2238 - A Prospective Pilot Trial of Multimodality Local Therapy Incorporating Histotripsy for Metastatic Pancreatic Ductal Adenocarcinoma

Purpose/Objective(s):

Metastatic pancreatic ductal adenocarcinoma (PDAC) is traditionally managed with systemic therapy alone; however, emerging data suggest that a biologically selected subset of patients with limited metastatic burden and favorable response to chemotherapy may benefit from local consolidation strategies. Retrospective series and early prospective experiences in oligometastatic PDAC have demonstrated improved local control and prolonged survival in carefully selected patients treated with multimodality approaches incorporating radiation therapy and surgical resection. Histotripsy is a non-thermal, focused ultrasound–based tissue ablation modality that induces mechanical tumor disruption without thermal injury. Early clinical studies in hepatic malignancies have demonstrated technical feasibility and acceptable safety profiles. Integration of histotripsy with established local therapies, including stereotactic body radiation therapy (SBRT) and radioembolization, may provide a strategy for comprehensive treatment of metastatic sites while preserving hepatic parenchyma. ctDNA dynamics represent a potential biomarker for treatment response and minimal residual disease in PDAC. This prospective pilot trial is designed to evaluate an integrated multidisciplinary treatment paradigm incorporating histotripsy within a multimodality local therapy framework for selected patients with metastatic PDAC.

Materials/Methods:

This is a prospective, non-randomized, pilot clinical trial enrolling patients with histologically confirmed metastatic PDAC and Eastern Cooperative Oncology Group performance status 0–1. Two predefined, non-comparative cohorts are included: (1) resectable or borderline resectable primary PDAC with liver-only metastases, and (2) resectable or borderline resectable primary PDAC with treatable multi-site metastatic disease. All patients receive induction systemic chemotherapy followed by radiographic restaging. Patients with stable or responding disease proceed to liver-directed therapy incorporating histotripsy. Additional local therapies, including SBRT and/or radioembolization, are permitted as needed to treat all known metastatic sites. Selected patients may undergo surgical resection of the primary tumor followed by adjuvant therapy per institutional standards. The primary endpoint is progression-free survival, defined as time from initiation of systemic therapy to radiographic progression or death. Secondary endpoints include treatment-related adverse events (graded by CTCAE), feasibility of multimodality sequencing, local control of treated lesions, and longitudinal ctDNA dynamics assessed at predefined treatment milestones. Statistical analyses are planned using descriptive and time-to-event methods appropriate for pilot evaluation. Enrollment is ongoing. No efficacy or safety analyses have been performed.

ClinicalTrials.gov Identifier: NCT06486454

Results: N/A

Conclusion: N/A