IMBdx

Our Solution

Early detection of cancer.

Publications

게시물 목록
NO	YEAR	SUBJECT	JOURNAL NAME	LINK
14	2023	Accurate Detection of Urothelial Bladder Cancer Using Targeted Deep Sequencing of Urine DNA Abstract Patients with hematuria are commonly given an invasive cystoscopy test to detect bladder cancer (BC). To avoid the risks associated with cystoscopy, several urine-based methods for BC detection have been developed, the most prominent of which is the deep sequencing of urine DNA. However, the current methods for urine-based BC detection have significant levels of false-positive signals. In this study, we report on uAL100, a method to precisely detect BC tumor DNA in the urine without tumor samples. Using urine samples fr\|om 43 patients with BC and 21 healthy donors, uAL100 detected BC with 83.7% sensitivity and 100% specificity. The mutations identified in the urine DNA by uAL100 for BC detection were highly associated with BC tumorigenesis and progression. We suggest that uAL100 has improved accuracy compared to other urine-based methods for early BC detection and can reduce unnecessary cystoscopy tests for patients with hematuria. Accurate Detection of Urothelial Bladder Cancer Using Targeted Deep Sequencing of Urine DNA LINK VIEW	Cancers	LINK _VIEW
13	2023	Circulating Tumor DNA Dynamics and Treatment Outcome of Regorafenib in Metastatic Colorectal Cancer ABSTRACT Purpose Circulating tumor DNA (ctDNA) is emerging as a valuable non-invasive tool to identify tumor heterogeneity and tumor burden. This study investigated ctDNA dynamics in metastatic colorectal cancer patients treated with regorafenib. Materials and Methods In this prospective biomarker study, plasma cell-free DNA (cfDNA) samples obtained at baseline, at the first response evaluation after 2 cycles of treatment, and at the time of progressive disease (PD) were sequenced using a targeted next-generation sequencing platform which included 106 genes. Results A total of 285 blood samples fr\|om 110 patients were analyzed. Higher baseline cfDNA concentration was associated with worse progression-free survival (PFS) and overall survival (OS). After 2 cycles of treatment, variant allele frequency (VAF) in the majority of ctDNA mutations decreased with a mean relative change of -31.6%. Decreases in the VAF of TP53, APC, TCF7L2, and ROS1 after 2 cycles of regorafenib were associated with longer PFS. We used the sum of VAF at each time point as a surrogate for the overall ctDNA burden. A reduction in sum (VAF) of ≥ 50% after 2 cycles was associated with longer PFS (6.1 vs. 2.7 months, p=0.002), OS (11.3 vs. 5.9 months, p=0.001), and higher disease control rate (86.3% vs. 51.1%, p<0.001). VAF of the majority of the ctDNA mutations increased at the time of disease progression, and VAF of BRAF increased markedly. Conclusion Reduction in ctDNA burden as estimated by sum (VAF) could be used to predict treatment outcome of regorafenib. Circulating Tumor DNA Dynamics and Treatment Outcome of Regorafenib in Metastatic Colorectal Cancer LINK VIEW	Cancer Research and Treatment	LINK _VIEW
12	2023	Practical Utility of Liquid Biopsy for Evaluating Genomic Alterations in Castration-Resistant Prostate Cancer Abstract Traditional tissue-based assessments of genomic alterations in castration-resistant prostate cancer (CRPC) can be challenging. To evaluate the real-world clinical utility of liquid biopsies for the evaluation of genomic alterations in CRPC, we preemptively collected available plasma samples and archival tissue samples fr\|om patients that were being treated for clinically confirmed CRPC. The cell-free DNA (cfDNA) and tumor tissue DNA were analyzed using the AlphaLiquid®100-HRR panel. Plasma samples fr\|om a total of 87 patients were included in this study. Somatic mutations fr\|om cfDNA were detected in 78 (89.7%) patients, regardless of the presence of overt metastasis or concomitant treatment given at the time of plasma sample collection. Twenty-three patients were found to have known deleterious somatic or germline mutations in HRR genes fr\|om their cfDNA. Archival tissue samples fr\|om 33 (37.9%) patients were available for comparative analysis. Tissue sequencing was able to yield an NGS result in only 51.5% of the tissue samples. The general sensitivity of cfDNA for detecting somatic mutations in tissues was 71.8%, but important somatic/germline mutations in HRR genes were found to have a higher concordance (100%). Liquid biopsies can be a reasonable substitute for tissue biopsies in CRPC patients when evaluating genomic alterations. Practical Utility of Liquid Biopsy for Evaluating Genomic Alterations in Castration-Resistant Prostate Cancer LINK VIEW	Cancers	LINK _VIEW
11	2023	Efficacy of Olaparib in Treatment-Refractory, Metastatic Breast Cancer with Uncommon Somatic BRCA Mutations Detected in Circulating Tumor DNA Abstact Poly(ADP-ribose) polymerase inhibitors have been shown dramatic responses in patients with BRCAness. However, clinical studies have been limited to breast cancer patients with germline mutations. Here, we describe a patient with metastatic breast cancer who had a rare BRCA1 somatic mutation (BRCA1 c.4336G>T (p.E1446)) detected by cell-free DNA analysis after failing standard therapies. This tier III variant of unknown significance was predicted to be a pathogenic variant in our assessment, leading us to consider off-label treatment with olaparib. The patient responded well to olaparib for several months, with a decrease in allele frequency of this BRCA1 somatic mutation in cfDNA. Olaparib resistance subsequently developed with an increase in the allele frequency and new BRCA1 reversion mutations. To our knowledge, this is the first report confirming BRCA1 c.4336G>T (p.E1446) as a mutation sensitive to olaparib in breast cancer and describing the dynamic changes in the associated mutations using liquid biopsy. Efficacy of Olaparib in Treatment-Refractory, Metastatic Breast Cancer with Uncommon Somatic BRCA Mutations Detected in Circulating Tumor DNA LINK VIEW	Cancer Research and Treatment	LINK _VIEW
10	2023	Marked Response to Larotrectinib in Pelvic Spindle Cell Sarcoma With Concurrent TPM3-NTRK1 Fusion and CDK4/MDM2 Amplification: A Case Report Background Primary pelvic sarcoma is rare and often involves adjacent organs including rectum and urinary bladder because of the anatomic constraints of the pelvis.1 This may impede the attempts to achieve wide excision with tumor-free margins. Here, we reported that perioperative targeted therapy against tyrosine receptor kinase is a promising therapeutic approach to significantly improve surgical outcomes in huge pelvic spindle cell sarcoma with neurotrophic tyrosine receptor kinase (NTRK) gene fusion. Marked Response to Larotrectinib in Pelvic Spindle Cell Sarcoma With Concurrent TPM3-NTRK1 Fusion and CDK4/MDM2 Amplification: A Case Report LINK VIEW	JCO Precision Oncology	LINK _VIEW