scholarly journals Circulating tumor DNA as prognostic markers for late stage NSCLC with bone metastasis

2018 ◽  
Vol 33 (2) ◽  
pp. 222-230 ◽  
Author(s):  
Jiguang Jia ◽  
Bin Huang ◽  
Zhengling Zhuang ◽  
Sen Chen
Keyword(s):  
Overall Survival ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Late Stage ◽  
Circulating Tumor Dna ◽  
Molecular Profile ◽  
Potential Biomarker ◽  
Patient Groups ◽  
Nsclc Patients ◽  
Tumor Dna

Purpose: Bone metastases from non-small cell lung cancer (NSCLC) are common, and current prognostic stratification methods are challenging to predict outcomes. The aim of the study is to examine circulating tumor DNA as a potential biomarker to gauge overall survival. Methods: Late stage NSCLC patients associated with bone metastasis were recruited for the study. Circulating tumor DNA was quantified using droplet digital polymerase chain reaction, a sensitive assay that is capable to pick up low mutant DNA frequencies. KRAS and EGFR genes were serially profiled at monthly intervals to ascertain their variations in different patients during monitoring. These were correlated to overall survival as an endpoint measure. Results: Analysis of circulating tumor DNA and tumor tissues samples yielded a 94.7% overall agreement for KRAS and EGFR mutations. Higher circulating tumor DNA quantities of more than 1.4-fold were also detected in patients with bone metastases. To gauge the prognostic utility of circulating tumor DNA for these patient groups, circulating tumor DNA quantities as well as the patients’ genotypes were used to stratify patients in the survival analysis. Hazard ratios for patient groups with and without bone metastasis was 1.63. Patients groups separated by circulating tumor DNA quantity and molecular profile were 1.51 and 1.58, respectively. The results showed that circulating tumor DNA was a useful marker to identify patients with better survival outcomes. Conclusion: The good overall concordance in genetic profiling and circulating tumor DNA measurements associated with NSCLC patients with bone metastases supports plasma-based testing. This study presents exploratory evidence of the prognostic role of circulating tumor DNA that can be of value in the management of the disease.

97 POSTER Analysis of EGFR and KRAS mutations in circulating tumor DNA (cTDNA) from plasma of NSCLC patients in phase 2 trials of XL647

2008 ◽  
Vol 6 (12) ◽  
pp. 33
Author(s):  
F. Schimmoller ◽  
N.A. Rizvi ◽  
V.S. Vysotskaia ◽  
R.P. Funke ◽  
S. Dixon ◽  
...  
Keyword(s):  
Circulating Tumor Dna ◽  
Phase 2 ◽  
Kras Mutations ◽  
Nsclc Patients ◽  
Tumor Dna

scholarly journals Meta-analysis of the studies dedicated to the predictive significance of circulating tumor DNA in pancreatic cancer

2020 ◽  
Vol 22 (3) ◽  
pp. 127-132
Author(s):  
A. S. Popova ◽  
M. Yu. Fedyanin ◽  
I. A. Pokataev ◽  
S. A. Tyulyandin
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Confidence Interval ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Poor Overall Survival ◽  
Risk Of Mortality ◽  
Before And After ◽  
Tumor Dna

The method of liquid biopsy allows detection of circulating tumor DNA (ctDNA) in patient blood, but the clinical significance of this approach in pancreatic cancer is still unclear. In this regard, we have carried out a meta-analysis of the studies dedicated to the predictive significance of ctDNA in pancreatic cancer. Materials and methods.We carried out the search for the articles and abstracts in PubMed, ASCO and ESMO databases published before February 2020, containing data about the connection between ctDNA and the prognosis of pancreatic cancer. The exclusion criteria were the studies including 10 or less participating patients, absence of the data about the relative risk of mortality and/or progression, and the 95% confidence interval. The meta-analysis was carried out by using the Review Manager software (RevMan), Version 5.3. Results.There were no significant systematic errors associated with the publications. The presence of ctDNA in patient blood showed poor overall survival of patients (odds ratio OR 2.21, 95% confidence interval CI 1.35-3.33,p=0.001) regardless of the prevalence of the disease. In case of the resectable process, the detection of ctDNA in patient blood both before and after surgery was a factor of worse progression-free survival (OR 2.32, 95% CI 1.543.5,p0.001 and OR 3.06, 95% CI 1.635.76,р=0.0005 and overall survival (OR2.01, 95% CI 1.123.63,р=0,02 and OR 3.39, 95% CI 2.125.44,р0.00001, respectively). Conclusions.The detection of ctDNA in the bloodstream in pancreatic cancer patients is a factor of poor prognosis in both localized and advanced cancer. It is very important to make further prospective studies to develop the optimal protocol for detecting ctDNA in patient bloodstream.

scholarly journals Serial Monitoring of Circulating Tumor DNA by Next-Generation Gene Sequencing as a Biomarker of Response and Survival in Patients With Advanced NSCLC Receiving Pembrolizumab-Based Therapy

2021 ◽  
pp. 510-524
Author(s):  
Jeffrey C. Thompson ◽  
Erica L. Carpenter ◽  
Benjamin A. Silva ◽  
Jamie Rosenstein ◽  
Austin L. Chien ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Variant Allele ◽  
Molecular Response ◽  
Next Generation ◽  
Free Survival ◽  
Variant Allele Fraction ◽  
Tumor Dna ◽  
Allele Fraction

