In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 459-459
Abstract:
459 Background: Liquid biopsy has become increasingly important in cancer diagnosis and disease progression monitoring. Copy number variation is an important characteristic for genitourinary cancer and many other cancer types, where bladder cancer was shown to have the largest copy number alternation among 33 human cancer types from TCGA. We developed PredicineCNB, a companion LP-WGS assay to robustly estimate genome-wide copy number burden (CNB) from plasma and urine clinical samples, which can provide longitudinal disease monitoring in a cost-effective way. Methods: By integrating both fragments coverage and fragments length from LP-WGS data, and quantifying copy number deviation at chromosome arm level, we greatly increase both sensitivity and specificity for CNB based cancer detection. Analytical evaluation was performed based on clinical plasma titration samples, and PredicineCNB has demonstrated high cancer detection sensitivity (LOD is 1%) with high specificity ( 〉 99%), using DNA input amounts as low as 1ng. We also validated CNB using Predicine panel-based tumor fraction for more than 200 clinical samples, results demonstrated both are highly concordant with correlation coefficient 0.84. Results: We performed clinical evaluation of PredicineCNB on 700 patients with prostate cancer and 300 patients with bladder cancer. For clinical patients with longitudinal samples under different disease stages or drug treatments, we demonstrated a promising potential using PredicineCNB for monitoring dynamic changes in ctDNA, that are caused by copy number variation. For 12 different bladder cancer patients, each with at least two longitudinal samples, we observed that CNB declines as early as two weeks after treatment initiation, providing an early signal of molecular response to therapy. In addition, when comparing conventional radiology-based imaging with CNB, we found that an increase in CNB preceded clinical progression of disease in majority of patients; and CNB shows a positive correlation between cancer stage revealed by CT scan. Conclusions: We conducted a comprehensive clinical study using PredicineCNB in 1,000 patients with prostate and bladder cancers, demonstrating the promising clinical application of liquid biopsy-based genome-wide copy number changes in therapy monitoring.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2023.41.6_suppl.459
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2023
detail.hit.zdb_id:
2005181-5