Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Translational Therapeutics

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

British Journal of Cancer volume 131, pages 565–576 (2024)Cite this article

Subjects

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: CONSORT diagram of OVHIPEC-1 participants and tissue availability.
Fig. 2: Summary of methods diagram.
Fig. 3: Bulk differential gene expression analysis.
Fig. 4: Deconvolution of bulk RNA sequencing data to estimate cell-type abundance using single-cell expression reference profiles.
Fig. 5: Predictive delta treatment score based on single-cell deconvolution.
Fig. 6: Forest plot of exploratory subgroup analysis for overall survival based on histopathological assessment.

Similar content being viewed by others

Data availability

Single-cell sequences for constructing reference profiles for deconvolution are publicly available [35], as well as count matrix and deconvolution results. The code used in generating the results is made available on https://github.com/cwlkr/DTSIC_HIPEC. Clinical data and RNA-seq data supporting this work are available upon reasonable request. Requests to access data should be made to the Netherlands Cancer Institute’s scientific repository at repository@nki.nl, which will contact the corresponding author. The institutional review board of the Netherlands Cancer Institute will review all requests.

References

  1. van Driel WJ, Koole SN, Sikorska K, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. New Engl J Med. 2018;378:230–40.

    Article  PubMed  Google Scholar 

  2. Aronson SL, Lopez-Yurda M, Koole SN, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, et al. Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial. Lancet Oncol. 2023;24:1109–18.

    Article  CAS  PubMed  Google Scholar 

  3. Auer RC, Sivajohanathan D, Biagi J, Conner J, Kennedy E, May T. Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery: a clinical practice guideline. Curr Oncol. 2020;27:146–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. National Comprehensive Cancer Network. Ovarian Cancer (Version 3.2022) [Available from: https://www.nccn.org/login?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf.

  5. Chicago Consensus Working Group. The Chicago Consensus on peritoneal surface malignancies: management of ovarian neoplasms. Cancer. 2020;126:2553–60.

    Article  Google Scholar 

  6. Lavoué V, Huchon C, Akladios C, Alfonsi P, Bakrin N, Ballester M, et al. [Part II drafted from the short text of the French guidelines entitled “Initial management of patients with epithelial ovarian cancer” developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa. (Systemic and intraperitoneal treatment, elderly, fertility preservation, follow-up)]. Gynecol Obstet Fertil Senol. 2019;47:111–9.

  7. Lim MC, Chang SJ, Park B, Yoo HJ, Yoo CW, Nam BH, et al. Survival after hyperthermic intraperitoneal chemotherapy and primary or interval cytoreductive surgery in ovarian cancer: a randomized clinical trial. JAMA Surg. 2022;157:374–83.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zhang AW, McPherson A, Milne K, Kroeger DR, Hamilton PT, Miranda A, et al. Interfaces of malignant and immunologic clonal dynamics in ovarian cancer. Cell. 2018;173:1755–69.e22.

    Article  CAS  PubMed  Google Scholar 

  9. Zhang Y, Tang H, Cai J, Zhang T, Guo J, Feng D, et al. Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion. Cancer Lett. 2011;303:47–55.

    Article  CAS  PubMed  Google Scholar 

  10. Dijkgraaf EM, Heusinkveld M, Tummers B, Vogelpoel LT, Goedemans R, Jha V, et al. Chemotherapy alters monocyte differentiation to favor generation of cancer-supporting M2 macrophages in the tumor microenvironment. Cancer Res. 2013;73:2480–92.

    Article  CAS  PubMed  Google Scholar 

  11. Sherman-Baust CA, Weeraratna AT, Rangel LB, Pizer ES, Cho KR, Schwartz DR, et al. Remodeling of the extracellular matrix through overexpression of collagen VI contributes to cisplatin resistance in ovarian cancer cells. Cancer Cell. 2003;3:377–86.

    Article  CAS  PubMed  Google Scholar 

  12. Hwang WT, Adams SF, Tahirovic E, Hagemann IS, Coukos G. Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol. 2012;124:192–8.

    Article  PubMed  Google Scholar 

  13. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19:1423–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Thibault B, Castells M, Delord J-P, Couderc B. Ovarian cancer microenvironment: implications for cancer dissemination and chemoresistance acquisition. Cancer Metastasis Rev. 2014;33:17–39.

    Article  CAS  PubMed  Google Scholar 

  15. Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12:453–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Tsoucas D, Dong R, Chen H, Zhu Q, Guo G, Yuan GC. Accurate estimation of cell-type composition from gene expression data. Nat Commun. 2019;10:2975.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Schelker M, Feau S, Du J, Ranu N, Klipp E, MacBeath G, et al. Estimation of immune cell content in tumour tissue using single-cell RNA-seq data. Nat Commun. 2017;8:2032.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kester L, Seinstra D, van Rossum AGJ, Vennin C, Hoogstraat M, van der Velden D, et al. Differential survival and therapy benefit of patients with breast cancer are characterized by distinct epithelial and immune cell microenvironments. Clin Cancer Res. 2022;28:960–71.

