Phd in ADVANCED SURGICAL TECHNOLOGIES

Thesis title: Chemioterapia neoadiuvante intraperitoneale, sistemica e orale, nel recupero alla chirurgia con intenti curativi dei pazienti con carcinoma gastrico avanzato e metastasi peritoneali sincrone

Background: Outcomes of patients with peritoneal metastases from gastric cancer (GCPMs) remain dismal, with an overall survival (OS) of less than 1 year. Several approaches reported from East Asia include normothermic intra-peritoneal systemic () chemotherapy, aimed at downstaging the disease, allowing an R0 resection. This is the first Western study evaluating a bidirectional regimen in a neoadjuvant setting of GCPMs. This phase II study evaluates tolerability, efficacy and conversion surgery rate. Methods: Patients with PCI<13 without ascites or HER2 overexpression and no extraperitoneal spread were enrolled starting in January 2018. After staging laparoscopy combined with PIPAC (cisplatin+doxorubicin), NIPS began following Yonemura’s schedule: cisplatin (30mg/m2) + docetaxel (30mg/m2) intraperitoneally (day 1); capecitabine 1000 mg/m², orally (days 2-15); cisplatin (30mg/m2) + docetaxel (30mg/m2), intravenous (day 8). After 3 cycles, patients with no progressive disease and negative peritoneal cytology underwent cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Three additional NIPS cycles were reserved for patients that underwent surgery. Results: Among the 25 patients treated with a 17.3 (95%CI: 10.4;NA)month OS, no adverse events (CTCAE) ≥ G3 arose. With a 52% conversion surgery rate, 13 patients underwent CRS combined with HIPEC (cisplatin 100 mg/m2), ten with CC0 status 3 with CC 1. No operative mortality arose and major complications Clavien-Dindo IIIB occurred in 2 patients (15.4%). The median OS for patients undergoing surgery was 26 (95%CI: 23.1-NA) months, with progression-free survival of 20 (95%CI: 16.7-NA) months.