Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Department of Medicine, University of Barcelona, Barcelona, Spain.
JAMA Netw Open. 2023 Jul 3;6(7):e2325332. doi: 10.1001/jamanetworkopen.2023.25332.
Liquid biopsy has emerged as a complement to tumor tissue profiling for advanced non-small cell lung cancer (NSCLC). The optimal way to integrate liquid biopsy into the diagnostic algorithm for patients with newly diagnosed advanced NSCLC remains unclear.
To evaluate the use of circulating tumor DNA (ctDNA) genotyping before tissue diagnosis among patients with suspected advanced NSCLC and its association with time to treatment.
DESIGN, SETTING, AND PARTICIPANTS: This single-group nonrandomized clinical trial was conducted among 150 patients at the Princess Margaret Cancer Centre-University Health Network (Toronto, Ontario, Canada) between July 1, 2021, and November 30, 2022. Patients referred for investigation and diagnosis of lung cancer were eligible if they had radiologic evidence of advanced lung cancer prior to a tissue diagnosis.
Patients underwent plasma ctDNA testing with a next-generation sequencing (NGS) assay before lung cancer diagnosis. Diagnostic biopsy and tissue NGS were performed per standard of care.
The primary end point was time from referral to treatment initiation among patients with advanced nonsquamous NSCLC using ctDNA testing before diagnosis (ACCELERATE [Accelerating Lung Cancer Diagnosis Through Liquid Biopsy] cohort). This cohort was compared with a reference cohort using standard tissue genotyping after tissue diagnosis.
Of the 150 patients (median age at diagnosis, 68 years [range, 33-91 years]; 80 men [53%]) enrolled, 90 (60%) had advanced nonsquamous NSCLC. The median time to treatment was 39 days (IQR, 27-52 days) for the ACCELERATE cohort vs 62 days (IQR, 44-82 days) for the reference cohort (P < .001). Among the ACCELERATE cohort, the median turnaround time from sample collection to genotyping results was 7 days (IQR, 6-9 days) for plasma and 23 days (IQR, 18-28 days) for tissue NGS (P < .001). Of the 90 patients with advanced nonsquamous NSCLC, 21 (23%) started targeted therapy before tissue NGS results were available, and 11 (12%) had actionable alterations identified only through plasma testing.
This nonrandomized clinical trial found that the use of plasma ctDNA genotyping before tissue diagnosis among patients with suspected advanced NSCLC was associated with accelerated time to treatment compared with a reference cohort undergoing standard tissue testing.
ClinicalTrials.gov Identifier: NCT04863924.
液体活检已成为晚期非小细胞肺癌（NSCLC）肿瘤组织分析的补充手段。将液体活检纳入新诊断的晚期 NSCLC 患者诊断算法的最佳方法仍不清楚。
评估在疑似晚期 NSCLC 患者进行组织诊断之前使用循环肿瘤 DNA（ctDNA）基因分型的方法及其与治疗时间的关系。
设计、地点和参与者：这项单组非随机临床试验于 2021 年 7 月 1 日至 2022 年 11 月 30 日在加拿大安大略省多伦多的玛格丽特公主癌症中心-大学健康网络（Princess Margaret Cancer Centre-University Health Network）进行，共纳入 150 名患者。如果患者在组织诊断前有影像学证据表明患有晚期肺癌，则有资格接受肺癌的调查和诊断。
在进行肺癌诊断之前，患者接受了下一代测序（NGS）检测的血浆 ctDNA 检测。根据标准护理进行诊断性活检和组织 NGS。
主要终点是使用 ctDNA 检测在诊断前对晚期非鳞状 NSCLC 患者进行检测（加速肺癌诊断通过液体活检[ACCELERATE]队列）的从转诊到治疗开始的时间。该队列与组织诊断后使用标准组织基因分型的参考队列进行比较。
在纳入的 150 名患者（中位诊断年龄为 68 岁[范围为 33-91 岁]；80 名男性[53%]）中，90 名（60%）患有晚期非鳞状 NSCLC。加速肺癌诊断通过液体活检队列的中位治疗时间为 39 天（IQR，27-52 天），参考队列为 62 天（IQR，44-82 天）（P<.001）。在加速肺癌诊断通过液体活检队列中，从样本采集到基因分型结果的中位时间为血浆 7 天（IQR，6-9 天），组织 NGS 为 23 天（IQR，18-28 天）（P<.001）。在 90 名患有晚期非鳞状 NSCLC 的患者中，有 21 名（23%）在组织 NGS 结果可用之前开始接受靶向治疗，有 11 名（12%）仅通过血浆检测发现了可治疗的改变。
这项非随机临床试验发现，与接受标准组织检测的参考队列相比，在疑似晚期 NSCLC 患者进行组织诊断之前使用血浆 ctDNA 基因分型与治疗时间的加快有关。
ClinicalTrials.gov 标识符：NCT04863924。
