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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorFucà, Giovanni
dc.contributor.authorCohen, Romain
dc.contributor.authorLonardi, Sara
dc.contributor.authorShitara, Kohei
dc.contributor.authorElez Fernandez, Mª Elena
dc.contributor.authorFakih, Marwan
dc.contributor.authorDiez Garcia, Marc
dc.date.accessioned2022-08-10T11:39:02Z
dc.date.available2022-08-10T11:39:02Z
dc.date.issued2022-02
dc.identifier.citationFucà G, Cohen R, Lonardi S, Shitara K, Elez ME, Fakih M, et al. Ascites and resistance to immune checkpoint inhibition in dMMR/MSI-H metastatic colorectal and gastric cancers. J Immunother Cancer. 2022 Feb;10(2):e004001.
dc.identifier.issn2051-1426
dc.identifier.urihttp://hdl.handle.net/11351/7983
dc.descriptionGastrointestinal neoplasms; Immunotherapy; Tumor biomarkers
dc.description.abstractBackground Despite unprecedented benefit from immune checkpoint inhibitors (ICIs) in patients with mismatch repair deficient (dMMR)/microsatellite instability high (MSI-H) advanced gastrointestinal cancers, a relevant proportion of patients shows primary resistance or short-term disease control. Since malignant effusions represent an immune-suppressed niche, we investigated whether peritoneal involvement with or without ascites is a poor prognostic factor in patients with dMMR/MSI-H metastatic colorectal cancer (mCRC) and gastric cancer (mGC) receiving ICIs. Methods We conducted a global multicohort study at Tertiary Cancer Centers and collected clinic-pathological data from a cohort of patients with dMMR/MSI-H mCRC treated with anti-PD-(L)1 ±anti-CTLA-4 agents at 12 institutions (developing set). A cohort of patients with dMMR/MSI-high mGC treated with anti-PD-1 agents±chemotherapy at five institutions was used as validating dataset. Results The mCRC cohort included 502 patients. After a median follow-up of 31.2 months, patients without peritoneal metastases and those with peritoneal metastases and no ascites had similar outcomes (adjusted HR (aHR) 1.15, 95% CI 0.85 to 1.56 for progression-free survival (PFS); aHR 0.96, 95% CI 0.65 to 1.42 for overall survival (OS)), whereas inferior outcomes were observed in patients with peritoneal metastases and ascites (aHR 2.90, 95% CI 1.70 to 4.94; aHR 3.33, 95% CI 1.88 to 5.91) compared with patients without peritoneal involvement. The mGC cohort included 59 patients. After a median follow-up of 17.4 months, inferior PFS and OS were reported in patients with peritoneal metastases and ascites (aHR 3.83, 95% CI 1.68 to 8.72; aHR 3.44, 95% CI 1.39 to 8.53, respectively), but not in patients with only peritoneal metastases (aHR 1.87, 95% CI 0.64 to 5.46; aHR 2.15, 95% CI 0.64 to 7.27) when compared with patients without peritoneal involvement. Conclusions Patients with dMMR/MSI-H gastrointestinal cancers with peritoneal metastases and ascites should be considered as a peculiar subgroup with highly unfavorable outcomes to current ICI-based therapies. Novel strategies to target the immune-suppressive niche in malignant effusions should be investigated, as well as next-generation ICIs or intraperitoneal approaches.
dc.language.isoeng
dc.publisherBMJ
dc.relation.ispartofseriesJournal for ImmunoTherapy of Cancer;10(12)
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceScientia
dc.subjectCòlon - Càncer - Tractament
dc.subjectRecte - Càncer - Tractament
dc.subjectAscites
dc.subject.meshAntineoplastic Agents
dc.subject.meshColorectal Neoplasms
dc.subject.mesh/drug therapy
dc.subject.meshAscites
dc.titleAscites and resistance to immune checkpoint inhibition in dMMR/MSI-H metastatic colorectal and gastric cancers
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1136/jitc-2021-004001
dc.subject.decsantineoplásicos
dc.subject.decsneoplasias colorrectales
dc.subject.decs/farmacoterapia
dc.subject.decsascitis
dc.relation.publishversionhttp://dx.doi.org/10.1136/jitc-2021-004001
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Fucà G] Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Cohen R] Sorbonne Université, Department of Medical Oncology, Hôpital Saint-Antoine, APHP and INSERM, Unité Mixte de Recherche Scientifique 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France. [Lonardi S] Medical Oncology 3 Medical Oncology 1, Istituto Oncologico Veneto IOV-IRCSS, Padua, Italy. [Shitara K] Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. [Elez ME, Díez García M] Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Fakih M] Department of Medical Oncology and Therapeutic Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA
dc.identifier.pmid35110358
dc.identifier.wos000758164800002
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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