Characterization of cell-free circulating tumor DNA in patients with brain metastases.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 2023-2023 ◽  
Author(s):  
Nadia Faiq ◽  
Sandip Pravin Patel ◽  
Lyudmila Bazhenova ◽  
Barbara A. Parker ◽  
Steven C. Plaxe ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Circulating Tumor Dna ◽  
Tumor Dna

Circulating tumor DNA mutation as a prognostic marker in melanoma with brain metastasis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21560-e21560
Author(s):  
Tapas Ranjan Behera ◽  
Jung Min Song ◽  
Donald Matthew Eicher ◽  
Brian Gastman ◽  
Daniel H. Farkas ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Metastatic Disease ◽  
Braf Mutation ◽  
Mutation Detection ◽  
Objective Response ◽  
Unmet Need ◽  
Circulating Tumor Dna ◽  
Metastatic Setting ◽  
Tumor Dna

e21560 Background: Prognosis in melanoma with brain metastasis is poor with a median survival of four months and a one-year survival rate of 10–20%. There is an unmet need for surveillance methods that can supplement imaging at regular intervals. Serial analysis of circulating tumor DNA (ctDNA) may aid surveillance and prognostication. A PCR-based, “specimen in/result out” testing device was employed to detect BRAF variants in plasma-derived ctDNA to evaluate the utility of rapid biomarker detection in the management of melanoma with brain metastasis. Methods: Serial blood samples from patients diagnosed with BRAF mutation-positive metastatic melanoma were collected at regular intervals. We employed a real-time PCR-based automated mutation detection system (Idylla; Biocartis, Belgium) to interrogate the plasma samples. The ctDNA mutation detection trend was analyzed relative to disease progression. Results: 39 patients with BRAF mutation positive melanoma were enrolled. 29 patients were treated in the metastatic setting, 10 in the adjuvant setting. 18 of the 29 patients with metastatic disease (62%) had brain metastases. Circulating BRAF mutation was detected in 17 of the 29 (59%) patients with metastatic disease, and was not detected in any patients treated adjuvantly. In the group with metastatic disease, this circulating biomarker changed from undetectable to detectable in eight (28%) and detectable to undetectable in three (10%). No change in circulating mutation status occurred in 18 (62%). In the eight patients who had an initial negative test that later became positive, seven (87%) had brain metastases. In three patients, ctDNA mutation detection occurred before the diagnosis of brain metastases on imaging, with a median lead time of five weeks (range, 3-12 weeks). In one patient with de novo metastatic disease admitted to the ICU, tissue was unavailable for BRAF testing but plasma was found to be positive for ctDNA BRAF detection. BRAF/MEK targeted therapy resulted in a sustained objective response. Five of six (83%) patients that had persistent ctDNA positivity had brain metastases. Among patients with brain metastases, median overall survival (mOS) of patients demonstrating >50% test positivity was numerically longer than those with <50% positivity (mOS 12.3 vs 53.5 months; p = 0.133). Conclusions: Plasma-based, rapid ctDNA testing may be useful as an aid in detecting progression and gauging prognosis in patients with melanoma treated in the metastatic setting. The dynamics of ctDNA test positivity may indicate a need for more urgent imaging, particularly of the brain. Blood-based, semi-automated ctDNA detection may serve as an attractive adjunct to scheduled imaging surveillance in melanoma.

scholarly journals Diagnostic value of circulating tumor DNA in molecular characterization of glioma

Medicine ◽  
2020 ◽  
Vol 99 (33) ◽  
pp. e21196
Author(s):  
Yin Kang ◽  
Xiaohua Lin ◽  
Dezhi Kang
Keyword(s):  
Molecular Characterization ◽  
Diagnostic Value ◽  
Circulating Tumor Dna ◽  
Tumor Dna

Comparison of tissue DNA to circulating tumor DNA in patients with brain metastases.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13546-e13546 ◽  
Author(s):  
Tyler A. Lanman ◽  
Santosh Kesari ◽  
Sandip Pravin Patel ◽  
Lyudmila Bazhenova ◽  
Barbara A. Parker ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Tumor Tissue ◽  
Late Complication ◽  
Median Number ◽  
Circulating Tumor Dna ◽  
Molecular Alterations ◽  
Dna Sampling ◽  
Next Generation Sequencing Ngs ◽  
Tumor Dna ◽  
Generation Sequencing

e13546 Background: Brain metastases are often a late complication of cancer, not easily amenable to biopsy, and may contain additional molecular alterations not found in the original tumor. We sought to analyze the concordance between tissue DNA and cell-free circulating tumor DNA (ctDNA) in patients who developed brain metastases, and determine how the ctDNA profile changed with time. Methods: We retrospectively analyzed 31 patients with brain metastases who underwent next-generation sequencing (NGS) from both ctDNA and tumor tissue DNA. Breast, lung, ovarian, renal, melanoma, and colon primaries were included (42, 32, 13, 7, 3, and 3%, respectively). Tissue DNA was from primary tumor, systemic metastasis or brain (39, 39, and 7%, respectively). A median number of five alterations was found in each tissue group. Alterations in ctDNA were compared to tumor DNA and analyzed for relative frequencies, concordance, and novel alterations. Overall survival (OS) and time between DNA sample collections was analyzed. Results: All 31 patients had detectable mutations in tumor tissue. 25 patients (80.6%) had detectable ctDNA alterations and 14 patients (45.2%) had at least one identical ctDNA alteration that was concordant with tissue DNA. The most commonly altered genes (in both ctDNA and tissue DNA) were TP53 and EGFR. Breast cancer had both the highest proportion of patients with ≥ 1 ctDNA alterations (92.3%) and the highest proportion of patients who had ≥ 1 alterations in common with tissue DNA (61.5%). 23 of the 25 patients (92%) with detectable ctDNA alterations had additional alterations not found in tissue DNA, which increased with time from tumor DNA sampling. Median time between ctDNA extraction and tissue biopsy was 6.5 months for cases with common alterations, and 12.4 months for those without common alterations. There was trend to decreased OS with increasing ctDNA burden. Conclusions: We found that ctDNA is comparable with tissue DNA sequencing in patients with brain metastases. This concordance decreases with increasing time from tissue diagnosis, reflecting the changing nature of tumor genetics and highlighting the utility of ctDNA as a feasible way to monitor changes and identify additional potentially targetable alterations.

