Dataset Information

Hyperthermic Intraperitoneal Chemotherapy-Induced Molecular Changes in Humans Validate Preclinical Data in Ovarian Cancer.

ABSTRACT:

Purpose

Hyperthermic intraperitoneal chemotherapy (HIPEC) confers a survival benefit in epithelial ovarian cancer (EOC) and in preclinical models. However, the molecular changes induced by HIPEC have not been corroborated in humans.

Patients and methods

A feasibility trial evaluated clinical and safety outcomes of HIPEC with cisplatin during optimal cytoreductive surgery (CRS) in patients with EOC diagnosed with stage III, IV, or recurrent EOC. Pre- and post-HIPEC biopsies were comprehensively profiled with genomic and transcriptomic sequencing to identify mutational and RNAseq signatures correlating with response; the tumor microenvironment was profiled to identify potential immune biomarkers; and transcriptional signatures of tumors and normal samples before and after HIPEC were compared to investigate HIPEC-induced acute transcriptional changes.

Results

Thirty-five patients had HIPEC at the time of optimal CRS; all patients had optimal CRS. The median progression-free survival (PFS) was 24.7 months for primary patients and 22.4 for recurrent patients. There were no grade 4 or 5 adverse events. Anemia was the most common grade 3 adverse event (43%). Hierarchical cluster analyses identified distinct transcriptomic signatures of good versus poor responders to HIPEC correlating with a PFS of 29.9 versus 7.3 months, respectively. Among good responders, significant HIPEC-induced molecular changes included immune pathway upregulation and DNA repair pathway downregulation. Within cancer islands, % programmed cell death protein 1 expression in CD8+ T cells significantly increased after HIPEC. An exceptional responder (PFS 58 months) demonstrated the highest programmed cell death protein 1 increase. Heat shock proteins comprised the top differentially upregulated genes in HIPEC-treated tumors.

Conclusion

Distinct transcriptomic signatures identify responders to HIPEC, and preclinical model findings are confirmed for the first time in a human cohort.

SUBMITTER: Dellinger TH

PROVIDER: S-EPMC8984280 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Hyperthermic Intraperitoneal Chemotherapy-Induced Molecular Changes in Humans Validate Preclinical Data in Ovarian Cancer.

Dellinger Thanh H TH Han Ernest S ES Raoof Mustafa M Lee Byrne B Wu Xiwei X Cho Hyejin H He Ting-Fang TF Lee Peter P Razavi Marianne M Liang Winnie S WS Schmolze Daniel D Priceman Saul J SJ Lee Stephen S Lin Wei-Chien WC Lin Jeff F JF Kebria Mehdi M Hakim Amy A Ruel Nora N Stewart Daphne B DB Wang Edward W EW Paz Benjamin I BI Wakabayashi Mark T MT Cristea Mihaela C MC Rodriguez-Rodriguez Lorna L

JCO precision oncology 20220301

<h4>Purpose</h4>Hyperthermic intraperitoneal chemotherapy (HIPEC) confers a survival benefit in epithelial ovarian cancer (EOC) and in preclinical models. However, the molecular changes induced by HIPEC have not been corroborated in humans.<h4>Patients and methods</h4>A feasibility trial evaluated clinical and safety outcomes of HIPEC with cisplatin during optimal cytoreductive surgery (CRS) in patients with EOC diagnosed with stage III, IV, or recurrent EOC. Pre- and post-HIPEC biopsies were co ...[more]

PMID: 35357903

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Project description:ObjectiveWe aimed to compare the survival outcomes and adverse events of hyperthermic intraperitoneal chemotherapy (HIPEC), intraperitoneal chemotherapy (IP)and intravenous chemotherapy (IP)for primary advanced ovarian cancer.MethodsPubMed, CENTRAL (Cochrane Central Registry of Controlled Trials), Embase, Web of Science and Scopus were searched using multiple terms for primary advanced ovarian cancer, including randomized controlled trials and comparative studies in both Chinese and English (up to date 15 August 2022). Outcomes include overall survival, progression-free survival and adverse events. The data were pooled and reported as hazard ratio (HRs) with 95% confidence intervals. The Newcastle-Ottawa Scales were used to assess the risk of bias in the included comparative study. The Cochrane Collaboration's Risk of Bias Tool was used for randomized controlled trials.ResultsIn total, 32 studies, including 6347 patients and 8 different platinum-based chemotherapy regimens, were included in this network meta-analysis. Our analysis results showed that HIPEC2 (carboplatin with area under the curve 10) exhibited a statistically significant OS benefit compared to IV, weekly dose-dense chemotherapy and HIPEC1 (cisplatin with 75/100 mg/m2). Intraperitoneal plus intravenous chemotherapy was associated with a statistically significantly better likelihood of overall survival compared to IV. For progression-free survival, our statistical results only suggest a better progression-free survival in ovarian cancer patients treated with HIPEC1 compared with weekly dose-dense chemotherapy. No evidence of difference was observed between the other comparison groups. Compared with the non-HIPEC group, HIPEC may had a higher incidence of electrolyte disturbances (≥grade 3).ConclusionOur statistical analysis suggests that the groups receiving HIPEC2 had a better OS than the groups receiving IV, weekly dose-dense chemotherapy and HIPEC1. For PFS, our analysis only showed HIPEC1 is better than IV. Moreover, HIPEC may lead to a higher incidence of electrolyte disturbances (≥grade 3). HIPEC therapy for advanced ovarian cancer is currently controversial.

Dataset Information

Hyperthermic Intraperitoneal Chemotherapy-Induced Molecular Changes in Humans Validate Preclinical Data in Ovarian Cancer.

Purpose

Patients and methods

Results

Conclusion

Publications

Hyperthermic Intraperitoneal Chemotherapy-Induced Molecular Changes in Humans Validate Preclinical Data in Ovarian Cancer.

Similar Datasets

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