scholarly journals Liquid biopsy and tumor heterogeneity in metastatic solid tumors: the potentiality of blood samples

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Marco Russano ◽  
Andrea Napolitano ◽  
Giulia Ribelli ◽  
Michele Iuliani ◽  
Sonia Simonetti ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Liquid Biopsy ◽  
Tumor Heterogeneity ◽  
Blood Samples

scholarly journals Correction to: Liquid biopsy and tumor heterogeneity in metastatic solid tumors: the potentiality of blood samples

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Marco Russano ◽  
Andrea Napolitano ◽  
Giulia Ribelli ◽  
Michele Iuliani ◽  
Sonia Simonetti ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Liquid Biopsy ◽  
Tumor Heterogeneity ◽  
Blood Samples

Circulating tumor DNA and their added value in molecular oncology

2020 ◽  
Vol 58 (2) ◽  
pp. 152-161 ◽  
Author(s):  
Math P.G. Leers
Keyword(s):  
Solid Tumors ◽  
Peripheral Blood ◽  
Liquid Biopsy ◽  
Gene Mutations ◽  
Circulating Tumor Dna ◽  
Added Value ◽  
Clinical Implementation ◽  
Primary Tumors ◽  
Blood Samples ◽  
Tumor Dna

AbstractNew methods for molecular diagnosis are now available in oncology thanks to the discovery of circulating tumor DNA molecules in the plasma of cancer patients. By utilizing blood samples, rather than traditional tissue sampling, clinical practice is on the verge of new discoveries from the analysis of cell-free DNA (cfDNA). The method, known as a “liquid biopsy”, consists of analyzing therapeutic targets and drug-resistant conferring gene mutations in circulating tumor cells (CTC) and cell-free circulating tumor DNA (ctDNA). These are subsequently released from primary tumors and metastatic deposits into the peripheral blood. The advantages of the method can be observed in the diagnosis, but also in the choice of treatment for solid tumors (e.g. non-small cell lung carcinomas [NSCLC]). In order to interpret the results, an understanding of the biological characteristics of circulating tumor DNA is required. Currently there is no consensus as to how a liquid biopsy should be conducted. In this review, we will assess the pros of ctDNA as analytes in peripheral blood samples and its impact on clinical applications in solid tumors and hematological malignancies. We will also address practical issues facing clinical implementation, such as pre-analytical factors. Moreover, we will emphasize the open questions that remain when considering the current state of personalized medicine and targeted therapy.

scholarly journals The molecular profiling of solid tumors by liquid biopsy: a position paper of the AIOM–SIAPEC-IAP–SIBioC–SIC–SIF Italian Scientific Societies

ESMO Open ◽  
2021 ◽  
Vol 6 (3) ◽  
pp. 100164
Author(s):  
A. Russo ◽  
L. Incorvaia ◽  
M. Del Re ◽  
U. Malapelle ◽  
E. Capoluongo ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Liquid Biopsy ◽  
Molecular Profiling ◽  
Position Paper ◽  
Scientific Societies

scholarly journals Combination of solid and liquid biopsy genomic profiling for tumor heterogeneity characterization

2017 ◽  
Vol 28 ◽  
pp. v450
Author(s):  
J. Garcia Foncillas ◽  
L. Álvarez ◽  
A. Rodrigo ◽  
A. Terrádez
Keyword(s):  
Liquid Biopsy ◽  
Tumor Heterogeneity ◽  
Genomic Profiling

Real world results of liquid biopsy in stage 3/4 solid tumors and potential ''clinical actionability."

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 2555-2555
Author(s):  
Rebecca Christian Arend ◽  
Angelina Londono ◽  
Alba Martínez ◽  
Andrew Ford ◽  
Charmaine Brown ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Real World ◽  
Liquid Biopsy

cfDNA for accurate determination of RAS and BRAF mutations using OncoBEAM liquid biopsy in metastatic colorectal cancer patients: Results of the real-world multicentric ColoBEAM study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3542-3542 ◽  
Author(s):  
Alexandre Harle ◽  
Celine Gavoille ◽  
Olivier Bouche ◽  
Meher Ben Abdelghani ◽  
Jérôme Edouard Plaza ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Metastatic Colorectal Cancer ◽  
Liquid Biopsy ◽  
Accurate Determination ◽  
Braf V600e ◽  
Molecular Testing ◽  
Braf Mutations ◽  
Blood Samples

