tbuckley/cabot-search huggingface dataset:
Abstract B010: Prognostic value of circulating tumor cells in stage III and IV melanoma: A systematic review and meta-analysis
Authors: Jennifer H. Chen, Hyunsoo Hwang, Bamboo Dong, Vanessa N. Sarli, Joshua R. Upshaw, Salyna Meas, Anthony Lucci
Journal: Clinical Cancer Research (2024)

Abstract Introduction: Previous studies have demonstrated a role for assessing circulating tumor cells (CTC) in melanoma, but significant heterogeneity among studies has limited application in the clinical setting. We sought to evaluate the prognostic value of CTCs in advanced stage melanoma using a standardized CTC enumeration platform. Methods: A PubMed literature search was conducted up to March 2024. All studies evaluating CTC enumeration using CellSearchTM with outcomes data were included. Student's t-test was used to compare differences between groups. Hazard ratios (HR) were pooled using random effects model to assess the association of CTCs with overall survival (OS). I 2 statistic and Cochran’s Q test, sensitivity analyses, and Egger’s test of asymmetry were used to assess study heterogeneity, differential impact of individual studies, and publication bias, respectively. Results: Of the 12 studies identified, nine met inclusion criteria. A total of 678 patients were included, of which 337 (49.6%) were stage III and 342 (50.4%) were stage IV. The majority of studies reported CTC rates using a cut-off of ≥ 1 (6 studies, 66.7%), while three studies used ≥ 2 and five studies used both. Median follow-up time was available for six studies and ranged from 5.9-48 months (median 13.4). Average CTC detection rate (≥ 1 or 2) was 41% (SD 14.0) and was significantly higher using a cut-off of ≥ 1 (45.4%, SD 12.6) compared to ≥ 2 (26.1%, SD 2.7, p = 0.02). Pooled analysis of two studies demonstrated significantly worse OS with CTC ≥ 1 (HR 1.6, 95% CI: 1.0-2.6, p = 0.04). Similarly, pooled analysis of five studies with available HRs demonstrated significantly worse OS with CTC ≥ 2 (HR 2.1, 95% CI: 1.4-3.1, p = 0.0003). Among these five studies, moderate heterogeneity was observed (I2 = 43.4%), although this was not statistically significant (Q statistic p = 0.13). Sensitivity analyses confirmed the prognostic value of CTC ≥ 2, with pooled HRs ranging from 1.9-2.4 after consecutive omission of each study from the overall analysis. Conclusion: Regardless of the CTC cutoff used (≥ 1 or 2), presence of any CTCs was a strong prognostic marker in patients with advanced stage melanoma. Incorporation of CTC assessments in clinical practice may help risk stratify patients and guide treatment decisions. Further studies are needed to determine the optimal cut-off point for CTC status in assessing prognosis. Citation Format: Jennifer H. Chen, Hyunsoo Hwang, Bamboo Dong, Vanessa N. Sarli, Joshua R. Upshaw, Salyna Meas, Anthony Lucci. Prognostic value of circulating tumor cells in stage III and IV melanoma: A systematic review and meta-analysis [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 B010.
Abstract A068: Evaluate the performance of FibraChek™ for non-invasive detection of hepatic fibrosis and hepatocellular carcinoma
Authors: Fernando Siguencia, Michitaka Matsuda, Vijay Pandyarajan, Sunao Tanaka, Steven M Smith, Ekihiro Seki, Charles J Rosser, Hideki Furuya
Journal: Clinical Cancer Research (2024)

Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD), fibrosis, and cirrhosis are risk factors for hepatocellular carcinoma (HCC). Blood-based assays to date have limited accuracy for detecting MASLD and cirrhosis, and thus have not been widely adopted in the clinical setting. The identification and validation of a multiplex molecular signature associated with liver disease may address this unmet need. This prospective single-center US study evaluated the performance of the non-invasive Liver FibraChek Dx serum assay for detecting MASLD. The study algorithm analyzes weighted values of five serum biomarkers (AST, ALT, taurocholic acid, L-tyrosine, and platelet count) plus age to derive a risk score. Samples comprised 14 MASLD cases, 19 HCC cases, and 12 healthy controls. Liver status was confirmed by tissue biopsy. Wilcoxon rank sum tests determined the association between the risk score and confirmed liver histology. Diagnostic performance was assessed using ROC curves. The probability of identifying MASLD and/or HCC by Liver FibraChek Dx, in conjunction with other patient parameters, was demonstrated by an AUROC of 0.890 (95% CI: 0.776-1.000), with 93.9% sensitivity, 75.0% specificity, 91.1% positive predictive value, 81.8% negative predictive value, and 88.9% accuracy. Risk scores associated with the biomarker panel enabled accurate discrimination of liver disease from healthy controls. The non-invasive multiplex Liver FibraChek Dx test can effectively and accurately detect and classify hepatic fibrosis risk in peripheral blood samples and may have utility in diagnosing and monitoring liver pathogenesis. Citation Format: Fernando Siguencia, Michitaka Matsuda, Vijay Pandyarajan, Sunao Tanaka, Steven M Smith, Ekihiro Seki, Charles J Rosser, Hideki Furuya. Evaluate the performance of FibraChek™ for non-invasive detection of hepatic fibrosis and hepatocellular 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 A068.
Abstract A039: A sensitive tool for the detection of RNA modifications in blood samples
Authors: Andrew Price, Zachary Miles, Byron Purse, Gudrun Stengel
Journal: Clinical Cancer Research (2024)

Abstract The epitranscriptome is the set of chemical modifications applied naturally to RNA to regulate seemingly all aspects of its function, including splicing, translation initiation and fidelity, trafficking, RNA folding and stability, and transcript lifetime. Detecting RNA in blood reliably continues to be a challenge due to its labile nature, and detecting RNA modifications is an even greater challenge. For this reason, current liquid biopsy approaches concentrate on determining the mutational burden in cell-free DNA and do not harness the potential of cfRNA. In contrast to cfDNA, cfRNA is a biomarker for dynamic events that are known to occur at early stages of carcinogenesis, such as alterations to transcriptional profiles and other aspects of the regulatory state of cells. In many RNA species, the modification state is linked to the RNA lifecycle, thus providing important insights into cell state. For example, pre-miRNA is modified before miRNA maturation, tRNA cleavage is initiated by changes to the modification pattern and mRNA is decapped for storage in stress granules. AlidaBio is introducing the EpiPlex platform, an assay platform with an integrated bioinformatics solution that is designed for ultra-low RNA input and has been tested with blood samples. In addition to its sensitivity, the EpiPlex platform has the advantage of detecting multiple RNA modifications in the same reaction, enabling users to elucidate how RNA modifications act in concert to fine-tune RNA function. The approach uses targeted, multiplexed barcoding to reveal co-localization of modifications on the same molecule and to provide semi-quantitative data on mod abundance. This sensitive, multiplexed target detection has the potential to advance the field of RNA liquid biopsy with new biomarker discovery. Citation Format: Andrew Price, Zachary Miles, Byron Purse, Gudrun Stengel. A sensitive tool for the detection of RNA modifications in blood samples [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 A039.
Abstract B040: Cell-free DNA captures inter- and intra-patient heterogeneity in advanced bladder cancer
Authors: Samantha L Schuster, Pushpa Itagi, Sonali Arora, Patricia C Galipeau, Thomas W Persse, Michael Yang, Allie Kreitman, Alan Min, Funda Vakar-Lopez, John K Lee, Petros Grivas, Robert B Montgomery, Jonathan L Wright, Andrew C Hsieh, Hung- Ming Lam, Gavin Ha
Journal: Clinical Cancer Research (2024)

