ctDNA

Bladder cancer (BC) is one of the most common malignancies in the United States, with over 80,000 new cases and 16,000 deaths each year. Urothelial carcinoma (UC) is the most common histology and accounts for 90% of cases. BC management is complicated by recurrence rates of over 50% in both muscle-invasive and non-muscle-invasive bladder cancer. As such, the American Urological Association (AUA) recommends that patients undergo close surveillance during and after treatment. This surveillance is in the form of cystoscopy or imaging tests, which can be invasive and costly tests...

INTRODUCTION: Oral Squamous Cell Carcinoma (OSCC), the sixth most widespread malignancy in the world, accounts for 90% of all cases of oral cancer. The primary risk factors are tobacco chewing, alcohol consumption, viral infection, and genetic modifications. OSCC has a high morbidity rate due to the lack of early diagnostic methods. Nowadays, liquid biopsy plays a vital role in the initial diagnosis of oral cancer. ctNAs extracted from saliva and serum/plasma offer meaningful insights into tumor genetics and dynamics...

While we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), the independent contribution of quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study of 394 NSCLC patients, we utilize pre-treatment computed tomography (CT) and 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) to establish a habitat imaging framework for assessing regional heterogeneity within individual tumors...

BACKGROUND: Circulating tumour DNA (ctDNA), contains tumour-specific gene mutation in blood circulation and could aid in postoperative risk stratification of non-metastatic breast cancer. In this study, we investigated the feasibility of detecting PIK3CA gene mutations in ctDNA in the preoperative (preop) and postoperative period (postop), and its prognostic significance in patients with breast cancer. METHODS: A cohort of patients with breast cancer undergoing curative surgery with available blood samples preoperatively and postoperatively (Post op) at either Post op time period; week 1-2, week 3-4 or weeks 5-12 were enrolled...

Terahertz (THz) spectroscopy has impressive capability for label-free biosensing, but its utility in clinical laboratories is rarely reported due to often unsatisfactory detection performances. Here, we fabricated metal-graphene hybrid THz metasurfaces (MSs) for the sensitive and enzyme-free detection of circulating tumor DNA (ctDNA) in pancreatic cancer plasma samples. The feasibility and mechanism of the enhanced effects of a graphene bridge across the MS and amplified by gold nanoparticles (AuNPs) were investigated experimentally and theoretically...

BACKGROUND: Despite efficacy of approved FGFR inhibitors, emergence of polyclonal secondary mutations in the FGFR kinase domain leads to acquired resistance. KIN-3248 is a selective, irreversible, orally bioavailable, small molecule inhibitor of FGFR1-4 that blocks both primary oncogenic and secondary kinase domain resistance FGFR alterations. MATERIALS AND METHODS: A first-in-human, Phase 1 study of KIN-3248 was conducted in advanced solid tumors patients harboring FGFR2 and/or FGFR3 gene alterations (NCT05242822)...

Treatment resistance remains a major issue in aggressive prostate cancer (PC), and novel genomic biomarkers may guide better treatment selection. Circulating tumor DNA (ctDNA) can provide minimally invasive information about tumor genomes, but the genomic landscape of aggressive PC based on whole-genome sequencing (WGS) of ctDNA remains incompletely characterized. Thus, we here performed WGS of tumor tissue (n = 31) or plasma ctDNA (n = 10) from a total of 41 aggressive PC patients, including 11 hormone-naïve, 15 hormone-sensitive, and 15 castration-resistant patients...

Cholangiocarcinomas (CCAs) are a subclass of biliary tract tumors that arise from the epithelial lining of bile ducts. They are subdivided broadly into intra- and extrahepatic CCA, with extrahepatic being the more common. Circulating tumor DNA (ctDNA) is a form of liquid biopsy obtained from dying tumor cells in the peripheral blood. Assays may be tumor-informed or tumor-agnostic, with the former requiring tissue sampling to evaluate detectable mutations present in an individual patient's tumor. Here we present a case of intrahepatic CCA managed with hepatectomy followed by adjuvant chemotherapy, with subsequent surveillance and management guided by tumor-informed ctDNA...

BACKGROUND: Liquid biopsy based on circulating tumor DNA (ctDNA) is a novel tool in clinical oncology, however, its use has been limited in glioma to date, due to low levels of ctDNA. In this study, we aimed to demonstrate that sequencing techniques optimized for liquid biopsy in glioma patients can detect ctDNA in plasma with high sensitivity and with potential clinical utility. METHODS: We investigated 10 glioma patients with tumor tissue available from at least 2 surgical operations, who had 49 longitudinally collected plasma samples available for analysis...

IMPORTANCE: The available evidence regarding anti-epidermal growth factor receptor (EGFR) inhibitor rechallenge in patients with refractory circulating tumor DNA (ctDNA) RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) is derived from small retrospective and prospective studies. OBJECTIVE: To evaluate the efficacy of anti-EGFR rechallenge in patients with refractory ctDNA RAS/BRAF wt mCRC. DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized controlled trial used a pooled analysis of individual patient data from patients with RAS/BRAF wt ctDNA mCRC enrolled in 4 Italian trials (CAVE, VELO, CRICKET, and CHRONOS) and treated with anti-EGFR rechallenge between 2015 and 2022 (median [IQR] follow-up, 28...