3542 Background: Determination of KRAS, NRAS ( RAS) and BRAF mutations is a standard of care for the management of patients with metastatic colorectal cancer (mCRC). RAS mutations are well characterized resistance biomarkers to anti-EGFR antibodies and BRAF V600 mutations indicate poor prognosis. Tissue biopsy has traditionally been used to determine RAS and BRAF status, but liquid biopsy analysis of circulating tumor DNA (ctDNA) has demonstrated utility as a less invasive tool to expedite molecular testing results to the clinic. The ColoBEAM study reports the performance of plasma mutation testing in a real-life prospective series of 278 patients across 8 centers. Methods: Plasma derived ctDNA was prepared from 20mL blood samples prospectively collected from mCRC patients who had not received chemotherapy in the prior 15 days. ctDNA was centrally assessed using OncoBEAM and results compared to those obtained by routine analysis of tissue. Both tissue and blood samples with discrepant RAS results were blindly reassessed with OncoBEAM. Results: Of 278 patients enrolled, 202 blood samples were available for OncoBEAM testing. RAS and BRAF V600E mutations were detected in tissue in 132/202 (65.4%) and 4/198 (2.0%) patients, respectively. Analysis of the first ctDNA sample as compared to tissue DNA resulted in a kappa coefficient (κ) of 0.52 [0.41 – 0.63] and accuracy of 75.2% (65.1% sensitivity; 94.3% specificity). OncoBEAM testing of a second sample resulted (κ) of 0.66 [0.56 - 0.76] and accuracy of 83.2% (77.3% sensitivity; 94.3% specificity). Of the 4 samples with a BRAF V600E mutation in tumor tissue 2 were detected in blood. In the subgroup of patients with liver metastasis (n=136), accuracy was 88.2% (87.4% sensitivity; 90.2% specificity) for RAS and BRAF status with (κ) of 0.73 [0.61 – 0.86]. In a subgroup of chemotherapy naïve patients with liver metastasis (n=49), accuracy was 91.8% (93.3% sensitivity; 89.5% specificity) for RAS and BRAF status with (κ) of 0.83 [0.67 – 0.99]. Conclusions: The results of the ColoBEAM study confirm plasma ctDNA as a credible surrogate marker to tissue DNA for RAS and BRAF status assessment and may be incorporated as a first-line theragnostic assessment. New testing on a second sample for wild-type status demonstrated 91.8% concordance between blood and tissue. Clinical trial information: NCT02751177.

CTC enumeration and characterization as a pharmacodynamic marker in the phase I clinical study of APX3330, an APE1/Ref-1 inhibitor, in patients with advanced solid tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14531-e14531 ◽  
Author(s):  
Lincy Chu ◽  
Amanda K. L. Anderson ◽  
Mark Andrew Landers ◽  
Yipeng Wang ◽  
Mark R. Kelley ◽  
...  
Keyword(s):  
Clinical Study ◽  
Phase I ◽  
Solid Tumors ◽  
Dual Function ◽  
Protective Function ◽  
Blood Samples ◽  
Steady State Serum ◽  
Downstream Analysis ◽  
Cancer Cell Signaling ◽  
Tumor Agent

