University of California, San Francisco, CA 94143-1724, USA.
Lancet. 2012 Mar 3;379(9818):823-32. doi: 10.1016/S0140-6736(11)61941-7. Epub 2012 Jan 27.
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.
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).
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.
Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection.
UCSF Thoracic Oncology Laboratory and Pinpoint Genomics.
早期非小细胞肺癌（NSCLC）的频繁复发通常归因于完全切除时未检测到的转移性疾病。此类患者的治疗取决于预后分期，以确定最有可能患有隐匿性疾病的个体。我们旨在开发和验证一种实用且可靠的检测方法，以提高与传统分期相比的风险分层能力。
我们在加利福尼亚大学旧金山分校接受手术切除的 361 例非鳞状 NSCLC 患者队列中开发了一种使用定量 PCR 在福尔马林固定石蜡包埋组织样本上运行并区分具有异质统计学预后的患者的 14 基因表达检测方法。然后，该检测方法在 Kaiser Permanente 北加州医院接受手术切除的 433 例 I 期非鳞状 NSCLC 患者的盲法 Kaiser 验证队列中进行了独立验证，并在由中国临床试验联盟（CCTC）的几家主要中国癌症中心组成的 1006 例 I-III 期非鳞状 NSCLC 患者队列中进行了验证。
Kaiser 验证队列的 Kaplan-Meier 分析显示，低危患者 5 年总生存率为 71.4%（95%CI 60.5-80.0），中危患者为 58.3%（48.9-66.6），高危患者为 49.2%（42.2-55.8）（p（趋势）=0.0003）。CCTC 队列的类似分析表明，低危患者 5 年总生存率为 74.1%（66.0-80.6），中危患者为 57.4%（48.3-65.5），高危患者为 44.6%（40.2-48.9）（p（趋势）<0.0001）。两个队列的多变量分析均表明，没有标准的临床危险因素可以解释或提供源自肿瘤基因表达的预后信息。该检测方法提高了超出国家综合癌症网络（National Comprehensive Cancer Network）I 期高危肿瘤标准的预后准确性（p<0.0001），并区分了所有疾病阶段的低危、中危和高危患者。
我们实用的基于定量 PCR 的检测方法可靠地识别了接受手术切除后具有高死亡率风险的早期非鳞状 NSCLC 患者。
加利福尼亚大学旧金山分校胸肿瘤学实验室和 Pinpoint Genomics。
