Homologous recombination deficiency as prognostic marker in metastatic gastric cancer.
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Le résumé fourni par la source
4040 Background: Gastric cancer is the 5th cancer diagnosis and 3rd cause of cancer death worldwide. Metastatic gastric cancer (mGC) has a median survival of 11 months. mGC is an heterogeneous disease and different biologic characteristics may justify differential therapeutic opportunities. Tumors with homologous recombination (HR) deficiency may benefit with treatment with PARP inhibitors or immune checkpoint inhibitors. The purpose of this study was to evaluate the prevalence and prognostic impact of altered expression of HR proteins as surrogates for homologous recombination deficiency (HRD) in mGC. Methods: Multicenter retrospective cohort of mGC treated with platinum-based chemotherapy. HRD defined as absence of at least one of the following proteins: ATM, ATR, CHK2, RAD51, RAD52, BRCA1, BRCA2, MRE11 by immunohistochemistry. Survival time calculated as the difference between first cycle of platinum-based chemotherapy and death or last observation. Association between HRD and survival examined with log-rank test. Results: 440 patients included, of which 70% male, with mean age of 58 years (SD: 11). 75% of patients had mGC at diagnosis, 43% had 2 or more organs involved and 63% were registered as ECOG 0 or 1 at the start of first line chemotherapy. The most common histologic subtype was tubular adenocarcinoma (44%) followed by diffuse carcinoma (32%). HRD was noted in 196 (45%) cases (95%CI: 40%-49%). The most commonly altered proteins were ATM (21%) and BRCA2 (18%). In HRD tumors, 99 (51%) had altered expression of only one HR protein; 47 (24%) had altered expression of two HR proteins; the remaining cases had altered expression of 3 or more proteins. After a median follow up of 11 months, median survival for the cohort was 11 months (95% CI 9-12). HRD was associated with an improved survival, HR = 0.61 (95%CI: 0.48-0.78, p < 0.001), that remained significant after adjustment for sex, age, performance status and disease status (HR = 0.63; 95%CI: 0.48-0.82; p < 0.001). Conclusions: HRD phenotype was present in 45% of mGC cases and is associated with improved prognosis for mGC treated with platinum-based first line chemotherapy.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Homologous recombination deficiency as prognostic marker in metastatic gastric cancer.
- Date Crossref
- 20/05/2019
- Éditeur
- American Society of Clinical Oncology (ASCO)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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IPO Porto pays non établi dans la noticeÉtablissement de santé
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Hospital de São João pays non établi dans la noticeÉtablissement de santé
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Hospital da Senhora da Oliveira Guimarães pays non établi dans la noticeÉtablissement de santé
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Centro Hospitalar de Vila Nova de Gaia pays non établi dans la noticeÉtablissement de santé
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Universidade do Porto CINTESIS–Center for Health Technology and Services Research pays non établi dans la noticeUniversité ou école supérieure
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Centre for Health Technology and Services Research pays non établi dans la noticeStructure de recherche
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Centro Hospitalar Universitário São João pays non établi dans la noticeÉtablissement de santé
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Instituto Português de Oncologia de Lisboa Francisco Gentil pays non établi dans la noticeStructure de recherche
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Hospital de Senhora da Oliveira pays non établi dans la noticeÉtablissement de santé
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Institute of Molecular Pathology and Immunology of the University of Porto pays non établi dans la noticeUniversité ou école supérieure
IPO Porto, Hospital de São João et Hospital da Senhora da Oliveira Guimarães, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.