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Hyperthermic Intraperitoneal Chemotherapy-Induced Molecular Changes in Humans Validate Preclinical Data in Ovarian
Thanh H Dellinger1, Ernest S Han1, Mustafa Raoof2
1Division of Gynecologic Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, CA.
JCO Precision Oncology
|March 31, 2022
Summary
Hyperthermic intraperitoneal chemotherapy (HIPEC) shows survival benefits for ovarian cancer. This study identifies molecular signatures in patients, confirming preclinical findings and revealing HIPEC-induced changes in immune pathways and heat shock proteins.
Area of Science:
- Oncology
- Genomics
- Immunology
Background:
- Hyperthermic intraperitoneal chemotherapy (HIPEC) offers survival advantages in epithelial ovarian cancer (EOC).
- Molecular alterations induced by HIPEC in humans remain largely uncharacterized.
Purpose of the Study:
- To evaluate the clinical and safety outcomes of HIPEC with cisplatin during cytoreductive surgery in advanced EOC.
- To identify molecular and transcriptomic signatures correlating with HIPEC response in EOC patients.
- To investigate HIPEC-induced transcriptional changes in the tumor microenvironment.
Main Methods:
- Feasibility trial involving 35 EOC patients undergoing HIPEC and cytoreductive surgery.
- Comprehensive genomic and transcriptomic profiling of pre- and post-HIPEC tumor biopsies.
- Analysis of tumor microenvironment, including immune cell markers and transcriptional signatures.
Main Results:
- Median progression-free survival (PFS) was 24.7 months (primary) and 22.4 months (recurrent).
- Distinct transcriptomic signatures differentiated good (PFS 29.9 months) from poor responders (PFS 7.3 months).
- HIPEC upregulated immune pathways, downregulated DNA repair pathways, and increased PD-1 expression in CD8+ T cells among good responders. Heat shock proteins were upregulated.
Conclusions:
- Transcriptomic signatures can identify HIPEC responders in epithelial ovarian cancer.
- Preclinical findings regarding HIPEC's molecular effects are confirmed in a human cohort.
- HIPEC induces significant molecular changes, including immune modulation, in EOC patients.
