamosi 1 0
N. medio di linfonodi 20.1 13.4
Tempo operatorio medio (min) 102 205
Perdita ematica media (cc) 105 82
Serie OSS 2005 - 2007
OSS policy st I OSS policy st I
• Ia G1, G2 osservazione• Ia G3RT pelvica se presenti RF• Ib G1, G2 osservazione• Ib G3 RT pelvica se presenti RF• Ic G1 osservazione• Ic G2, G3 RT pelvica + CT istotipi
speciali• RF età>60a, LVI, dimensioni del T, coinvolgimento
della parte bassa del corpo
OSS policy st II, IIIOSS policy st II, III
• IIa G1 osservazione
• IIb G2, G3 RT pelvica
• IIIa G1, G2 osservazione se solo cit +
• IIIa G3 RT pelvica + CT
• IIIb CT + RT
• IIIc CT + RT pelvi ev LA