Future Perspectives in Detecting EGFR and ALK Gene Alterations in Liquid Biopsies of Patients with NSCLC

Non-small-cell lung cancer (NSCLC) is a major cause of death worldwide. Alterations in such genes as EGFR and ALK are considered important biomarkers in NSCLC due to the existence of targeted therapies with specific tyrosine kinase inhibitors (TKIs). However, specific resistance-related mutations can occur during TKI treatment, which often result in therapy inefficacy. Liquid biopsies arise as a reliable tool for the early detection of these types of alterations, allowing a non-invasive follow-up of the patients. Furthermore, they can be essential for cancer screening, initial diagnosis and to check surgery success. Despite the great advantages of liquid biopsies in NSCLC and the high input that next-generation sequencing (NGS) approaches can provide in this field, its use in oncology is still limited. With improvement of assay sensitivity and the establishment of clinical guidelines for liquid biopsy analysis, it is expected that they will be used in routine procedures. This review focuses on the usefulness of liquid biopsies of NSCLC patients as a means to detect alterations in EGFR and ALK genes and in disease management, highlighting the impact of NGS methods.

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Novel MRPS9-ALK Fusion Mutation in a Lung Adenocarcinoma Patient: A Case Report

Frontiers in Oncology ◽

10.3389/fonc.2021.670907 ◽

2021 ◽

Vol 11 ◽

Author(s):

Huamiao Zhou ◽

Binyue Xu ◽

Jili Xu ◽

Guomeng Zhu ◽

Yong Guo

Keyword(s):

Lung Adenocarcinoma ◽

Kinase Inhibitors ◽

Clinical Symptoms ◽

Progression Free Survival ◽

Anaplastic Lymphoma ◽

Lung Adenocarcinoma Patient ◽

Tki Treatment ◽

Nsclc Patients ◽

First And Second Generation

Anaplastic lymphoma kinase (ALK) rearrangements account for approximately 5–6% of non–small-cell lung cancer (NSCLC) patients. In this study, a case of lung adenocarcinoma harboring a novel MRPS9-ALK fusion is reported. The patient responded well to the first and second generation of ALK-tyrosine kinase inhibitors (ALK-TKIs) (crizotinib then alectinib), as her imaging findings and clinical symptoms significantly improved. At last follow-up, over 21 months of overall survival (OS) has been achieved since ALK-TKI treatment. The progression-free survival (PFS) is already ten months since alectinib. The adverse effects were manageable. The case presented here provides first clinical evidence of the efficacy of ALK-TKIs in NSCLC patients with MRPS9-ALK fusion.

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The impact of direct-acting antivirals on liver fibrosis in Egyptian hepatitis C virus patients: a single center experience

QJM ◽

10.1093/qjmed/hcab107.007 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Nadia Abdelaaty Abdelkader ◽

Amira Mahmoud AlBalakosy ◽

Ahmed Fouad Helmy Sherief ◽

Mohamed Soliman Gado

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Liver Fibrosis ◽

Transient Elastography ◽

Liver Stiffness ◽

Treatment Unit ◽

Non Invasive ◽

One Year ◽

The Impact

Abstract Background Hepatitis C virus (HCV) infection affects approximately 170 million people worldwide, causing liver cirrhosis and hepatocellular carcinoma (HCC) and leading to liver transplantation and ultimately death. Accurate evaluation of liver fibrosis in patients with chronic liver diseases is crucial, as liver fibrosis is important in order to make therapeutic decisions, determine prognosis of liver disease and to follow-up disease progression. Multiple non-invasive methods have been used successfully in the prediction of fibrosis; however, early changes in noninvasive biomarkers of hepatic fibrosis under effective antiviral therapy are widely unknown. The aim of this study is to evaluate changes of transient elastography values as well as FIB-4 and AST to platelet ratio index (APRI) in patients treated with DAAs. Objectives The aim beyond this study is to evaluate the changes in liver stiffness in hepatitis C Egyptian patients before and at least one year after treatment with DAAs using transient elastography and non-invasive liver fibrosis indices as FIB-4 and APRI scores. Patients and methods The present study was conducted on 100 patients with chronic hepatitis C patients attended to Ain Shams University Hospitals, Viral hepatitis treatment unit between October 2017 and December 2018, who were followed-up during treatment and after treatment for at least one year (retrospective and prospective study). Total number of cases during the study period was 117 patients. 17 patients were excluded from the study due to missed follow-up. Eventually, 100 patients were enrolled in the study fulfilling the inclusion criteria. Results The mean age of our patients is 47.9 years with Male predominance (52 males and 48 females). There was a significant improvement of, platelets counts, ALT and AST levels, which in turn cause significant improvement in FIB-4 and APRI scores. There was a significant improvement of liver stiffness after end of treatment, regardless of the DAA regimen used, as evidenced by Fibroscan. Conclusion Fibrosis regression –assessed by non-invasive markers of fibrosis is achievable upon removal of the causative agent.

