Megahed Ahmed I, Zheng Dominick, Chen Lie Hong, Haque Reina, McGary Eric C
Kaiser Permanente Southern California, Research & Evaluation, Pasadena, CA, USA.
Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA, USA.
Heliyon. 2024 Aug 15;10(16):e36308. doi: 10.1016/j.heliyon.2024.e36308. eCollection 2024 Aug 30.
Next generation sequencing (NGS) testing is used to identify driver mutation(s) in non-small cell lung cancer (NSCLC) that are amenable to targeted therapy, resulting in superior outcomes and improved tolerability. We characterized how clinicians in a large integrated healthcare system utilized NGS testing to inform first line treatment decisions in patients with stage IV NSCLC shortly after diagnosis.
We conducted a cross-sectional study of 964 patients within an integrated healthcare system, Kaiser Permanente Southern California (KPSC), who were diagnosed with stage IV NSCLC and completed NGS testing (Strata Oncology) between May 2019 to June 2021. Treatment start dates were used to divide patients into those who started treatment before or after NGS results, or those who did not receive treatment after NGS results. Patients harboring alterations in seven genes (EGFR, ALK, ROS-1, BRAF, KRAS, RET, and MET) were considered candidates for targeted first line therapy.
First line treatment was initiated in half (52 %; n = 284) of all treated patients prior to NGS results. Just under half (48 %; n = 137) of these patients were found to have a targetable mutation by NGS, of whom 59 % received first line chemotherapy and/or immunotherapy, rather than targeted therapy. Nearly 27 % of the sample never received treatment, of which 31 % had a targetable mutation, and may have been candidates for targeted therapy. Not undergoing first line treatment was correlated with older age, higher comorbidity index, smoking history, and the lack of an identifiable driver mutation.
NGS tests results were not exclusively used to inform first line treatment decisions in most patients with stage IV NSCLC, and most patients with a targetable mutation were not treated with targeted therapy. Possible explanations include lengthy turnaround times for NGS testing and the availability of timelier but less accurate single gene testing.
下一代测序（NGS）检测用于识别非小细胞肺癌（NSCLC）中适合靶向治疗的驱动突变，从而带来更好的治疗效果和更高的耐受性。我们对一个大型综合医疗系统中的临床医生如何利用NGS检测为IV期NSCLC患者在诊断后不久的一线治疗决策提供信息进行了特征分析。
我们对南加州凯撒永久医疗集团（KPSC）这个综合医疗系统内964例被诊断为IV期NSCLC并在2019年5月至2021年6月期间完成NGS检测（Strata Oncology）的患者进行了横断面研究。治疗开始日期用于将患者分为在NGS结果出来之前或之后开始治疗的患者，以及在NGS结果出来后未接受治疗的患者。携带七种基因（EGFR、ALK、ROS-1、BRAF、KRAS、RET和MET）改变的患者被视为一线靶向治疗的候选者。
在所有接受治疗的患者中，有一半（52%；n = 284）在NGS结果出来之前就开始了一线治疗。在这些患者中，不到一半（48%；n = 137）被NGS检测发现有可靶向的突变，其中59%接受了一线化疗和/或免疫治疗，而不是靶向治疗。近27%的样本从未接受过治疗，其中31%有可靶向的突变，可能是靶向治疗的候选者。未接受一线治疗与年龄较大、合并症指数较高、吸烟史以及缺乏可识别的驱动突变有关。
在大多数IV期NSCLC患者中，NGS检测结果并非唯一用于指导一线治疗决策，并且大多数有可靶向突变的患者未接受靶向治疗。可能的解释包括NGS检测周转时间长以及有更及时但准确性较低的单基因检测可用。