e14531 Background: APE1/Ref-1 is a dual-function protein with a pleiotropic role in regulating transcription factors involved in cancer cell signaling via redox control, as well as responding to oxidative and base DNA damage. APX3330 is a highly selective inhibitor of the Ref-1 mediated redox function in tumors, while enhancing the neuronal protective function of APE1. APX3330 is undergoing clinical development as an anti-tumor agent that also protects and reverses oxidative damage to neurons. We now report on the CTC analysis conducted as part of the study (NCT0337508). Results of the clinical study are reported in a separate abstract. Methods: A total of 19 patients with 10 various solid tumors, including rectal, pancreatic, colon, endometrial, gall bladder, hepatocellular, prostate, melanoma, bladder, and ovarian cancers received APX3330 in escalating divided daily doses of 240, 360, 480, 600, and 720mg. Blood samples were collected from all patients prior to receiving APX3330 and after achieving steady-state serum concentrations of the drug. Samples were sent to Epic Sciences to analyze circulating tumor cells (CTCs) in peripheral blood via their CTC Platform. Results: Cumulatively, 37 samples from 19 patients were received. 35/37 (95%) samples passed technical quality control and were feasible for downstream analysis. 9/17 (53%) baseline samples (BL) had CTCs detected, while 9/18 (50%) on-treatment (OTx) draws had CTCs detected. 16 patients had BL and OTx samples that were further evaluated with the longitudinal analysis. Of these, 7/16 (44%), 6/16 (38%), and 3/16 (19%) patients showed a reduction trend, an increase trend, and no change in all CTC populations (delta greater than or equal to 0 CTC/ml), respectively. Patient follow-up is ongoing and the correlation of CTC biomarkers with clinical outcomes is pending. Conclusions: APX3330 is undergoing clinical evaluation as an anti-tumor agent that protects against and reverses CIPN. In this phase I study, 44% of evaluable blood samples showed a reduction in CTCs after initiation of treatment with APX3330. Additional studies are now being planned. Clinical trial information: NCT0337508.

Targeted PCR vs NGS for molecular diagnostic in solid tumors and liquid biopsies. How to choose in real-life.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15576-e15576
Author(s):  
Jean-Louis Merlin ◽  
Pauline Gilson ◽  
Marie Husson ◽  
Alexandre Harle
Keyword(s):  
Tumor Cell ◽  
Solid Tumors ◽  
Liquid Biopsy ◽  
Real Life ◽  
Egfr Mutations ◽  
Molecular Diagnostic ◽  
Liquid Biopsies ◽  
Cell Content ◽  
Iso 15189 ◽  
Significant Difference

e15576 Background: Molecular diagnostic is now part of routine diagnosis in many solid tumors and multiple technical options are available from extensive sequencing (NGS) to fully-automated targeted PCR (FAPCR). Tumor tissue testing is the gold standard, liquid biopsy is becoming a valuable option. Methods: 417 FFPE tumors, and 28 liquid biopsies were analyzed from 233 non small cell lung cancer (NSCLC), 177 colorectal cancer (CRC), 35 melanoma (MEL) in an ISO 15189 certified, French NCI molecular genetics platform. FAPCR analyses were performed individually, every day, using CE-IVD kits for the exclusive analysis of KRAS, NRAS, BRAF and EGFR mutations in NSCLC, CRC and MEL. NGS analyses were performed weekly as 12 or 24 sample runs using custom multiple gene panel capture sequencing. In all cases, prior to analysis, the specimens were macrodissected to warrant tumor cell content > 10% after examination of hematoxylin eosin stained slide by a pathologist. For liquid biopsy, cfDNA was extracted within 3 days from blood samples collected in cfDNA BCT tubes and analyzed using CE-IVD EGFR mutation kits. Time to results was recorded from registration of the specimen to validation of the results. Results: All FFPE tumors were analyzed using either FAPCR (N = 321) or NGS (N = 110) according to the clinician choice. Less than 2% of samples were not analyzable because of tumor cell content < 10% or degradated DNA. Median time to results was 6 days for FA-PCR (range 1-19) and 18 days for NGS (range 7-28). No significant difference was observed between NSCLC, CRC and MEL. Most cases of delay > median were related to pre-analytical defects and the need for a second specimen. For liquid biopsies, time to result was 6 days (range 1-18). The mutation rates were respectively, 13% for EGFR in NSCLC, 57% for KRAS/NRAS/BRAF in CRC and 69% for BRAF/NRAS in MEL. Using NGS led to the identification of additional molecular targetable alterations that were not analyzed by FAPCR in 44% of NSCLC, 22% of CRC and 14% of MEL. Among the 28 liquid biopsies analyzed mostly at progression under anti-EGFR TKI, EGFR mutations including T790M, were detected in 61% of the cases. Conclusions: Independently of cost-effectiveness, using PCR reduces time to results and can accelerate the initiation of targeted therapy but restricts the range of analysis, while extensive NGS delays time to results but identifies additional biomarkers that could be useful for therapeutic stratification. Using liquid biopsy testing could be an alternative and allow dynamic molecular diagnostic at 1st line and during follow-up.

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