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R-Score: A New Parameter to Assess the Quality of Variants’ Calls Assessed by NGS Using Liquid Biopsies

Biology ◽

10.3390/biology10100954 ◽

2021 ◽

Vol 10 (10) ◽

pp. 954

Author(s):

Roberto Serna-Blasco ◽

Estela Sánchez-Herrero ◽

María Berrocal Renedo ◽

Silvia Calabuig-Fariñas ◽

Miguel Ángel Molina-Vila ◽

...

Keyword(s):

Egfr Mutation ◽

False Negative ◽

Digital Pcr ◽

Liquid Biopsies ◽

Molecular Alterations ◽

Significant Linear Correlation ◽

Molecular Landscape ◽

Nsclc Patients ◽

Next Generation Sequencing Ngs

Next-generation sequencing (NGS) has enabled a deeper knowledge of the molecular landscape in non-small cell lung cancer (NSCLC), identifying a growing number of targetable molecular alterations in key genes. However, NGS profiling of liquid biopsies risk for false positive and false negative calls and parameters assessing the quality of NGS calls remains lacking. In this study, we have evaluated the positive percent agreement (PPA) between NGS and digital PCR calls when assessing EGFR mutation status using 85 plasma samples from 82 EGFR-positive NSCLC patients. According to our data, variant allele fraction (VAF) was significantly lower in discordant calls and the median of the absolute values of all pairwise differences (MAPD) was significantly higher in discordant calls (p < 0.001 in both cases). Based on these results, we propose a new parameter that integrates both variables, named R-score. Next, we sought to evaluate the PPA for EGFR mutation calls between two independent NGS platforms using a subset of 40 samples from the same cohort. Remarkably, there was a significant linear correlation between the PPA and the R-score (r = 0.97; p < 0.001). Specifically, the PPA of samples with an R-score ≤ −1.25 was 95.83%, whereas PPA falls to 81.63% in samples with R-score ≤ 0.25. In conclusion, R-score significantly correlates with PPA and can assist laboratory medicine specialists and data scientists to select reliable variants detected by NGS.

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Dynamic cfDNA Analysis by NGS in EGFR T790M-Positive Advanced NSCLC Patients Failed to the First-Generation EGFR-TKIs

Frontiers in Oncology ◽

10.3389/fonc.2021.643199 ◽

2021 ◽

Vol 11 ◽

Author(s):

Li Ma ◽

Haoyang Li ◽

Dongpo Wang ◽

Ying Hu ◽

Mengjun Yu ◽

...

Keyword(s):

First Generation ◽

Univariate Analysis ◽

Third Generation ◽

T790m Mutation ◽

The Third ◽

Tki Treatment ◽

Nsclc Patients ◽

Next Generation Sequencing Ngs ◽

Egfr Tkis

PurposeCirculating cell-free DNA (cfDNA) level has been demonstrated to be associated with efficacy in first generation EGFR TKIs in non-small cell lung cancer (NSCLC). However, the role of dynamic cfDNA analysis using next-generation sequencing (NGS) in patients with subsequent third-generation EGFR TKIs remains unclear.MethodsFrom 2016 to 2019, 81 NSCLC patients with EGFR T790M mutation either in tissue or plasma who received third-generation EGFR TKIs treatment were enrolled. CfDNA were sequenced by NGS with a 425-gene panel. The association of clinical characteristics, pretreatment, dynamic cfDNA and T790M level with outcomes in patients treated with the third-generation TKIs were analyzed.ResultsIn univariate analysis, the median PFS of patients with undetectable cfDNA level during treatment was significantly longer than those with detectable cfDNA (16.97 vs. 6.10 months; HR 0.2109; P < 0.0001). The median PFS of patients with undetectable T790M level during treatment was significantly longer than those with detectable T790M (14.1 vs. 4.4 months; HR 0.2192; P < 0.001). Cox hazard proportion model showed that cfDNA clearance was an independent predictor for longer PFS (HR 0.3085; P < 0.001) and longer OS (HR 0.499; P = 0.034). The most common resistant mutations of the third-generation TKIs were EGFR C797S (24%). CDK6 CNV, GRIN2A, BRCA2, EGFR D761N, EGFR Q791H, EGFR V843I, and ERBB4 mutation genes may possibly be new resistant mechanisms.ConclusionsPatients with undetectable cfDNA during the third-generation EGFR TKI treatment have superior clinical outcomes, and dynamic cfDNA analysis by NGS is valuable to explore potential resistant mechanisms.

