tbuckley/cabot-search huggingface dataset:
Abstract B013: An mDETECT assay for monitoring treatment response in metastatic breast cancer patients
Authors: Keira Frosst, Brooke Wilson, Katrina Cristall, Catherine Crawford-Brown, Christopher R Mueller
Journal: Clinical Cancer Research (2024)

Abstract Metastatic breast cancer treatment response is currently assessed every 3-6 months and this long delay results in many patients undergoing ineffective and toxic treatments for long periods of time. We have developed the methylation DETEction of Circulating Tumour DNA (mDETECT) assay, a targeted DNA methylation-based Next Generation Sequencing liquid biopsy that detects cancer-specific patterns in all subtypes of breast cancer. The assay targets 60 differentially hypermethylated regions in breast cancer across the genome and assesses over 400 individual CpGs with an average of 8 CpGs per target amplicon. The assay has been assessed on DNA from 73 breast cancer tumour samples which on average had 40 regions hypermethylated per patient with similar rates across all subtypes. We will present results from plasma samples from locally advanced and metastatic breast cancer patients along with plasma from age-matched, healthy female controls. A prospective, multi-centre observational cohort study to monitor metastatic breast cancer patients using the mDETECT liquid biopsy as they undergo treatment is active and recruiting patients. Blood is drawn with every standard-of-care blood draw for up to 3 years. Plasma has been assessed using the mDETECT assay to determine the methylation status of the DNA at each time point. 35 patients have been enrolled to date with ongoing recruitment up to 150 patients. Patients are being monitored with the mDETECT assay for earlier detection of disease progression on a treatment. They will also be monitored through treatment changes to assess a patient’s initial response to a given treatment. Changes in mDETECT levels will be correlated with clinical response to determine if the mDETECT breast cancer assay can detect a response to treatment at an earlier timepoint. This assay could allow for improved monitoring of treatment response allowing clinicians to make informed decisions, improving outcomes and prolonging patient’s lives. Citation Format: Keira Frosst, Brooke Wilson, Katrina Cristall, Catherine Crawford-Brown, Christopher R Mueller. An mDETECT assay for monitoring treatment response in metastatic breast cancer patients [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B013.
Abstract A072: Oncuria®-Monitor, a non-invasive test for the detection of recurrent bladder cancer: Cross sectional performance evaluation from a multicenter study
Authors: Zhen Zhang, Florence Le Calvez-Kelm, Makito Miyake, Ian Pagano, Takuto Shimizu, Sergei Tikhonenkov, Sunao Tanaka, Charles J Rosser, Steve Goodison, Hideki Furuya
Journal: Clinical Cancer Research (2024)

Abstract Up to 70% of patients with non-muscle invasive bladder cancer (NMIBC) experience disease recurrence, making it one of the most prevalent cancers in the US. The purpose of this study was to test the performance of Oncuria®-Monitor, a multiplex urinary biomarker assay for the monitoring of voided urine for recurrent bladder cancer. This cross-sectional, multicenter study included a total of 283 subjects with a history of bladder cancer. Voided urine specimens were collected prior to any procedures for multiplex analysis. The diagnostic performance of the biomarker panel was assessed using receiver operator curves (ROC) and descriptive statistical values (e.g., sensitivity and specificity) and compared with the patients’ clinical data and final diagnosis as defined by the results of cystoscopy. Oncuria®-Monitor achieved an overall sensitivity of 94.3%, specificity of 83.6% and negative predictive valuer (NPV) of 96.2% for the detection of recurrent bladder cancer. Patient summary: We conducted a large cross-sectional clinical study for detecting recurrent bladder cancer with a novel, simple urine test (Oncuria®- Monitor), which measures 10 bladder cancer associated proteins in a single voided urine and can be used to detect recurrent bladder cancer. We analyzed urines from 283 patients and demonstrated that Oncuria®-Monitor can detect recurrent bladder cancer with a high degree of accuracy, specifically in patients with high grade or high stage disease. In conclusion, the novel Oncuria®-Monitor urine test can be used to surveil patients with a history of bladder cancer. Citation Format: Zhen Zhang, Florence Le Calvez-Kelm, Makito Miyake, Ian Pagano, Takuto Shimizu, Sergei Tikhonenkov, Sunao Tanaka, Charles J Rosser, Steve Goodison, Hideki Furuya. Oncuria®-Monitor, a non-invasive test for the detection of recurrent bladder cancer: Cross sectional performance evaluation from a multicenter study [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A072.
Abstract B051: A T-cell signature in circulating cell-free DNA at time of diagnosis predicts response to checkpoint inhibition
Authors: Phil Xie, Zohar Etzioni, Chun-Xiao Song, Richard P Owen, Mark R Middleton, Xin Lu, Benjamin Schuster-Boeckler
Journal: Clinical Cancer Research (2024)

