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

S. Lot Aronson; C. dric Walker; Bram Thijssen; Koen K. van de Vijver; Hugo M. Horlings; Joyce Sanders; Maartje Alkemade; Simone N. Koole; Marta Lopez-Yurda; Christianne A. R. Lok; Sven Rottenberg; Jacco van Rheenen; Gabe S. Sonke; Willemien J. van Driel; Lennart A. Kester; Kerstin Hahn; van Driel; Hermans; van Leeuwen; Schreuder; van Gent; van Ham; Arts; van Dam; OVHIPEC-1 Study Group

doi:10.1038/s41416-024-02731-6

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

S. Lot Aronson
, C. dric Walker
, Bram Thijssen
, Koen K. van de Vijver
, Hugo M. Horlings
, Joyce Sanders
, Maartje Alkemade
, Simone N. Koole
, Marta Lopez-Yurda
, Christianne A. R. Lok
, Sven Rottenberg
, Jacco van Rheenen
, Gabe S. Sonke
, Willemien J. van Driel^*
, Lennart A. Kester
, Kerstin Hahn
, van Driel
, Hermans
, van Leeuwen
, Schreuder

van Gent, van Ham, Arts, van Dam, OVHIPEC-1 Study Group

^*Corresponding author for this work

Netherlands Cancer Institute
University of Bern, Institute of Animal Pathology
University of Bern
Oncode Institute
Ghent University
Princess Máxima Center for Pediatric Oncology
Catharina Hospital
St. Antonius Ziekenhuis
Utrecht University
Amsterdam UMC - University of Amsterdam
Radboud University Nijmegen
University of Groningen
University of Antwerp
CHU Site Sainte-Elisabeth-UCL Namur

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	565-576
Number of pages	12
Journal	British journal of cancer
Volume	131
Issue number	3
DOIs	https://doi.org/10.1038/s41416-024-02731-6
Publication status	Published - 24 Aug 2024

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Aronson, S. L., Walker, C. D., Thijssen, B., van de Vijver, K. K., Horlings, H. M., Sanders, J., Alkemade, M., Koole, S. N., Lopez-Yurda, M., Lok, C. A. R., Rottenberg, S., van Rheenen, J., Sonke, G. S., van Driel, W. J., Kester, L. A., Hahn, K., van Driel, Hermans, van Leeuwen, ... OVHIPEC-1 Study Group (2024). Tumour microenvironment characterisation to stratify patients for hyperthermic intraperitoneal chemotherapy in high-grade serous ovarian cancer (OVHIPEC-1). British journal of cancer, 131(3), 565-576. https://doi.org/10.1038/s41416-024-02731-6

@article{0005707355804ae59b3eea3bb106f160,

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

abstract = "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.",

author = "Aronson, \{S. Lot\} and Walker, \{C. dric\} and Bram Thijssen and \{van de Vijver\}, \{Koen K.\} and Horlings, \{Hugo M.\} and Joyce Sanders and Maartje Alkemade and Koole, \{Simone N.\} and Marta Lopez-Yurda and Lok, \{Christianne A. R.\} and Sven Rottenberg and \{van Rheenen\}, Jacco and Sonke, \{Gabe S.\} and \{van Driel\}, \{Willemien J.\} and Kester, \{Lennart A.\} and Kerstin Hahn and \{van Driel\} and Hermans and \{van Leeuwen\} and Schreuder and \{van Gent\} and \{van Ham\} and Arts and \{van Dam\} and \{OVHIPEC-1 Study Group\} and Vuylsteke",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature Limited 2024.",

year = "2024",

month = aug,

day = "24",

doi = "10.1038/s41416-024-02731-6",

language = "English",

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Aronson, SL, Walker, CD, Thijssen, B, van de Vijver, KK, Horlings, HM, Sanders, J, Alkemade, M, Koole, SN, Lopez-Yurda, M, Lok, CAR, Rottenberg, S, van Rheenen, J, Sonke, GS, van Driel, WJ, Kester, LA, Hahn, K, van Driel, Hermans, van Leeuwen, Schreuder, van Gent, van Ham, Arts, van Dam & OVHIPEC-1 Study Group 2024, 'Tumour microenvironment characterisation to stratify patients for hyperthermic intraperitoneal chemotherapy in high-grade serous ovarian cancer (OVHIPEC-1)', British journal of cancer, vol. 131, no. 3, pp. 565-576. https://doi.org/10.1038/s41416-024-02731-6

TY - JOUR

T1 - Tumour microenvironment characterisation to stratify patients for hyperthermic intraperitoneal chemotherapy in high-grade serous ovarian cancer (OVHIPEC-1)

AU - Aronson, S. Lot

AU - Walker, C. dric

AU - Thijssen, Bram

AU - van de Vijver, Koen K.

AU - Horlings, Hugo M.

AU - Sanders, Joyce

AU - Alkemade, Maartje

AU - Koole, Simone N.

AU - Lopez-Yurda, Marta

AU - Lok, Christianne A. R.

AU - Rottenberg, Sven

AU - van Rheenen, Jacco

AU - Sonke, Gabe S.

AU - van Driel, Willemien J.

AU - Kester, Lennart A.

AU - Hahn, Kerstin

AU - van Driel, null

AU - Hermans, null

AU - van Leeuwen, null

AU - Schreuder, null

AU - van Gent, null

AU - van Ham, null

AU - Arts, null

AU - van Dam, null

AU - OVHIPEC-1 Study Group

AU - Vuylsteke, null

PY - 2024/8/24

Y1 - 2024/8/24

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85195697228

U2 - 10.1038/s41416-024-02731-6

DO - 10.1038/s41416-024-02731-6

M3 - Article

C2 - 38866963

SN - 0007-0920

VL - 131

SP - 565

EP - 576

JO - British journal of cancer

JF - British journal of cancer

IS - 3

ER -

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

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