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Pro-Inflammatory and Pro-Oxidative Changes during Nilotinib Treatment in CML Patients: Results of a Prospective Multicenter Front-Line TKIs Study (KIARO Study)

Blood ◽

10.1182/blood-2021-152530 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1479-1479

Author(s):

Anna Sicuranza ◽

Ilaria Ferrigno ◽

Elisabetta Abruzzese ◽

Alessandra Iurlo ◽

Sara Galimberti ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Kinase Inhibitors ◽

Active Role ◽

Inflammatory Status ◽

Increased Risk ◽

Formal Statistical Analysis ◽

Anti Inflammatory ◽

Hs Crp ◽

Tki Treatment

Abstract Background: Tyrosine kinase inhibitors (TKI) may offer a normal life expectancy to Chronic Myeloid Leukemia (CML) patients. However, during treatment with nilotinib, a higher than expected incidence of arterial occlusive events (AOEs) was observed. We retrospectively showed an "inflammatory status" during nilotinib treatment that may explain this increased incidence of AOEs. Here, we report results of a prospective multicenter (KIARO) study including 186 CML patients (89 imatinib, 59 nilotinib, 38 dasatinib) in which pro/anti-inflammatory cytokines were measured at diagnosis and during treatment, with the aim to investigate potential changes in each patient's inflammatory status possibly favoring AOEs. Aims: The aims of this study are: 1) to analyze prospectively inflammation status during TKI treatment; 2) to record AOEs; 3) to calculate the SCORE and evaluate its predictive role for AOEs; 4) to analyze possible associations of AOEs with altered inflammation status. Methods: Inflammatory status was evaluated by measuring IL6, IL10, TNFα, oxLDL and hs-CRP plasma levels at diagnosis and during treatment (+1, +3, +6, +12 months); additionally, clinical and biochemical pro-atherothrombotic profiles and the 10-year SCORE chart were also evaluated. Results: 186 newly-diagnosed CML patients starting either imatinib, nilotinib or dasatinib treatment, entered this study. Regarding the inflammation status, we observed that TNFα and IL6 levels were high at diagnosis and decreased during the first 12 months of treatment regardless the type of TKI; instead, IL10 levels were comparable among the 3 TKI cohorts at baseline, but showed a remarkably different evolution during treatment. In fact, IL10 levels were significantly higher after 6 and 12 months of imatinib (p=0.012 and p=0.009, respectively) and dasatinib (p=0.032 and p=0.014, respectively) compared to nilotinib. Consequently, TNFα/IL10 ratio was significantly higher in nilotinib cohort at 6 and 12 months respect to imatinib (p=0.044 at 6 months and p=0.041 at 12 months) and dasatinib (p=0.040 at 6 months and p=0.044 at 12 months). As well, IL6/IL10 ratio was significantly higher in nilotinib cohort compared to imatinib and dasatinib both at 6 (p=0.042 and p=0.049, respectively) and 12 months (p=0.040 and p=0.041, respectively) (Figure 1). OxLDL levels were similar in the 3 groups for the first 6 months. At 12 months we detected a significant increase of oxLDL levels in the nilotinib cohort (p=0.041), respect to imatinib and dasatinib. We did not find significant differences in hs-CRP levels across the 3 TKIs, although a trend for higher levels was observed in nilotinib cohort. Overall, these results suggest a TKI-driven pro-inflammatory status in nilotinib treated patients. After a median follow-up of 23.3 months of TKI treatment, 10 patients (5.4%) suffered an AOE, specifically: 6 ACS, 2 PAOD, 1 TIA and 1 stroke. 5 events (50%) occurred in patients treated with nilotinib, either in first line (4 patients) or in third line (1 patient, after failure following brief treatment with imatinib and dasatinib). In this subgroup of 10 patients experiencing an AOE, we observed a trend of increased IL6 and TNFα median values both at diagnosis and at each time point, compared with the remaining no-AOE patients. IL10 and oxLDL had similar median concentrations in both AOE and no-AOE cohorts, except for oxLDL at 12 months which resulted higher in patients who experienced AOEs. Moreover, regarding AOEs, nilotinib treatment showed a 3.1 times increased risk compared to other TKIs (HR 3.1, 95% CI 2.6-4.4 p< 0.001), whereas 10-year SCORE was not predictive in the whole cohort (HR 0.6, 95% CI 0.33-0.94 p= 0.094) or in any subgroup (imatinib HR 0.8, 95% CI 0.49-1.03 p= 0.067; nilotinib HR 0.4, 95% CI 0.29-0.76 p= 0.112, dasatinib HR 0.6, 95% CI 0.37-0.92 p= 0.082). Conclusions: Our results showed a pro-inflammatory/oxidative milieu increasing along treatment with nilotinib compared with imatinib or dasatinib, as demonstrated by higher IL6/IL10 and TNFα/IL10 ratios, higher levels of oxLDL and a trend for higher hs-CRP only in nilotinib cohort. However, due to the low number of observed events, a formal statistical analysis for any association between AOEs and pro/anti-inflammatory cytokines levels was not possible. Therefore, a longer follow-up is needed to further confirm the active role of nilotinib in AOEs pathogenesis. Figure 1 Figure 1. Disclosures Abruzzese: Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Galimberti: Incyte: Speakers Bureau; AbbVie, Janssen: Honoraria, Other: Travel grants. Stagno: Pfizer: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; InCyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Support for attending meetings and/or travel, Research Funding.

