ArticlesA practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies
Section snippets
Background
By contrast with other common solid tumours such as breast and colon cancer, outcomes after resection of early-stage non-small-cell lung cancer (NSCLC) are poor, with 35–50% recurrence rates.1 Little progress has been made in the past 30 years in the reduction of distant recurrence and subsequent mortality,1 which remain unacceptably high, even for patients with stage I disease in whom no nodal or other metastatic involvement can be detected at the time of surgery.2 Despite the high rate of
Study design and participants
A 14-gene assay that uses quantitative PCR analysis of formalin-fixed, paraffin-embedded tissues was developed with a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco (UCSF), USA. This assay, developed and run at an independent laboratory certified by Clinical Laboratory Improvement Amendments (CLIA), was then validated by the Kaiser Permanente Division of Research (KPDOR) with a blinded study design in a cohort of 433 patients with stage I
Results
A total of 399 patients were identified who had undergone resection of non-squamous NSCLC at UCSF during the study period; of these, 361 met criteria for inclusion in the training cohort. 460 patients at Kaiser Northern California had undergone resections of stage I non-squamous NSCLC, of whom 433 met criteria for inclusion in the independent validation cohort. 1006 patients were identified in the CCTC institutions that met criteria for inclusion in that validation study. Relevant clinical and
Discussion
Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection, discriminating such patients with greater accuracy than use of NCCN criteria alone.
Outcomes after the diagnosis of stage I NSCLC are poor compared with other solid tumours, despite advances in the molecular understanding of lung cancer. Several randomised controlled trials32, 33, 34, 35, 36 have shown improved survival with
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These authors share first authorship