Abstract 1800P
Background
Tumour biopsies may be difficult to obtain and may not capture genetic variations due to tumour heterogeneity. Using ctDNA can be an alternative, non-invasive approach for detecting genetic variations. Assessing plasma as a surrogate sample for the identification of tissue mutations across cancer types requires further investigation.
Methods
Matched plasma and tissue samples were collected from 54 SCLC and 36 NSCLC treatment-naive late stage subjects. Tumour tissue and plasma samples were analysed with the AVENIO® Tumor Tissue and ctDNA Surveillance Kits*. Mutations were identified and reported by the AVENIO® software v2.0*. A machine learning algorithm was applied to identify somatic mutations. Mutations in tissue samples were compared with those identified in matched ctDNA in all targeted regions and also filtered based on well-known somatic mutations. *For Research Use Only. Not for use in diagnostic procedures.
Results
Sufficient, high quality DNA was extracted from all plasma samples for sequencing, in contrast to tissue. 38 (70.4%) SCLC and 29 (80.6%) NSCLC subjects remained for analysis. The median number of mutations in SCLC/NSCLC was 5/4 in tissue and 5.5/5 in ctDNA, and 1/1 in both sample types after filtering. The rate of tissue mutations detected in ctDNA was lower in NSCLC (66%) than SCLC (95%), and in NSCLC (81%) and SCLC (97%) after filtering. 34 (89.5%) SCLC and 16 (55.2%) NSCLC subjects had all tissue mutations detected in ctDNA. After filtering, this was observed in 37 (97.4%) SCLC and 23 (79.3%) NSCLC subjects. In NSCLC, subjects with < 30 ng ctDNA inputs and < 3% mean allelic frequency (AF) in ctDNA had lower concordance using either tissue (P = 0.0066) or ctDNA (P = 0.0307) as reference. Samples with above median of either mutated molecules per ml plasma (P = 0.0007) or maximum AF (P = 0.0105) in cfDNA had higher rates of tissue mutations detected in ctDNA for NSCLC.
Conclusions
By utilizing a machine learning algorithm of variant calling, the study demonstrated high concordance between plasma and tissue, and showed that ctDNA assays could be an alternative approach for genomic profiling of late stage SCLC and NSCLC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Roche Sequencing Solutions, Inc.
Funding
Roche Sequencing Solutions, Inc.
Disclosure
C. Woestmann: Full/Part-time employment: Roche (Signature Diagnostics). J. Jiang: Full/Part-time employment: Roche; Shareholder/Stockholder/Stock options: Roche. J.F. Palma: Full/Part-time employment: Roche; Shareholder/Stockholder/Stock options: Roche. C. Ju: Full/Part-time employment: Roche. C.P. Heussel: Advisory/Consultancy: Pfizer; Advisory/Consultancy: Basilea; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Novartis; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: Gilead Sciences; Advisory/Consultancy: MSD; Advisory/Consultancy: Lilly; Advisory/Consultancy: InterMune; Advisory/Consultancy: Fresenius; Advisory/Consultancy: Essex; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: Bracco Diagnostics; Advisory/Consultancy: Meda Pharmaceuticals; Speaker Bureau/Expert testimony: Chiesi; Speaker Bureau/Expert testimony: Siemens; Speaker Bureau/Expert testimony: Covidien; Speaker Bureau/Expert testimony: Pierre Fabre; Speaker Bureau/Expert testimony: Grifols. S. Yaung: Full/Part-time employment: Roche. M. Thomas: Honoraria (institution): Lilly, Roche, Celgene, BMS, AbbVie, AstraZeneca and MSD; Advisory/Consultancy: Lilly, Roche, BMS, AbbVie, Celgene, Novartis, Pfizer, AstraZeneca, and MSD. M. Meister: Research grant/Funding (institution): Roche Diagnostics. M. Schneider: Research grant/Funding (institution): Roche. F. Herth: Advisory/Consultancy: Pulmonx, BTG, Uptake Medical, Olympus Medical, and Holaira; Research grant/Funding (institution): Roche Diagnostics. T. Muley: Research grant/Funding (institution): Roche Diagnostics; Travel/Accommodation/Expenses: Roche Diagnostics; Honoraria (self): Roche Diagnostics. B. Wehnl: Full/Part-time employment: Roche. B. Hinzmann: Full/Part-time employment: Roche (Signature Diagnostics); Shareholder/Stockholder/Stock options: Roche. All other authors have declared no conflicts of interest.