Dataset Information

BC-Monitor: Towards a Routinely Accessible Circulating Tumor DNA-Based Tool for Real-Time Monitoring Breast Cancer Progression and Treatment Effectiveness.

ABSTRACT: Circulating tumor DNA (ctDNA) is increasingly employed in the screening, follow-up, and monitoring of the continuously evolving tumor; however, most ctDNA assays validated for clinical use cannot maintain the right balance between sensitivity, coverage, sample requirements, time, and cost. Here, we report our BC-monitor, a simple, well-balanced ctDNA diagnostic approach using a gene panel significant in breast cancer and an optimized multiplex PCR-based NGS protocol capable of identifying allele variant frequencies below 1% in cell-free plasma DNA. We monitored a cohort of 45 breast cancer patients prospectively enrolled into our study receiving neoadjuvant chemotherapy or endocrine therapy or palliative therapy for metastatic diseases. Their tumor mutation status was examined in the archived tumor samples and plasma samples collected before and continuously during therapy. Traceable mutations of the used 38-plex NGS assay were found in approximately two-thirds of the patients. Importantly, we detected new pathogenic variants in follow-up plasma samples that were not detected in the primary tumor and baseline plasma samples. We proved that the BC-monitor can pre-indicate disease progression four-six months earlier than conventional methods. Our study highlights the need for well-designed ctDNA monitoring during treatment and follow-up, integrated into a real-time treatment assessment, which could provide information on the active tumor DNA released into the blood.

SUBMITTER: Priskin K

PROVIDER: S-EPMC8305126 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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BC-Monitor: Towards a Routinely Accessible Circulating Tumor DNA-Based Tool for Real-Time Monitoring Breast Cancer Progression and Treatment Effectiveness.

Priskin Katalin K Pólya Sára S Pintér Lajos L Jaksa Gábor G Csányi Bernadett B Enyedi Márton Zsolt MZ Sági-Zsigmond Eszter E Sükösd Farkas F Oláh-Németh Orsolya O Kelemen Gyöngyi G Nikolényi Alíz A Uhercsák Gabriella G Sántha Dóra D Dobi Ágnes Á Szilágyi Éva É Valicsek Erzsébet E Tordai László L Tóth Rozália R Kahán Zsuzsanna Z Haracska Lajos L

Cancers 20210712 14

Circulating tumor DNA (ctDNA) is increasingly employed in the screening, follow-up, and monitoring of the continuously evolving tumor; however, most ctDNA assays validated for clinical use cannot maintain the right balance between sensitivity, coverage, sample requirements, time, and cost. Here, we report our BC-monitor, a simple, well-balanced ctDNA diagnostic approach using a gene panel significant in breast cancer and an optimized multiplex PCR-based NGS protocol capable of identifying allele ...[more]

PMID: 34298704

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Project description:BackgroundGlioblastoma (GBM) is associated with fatal outcomes and devastating neurological presentations especially impacting the elderly. Management remains controversial and representation in clinical trials poor. We generated 2 nomograms and a clinical decision making web tool using real-world data.MethodsPatients ≥60 years of age with histologically confirmed GBM (ICD-O-3 histology codes 9440/3, 9441/3, and 9442/3) diagnosed 2005-2015 were identified from the BC Cancer Registry (n = 822). Seven hundred and twenty-nine patients for which performance status was captured were included in the analysis. Age, performance and resection status, administration of radiation therapy (RT), and chemotherapy were reviewed. Nomograms predicting 6- and 12-month overall survival (OS) probability were developed using Cox proportional hazards regression internally validated by c-index. A web tool powered by JavaScript was developed to calculate the survival probability.ResultsMedian OS was 6.6 months (95% confidence interval [CI] 6-7.2 months). Management involved concurrent chemoradiation (34%), RT alone (42%), and chemo alone (2.3%). Twenty-one percent of patients did not receive treatment beyond surgical intervention. Age, performance status, extent of resection, chemotherapy, and RT administration were all significant independent predictors of OS. Patients <80 years old who received RT had a significant survival advantage, regardless of extent of resection (hazard ratio range from 0.22 to 0.60, CI 0.15-0.95). A nomogram was constructed from all 729 patients (Harrell's Concordance Index = 0.78 [CI 0.71-0.84]) with a second nomogram based on subgroup analysis of the 452 patients who underwent RT (Harrell's Concordance Index = 0.81 [CI 0.70-0.90]). An online calculator based on both nomograms was generated for clinical use.ConclusionsTwo nomograms and accompanying web tool incorporating commonly captured clinical features were generated based on real-world data to optimize decision making in the clinic.

Project description:Background: Currently-used tools for early recognition of clinical deterioration have high sensitivity, but with low specificity and are based on infrequent measurements. We aimed to develop a pre-symptomatic and real-time detection and warning tool for potential patients' deterioration based on multi-parameter real-time warning score (MPRT-WS). Methods: A total of more than 2 million measurements were collected, pooled, and analyzed from 521 participants, of which 361 were patients in general wards defined at high-risk for deterioration and 160 were healthy participants allocation as controls. The risk score stratification was based on cutoffs of multiple physiological parameters predefined by a panel of specialists, and included heart rate, blood oxygen saturation (SpO2), respiratory rate, cuffless systolic and diastolic blood pressure (SBP and DBP), body temperature, stroke volume (SV), cardiac output, and systemic vascular resistance (SVR), recorded every 5 min for a period of up to 72 h. The data was used to define the various risk levels of a real-time detection and warning tool, comparing it with the clinically-used National Early Warning Score (NEWS). Results: When comparing risk levels among patients using both tools, 92.6%, 6.1%, and 1.3% of the readings were defined as "Low", "Medium", and "High" risk with NEWS, and 92.9%, 6.4%, and 0.7%, respectively, with MPRT-WS (p = 0.863 between tools). Among the 39 patients that deteriorated, 30 patients received 'High' or 'Urgent' using the MPRT-WS (42.7 ± 49.1 h before they deteriorated), and only 6 received 'High' score using the NEWS. The main abnormal vitals for the MPRT-WS were SpO2, SBP, and SV for the "Urgent" risk level, DBP, SVR, and SBP for the "High" risk level, and DBP, SpO2, and SVR for the "Medium" risk level. Conclusion: As the new detection and warning tool is based on highly-frequent monitoring capabilities, it provides medical teams with timely alerts of pre-symptomatic and real-time deterioration.

Dataset Information

BC-Monitor: Towards a Routinely Accessible Circulating Tumor DNA-Based Tool for Real-Time Monitoring Breast Cancer Progression and Treatment Effectiveness.

Publications

BC-Monitor: Towards a Routinely Accessible Circulating Tumor DNA-Based Tool for Real-Time Monitoring Breast Cancer Progression and Treatment Effectiveness.

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