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR017) of the Conference Program/Proceedings. Citation Format: Phil Xie, Zohar Etzioni, Chun-Xiao Song, Richard P Owen, Mark R Middleton, Xin Lu, Benjamin Schuster-Boeckler. A T-cell signature in circulating cell-free DNA at time of diagnosis predicts response to checkpoint inhibition [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B051.
Abstract B054: Using FRAGILE score to capture context-dependent cfDNA fragmentation patterns for inference on their tissues-of-origin
Authors: Subhajyoti De
Journal: Clinical Cancer Research (2024)

Abstract Cell-free nucleic acids circulating in blood and other body fluids are usually highly fragmented and derived from multiple different tissue types, which makes it challenging to obtain information about their cellular and contextual origin. Analyzing low coverage cell-free DNA whole genome sequencing data from 243 healthy individuals, we showed that cfDNA fragmentation and degradation patterns vary depending on their underlying genomic and epigenomic contexts. We developed a composite index called FRAGILE Score (FRagment of Atypical GC and Irregular Length Enrichment Score) to capture the structure, sequence, and fragmentation-related properties of cell-free, and showed that the score carried information about the epigenomic contexts of the cfDNA fragments. A deconvolution approach based on the score predicts the cell type contribution in serum cfDNA from healthy individuals and cancer patients. We collected blood and urine of a cohort of 30 bladder urothelial carcinoma patients, and found that cfDNA derived from blood and urine had very different fragmentation characteristics. An analysis of cfDNA from paired urine and blood samples from this showcased utility of the score in predicting clinical and pathological characteristics non-invasively for clinical management of the patients. Citation Format: Subhajyoti De. Using FRAGILE score to capture context-dependent cfDNA fragmentation patterns for inference on their tissues-of-origin [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B054.
Abstract B069: Spatial and single-cell proteomic landscaping of the hypoxic microenvironment in glioblastoma
Authors: Shreya Gandhi, Sheila Mansouri, Olivia Singh, Mark Zaidi, Ronald Wu, Andrew Gao, Bradley Wouters, Gelareh Zadeh
Journal: Clinical Cancer Research (2024)

