Dataset Information

A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies.

ABSTRACT:

Background

The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging.

Methods

A 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I-III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC).

Findings

Kaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71·4% (95% CI 60·5-80·0) in low-risk, 58·3% (48·9-66·6) in intermediate-risk, and 49·2% (42·2-55·8) in high-risk patients (p(trend)=0·0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74·1% (66·0-80·6) in low-risk, 57·4% (48·3-65·5) in intermediate-risk, and 44·6% (40·2-48·9) in high-risk patients (p(trend)<0·0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0·0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages.

Interpretation

Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection.

Funding

UCSF Thoracic Oncology Laboratory and Pinpoint Genomics.

SUBMITTER: Kratz JR

PROVIDER: S-EPMC3294002 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Publications

A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies.

Kratz Johannes R JR He Jianxing J Van Den Eeden Stephen K SK Zhu Zhi-Hua ZH Gao Wen W Pham Patrick T PT Mulvihill Michael S MS Ziaei Fatemeh F Zhang Huanrong H Su Bo B Zhi Xiuyi X Quesenberry Charles P CP Habel Laurel A LA Deng Qiuhua Q Wang Zongfei Z Zhou Jiangfen J Li Huiling H Huang Mei-Chun MC Yeh Che-Chung CC Segal Mark R MR Ray M Roshni MR Jones Kirk D KD Raz Dan J DJ Xu Zhidong Z Jahan Thierry M TM Berryman David D He Biao B Mann Michael J MJ Jablons David M DM

Lancet (London, England) 20120127 9818

<h4>Background</h4>The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging.<h4>Methods</h4>A 14-gene expression assay that uses quantitative PCR, ru ...[more]

PMID: 22285053

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Dataset Information

A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies.

Background

Methods

Findings

Interpretation

Funding

Publications

A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies.

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