Abstract Metastatic bladder cancer (BLCA) is an aggressive disease complicated by the emergence of variant histological subtypes. The UW/Fred Hutch metastatic BLCA rapid autopsy program is a first-of-its-kind program collecting cell-free DNA (cfDNA) and matched normal tissue, primary tumor, and metastatic tumor samples from advanced BLCA patients, with a focus on these variant subtype tumors. This dataset, consisting of 20 patients with up to five metastases per patient, is a unique opportunity to assess how cfDNA is able to capture heterogeneity across BLCA. We assessed both inter-patient heterogeneity between BLCA subtypes and inter-tumoral heterogeneity within each patient using epigenetic and genomic profiling. Using nucleosome profiling, we identified the activity of lineage markers and transcription factors that distinguish healthy individuals from BLCA patients, and between BLCA subtypes. Furthermore, we conducted a detailed analysis of whole genome (30X) and targeted (4,000X) cfDNA sequencing in their ability to capture the evolutionary history of tumor mutations. Detection of tumor mutations by cfDNA is highly dependent on clonality, with &amp;gt;90% of founder tumor mutations captured by either sequencing method, while capture is decreased for either subclonal mutations or those private to a single metastasis. Importantly, deleterious mutations in BLCA driver genes had close to 100% detection using targeted panel sequencing, even for subclonal mutations. These findings lay the groundwork for the use of cfDNA in clinical BLCA decision-making, including tracking the emergence of pathogenic, targetable mutations and variant subtypes. Citation Format: Samantha L Schuster, Pushpa Itagi, Sonali Arora, Patricia C Galipeau, Thomas W Persse, Michael Yang, Allie Kreitman, Alan Min, Funda Vakar-Lopez, John K Lee, Petros Grivas, Robert B Montgomery, Jonathan L Wright, Andrew C Hsieh, Hung- Ming Lam, Gavin Ha. Cell-free DNA captures inter- and intra-patient heterogeneity in advanced bladder cancer [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 B040.
Abstract IA021: Plasma-only ultrasensitive liquid biopsy to monitor tumor burden and clonal evolution
Authors: Adam Widman, Alexandre P. Cheng, John Zinno, Srinivas Rajagopalan, Ashish Saxena, Nasser Altorki, Dan A. Landau
Journal: Clinical Cancer Research (2024)

Abstract Individual bulk tumor biopsies are invasive and may fail to capture clonal heterogeneity within primary tumors and metastatic sites of disease. Further, analyses of subclonal variants are often hindered by background error rates related to tissue preservation methods (e.g. FFPE) and sequencing artifact. Use of plasma-only ultrasensitive liquid biopsy approaches may allow for noninvasive inference of clonality and dynamically track changes in tumor burden. We previously developed MRD-EDGE, a tumor-informed machine learning classifier for ultrasensitive liquid biopsy monitoring of single nucleotide variants (SNVs) and copy number variants (CNVs) using standard plasma whole genome sequencing. For SNVs, MRD- EDGE uses a novel machine learning framework to classify individual cell free DNA (cfDNA) fragments as circulating tumor DNA or cfDNA sequencing artifact. We demonstrated the potential of plasma-only MRD-EDGE to identify SNVs in advanced melanoma and monitor tumor burden throughout treatment with immune checkpoint inhibiton. In tumor-informed settings, MRD-EDGE was used to identify minimal residual disease at tumor fractions (TFs) of 1:100,000 and below. Accurate SNV classification is a function of classifier performance and background error rate. To reduce error rates, we combined MRD-EDGE SNV with paired plus- minus sequencing (ppmSeq) from Ultima Genomics. ppmSeq is a PCR-free approach that leverages the hydrogen bonds of complementary DNA to carry matched native strands directly into sequencing, enabling scalable duplex sequencing. Use of MRD-EDGE SNV together with ppmSeq enables ultrasensitive tracking of early-stage non-small cell lung cancer throughout neoadjuvant immunotherapy. Plasma-only MRD-EDGE is therefore poised to enable dynamic monitoring of tumor burden and clonal composition outside the scope of tumor-informed approaches, including the comparison of SNV composition in cancer recurrence with preoperative disease. Citation Format: Adam Widman, Alexandre P. Cheng, John Zinno, Srinivas Rajagopalan, Ashish Saxena, Nasser Altorki, Dan A. Landau. Plasma-only ultrasensitive liquid biopsy to monitor tumor burden and clonal evolution [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 IA021.
Abstract B006: Qualitative research study on the use of minimal residual disease as an intermediate endpoint in multiple myeloma clinical trials in Saudi Arabia
Authors: Albandari A Alnasser, Tariq H Alqurayshah
Journal: Clinical Cancer Research (2024)

