Mp41-06 Implications of Neoadjuvant Chemotherapy on Cost and Outcomes in Muscle Invasive Bladder Cancer
Year: 2018
Type: article
Abstract: subjected to targeted NGS using a panel of 50 MIBC-relevant genes with sample indices and unique molecular barcodes.Their pre-AMVAC TURBT tissue also underwent whole exome sequencing (WES) as a benchmark for urine biopsy.Persistence or clearance of pre-AMVAC mutations was correlated to residual disease status.RESULTS: 99% of tumors in the TCGA BLCA cohort have mutation in at least one gene in the panel, with median 4 mutations per patient.Six patients had residual disease, and two patients had pathological complete response (pCR).In 6 of 8 patients, SNV T (single nucleotide variants found in the pre-AMVAC TURBT tissue) were also found in the cfuDNA.In patient YM-018, 0 of 7 SNV T were detected in the cfuDNA despite median 2127X sequencing depth, suggesting possible pCR prior to AMVAC or false negative.However, in one nonresponder, 0/1 SNV T was detected in the cfuDNA despite 1660X coverage at that particular variant.In these 8 patients, 24/37 SNV T were also identified in the cfuDNA; 7/13 nondetected SNV T came from YM-018, 4/13 nondetected SNV T were subclonal in the TURBT, and 2/13 clonal SNV T mutations were undetected.In the 2 complete responders, no SNV T were seen in the cfuDNA.In comparison, SNV T were detected in the post-AMVAC urine in 5/6 nonresponders.In addition, 3 TERT promoter hotspot mutations were detected using this approach that are not detectable using WES-based approaches.CONCLUSIONS: This pilot data engenders confidence that mutation persistence in cfuDNA associates with residual disease status.Additional samples from NCT01031420 and other clinical protocols are currently being analyzed.Further study may encourage development of this biomarker to improve residual disease detection in cystectomy avoidance algorithms.
Source: The Journal of Urology
Authors: Timothy Clinton, Solomon Woldu, Oner Sanli, Richard Wang, Louis Gianni, Ganesh Raj, Arthur Sagalowsky, Vitaly Margulis, Yair Lotan
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2795909406