scholarly journals The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Ying Jin ◽  
Dong-Liang Chen ◽  
Feng Wang ◽  
Chao-pin Yang ◽  
Xu-Xian Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Allelic Frequency ◽  
Potential Biomarker ◽  
Antibody Immunotherapy ◽  
Gastric Cancer Patients ◽  
Next Generation Sequencing Ngs ◽  
Tumor Dna

Abstract A more common and noninvasive predicting biomarker for programmed cell death 1 (PD-1) antibody remains to be explored. We assessed 46 patients with advanced gastric cancer who received PD-1 antibody immunotherapy and 425-genes next-generation sequencing (NGS) testing. Patients who had a > 25% decline in maximal somatic variant allelic frequency (maxVAF) had a longer progression free survival (PFS) and higher response rate than those who did not (7.3 months vs 3.6 months, p = 0.0011; 53.3% vs 13.3%, p = 0.06). The median PFS of patients with undetectable and detectable post-treatment circulating tumor DNA (ctDNA) was 7.4 months vs. 4.9 months (p = 0.025). Mutation status of TGFBR2, RHOA, and PREX2 in baseline ctDNA influenced the PFS of immunotherapy (p < 0.05). Patients with alterations in CEBPA, FGFR4, MET or KMT2B (p = 0.09) gene had greater likelihood of immune-related adverse events (irAEs). ctDNA can serve as a potential biomarker of the response to immunotherapy in advanced gastric cancers, and its potential role in predicting irAEs worth further exploration.

scholarly journals Limited Sensitivity of Circulating Tumor DNA Detection by Droplet Digital PCR in Non-Metastatic Operable Gastric Cancer Patients

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 396 ◽  
Author(s):  
Luc Cabel ◽  
Charles Decraene ◽  
Ivan Bieche ◽  
Jean-Yves Pierga ◽  
Mostefa Bennamoun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Metastatic Gastric Cancer ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Allelic Frequency ◽  
Droplet Digital Pcr ◽  
Perioperative Chemotherapy ◽  
Plasma Samples ◽  
Tumor Dna

This study was designed to monitor circulating tumor DNA (ctDNA) levels during perioperative chemotherapy in patients with non-metastatic gastric adenocarcinoma. Plasma samples were prospectively collected in patients undergoing perioperative chemotherapy for non-metastatic gastric adenocarcinoma (excluding T1N0) prior to the initiation of perioperative chemotherapy, before and after surgery (NCT02220556). In each patient, mutations retrieved by targeted next-generation sequencing (NGS) on tumor samples were then tracked in circulating cell-free DNA from 4 mL of plasma by droplet digital PCR. Thirty-two patients with a diagnosis of non-metastatic gastric adenocarcinoma were included. A trackable mutation was identified in the tumor in 20 patients, seven of whom experienced relapse during follow-up. ctDNA was detectable in four patients (N = 4/19, sensitivity: 21%; 95% confidence interval CI = 8.5–43%, no baseline plasma sample was available for one patient), with a median allelic frequency (MAF) of 1.6% (range: 0.8–2.3%). No patient with available plasma samples (N = 0/18) had detectable ctDNA levels before surgery. After surgery, one of the 13 patients with available plasma samples had a detectable ctDNA level with a low allelic frequency (0.7%); this patient experienced a very short-term distant relapse only 3 months after surgery. No ctDNA was detected after surgery in the other four patients with available plasma samples who experienced a later relapse (median = 14.4, range: 9.3–26 months). ctDNA monitoring during preoperative chemotherapy and after surgery does not appear to be a useful tool in clinical practice for non-metastatic gastric cancer to predict the efficacy of chemotherapy and subsequent relapse, essentially due to the poor sensitivity of ctDNA detection.

scholarly journals Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Olga Martínez-Sáez ◽  
Tomás Pascual ◽  
Fara Brasó-Maristany ◽  
Nuria Chic ◽  
Blanca González-Farré ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Endocrine Therapy ◽  
Methodological Approach ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Advanced Breast ◽  
Dna Dynamics ◽  
Ca 15.3 ◽  
Tumor Dna