Abstract Introduction: The U.S. Food and Drug Administration has recently considered minimal residual disease (MRD) as an acceptable accelerated approval endpoint in multiple myeloma (MM). Meta-analysis studies have shown the clinical benefit of MRD negativity in certain hematological cancers such as MM. Objectives: This qualitative research study, with a unique focus on the Saudi context, aims to assess the opinions and experiences of hematology and oncology specialists and consultants in Saudi Arabia. The study is particularly interested in their views on the use of MRD as an intermediate endpoint in early-phase clinical trials for fast-track drug approval by the Saudi Food and Drug Authority in the context of multiple myeloma. This includes assessing the use of MRD in both newly diagnosed and relapsed/refractory MM. The secondary objective is to gather information about the feasibility and availability of sensitive MRD detection methods in real-world medical practice and clinical trials in Saudi Arabia. Study Design: The study will involve interviewing 30 registered male or female physicians specialized in hematology and oncology in Saudi Arabia. The physicians will be included in the study using purposive sampling methods. The study will collect the physicians’ opinions and experiences about MRD. The interviews will be conducted through a single focus group and several face-to- face interviews or performed online, using ZOOM. Participants should have more than one year of experience post-residency or post-fellowship training. The predetermined set of semi- structured questions will cover topics such as the definition of MRD, its clinical and research significance, MRD detection thresholds, duration of MRD negativity, and its correlation with other clinical endpoints, such as progression-free survival and overall survival. The interviews will be conducted by scientific oncology and hematology evaluation experts at the Saudi Food and Drug Authority, who play a crucial role in this study. The study will consist of 5–10 semi- structured one-to-one interviews and focused group discussions of as few as four participants. Before starting any interview, participants will complete consent forms, including the study’s goals and who will conduct the study. Qualitative data will be prepared and analyzed by an expert in data analysis, ensuring the highest research standards. The results will be presented using descriptive and interpretive methods. Citation Format: Albandari A Alnasser, Tariq H Alqurayshah. Qualitative research study on the use of minimal residual disease as an intermediate endpoint in multiple myeloma clinical trials in Saudi Arabia [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 B006.
Abstract A023: Advancing RNA liquid biopsy technology via long-read sequencing
Authors: Daniel H. Kim
Journal: Clinical Cancer Research (2024)

Abstract Recent studies have begun to highlight the advantages of RNA-based liquid biopsy technology for cancer early detection, and we sought to further advance the development of RNA liquid biopsies by incorporating single-molecule, long-read sequencing technology. Cell-free RNAs are dynamically secreted by the cells that comprise our tissues and organs but are thought to be largely degraded in the blood. To determine the true length of cell-free RNAs, we performed long-read nanopore sequencing on cell-free RNAs isolated from pancreatic and esophageal cancer patient plasma and found that thousands of genes are detectable as full-length cell-free RNAs in vivo. By creating a custom annotation of the transcriptome for cell-free RNA quantification, we found that cancer patients exhibit high levels of repetitive cell-free RNAs in plasma, with full-length, SINE-derived cell-free RNAs being among the most abundant repetitive RNAs. Moreover, we found that utilizing repetitive cell-free RNA features substantially improved the performance of our machine learning models for cancer classification. Notably, nanopore sequencing enabled us to discover over 250,000 novel cell-free RNAs that have not been previously annotated in the human genome. Our findings highlight the value and utility of long-read nanopore sequencing of cell-free RNAs for discovering and leveraging novel RNA biomarkers for cancer early detection via RNA liquid biopsy technology. Citation Format: Daniel H. Kim. Advancing RNA liquid biopsy technology via long-read sequencing [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 A023.
Abstract A054: Oncogenic functions of alternatively spliced <i>MDM2-ALT2</i> isoform in retroperitoneal liposarcoma
Authors: Fernanda Costas C. de Faria, Safiya Khurshid, Patricia Sarchet, Sayumi Tahara, Lucia Casadei, Valerie Grignol, Roma Karna, Sydney Rentsch, Nippin Sp, Joal D Beane, Luciano Mazzoccoli, Matias Montes, Giovanni Nigita, Joe T Sharick, Jennifer L Leigth, Federica Calore, Dawn Chandler, Raphael E Pollock
Journal: Clinical Cancer Research (2024)