Abstract Glioblastoma (GBM) is a fatal adult solid tumour with median overall survival of 18-20 months post-diagnosis; contributing factors to therapeutic inefficacy include acquisition of genomic alterations post-therapy, immune evasion, deregulated hypervascularization, and tumor microenvironmental factors such as hypoxia. Combined with extensive inter- and intra-tumoral heterogeneity at bulk and single-cell level, hypoxia contributes to a gradient of molecular alterations that are specific to different cell populations that make up tumour bulk and reside in specific niches. Hitherto, high-dimensional histopathologic analyses of hypoxic regions within GBM tissue have not been performed. We took a combined spatial and single-cell proteomic profiling approach to investigate the histopathologic features of hypoxia by leveraging a unique clinical study wherein the exogenous hypoxia marker, pimonidazole (PIMO), was administered to GBM-patients preoperatively. Tissue specimens were subjected to imaging mass cytometry, high-resolution imaging, and serial immunohistochemistry using a panel of markers associated with cellular hallmarks of hypoxia, metabolism, proliferation, stemness, angiogenesis, and immune cell types. Our findings showed that PIMO staining is associated with histopathologic features of hypoxia and correlates with specific metabolic, immune, and stemness markers in GBM; specific lymphocyte populations were depleted from hypoxic regions alongside alterations in macrophagic and microglial landscape in a niche-specific manner; hypoxia reduced the proportion of proliferating glioma initiating cells and altered the proliferative, transcriptional, and translational capacity of different cell populations; microvessel density was reduced in hypoxic microenvironment. Cytometry by time-of-flight further validated the altered proportions of specific immune cell types enriched in hypoxic populations of GBM microenvironment. Our study is the first to report use of PIMO to interrogate spatial, single-cell, and phenotypic architecture associated with tissue hypoxia and altered expression of biomarkers associated with hypoxia/glycolysis, immune infiltration, proliferation, and stemness. Identification of targetable biomarkers and mediators of hypoxia-driven habitats in GBM may provide direction for future immunotherapeutic research. Citation Format: Shreya Gandhi, Sheila Mansouri, Olivia Singh, Mark Zaidi, Ronald Wu, Andrew Gao, Bradley Wouters, Gelareh Zadeh. Spatial and single-cell proteomic landscaping of the hypoxic microenvironment in glioblastoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B069.
Abstract B034: Prevalence and implication of aflatoxin B1 expression in colon cancers diagnosed in Southern Nigeria
Authors: Chiagoziem Moral Delu-mozie, Jude Ogechukwu Okoye
Journal: Clinical Cancer Research (2024)

Abstract Introduction: Mounting evidence shows that there is a high prevalence of late-stage, aggressive, and metastatic adenocarcinoma of the colon (AdCC) in Africa, with high mortality and low survival rate among patients. Literature finger food contaminants such as mycotoxin, especially Aflatoxin, as an attributable factor to the high incidence of abdominal cancers. However, there is a paucity of studies to confirm the hypothesis. Hence, this study determined the prevalence of Aflatoxin B1 in AdCC in Southern Nigeria. Citation Format: Chiagoziem Moral Delu-mozie, Jude Ogechukwu Okoye. Prevalence and implication of aflatoxin B1 expression in colon cancers diagnosed in Southern Nigeria [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B034.
Abstract A044: Utilizing breast cancer-specific micronuclei DNA features from erythrocytes for early detection of breast carcinoma
Authors: Wenjv Mo, Xingyun Yao, Haobo Sun, Honghao Liang, Jie Jin, Xiaowen Ding, Xiaofei Gao
Journal: Clinical Cancer Research (2024)

