Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for pancreatic cancer peritoneal metastases: A retrospective multicentric study from the ISSPP PIPAC Database

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive malignancies, and peritoneal metastases (PM) represent the second most common site of dissemination, carrying a particularly poor prognosis. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an emerging locoregional approach for intraperitoneal drug delivery. However, its role in PDAC-related PM remains poorly defined. METHODS: This retrospective, multicentric study based on the ISSPP registry included patients with PM from PDAC treated with PIPAC from the International Society for the Study of Pleura and Peritoneum (ISSPP) registry. Outcome measures were safety, reason for stopping PIPAC, overall survival (OS), treatment response and prognostic factors for suvival at the time of the first PIPAC. RESULTS: One hundred fifty six patients were treated with 350 PIPAC procedures in 6 centers. Three or more PIPAC were completed in 55 (35.2%) patients. No major surgical complications (Clavien-Dindo ≥3) occurred; grade 3-4 adverse events (CTCAE v5.0) were recorded in 10 of 350 procedures (2.9%), and 30-day mortality was 3.8% per patient (6/156), in all cases due to disease progression. The main reason for discontinuation were disease progression and poor general conditions in 77 (49.35%) and 10 (6.41%) patients respectively. Median OS was 19 months from diagnosis and 9 months from PIPAC1. Survival analysis from PM diagnosis based on intraperitoneal drug choice showed a median OS of 15 months in patients with cisplatin and doxorubicin and 23 months with nab-paclitaxel (p = 0.027). Multivariable ananlysis showed that an higher Peritoneal Cancer Index (PCI) at PIPAC1 (p = 0.008) was associated with worse survival, whereas the use of intraperitoneal nabpaclitaxel (p = 0.004). After a 120 days landmark analysis accounting for immortal-time bias, completion of ≥3 PIPAC procedures remained independently associated with survival (adjusted p = 0.005) CONCLUSION: PIPAC appears to be a safe treatment option for patients with PM from PDAC, with a low rate of major complications, however its feasibility is limited, as only about one third completed ≥3 procedures. In this multicentric cohort a hypothesis generating survival signal and histological response were observed, particularly with nab-paclitaxel-based regimens. Prospective studies are needed to validate PIPAC for palliative treatment of PM of pancreatic origin.