Introduction: Lung cancer patients with tumors harboring actionable alterations can achieve very durable responses to first‐line targeted therapy. However, identifying targetable alterations using next‐generation sequencing (NGS) is a complex and time‐intensive process. As actionable genetic alterations are enriched in lung cancers arising in patients with limited smoking history, we designed a workflow to expedite NGS testing for this group. Methods: We developed a protocol to allow for next‐day extraction of nucleic acids from frozen tissue. Specimens were designated as high priority during sequencing. We determined the interval between biopsy and NGS results to evaluate whether the workflow reduced the pre‐analytical period and in‐laboratory turnaround time and allowed for rapid initiation of genotype‐matched therapy. Results: Between January 2017 and May 2018, 21 patients participated in the expedited sequencing program. The median interval between biopsy and NGS results was 10.7 days. Six patients received results within 1 week of biopsy. Performing molecular analysis on frozen tissue and prioritizing sequencing and analysis of these specimens reduced the pre‐analytical period from 3.5 to 1.3 days (p < 0.0001) and shortened in‐laboratory turnaround time by 3 days (11.8 versus 8.4 business days, p < 0.0001). Ninety‐three percent of patients with an actionable molecular alteration received first‐line targeted therapy. The median time‐to‐initiation of treatment was 19.7 days from biopsy. Conclusions: Sequencing and analyzing nucleic acids from frozen tissue is a practical strategy for shortening the time to matched therapy. The significant advantage of upfront treatment with targeted therapies in subsets of lung cancer patients provides rationale for developing workflows that accelerate comprehensive molecular analysis.

中文翻译：

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加速综合分子分析以优化吸烟史最小的肺癌患者的初始治疗

简介：具有可操作改变的肿瘤的肺癌患者可以对一线靶向治疗产生非常持久的反应。然而，使用下一代测序（NGS）识别可靶向的改变是一个复杂且耗时的过程。由于可操作的基因改变在吸烟史有限的患者中出现的肺癌中富集，我们设计了一个工作流程来加快该组的 NGS 检测。方法：我们制定了一个协议，允许第二天从冷冻组织中提取核酸。在测序过程中，样本被指定为高优先级。我们确定了活检和 NGS 结果之间的间隔，以评估工作流程是否缩短了分析前时间和实验室内周转时间，并允许快速启动基因型匹配治疗。结果：2017 年 1 月至 2018 年 5 月期间，21 名患者参与了快速测序计划。活检和 NGS 结果之间的中位间隔为 10.7 天。6 名患者在活检后 1 周内收到结果。对冷冻组织进行分子分析并优先对这些标本进行测序和分析，将分析前时间从 3.5 天缩短到 1.3 天（p < 0.0001），并将实验室周转时间缩短了 3 天（11.8 对 8.4 个工作日，p < 0.0001） ）。93% 具有可操作分子改变的患者接受了一线靶向治疗。从活检到开始治疗的中位时间为 19.7 天。结论：对冷冻组织中的核酸进行测序和分析是缩短匹配治疗时间的实用策略。