Abstract Background: Alongside traditional imaging, current development in non-invasive breast carcinoma (BC) diagnosis, such as cell-free DNA-based technologies, have demonstrated promising potential in BC diagnosis. However, achieving early detection remains a challenge. Micronuclei (MN) are extranuclear bodies containing damaged chromosome segments indicative of genomic instability. Elevated levels of MN-containing erythrocytes have been studied in genotoxicity testing and cancer diagnosis. Here, we sequenced the isolated and purified micronuclei DNA (MN-DNA) from erythrocytes in 2ml peripheral blood using a method we previously developed (WO2021/228246 A1) and identified a series of distinct features in read counts that enabled to detect early-stage BC patients. Methods: We collected a clinical study cohort of 172 BC patients and 216 non-BC controls from 1-2ml peripheral blood. MN-DNA was isolated from erythrocytes and performed whole-genome sequencing. We selected distinctive tumor-associated MN-DNA features identified by genome-wide analysis to differentiate between controls and BC for KEGG pathway enrichment and constructed a classification model based on these features. Results: Genome-wide analysis of MN-DNA revealed significant regions between controls and BC patients. Based on covered genes, we observed significant enrichment in the estrogen signaling pathway. Utilizing these distinct MN- DNA features, we constructed a classification model that achieved an AUC of 96%, with a 95% specificity and 88% sensitivity in the test cohort. The model identified early BC (stage 0-I) and advanced BC (stage II-IV) with sensitivities of 100% or 84%, respectively. Conclusions: Our findings highlight that MN-DNA, a form of cytoplasmic DNA, provides a valuable tool for the accurate detection of BC, particularly in its early stages. The MN-DNA pattern is linked to the estrogen signaling pathway, offering novel insights and mechanisms that differ from current diagnostic approaches. Research sponsor: Timing Biotech. Early Detection of Primary Cancer and Relapse Citation Format: Wenjv Mo, Xingyun Yao, Haobo Sun, Honghao Liang, Jie Jin, Xiaowen Ding, Xiaofei Gao. Utilizing breast cancer-specific micronuclei DNA features from erythrocytes for early detection of breast carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A044.
Abstract A070: Diagnostic accuracy of Oncuria®-Detect in the detection of upper tract urothelial tumors
Authors: Kazutoshi Fujita, Makito Miyake, Takuto Shimizu, Jennifer Linehan, Joshua Gottlieb, Ian Pagano, Sergei Tikhonenkov, Kaoru Murakami, Riko Lee, Toru Sakatani, Sunao Tanaka, Charles J Rosser, Hideki Furuya
Journal: Clinical Cancer Research (2024)

Abstract Due to insufficient accuracy, urine-based assays currently have a limited role in the management of patients with upper tract urothelial carcinoma. The robust urine-based multiplex assay for diagnosis of upper tract urothelial carcinoma has the potential to address this deficiency and to assist with accurate, non-invasive diagnosis.We previously developedOncuria®-Detect, a multiplex immunoassay capable of detecting bladder cancer using a single voided urine. In this study, its application to upper tract urothelial cancer was evaluated in a multi-institutional cohort of 61 prospectively collected subjects presenting for evaluation of upper tract mass along with 61 prospective collected matched controls. The ability of the test to identify patients harboring upper tract urothelial carcinoma was assessed. Cancer status was confirmed by endoscopy and tissue biopsy or definitive surgery. Oncuria®-Detect provided an AUC of 0.868 (95% CI: 0.802- 0.933) with an overall sensitivity of 96.7%, specificity of 59.0%, NPV 94.7% and PPV 70.2%. Sensitivity values of Oncuria®-Detect for low-grade, high-grade, non-invasive and invasive upper tract urothelial cancer were 100%, 89.7%, 93.3% and 96.2%, respectively. Voided urine cytology showed an overall sensitivity of 54.5%, specificity of 100%, NPV 31.0% and PPV 100%. As a non-invasive test, Oncuria®-Detect outperformed both voided urinary cytology and selective cytology (sensitivities 96.7% vs. 54.5% vs. 81.8%, respectively). Oncuria®-Detect enabled the accurate discrimination of upper tract urothelial carcinoma and controls non-tumor bearing individuals. The Oncuria®-Detect test can achieve the efficient and accurate detection of upper tract urothelial carcinoma in a non-invasive patient setting. Citation Format: Kazutoshi Fujita, Makito Miyake, Takuto Shimizu, Jennifer Linehan, Joshua Gottlieb, Ian Pagano, Sergei Tikhonenkov, Kaoru Murakami, Riko Lee, Toru Sakatani, Sunao Tanaka, Charles J Rosser, Hideki Furuya. Diagnostic accuracy of Oncuria®-Detect in the detection of upper tract urothelial tumors [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A070.
Abstract A002: The clinical relevance of circulating tumor cell size in head and neck squamous cell carcinoma patients
Authors: Hyeongjung Woo, Hyun Young Shin, So Yeon Oh, Sun Min Lee, Minseok S. Kim
Journal: Clinical Cancer Research (2024)

