Evidence map›Paper›PMID 26416897›Full record

Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2015

Variations in genes regulating tumor-associated macrophages (TAMs) to predict outcomes of bevacizumab-based treatment in patients with metastatic colorectal cancer: results from TRIBE and FIRE3 trials.

Y Sunakawa, S Stintzing, S Cao, V Heinemann, C Cremolini, A Falcone, D Yang, W Zhang, Y Ning, S Stremitzer and 10 more

2 registry-linked trialsOpen access · greenAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
1.3field-weighted citation impact, top 17% 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.

NCT00433927 phase3unknown statusnot on this map

Multicenter Randomized Trial Evaluating FOLFIRI Plus Cetuximab Versus FOLFIRI Plus Bevacizumab in First Line Treatment of Metastatic Colorectal Cancer.

TypeinterventionalSponsorPD Dr. med. Volker HeinemannRan2007 to 2016Enrolled568ConditionsNeoplasm Metastasis, Colorectal CancerArms5-FU, folinic acid, irinotecan, cetuximab, bevacizumab
NCT00719797 phase3completednot on this map

A phase iii randomized trial of folfoxiri + bevacizumab versus folfiri + bevacizumab as first- line treatment for metastatic colorectal cancer

TypeinterventionalSponsorGruppo Oncologico del Nord-OvestRan2008Enrolled509ConditionsColorectal CancerArmsbevacizumab, fluorouracil, irinotecan hydrochloride, leucovorin calcium, oxaliplatin
3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 54 citations in OpenAlex.

  1. Trial
  2. TargetingJournal for immunotherapy of cancer · 2026
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  3. [ERI3 expression is elevated in hepatocellular carcinoma and correlates with poor patient prognosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026
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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

20 authors at 3 institutions in 4 countries.

Y SunakawaDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA Division of Medical Oncology, Department of Internal Medicine, Showa University Northern Yokohama Hospital, Yokohama, Japan y.suna0825@gmail.com.
S StintzingDepartment of Hematology and Oncology, Klinikum der Universität München, Munich, Germany.
S CaoDepartment of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
V HeinemannDepartment of Hematology and Oncology, Klinikum der Universität München, Munich, Germany.
C CremoliniU.O. Oncologia Medica, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy.
A FalconeU.O. Oncologia Medica, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy.
D YangDepartment of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
W ZhangDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Y NingDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
S StremitzerDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
S MatsusakaDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
S YamauchiDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
A ParekhDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
S OkazakiDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
M D BergerDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
S GraverDepartment of Physiological Chemistry, Biocenter, University of Wuerzburg, Wuerzburg, Germany.
A MendezDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
S J SchererDepartment of Physiological Chemistry, Biocenter, University of Wuerzburg, Wuerzburg, Germany.
F LoupakisU.O. Oncologia Medica, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy.
H-J LenzDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
University of Southern California · USAzienda Ospedaliera Universitaria Pisana · ITUniversity of Würzburg · DE

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
Efficacy of Novel Wnt Modulator in Colon CancerR01CA166161 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KAHN, MICHAEL, LENZ, HEINZ JOSEF · 2013 to 2017
$2.3M
NCI NIH HHS P30 CA014089NCI NIH HHS P30CA14089-27S1NCI NIH HHS R01 CA166161
6 · The paper itself

Abstract

backgroundTumor-associated macrophages (TAMs) with the M2-like phenotype are regulated by mainly NF-kB pathway including TBK1, which can influence tumor progression by secretion of proangiogenic factors such as vascular endothelial growth factor. The CCL2/CCR2 axis, histidine-rich glycoprotein (HRG), and placenta growth factor (PIGF) play a critical role in the polarization of M1/M2 phenotypes and the recruitment of TAMs to tumor microenvironment. We therefore hypothesized that variations in genes involved in regulating TAMs may predict clinical outcomes of bevacizumab treatment in patients with metastatic colorectal cancer (mCRC). PATIENTS AND

methodsWe analyzed genomic DNA extracted from samples of patients receiving bevacizumab plus FOLFIRI as a first-line treatment using PCR-based direct sequencing. Twelve functional single-nucleotide polymorphisms in eight genes (CCL2, CCR2, HRG, PIGF, NFKB1, TBK1, CCL18, and IRF3) were tested for associations with clinical outcomes in a discovery cohort of 228 participants in TRIBE trial (NCT00719797), then validated in 248 KRAS exon2 (KRAS) wild-type participants in FIRE3 trial (NCT00433927). FIRE3-cetuximab cohort served as a negative control.

resultsTBK1 rs7486100 was significantly associated with overall survival in 95 KRAS wild-type patients of TRIBE cohort in univariate analysis and had a strong trend in multivariable analysis; furthermore, the association of the T allele was observed for progression-free survival (PFS) in both univariate and multivariable analyses in FIRE3-bevacizumab but not cetuximab cohort. CCL2 rs4586, CCL18 rs14304, and IRF3 rs2304205 had univariate and multivariable correlations with PFS in KRAS mutant patients of the TRIBE cohort, whereas they had no correlations in KRAS wild-type patients of the TRIBE cohort. No association was seen in control cohort.

conclusionsOur study demonstrates for the first time that variations in genes regulating TAMs-related functions are significantly associated with clinical outcomes in mCRC patients treated with bevacizumab-containing chemotherapy. These results also suggest that some TAM-related gene variations may predict outcomes of bevacizumab treatment in KRAS status-dependent manner.

Indexed as

AdultAgedBevacizumabBiomarkers, TumorCohort StudiesColorectal NeoplasmsFemaleGenetic VariationHumansMacrophagesMaleMiddle AgedPredictive Value of TestsRetrospective StudiesTreatment OutcomeBevacizumabBiomarkers, Tumorcolorectal cancerKRASpolymorphismTBK1tumor-associated macrophage

Identifiers

PMID26416897
PMCPMC4658546
OpenAlexW2252567929

What OpenQuestion holds

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Registered trials

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.