Abstract
BackgroundClinical 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.MethodsA 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.ResultsPathogenic 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.ConclusionsOur 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.
Highlights
Several studies have defined the genomic landscape of cancer with the use of next-generation sequencing (NGS) technology, and they have detected some candidate driver-gene alterations of cancer that allow the tumor cells to survive and spread [1,2,3,4]
We identified 36 patients whose tissue samples were of suitable quality for clinical sequencing, and we analyzed the genomic profiles of these tumors
Clinical sequencing using cancer panel testing novel molecular-targeted therapy based on their actionable gene alterations, but only one case ended up receiving novel targeted therapy following the genetic tests
Summary
Several studies have defined the genomic landscape of cancer with the use of next-generation sequencing (NGS) technology, and they have detected some candidate driver-gene alterations of cancer that allow the tumor cells to survive and spread [1,2,3,4]. In Japan, a total of 230 patients with advanced solid tumors underwent clinical sequencing using the NCC Oncopanel as part of the TOP-GEAR project at the National Cancer Center Hospital (UMIN000011141), and the genetic tests revealed that 13% of the patients were candidates for novel targeted therapy [11]. In this context, the use of the NCC Oncopanel as well as the FoundationOne CDx has been covered under Japan’s national health insurance since June 2019. We sought to clarify the feasibility and utility of clinical sequencing in the treatment of refractory tumors at our hospital
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