481MO - Next-generation sequencing (NGS) of paired tumor tissue and blood samples from patients with advanced solid cancers: A complementary approach

Background

Tissue-based NGS is the traditional approach for identifying actionable mutations in solid tumors, while blood-based NGS of circulating tumor DNA (ctDNA) has similar sensitivity and faster turnaround time. Because neither technique has perfect detection of clinically informative (CI) genomic alterations, we evaluated the utility of combining both tests in clinical practice in the largest study of its kind in India.

Methods

We retrospectively analyzed ctDNA and tissue NGS results (Guardant360® and Guardant360 TissueNext™, Guardant Health, USA) from patients with advanced solid malignancies collected between November 2022 and June 2024 at a single tertiary care center. Tests were part of routine practice, comparing only genes common between blood and tissue assays. CI alterations included those with FDA-approved therapies (for the given or another indication), resistance-causing alterations, bTMB high (>16 Mut/Mb), Tissue TMB high (>10 Mut/Mb), or MSI high as of the report date.

Results

Among 334 samples (208 blood and 126 tissue), report success rates were 90.4% for ctDNA and 84.1% for tissue NGS. The median turnaround time from sample reaching lab to results was 7 days for ctDNA and 13 days for tissue. In 97 patients with paired samples (lung: 15, breast: 12, colorectal: 10, pancreatic: 8, gynecological: 8, biliary tract: 8 and others), CI alterations were found by either technique for 69 (71%); ctDNA only 26 (27%), tissue only 12 (12.3%). Among 148 alterations detected in ctDNA, 20 (13.5%) had FDA-approved therapies in the given indication. Among 75 alterations found in tissue, 16 (21.3%) had FDA-approved therapies. Additionally, 64.2% and 58.7% of ctDNA and tissue alterations, respectively, were associated with FDA-approved therapies for other indications. Simultaneous ctDNA and tissue NGS led to changes in planned treatment for 44 (45%) of patients across various lines of therapy.

Conclusions

ctDNA NGS offered quicker turnaround and found a similar number of CI mutations as tissue NGS therefore a ctDNA NGS first approach could be preferred. However, concurrent use of both the techniques offers broadest coverage of mutation detection.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

N. Rohatgi: Financial Interests, Personal, Advisory Role: Guardant Health. R. Bharat: Financial Interests, Personal, Full or part-time Employment: Guardant Health. N. Joshi: Financial Interests, Institutional, Full or part-time Employment: Guardant Health. A. Bahl: Financial Interests, Personal and Institutional, Advisory Role: Guardant Health. S.S. Jain: Financial Interests, Personal, Stocks or ownership: Guardant Health; Financial Interests, Institutional, Full or part-time Employment: Guardant Health. All other authors have declared no conflicts of interest.