ArticleCancer discovery2018
Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Cancer discovery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01191697 (Phase II Trial of CAPOX, Bevacizumab and Trastuzumab for Patients With HER2-Positive Metastatic Esophagogastric Cancer), which is not on this map. Cited by 186 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
186citing papers in PubMed, 1 pooled it
10.4field-weighted citation impact, top 1% of its field
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.
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.
Phase II Trial of CAPOX, Bevacizumab and Trastuzumab for Patients With HER2-Positive Metastatic Esophagogastric Cancer
Who cites it
186 citing papers in PubMed, 1 synthesis or guideline pooled it, 297 citations in OpenAlex.
- Chinese guidelines for HER2-targeted therapy in gastric and gastroesophageal junction adenocarcinoma (2025 Edition).Journal of hematology & oncology · 2026Guideline
- Clinical outcomes and ctDNA correlates for CAPOX BETR: a phase II trial of capecitabine, oxaliplatin, bevacizumab, trastuzumab in previously untreated advanced HER2+ gastroesophageal adenocarcinoma.Nature communications · 2024Trial
- Cytoreduction and HIPEC for Gastric Carcinomatosis: Multi-institutional Analysis of Two Phase II Clinical Trials.Annals of surgical oncology · 2023Trial
- Trastuzumab with trimodality treatment for oesophageal adenocarcinoma with HER2 overexpression (NRG Oncology/RTOG 1010): a multicentre, randomised, phase 3 trial.The Lancet. Oncology · 2022Trial
- Trial
- Personalized Antibodies for Gastroesophageal Adenocarcinoma (PANGEA): A Phase II Study Evaluating an Individualized Treatment Strategy for Metastatic Disease.Cancer discovery · 2021Trial
- Use of Gefitinib in EGFR-Amplified Refractory Solid Tumors: An Open-Label, Single-Arm, Single-Center Prospective Pilot Study.Targeted oncology · 2020Trial
- Efficacy of Combined VEGFR1-3, PDGFα/β, and FGFR1-3 Blockade Using Nintedanib for Esophagogastric Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- Initial Report of Second-Line FOLFIRI in Combination with Ramucirumab in Advanced Gastroesophageal Adenocarcinomas: A Multi-Institutional Retrospective Analysis.The oncologist · 2019Trial
- Trial
- Navigating Antibody-Drug Conjugate Sequencing in Gastric Cancer: Cross-Resistance Biology, Target Switching, and Decision-Making Frameworks for the Post-Progression Landscape.Current oncology reports · 2026Review
- Claudin 18.2 expression-concordance between primary and metastatic lesions in gastric and gastroesophageal adenocarcinomas: a systematic review and meta-analysis.ESMO gastrointestinal oncology · 2026Review
- Intratumoral heterogeneity of intermediate CLDN18.2 expression in gastric cancer.International journal of clinical oncology · 2026Article
- Spectral CT-based Nomogram for Noninvasive Assessment and Prognostic Prediction of MSI/dMMR in Esophagogastric Junction Adenocarcinoma.Radiology. Imaging cancer · 2026Article
- Dynamic HER2 reassessment and precision sequencing after trastuzumab in HER2-positive advanced gastric cancer.ESMO gastrointestinal oncology · 2026Review
- CAR-T and TIL therapies in solid tumors: barriers, clinical lessons, and convergent solutions.Cancer cell international · 2026Review
- Impact of Anatomical Site on RNA-Based Molecular Subtypes in Paired High-Grade Serous Ovarian Carcinoma Samples.Cancers · 2026Article
- MYC amplification is common in cancer of the stomach and gastroesophageal junction, correlates with male sex and reduced response to neoadjuvant therapy.BMC cancer · 2026Article
- AXL-SHC1 signaling axis mediates adaptive resistance to HER2-targeted tyrosine kinase inhibitors in HER2-aberrant lung and gastric cancers.NPJ precision oncology · 2026Article
- Diagnostic and Therapeutic Challenges Related to HER2 Heterogeneity in Gastric Cancer: Bridging Molecular Pathology and Clinical Decision-Making.International journal of molecular sciences · 2026Review
126 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
57 authors at 12 institutions in 4 countries.
Eirini Pectasides *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Matthew D Stachler *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Sarah Derks *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Yang Liu *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Steven Maron *Department of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Mirazul IslamDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Lindsay AlpertDepartment of Pathology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Heewon KwakDepartment of Pathology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Hedy KindlerDepartment of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Blase PoliteDepartment of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Manish R SharmaDepartment of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Kenisha AllenDepartment of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Emily O'DayDepartment of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Samantha LomnickiDepartment of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Melissa MarantoDepartment of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Rajani KantetiDepartment of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Carrie FitzpatrickDepartment of Pathology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Christopher WeberDepartment of Pathology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Namrata SetiaDepartment of Pathology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Shu-Yuan XiaoDepartment of Pathology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
John HartDepartment of Pathology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Rebecca J NagyGuardant Health, Inc., Redwood City, California.
Kyoung-Mee KimDepartment of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Min-Gew ChoiDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Byung-Hoon MinDepartment of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Katie S NasonUniversity of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
Lea O'KeefeUniversity of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
Masayuki WatanabeGastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Hideo BabaDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Rick LanmanGuardant Health, Inc., Redwood City, California.
Agoston T AgostonDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
David J OhUniversity of New England College of Osteopathic Medicine, Biddeford, Maine.
