Ondine Becker, Alice Durand, Marion Chevrier, Laetitia Collet, Laurence Gladieff, Florence Joly, Baptiste Sauterey, Christophe Pomel, Hélène Costaz, Patricia Pautier, Cécile Guillemet, Thibault de la Motte Rouge, Renaud Sabatier, Jean-Marc Classe, Thierry Petit, Eric Leblanc, Frédéric Marchal, Pierre-Emmanuel Colombo, Emmanuel Barranger, Aude-Marie Savoye, Lise Bosquet, Isabelle Ray-Coquard, Matthieu Carton, Oliver Colomban, Benoit You, Manuel Rodrigues
{"title":"通过 KELIM 评估晚期卵巢癌患者的肿瘤内在化疗敏感性，并通过 BRCA 状态评估预后。","authors":"Ondine Becker, Alice Durand, Marion Chevrier, Laetitia Collet, Laurence Gladieff, Florence Joly, Baptiste Sauterey, Christophe Pomel, Hélène Costaz, Patricia Pautier, Cécile Guillemet, Thibault de la Motte Rouge, Renaud Sabatier, Jean-Marc Classe, Thierry Petit, Eric Leblanc, Frédéric Marchal, Pierre-Emmanuel Colombo, Emmanuel Barranger, Aude-Marie Savoye, Lise Bosquet, Isabelle Ray-Coquard, Matthieu Carton, Oliver Colomban, Benoit You, Manuel Rodrigues","doi":"10.1136/ijgc-2024-005815","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Treatment of high-grade serous ovarian carcinomas relies on surgery and chemotherapy, potentially followed by bevacizumab and/or poly (ADP-ribose) polymerase inhibitors (PARPi). The modeled CA-125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor primary chemosensitivity. Although it is well established that <i>BRCA</i> mutations are associated with platinum sensitivity, the relationship between <i>BRCA</i> status and KELIM score has yet to be elucidated. This study aimed to evaluate the interactions between <i>BRCA</i> and KELIM, and their respective prognostic values.</p><p><strong>Methods: </strong>We retrospectively collected data from 743 patients with high-grade serous ovarian carcinomas included in a French nationwide registry (NCT03275298) treated with neoadjuvant platinum-based chemotherapy followed by surgery. We analyzed the interactions between <i>BRCA</i> and KELIM, and their impacts on progression-free survival and overall survival.</p><p><strong>Results: </strong><i>BRCA</i>-mutated <i>(BRCA</i>m) patients had higher standardized KELIM than <i>BRCA</i>-wild type (<i>BRCA</i>wt) tumors (median 1.16 vs 1.06, respectively; p=0.001). The prognostic value of the KELIM score was independent of <i>BRCA</i> in multivariate analyses. KELIM score and <i>BRCA</i> could be combined to define three prognostic groups: (1) an unfavorable prognostic group with both <i>BRCA</i>wt and unfavorable KELIM (median progression-free survival 12.0 months); (2) an intermediate prognostic group with either <i>BRCA</i>m and unfavorable KELIM, or <i>BRCA</i>wt and favorable KELIM (median progression-free survival of 16.0 and 18.8 months, respectively; HR 0.64 compared with the unfavorable group, p<0.001); and (3) a favorable prognostic group with both <i>BRCA</i>m and favorable KELIM (median progression-free survival 28.8 months; HR 0.37 compared with the unfavorable group, p<0.001).</p><p><strong>Conclusions: </strong>The KELIM score provides complementary prognostic information with respect to <i>BRCA,</i> and discriminates different prognoses within <i>BRCA</i>m or <i>BRCA</i>wt patients. Patients with both <i>BRCA</i>wt/unfavorable KELIM have a poor prognosis, underscoring the urgent need for novel therapeutic strategies.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":" ","pages":""},"PeriodicalIF":4.1000,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Tumor-intrinsic chemosensitivity assessed by KELIM and prognosis by <i>BRCA</i> status in patients with advanced ovarian carcinomas.\",\"authors\":\"Ondine Becker, Alice Durand, Marion Chevrier, Laetitia Collet, Laurence Gladieff, Florence Joly, Baptiste Sauterey, Christophe Pomel, Hélène Costaz, Patricia Pautier, Cécile Guillemet, Thibault de la Motte Rouge, Renaud Sabatier, Jean-Marc Classe, Thierry Petit, Eric Leblanc, Frédéric Marchal, Pierre-Emmanuel Colombo, Emmanuel Barranger, Aude-Marie Savoye, Lise Bosquet, Isabelle Ray-Coquard, Matthieu Carton, Oliver Colomban, Benoit You, Manuel Rodrigues\",\"doi\":\"10.1136/ijgc-2024-005815\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Treatment of high-grade serous ovarian carcinomas relies on surgery and chemotherapy, potentially followed by bevacizumab and/or poly (ADP-ribose) polymerase inhibitors (PARPi). The modeled CA-125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor primary chemosensitivity. Although it is well established that <i>BRCA</i> mutations are associated with platinum sensitivity, the relationship between <i>BRCA</i> status and KELIM score has yet to be elucidated. This study aimed to evaluate the interactions between <i>BRCA</i> and KELIM, and their respective prognostic values.