scholarly journals Circulating Tumor DNA Detection by Digital-Droplet PCR in Pancreatic Ductal Adenocarcinoma: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 994
Author(s):  
Marisol Huerta ◽  
Susana Roselló ◽  
Luis Sabater ◽  
Ana Ferrer ◽  
Noelia Tarazona ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Residual Disease ◽  
Malignant Tumors ◽  
Circulating Tumor Dna ◽  
Ductal Adenocarcinoma ◽  
Epigenetic Alterations ◽  
Non Invasive ◽  
Droplet Pcr ◽  
Tumor Dna

Pancreatic cancer (PC) is one of the most devastating malignant tumors, being the seventh leading cause of cancer-related death worldwide. Researchers and clinicians are endeavoring to develop strategies for the early detection of the disease and the improvement of treatment results. Adequate biopsy is still challenging because of the pancreas’s poor anatomic location. Recently, circulating tumor DNA (ctDNA) could be identified as a liquid biopsy tool with huge potential as a non-invasive biomarker in early diagnosis, prognosis and management of PC. ctDNA is released from apoptotic and necrotic cancer cells, as well as from living tumor cells and even circulating tumor cells, and it can reveal genetic and epigenetic alterations with tumor-specific and individual mutation and methylation profiles. However, ctDNA sensibility remains a limitation and the accuracy of ctDNA as a biomarker for PC is relatively low and cannot be currently used as a screening or diagnostic tool. Increasing evidence suggests that ctDNA is an interesting biomarker for predictive or prognosis studies, evaluating minimal residual disease, longitudinal follow-up and treatment management. Promising results have been published and therefore the objective of our review is to understand the current role and the future perspectives of ctDNA in PC.

scholarly journals Circulating tumor DNA is detectable in canine histiocytic sarcoma, oral malignant melanoma, and multicentric lymphoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anaïs Prouteau ◽  
Jérôme Alexandre Denis ◽  
Pauline De Fornel ◽  
Edouard Cadieu ◽  
Thomas Derrien ◽  
...  
Keyword(s):  
Residual Disease ◽  
Specific Antigen ◽  
Point Mutations ◽  
Antigen Receptor ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Histiocytic Sarcoma ◽  
Oncology Research ◽  
Tumor Dna

AbstractCirculating tumor DNA (ctDNA) has become an attractive biomarker in human oncology, and its use may be informative in canine cancer. Thus, we used droplet digital PCR or PCR for antigen receptor rearrangement, to explore tumor-specific point mutations, copy number alterations, and chromosomal rearrangements in the plasma of cancer-affected dogs. We detected ctDNA in 21/23 (91.3%) of histiocytic sarcoma (HS), 2/8 (25%) of oral melanoma, and 12/13 (92.3%) of lymphoma cases. The utility of ctDNA in diagnosing HS was explored in 133 dogs, including 49 with HS, and the screening of recurrent PTPN11 mutations in plasma had a specificity of 98.8% and a sensitivity between 42.8 and 77% according to the clinical presentation of HS. Sensitivity was greater in visceral forms and especially related to pulmonary location. Follow-up of four dogs by targeting lymphoma-specific antigen receptor rearrangement in plasma showed that minimal residual disease detection was concordant with clinical evaluation and treatment response. Thus, our study shows that ctDNA is detectable in the plasma of cancer-affected dogs and is a promising biomarker for diagnosis and clinical follow-up. ctDNA detection appears to be useful in comparative oncology research due to growing interest in the study of natural canine tumors and exploration of new therapies.

Non-Invasive Monitoring of Urinary KRAS Circulating Tumor DNA for Treatment Response and Minimal Residual Disease in Patients with Lung Adenocarcinoma.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e19092-e19092 ◽  
Author(s):  
James Michael Randall ◽  
Mark G. Erlander ◽  
Cecile Rose T. Vibat ◽  
Saege Hancock ◽  
Vlada Melnikova ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Treatment Response ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Circulating Tumor Dna ◽  
Invasive Monitoring ◽  
Non Invasive ◽  
Tumor Dna ◽  
Minimal Residual