Abstract Retroperitoneal liposarcoma (RPLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS). Complete surgical resection remains the mainstay treatment while the high rate of locoregional recurrence constitutes the predominant cause of mortality. Well- differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcoma are the most frequent subtypes of RPLPS and present amplified MDM2 gene as a hallmark. However, there are few reports evaluating the role of alternatively spliced MDM2 transcripts in RPLPS. In this study, we assessed MDM2-ALT2 expression levels in a cohort of RPLPS patients and evaluated biological functions of MDM2-ALT2 isoform in vitro in DDLPS cell lines. Using BaseScope™ and qPCR, we demonstrated that MDM2-Full Length (MDM2-FL) and MDM2-ALT2 expression levels were upregulated in RPLPS patient-derived tissue samples compared to normal adjacent to tumor tissue (NAT). DDLPS cells overexpressing MDM2-FL or MDM2-ALT2 had higher proliferation rates and increased migration and invasion capacities, as well as increased protein levels of p- AKT, mTOR, p70S6K, MMP2 and cJun. Simultaneous overexpression of MDM2-ALT2 and AKT silencing showed that AKT inhibition impaired p-p70S6K and MMP2 protein increased levels and led to significantly decreased proliferation and migration rates compared to cells overexpressing MDM2-ALT2 only. Taken together, our data suggest that MDM2-ALT2 may promote RPLPS progression. Citation Format: Fernanda Costas C. de Faria, Safiya Khurshid, Patricia Sarchet, Sayumi Tahara, Lucia Casadei, Valerie Grignol, Roma Karna, Sydney Rentsch, Nippin Sp, Joal D Beane, Luciano Mazzoccoli, Matias Montes, Giovanni Nigita, Joe T Sharick, Jennifer L Leigth, Federica Calore, Dawn Chandler, Raphael E Pollock. Oncogenic functions of alternatively spliced MDM2-ALT2 isoform in retroperitoneal liposarcoma [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 A054.
Abstract A071: Performance of the Oncuria®-Detect test for the evaluation of patients presenting with hematuria: Results from a real world clinical setting
Authors: Ian Pagano, Sergei Tikhonenkov, Florence Le Calvez-Kelm, Steve Goodison, Zhen Zhang, Toru Sakatani, Kaoru Murakami, Howard Kim, Riko Lee, Sunao Tanaka, Charles J Rosser, Hideki Furuya
Journal: Clinical Cancer Research (2024)

Abstract Bladder cancer is the 9th most diagnosed cancer worldwide with higher incidences reported in Europe and the United States. Here, we evaluate the performance of a novel, commercially available multiplex immunoassay querying for 10 proteins associated with a bladder cancer diagnostic signature (Oncuria®-Detect, Nonagen Bioscience Corp, Los Angeles, CA, US) for the detection of de novo bladder cancer, in a large prospectively collected real world cohort comprised of 995 patients, across seven centers, presenting with hematuria. The results were compared with the patients’ clinical data and final diagnosis as defined by the results of cystoscopy, with a prevalence of bladder cancer of 15.9%. In the test cohort, Oncuria®-Detect detected bladder tumors in 94/109 cancers, giving overall sensitivity of 86.2% and an overall negative predictive value (NPV) of 96.7% with corresponding specificity of 80.2% with favorable performance characteristics in high grade bladder cancer and muscle-invasive bladder cancer. Patient summary: We conducted a large cross-sectional clinical study for detecting de novo bladder cancer with a novel, simple urine test (Oncuria®-Detect), which measures 10 bladder cancer associated proteins in a single voided urine sample. We analyzed urines from 995 patients and demonstrated that the new urine test can detect bladder cancer with a high degree of accuracy, specifically in patients with high grade or high stage disease. In conclusion, the novel Oncuria®-Detect urine test can be used to help detect new bladder cancers. Citation Format: Ian Pagano, Sergei Tikhonenkov, Florence Le Calvez-Kelm, Steve Goodison, Zhen Zhang, Toru Sakatani, Kaoru Murakami, Howard Kim, Riko Lee, Sunao Tanaka, Charles J Rosser, Hideki Furuya. Performance of the Oncuria®-Detect test for the evaluation of patients presenting with hematuria: Results from a real world clinical setting [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 A071.