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Cost-effectiveness analysis of icotinib versus whole-brain irradiation with or without chemotherapy in EGFR-mutant NSCLC patients with brain metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e20556 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e20556-e20556

Author(s):

Wenqian Li ◽

Rilan Bai ◽

Lei Qian ◽

Naifei Chen ◽

Yuguang Zhao ◽

...

Keyword(s):

Cost Effectiveness ◽

Brain Metastases ◽

Kinase Inhibitors ◽

Growth Factor Receptor ◽

Cost Effective ◽

Sensitivity Analyses ◽

Net Benefit ◽

Whole Brain Irradiation ◽

Nsclc Patients ◽

The Impact

e20556 Background: Non-small-cell lung cancer (NSCLC) patients with brain metastases had a poor prognosis. Despite the traditional methods including radiotherapy and chemotherapy, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) might benefit patients on survival and quality of life. We investigated the cost-effectiveness of icotinib compared with WBI with or without chemotherapy for NSCLC patients with brain metastases. Methods: A markov model was conducted based on the data of BRAIN trial. We compared the economic benefit between icotinib and the combination of WBI and WBI plus chemotherapy group. We considered disease progression as intracranial progression and overall progression separately. Sensitivity analyses were performed to observe the stability of the model. The willingness-to-pay (WTP) was set as 3× per capita gross domestic product ($25929/quality-adjusted life year [QALY]). Results: When considering progression as intracranial progression and overall progression respectively, the incremental cost-effectiveness ratio (ICER) was $930.17/QALY and $842.76/QALY between icotinib and WBI/WBI-chemotherapy. Besides, both of the average cost-effective ratio (average CE) and net benefit showed advantage of icotinib (average CE: $2157.59/QALY for intracranial progression, $2285.16/QALY for overall progression; net benefit: $372153.35 for intracranial progression, $349938.32 for overall progression). One-way sensitivity analyses demonstrated the impact of the utilities of icotinib group. The probabilistic sensitivity analyses showed even at a WTP under $6000/QALY, icotinib could be cost-effective. Conclusions: Icotinib was cost-effective compared with WBI with or without chemotherapy. [Table: see text]

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Detection of any-stage cancer using plasma and urine glycosaminoglycans.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3034 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 3034-3034

Author(s):

Francesco Gatto ◽

Sinisa Bratulic ◽

Ilaria Teresa Rita Cavarretta ◽

Massimo Alfano ◽

Francesca Maccari ◽

...

