![]() ![]() 21A-21E show that tumor organoids recapitulate patient tumor molecular landscapes. (Bottom) positive control (non-patient paired, genotype-matched (HLA-A02 positive) PBMC negative control (unrelated HLA-A02 negative) PBMC and patient-derived TO) fluorescence-activated cell sorting (FACS) data by panMHC and HLA-A02 antibodies. F: (Top)Three paired panels of Tempus xT sequencing coverage in the HLA-A locus (by normal, source tumor, and patient-derived TO). Highlighted is a region on chromosome 6 that is depicted as having a normal copy number in the sequenced tumor, but a predicted loss of heterozygosity in the paired patient derived TO. Major copy-number alterations >3 megabases (Mb) are depicted as blocks and copy-number alterations <3 Mb are depicted as points. E: Representative copy-number plots depicting a colon cancer tumor and corresponding patient-derived TO. Unpaired correlation represents all other pairwise comparisons between tumors and organoids. D: Transcriptome correlation between source tumors and tumor organoids. For A-C, variants included were classified as pathogenic, likely pathogenic or of unknown significance. C: VAF correlation of recapitulated variants. B: Somatic recapitulation and CNV concordance across cancers. ![]() For each gene, the top row represents source tumor mutations and the bottom row represents TO mutations. Genes presented were the top 10 most frequently mutated genes. 20A-20F show the genomic and transcriptomic concordance between TOs and source tumors. Estimates of the proportion of patients for whom genetic testing changes the trajectory of their care vary widely, from approximately 10% to more than 50%. “2018 ASCO: IMPACT Trial Matches Treatment to Genetic Changes in the Tumor to Improve Survival Across Multiple Cancer conditions.” The ASCO POST. The IMPACT study further found that the three-year overall survival for patients given a molecularly matched therapy was more than twice that of non-matched patients (15% vs. “IMPACT Trial: Support for Targeted Cancer Tx Approaches.” MedPageToday. ![]() Further, recent evidence reported from the IMPACT trial, which involved genetic testing of advanced stage tumors from 3,743 patients and where approximately 19% of patients received matched targeted therapies based on their tumor biology, showed a response rate of 16.2% in patients with matched treatments versus 5.2% in patients with non-matched treatments. Targeted therapies have shown significant improvements in patient outcomes, especially in terms of progression-free survival. Such methods may be particularly useful for patients who have already failed multiple lines of therapy. who used matching scores (e.g., scores based on the number of therapeutic associations and genomic aberrations per patient) to demonstrate that patients with higher matching scores have a greater frequency of stable disease, longer time to treatment failure, and greater overall survival (2016 Cancer Res. There is growing evidence that patients who receive therapeutic advice guided by genetics have better outcomes. Indeed, recent studies indicate that clinical care is guided by NGS assay results for 30-40% of patients receiving such testing. Genomic analysis of tumors is rapidly becoming routine clinical practice to provide tailored patient treatments and improve outcomes.
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