Andrew DunfordEli and Edythe L. Broad Institute, Cambridge, Massachusetts.
Aaron R ThornerCenter for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts.
Matthew D DucarCenter for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts.
Bruce M WollisonCenter for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts.
Haley A ColemanCenter for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts.
Yuan JiDepartment of Public Health Sciences, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Mitchell C PosnerDepartment of Surgery, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Kevin RogginDepartment of Surgery, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Kiran TuragaDepartment of Surgery, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Paul ChangDepartment of Radiology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Kyle HogarthDepartment of Medicine, Section of Pulmonary and Critical Care, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Uzma SiddiquiDepartment of Medicine, Section of Gastroenterology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Andres GelrudDepartment of Medicine, Section of Gastroenterology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
Gavin HaEli and Edythe L. Broad Institute, Cambridge, Massachusetts.
Samuel S FreemanEli and Edythe L. Broad Institute, Cambridge, Massachusetts.
Justin RhoadesEli and Edythe L. Broad Institute, Cambridge, Massachusetts.
Sarah ReedEli and Edythe L. Broad Institute, Cambridge, Massachusetts.
Greg GydushEli and Edythe L. Broad Institute, Cambridge, Massachusetts.
Denisse RotemEli and Edythe L. Broad Institute, Cambridge, Massachusetts.
Jon DavisonUniversity of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
Yu ImamuraGastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Viktor AdalsteinssonEli and Edythe L. Broad Institute, Cambridge, Massachusetts.
Jeeyun LeeDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Adam J Bass *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Adam_bass@dfci.harvard.edu dcatenac@bsd.uchicago.edu.
Daniel V Catenacci *Department of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois. Adam_bass@dfci.harvard.edu dcatenac@bsd.uchicago.edu.
University of Chicago Medical Center · USBroad Institute · USDana-Farber Cancer Institute · USSamsung Medical Center · KRUPMC Hillman Cancer Center · USBrigham and Women's Hospital · USGuardant (United States) · USJapanese Foundation For Cancer Research · JPBeth Israel Deaconess Medical Center · USChicago Department of Public Health · USKumamoto University · JPUniversity of New England · US
Funding
VIRAL ONCOLOGY CORE FACILITYP30CA014599 · NCI · UNIVERSITY OF CHICAGO · PI MARK W. LINGEN · 1985 to 2026
$122.1MTissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI EL-BARDEESY, NABEEL, SELLERS, WILLIAM R · 2007 to 2023
$33.2MTransformed Esophageal Epithelial Cells and the Tumor MicroenvironmentP01CA098101 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RUSTGI, ANIL K · 2003 to 2023
$31.7MTRAINING GRANT IN GENETICST32GM007748 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Anne O'Donnell-Luria, Louise Wilkins-Haug · 1985 to 2026
$12.0MHarvard Clinical and Translational Science CenterKL2TR001100 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$8.5MTherapeutic targeting of Fibroblast Growth Factor Receptors in Squamous CancersR01CA196932 · NCI · DANA-FARBER CANCER INST · PI BASS, ADAM JOEL · 2015 to 2019
$1.9MEarly TP53 Mutations and Genomic Doubling as a Novel Path for Barrett's Esophagus ProgressionK08DK109209 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STACHLER, MATTHEW D · 2016 to 2021
$929kPANGEA: Personalized Antibodies for GastroEsophageal Adenocarcinoma Pilot TrialK23CA178203 · NCI · UNIVERSITY OF CHICAGO · PI CATENACCI, DANIEL · 2014 to 2016
$507kNCATS NIH HHS KL2 TR001100NCI NIH HHS K23 CA178203NCI NIH HHS P01 CA098101NCI NIH HHS P30 CA014599NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA196932NIDDK NIH HHS K08 DK109209NIGMS NIH HHS T32 GM007748
Abstract
Gastroesophageal adenocarcinoma (GEA) is a lethal disease where targeted therapies, even when guided by genomic biomarkers, have had limited efficacy. A potential reason for the failure of such therapies is that genomic profiling results could commonly differ between the primary and metastatic tumors. To evaluate genomic heterogeneity, we sequenced paired primary GEA and synchronous metastatic lesions across multiple cohorts, finding extensive differences in genomic alterations, including discrepancies in potentially clinically relevant alterations. Multiregion sequencing showed significant discrepancy within the primary tumor (PT) and between the PT and disseminated disease, with oncogene amplification profiles commonly discordant. In addition, a pilot analysis of cell-free DNA (cfDNA) sequencing demonstrated the feasibility of detecting genomic amplifications not detected in PT sampling. Lastly, we profiled paired primary tumors, metastatic tumors, and cfDNA from patients enrolled in the personalized antibodies for GEA (PANGEA) trial of targeted therapies in GEA and found that genomic biomarkers were recurrently discrepant between the PT and untreated metastases. Divergent primary and metastatic tissue profiling led to treatment reassignment in 32% (9/28) of patients. In discordant primary and metastatic lesions, we found 87.5% concordance for targetable alterations in metastatic tissue and cfDNA, suggesting the potential for cfDNA profiling to enhance selection of therapy.
Indexed as
Precision MedicineAdenocarcinomaCohort StudiesEsophageal NeoplasmsExome SequencingGenomicsHumansStomach Neoplasms
Identifiers
What OpenQuestion holds
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Read underepoch 390
Registered trials
NCT01191697ClinicalTrials.gov
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.