Feasibility and utility of a panel testing for 114 cancer-associated genes in a clinical setting: A hospital-based study

Abstract

Next-generation sequencing (NGS) of tumor tissue (ie, clinical sequencing) can guide clinical management by providing information about actionable gene aberrations that have diagnostic and therapeutic significance. Here, we undertook a hospital-based prospective study (TOP-GEAR project, 2nd stage) to investigate the feasibility and utility of NGS-based analysis of 114 cancer-associated genes (the NCC Oncopanel test). We examined 230 cases (comprising more than 30 tumor types) of advanced solid tumors, all of which were matched with nontumor samples. Gene profiling data were obtained for 187 cases (81.3%), 111 (59.4%) of which harbored actionable gene aberrations according to the Clinical Practice Guidelines for Next Generation Sequencing in Cancer Diagnosis and Treatment (Edition 1.0) issued by 3 major Japanese cancer-related societies. Twenty-five (13.3%) cases have since received molecular-targeted therapy according to their gene aberrations. These results indicate the utility of tumor-profiling multiplex gene panel testing in a clinical setting in Japan. This study is registered with UMIN Clinical Trials Registry (UMIN 000011141).

Keywords: NCC Oncopanel; actionable gene aberration; clinical sequencing; gene panel test; insurance reimbursement.

Figure 1

Feasibility of the NCC Oncopanel test for 114 cancer‐associated genes in a cohort of Japanese patients with solid tumors who would complete or had completed standard chemotherapy. A, Success rate. Among the 230 cases analyzed, 18 were excluded due to insufficient quantity or quality of DNAs. Then 212 cases were subjected next‐generation sequencing analysis and gene profiling data were obtained for 187 cases (success rate, 81.3%). B, Tumor types of the 187 cases for which gene profiling data were available

Figure 2

Utility of the NCC Oncopanel test in a cohort of Japanese patients with solid tumors who would complete or had completed standard chemotherapy. A, Gene aberration detected in 187 cases. Cases are categorized according to maximum evidence for drug selection. The percentage of cases with actionable gene aberrations was calculated taking (or not) into account a high tumor mutational burden (TMB; defined as ≥10 mutations/Mb). B, Percentage of cases with actionable gene aberrations according to tumor type. The number of cases is presented on the graph according to maximum evidence for drug selection

Figure 3

Assessment of tumor mutation burden by the NCC Oncopanel test in a cohort of Japanese patients with solid tumors who had completed standard chemotherapy. Comparison of tumor mutation burden measured by whole exome sequencing vs that by NCC Oncopanel testing. Tumor mutation burden (mutations [Mut]/Mb) was measured in 20 samples assessed previously by whole exome sequencing, and the results were compared. The NCC Oncopanel test assessed matched tumor and nontumor samples. The line y = x is plotted in red