Division of Adult Cardiothoracic Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA.
Hong Kong Institute of Cell and Molecular Medicine, Hong Kong.
Clin Lung Cancer. 2018 Jan;19(1):58-64. doi: 10.1016/j.cllc.2017.05.015. Epub 2017 May 31.
Many early stage non-small-cell lung cancer (NSCLC) patients who are not considered candidates for adjuvant treatment according to current guidelines do harbor occult metastasis, and have disease recurrence despite complete resection. Although National Comprehensive Cancer Network (NCCN) guidelines suggest clinicopathologic characteristics to identify high-risk patients for adjuvant intervention, molecular profiling more accurately predicts 5-year survival. Early evidence of clinical benefit from application of this molecular-based management strategy, however, has not been reported.
An internationally validated, prognostic, 14-gene quantitative polymerase chain reaction expression assay was used to stratify risk prospectively in 100 consecutive patients with stage IA, IB, and IIA nonsquamous NSCLC. Kaplan-Meyer estimates, log rank analysis, and Cox regression were used to compare disease-free survival (DFS) between high-risk patients who did or did not elect adjuvant chemotherapy.
Forty-eight patients (48%) were deemed high-risk according to molecular testing and 36 (36%) met NCCN high-risk criteria; risk designations were discordant in 34 (34%) of all patients. Estimated 5-year DFS was 48.9% among molecular high-risk patients who did not undertake adjuvant chemotherapy, 93.8% among untreated molecular low-risk patients, and 91.7% in molecular high-risk patients who did undergo chemotherapy (P = .004). In contrast, DFS was only 75.2% in untreated NCCN low-risk patients, and 61.9% in untreated NCCN high-risk patients (P = .183).
This prospective, nonrandomized study provides initial evidence that high-risk designation according to the 14-gene prognostic assay also predicts benefit from adjuvant chemotherapy for very early stage NSCLC, and further supports the superiority of molecular stratification over current NCCN criteria at identifying high-risk patients.
许多不符合当前指南建议进行辅助治疗的早期非小细胞肺癌（NSCLC）患者实际上存在隐匿性转移，尽管完全切除，仍会出现疾病复发。尽管美国国家综合癌症网络（NCCN）指南建议使用临床病理特征来识别辅助干预的高危患者，但分子谱分析更准确地预测了 5 年生存率。然而，目前尚未报道这种基于分子的管理策略应用的早期临床获益证据。
我们前瞻性地使用国际验证的、预后的 14 基因定量聚合酶链反应表达检测对 100 例连续的 I 期、IB 期和 IIA 期非鳞状 NSCLC 患者进行分层风险评估。使用 Kaplan-Meier 估计、对数秩分析和 Cox 回归比较高风险患者中接受或未接受辅助化疗的无病生存率（DFS）。
根据分子检测，48 例患者（48%）被认为是高危患者，36 例（36%）符合 NCCN 高危标准；所有患者中有 34 例（34%）的风险分类不一致。未接受辅助化疗的分子高风险患者的 5 年 DFS 估计为 48.9%，未接受治疗的分子低风险患者为 93.8%，接受化疗的分子高风险患者为 91.7%（P =.004）。相比之下，未接受治疗的 NCCN 低危患者的 DFS 仅为 75.2%，未接受治疗的 NCCN 高危患者为 61.9%（P =.183）。
这项前瞻性、非随机研究提供了初步证据，表明根据 14 基因预后检测确定的高危患者还可以从辅助化疗中获益，用于非常早期的 NSCLC，并且进一步支持分子分层优于当前 NCCN 标准，用于识别高危患者。
