Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan.
PLoS One. 2021 Feb 26;16(2):e0247090. doi: 10.1371/journal.pone.0247090. eCollection 2021.
Clinical sequencing using a panel of genes has recently been applied worldwide for patients with refractory solid tumors, but the significance of clinical sequencing using gene panel testing remains uncertain. Here we sought to clarify the feasibility and utility of clinical sequencing in the treatment of refractory tumors at our hospital.
A total of 39 patients with advanced solid tumors treated at our hospital between 2018 and 2020 were enrolled in the clinical sequencing. Among them, we identified 36 patients whose tissue samples were of suitable quality for clinical sequencing, and we analyzed the genomic profiles of these tumors.
Pathogenic alterations were detected in 28 (78%) of the 36 patients. The most common mutation was TP53 (55%), followed by KRAS (22%), and the highest frequency of gene amplification was ERBB2 (17%). Nine of the 36 patients were identified as candidates for novel molecular-targeted therapy based on their actionable gene alterations, but only one case ended up receiving novel targeted therapy following the genetic tests.
Our current results suggested that clinical sequencing might be useful for the detection of pathogenic alterations and the management of additional cancer treatment. However, molecular target based on actionable genomic alteration does not always bridge to subsequent therapy due to clinical deterioration, refusal for unapproved drug, and complexity of clinical trial access. Both improved optimal timing of clinical sequencing and a consensus about its off-label use might help patients receive greater benefit from clinical sequencing.
最近,全球范围内已将基因面板的临床测序应用于难治性实体瘤患者,但基因面板检测的临床测序的意义仍不确定。在此,我们旨在阐明我院难治性肿瘤治疗中临床测序的可行性和实用性。
我们共纳入了 2018 年至 2020 年在我院治疗的 39 例晚期实体瘤患者进行临床测序。其中,我们鉴定了 36 例组织样本适合临床测序的患者,并分析了这些肿瘤的基因组特征。
在 36 例患者中,检测到致病性改变的有 28 例(78%)。最常见的突变是 TP53(55%),其次是 KRAS(22%),基因扩增频率最高的是 ERBB2(17%)。根据可操作的基因改变,9 例患者被鉴定为新型分子靶向治疗的候选者,但只有 1 例在基因检测后接受了新型靶向治疗。
我们目前的结果表明,临床测序可能有助于检测致病性改变,并管理额外的癌症治疗。然而,基于可操作的基因组改变的分子靶标并不总是能转化为后续治疗,这可能是由于临床恶化、拒绝使用未批准的药物以及临床试验准入的复杂性。改善临床测序的最佳时机和对其非适应证使用的共识,可能有助于患者从临床测序中获得更大的获益。