Evidence map›Paper›PMID 23045248›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012

Mutation profiling and microsatellite instability in stage II and III colon cancer: an assessment of their prognostic and oxaliplatin predictive value.

Patrick G Gavin, Linda H Colangelo, Debora Fumagalli, Noriko Tanaka, Matthew Y Remillard, Greg Yothers, Chungyeul Kim, Yusuke Taniyama, Seung Il Kim, Hyun Joo Choi and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers, 15 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
166citing papers in PubMed, 15 pooled it
11.8field-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

166 citing papers in PubMed, 15 syntheses or guidelines pooled it, 313 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Guideline
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Pooled it
  11. Pooled it
  12. Guideline
  13. Molecular Biomarkers for the Evaluation of Colorectal Cancer.American journal of clinical pathology · 2017
    Guideline
  14. Prognostic role of tumor PIK3CA mutation in colorectal cancer: a systematic review and meta-analysis.Annals of oncology : official journal of the European Society for Medical Oncology · 2016
    Pooled it
  15. Pooled it
  16. Trial
  17. Trial
  18. Trial
  19. Trial
  20. Trial

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 1 country.

Patrick G GavinNational Surgical Adjuvant Breast and Bowel Project, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15212, USA.
Linda H Colangelo
Debora Fumagalli
Noriko Tanaka
Matthew Y Remillard
Greg Yothers
Chungyeul Kim
Yusuke Taniyama
Seung Il Kim
Hyun Joo Choi
Nicole L Blackmon
Corey Lipchik
Nicholas J Petrelli
Michael J O'Connell
Norman Wolmark
Soonmyung Paik
Kay L Pogue-Geile
Allegheny General Hospital · USChristiana Care Health System · USNSABP Foundation · USUniversity of Pittsburgh · US

Funding

PRIMARY CANCER THERAPY GROUP--NSABP (HEADQUARTERS)U10CA012027 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WOLMARK, NORMAN · 1985 to 2012
$117.2M
NSABP Foreign AccrualsU10CA037377 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WOLMARK, NORMAN · 1985 to 2014
$116.5M
STUDY TO ASSESS RALOXIFENE FOR PREVENTING BREAST CANCERU10CA069974 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI COSTANTINO, JOSEPH P. · 1995 to 2013
$62.4M
PRIMARY BREAST CANCER THERAPY--BIOSTATISTICS CENTERU10CA069651 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI COSTANTINO, JOSEPH P. · 1995 to 2012
$52.1M
NSABP Biological Specimen BanksU24CA114732 · NCI · NSABP FOUNDATION, INC. · PI WOLMARK, NORMAN · 2005 to 2014
$9.4M
NCI NIH HHS U10 CA012027NCI NIH HHS U10 CA037377NCI NIH HHS U10 CA069651NCI NIH HHS U10 CA069974NCI NIH HHS U10-CA-12027NCI NIH HHS U10-CA-37377NCI NIH HHS U10-CA-69651NCI NIH HHS U10-CA-69974NCI NIH HHS U24 CA114732NCI NIH HHS U24-CA-114732
6 · The paper itself

Abstract

purposeThe purpose of this study was to examine the prognostic and oxaliplatin predictive value of mismatch repair (MMR) status and common hot spot mutations, which we previously identified in stage II and III colon cancer. EXPERIMENTAL

designMutations in BRAF, KRAS, NRAS, MET, and PIK3CA were profiled in 2,299 stage II and III colon tumors from National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trials C-07 (n = 1,836) and C-08 (n = 463) with Type Plex chemistry and mass spectrometry. C-07 tested the worth of adding oxaliplatin to 5-fluorouracil plus leucovorin, and C-08 tested the worth of adding bevacizumab to FOLFOX. Cox proportional hazard models were used to assess prognostic or oxaliplatin predictive value of mutations for tumor recurrence, overall survival (OS), and survival after recurrence (SAR).

resultsBRAF mutations were associated with MMR-deficient tumors (P < 0.0001), poor OS [HR, 1.46; 95% confidence interval (CI), 1.20-1.79; P ≤ 0.0002], and poor SAR (HR, 2.31; 95% CI, 1.83-2.95; P < 0.0001). Mutations in KRAS, NRAS, MET, and PIK3CA were not associated with recurrence, OS, or SAR. MMR-deficient tumors were associated with an improved prognosis based on recurrence (HR, 0.48; 95% CI, 0.33-0.70; P < 0.0001). Mutations and MMR status were not predictive for oxaliplatin benefit.

conclusionsThis study shows that BRAF mutations profiled from stage II and III colon cancer tumors were associated with poor SAR and validates and explains, at least in part, previous observations associating it with poor OS. Profiling of all of these mutations is warranted for future clinical trials testing new targeted therapies that block relevant signaling pathways. Such clinical trials are under development at NSABP.

Indexed as

Microsatellite InstabilityMutationAntineoplastic AgentsColonic NeoplasmsDNA Mismatch RepairHumansMutation RateNeoplasm StagingOrganoplatinum CompoundsOxaliplatinPrognosisProto-Oncogene Proteins B-rafTreatment OutcomeAntineoplastic AgentsOrganoplatinum CompoundsOxaliplatinProto-Oncogene Proteins B-raf

Identifiers

PMID23045248
PMCPMC4273673
OpenAlexW2111807726

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.