AbstractCirculating tumor DNA (ctDNA) levels may predict response to anticancer drugs, including CDK4/6 inhibitors and endocrine therapy combinations (CDK4/6i+ET); however, critical questions remain unanswered such as which assay or statistical method to use. Here, we obtained paired plasma samples at baseline and week 4 in 45 consecutive patients with advanced breast cancer treated with CDK4/6i+ET. ctDNA was detected in 96% of cases using the 74-gene Guardant360 assay. A variant allele fraction ratio (VAFR) was calculated for each of the 79 detected mutations between both timepoints. Mean of all VAFRs (mVAFR) was computed for each patient. In our dataset, mVAFR was significantly associated with progression-free survival (PFS). Baseline VAF, on-treatment VAF or absolute changes in VAF were not associated with PFS, nor were CA-15.3 levels at baseline, week 4 or the CA-15.3 ratio. These findings demonstrate that ctDNA dynamics using a standardized multi-gene panel and a unique methodological approach predicts treatment outcome. Clinical trials in patients with an unfavorable ctDNA response are needed.

scholarly journals BIOM-47. LONGITUDINAL MONITORING OF PLASMA H3K27M IN DIFFUSE MIDLINE GLIOMA PATIENTS TREATED WITH ONC201

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii11-ii11
Author(s):  
Rohinton S Tarapore ◽  
Amanda Field ◽  
D Ashley Hill ◽  
Joshua Allen
Keyword(s):  
Radiographic Progression ◽  
Low Frequency ◽  
Circulating Tumor Dna ◽  
Allelic Frequency ◽  
Who Grade ◽  
Line Radiation ◽  
Complication Risk ◽  
Droplet Pcr ◽  
Tumor Dna ◽  
Diffuse Midline Glioma

Abstract Diffuse midline glioma, H3 K27M-mutant (DMG) is a 2016 WHO Grade IV glioma that has no established treatment beyond first-line radiation. ONC201 is an investigational small molecule that has been shown to be clinically active in recurrent DMG clinical trials. While biopsies of DMG are sometimes feasible, many patients defer secondary to complication risk. MR scans have many limitations in monitoring DMG progression, including distinguishing pseudoprogression and pseudoresponse and measuring diffuse lesions that often do not contrast enhance. Digital droplet PCR (ddPCR) is capable of sensitively detecting and quantifying the allelic frequency of circulating-tumor DNA (ctDNA) fragments against a backdrop of non-tumor DNA. Using sequence-specific probes for H3F3A (H3.3 K27M) and HIST1H3B (H3.1 K27M) ddPCR detects very low frequency variants and provides an assessment of mutational burden. A pilot cohort of 5 patients treated with ONC201 who had a range of outcomes were assessed with serial ctDNA analyses. Two patients with immediately progressive disease had a concordant H3 K27M ctDNA increase that precedes radiographic detection by 4 weeks. Two patients with &gt;50% tumor regressions while on ONC201 had concordant H3 K27M ctDNA burden at the onset of response and subsequent radiographic progression was preceded by increases in ctDNA 8–16 weeks prior. One patient who had prolonged stable disease had decreased H3 K27M ctDNA burden over time. Upon radiographic progression, the addition of bevacizumab with ONC201 caused a radiographic pseudoresponse, however H3 K27M ctDNA remained stable. These pilot results suggest H3 K27M ctDNA may be a sensitive and accurate biomarker of disease burden. Longitudinal evaluation of H3 K27M ctDNA in a cohort of 34 recurrent contrast-enhancing H3 K27M-mutant glioma patients while on ONC201 will be reported. Primary tumor locations range across the thalamus, cerebellum, basal ganglia, temporal lobe, and midbrain; median age is 31 years old (range 20–70).

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.

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