Evidence map›Paper›PMID 30197261›Full record

ArticleClinical lung cancer2018

First-line Chemotherapy Responsiveness and Patterns of Metastatic Spread Identify Clinical Syndromes Present Within Advanced KRAS Mutant Non-Small-cell Lung Cancer With Different Prognostic Significance.

Wade T Iams, Hui Yu, Yu Shyr, Tejas Patil, Leora Horn, Caroline McCoach, Karen Kelly, Robert C Doebele, D Ross Camidge

Abstract readMulticenter Study
In one paragraph

Article in Clinical lung cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
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

9 authors.

Wade T IamsDivision of Hematology/Oncology, Department of Medicine, Northwestern University, Chicago, IL.
Hui YuDepartment of Internal Medicine, University of New Mexico, Albuquerque, NM.
Yu ShyrDepartment of Statistics, Vanderbilt-Ingram Cancer Center, Nashville, TN.
Tejas PatilDivision of Medical Oncology, Department of Medicine, University of Colorado, Denver, CO.
Leora HornDivision of Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN.
Caroline McCoachDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA.
Karen KellyDepartment of Medical Oncology, University of California, Davis, Sacramento, CA.
Robert C DoebeleDivision of Medical Oncology, Department of Medicine, University of Colorado, Denver, CO.
D Ross CamidgeDivision of Medical Oncology, Department of Medicine, University of Colorado, Denver, CO. Electronic address: ross.camidge@ucdenver.edu.

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
Tissue Bank and Biomarkers CoreP50CA058187 · NCI · UNIVERSITY OF COLORADO DENVER · PI MILLER, YORK E · 1992 to 2018
$43.8M
Vanderbilt Clinical Oncology Research Career Development ProgramK12CA090625 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Debra L. Friedman, Paula Jill Hurley · 2001 to 2026
$16.9M
Paul Calabresi Clinical Oncology AwardK12CA088084 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI David S. Hong, Scott Kopetz · 2000 to 2026
$14.0M
NCI NIH HHS K12 CA088084NCI NIH HHS K12 CA090625NCI NIH HHS P30 CA068485NCI NIH HHS P50 CA058187
6 · The paper itself

Abstract

backgroundUnsuccessful KRAS-specific treatment approaches in non-small-cell lung cancer (NSCLC) might reflect underlying disease heterogeneity. We sought to define clinical "syndromes" within advanced KRAS mutant NSCLC to improve future clinical trials and create a clinical framework for future molecular development. PATIENTS AND

methodsTo test a series of a priori hypotheses regarding KRAS-mutant NSCLC clinical syndromes, we conducted a multi-institutional retrospective medical record review. Survival probabilities were estimated using the Kaplan-Meier model. Between-group differences were assessed using the log-rank test. Multivariate Cox regression analyses and Wilcoxon rank sum testing were used to assess progression-free survival and overall survival (OS) differences.

resultsAmong 218 patients with advanced KRAS-mutant NSCLC, OS and progression-free survival with first-line chemotherapy did not differ by intrathoracic versus extrathoracic spread, smoking intensity, or the specific KRAS mutation. Metastatic disease at diagnosis resulted in significantly worse OS than recurrent, unresectable disease (median OS, 14.6 vs. 40.9 months; P = .001). Among the patients with metastatic disease at diagnosis, nonscalp, soft tissue metastases (syndrome X; 6% of cases; 95% confidence interval [CI], 2.5%-10.1%) signified a poor prognosis (median OS, 7.5 vs. 15.9 months for the controls; P = .021). The response to first-line chemotherapy (syndrome Y; 41% of cases; 95% CI, 32.3%-50.6%) signified a good prognosis (median OS, 26.7 vs. 11.9 months; P = .002). The overlap between these 2 syndromes was minimal (2 of 111). Multivariate analysis confirmed these observations. The hazard ratio for death for syndromes X and Y was 2.64 (95% CI, 1.13-6.14) and 0.45 (95% CI, 0.28-0.76), respectively.

conclusionChemotherapy-responsive disease and nonscalp, soft tissue spread might represent distinct clinical syndromes within KRAS-mutant NSCLC. The molecular biology underlying this heterogeneity warrants future studies.

Indexed as

AgedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungClinical Trials as TopicDrug Resistance, NeoplasmFemaleHumansLung NeoplasmsMaleMiddle AgedMutationNeoplasm MetastasisProto-Oncogene Proteins p21(ras)Retrospective StudiesSurvival AnalysisKRAS protein, humanProto-Oncogene Proteins p21(ras)Chemotherapy-responsiveKRAS clinical syndromesMetastaticNSCLCSoft tissue metastasis

Identifiers

PMID30197261
PMCPMC6204301

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Registered trials

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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.