Treatment monitoring of colorectal cancer by integrated analysis of plasma concentration and sequencing of circulating tumor DNA

Yeh, Yu Min; Lin, Peng; Chen, Shang Hung; Lin, Bo; Lin, Shao Chieh; Chen, Po Chuan; Chan, Ren Hao; Shen, Meng‐Ru

doi:10.1186/s12943-020-01273-8

Cited by 9 publications

(10 citation statements)

References 10 publications

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“…We demonstrate an overall ctDNA persistence of ∼9% in stage II CRC patients after surgery, which confirms recent data on the frequency of postoperative ctDNA persistence (Tie et al, 2016;Reinert et al, 2019). In addition, tumor-informed ctDNA was detected 1-8 months prior to imaging-based detection of progression in 92.85% of CRC patients with relapse, which is in the range or superior to rates (72-92.3%) determined previously (Tie et al, 2015;Schøler et al, 2017;Reinert et al, 2019;Wang et al, 2019;Luo et al, 2020;Yeh et al, 2020). Interestingly, in two patients (Pat.…”

Section: Discussionsupporting

confidence: 88%

“…In line, sensitivity for low-level ctDNA increased by increasing the input of cfDNA as PCR template and by the integration of sequencing reads from triplicate PCRs, pointing to an “all-or-nothing” positive amplification in samples with low mutant DNA copy numbers and a potential benefit of binning for barcoded sequencing reads. In combination with sufficient sequencing depth (≥100.000 reads), the sensitivity of our error-reduced NGS approach (0.01% VAF) is one to two orders of magnitude higher than conventional targeted NGS procedures (typically 0.1–1% error) ( Rachiglio et al, 2016 ; Osumi et al, 2019 ) and similar to sensitivities determined for digital droplet PCR ( Demuth et al, 2018 ) or for other modified NGS protocols ( Yeh et al, 2020 ). Turnaround time for analysis (24–48 h) and costs (∼45€ per sample) of our NGS-based procedure are slightly higher than ddPCR (8 h, <20€) and are in the range of other PCR-based approaches with similar sensitivities for cfDNA analysis such as BEAMing ( Demuth et al, 2018 ; Garcia et al, 2018 ).…”

Section: Discussionmentioning

confidence: 63%

“…The potential of ctDNA analysis as liquid biopsy in CRC for somatic tumor profiling ( Strickler et al, 2018 ), the detection of treatment response ( Siravegna et al, 2015 ; Tie et al, 2015 ; Reinert et al, 2016 ; Schøler et al, 2017 ; Tie et al, 2019 ), and disease progression ( El Messaoudi et al, 2016 ; Tie et al, 2016 ; Reinert et al, 2019 ; Wang et al, 2019 ; Luo et al, 2020 ; Yeh et al, 2020 ) has been outlined previously. Typically, 15–20% of stage II CRC patients with curative resection will face disease recurrence ( Böckelman et al, 2015 ), highlighting the need for sensitive monitoring strategies.…”

Section: Discussionmentioning

confidence: 99%

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Sensitive Quantification of Cell-Free Tumor DNA for Early Detection of Recurrence in Colorectal Cancer

Stasik

Mende²,

Schuster³

et al. 2022

Front. Genet.

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The detection of plasma cell–free tumor DNA (ctDNA) is prognostic in colorectal cancer (CRC) and has potential for early prediction of disease recurrence. In clinical routine, ctDNA-based diagnostics are limited by the low concentration of ctDNA and error rates of standard next-generation sequencing (NGS) approaches. We evaluated the potential to increase the stability and yield of plasma cell–free DNA (cfDNA) for routine diagnostic purposes using different blood collection tubes and various manual or automated cfDNA extraction protocols. Sensitivity for low-level ctDNA was measured in KRAS-mutant cfDNA using an error-reduced NGS procedure. To test the applicability of rapid evaluation of ctDNA persistence in clinical routine, we prospectively analyzed postoperative samples of 67 CRC (stage II) patients. ctDNA detection was linear between 0.0045 and 45%, with high sensitivity (94%) and specificity (100%) for mutations at 0.1% VAF. The stability and yield of cfDNA were superior when using Streck BCT tubes and a protocol by Zymo Research. Sensitivity for ctDNA increased 1.5-fold by the integration of variant reads from triplicate PCRs and with PCR template concentration. In clinical samples, ctDNA persistence was found in ∼9% of samples, drawn 2 weeks after surgery. Moreover, in a retrospective analysis of 14 CRC patients with relapse during adjuvant therapy, we successfully detected ctDNA (median 0.38% VAF; range 0.18–5.04% VAF) in 92.85% of patients significantly prior (median 112 days) to imaging-based surveillance. Using optimized pre-analytical conditions, the detection of postoperative ctDNA is feasible with excellent sensitivity and allows the prediction of CRC recurrence in routine oncology testing.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

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Sensitive Quantification of Cell-Free Tumor DNA for Early Detection of Recurrence in Colorectal Cancer

Stasik

Mende²,

Schuster³

et al. 2022

Front. Genet.

