TY - JOUR
T1 - Tumour microenvironment characterisation to stratify patients for hyperthermic intraperitoneal chemotherapy in high-grade serous ovarian cancer (OVHIPEC-1)
AU - OVHIPEC-1 Study Group
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 - van Driel, Driel
AU - Hermans,
AU - van Leeuwen, Leeuwen
AU - Schreuder,
AU - van Gent, Gent
AU - van Ham, Ham
AU - Arts, null
AU - van Dam, Dam
AU - Vuylsteke,
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.
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
AN - SCOPUS:85195697228
SN - 0007-0920
VL - 131
SP - 565
EP - 576
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 3
ER -