Medical Oncology Department, Hospital Universitario 12 de Octubre and Instituto de Investigación i+12, Madrid, Spain; Lung Cancer Group, Clinical Research Program, CNIO (Centro Nacional de Investigaciones Oncológicas) and Instituto de Investigación i+12, Madrid, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
Biochemistry Department, Hospital Universitario 12 de Octubre and Instituto de Investigación i+12, Madrid, Spain.
Clin Lung Cancer. 2018 Jan;19(1):65-73.e7. doi: 10.1016/j.cllc.2017.06.008. Epub 2017 Jun 23.
A substantial fraction of non-small-cell lung cancers (NSCLCs) harbor targetable genetic alterations. In this study, we analyzed the feasibility and clinical utility of integrating a next-generation sequencing (NGS) panel into our routine lung cancer molecular subtyping algorithm.
After routine pathologic and molecular subtyping, we implemented an amplicon-based gene panel for DNA analysis covering mutational hot spots in 22 cancer genes in consecutive advanced-stage NSCLCs.
We analyzed 109 tumors using NGS between December 2014 and January 2016. Fifty-six patients (51%) were treatment-naive and 82 (75%) had lung adenocarcinomas. In 89 cases (82%), we used samples derived from lung cancer diagnostic procedures. We obtained successful sequencing results in 95 cases (87%). As part of our routine lung cancer molecular subtyping protocol, single-gene testing for EGFR, ALK, and ROS1 was attempted in nonsquamous and 3 squamous-cell cancers (n = 92). Sixty-nine of 92 samples (75%) had sufficient tissue to complete ALK and ROS1 immunohistochemistry (IHC) and NGS. With the integration of the gene panel, 40 NSCLCs (37%) in the entire cohort and 30 NSCLCs (40%) fully tested for ALK and ROS1 IHC and NGS had actionable mutations. KRAS (24%) and EGFR (10%) were the most frequently mutated actionable genes. Ten patients (9%) received matched targeted therapies, 6 (5%) in clinical trials.
The combination of IHC tests for ALK and ROS1 and amplicon-based NGS is applicable in routine clinical practice, enabling patient selection for genotype-tailored treatments.
相当一部分非小细胞肺癌（NSCLC）存在可靶向的遗传改变。在这项研究中，我们分析了将下一代测序（NGS）面板整合到我们常规肺癌分子分型算法中的可行性和临床实用性。
在常规病理和分子分型后，我们实施了基于扩增子的基因面板进行 DNA 分析，该面板覆盖了 22 个癌症基因中的突变热点，这些基因在连续的晚期 NSCLC 中。
我们在 2014 年 12 月至 2016 年 1 月期间使用 NGS 分析了 109 例肿瘤。56 例患者（51%）为初治患者，82 例（75%）为肺腺癌。在 82 例（75%）的 89 例病例中，我们使用了来自肺癌诊断程序的样本。在 95 例（87%）的病例中，我们获得了成功的测序结果。作为我们常规肺癌分子分型方案的一部分，在非鳞状细胞癌和 3 例鳞状细胞癌（n=92）中尝试了 EGFR、ALK 和 ROS1 的单基因检测。在 92 个样本中，有 69 个（75%）有足够的组织完成 ALK 和 ROS1 免疫组化（IHC）和 NGS。通过整合基因面板，在整个队列的 40 例 NSCLC（37%）和 30 例完全接受 ALK 和 ROS1 IHC 和 NGS 检测的 NSCLC 中，有可操作的突变。KRAS（24%）和 EGFR（10%）是最常突变的可操作基因。10 名患者（9%）接受了匹配的靶向治疗，其中 6 名（5%）在临床试验中。
ALK 和 ROS1 的 IHC 检测与基于扩增子的 NGS 的结合适用于常规临床实践，使患者能够选择适合基因分型的治疗方法。