    Article  CAS  PubMed  Google Scholar 

  19. Newman AM, Steen CB, Liu CL, Gentles AJ, Chaudhuri AA, Scherer F, et al. Determining cell type abundance and expression from bulk tissues with digital cytometry. Nat Biotechnol. 2019;37:773–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chen B, Khodadoust MS, Liu CL, Newman AM, Alizadeh AA. Profiling tumor infiltrating immune cells with CIBERSORT. Methods Mol Biol. 2018;1711:243–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhang SC, Hu ZQ, Long JH, Zhu GM, Wang Y, Jia Y, et al. Clinical implications of tumor-infiltrating immune cells in breast cancer. J Cancer. 2019;10:6175–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ali HR, Chlon L, Pharoah PD, Markowetz F, Caldas C. Patterns of immune infiltration in breast cancer and their clinical implications: a gene-expression-based retrospective study. PLoS Med. 2016;13:e1002194.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ge P, Wang W, Li L, Zhang G, Gao Z, Tang Z, et al. Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of colorectal cancer. Biomed Pharmacother. 2019;118:109228.

    Article  CAS  PubMed  Google Scholar 

  24. Tamminga M, Hiltermann TJN, Schuuring E, Timens W, Fehrmann RS, Groen HJ. Immune microenvironment composition in non-small cell lung cancer and its association with survival. Clin Transl Immunol. 2020;9:e1142.

    Article  CAS  Google Scholar 

  25. Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. New Engl J Med. 2018;379:2495–505.

    Article  CAS  PubMed  Google Scholar 

  26. Rustin GJ, Vergote I, Eisenhauer E, Pujade-Lauraine E, Quinn M, Thigpen T, et al. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer. 2011;21:419–23.

    Article  PubMed  Google Scholar 

  27. Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73:2680–6.

    Article  CAS  PubMed  Google Scholar 

  28. Li B, Dewey CN. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinforma. 2011;12:323.

    Article  CAS  Google Scholar 

  29. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15–21.

    Article  CAS  PubMed  Google Scholar 

  30. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Bismeijer T, Kim Y. FlexGSEA: flexible gene set enrichment analysis (Version v1.3). Zenodo 2019. https://doi.org/10.5281/zenodo.2616660.

  32. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102:15545–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Liberzon A, Birger C, Thorvaldsdóttir H, Ghandi M, Mesirov JP, Tamayo P. The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst. 2015;1:417–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Supek F, Bošnjak M, Škunca N, Šmuc T. REVIGO summarizes and visualizes long lists of gene ontology terms. PLoS ONE. 2011;6:e21800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Olbrecht S, Busschaert P, Qian J, Vanderstichele A, Loverix L, Van Gorp T, et al. High-grade serous tubo-ovarian cancer refined with single-cell RNA sequencing: specific cell subtypes influence survival and determine molecular subtype classification. Genome Med. 2021;13:111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hao Y, Hao S, Andersen-Nissen E, Mauck WM 3rd, Zheng S, Butler A, et al. Integrated analysis of multimodal single-cell data. Cell 2021;184:3573–87.e29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Oza AM, Castonguay V, Tsoref D, Diaz-Padilla I, Karakasis K, Mackay H, et al. Progression-free survival in advanced ovarian cancer: a Canadian review and expert panel perspective. Curr Oncol. 2011;18:S20–7.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kang Y, Nagaraja AS, Armaiz-Pena GN, Dorniak PL, Hu W, Rupaimoole R, et al. Adrenergic stimulation of DUSP1 impairs chemotherapy response in ovarian cancer. Clin Cancer Res. 2016;22:1713–24.

