Blood based multigene testing using next generation sequencing to guide management in solid tumors: Experience from Augusta-Georgia.

Abstract

e15023 Background: The pool of somatic alterations with prognostic and predictive significance in management of solid tumors is rapidly expanding. Multigene panel testing using next generation sequencing (NGS) technology from peripheral blood specimen is convenient and readily available in most oncology practices. Widespread adoption is lagging, in part due to anticipation of low probability of finding an actionable information. We share our experience of real-world utilization of this technology. Methods: Blood based next generation testing ordered by providers in Georgia (outside Atlanta) between January 1, 2015, and December 31, 2021, via Guardant platform for all solid tumors was included in this analysis. Guardant360 and Guardant360CDx assays sequenced circulating cell-free DNA to detect somatic alterations in up to 83 cancer associated genes. Data was obtained from Guardant360 on site of cancer, comprehensive genomic profile, and therapeutic options at the time of report. Results: 25 providers in Georgia from 11 institutions sent 335 blood samples from solid cancer patients. There were 192 males and 143 females. Most common cancers were lung and bronchus (45%), prostate (13%), breast (11%), pancreaticobiliary (8%), colorectal (4%), melanoma (3%) and kidney (3%). Any somatic mutations were detected in 85% (285/335) patients. A total 1524 alterations comprising of 977 unique alterations involving 83 genes were detected, with an average of 5.3 unique genomic alterations per patient. The genes that were altered at least 2% of times were TP53 (20%), ATM (5.5%), PI3KCA (4.3%), KRAS (3.8%), APC (3.5%), AR (2.8%), PDGFRA (2.8%), ARIDIA (2.5%) and BRAF (2.2%). Of all alterations, 11% (170/1524) were synonymous and 31% (474/1524) were variant of unknown significance. 85 samples had tumor mutational burden (TMB) results available, with 55% (47/85) having TMB > 10 mut/Mb. The average TMB was 14.9 mutations/Mb. Out of 252 specimens evaluated for microsatellite instability (MSI), 1 had high MSI. An FDA approved drug targeting the alteration/pathway was available for the same cancer in 4% (77/1524) and for other cancers in 19% (291/1524) of alterations. An approved drug matched to the alteration was available for the same cancer in 16% (54/335) patients and for other cancers in 45% (153/335) patients. 12.5% (42/335) patients were predicted not to benefit from certain drugs. 74% (249/335) had a clinical trial available for the mutations present. Conclusions: Eighty five percent solid tumor patients had a positive result in blood based NGS. Seventy four percent patients had at least one therapeutically applicable (suggestion for a drug to target the alteration approved for the same/different cancers or lack of benefit due to the alteration) information. Thus, blood based NGS yields clinically relevant and actionable information to guide management in solid tumors.