加压腹腔内气溶胶化疗（PIPAC）用于胰腺导管腺癌仅腹膜转移的患者

Background : Patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) and peritoneal metastasis are currently treated with standard systemic therapy. However, peritoneal-only metastasis represents a “regional” subtype of stage IV PDAC, and in select patients there may be an opportunity for a more aggressive locoregional approach. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) delivers low-dose intraperitoneal chemotherapy with enhanced pharmacokinetics, achieving high local tissue penetration while minimizing systemic toxicity, and uses aerosolization to promote homogeneous distribution throughout the peritoneal cavity. This trial will evaluate the feasibility, safety, and preliminary therapeutic activity of PIPAC in patients with PDAC and peritoneal-only metastasis. Methods: This is a prospective, single-center, non-randomized phase I trial evaluating the safety and tolerability of PIPAC with nab-paclitaxel administered in conjunction with standard-of-care systemic therapy (NCT07253662). Up to 10 patients with histologically confirmed PDAC and peritoneal-only metastases will be enrolled. Eligible patients are ≥18 years old, have ECOG performance status of 0-2, and are candidates for diagnostic laparoscopy. Key exclusion criteria include patients with bowel obstruction, life expectancy <4 months, >5 L abdominal ascites, or immunocompromised status; prior systemic chemotherapy is permitted. Patients will undergo up to 3 separate PIPAC treatments at 6-week intervals. Each procedure includes diagnostic laparoscopy to assess metastasis and obtain tissue biopsies for pathologic assessment and research correlatives, followed by PIPAC administration of nab-paclitaxel (112.5mg/m 2 ) for 30 minutes.The primary objective is safety, including dose limiting toxicities, and tolerability of treatment in conjunction with standard-of-care systemic therapy. Secondary objectives include preliminary efficacy (disease control rate, peritoneal regression grading score, peritoneal carcinomatosis index, biochemical tumor response), treatment compliance (rate of completion of three treatments, delay or dose reduction of systemic therapy), and additional safety outcomes (adverse events, post-operative surgical complications, hospital readmissions, extended length of stay). Exploratory objectives include genomic and transcriptomic characterization of PDAC peritoneal metastasis with single cell RNA-sequencing to evaluate drivers that may lead to increased risk of peritoneal metastasis. In vitro tumor model chemotherapy response will be assessed in parallel and compared with patients via patient derived organoid cultures. Finally, circulating tumor DNA will be collected longitudinally to evaluate its utility as a biomarker of treatment response during standard-of-care systemic therapy with PIPAC. This trial opened for enrollment in December 2025, and as of January 2026, two patients have been enrolled.