Steven D. Forsythe, PhD
Assistant Professor
Wake Forest School of Medicine
Birmingham, Alabama, United States
Jennifer A. Wylie, MD (she/her/hers)
General Surgery Resident
Atrium Health Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, United States
Cecilia Schaaf, DVM PhD
Assistant Professor
Wake Forest School of Medicine
Winston-Salem, North Carolina, United States
Daniel Gironda, BA
PhD Candidate
Wake Forest School of Medicine
Winston-Salem, North Carolina, United States
Nicholas Edenhoffer, MS
PhD Candidate
Wake Forest Organoid Research Center
Winston-Salem, North Carolina, United States
Eleftherios A. Makris, MD, PhD
Assistant Professor
Wake Forest School of Medicine
Winston Salem, North Carolina, United States
Perry Shen, MD (he/him/his)
Professor
Department of Surgery, Wake Forest University School of Medicine
Winston Salem, North Carolina, United States
Edward Levine, MD (he/him/his)
Chief, Surgical Oncology
Wake Forest School of Medicine
Winston Salem, North Carolina, United States
Shay Soker, PhD
Professor
Wake Forest School of Medicine
Winston-Salem, North Carolina, United States
Konstantinos I. Votanopoulos, MD, PhD
Professor
Department of Surgery, Wake Forest Organoid Research Center, Wake Forest University School of Medicine
Winston-Salem, North Carolina, United States
Richard A. Erali, MD MPH
Complex General Surgical Oncology Fellow
Roswell Park Cancer Institute
Buffalo, New York, United States
Patient-derived tumor organoids (PTOs) have been utilized to study the effects of HIPEC in patients with peritoneal surface malignancies (PSM). Here we evaluate the long-term clinical correlation of PTO drug screen data in PSM.
Methods:
After IRB approval, tumor samples were obtained from patients with appendiceal, colon (CRC), and peritoneal mesothelioma (PM) cancers with peritoneal dissemination undergoing CRS/HIPEC. PTOs were biofabricated with a collagen-based hydrogel, then treated in an in-vitro HIPEC system with mitomycin C (MMC), oxaliplatin (Ox), and/or cisplatin. Post-treatment viability determined through ATP analysis. Matched PTO responses are defined as instances when the clinically utilized HIPEC drug demonstrated a significant treatment response in the matched PTO.
Results:
From June 2019 - June 2022, 108 tumor specimens were collected from 76 patients who underwent CRS/HIPEC for low grade appendiceal (LGA) (40/108, 37%), high grade appendiceal cancer (29/108, 26.8%), CRC (23/108, 21.3%), and PM (16/108, 14.8%). Successful PTO studies were conducted in 97/108 specimens (89.8%). Median follow-up was 34.4 months. Thirty-nine patients demonstrated matched PTO responses, while 17 demonstrated non-matched responses. Patients with matched PTO responses were observed to have longer median overall survival (OS; 48.5 months vs. 35.9 months, [HR 1.342, 95% CI 0.6721 to 2.682]). LGA matched responses had improved progression free (21.6 months vs. 12.6 months [HR 1.45, 95% CI 0.3473 to 6.049]) and OS (59.0 months vs. 44.6 months, [HR 2.0, 95% CI 0.4027 to 10.35]). The average post-treatment viability was significantly lower (more cell killing) in matched PTO responses compared to non-matched responses for appendiceal (MMC 30.5% vs. 57.9%, p< 0.001; Ox 33.6% vs. 63.1%, p< 0.0001) and CRC (MMC 23.4% vs. 64.7%, p< 0.0001; Ox 24.5% vs. 62.8%, p< 0.01) PTOs.
Conclusions:
Assessing PTO viability responses may help guide perfusion selection parameters and maximize survival benefit in PSM. Longer follow up may be needed to identify survival differences.