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

S Lot Aronson; Cédric 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

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, Cédric 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,

^*Corresponding author for this work

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

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

Keywords

Aged
Biomarkers, Tumor/genetics
Cystadenocarcinoma, Serous/pathology
Cytoreduction Surgical Procedures
Female
Humans
Hyperthermic Intraperitoneal Chemotherapy/methods
Macrophages/pathology
Middle Aged
Ovarian Neoplasms/pathology
Tumor Microenvironment

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10.1038/s41416-024-02731-6

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Aronson, S. L., Walker, C., 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. (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

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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.",

keywords = "Aged, Biomarkers, Tumor/genetics, Cystadenocarcinoma, Serous/pathology, Cytoreduction Surgical Procedures, Female, Humans, Hyperthermic Intraperitoneal Chemotherapy/methods, Macrophages/pathology, Middle Aged, Ovarian Neoplasms/pathology, Tumor Microenvironment",

author = "Aronson, {S Lot} and C{\'e}dric Walker 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 Henk Schreuder",

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",

volume = "131",

pages = "565--576",

journal = "British Journal of Cancer",

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Aronson, SL, Walker, C, 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 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, Cédric

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 - Schreuder, Henk

N1 - Publisher Copyright: © The Author(s), under exclusive licence to Springer Nature Limited 2024.

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.

KW - Aged

KW - Biomarkers, Tumor/genetics

KW - Cystadenocarcinoma, Serous/pathology

KW - Cytoreduction Surgical Procedures

KW - Female

KW - Humans

KW - Hyperthermic Intraperitoneal Chemotherapy/methods

KW - Macrophages/pathology

KW - Middle Aged

KW - Ovarian Neoplasms/pathology

KW - Tumor Microenvironment

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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