Tumour microenvironment characterisation to stratify patients for hyperthermic intraperitoneal chemotherapy in high-grade serous ovarian cancer (OVHIPEC-1).

Autor: Aronson SL; Center for Gynecologic Oncology Amsterdam, Department of Gynecologic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Walker C; Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland., Thijssen B; Division of Molecular Carcinogenesis, Oncode Institute, Netherlands Cancer Institute, Amsterdam, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., van de Vijver KK; Center for Gynecologic Oncology Amsterdam, Department of Gynecologic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.; Department of Pathology & Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent, Belgium., Horlings HM; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Sanders J; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Alkemade M; Core Facility Molecular Pathology and Biobanking, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Koole SN; Center for Gynecologic Oncology Amsterdam, Department of Gynecologic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Lopez-Yurda M; Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Lok CAR; Center for Gynecologic Oncology Amsterdam, Department of Gynecologic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Rottenberg S; Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.; Bern Center for Precision Medicine, University of Bern, Bern, Switzerland., van Rheenen J; Department of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Sonke GS; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., van Driel WJ; Center for Gynecologic Oncology Amsterdam, Department of Gynecologic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. w.v.driel@nki.nl., Kester LA; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Hahn K; Department of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2024 Aug; Vol. 131 (3), pp. 565-576. Date of Electronic Publication: 2024 Jun 12.
DOI: 10.1038/s41416-024-02731-6
Abstrakt: Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with Stage III ovarian cancer following interval cytoreductive surgery (CRS). Optimising patient selection is essential to maximise treatment efficacy and avoid overtreatment. This study aimed to identify biomarkers that predict HIPEC benefit by analysing gene signatures and cellular composition of tumours from participants in the OVHIPEC-1 trial.
Methods: Whole-transcriptome RNA sequencing data were retrieved from high-grade serous ovarian cancer (HGSOC) samples from 147 patients obtained during interval CRS. We performed differential gene expression analysis and applied deconvolution methods to estimate cell-type proportions in bulk mRNA data, validated by histological assessment. We tested the interaction between treatment and potential predictors on progression-free survival using Cox proportional hazards models.
Results: While differential gene expression analysis did not yield any predictive biomarkers, the cellular composition, as characterised by deconvolution, indicated that the absence of macrophages and the presence of B cells in the tumour microenvironment are potential predictors of HIPEC benefit. The histological assessment confirmed the predictive value of macrophage absence.
Conclusion: Immune cell composition, in particular macrophages absence, may predict response to HIPEC in HGSOC and these hypothesis-generating findings warrant further investigation.
Clinical Trial Registration: NCT00426257.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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