Steven D. Forsythe, MSc
Graduate Student
Wake Forest School of Medicine
winston Salem, North Carolina, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Peritoneal mesothelioma (PM) is a rare malignancy (2 patients per million) with poor prognosis, representing about 10-15% of all mesothelioma cases per year. We previously reported on the feasibility of generating PM patient-derived tumor organoids (PTOs). Herein we present the application of PM PTOs in elucidating personalized response to HIPEC.
Methods:
After IRB approval, tumor samples were obtained from patients with PM undergoing cytoreductive surgery with HIPEC. PTOs were fabricated with tumor cells suspended in a collagen-based hydrogel and treated with HIPEC regimen mimicry. Viability, live/dead imaging, and IHC analysis were performed post-treatment. Treatment efficacy was defined as killing at least 50% of organoid cells.
Results:
Eight specimens were processed from 4 patients from October 2020 through June 2021, with two patients producing multiple specimens derived from distinct tumor metastases. All underwent successful organoid fabrication, with 7/8 (87.5%) sites undergoing comparative 37° and 42° HIPEC treatments with cisplatin and MMC. Response to HIPEC was patient and site specific. Hyperthermia enhanced the cytotoxicity of both drugs which averaged post treatment viability drop of 26.1% and 34.2% respectively compared to normothermia. Heated cisplatin displayed the greatest cytotoxicity with an average post-treatment viability of 48.5% (19.4-79.0%). Overall, heated cisplatin demonstrated efficacy in 5/7 (71.4%) tumors, with statistically significant superiority in 3/7 (42.8%) PTOs when compared to mitomycin C. Heated mitomycin C demonstrated efficacy in only 1/7 (14.2%) of specimens with an average post treatment viability of 62.6% (18.6-92.3%); this PTO group not responsive to cisplatin in the hyperthermic condition.
Conclusions:
Peritoneal mesothelioma PTOs treated with HIPEC exhibit patient and site specific responses to treatment. Cisplatin exhibits superior cytotoxic activity over MMC. Organoids have the potential to personalize HIPEC regimens for PM patients.