Utilizing phenotypic characteristics of metastatic brain tumors to predict the probability of circulating tumor DNA detection from cerebrospinal fluid.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2507-2507
Author(s):  
Meichen Li ◽  
Delan Li ◽  
Xue Hou ◽  
Xiangheng Zhang ◽  
Na Wang ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Metastases ◽  
Detection Rate ◽  
Cross Validation ◽  
Lesion Size ◽  
Circulating Tumor Dna ◽  
Intracranial Lesion ◽  
Shortest Distance ◽  
The Impact ◽  
Tumor Dna

2507 Background: Brain metastases occur in approximately 20% of tumor patients and is often associated with terminal events and poor prognosis. Cerebrospinal fluid (CSF) can be a promising source for detecting circulating tumor DNA (ctDNA) specific to the central nervous system (CNS) instead of peripheral blood due to the blood-brain barrier. However, CSF’s suboptimal ctDNA detection rate might limit its clinical application. Precise screening of suitable patients is needed to maximize clinical benefit. Methods: We sequenced 425 cancer-relevant genes in CSF and matched extracranial tissue or blood samples obtained from 67 lung cancer patients with brain metastases. The impact of clinical factors, including age, gender, tumor size, number of lesions, and distance of lesions to the ventricle on CSF ctDNA detection was then evaluated by univariate logistic regression. To predict the probability of successful CSF ctDNA detection, best subsets regression was employed for feature selection and cross validation was used for performance assessment to determine the final model. Results: We detected somatic alterations in 39/67 (58%) CSF ctDNA, 57/66 (86%) plasma ctDNA and 45/49 (92%) tissue samples. Mutation detection rate of CSF ctDNA was significantly lower than that from extracranial tissue and plasma (P < 0.001). Univariate analysis revealed significant association (P < 0.05) of high CSF ctDNA detection rate with the following features: (1) intracranial lesion size ( T), (2) shortest distance between the largest lesion and the ventricle ( Dtop), and (3) shortest distance between all intracranial lesion and the ventricle ( Dall). We also revealed a trend of higher detection rate in patients with CNS symptoms ( SCNS). Subsequent best subsets analysis and cross validation suggested best prediction power with lesion size and largest lesion-ventriclar distance (area under curve [AUC], 0.76 [95% CI, 0.71 to 0.85]; accuracy, 0.75 [95% CI, 0.70 to 0.81]). Final probability can then be derived from Logit P = 0.11×T−0.16×Dall (AUC, 0.82; sensitivity, 0.91; specificity, 0.74). The detection of CSF ctDNA was significantly improved from 58% to 83% (P = 0.03) based on the model. Conclusions: This study established a regression model to predict the probability of CSF ctDNA that can be useful to facilitate clinical decisions and avoid excessive practice when monitoring tumor evolution in the brain.

scholarly journals Recent Advances in Device Engineering and Computational Analysis for Characterization of Cell-Released Cancer Biomarkers

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 288
Author(s):  
Hesam Abouali ◽  
Seied Ali Hosseini ◽  
Emma Purcell ◽  
Sunitha Nagrath ◽  
Mahla Poudineh
Keyword(s):  
Cancer Progression ◽  
Computational Analysis ◽  
Cancer Biomarkers ◽  
Circulating Tumor Dna ◽  
Treatment Monitoring ◽  
The Subject ◽  
In Silico Models ◽  
Tumor Dna

During cancer progression, tumors shed different biomarkers into the bloodstream, including circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating cell-free DNA (cfDNA), and circulating tumor DNA (ctDNA). The analysis of these biomarkers in the blood, known as ‘liquid biopsy’ (LB), is a promising approach for early cancer detection and treatment monitoring, and more recently, as a means for cancer therapy. Previous reviews have discussed the role of CTCs and ctDNA in cancer progression; however, ctDNA and EVs are rapidly evolving with technological advancements and computational analysis and are the subject of enormous recent studies in cancer biomarkers. In this review, first, we introduce these cell-released cancer biomarkers and briefly discuss their clinical significance in cancer diagnosis and treatment monitoring. Second, we present conventional and novel approaches for the isolation, profiling, and characterization of these markers. We then investigate the mathematical and in silico models that are developed to investigate the function of ctDNA and EVs in cancer progression. We convey our views on what is needed to pave the way to translate the emerging technologies and models into the clinic and make the case that optimized next-generation techniques and models are needed to precisely evaluate the clinical relevance of these LB markers.

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