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.

A Systematic Review and Meta-analysis of the Association Between Circulating Tumor DNA (ctDNA) and Prognosis in Pancreatic Cancer

2021 ◽  
pp. 103528
Author(s):  
Deniz Can Guven ◽  
Taha Koray Sahin ◽  
Hasan Cagri Yildirim ◽  
Oktay Halit Aktepe ◽  
Omer Dizdar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pancreatic Cancer ◽  
Meta Analysis ◽  
Circulating Tumor Dna ◽  
Tumor Dna

scholarly journals Prognostic value of the C-reactive protein to albumin ratio in colorectal cancer: an updated systematic review and meta-analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chun-Kai Liao ◽  
Yen-Lin Yu ◽  
Yueh-Chen Lin ◽  
Yu-Jen Hsu ◽  
Yih-Jong Chern ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Pre Treatment ◽  
Disease Free

Abstract Backgrounds The inflammatory biomarker “C-reactive protein to albumin ratio (CAR)” has been reported to significantly correlate to a variety of human cancers. However, there are conflicting results regarding the prognostic value of CAR in colorectal cancer. Previous studies mainly assessed patients in Eastern countries, so their findings may not be applicable to the Western population. Therefore, this updated meta-analysis aimed to investigate the prognostic value of pre-treatment CAR and outcomes of patients with colorectal cancer. Methods We conducted a systematic search for eligible literature until October 31, 2020, using PubMed and Embase databases. Studies assessing pre-treatment CAR and outcomes of colorectal cancer were included. Outcome measures included overall survival, disease-free survival, progression-free survival, and clinicopathological features. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values. Results A total of 15 studies involving 6329 patients were included in this study. The pooled results indicated that a high pre-treatment CAR was associated with poor overall survival (HR 2.028, 95% CI 1.808−2.275, p < 0.001) and poor disease-free survival/progression-free survival (HR 1.768, 95% CI 1.321–2.365, p < 0.001). Subgroup analysis revealed a constant prognostic value of the pre-treatment CAR despite different study regions, sample size, cancer stage, treatment methods, or the cut-off value used. We also noted a correlation between high pre-treatment CAR and old age, male sex, colon cancer, advanced stage (III/IV), large tumor size, poor differentiation, elevated carcinoembryonic antigen levels, neutrophil-to-lymphocyte ratio, and the modified Glasgow prognostic score. Conclusions High pre-treatment CAR was associated with poor overall survival, disease-free survival, and progression-free survival in colorectal cancer. It can serve as a prognostic marker for colorectal cancer in clinical practice.

scholarly journals Diagnostic and prognostic values of KRAS mutations on EUS-FNA specimens and circulating tumor DNA in patients with pancreatic cancer

2020 ◽  
Author(s):  
Ronghua Wang ◽  
Jinlin Wang ◽  
Yuchong Zhao ◽  
Yun Wang ◽  
Zhenxiong Zhao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mutation Analysis ◽  
Fine Needle Aspiration ◽  
Kras Mutation ◽  
Needle Aspiration ◽  
Circulating Tumor Dna ◽  
Rank Test ◽  
Poor Overall Survival ◽  
Fine Needle ◽  
Tumor Dna

Abstract Background: Early diagnosis is critical in reducing pancreatic cancer mortality. We explore the diagnostic values of detecting KRAS gene mutations and plasma circulating tumor DNA (ctDNA) in patients with primary pancreatic cancer. Methods: The cohort study is comprised of 149 consecutive patients with pancreatic solid mass underwent Endoscopic ultrasound fine needle aspiration (EUS-FNA) between September, 2014 and May, 2016. KRAS point mutations (G12V, G12D, and G12R) were analyzed by droplet digital PCR (ddPCR) in EUS-guided fine needle aspiration (FNA) histopathology tissue samples and blood samples were tested for plasma ctDNA. The final diagnosis was based on surgical resection pathology or follow up for at least 2 years. Results: The sensitivity and accuracy of EUS-FNA diagnose was increased from 71.4% to 91.6% (P<0.001) and 75.8% to 88.6% (P <0.001), respectively, when KRAS mutation ddPCR analysis was added to standard EUS-FNA assessment. The sensitivity and accuracy of circulating biomarkers combination (ctDNA and CA19-9) were 78.9% and 76.2%, respectively. The median survival time was significantly shorter in patients with G12D mutations (180 days) compared to patients with other mutations (240 days) (long-rank test, P<0.001). Conclusions: KRAS mutation analysis in tissues significantly improves the sensitivity and accuracy of cyto/histopathological evaluation in EUS-FNA samples. The accuracy of KRAS mutation analysis in EUS-FNA samples was obviously higher than non-invasive blood-based ctDNA KRAS mutation in detecting pancreatic cancer. G12D KRAS mutation in pancreatic cancer were independently associated with poor overall survival.

