Establishment of an NGS-based genomic testing system
We developed an NGS-based in-house genomic testing system to identify somatic gene mutations, amplifications, and fusions using an original cancer gene panel (NCC oncopanel), and have been continuously improving this system to become a clinically useful in vitro diagnostics (IVD) system in cooperation with the Department of Clinical Genomics and the Department of Bioinformatics of the National Cancer Center Research Institute (NCCRI). In cooperation with staff of the Department of Pathology and Clinical Laboratories in the National Cancer Center Hospital (NCCH), the SCI-Lab was opened in the NCCH, where our clinical sequencing system is operated under an international standard quality assurance.
Implementation of NGS-based genomic testing in the NCCH
In cooperation with staff of the Department of Experimental Therapeutics and the Department of Pathology and Clinical Laboratories in the NCCH, prospective clinical studies were performed to examine the feasibility and utility of our NGS-based genomic testing system for patients enrolled into early-phase clinical trials. The result of the TOPICS-1 (TOP-GEAR-1) study, in which patients were enrolled in 2013 and 2014, indicated that patients who received investigational drug therapies matched to their genomic aberrations showed better progression-free survivals than those who received non-matched therapies (Figure 1).
Fig. 1. Progression-free survival of matched and non-matched therapy-received patients in the TOPICS-1 study.
In 2016, 85 patients were analyzed in the TOP-GEAR-1ex study in which NGS testing was performed in the NCCH (Figure 2), and additional 94 patients were analyzed in the TOP-GEAR-2 study in which NGS testing was performed in the SCI-Lab. In the TOP-GEAR-2 study, actionable genomic aberrations were identified in 64 (68%) patients. Germline mutations in genes responsible for hereditary cancers were identified in two patients as a secondary finding. Diagnosis, treatment, and care for patients with germline mutations are undertaken by staff of the Department of Genetic Medicine and Services (GeMS) in the NCCH.
Fig. 2. Tumor types analyzed and detected genomic aberrations in the TOPICS-1ex study.
Feasibility and clinical utility of our genomic testing system with international standard quality assurance will be shown. Clinical study for approval of our system by PMDA (Pharmaceuticals and Medical Devices Agency) will be launched shortly.