Evidence map›Paper›PMID 35110358›Full record

ArticleJournal for immunotherapy of cancer2022

Ascites and resistance to immune checkpoint inhibition in dMMR/MSI-H metastatic colorectal and gastric cancers.

Giovanni Fucà, Romain Cohen, Sara Lonardi, Kohei Shitara, Maria Elena Elez, Marwan Fakih, Joseph Chao, Samuel J Klempner, Matthew Emmett, Priya Jayachandran and 21 more

Open access · goldAbstract readMulticenter Study
In one paragraph

Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 3 pooled it
10.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

74 citing papers in PubMed, 3 syntheses or guidelines pooled it, 110 citations in OpenAlex.

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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors at 15 institutions in 5 countries.

Giovanni FucàDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.ORCID 0000-0002-1560-2253
Romain CohenSorbonne Université, Department of Medical Oncology, Hôpital Saint-Antoine, AP-HP 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.ORCID 0000-0001-9602-5162
Sara LonardiMedical Oncology 3 and Medical Oncology 1, Istituto Oncologico Veneto IOV-IRCSS, Padua, Italy.ORCID 0000-0002-7593-8138
Kohei ShitaraDepartment of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Maria Elena ElezDepartment of Medical Oncology, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VHIO), Universitat Autonoma de Barcelona, Barcelona, Spain.
Marwan FakihDepartment of Medical Oncology and Therapeutic Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Joseph ChaoDepartment of Medical Oncology and Therapeutic Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA.ORCID 0000-0002-1809-504X
Samuel J KlempnerMass General Cancer Center and Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Matthew EmmettMass General Cancer Center and Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Priya JayachandranDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Francesca BergamoMedical Oncology 1, Istituto Oncologico Veneto IOV-IRCSS, Padua, Italy.
Marc Díez GarcíaDepartment of Medical Oncology, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology (VHIO), Universitat Autonoma de Barcelona, Barcelona, Spain.
Giacomo MazzoliDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Leonardo ProvenzanoDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Raphael ColleSorbonne Université, Department of Medical Oncology, Hôpital Saint-Antoine, AP-HP 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.
Magali SvrcekSorbonne Université, Department of Pathology, Hôpital Saint-Antoine, AP-HP, 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.
Margherita AmbrosiniDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Giovanni RandonDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Aakash Tushar ShahBaylor College of Medicine, Houston, Texas, USA.
Massimiliano SalatiDivision of Oncology, Department of Oncology and Hematology, University Hospital of Modena, PhD Clinical and Experimental Medicine (CEM), University of Modena and Reggio Emilia, Modena, Italy.
Elisabetta FenocchioMultidisciplinary Outpatient Oncology Clinic, Candiolo Cancer Institute FPO-IRCCS, Candiolo, Italy.
Lisa SalvatoreDepartment of Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Keigo ChidaDepartment of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Akihito KawazoeDepartment of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Veronica ConcaUnit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Giuseppe CuriglianoEuropean Institute of Oncology (IEO), IRCCS, Milan, Italy.
Francesca CortiDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Chiara CremoliniUnit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Michael OvermanDepartment of Gastrointestinal Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Thierry AndreSorbonne Université, Department of Medical Oncology, Hôpital Saint-Antoine, AP-HP 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.ORCID 0000-0002-5103-7095
Filippo PietrantonioDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy filippo.pietrantonio@istitutotumori.mi.it.ORCID 0000-0002-8530-8420
Tumori Foundation · USInserm · FRNational Cancer Center Hospital East · JPCity of Hope · USHarvard University · USIstituto Oncologico Veneto · ITUniversitat Autònoma de Barcelona · ESUniversity of Pisa · ITAgostino Gemelli University Polyclinic · ITBaylor College of Medicine · USCandiolo Cancer Institute · ITThe University of Texas MD Anderson Cancer Center · USUniversity of Milan · ITUniversity of Modena and Reggio Emilia · ITUniversity of Southern California · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDespite 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.

methodsWe 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.

resultsThe 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.

conclusionsPatients 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.

Indexed as

AgedAscitesColorectal NeoplasmsFemaleHumansImmune Checkpoint InhibitorsMaleMicrosatellite InstabilityNeoplasm MetastasisRetrospective StudiesStomach NeoplasmsSurvival AnalysisImmune Checkpoint Inhibitorsgastrointestinal neoplasmsimmunotherapytranslational medical researchtumor biomarkers

Identifiers

PMID35110358
PMCPMC8811606
OpenAlexW4210300714

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.