scholarly journals MLH1 single-nucleotide variant in circulating tumor DNA predicts overall survival of patients with hepatocellular carcinoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Soon Sun Kim ◽  
Jung Woo Eun ◽  
Ji-Hye Choi ◽  
Hyun Goo Woo ◽  
Hyo Jung Cho ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Circulating Tumor Dna ◽  
Single Nucleotide Variants ◽  
Poor Overall Survival ◽  
Single Nucleotide ◽  
Strong Basis ◽  
Polymerase Chain ◽  
Digital Polymerase Chain Reaction ◽  
Tumor Dna

Abstract Liquid biopsy can provide a strong basis for precision medicine. We aimed to identify novel single-nucleotide variants (SNVs) in circulating tumor DNA (ctDNA) in patients with hepatocellular carcinoma (HCC). Deep sequencing of plasma-derived ctDNA from 59 patients with HCC was performed using a panel of 2924 SNVs in 69 genes. In 55.9% of the patients, at least one somatic mutation was detected. Among 25 SNVs in 12 genes, four frequently observed SNVs, MLH1 (13%), STK11 (13%), PTEN (9%), and CTNNB1 (4%), were validated using droplet digital polymerase chain reaction with ctDNA from 62 patients with HCC. Three candidate SNVs were detected in 35.5% of the patients, with a frequency of 19% for MLH1 chr3:37025749T>A, 11% for STK11 chr19:1223126C>G, and 8% for PTEN chr10:87864461C>G. The MLH1 and STK11 SNVs were also confirmed in HCC tissues. The presence of the MLH1 SNV, in combination with an increased ctDNA level, predicted poor overall survival among 107 patients. MLH1 chr3:37025749T>A SNV detection in ctDNA is feasible, and thus, ctDNA can be used to detect somatic mutations in HCC. Furthermore, the presence or absence of the MLH1 SNV in ctDNA, combined with the ctDNA level, can predict the prognosis of patients with HCC.

scholarly journals Network Meta-Analysis of Efficacy and Safety of Chemotherapy and Target Therapy in the First-Line Setting of Advanced Pancreatic Cancer

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1746 ◽  
Author(s):  
Kun-I Lin ◽  
Jia-Lian Yang ◽  
Yu-Chao Lin ◽  
Che-Yi Chou ◽  
Jin-Hua Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Meta Analysis ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Current Evidence ◽  
P Value ◽  
Efficacy And Safety ◽  
First Line ◽  
Free Survival

Both gemcitabine and fluoropyrimidine are recommended backbones in the first-line treatment of pancreatic ductal adenocarcinoma (PDAC). To compare the efficacy and safety of these two therapeutic backbones, and to investigate the optimal therapies, we conducted a network meta-analysis. By retrospective analysis of randomized controlled trials (RCT), the most preferred therapeutic regimen may be predicted. The eligible RCTs of the gemcitabine-based therapies and fluoropyrimidine-based therapies were searched up to 31 August 2019. In a frequentist network meta-analysis, treatments were compared and ranked according to overall survival (OS) and progression-free survival (PFS). Thirty-two trials with 10,729 patients were included. The network meta-analyses results for overall survival and progression-free survival showed that fluoropyrimidine-based therapy seems to be the most effective treatment choice. Compared to gemcitabine combined with taxanes or immunotherapy, fluoropyrimidine-based therapy had comparable treatment effects (PFS: 0.67, p-Value = 0.11; 0.76, p-Value = 0.32; OS: 0.80, p-Value = 0.16; 0.77, p-Value = 0.21). Moreover, the combination of immunotherapy and gemcitabine had tolerable toxicities. Based on current evidence, fluoropyrimidine-based therapies and the combination of gemcitabine and taxanes were the most effective therapies in the advanced pancreatic cancer, and the combination of immunotherapy and gemcitabine can be developed into a new form of therapy.