PURPOSE Although the majority of patients with metastatic non–small-cell lung cancer (mNSCLC) lacking a detectable targetable mutation will receive pembrolizumab-based therapy in the frontline setting, predicting which patients will experience a durable clinical benefit (DCB) remains challenging. MATERIALS AND METHODS Patients with mNSCLC receiving pembrolizumab monotherapy or in combination with chemotherapy underwent a 74-gene next-generation sequencing panel on blood samples obtained at baseline and at 9 weeks. The change in circulating tumor DNA levels on-therapy (molecular response) was quantified using a ratio calculation with response defined by a > 50% decrease in mean variant allele fraction. Patient response was assessed using RECIST 1.1; DCB was defined as complete or partial response or stable disease that lasted > 6 months. Progression-free survival and overall survival were recorded. RESULTS Among 67 patients, 51 (76.1%) had > 1 variant detected at a variant allele fraction > 0.3% and thus were eligible for calculation of molecular response from paired baseline and 9-week samples. Molecular response values were significantly lower in patients with an objective radiologic response (log mean 1.25% v 27.7%, P < .001). Patients achieving a DCB had significantly lower molecular response values compared to patients with no durable benefit (log mean 3.5% v 49.4%, P < .001). Molecular responders had significantly longer progression-free survival (hazard ratio, 0.25; 95% CI, 0.13 to 0.50) and overall survival (hazard ratio, 0.27; 95% CI, 0.12 to 0.64) compared with molecular nonresponders. CONCLUSION Molecular response assessment using circulating tumor DNA may serve as a noninvasive, on-therapy predictor of response to pembrolizumab-based therapy in addition to standard of care imaging in mNSCLC. This strategy requires validation in independent prospective studies.

scholarly journals Liquid biopsy in NSCLC: a new challenge in radiation therapy

2021 ◽  
Author(s):  
Annarita Perillo ◽  
Mohamed Vincenzo Agbaje Olufemi ◽  
Jacopo De Robbio ◽  
Rossella Margherita Mancuso ◽  
Anna Roscigno ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Biological Fluids ◽  
Circulating Tumor Dna ◽  
Minimum Residual ◽  
Nsclc Patients ◽  
Choice Of Therapy ◽  
Tumor Dna

Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide. To date, tissue biopsy has been the gold standard for the diagnosis and the identification of specific molecular mutations, to guide choice of therapy. However, this procedure has several limitations. Liquid biopsy could represent a solution to the intrinsic limits of traditional biopsy. It can detect cancer markers such as circulating tumor DNA or RNA (ctDNA, ctRNA), and circulating tumor cells, in plasma, serum or other biological fluids. This procedure is minimally invasive, reproducible and can be used repeatedly. The main clinical applications of liquid biopsy in non-small cell lung cancer (NSCLC) patients are the early diagnosis, stratification of the risk of relapse, identification of mutations to guide application of targeted therapy and the evaluation of the minimum residual disease. In this review, the current role of liquid biopsy and associated markers in the management of NSCLC patients was analyzed, with emphasis on ctDNA and CTCs, and radiotherapy.

Evaluation of liquid biopsies for molecular profiling in patients with advanced non-small cell lung cancer (NSCLC) in the relapse treatment setting.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11532-11532
Author(s):  
Jordi Remon ◽  
Benjamin Besse ◽  
Ludovic Lacroix ◽  
Laura Mezquita ◽  
Cecile Jovelet ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Dynamic Change ◽  
Molecular Profiling ◽  
Molecular Profile ◽  
Blood Collection ◽  
Liquid Biopsies ◽  
Molecular Abnormalities ◽  
Nsclc Patients ◽  
Tumor Dna ◽  
Allele Fraction

11532 Background: Molecular profiling is limited by access to sufficient tumor tissue for comprehensive analysis and due to tumor heterogeneity, the complete range of tumor DNA abnormalities may not be represented nor accurately reflect the clinical evolution of disease. Circulating tumor DNA (ctDNA) can be used as a minimally-invasive liquid biopsy for the detection, quantification and monitoring of molecular abnormalities for personalized treatment strategies. Methods: In a prospectively designed program, to date, we have recruited 227 advanced NSCLC patients having received prior therapy, with unknown molecular profile at time of blood collection. Blood collections (10ml K2-EDTA) were performed to assess molecular profile prior to or at time of relapse. Repeat samples were performed on patients initiated on treatment and followed for up to 18months. Patient samples were analyzed with InVision (enhanced tagged-amplicon sequencing) using a 34 gene panel. Interim analysis performed with full descriptive summary statistical analyses to be presented at conference. Results: ctDNA profiling detected somatic mutations in 182pts (80.2%), predominantly located in TP53 (46%), EGFR (28%), KRAS (11%) and STK11 (7%, half of which had concurrent KRAS). Of note, clinically actionable mutations were detected: T790M (25pts, median 1.4% AF), ERBB2 (8 pts), MET (8pts) and BRAF (4pts) providing eligibility for new therapy options. 20pts including 12 EGFR/T790M+ve were evaluated for ctDNA monitoring up to 18 months (median 10m); correlation between dynamic change in mutation allele fraction and clinical response was observed, especially predictive of relapse to treatment. 10 patients demonstrated SD/PR response to osimertinib treatment with T790M detection at low allele fraction (7/10 < 1% AF with 1pt at 0.08% AF). Conclusions: ctDNA can be used as a non-invasive ‘liquid biopsy’ for molecular profiling of NSCLC patients to detect clinically relevant and actionable mutations when tissue biopsy is unavailable. Liquid biopsies can be repeated as needed where tissue is not feasible, providing real-time information to support personalised treatment.

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