Clinical implications of monitoring circulating tumor DNA in early- and late-stage non-small cell lung cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20607-e20607
Author(s):  
Muyun Peng ◽  
Lihan Chin ◽  
Qi Huang ◽  
Wei Yin ◽  
Sichuang Tan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Somatic Mutations ◽  
Residual Disease ◽  
Lung Squamous Cell Carcinoma ◽  
Circulating Tumor Dna ◽  
Small Cell Lung ◽  
Tumor Dna

e20607 Background: Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers, and the most common types of NSCLC are squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. The development of noninvasive methods to monitor circulating tumor DNA (ctDNA) continues to be a major challenge in NSCLC. Methods: We investigated if detection of ctDNA after resection of NSCLC identifies the patients with risk of relapse, and furthermore, informs about response to management.In this cohort study, high-throughput 168 target-gene capture technology and high-sensitivity circulating single molecule amplification and re-sequencing technology (cSMART) were used to detect the somatic mutations in tissues and plasma of patients with NSCLC, respectively. Moreover, ctDNA somatic mutations were used to monitor changes in minimal residual disease during a follow-up period. Results: A total of 169 patients with lung squamous cell carcinoma and adenocarcinoma were included. Detectable levels of ctDNA were present in 60.7% of patients with stage I and 68.8% of patients with late-stage. In patients not treated with adjuvant chemotherapy, ctDNA was detected preoperatively in 46 of 81 (56.8%) patients, 14 (30.4%) of whom had recurred at follow-up of 44 months; recurrence occurred in only 2 (5.7 %) of 35 patients with negative ctDNA. Serial ctDNA status changed from positive to negative during the initial phase of post operation in four patients. Then, ctDNA became positive again after 2 weeks to 3 months, all the four patients with relapse during the follow-up of 44 months. Conclusions: Detection of ctDNA supplies evidence of residual disease and identifies patients at risk of relapse. These observations have implications for the intervention of lung squamous cell carcinoma and adenocarcinoma patients.

scholarly journals ctDNAtools: An R package to work with sequencing data of circulating tumor DNA

2020 ◽  
Author(s):  
Amjad Alkodsi ◽  
Leo Meriranta ◽  
Annika Pasanen ◽  
Sirpa Leppä
Keyword(s):  
Residual Disease ◽  
Fragment Size ◽  
R Package ◽  
Monte Carlo Sampling ◽  
Circulating Tumor Dna ◽  
Cancer Diagnostics ◽  
Sequencing Data ◽  
Liquid Biopsies ◽  
Tumor Dna

AbstractSummarySequencing of cell-free DNA (cfDNA) including circulating tumor DNA (ctDNA) in minimally-invasive liquid biopsies is rapidly maturing towards clinical utility for cancer diagnostics. However, the publicly available bioinformatics tools for the specialized analysis of ctDNA sequencing data are still scarce. Here, we present the ctDNAtools R package, which provides functionalities for testing minimal residual disease (MRD) and analyzing cfDNA fragmentation. MRD detection in ctDNAtools utilizes a Monte Carlo sampling approach to test ctDNA positivity through tracking a set of pre-detected reporter mutations in follow-up samples. Additionally, ctDNAtools includes various functionalities to study cfDNA fragment size histograms, profiles and fragment ends patterns.AvailabilityThe ctDNAtools package is freely available under MIT license at https://github.com/alkodsi/ctDNAtools.

Non-invasive diagnosis and tracking of tumor evolution by targeted sequencing of circulating tumor DNA in metastatic pancreatic cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15769-e15769
Author(s):  
Thomas Seufferlein ◽  
Andreas W. Berger ◽  
Daniel Schwerdel ◽  
Thomas Jens Ettrich ◽  
Stefan A. Schmidt ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Early Stage ◽  
Therapy Monitoring ◽  
Circulating Tumor Dna ◽  
Ductal Adenocarcinoma ◽  
Tumor Evolution ◽  
Imaging Data ◽  
Non Invasive ◽  
Outcome Monitoring ◽  
Tumor Dna

e15769 Background: Treatment of stage IV pancreatic ductal adenocarcinoma (PDAC) has made substantial progress over the last years, therapy monitoring still is at an early stage. This could be substantially supported by tools that allow to establish and monitor the molecular setup of the tumor even during treatment. In particular, non-invasive approaches are desirable. Characterization of circulating tumor DNA (ctDNA) may help to achieve this goal. Methods: We analyzed a cohort of 20 patients with histologically confirmed metastatic PDAC (mPDAC) prior to and during palliative treatment including disease progression. ctDNA and corresponding tumor tissue were analyzed by targeted NGS and droplet digital PCR for the 7 most frequently mutated genes in PDAC ( TP53, SMAD4, CDKN2A, KRAS, APC, ATM, FBXW7). Findings were correlated with clinical and imaging data to establish its prognostic and predictive value. Results: ctDNA was analyzed at baseline prior to initiation of the respective line of treatment. Mutations in either of the genes examined were detectable in 15/20 patients (75%). Tissue-blood concordance was 80% in therapy naïve patients. 96% of mutations in ctDNA of therapy naïve patients were in KRAS and/or TP53. The combined mutated allele frequencies (CMAF) of theese 2 genes significantly decreased (p = 0.0173) during therapy and increased at progression (p = 0.0145) across all treatment lines. By sequential ctDNA analyses we detected a change in the mutational landscape compared to the respective baseline ctDNA status in 7/11 patients during 1st line, in 3/7 patients during 2nd line and 2/2 patients during 3rdline treatment. In therapy naïve patients, the decline of the CMAF during therapy significantly correlated with progression-free survival (p = 0.0013). Conclusions: Molecular genotyping of ctDNA in mPDAC patients proved to be feasible and there was a high concordance between tumor tissue and ctDNA. The molecular genotype changed significantly during treatment and changes correlated with outcome. Monitoring of ctDNA may enable to adapt therapeutic strategies to the specific molecular changes present at a certain time during treatment of mPDAC.

