TY - JOUR
T1 - A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer
T2 - Development and international validation studies
AU - Kratz, Johannes R.
AU - He, Jianxing
AU - Van Den Eeden, Stephen K.
AU - Zhu, Zhi Hua
AU - Gao, Wen
AU - Pham, Patrick T.
AU - Mulvihill, Michael S.
AU - Ziaei, Fatemeh
AU - Zhang, Huanrong
AU - Su, Bo
AU - Zhi, Xiuyi
AU - Quesenberry, Charles P.
AU - Habel, Laurel A.
AU - Deng, Qiuhua
AU - Wang, Zongfei
AU - Zhou, Jiangfen
AU - Li, Huiling
AU - Huang, Mei Chun
AU - Yeh, Che Chung
AU - Segal, Mark R.
AU - Ray, M. Roshni
AU - Jones, Kirk D.
AU - Raz, Dan J.
AU - Xu, Zhidong
AU - Jahan, Thierry M.
AU - Berryman, David
AU - He, Biao
AU - Mann, Michael J.
AU - Jablons, David M.
PY - 2012/3
Y1 - 2012/3
N2 - 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 (ptrend= 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 (ptrend<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.
AB - 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 (ptrend= 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 (ptrend<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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84861985508&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(11)61941-7
DO - 10.1016/S0140-6736(11)61941-7
M3 - Article
C2 - 22285053
AN - SCOPUS:84861985508
SN - 0140-6736
VL - 379
SP - 823
EP - 832
JO - The Lancet
JF - The Lancet
IS - 9818
ER -
