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

详细信息	查看全文 | 推荐本文 |

• 作者：Johannes R Kratz ; MD^a ; ^&Dagger ; ; Prof Jianxing He ; MD^b ; ^&Dagger ; ; Stephen K Van Den Eeden ; PhD^c ; Prof Zhi-Hua Zhu ; MD^d ; Prof Wen Gao ; MD^e ; Patrick T Pham ; BS^a ; Michael S Mulvihill ; BS^a ; Fatemeh Ziaei ; BS^f ; Huanrong Zhang ; MD^b ; Bo Su ; MD^e ; Prof Xiuyi Zhi ; MD^g ; Charles P Quesenberry ; PhD^c ; Laurel A Habel ; BS^c ; Qiuhua Deng ; BS^b ; Zongfei Wang ; BS^b ; Jiangfen Zhou ; BS^b ; Huiling Li ; PhD^b ; Mei-Chun Huang ; PhD^f ; Che-Chung Yeh ; PhD^a ; Prof Mark R Segal ; PhD^a ; M Roshni Ray ; BS^a ; Prof Kirk D Jones ; MD^a ; Dan J Raz ; MD^a ; Zhidong Xu ; MD^a ; Thierry M Jahan ; MD^a ; David Berryman ; PharmD^f ; Biao He ; PhD^a ; Dr Michael J Mann ; MD^a ; ^{michael.mann@ucsfmedctr.org} ; Prof David M Jablons ; MD^a ; ^{david.jablons@ucsfmedctr.org}
• 刊名：The Lancet
• 出版年：2012
• 期刊代码：182_01406736
• 类别：med
• 出版时间：3-9 March, 2012
• 卷：379
• 期：9818
• 页码：823-832
• 文件大小：282 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferencesml version="1.0" encoding="UTF-8"?>

Summary

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路4%(95%CI 60路5-80路0) in low-risk, 58路3%(48路9-66路6) in intermediate-risk, and 49路2%(42路2-55路8) in high-risk patients (p_trend=0路0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74路1%(66路0-80路6) in low-risk, 57路4%(48路3-65路5) in intermediate-risk, and 44路6%(40路2-48路9) in high-risk patients (p_trend<0路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路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.