Rangachari Deepa, VanderLaan Paul A, Le Xiuning, Folch Erik, Kent Michael S, Gangadharan Sidharta P, Majid Adnan, Haspel Richard L, Joseph Loren J, Huberman Mark S, Costa Daniel B
Department of Medicine, 330 Brookline Avenue, Boston, MA 02215, USA.
Department of Pathology, 330 Brookline Avenue, Boston, MA 02215, USA.
Cancer Treat Commun. 2015;4:174-181. doi: 10.1016/j.ctrc.2015.10.004.
Tumor genotyping using single gene assays (SGAs) is standard practice in advanced non-small-cell lung cancer (NSCLC). We evaluated how the introduction of next generation sequencing (NGS) into day-to-day clinical practice altered therapeutic decision-making.
Clinicopathologic data, tumor genotype, and clinical decisions were retrospectively compiled over 6 months following introduction of NGS assay use at our institution in 82 patient-tumor samples (7 by primary NGS, 22 by sequential SGAs followed by NGS, and 53 by SGAs).
SGAs identified abnormalities in 34 samples, and all patients with advanced -mutated or -rearranged tumors received approved tyrosine kinase inhibitors (TKIs) or were consented for clinical trials. NGS was more commonly requested for , , and -negative tumors (p<0.0001). NGS was successful in 24/29 (82.7%) tumors. Of 17 adenocarcinomas (ACs), 11 (7 from patients with ≤15 pack-years of smoking) had abnormalities in a known driver oncogene. This led to a change in decision-making in 8 patients, trial consideration in 6, and off-label TKI use in 2. Of 7 squamous cell (SC) carcinomas, 1 had a driver aberration (); 6 had other genomic events (all with mutations). In no cases were clinical decisions altered (p=0.0538 when compared to ACs).
Targeted NGS can identify a significant number of therapeutically-relevant driver events in lung ACs; particularly in never or light smokers. For SC lung cancers, NGS is less likely to alter current practice. Further research into the cost effectiveness and optimal use of NGS and improved provider training in genomic oncology are warranted.
使用单基因检测（SGA）进行肿瘤基因分型是晚期非小细胞肺癌（NSCLC）的标准做法。我们评估了将下一代测序（NGS）引入日常临床实践如何改变治疗决策。
回顾性收集了2016年6月在我们机构引入NGS检测方法后82例患者肿瘤样本的临床病理数据、肿瘤基因型和临床决策（7例采用原发性NGS，22例先采用序贯SGA再进行NGS，53例采用SGA）。
SGA在34个样本中发现了异常，所有晚期突变或重排肿瘤患者均接受了批准的酪氨酸激酶抑制剂（TKI）治疗或同意参加临床试验。对于EGFR、ALK和ROS1阴性肿瘤，更常要求进行NGS检测（p<0.0001）。NGS在24/29例（82.7%）肿瘤中检测成功。在17例腺癌（AC）中，11例（7例来自吸烟史≤15包年的患者）在已知驱动癌基因中存在异常。这导致8例患者的决策发生改变，6例考虑参加试验，2例使用非标签TKI。在7例鳞状细胞（SC）癌中，1例存在驱动畸变（PIK3CA）；6例有其他基因组事件（均有TP53突变）。在任何情况下，临床决策均未改变（与AC相比，p=0.0538）。
靶向NGS可在肺腺癌中识别大量与治疗相关的驱动事件；尤其是在从不吸烟或轻度吸烟的患者中。对于肺鳞癌，NGS不太可能改变当前的治疗实践。有必要进一步研究NGS的成本效益和最佳使用方法，并加强肿瘤基因组学方面的医疗人员培训。