    Article  CAS  PubMed  Google Scholar 

  39. Emont MP, Jacobs C, Essene AL, Pant D, Tenen D, Colleluori G, et al. A single-cell atlas of human and mouse white adipose tissue. Nature. 2022;603:926–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Heath O, Berlato C, Maniati E, Lakhani A, Pegrum C, Kotantaki P, et al. Chemotherapy induces tumor-associated macrophages that aid adaptive immune responses in ovarian cancer. Cancer Immunol Res. 2021;9:665–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Montfort A, Barker-Clarke RJ, Piskorz AM, Supernat A, Moore L, Al-Khalidi S, et al. Combining measures of immune infiltration shows additive effect on survival prediction in high-grade serous ovarian carcinoma. Br J Cancer. 2020;122:1803–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Huffman OG, Chau DB, Dinicu AI, DeBernardo R, Reizes O. Mechanistic insights on hyperthermic intraperitoneal chemotherapy in ovarian cancer. Cancers. 2023;15:1402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Jiménez-Sánchez A, Cybulska P, Mager KL, Koplev S, Cast O, Couturier D-L, et al. Unraveling tumor–immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy. Nat Genet. 2020;52:582–93.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Schweer D, McAtee A, Neupane K, Richards C, Ueland F, Kolesar J. Tumor-associated macrophages and ovarian cancer: implications for therapy. Cancers. 2022;14:2220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hensler M, Kasikova L, Fiser K, Rakova J, Skapa P, Laco J, et al. M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer. J Immunother Cancer. 2020;8:e000979.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Zhang M, He Y, Sun X, Li Q, Wang W, Zhao A, et al. A high M1/M2 ratio of tumor-associated macrophages is associated with extended survival in ovarian cancer patients. J Ovarian Res. 2014;7:19.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Cohen-Sfady M, Nussbaum G, Pevsner-Fischer M, Mor F, Carmi P, Zanin-Zhorov A, et al. Heat shock protein 60 activates B cells via the TLR4-MyD88 pathway. J Immunol. 2005;175:3594–602.

    Article  CAS  PubMed  Google Scholar 

  48. Maleki F, Ovens K, Hogan DJ, Kusalik AJ. Gene set analysis: challenges, opportunities, and future research. Front Genet. 2020;11:654.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ambroise C, McLachlan GJ. Selection bias in gene extraction on the basis of microarray gene-expression data. Proc Natl Acad Sci USA. 2002;99:6562–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Goeman JJ, Bühlmann P. Analyzing gene expression data in terms of gene sets: methodological issues. Bioinformatics. 2007;23:980–7.

    Article  CAS  PubMed  Google Scholar 

  51. Gharpure KM, Pradeep S, Sans M, Rupaimoole R, Ivan C, Wu SY, et al. FABP4 as a key determinant of metastatic potential of ovarian cancer. Nat Commun. 2018;9:2923.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med. 2011;17:1498–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Corlan AS, Cîmpean AM, Jitariu AA, Melnic E, Raica M. Endocrine gland-derived vascular endothelial growth factor/prokineticin-1 in cancer development and tumor angiogenesis. Int J Endocrinol. 2017;2017:3232905.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Sanders BE, Yamamoto TM, McMellen A, Woodruff ER, Berning A, Post MD, et al. Targeting DUSP activity as a treatment for high-grade serous ovarian carcinoma. Mol Cancer Ther. 2022;21:1285–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Koole SN, Schouten PC, Hauke J, Kluin RJC, Nederlof P, Richters LK, et al. Effect of HIPEC according to HRD/BRCAwt genomic profile in stage III ovarian cancer—results from the phase III OVHIPEC trial. Int J Cancer. 2022;151:1394–404.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank all patients and their families and caregivers for participating in the present study. We thank the Core Facility of Molecular Pathology and Biobanking, S Cornelissen and D Peters for their support in processing of the samples; RJC Kluin, W Brugman, and the Genomics Core Facility for their support with sequencing; the principal investigators of the participating sites in patient recruitment and sample acquisition. The present study was funded by the Dutch National Cancer Foundation (KWF) and sponsored by the NKI. The funding sources had no role in the design and execution of the study, data analysis or writing of the manuscript.

Funding

The OVHIPEC-1 trial was funded by the Dutch Cancer Foundation (KWF Kankerbestrijding; NKI 2006–4176, to WJvD). Further financial support came from the Department of Defense Ovarian Cancer Research Program (Award No. W81XWH-22-1-0557), the Swiss National Science Foundation (320030M_219453), the Swiss Cancer League (KFS-5519-02-2022), and the ISREC Foundation (to SR). JvR received funding from the Josef Steiner Cancer Research Foundation.

Author information

Author notes

  1. These authors contributed equally: S. Lot Aronson, Cédric Walker.

  2. These authors jointly supervised this work: Lennart A. Kester, Kerstin Hahn.

  3. A full list of members and their affiliations appears in the Supplementary Information.

Authors and Affiliations

  1. Center for Gynecologic Oncology Amsterdam, Department of Gynecologic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    S. Lot Aronson, Koen K. van de Vijver, Simone N. Koole, Christianne A. R. Lok, W. J. van Driel & Willemien J. van Driel

  2. Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    S. Lot Aronson & Gabe S. Sonke

