Effect of HIPEC according to HRD/BRCAwt genomic profile in stage III ovarian cancer: Results from the phase III OVHIPEC trial

Autor: Koole, Simone N., 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., Linn, Sabine C.
Přispěvatelé: Obstetrics and gynaecology, CCA - Cancer Treatment and quality of life, CCA - Cancer biology and immunology, Amsterdam Reproduction & Development (AR&D), Targeted Gynaecologic Oncology (TARGON)
Rok vydání: 2022
Předmět:
Zdroj: Koole, S N, Schouten, P C, Hauke, J, Kluin, R J C, Nederlof, P, Richters, L K, Krebsbach, G, Sikorska, K, Alkemade, M, Opdam, M, Schagen van Leeuwen, J H, Schreuder, H W R, Hermans, R H M, de Hingh, I H J T, Mom, C H, Arts, H J G, van Ham, M, van Dam, P, Vuylsteke, P, Sanders, J, Horlings, H M, van de Vijver, K K, Hahnen, E, van Driel, W J, Schmutzler, R, Sonke, G S & Linn, S C 2022, ' Effect of HIPEC according to HRD/BRCAwt genomic profile in stage III ovarian cancer : Results from the phase III OVHIPEC trial ', International Journal of Cancer, vol. 151, no. 8, pp. 1394-1404 . https://doi.org/10.1002/ijc.34124
International Journal of Cancer, 151, 1394-1404
International Journal of Cancer, 151, 8, pp. 1394-1404
International journal of cancer
International Journal of Cancer, 151(8), 1394-1404. Wiley-Liss Inc.
International Journal of Cancer, 151(8), 1394-1404. Wiley
ISSN: 0020-7136
Popis: Contains fulltext : 282977.pdf (Publisher’s version ) (Closed access) 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.
Databáze: OpenAIRE
Externí odkaz: