2. Academic Validation
  3. Intra- and Interpatient Drug Response Heterogeneity Exist in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Nongynecologic Cancers

Intra- and Interpatient Drug Response Heterogeneity Exist in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Nongynecologic Cancers

  • Ann Surg Oncol. 2024 Jan 4. doi: 10.1245/s10434-023-14696-6.
Shannon N Radomski 1 2,  Matthew Dunworth 2,  Junior J West 2,  Jonathan B Greer 1,  Fabian M Johnston 1 3,  Andrew J Ewald 4 5 6
Affiliations

Affiliations

  • 1 Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • 2 Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • 3 Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
  • 4 Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. [email protected].
  • 5 Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA. [email protected].
  • 6 Giovanis Institute for Translational Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. [email protected].
PMID: 38175427 DOI: 10.1245/s10434-023-14696-6
Abstract

Background: Select patients with peritoneal metastases are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). We assayed for intra- and interpatient drug response heterogeneity through testing of patient-derived tumor organoids (PDTOs).

Methods: PDTOs were generated from CRS/HIPEC patients from December 2021 to September 2022 and subjected to an in vitro HIPEC drug screen. Drug response was assessed with a cell viability assay and cleaved Caspase-3 staining.

Results: A total of 31 patients were consented for tissue collection. Viable tissue was harvested from 23, and PDTO generation was successful in 13 (56%). PDTOs were analyzed from six appendiceal, three colorectal, two small bowel, one gastric, and one adrenal tumor. Drug screen results were generated in as few as 7 days (62%), with an average time of 12 days. Most patients received mitomycin-C (MMC) intraoperatively (n = 9); however, in only three cases was this agent considered the optimal choice in vitro. Three sets of PDTOs were resistant (defined as > 50% PDTO viability) to all agents tested and two were pan-sensitive (defined as 3 or more agents with < 50% PDTO viability). In three patients, organoids were generated from multiple metastatic sites and intrapatient drug response heterogeneity was observed.

Conclusions: Both intra- and interpatient drug response heterogeneity exist in patients undergoing CRS/HIPEC for nongynecologic abdominal cancers. Caution must be used when interpreting patient response to chemotherapeutic agents based on a single site of testing in those with metastatic disease.

Keywords

Cytoreductive surgery; HIPEC; Organoids; Peritoneal surface malignancies; Translational research.

Figures
Products