Teuwen Laure-Anne, Roets Evelyne, D'Hoore Pieter, Pauwels Patrick, Prenen Hans
Department of Oncology, Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium.
Department of Pathology, Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium.
Diagnostics (Basel). 2023 May 3;13(9):1619. doi: 10.3390/diagnostics13091619.
Next-generation sequencing (NGS) can be used to detect tumor-specific genomic alterations. This retrospective single-center study aims to assess the application of an extensive NGS panel to identify actionable alterations and initiate matched targeted treatment for patients with advanced cancer. We analyzed genomic alterations in solid tumor biopsies from 464 patients with advanced cancer with the Foundation Medicine assay (FoundationOneCDx). Therapeutic implications were determined using the Memorial Sloan Kettering Precision Oncology Knowledge Base (OncoKB) classification. The FoundationOneCDx was successfully applied in 464/521 patients (89%). The most common altered genes were TP53 (61%), KRAS (20%), CDKN2A (20%), TERT (16%), and APC (16%). Among the 419 patients with successfully analyzed tumor mutational burden (TMB), 43 patients presented with a high TMB (≥10 mutations/megabase). Out of the 126 patients with an actionable target, 40 patients received matched treatment (32%) of which 17 were within a clinical trial. This study shows that the application of NGS is feasible in an academic center and increases the detection of actionable alterations and identification of patients eligible for targeted treatment or immunotherapy regardless of tumor histology. Strategies such as early referral for NGS, inclusion in clinical (basket) trials, and the development of new targeted drugs are necessary to improve the matched treatment rate.
下一代测序（NGS）可用于检测肿瘤特异性基因组改变。这项回顾性单中心研究旨在评估广泛的NGS检测板在识别可操作改变并为晚期癌症患者启动匹配的靶向治疗方面的应用。我们使用Foundation Medicine检测法（FoundationOneCDx）分析了464例晚期癌症患者实体瘤活检中的基因组改变。使用纪念斯隆凯特琳精准肿瘤学知识库（OncoKB）分类确定治疗意义。FoundationOneCDx在464/521例患者（89%）中成功应用。最常发生改变的基因是TP53（61%）、KRAS（20%）、CDKN2A（20%）、TERT（16%）和APC（16%）。在419例成功分析肿瘤突变负担（TMB）的患者中，43例患者表现出高TMB（≥10个突变/兆碱基）。在126例具有可操作靶点的患者中，40例患者接受了匹配治疗（32%），其中17例在临床试验中。这项研究表明，NGS在学术中心的应用是可行的，并且增加了可操作改变的检测以及适合靶向治疗或免疫治疗患者的识别，而不考虑肿瘤组织学。早期转诊进行NGS、纳入临床（篮子）试验以及开发新的靶向药物等策略对于提高匹配治疗率是必要的。