Keyword(s):

Brain Tumors ◽

Cox Regression ◽

Early Stage ◽

Healthy Adults ◽

Low Grade ◽

Cancer Type ◽

Liquid Biopsies ◽

Non Invasive ◽

Validation Set

3034 Background: Non-invasive liquid biopsies promise to enable early cancer detection and improve patient outcomes. However, virtually all liquid biopsies rely on genomic biomarkers, with limited sensitivity to early-stage tumors and poor detection of cancers shedding little cell-free DNA, like genitourinary or brain tumors. Here, we explored the use of plasma and urine glycosaminoglycan (GAGs) profiles, or GAGomes, as biomarkers reflective of tumor metabolism to serve as an alternative pan-cancer liquid biopsy. Methods: In this case-control study, we enrolled retrospective and prospective cohorts from Sweden and Italy. Included cases were treatment-naïve early-stage/low-grade cancers or metastatic/high-grade cancers across 14 histological types. Included controls were healthy 22-78 y/o adults with no history of cancer. We measured GAGomes – encompassing 17 chondroitin sulfate (CS), heparan sulfate (HS), and hyaluronate (HA) disaccharides - using a standardized UHPLC-MS/MS-based kit in a central blind laboratory. We tested the top GAGome features different in cancer using Bayesian estimation. These were used to design one plasma and one urine GAG score for the binary classification of cancer vs. control in a discovery set. We computed the area-under-the-curve (AUC), and sensitivity at 98% specificity of each GAG score in the validation set. A subset analysis was performed in early-stage/low-grade cancers only. In the subset of cases with survival records, we used multivariable Cox regression to estimate the hazard ratio (HR) for overall survival (OS) on each GAG score adjusted for cancer type, age, and gender. Results: GAGomes were measured in 753 plasma samples (460 cancers across 14 types, median age = 66 y/o, 51% female vs. 293 healthy adults, median age = 58 y/o, 57% female) and 559 urine samples (219 cancers across 5 types, median age = 69 y/o, 23% female vs. 340 healthy adults, median age = 56 y/o, 60% female). In the discovery set, the urine GAG score had an AUC = 0.80 (95% CI: 0.74-0.85, 124 cancers across 5 types vs. 184 controls) while the plasma GAG score had an AUC = 0.82 (95% CI: 0.78-0.86, 153 cancers across 14 types vs. 282 controls). In the validation set, the urine GAG score had an AUC = 0.78 (95% CI: 0.71-0.84, 95 cancers across 5 types vs. 156 controls) with 35% sensitivity at 98% specificity. The plasma GAG score had an AUC = 0.84 (95% CI: 0.79-0.88, 178 cancers across 14 types vs. 140 controls) with 41% sensitivity at 98% specificity. In the subset of early-stage/low-grade cancers, the AUC was 0.78 and 0.72 in plasma and urine, respectively. The plasma and urine GAG scores were independent predictors of OS regardless of cancer type (HR = 1.39, p = 0.005 in plasma [ N = 283, 11 types, 67 deaths, median follow-up 17 months] and HR = 1.53, p = 0.016 in urine [ N = 161, 4 types, 32 deaths, median follow-up 15 months]). Conclusions: GAGomes were sensitive non-invasive metabolic biomarkers for any-stage cancer, including genitourinary and brain tumors.

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Molecular characteristics of EGFR exon 19 deletion subtypes in NSCLC patients.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8530 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8530-8530

Author(s):

Weiquan Gu ◽

Zhongyu Lu ◽

Shulin Shi ◽

Juan Ma ◽

Guanghua Lu ◽

...

Keyword(s):

