Clinical application of comprehensive genomic profiling panel to thoracic malignancies: A single‐center retrospective study

Abstract

Background: The usefulness of comprehensive genomic profiling (CGP) panels for thoracic malignancies after completion of the standard treatment is unclear. Methods: The results of CGP panels for malignant thoracic diseases performed at our hospital between December 2019 and June 2022 were collected. We examined whether CGP panel results led to new treatment, correlated with the effectiveness of immune checkpoint inhibitors (ICIs), or revealed secondary findings related to hereditary tumors. Results: A total of 60 patients were enrolled, of which 52 (86.6%) had lung cancer. In six (10%) patients, the panel results led to treatment with insurance-listed molecular-targeted agents; four patients had EGFR mutations not detected by the real-time polymerase chain reaction assay and two had MET ex.14 skipping mutations. In small-cell lung cancer, the tumor mutation burden was high in 4/6 (66.7%) patients and pembrolizumab was available. Another MET ex.14 skipping mutation was detected in two cases with EGFRtyrosine kinase inhibitor resistance. ICI efficacy was ≤1 year in patients with STK-11, KEAP1, and NEF2L2 mutations. A BRCA2 mutation with a high probability of germline mutation was detected in one patient. A thymic carcinoma with no detectable oncogenic mutation responded to second-line treatment with Tegafur-Gimeracil-Oteracil Potassium (TS-1) for ≥9 years. Conclusions: CGP panels are useful in thoracic malignancies, especially lung cancer, because they can detect overlooked driver mutations and genetic alterations. We believe that the significance of conducting a CGP panel prior to treatment may also exist, as it may lead to the prediction of ICI treatment efficacy.

Performance of Ultra-Rapid Idylla™ EGFR Mutation Test in Non-Small-Cell Lung Cancer and Its Potential at Clinical Molecular Screening

“…Notably, PCR-based single-plex EGFR mutation analyses, including the Idylla and Cobas assays, have a disadvantage of EGFR mutation coverages (87-98%) compared with NGS [12,13,20]. These data support the usefulness of comprehensive genomic profiling during the treatment course of NSCLC patients [21]. In this analysis, we incidentally observed that the Cobas assay reported false-positive results (calling EGFR exon 19 deletion in specimens with EGFR exon 19 L747P point mutation or exon 19 insertion).…”

Nationwide data from comprehensive genomic profiling assays for detecting driver oncogenes in non‐small cell lung cancer

“…CGP assays would be beneficial for the population with undetected driver oncogenes using single‐plex testing. In addition, among patients with undetected driver oncogenes using multigene panel assays, driver oncogenes newly detected using CGP assays have been reported 35,36 . This difference in the results may be due to the difference in the characteristics of these tests, samples used for testing, and the variants covered by CGP assays and multiplex gene panel testing.…”

“…In addition, among patients with undetected driver oncogenes using multigene panel assays, driver oncogenes newly detected using CGP assays have been reported. 35 , 36 This difference in the results may be due to the difference in the characteristics of these tests, samples used for testing, and the variants covered by CGP assays and multiplex gene panel testing. Therefore, irrespective of whether the initial evaluation is performed using single‐plex tests or multigene panel assays, CGP assays should be considered for individuals in whom driver oncogenes are not detected.…”

FoundationOne CDx detected an uncovered variant of epidermal growth factor receptor exon 19 deletion by Oncomine Dx target test in a patient with lung adenocarcinoma

“…Kunimasa et al reported that CGP tests led to treatment with molecular-targeted agents in 6 out of 60 patients (10%) with thoracic malignancies who underwent these tests. Furthermore, four patients with EGFR mutations that had not been detected by PCR-based single-gene tests were included among them [ 17 ]. Tsuda et al also reported that F1CDx identified a rare MYH9-ROS1 fusion gene that had not been detected by the ODxTT, leading to treatment with a ROS1-TKI [ 18 ].…”