</p><p><strong>Methods: </strong>We retrospectively collected data from 743 patients with high-grade serous ovarian carcinomas included in a French nationwide registry (NCT03275298) treated with neoadjuvant platinum-based chemotherapy followed by surgery. We analyzed the interactions between <i>BRCA</i> and KELIM, and their impacts on progression-free survival and overall survival.</p><p><strong>Results: </strong><i>BRCA</i>-mutated <i>(BRCA</i>m) patients had higher standardized KELIM than <i>BRCA</i>-wild type (<i>BRCA</i>wt) tumors (median 1.16 vs 1.06, respectively; p=0.001). The prognostic value of the KELIM score was independent of <i>BRCA</i> in multivariate analyses. KELIM score and <i>BRCA</i> could be combined to define three prognostic groups: (1) an unfavorable prognostic group with both <i>BRCA</i>wt and unfavorable KELIM (median progression-free survival 12.0 months); (2) an intermediate prognostic group with either <i>BRCA</i>m and unfavorable KELIM, or <i>BRCA</i>wt and favorable KELIM (median progression-free survival of 16.0 and 18.8 months, respectively; HR 0.64 compared with the unfavorable group, p<0.001); and (3) a favorable prognostic group with both <i>BRCA</i>m and favorable KELIM (median progression-free survival 28.8 months; HR 0.37 compared with the unfavorable group, p<0.001).</p><p><strong>Conclusions: </strong>The KELIM score provides complementary prognostic information with respect to <i>BRCA,</i> and discriminates different prognoses within <i>BRCA</i>m or <i>BRCA</i>wt patients. Patients with both <i>BRCA</i>wt/unfavorable KELIM have a poor prognosis, underscoring the urgent need for novel therapeutic strategies.</p>\",\"PeriodicalId\":14097,\"journal\":{\"name\":\"International Journal of Gynecological Cancer\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2024-10-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Gynecological Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/ijgc-2024-005815\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OBSTETRICS & GYNECOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Gynecological Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/ijgc-2024-005815","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
Tumor-intrinsic chemosensitivity assessed by KELIM and prognosis by BRCA status in patients with advanced ovarian carcinomas.
Objective: Treatment of high-grade serous ovarian carcinomas relies on surgery and chemotherapy, potentially followed by bevacizumab and/or poly (ADP-ribose) polymerase inhibitors (PARPi). The modeled CA-125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor primary chemosensitivity. Although it is well established that BRCA mutations are associated with platinum sensitivity, the relationship between BRCA status and KELIM score has yet to be elucidated. This study aimed to evaluate the interactions between BRCA and KELIM, and their respective prognostic values.
Methods: We retrospectively collected data from 743 patients with high-grade serous ovarian carcinomas included in a French nationwide registry (NCT03275298) treated with neoadjuvant platinum-based chemotherapy followed by surgery. We analyzed the interactions between BRCA and KELIM, and their impacts on progression-free survival and overall survival.
Results: BRCA-mutated (BRCAm) patients had higher standardized KELIM than BRCA-wild type (BRCAwt) tumors (median 1.16 vs 1.06, respectively; p=0.001). The prognostic value of the KELIM score was independent of BRCA in multivariate analyses. KELIM score and BRCA could be combined to define three prognostic groups: (1) an unfavorable prognostic group with both BRCAwt and unfavorable KELIM (median progression-free survival 12.0 months); (2) an intermediate prognostic group with either BRCAm and unfavorable KELIM, or BRCAwt and favorable KELIM (median progression-free survival of 16.0 and 18.8 months, respectively; HR 0.64 compared with the unfavorable group, p<0.001); and (3) a favorable prognostic group with both BRCAm and favorable KELIM (median progression-free survival 28.8 months; HR 0.37 compared with the unfavorable group, p<0.001).
Conclusions: The KELIM score provides complementary prognostic information with respect to BRCA, and discriminates different prognoses within BRCAm or BRCAwt patients. Patients with both BRCAwt/unfavorable KELIM have a poor prognosis, underscoring the urgent need for novel therapeutic strategies.
期刊介绍：
The International Journal of Gynecological Cancer, the official journal of the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology, is the primary educational and informational publication for topics relevant to detection, prevention, diagnosis, and treatment of gynecologic malignancies. IJGC emphasizes a multidisciplinary approach, and includes original research, reviews, and video articles. The audience consists of gynecologists, medical oncologists, radiation oncologists, radiologists, pathologists, and research scientists with a special interest in gynecological oncology.
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