scholarly journals Circulating Tumor DNA Testing Opens New Perspectives in Melanoma Management

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2914 ◽  
Author(s):  
Alessandra Sacco ◽  
Laura Forgione ◽  
Marianeve Carotenuto ◽  
Antonella De Luca ◽  
Paolo A. Ascierto ◽  
...  
Keyword(s):  
Residual Disease ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Prognostic Information ◽  
Skin Cancers ◽  
Highly Sensitive ◽  
Ctdna Analysis ◽  
Next Generation Sequencing Ngs ◽  
Tumor Dna

Malignant melanoma accounts for about 1% of all skin cancers, but it causes most of the skin cancer-related deaths. Circulating tumor DNA (ctDNA) testing is emerging as a relevant tool for the diagnosis and monitoring of cancer. The availability of highly sensitive techniques, including next generation sequencing (NGS)-based panels, has increased the fields of application of ctDNA testing. While ctDNA-based tests for the early detection of melanoma are not available yet, perioperative ctDNA analysis in patients with surgically resectable melanoma offers relevant prognostic information: i) the detection of ctDNA before surgery correlates with the extent and the aggressiveness of the disease; ii) ctDNA testing after surgery/adjuvant therapy identifies minimal residual disease; iii) testing ctDNA during the follow-up can detect a tumor recurrence, anticipating clinical/radiological progression. In patients with advanced melanoma, several studies have demonstrated that the analysis of ctDNA can better depict tumor heterogeneity and provides relevant prognostic information. In addition, ctDNA testing during treatment allows assessing the response to systemic therapy and identifying resistance mechanisms. Although validation in prospective clinical trials is needed for most of these approaches, ctDNA testing opens up new scenarios in the management of melanoma patients that could lead to improvements in the diagnosis and therapy of this disease.

scholarly journals Circulating Tumor Cells, Circulating Tumor DNA and Other Blood-based Prognostic Scores in Pancreatic Ductal Adenocarcinoma – Mini-Review

In Vivo ◽  
2021 ◽  
Vol 35 (1) ◽  
pp. 31-39
Author(s):  
MARIAN LIBERKO ◽  
KATARINA KOLOSTOVA ◽  
ARPAD SZABO ◽  
ROBERT GURLICH ◽  
MARTIN OLIVERIUS ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Circulating Tumor Dna ◽  
Prognostic Scores ◽  
Ductal Adenocarcinoma ◽  
Tumor Dna

Potentials, challenges and limitations of a molecular characterization of circulating tumor DNA for the management of cancer patients

2016 ◽  
Vol 40 (5) ◽  
Author(s):  
Peter Ulz ◽  
Armin Gerger ◽  
Jelena Belic ◽  
Ellen Heitzer
Keyword(s):  
Cancer Patients ◽  
Residual Disease ◽  
Metastatic Cancer ◽  
Circulating Tumor Dna ◽  
Disease Assessment ◽  
Tumor Evolution ◽  
Non Invasive ◽  
New Findings ◽  
Technological Improvements ◽  
Tumor Dna

Abstract:A liquid profiling, i.e. the analysis of cell-free circulating tumor DNA (ctDNA), enables a continuous non-invasive monitoring of tumor-specific changes during the entire course of the disease with respect to early detection, identification of minimal residual disease, assessment of treatment response and monitoring tumor evolution. Technological improvements, advances in understanding the nature of ctDNA, the implementation of ctDNA analyses in clinical trials as well as efforts for the establishment of benchmarks, will bring an actual widespread clinic use within reach in the near future. However, despite this progress there are still hurdles that have to be overcome, which are discussed in this review. Moreover, present knowledge and new findings about the biology of ctDNA as well as selected potential clinical applications for metastatic cancer patients are pointed out.