OBJECTIVE: Circulating tumor DNA (ctDNA) detection is an emerging technique that identifies minimal residual disease in patients with solid tumors. ctDNA can act as an adjunct method to help overcome the limitations of positron emission tomography (PET) and select patients who are at high risk for recurrence. STUDY DESIGN: Retrospective Single Institutional Study. SETTING: University Hospital Setting. METHODS: Twenty-nine patients who underwent definitive treatment for squamous cell carcinoma of the head and neck (HNSCC) from 8/2021 to 01/2023 had ctDNA levels analyzed at 1 to 3, 6, 9, and 12 months after definitive treatment...

BACKGROUND: Biliary tract cancers (BTCs) are rare and lethal cancers, with a 5-year survival inferior to 20%(1-3). The only potential curative treatment is surgical resection. However, despite complex surgical procedures that have a remarkable risk of postoperative morbidity and mortality, the 5-year survival rate after radical surgery (R0) is 20-40% and recurrence rates are up to ~ 75%(4-6). Up to ~ 40% of patients relapse within 12 months after resection, and half of these patient will recur systemically(4-6)...

MOTIVATION: Blood-based profiling of tumor DNA ("liquid biopsy") has offered great prospects for non-invasive early cancer diagnosis, treatment monitoring, and clinical guidance, but require further advances in computational methods to become a robust quantitative assay of tumor clonal evolution. We propose new methods to better characterize tumor clonal dynamics from circulating tumor DNA (ctDNA), through application to two specific questions: 1) How to apply longitudinal ctDNA data to refine phylogeny models of clonal evolution, and 2) how to quantify changes in clonal frequencies that may be indicative of treatment response or tumor progression...

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The clinical use of cell-free DNA (cfDNA) methylation in managing lung cancer depends on its ability to differentiate between malignant and healthy cells, assign methylation changes to specific tissue sources, and elucidate opportunities for targeted therapy. From a technical standpoint, cfDNA methylation analysis is primed as a potential clinical tool for lung cancer screening, early diagnosis, prognostication, and treatment, pending the outcome of elaborate validation studies. Here, we discuss the current state of the art in cfDNA methylation analysis, examine the unique features and limitations of these new methods in a clinical context, propose two models for applying cfDNA methylation data for lung cancer screening, and discuss future research directions...

PURPOSE: Although changes in circulating tumour DNA (ctDNA) in breast cancer are well described, the kinetics of their fluctuations has not been described over short timescales. We investigated ctDNA dynamics during alternating cycles of chemotherapy and hormonal treatment in pre-treated patients with oestrogen receptor-positive metastatic breast cancer. METHODS: Patients received alternating, 9-week cycles of eribulin and aromatase inhibitors (AIs). The clinical primary endpoint, progression-free survival (PFS), was monitored at 3, 6 and 9 months; secondary endpoints, clinical benefit rate (CBR), safety and tolerability profiles, were also assessed...

Epithelial ovarian cancer (EOC) is one of the leading causes of cancer-related death in women worldwide, and is characterized by a high rate of recurrence after surgery and chemotherapy. We sought to implement a circulating tumor DNA (ctDNA)-based blood test for more accurate post-operative surveillance of this disease. We analyzed 264 plasma samples collected between June 2016 and September 2021 from 63 EOC patients using tumor-guided plasma cell-free DNA analysis to detect residual disease after treatment...

BACKGROUND: Biological heterogeneity of large B cell lymphomas (LBCLs) is poorly captured by current prognostic tools, hampering optimal treatment decisions. METHODS: We dissected the levels of 1,463 serum proteins in a uniformly treated trial cohort of 109 patients with high-risk primary LBCL (ClinicalTrials.gov: NCT01325194) and correlated the profiles with molecular data from tumor tissue and circulating tumor DNA (ctDNA) together with clinical data. FINDINGS: We discovered clinically and biologically relevant associations beyond established clinical estimates and ctDNA...

PURPOSE: There are limited data available on the real-world patterns of molecular testing in men with advanced prostate cancer. We thus sought to evaluate next-generation sequencing (NGS) testing in the United States, focused on single versus serial NGS testing, the different disease states of testing (hormone-sensitive v castration-resistant, metastatic vs nonmetastatic), tissue versus plasma circulating tumor DNA (ctDNA) assays, and how often actionable data were found on each NGS test...

OBJECTIVES: We analysed whether temporal heterogeneity of ctDNA encodes evolutionary patterns in ovarian cancer. METHODS: Targeted sequencing of 275 cancer-associated genes was performed in a primary tumor biopsy and in ctDNA of six longitudinal plasma samples from 15 patients, using the Illumina platform. RESULTS: While there was low overall concordance between the mutational spectrum of the primary tumor biopsies vs. ctDNA, TP53 variants were the most commonly shared somatic alterations...