Koole, Simone N. ORCID: 0000-0002-8909-1935, Schouten, Philip C., Hauke, Jan, Kluin, Roel J. C., Nederlof, Petra, Richters, Lisa K., Krebsbach, Gabriele, Sikorska, Karolina, Alkemade, Maartje, Opdam, Mark, van Leeuwen, Jules H. Schagen, Schreuder, Henk W. R., Hermans, Ralph H. M., de Hingh, Ignace H. J. T., Mom, Constantijne H., Arts, Henriette J. G., van Ham, Maaike, van Dam, Peter, Vuylsteke, Peter, Sanders, Joyce, Horlings, Hugo M., van de Vijver, Koen K., Hahnen, Eric, van Driel, Willemien J., Schmutzler, Rita, Sonke, Gabe S. and Linn, Sabine C. (2022). Effect of HIPEC according to HRD/BRCAwt genomic profile in stage III ovarian cancer: Results from the phase III OVHIPEC trial. Int. J. Cancer, 151 (8). S. 1394 - 1405. HOBOKEN: WILEY. ISSN 1097-0215

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Abstract

The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin to interval cytoreductive surgery improves recurrence-free (RFS) and overall survival (OS) in patients with stage III ovarian cancer. Homologous recombination deficient (HRD) ovarian tumors are usually more platinum sensitive. Since hyperthermia impairs BRCA1/2 protein function, we hypothesized that HRD tumors respond best to treatment with HIPEC. We analyzed the effect of HIPEC in patients in the OVHIPEC trial, stratified by HRD status and BRCAm status. Clinical data and tissue samples were collected from patients included in the randomized, phase III OVHIPEC-1 trial. DNA copy number variation (CNV) profiles, HRD-related pathogenic mutations and BRCA1 promotor hypermethylation were determined. CNV-profiles were categorized as HRD or non-HRD, based on a previously validated algorithm-based BRCA1-like classifier. Hazard ratios (HR) and corresponding 99% confidence intervals (CI) for the effect of RFS and OS of HIPEC in the BRCAm, the HRD/BRCAwt and the non-HRD group were estimated using Cox proportional hazard models. Tumor DNA was available from 200/245 (82%) patients. Seventeen (9%) tumors carried a pathogenic mutation in BRCA1 and 14 (7%) in BRCA2. Ninety-one (46%) tumors classified as BRCA1-like. The effect of HIPEC on RFS and OS was absent in BRCAm tumors (HR 1.25; 99%CI 0.48-3.29), and most present in HRD/BRCAwt (HR 0.44; 99%CI 0.21-0.91), and non-HRD/BRCAwt tumors (HR 0.82; 99%CI 0.48-1.42), interaction P value: 0.024. Patients with HRD tumors without pathogenic BRCA1/2 mutation appear to benefit most from treatment with HIPEC, while benefit in patients with BRCA1/2 pathogenic mutations and patients without HRD seems less evident.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Koole, Simone N.UNSPECIFIEDorcid.org/0000-0002-8909-1935UNSPECIFIED
Schouten, Philip C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hauke, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kluin, Roel J. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nederlof, PetraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Richters, Lisa K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krebsbach, GabrieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sikorska, KarolinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alkemade, MaartjeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Opdam, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Leeuwen, Jules H. SchagenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schreuder, Henk W. R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hermans, Ralph H. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Hingh, Ignace H. J. T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mom, Constantijne H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arts, Henriette J. G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Ham, MaaikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Dam, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vuylsteke, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanders, JoyceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Horlings, Hugo M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van de Vijver, Koen K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hahnen, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Driel, Willemien J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmutzler, RitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sonke, Gabe S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Linn, Sabine C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-692929
DOI: 10.1002/ijc.34124
Journal or Publication Title: Int. J. Cancer
Volume: 151
Number: 8
Page Range: S. 1394 - 1405
Date: 2022
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1097-0215
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HOMOLOGOUS RECOMBINATION DEFICIENCY; BREAST-CANCER; CHEMOTHERAPY; DIAGNOSIS; SURVIVAL; BENEFIT; HSP90; BRCA1Multiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69292

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