Next generation sequencing (NGS) of malignant effusions and comparison to blood liquid biopsy (ctDNA): A community experience.

Abstract

e20661 Background: NGS of cancer cells is critical in guiding personalized cancer treatment. While tissue-based NGS is the gold standard, obtaining sufficient tissue for analysis is often a challenge. Malignant effusions offer an alternative source of tumor DNA. ctDNA from blood-based liquid biopsies provides a minimally invasive option for NGS. This study evaluates the feasibility and clinical relevance of NGS in malignant effusions and compares the findings to blood-based ctDNA analysis in a community setting. Methods: From May 2021 to Jul 2024, malignant effusion and blood samples were collected from 31 pts. 19 males (61%) and 12 females (39%). Median age: 62 years (range: 31-79). Twenty two pts. had pleural effusions (71%), 9 had ascites (29%). Cancer types: 17 lung (55%), 7 GI (23%), 4 GYN (13%), 2 breast (6%), 1 other (3%). 3 samples (9%) were collected prior to any treatments. Four/31 (13%), 8/31(26%), 11/31(35%), 5/31(16%) samples were collected, after 1st, 2nd, 3rd and 4th line treatment, respectively. Genomic alterations, including somatic mutations, gene fusions, and copy number variations, were analyzed and compared between malignant effusions and ctDNA. Clinical outcomes, including treatment modifications and response rates, were monitored. Results: NGS of malignant effusions identified genomic alterations in 24/31 cases (77%). The most frequent mutations were: TP53 (17 pts, 52%), KRAS (10 pts, 31%), EGFR (7 pts, 19%) and PIK3CA (6 pts, 14%). Blood-based ctDNA analysis detected alterations in 19/31 cases (62%), with a 68% concordance for key driver mutations. Malignant effusions revealed additional alterations in 7/31 cases (22%), including novel gene fusions and copy number variations not detected in ctDNA. Among 3 treatment-naïve samples (9%), malignant effusions provided a higher yield of actionable alterations compared to ctDNA (2/3 case (66%) vs. 1/3 cases (33%). The median turnaround time was14 days for effusion analysis and 10 days for ctDNA analysis. Based on NGS findings, 12/31 patients (38%) received targeted therapies, with an ORR of 66% (8/12 patients). PD-L1 expression was identified in 3/31 malignant effusion samples (10%), a limitation of plasma-based liquid biopsies, as PD-L1 expression cannot be assessed through ctDNA. Conclusions: This study demonstrates the feasibility and clinical utility of NGS in malignant effusions in a community setting, particularly when obtaining adequate tissue biopsies is challenging. While blood-based ctDNA analysis offers a less invasive and faster alternative, malignant effusions provide additional genomic insights, including novel alterations and PD-L1 expression. The integration of both approaches enhances diagnostic accuracy for personalized treatment plans, thus, underscoring the potential of precision oncology in community-based practice.