  3. Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland

    Cédric Walker & Sven Rottenberg

  4. Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland

    Cédric Walker

  5. Division of Molecular Carcinogenesis, Oncode Institute, Netherlands Cancer Institute, Amsterdam, The Netherlands

    Bram Thijssen

  6. Oncode Institute, Utrecht, The Netherlands

    Bram Thijssen

  7. Department of Pathology & Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent, Belgium

    Koen K. van de Vijver

  8. Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Hugo M. Horlings & Joyce Sanders

  9. Core Facility Molecular Pathology and Biobanking, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Maartje Alkemade

  10. Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Marta Lopez-Yurda

  11. Bern Center for Precision Medicine, University of Bern, Bern, Switzerland

    Sven Rottenberg

  12. Department of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Jacco van Rheenen & Kerstin Hahn

  13. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

    Lennart A. Kester

  14. Department of Gynecology and Obstetrics, Catharina Hospital, Eindhoven, The Netherlands

    H. M. Hermans

  15. Department of Obstetrics & Gynecology, Sint Antonius Hospital, Nieuwegein, The Netherlands

    J. H. Schagen van Leeuwen

  16. Department of Gynecologic Oncology, UMC Utrecht Cancer Center, Utrecht, The Netherlands

    H. W. R. Schreuder

  17. Center for Gynecologic Oncology Amsterdam, Department of Obstetrics and Gynecology, Amsterdam University Medical Center, Amsterdam, The Netherlands

    M. D. J. M. van Gent

  18. Department of Gynecologic Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands

    M. A. P. C. van Ham

  19. Department of Gynecologic Oncology, University Medical Center Groningen, Groningen, The Netherlands

    H. J. G. Arts

  20. Department of Gynecologic Oncology, University Hospital Antwerp, Antwerp, Belgium

    P. A. van Dam

  21. Department of Medical Oncology, UCL Louvain, CHU Namur Sainte-Elisabeth, Namur, Belgium

    P. Vuylsteke

Authors
  1. S. Lot Aronson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cédric Walker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bram Thijssen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Koen K. van de Vijver
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hugo M. Horlings
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joyce Sanders
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maartje Alkemade
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Simone N. Koole
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Marta Lopez-Yurda
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Christianne A. R. Lok
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sven Rottenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jacco van Rheenen
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Gabe S. Sonke
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Willemien J. van Driel
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Lennart A. Kester
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Kerstin Hahn
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

OVHIPEC-1 Study Group

  • W. J. van Driel
  • , H. M. Hermans
  • , J. H. Schagen van Leeuwen
  • , H. W. R. Schreuder
  • , M. D. J. M. van Gent
  • , M. A. P. C. van Ham
  • , H. J. G. Arts
  • , P. A. van Dam
  •  & P. Vuylsteke

Contributions

KH, LvK, JvR, SR, WJvD, GSS, SNK and CARL were involved in the conceptualisation. WJvD was the coordinating principal investigator for the clinical study and was responsible for funding acquisition. SR, JvR and GSS were also responsible for funding acquisition. SLA, SNK, GSS and WJvD were involved in clinical data collection. KKvdV, JS and HMH performed manual pathology scoring. MA performed the processing of the tissue samples. SLA performed the histopathological analysis under the supervision of MLY. CW performed the deconvolution analyses under the supervision of LvK, KH and SR. BT performed the gene expression analyses. SLA, CW, BT, KH and LvK, interpreted the data. SLA, CW, BT and KH wrote the original draft of the manuscript. KH, LvK, JvR, SR, WJvD and GSS supervised the study. All authors were involved in critically revising the report. All authors approved the final version and took responsibility for the decision to submit the manuscript for publication.

Corresponding author

Correspondence to Willemien J. van Driel.

Ethics declarations

Competing interests

KKVdV has served on advisory boards for Exact Sciences and AstraZeneca. HMH received honoraria from Roche Diagnostics BV. GSS has received institutional research support from Merck Sharp & Dohme, Agendia, AstraZeneca, Roche, and Novartis, and consulting fees from Biovica and Seagen. KH is a former employee at the Netherlands Cancer Institute and is currently working for Roche, Pharmaceutical Sciences, Basel, Switzerland. The research for this project was conducted in her position of researcher at the NKI. The remaining authors declare no competing interests.

Ethics approval and consent to participate

The protocol was approved by the local ethics committee at each of the participating centres. All patients provided written informed consent prior to enrolment. This study was performed in accordance with the Declaration of Helsinki.

Consent for publication

Not applicable.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aronson, S.L., Walker, C., Thijssen, B. et al. Tumour microenvironment characterisation to stratify patients for hyperthermic intraperitoneal chemotherapy in high-grade serous ovarian cancer (OVHIPEC-1). Br J Cancer 131, 565–576 (2024). https://doi.org/10.1038/s41416-024-02731-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41416-024-02731-6

Search

Advanced search

Quick links