scholarly journals Circulating Tumor DNA and Minimal Residual Disease (MRD) in Solid Tumors: Current Horizons and Future Perspectives

2021 ◽  
Vol 11 ◽  
Author(s):  
Yan Peng ◽  
Wuxuan Mei ◽  
Kaidong Ma ◽  
Changchun Zeng
Keyword(s):  
Solid Tumors ◽  
Clinical Decision Making ◽  
Residual Disease ◽  
Malignant Tumors ◽  
Circulating Tumor Dna ◽  
Detection Methods ◽  
Risk Of Recurrence ◽  
Increased Risk ◽  
Ctdna Analysis ◽  
Tumor Dna

Circulating tumor DNA (ctDNA) is cell-free DNA (cfDNA) fragment in the bloodstream that originates from malignant tumors or circulating tumor cells. Recently, ctDNA has emerged as a promising non-invasive biomarker in clinical oncology. Analysis of ctDNA opens up new avenues for individualized cancer diagnosis and therapy in various types of tumors. Evidence suggests that minimum residual disease (MRD) is closely associated with disease recurrence, thus identifying specific genetic and molecular alterations as novel MRD detection targets using ctDNA has been a research focus. MRD is considered a promising prognostic marker to identify individuals at increased risk of recurrence and who may benefit from treatment. This review summarizes the current knowledge of ctDNA and MRD in solid tumors, focusing on the potential clinical applications and challenges. We describe the current state of ctDNA detection methods and the milestones of ctDNA development and discuss how ctDNA analysis may be an alternative for tissue biopsy. Additionally, we evaluate the clinical utility of ctDNA analysis in solid tumors, such as recurrence risk assessment, monitoring response, and resistance mechanism analysis. MRD detection aids in assessing treatment response, patient prognosis, and risk of recurrence. Moreover, this review highlights current advancements in utilizing ctDNA to monitor the MRD of solid tumors such as lung cancer, breast cancer, and colon cancer. Overall, the clinical application of ctDNA-based MRD detection can assist clinical decision-making and improve patient outcomes in malignant tumors.

Analysis of circulating tumor DNA (ctDNA) in pseudoprogression in anti-PD1 treated metastatic melanoma (MM).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9546-9546
Author(s):  
Jenny HJ Lee ◽  
Georgina V. Long ◽  
Alexander M. Menzies ◽  
Alexander David Guminski ◽  
Richard Kefford ◽  
...  
Keyword(s):  
Disease Progression ◽  
Circulating Tumor Dna ◽  
The Other ◽  
Clinical Progression ◽  
Radiological Progression ◽  
Digital Droplet Pcr ◽  
Droplet Pcr ◽  
True Progression ◽  
Tumor Dna

9546 Background: We have previously shown that undetectable ctDNA either at baseline or during therapy predicted response in mm patients (pts) treated with anti-PD1 antibodies (aPD1). Pseudoprogression, defined as radiological progression prior to response, occurs in 8% of pts treated with aPD1. We sought to determine if ctDNA could differentiate pseudoprogression from true progression, defined as continued clinical or radiological disease progression. Methods: Between July 2014 and May 2016, pts receiving aPD1 had serial bloods for ctDNA. Included pts either had RECIST PD at first restaging or early clinical progression. Those with untreated brain metastases were excluded from the analysis. ctDNA was quantified using digital droplet PCR for mutations (BRAF/NRAS) at baseline and during the first 12 wks of treatment. Based on our prior studies, ctDNA results were grouped in to ‘favorable’ and ‘unfavorable’ ctDNA profiles (see Table), and these were compared in pts with true and pseudoprogression. Results: 29 pts were included, 28 with RECIST PD at first restaging and one with early clinical progression. 9 (31%) pts had a subsequent RECIST PR or SD and were considered pseudoprogression and 20 (69%) had true progression. Of the pseudoprogressors, 7/9 pts remained in response with a median follow-up of 20 months (mths). 2/9 pts had disease progression at 7 and 18 mths, with ctDNA that remained detectable with a > 10-fold decrease during treatment in both patients. Of those with true progression and a favourable profile, 1 had a > 10-fold decrease in ctDNA by wk 12 and was switched to MAPK therapy prior to further imaging, and the other had an undetectable ctDNA at wk 6 which increased again at wk 12. The latter pt had a new lesion on first restaging CT scan despite PR in all existing lesions with true PD on second restaging at wk 24. Conclusions: ctDNA in patients with mm at baseline and early on aPD1 treatment differentiates pseudo from true progression. [Table: see text]

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