Dall'Olio Filippo G, Conci Nicole, Rossi Giulio, Fiorentino Michelangelo, De Giglio Andrea, Grilli Giada, Altimari Annalisa, Gruppioni Elisa, Filippini Daria M, Di Federico Alessandro, Nuvola Giacomo, Ardizzoni Andrea
Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni - 15, Bologna, Italy.
Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni - 15, Bologna, Italy.
Lung Cancer. 2020 Nov;149:5-9. doi: 10.1016/j.lungcan.2020.08.008. Epub 2020 Sep 3.
Molecular diagnosis determines therapeutic strategies for patients with non-small-cell lung cancer - adenocarcinoma (NSCLC-A) but depends on resources availability. We compared a sequential single-gene testing algorithm to next generation sequencing in NSCLC-A to assess differences in terms of effectiveness, costs, tissue consumption and time.
We analyzed a retrospective cohort of advanced NSCLC-A patients treated at the Sant'Orsola-Malpighi University Hospital. The sequential testing includes a first analysis of EGFR and KRAS status with further molecular testing physician driven. The available NGS panel detects 35 hotspot mutations,19 amplifications and 23 rearrangements.
We included 1758 patients; 1221 characterized with the sequential algorithm between January 2014 to February 2019 and 537 with Next Generation Sequencing (NGS) until January 2020. The prevalence of EGFR, ALK and KRAS alterations was similar between the stepwise and NGS group (16.5% vs 14.3%, 6.3% vs 6.3% and 36% vs 33.5%, respectively). Differently, ROS-1 rearrangements prevalence was higher in stepwise respect to NGS group (4.7% vs 0.7%). Similarly, the stepwise group presented higher prevalence than NGS for MET amplification (11.2% vs 2.2%), MET mutations (9.0% vs 2.4%), HER2 amplification (3.3% vs 1.9%) and mutations (9.8% vs 3.0%), and BRAF mutations (4.5% vs 5.6%). Among the NGS group other mutations were found in 141 patients (26.3%) and the presence of concurrent mutations in 131 (24.4%). The stepwise algorithm presented a relevant dropout rate that increased at each step, with 11.4%, 16.4% and 49.3% respectively for ALK, ROS1 and other analysis. Sequential testing's expenditure was 1375 € per patient, vs 770 € for NGS. Moreover, NGS testing can be performed with just a 25 μm slide respect to an estimated 33.3 μm slide for sequential strategy.
NGS offered a less expensive and more reliable model of diagnosis respect to sequential one for patients affected by NSCLC-A.
分子诊断可确定非小细胞肺癌腺癌（NSCLC-A）患者的治疗策略，但这取决于资源的可用性。我们比较了NSCLC-A患者中序贯单基因检测算法与下一代测序，以评估在有效性、成本、组织消耗和时间方面的差异。
我们分析了在圣奥索拉-马尔皮基大学医院接受治疗的晚期NSCLC-A患者的回顾性队列。序贯检测包括首先分析EGFR和KRAS状态，并由医生推动进一步进行分子检测。可用的NGS panel可检测35个热点突变、19个扩增和23个重排。
我们纳入了1758例患者；2014年1月至2019年2月期间，1221例采用序贯算法进行特征分析，截至2020年1月，537例采用下一代测序（NGS）。逐步检测组和NGS组之间EGFR、ALK和KRAS改变的患病率相似（分别为16.5%对14.3%、6.3%对6.3%和36%对33.5%）。不同的是，逐步检测组中ROS-1重排的患病率高于NGS组（4.7%对0.7%）。同样，逐步检测组中MET扩增（11.2%对2.2%）、MET突变（9.0%对2.4%）、HER2扩增（3.3%对1.9%）和突变（9.8%对3.0%）以及BRAF突变（4.5%对5.6%）的患病率均高于NGS组。在NGS组中，141例患者（26.3%）发现了其他突变，131例患者（24.4%）存在并发突变。逐步检测算法呈现出较高的漏检率，且在每个步骤中均有所增加，ALK、ROS1和其他分析的漏检率分别为11.4%、16.4%和49.3%。序贯检测的费用为每位患者1375欧元，而NGS为770欧元。此外，NGS检测仅需一张25μm的玻片，而序贯策略估计需要一张33.3μm的玻片。
对于NSCLC-A患者，与序贯检测相比，NGS提供了一种成本更低且更可靠的诊断模式。