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR002) of the Conference Program/Proceedings. Citation Format: Hyeongjung Woo, Hyun Young Shin, So Yeon Oh, Sun Min Lee, Minseok S. Kim. The clinical relevance of circulating tumor cell size in head and neck squamous cell carcinoma patients [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A002.
Abstract B033: Towards magnetic resonance microscopy for liquid biopsy in cancer therapy monitoring
Authors: Karl D. Briegel, Robin D. Allert, Dominik B. Bucher, Julia D. Draeger, Nick R v. Grafenstein, Linyan Nie
Journal: Clinical Cancer Research (2024)

Abstract The advancement of liquid biopsy techniques promises to revolutionize cancer diagnostics and therapy monitoring, by offering a minimally invasive approach to track tumor progression and treatment efficacy. One central issue preventing advancements are innovations in sensor technology, necessary to enable the detection of molecular and cellular biomarkers with sufficient precision. Over the past decade, atomic-scale quantum sensors have emerged as powerful detectors, offering the ability to perform precise measurements of temperature, pressure, and magnetic fields on the single cell scale. These sensors, based on the interaction of spin qubits with their environment, have the unique capability to amplify and exploit environmental interactions for highly accurate detection, making them ideal for complex biological applications. In this context, we present an advanced quantum sensing platform specifically tailored for liquid biopsy applications in cancer therapy monitoring. This platform integrates the capabilities of optical microscopy with magnetic resonance imaging (MRI) techniques, utilizing nitrogen-vacancy (NV) centers in diamond as quantum sensors by converting magnetic resonance signals into optical signals, which are subsequently captured by a high-speed camera. Our platform offers a novel approach, promising quantitative analysis of single cancer cells from liquid samples with unprecedented accuracy. Unlike traditional MRI, our method captures signals over a wide field of view directly in real space. Each camera pixel records a magnetic resonance spectrum, providing detailed multicomponent information about the sample, such as molecular concentration, diffusion, and relaxation behavior, which are critical for understanding the tumor’s microenvironment. Our quantum sensing technology holds significant potential for enhancing the sensitivity of liquid biopsies. By capturing detailed molecular information from blood or other body fluids, it will enable in-depth analysis of Circulating Tumor Cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and other biomarkers. Citation Format: Karl D. Briegel, Robin D. Allert, Dominik B. Bucher, Julia D. Draeger, Nick R v. Grafenstein, Linyan Nie. Towards magnetic resonance microscopy for liquid biopsy in cancer therapy monitoring [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B033.
Abstract IA018: Liquid biopsy in head and neck cancers: A model for tissue-agnostic MRD detection
Authors: Scott V Bratman
Journal: Clinical Cancer Research (2024)

Abstract Head and neck cancer (HNC) is a molecularly heterogenous disease with a variable clinical course. Current treatment decisions rely primarily on pre-treatment prognostic factors without consideration of treatment response. This presentation will introduce liquid biopsy biomarkers that can be repeated in HNC patients for the purpose of dynamic risk stratification, treatment adaptation, and post-treatment surveillance. Novel approaches to measuring circulating tumor DNA (ctDNA) will be described, with particular attention to viral-associated and non-viral- associated subtypes of HNC. Detection of molecular residual disease (MRD) using ctDNA will be discussed. As HNC is often treated by non-surgical means, there is a pressing need for tissue- agnostic methods for ctDNA-based MRD detection. Analysis of tumor-specific genetic and epigenetic aberrations within ctDNA each present distinct opportunities and challenges for tissue-agnostic characterization of ctDNA. Viral ctDNA has emerged as a convenient target for MRD detection in viral-associated HNC, while ctDNA methylome profiling offers a versatile approach for tissue-agnostic MRD detection across HNC subtypes. Future applications of these methods may improve individualized management of HNC patients without requiring access to precious tumor tissue samples. Citation Format: Scott V Bratman. Liquid biopsy in head and neck cancers: A model for tissue-agnostic MRD detection [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr IA018.