Intracystic injection of large surface area microparticle paclitaxel for chemoablation of intraductal papillary mucinous neoplasms: Insights from an expanded access protocol

Somashekar G Krishna; Devarshi R Ardeshna; Zarine K Shah; Phil A Hart; Stacey Culp; Dan Jones; Wei Chen; Georgios I Papachristou; Samuel Han; Peter J Lee; Hamza Shah; Timothy M Pawlik; Mary Dillhoff; Andrei Manilchuk; Jordan M Cloyd J; Aslam Ejaz; Megan Fry; Anne M Noonan

doi:10.1016/j.pan.2023.12.014

Intracystic injection of large surface area microparticle paclitaxel for chemoablation of intraductal papillary mucinous neoplasms: Insights from an expanded access protocol

Pancreatology. 2024 Mar;24(2):289-297. doi: 10.1016/j.pan.2023.12.014. Epub 2024 Jan 11.

Authors

Somashekar G Krishna¹, Devarshi R Ardeshna², Zarine K Shah³, Phil A Hart², Stacey Culp⁴, Dan Jones⁵, Wei Chen⁶, Georgios I Papachristou², Samuel Han², Peter J Lee², Hamza Shah², Timothy M Pawlik⁷, Mary Dillhoff⁷, Andrei Manilchuk⁷, Jordan M Cloyd J⁷, Aslam Ejaz⁷, Megan Fry², Anne M Noonan⁸

Affiliations

¹ Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA. Electronic address: Somashekar.krishna@osumc.edu.
² Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
³ Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
⁴ Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH, 43210, USA.
⁵ James Molecular Laboratory, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA; Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
⁶ Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
⁷ Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
⁸ Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.

PMID: 38238194
DOI: 10.1016/j.pan.2023.12.014

Abstract

Aims: A novel large surface area microparticle paclitaxel (LSAM-PTX) has unique properties of long retention in cystic spaces while maintaining high drug concentration. We prospectively evaluated the safety and response of EUS-guided fine needle injection (EUS-FNI) of LSAM-PTX to chemoablate branch duct (BD)-IPMNs.

Methods: Subjects diagnosed with BD-IPMNs exhibiting at least one worrisome criteria and considered non-surgical were enrolled in a multicenter clinical trial (NCT03188991) and subsequently included in an Expanded Access Protocol (EAP) where they received EUS-FNI of LSAM-PTX (15 mg/mL).

Results: Six BD-IPMNs measuring (mean ± SD) 3.18 ± 0.76 cm in diameter among 5 subjects (mean age: 66 years) were treated by EUS-FNI of LSAM-PTX. A mean of 4 doses of LSAM-PTX (mean dose/cyst: 73 ± 31 mg) were administered, and subjects were followed for up to 32 months. The mean volume reduction/cyst ranged from 42 to 89% (9.58 ± 5.1 ml to 2.2 ± 1.1 ml (p = 0.016)). The mean surface area reduction ranged from 31 to 83% (21.9 ± 8.7 cm² to 5.7 ± 2.5 cm² (p = 0.009)). Higher dosing-frequency of EUS-FNI of LSAM-PTX significantly correlated with a reduction in cyst volume (R² = 0.87, p = 0.03) and surface area (R² = 0.83, p = 0.04). Comparing pre- and post-ablation samples, molecular analysis of the cyst fluid revealed a loss of IPMN-associated mutations in 5 cases (83.3%), while reemergence was observed in 1 case and persistence in 1 case. Intracystic changes (fibrosis/calcification) were observed in 83.3% (n = 5). One subject developed mild acute pancreatitis (1 of 22 EUS-FNIs of LSAM-PTX).

Conclusion: In this EAP, EUS-FNI of LSAM-PTX into BD-IPMNs was safe and resulted in volume and surface area reduction, morphological changes, and loss of pathogenic mutations.

Keywords: EUS; EUS-guided chemoablation; IPMN; Pancreatic cancer; Pancreatic cyst.

MeSH terms

Acute Disease
Aged
Carcinoma, Pancreatic Ductal* / pathology
Cysts*
Humans
Multicenter Studies as Topic
Neoplasms, Cystic, Mucinous, and Serous*
Pancreatic Neoplasms* / pathology
Pancreatitis*
Retrospective Studies