scholarly journals Pharmacoethnicity of FOLFIRINOX versus gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer: a systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoon Suk Lee ◽  
Jong-chan Lee ◽  
Jae-Hyeong Kim ◽  
Jaihwan Kim ◽  
Jin-Hyeok Hwang
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Survival Benefit ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Cochrane Library ◽  
Chemotherapeutic Regimen ◽  
Free Survival ◽  
Ethnic Subgroups

AbstractTreatment outcomes between FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and GNP (gemcitabine with albumin-bound paclitaxel) as first-line chemotherapy regimens for metastatic pancreatic cancer (PC) were assessed according to ethnic groups categorized as Western or Asian subgroups. PubMed, EMBASE, and Cochrane library were searched. Thirteen studies were eligible in this meta-analysis. Overall survival was not significantly different between FOLFIRINOX and GNP (HR 1.00, 95% CI 0.83–1.20, P = 0.990). However, the Western subgroup showed a higher survival benefit for FOLFIRINOX over GNP (HR 0.84, 95% CI 0.74–0.95, P = 0.006) whereas the Asian subgroup showed the survival benefit for GNP over FOLFIRINOX (HR 1.29, 95% CI 1.03–1.60, P = 0.030). Progression free survival was not significantly different between the two regimens in the Western subgroup (HR 1.01, 95% CI 0.84–1.20, P = 0.950) and the Asian subgroup (HR 1.13, 95% CI 0.97–1.33, P = 0.110). Occurrence of febrile neutropenia was significantly higher in FOLFIRINOX at both ethnic subgroups; however, that of peripheral neuropathy was significantly higher only in GNP of the Asian subgroup. Therefore, pharmacoethnicity might be a factor worth considering when deciding on a frontline chemotherapeutic regimen although the overall survival was not significantly different between FOLFIRINOX and GNP for metastatic PCs.

scholarly journals Circulating Tumor DNA Profiling From Breast Cancer Screening Through to Metastatic Disease

2021 ◽  
pp. 1768-1776
Author(s):  
Karen Page ◽  
Luke J. Martinson ◽  
Daniel Fernandez-Garcia ◽  
Allison Hills ◽  
Kelly L. T. Gleason ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Breast Screening ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Healthy Controls ◽  
Breast Cancers ◽  
Poor Overall Survival ◽  
Tumor Dna

PURPOSE We investigated the utility of the Oncomine Breast cfDNA Assay for detecting circulating tumor DNA (ctDNA) in women from a breast screening population, including healthy women with no abnormality detected by mammogram, and women on follow-up through to advanced breast cancer. MATERIALS AND METHODS Blood samples were taken from 373 women (127 healthy controls recruited through breast screening, 28 ductal carcinoma in situ, 60 primary breast cancers, 47 primary breast cancer on follow-up, and 111 metastatic breast cancers [MBC]) to recover plasma and germline DNA for analysis with the Oncomine Breast cfDNA Assay on the Ion S5 platform. RESULTS One hundred sixteen of 373 plasma samples had one or more somatic variants detected across eight of the 10 genes and were called ctDNA-positive; MBC had the highest proportion of ctDNA-positive samples (61; 55%) and healthy controls the lowest (20; 15.7%). ESR1, TP53, and PIK3CA mutations account for 93% of all variants detected and predict poor overall survival in MBC (hazard ratio = 3.461; 95% CI, 1.866 to 6.42; P = .001). Patients with MBC had higher plasma cell-free DNA levels, higher variant allele frequencies, and more polyclonal variants, notably in ESR1 than in all other groups. Only 15 individuals had evidence of potential clonal hematopoiesis of indeterminate potential mutations. CONCLUSION We were able detect ctDNA across the breast cancer spectrum, notably in MBC where variants in ESR1, TP53, and PIK3CA predicted poor overall survival. The assay could be used to monitor emergence of resistance mutations such as in ESR1 that herald resistance to aromatase inhibitors to tailor adjuvant therapies. However, we suggest caution is needed when interpreting results from a single plasma sample as variants were also detected in a small proportion of HCs.