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“…a study conducted on 158 plasma samples from disease positive and negative groups showed that low level (< 10 ng/ml) of ccfDNA were observed in disease negative group while elevated ccfDNA concentration (1.180 to 321 ng/ml) was detected in CRC patients [ 130 ]. Furthermore, the study also determined an optimal ccfDNA concentration cutoff of 7.0 ng/ml as sensitive and specific concentration to discriminate diseased from control groups [ 130 ]. Though an interesting finding, there are several limitations to this approach.…”

Section: Introductionmentioning

confidence: 99%

Dynamic liquid biopsy components as predictive and prognostic biomarkers in colorectal cancer

Raza

Khan

Inchakalody

et al. 2022

J Exp Clin Cancer Res

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Colorectal cancer (CRC) is one of the most common cancers worldwide. The diagnosis, prognosis and therapeutic monitoring of CRC depends largely on tissue biopsy. However, due to tumor heterogeneity and limitations such as invasiveness, high cost and limited applicability in longitudinal monitoring, liquid biopsy has gathered immense attention in CRC. Liquid biopsy has several advantages over tissue biopsy including ease of sampling, effective monitoring, and longitudinal assessment of treatment dynamics. Furthermore, the importance of liquid biopsy is signified by approval of several liquid biopsy assays by regulatory bodies indicating the powerful approach of liquid biopsy for comprehensive CRC screening, diagnostic and prognostics. Several liquid biopsy biomarkers such as novel components of the microbiome, non-coding RNAs, extracellular vesicles and circulating tumor DNA are extensively being researched for their role in CRC management. Majority of these components have shown promising results on their clinical application in CRC including early detection, observe tumor heterogeneity for treatment and response, prediction of metastases and relapse and detection of minimal residual disease. Therefore, in this review, we aim to provide updated information on various novel liquid biopsy markers such as a) oral microbiota related bacterial network b) gut microbiome-associated serum metabolites c) PIWI-interacting RNAs (piRNAs), microRNA(miRNAs), Long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and d) circulating tumor DNAs (ctDNA) and circulating tumor cells (CTC) for their role in disease diagnosis, prognosis, treatment monitoring and their applicability for personalized management of CRC.

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“… 18 , 20 For example, the cfDNA concentrations in patients with colorectal cancer could serve as the first threshold to categorize ‘disease-positive’ and ‘disease-negative’ recurrent groups. 33 In the present study, we used the average cfDNA value between the initial and after two cycles of chemotherapy as the threshold to determine whether NDM occurred. There were no evident cfDNA levels in patients without NDMs, implying that there was a baseline cfDNA level in the blood.…”

Section: Discussionmentioning

confidence: 99%

Cancer-cell-derived cell-free DNA can predict distant metastasis earlier in pancreatic cancer: a prospective cohort study

Huang

Chen

et al. 2022

Ther Adv Med Oncol

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Background: Carbohydrate antigen 19-9 (CA19-9) is the only biomarker for monitoring responses during treatments of pancreatic cancer, but its accuracy for disease outcome is controversial. Fluid biopsy is a new method for diagnosis and monitoring treatment response. In this study, we investigate the usefulness of cell-free DNA (cfDNA) in predicting disease progression during the treatment of pancreatic cancer. Methods: Biopsy-proved advanced pancreatic cancer patients who received systemic chemotherapy were enrolled after signed informed consent. CA19-9 and cfDNA in blood were measured before and after every two cycles of treatments, and the disease progression was monitored by computed tomography (CT) with 3-month interval. Results: In total, 74 patients and 148 blood samples were enrolled in this study. Patients whose average blood cfDNA concentration of >9.71 ng/mL before and after first two courses of chemotherapy would subsequently show new distant metastasis (NDM) on CT scans 3 months later. The accuracy was 94.37% (AUC 0.9705, p < 0.0001) and the progression-free survival (PFS) and overall survival (OS) of patients with cfDNA concentration of >9.71 ng/mL were worse than those patients with cfDNA concentration of <9.71 ng/mL (median PFS: 95 days versus 322 days, p < 0.0001; median OS: 150 days versus 431 days, p < 0.0001). The cfDNA concentration of >9.71 ng/mL is a predictor for PFS, OS, and distant metastasis-free survival by multivariate analysis. Comparison of KRAS G12 variants detected by next-generation sequencing from tumor tissue issue and remnant DNA of cfDNA showed that increased cfDNA was primarily derived from cancer cells. Conclusion: The cancer-cell-derived cfDNA levels could be served as a powerful biomarker for prediction of NDM in patients with advanced/metastatic pancreatic cancer.

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Treatment monitoring of colorectal cancer by integrated analysis of plasma concentration and sequencing of circulating tumor DNA

Cited by 9 publications

References 10 publications

Sensitive Quantification of Cell-Free Tumor DNA for Early Detection of Recurrence in Colorectal Cancer

Sensitive Quantification of Cell-Free Tumor DNA for Early Detection of Recurrence in Colorectal Cancer

Dynamic liquid biopsy components as predictive and prognostic biomarkers in colorectal cancer

Cancer-cell-derived cell-free DNA can predict distant metastasis earlier in pancreatic cancer: a prospective cohort study

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