PSM
CME
Richard A. Erali, MD MPH
General Surgery Resident
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States
Disclosure(s): No financial relationships to disclose
Richard A. Erali, MD MPH
General Surgery Resident
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States
Disclosure(s): No financial relationships to disclose
Steven D. Forsythe, MSc
Graduate Student
Wake Forest School of Medicine
winston Salem, North Carolina, United States
Disclosure information not submitted.
Daniel Gironda, MS
Graduate Research Student
Wake Forest University, United States
Disclosure information not submitted.
Nadeem Wajih, PhD
Research Assistant
Wake Forest University, United States
Disclosure information not submitted.
Chris W. Mangieri, MD
Chief of Surgical Oncology
Tripler Army Medical Center, United States
Disclosure information not submitted.
Perry Shen, MD
Professor
Atrium Health Wake Forest Baptist, United States
Disclosure information not submitted.
Edward A. Levine, MD
Chief, Surgical Oncology
Wake Forest University
Winston-Salem, North Carolina, United States
Disclosure information not submitted.
Shay Soker, PhD
Professor
Wake Forest University, United States
Disclosure information not submitted.
Konstantinos I. Votanopoulos, MD, PhD
Professor Surgical Oncology; Director, Wake Forest Organoid Research Center (WFORCE)
Wake Forest University
Winston-Salem, North Carolina, United States
Disclosure information not submitted.
Repeat cytoreductive surgery (CRS) with HIPEC offers survival advantage in select patients with peritoneal surface disease. Patient-derived tumor organoids (PTOs) established after the 1st CRS/HIPEC may generate additional selection parameters for patients who are candidates for repeat cytoreduction. Herein, we explore PTO drug efficacy in patients who have undergone repeat CRS/HIPEC.
Methods:
After IRB approval, tumor samples were obtained from patients with appendiceal cancer undergoing CRS/HIPEC at our institution. PTOs were biofabricated utilizing unsorted tumor cells resuspended in a collagen-based hydrogel and underwent HIPEC treatment with mitomycin C (MMC) and oxaliplatin and endpoint analysis with ATP viability. Significant PTO responses demonstrated < 50% post-treatment viability and were significantly different than untreated controls (p < 0.05).
Results:
From June 2019 through June 2022, 74 specimens were collected from 51 patients who underwent CRS/HIPEC for low grade appendiceal (35/68, 51.5%) and high grade appendiceal (16/68, 23.5%) cancer. 7 patients (13.7%) underwent repeat CRS/HIPEC. Successful PTO studies were conducted in 67/74 specimens (90.5%). MMC demonstrated improved cytotoxicity in repeat HIPEC PTOs compared to oxaliplatin (32.5% vs. 46.2%). When oxaliplatin was utilized as the perfusate during the first CRS/HIPEC, only 2/8 (25%) PTOs fabricated from repeat CRS/HIPECs of the same patient displayed significant treatment efficacy to MMC (n=1, 17% viability) and oxaliplatin (n=1, 25.6%) with an average viability of 45.9%. When MMC was utilized as the first HIPEC, 9/10 (90%) PTOs fabricated from repeat CRS/HIPEC demonstrated significant treatment responses to both MMC (n=5, avg viability 26.8%) and oxaliplatin (n=4, avg viability 41.4%), with an average viability of 34.1%. Further, repeat PTOs fabricated from patients who received MMC during their first HIPEC demonstrated improved cytotoxicity to both oxaliplatin (38.8% vs. 61.0%) and MMC (25.2% vs. 47.2%) compared to those receiving oxaliplatin.
Conclusions:
Tumor organoids represent a unique platform to study drug sensitivity in CRS/HIPEC patients. PTO studies performed from specimens HIPEC patients may help improve selection of perfusates utilized in subsequent cytoreduction surgeries.