Laparoscopia & carcinosi ovarica. Anna Fagotti Gynecologic Oncology

Transcription

1 Laparoscopia & carcinosi ovarica Anna Fagotti Gynecologic Oncology

2 Genital tumor (ovary, endometrium, Cervix) Breast cancer Neuroendocrine tumors CANCER LPS Peritoneal tumors (primary peritoneal, mesothelioma, Desmoplatic small round cell tumor Psammocarcinoma ) Gastrointestinal tumor (stomach, bowel, pancreas hepathobiliary) Leiomyomatosis peritonealis disseminata

3 Peritoneal carcinomatosis is no longer an absolute sentence of death Outcomes of patients with peritoneal carcinomatosis still depend largely on the origin and histology of the tumor Modern multimodality approaches to treatment includng systemic chemotherapy, cytoreductive surgery and intraperitoneal chemotherapy have significantly improved outcomes for selected patients with peritoneal carcinomatosis Novel approaches to treating peritoneal carcinomatosis are the subject of a number of active clinical trials A multidisciplinary team approach including early palliative care is essential to the comprehensive management of peritoneal carcinomatosis

4 Rationale for S-LPS in carcinomatosis S-LPS allows a simple access for histological diagnosis and molecular characterization. Ip diffusion of disease can be easily assessed by LPS. A variable percentage of patients still undergo explorative laparotomy to assess chances of optimal cytoreduction. The surgeon may be more confident with a direct visualization of the cancer spread. Pts undergoing S-LPS can start CHT immediately. LPS could reduce some laparotomy-related complications (incisional hernia).

5 Role of laparoscopy in the natural history of AOC S-LPS TIME Primary surgery IDS II look Secondary cytoreduction Palliation

6 I Am J Obstet Gynecol, 2010

7 Titolo della Presentazione mag. 17 7

8 Petrillo et al, 2015

9 Futile LPT if RT > 1 cm or any RT > 0 after PDS

10 Site All 54 (%) Small bowel carcinomatosis 36 (66.6) Stomach/duodenum/pancreas 6 (11.1) Liver (ilum/intrahepatic) 6 (11.1) Supra diaphragmatic/truncus celiacus 6 (11.1) Heitz et al, Gynecol Oncol 141, , 2016 Petrillo et al, Gynecol Oncol 139,5-9, 2015

11 Predictor* ECOG- PS 2 > 2 Ascites ( 500 ml) Yes No CA U/mL > 1000 U/mL Tumor Load Low PIV < 4 Intermediate 4-6 High > 8 Regression coefficient β Odds Ratio (β) p value Shrunk coefficient β Shrunk Odds Ratio (β) Risk score

12 Rate of major post-operative complications based on an integrated clinico - LPS risk score. 13

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14 II Predictive Index parameter Spec NPV PPV Acc. Point value Omental cake Diaphragmatic carcinosis Peritoneal carcinosis Mesenteric retraction Bowel infiltration Stomach infiltration Liver metastases

15 98 AOC pts submitted to NACT A RECIST CRITERIA RECIST CRITERIA B 68 responses C+P 30 NC+P 68 responses C+P 30 NC+P LAPAROTOMY II-line CT LAPAROSCOPY 55 optimal RT 13 not debulked 61 to LPT 55 optimal RT 7 only LPS 6 not debulked 7 to LPT 7 optimal RT 23 only LPS

16 III Criteria for Complete SCS Complete resection at first surgery Good ECOG-performance status Absence of ascites ECOG performance status and number of disease sites at recurrence, and length of the disease-free interval were all significantly (p < 0.05) associated with PFS and OS at the multivariate analysis.

17 2008 FDG-PET can evaluate distant sites of disease and retroperitoneum LPS can assess the IP diffusion of the disease Procedure NPV Spec. PPV Sens. Accuracy FDG-PET/CT + S-LPS AGO-DESKTOP score

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19 Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) as an alternative to liquid solution in PC Homogenous repartition of the drug within a closer space (larger distribution of vital staining and deeper penetration into the peritoneum in animal models and humans). Artificial pressure gradient to counterbalance tumoral interstitial fluid pressure. Tempfer & Reymond, Gyn Onc, 2014

20 PIPAC: up-date on literature N. Of Publications Years

21 PARROT (NCT ): PIPAC Applied to platinum- Resistance Recurrence of Ovarian Tumor Eligibility Platinum-resistant recurrent epithelial ovarian cancer Primary end-point To evaluate the clinical benefit rate (CBR) of PIPAC Study Design Multicentric, open label, non-randomized, single-arm, repeated single dose study to explore the efficacy, safety, and pharmakokinetics of cisplatin and doxorubicin when given as a PIPAC to resistant AEOC Trial Group: 50 patients Investigational product, dosage, and mode of administration Cisplatin 7.5 mg/m2 in 150 ml NaCl 0,9% q6 weeks, applied intraperitoneally as pressurized aerosol (PIPAC) followed by doxorubicin at a dose of 1.5 mg/m2 body surface in a 50 ml NaCl 0.9% solution will be applied via a nebulizer immediately

22 PTS 1 DIAGN WHY NOT PRESSURIZED INTRAPERITONEAL AEROSOL CHEMOTHERAPY (PIPAC)? Prev CT regimen ECOG UCSC INITIAL EXPERIENCE PIV before PIPAC N PIPAC IP response Tumor ascites control # CDDC-TAX SD Yes 75 days # CDDC-TAX n.a. n.a. 62 days # CDDC-TAX 1 12 Not feasible OS n.a. n.a. 25 days # CDDC-TAX n.a. n.a. 64 days # CDDC-TAX- BEVA # CDDC-TAX- BEVA PR Yes On-going n.a. n.a. On-going

23 Preliminary anatomo-pathological analysis PRE-PIPAC POST PIPAC b a b Sclerosis of peritoneal nodules (a) Acute and chronic inflammation (b) Regressive tumor changes and necrosis (c)

24 PIPAC the next evolution PIPAC as neoadiuvant treatment Analysis of molecular expression after PIPAC PIPAC administered simultaneosly with chemotherapy

25 S-LPS TIME Primary Surgery IDS II look Secondary cytoreduction Palliation

26 Master Internazionale Biennale di II Livello Gynecologic Oncology D irettore del M aster Giovanni Scambia, M D Direttore Scientifico Anna Fagotti, M D / roma.unicatt.it/ offerta-formativa-master-universitari