Multigene testing via NGS can detect multiple genomic alterations (GA). The use of current levels of evidence (LOE) requires understanding the functional consequences of the GA and an extensive literature search and have less practical value for narrowing down therapy recommendations if multiple GAs with the same LOE are found.
For each type of GA, depending on the gene and tumor type, a score from 1 to 10 was assigned independently by a group of biologists and oncologists; average scores were used for DB. Scores reflected the theoretical estimation of percentage of patients with biomarker that could be matched with such therapy, the efficacy of therapy based on expected benefit, quality of data, expert opinion; potential obstacles associated with access to therapy. To test the utility of the DB, we analyzed comprehensive molecular profiling (150+ gene NGS panels) (CMPR). GA were ranked using ESCAT and CRAC.
A total of 134 genes were selected for 16 malignancies with 2 GA for each in average (234 GA in total). GA with scores 2-3 outnumbered GA with scores 9-10 (36 vs 2%). The majority (17 vs 13%) of genes have average scores of 2-2.5, 3.5-4, within one tumor type. To test CRAC practical value 208 CMPR (23.5% CRC, 16.3% PAAD, 11% BRCA, 49% - other) with 210 GA analyzed. 64 (31%) reports contained 79 GA of I-III ESCAT, 114 (55%) - 131 level IV GA. The highest scores reflected the highest LOE. No GA with the same LOE had the same score; GA IIIA and IV LOE had the largest range of scores (2-10 and 1-9). CRAC made it possible to identify additional targetable GA with scores 2-4 (45% were not present in CMPR).
Using CRAC scores to identify clinically significant GA proved to be a more comprehensive approach compared to ESCAT LOE (each LOE was represented by ⩾3 scores; each CMPR had BM with ⩾2 scores). CRAC available at crac.oncoatlas.ru.
The authors.
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All authors have declared no conflicts of interest.