scholarly journals Genomic Instability of Circulating Tumor DNA as a Prognostic Marker for Pancreatic Cancer Survival: A Prospective Cohort Study

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5466
Author(s):  
Sang Myung Woo ◽  
Min Kyeong Kim ◽  
Boram Park ◽  
Eun-Hae Cho ◽  
Tae-Rim Lee ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Genomic Instability ◽  
Copy Number ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Free Survival ◽  
Genome Wide ◽  
Tumor Dna

Genomic instability of circulating tumor DNA (ctDNA) as a prognostic biomarker has not been evaluated in pancreatic cancer. We investigated the role of the genomic instability index of ctDNA in pancreatic ductal adenocarcinoma (PDAC). We prospectively enrolled 315 patients newly diagnosed with resectable (n = 110), locally advanced (n = 78), and metastatic (n = 127) PDAC from March 2015 through January 2020. Low-depth whole-genome cell-free DNA sequencing identified genome-wide copy number alterations using instability score (I-score) to reflect genome-wide instability. Plasma cell-free and matched tumor tissue DNA from 15 patients with resectable pancreatic cancer was sequenced to assess the concordance of chromosomal copy number alteration profiles. Associations of I-score with clinical factors or survival were assessed. Seventy-six patients had high genomic instability with I-score >7.3 in pre-treatment ctDNA; proportions of high I-score were 5.5%, 5.1%, and 52% in resectable, locally advanced, and metastatic stages, respectively. Correlation coefficients between Z-scores of plasma and tissue DNA at segment resolution were high (r2 = 0.82). Univariable analysis showed the association of I-score with progression-free survival in each stage. Multivariable analyses demonstrated that clinical stage-adjusted I-scores were significant factors for progression-free and overall survival. In these patients, ctDNA genomic I-scores provided prognostic information relevant to progression-free survival in each clinical stage.

scholarly journals The impact of LncRNA dysregulation on clinicopathology and survival of pancreatic cancer: a systematic review and meta-analysis (PRISMA compliant)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Elahe Seyed Hosseini ◽  
Ali Nikkhah ◽  
Amir Sotudeh ◽  
Marziyeh Alizadeh Zarei ◽  
Fatemeh Izadpanah ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Random Effects ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
Diagnosis And Prognosis ◽  
The Impact ◽  
Disease Free

Abstract Purpose An increasing number of studies have reported a significant association between long non-coding RNAs (lncRNAs) dysregulation and pancreatic cancers. In the present study, we aimed to gather articles to evaluate the prognostic value of long non coding RNA in pancreatic cancer. Experimental design We systematically searched all eligible articles from databases of PubMed, Web of Science, and Scopus to meta-analysis of published articles and screen association of multiple lncRNAs expression with clinicopathology and/or survival of pancreatic cancer. The pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were used to analysis of overall survival, disease-free survival and progression-free survival were measured with a fixed or random effects model. Results A total of 39 articles were included in the present meta-analysis. Our results showed that dysregulation of lncRNAs were linked to overall survival (39 studies, 4736 patients HR = 0.41, 95% CI 0.25 ± 0.58, random-effects in pancreatic cancer. Moreover, altered lncRNAs were also contributed to progression-free survival (8 studies, 1180 patients HR: 1.88, 95% CI (1.35–2.62) and disease-free survival (2 studies, 285 patients, HR: 6.07, 95% CI 1.28–28.78). In addition, our findings revealed the association between dysregulated RNAs and clinicopathological features in this type of cancer. Conclusions In conclusion, dysregulated lncRNAs could be served as promising biomarkers for diagnosis and prognosis of pancreatic cancer.

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