Kinase Inhibitors ◽

Egfr Mutations ◽

Molecular Characteristics ◽

Three Samples ◽

Egfr Tyrosine Kinase Inhibitors ◽

Exon 19 Deletion ◽

Clinical Responses ◽

Tki Treatment ◽

Nsclc Patients ◽

Exon 19

8530 Background: EGFR exon 19 deletion mutations are well characterized, known to be activating, and are associated with responses to EGFR tyrosine kinase inhibitors (TKIs). A variety of methods have been developed to identify EGFR mutations. Deletions of EGFR exon 19 are more complex compare to the other because they consist of different subtypes. Methods: In this study, we retrospectively analyzed the different subtypes of EGFR exon 19 deletions using next-generation sequencing(NGS). From May 2019 to December 2020, 3275 patients who were diagnosed with Non-small cell lung cancer (NSCLC)were detected. Results: In this analyzed cohort, the average age of patients was 62 years (range, 24-92 years). Most of the patients were female (61.07%) and were diagnosed with lung adenocarcinoma (82.60%). It is worth noting that the deletions in exon 19 of EGFR were also detected in 35 patients (1.07%) with squamous cell carcinoma and 1 patient (0.03%) with sarcomatoid. The most frequent EGFR exon 19 deletions were delE746-A750 (63.4%), followed by delL747-P753insS (9.7%) and L747-T751 (6.9%). The characteristics of the patients in this study are presented. Significantly, three samples with compound EGFR exon 19 deletions were detected: 1) S1:E746_A750delinsFP+E746_A750del; 2) S2: E746_S752delinsV+L747_P753delinsS; 3) S3:E746_P753delinsVS + L747_P753delinsS. Conclusions: EGFR exon 19 starting at codon 729 to 761, our data showed the deletions occur throughout almost the entire exon 19 amino acid. As our integrated data results, EGFR exon 19 has many different deletions and insertion subtypes could be defined as 79 subtypes. Among those subtypes,70 were complex with an accompanying insertion. The most frequent deletions were starting at E746 and L747. Based on several clinical researches, different deletion subtypes may have significantly different clinical responses after TKI treatment. However, more clinical research is needed to support this finding.

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The impact of prostate artery embolization (PAE) on the the physical history and pathophysiology of benign prostatic hyperplasia (BPH)

Archivio Italiano di Urologia e Andrologia ◽

10.4081/aiua.2018.1.40 ◽

2018 ◽

Vol 90 (1) ◽

pp. 40

Author(s):

Konstantinos Stamatiou

Keyword(s):

Outcome Measures ◽

Clinical Success ◽

Artery Embolization ◽

Prostate Artery Embolization ◽

Non Invasive ◽

Benign Prostate Hypertrophy ◽

Urinary Tract Symptoms ◽

The Impact ◽

Benign Prostate

Aim: Prostate artery embolization (PAE) is a non invasive modality for the treatment of benign prostate hypertrophy (BPH) related lower urinary tract symptoms (LUTS). As a relatively new procedure, data determining the clinical success is somehow scarce. In the present article we examine the current clinical outcome measures in order to identify the most accurate. Results: Current imaging outcome measures are consistent with clinical ones only in the group of patients with adenomatous- dominant BPH while are inconsistent in patients with small sized adenomas. Conclusions: Additional studies and/or evaluation tools are needed in order to provide accurate evaluation of clinical success in the subgroup of patients with non- adenomatous-dominant BPH while they may inspire new options and novel techniques for both BPH treatment and treatment-follow up.

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DNA methylation markers detected in blood, stool, urine, and tissue in colorectal cancer: a systematic review of paired samples

International Journal of Colorectal Disease ◽

10.1007/s00384-020-03757-x ◽

2020 ◽

Cited By ~ 1

Author(s):

Eivor Alette Laugsand ◽

Siv Sellæg Brenne ◽

Frank Skorpen

Keyword(s):

Colorectal Cancer ◽

Dna Methylation ◽

Data Extraction ◽

Meta Analysis ◽

Methylation Status ◽

High Sensitivity ◽

Liquid Biopsies ◽

Non Invasive ◽

Paired Samples

Abstract Purpose Methylated cell-free DNA in liquid biopsies are promising non-invasive biomarkers for colorectal cancer (CRC). Optimal markers would have high sensitivity and specificity for early detection of CRC and could be detected in more than one type of material from the patient. We systematically reviewed the literature on DNA methylation markers of colorectal cancer, detected in more than one type of material, regarding their potential as contributors to a panel for screening and follow-up of CRC. Methods The databases MEDLINE, Web of Science, and Embase were systematically searched. Data extraction and review was performed by two authors independently. Agreement between methylation status in tissue and other materials (blood/stool/urine) was analyzed using the McNemar test and Cohen’s kappa. Results From the 51 included studies, we identified seven single markers with sensitivity ≥ 75% and specificity ≥ 90% for CRC. We also identified one promising plasma panel and two stool panels. The correspondence of methylation status was evaluated as very good for four markers, but only marginal for most of the other markers investigated (12 of 21). Conclusion The included studies reported only some of the variables and markers of interest and included few patients. Hence, a meta-analysis was not possible at this point. Larger, prospective studies must be designed to study the discordant detection of markers in tissue and liquid biopsies. When reporting their findings, such studies should use a standardized format.

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