144P - Is it time to incorporate next generation sequencing of body fluids for detection of circulating tumor DNA (ctDNA) alterations?

Background

Fluid cytology may provide false-negative or false-positive results, partly due to reactive cells mimicking malignant cells. This study aims to evaluate the utility of body fluids as source for detecting actionable molecular alterations associated with malignancy.

Methods

ctDNA derived from cerebrospinal (CSF) (n=7), pleural (n=10), and ascitic (n=24) fluids collected from 41 pts. with various malignancies, including lung (11), breast (8), ovary (8), pancreas (4), and others (10), were analyzed for detection of pathogenic molecular alterations using NGS. Concordant analysis body fluid (n=24) and tissue (n=9) was conducted in a subset.

Results

Pathogenic fluid ctDNA findings were observed in 78% (32/41) of samples. Potentially actionable alterations were observed in genes such as KRAS, BRAF, NRAS, PIK3CA and EGFR. Table: 144P

ESCAT categorization of variants in body fluids

Simultaneous analysis of tissue and fluid samples in 9 cases showed concordant findings in 67% (6/9) samples. Unique molecular alterations were observed in 4 fluid samples (not found in the tissue), providing potentially valuable insights into molecular heterogeneity. In the simultaneous body fluid and blood analysis (n=24), 30 variants were detected. Of these, 14 variants were detected in both sample types whereas 3 were missed in fluid. The most relevant finding was presence of 13 unique variants in body fluids (not found in blood liquid biopsy). Out of 13 samples with available fluid cytology, 7 samples showed both cytology positivity for malignancy and ctDNA. From the remaining 6 cytology-negative samples, 4 were positive for ctDNA, potentially demonstrating the utility of fluid molecular profiling for establishing malignant involvement.

Conclusions

This study emphasizes potential of fluid ctDNA profiling to detect pathogenic molecular alterations, providing insights into potentially actionable targets and the presence of malignancy. Validation in larger cohorts is warranted.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Datar Cancer Genetics.

Funding

Has not received any funding.

Disclosure

S. Limaye, A.K. Vaid, T. Crook, A. Gaya, R. Kurzrock: Non-Financial Interests, Personal, Advisory Board: Datar Cancer Genetics. D.S. Patil: Financial Interests, Personal, Full or part-time Employment: Datar Cancer Genetics. All other authors have declared no conflicts of interest.