Local biliary injection of cisplatin for chemotherapy delivery in patients with cholangiocarcinoma

Sunday, March 5, 2023

3:27 PM – 3:36 PM

Location: Phoenix Convention Center, 225AB

Presenting Author(s)

Avik Som, MD, PhD

Integrated IR/DR Radiology Resident
MGH

Disclosure(s): Boston Scientific: Consultant (); CareSignal Health: Ownership Interest ()

Author/Co-author(s)

JR

Jan-Georg Rosenboom, PhD

Post-doctoral Scientist
MIT
EC

Eric Chen, n/a

Undergraduate Engineer
MIT
TM

Ted Michelakos, MD

Resident Physician
MGH
CF

Cristina Ferrone, MD

Professor
MGH
Sanjeeva Kalva, MD, FSIR, FCIRSE, FACR (he/him/his)

Professor
Massachusetts General Hospital
GT

Giovanni Traverso, MD, PhD

Faculty
BWH

Disclosure(s):

Avik Som, MD, PhD: Boston Scientific: Consultant (); CareSignal Health: Ownership Interest ()

Sanjeeva Kalva, MD, FSIR, FCIRSE, FACR: BD Bard: Consultant (Ongoing); Biogen Inc, Clover Health Investments Corp, Inovio Pharmaceuticals, Moderna Inc, Pfizer Inc, Novavax Inc, Orphazyme, Cassava Sciences Inc, Vivos Therapeutics Inc, Ardelyx Inc, Althea Health, Sarepta Therapeutics, Clover Health Investments Corp, CureV: Ownership Interest (Ongoing), Stocks (Ongoing); Boston Scientific Corp: Consultant (Ongoing); Canon Medical: Consultant (Ongoing), Speaking and Teaching (Ongoing); Covidien/Medtronic: Consultant (Ongoing); Instylla, Inc.: Consultant (Ongoing); Okami Medical: Consultant (Ongoing); Penumbra Inc.: Consultant (Terminated), Speaking and Teaching (Terminated); Sirtex Medical: Consultant (Ongoing); Varian: Consultant (Ongoing)

Purpose:

Extrahepatic cholangiocarcinoma is an aggressive cancer whose incidence is rising worldwide. Mortality for patients with this aggressive disease is from locoregional obstruction of the biliary tree, leading to obstructive jaundice, and preventing patients from tolerating systemic chemotherapy, radiation therapy, or anesthesia’s post-surgical recovery. Percutaneously placed or endoscopically placed biliary stents open the area for biliary drainage, but currently deliver no therapeutic treatments. In this study, we explore the delivery of intrabiliary cisplatin delivery and development of a bidirectional drainage and chemotherapy infusion system.

Materials and Methods:

A bidirectional dual catheter infusion and drainage system was designed and built utilizing 3D print silicone molding and modification of existing catheters. Cisplatin dosing was calibrated on HuCCT1 cholangiocarcinoma cell lines. Distribution of drug dosing was done ex vivo on porcine gallbladder and common bile duct, and in a live Yorkshire pig model via injection into the biliary tree with biodistribution measured at 1 hour. Concentration of cisplatin delivery to tissues was quantified using ICP-MS/absorbance and HPLC absorbance. All animal studies were done using IACUC approved protocols.

Results: In vitro HuCCT1 cholangiocarcinoma lines showed cytotoxicity with at least 12 hours of incubation at 250 uM concentrations. Ex vivo, cisplatin with gluconic acid as an excipient was found to have the highest absorbance into biliary tissues. The bidirectional dual catheter system was able to infuse cisplatin and drain bile ex vivo. In vivo, 40 mL of 1.5 mg/mL (1.5 mg/Kg dosing) cisplatin dose within the bile ducts for one hour delivered 3x the dose to the liver and bile ducts compared to blood concentrations.

Conclusion:

Extrahepatic cholangiocarcinoma remains a lethal disease based on locoregional obstruction. The delivery of local cisplatin into the CBD can be potentially applied to deliver chemotherapy to the biliary tract at therapeutic levels, using dosing significantly below current IV dosing. Future chronic studies will be used to evaluate the safety for intrabiliary chemotherapy.