scholarly journals Updates on Clinical Use of Liquid Biopsy in Colorectal Cancer Screening, Diagnosis, Follow-Up, and Treatment Guidance

2021 ◽  
Vol 9 ◽  
Author(s):  
Omayma Mazouji ◽  
Abdelhak Ouhajjou ◽  
Roberto Incitti ◽  
Hicham Mansour
Keyword(s):  
Colorectal Cancer ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Early Stage ◽  
Treatment Decision ◽  
Short Review ◽  
Genetic Components ◽  
Monitor Treatment Response ◽  
Gene Alterations

Colorectal cancer (CRC) is one of the most common cancers worldwide, being the third most diagnosed in the world and the second deadliest. Solid biopsy provides an essential guide for the clinical management of patients with colorectal cancer; however, this method presents several limitations, in particular invasiveness, and cannot be used repeatedly. Recently, clinical research directed toward the use of liquid biopsy, as an alternative tool to solid biopsy, showed significant promise in several CRC clinical applications, as (1) detect CRC patients at early stage, (2) make treatment decision, (3) monitor treatment response, (4) predict relapses and metastases, (5) unravel tumor heterogeneity, and (6) detect minimal residual disease. The purpose of this short review is to describe the concept, the characteristics, the genetic components, and the technologies used in liquid biopsy in the context of the management of colorectal cancer, and finally we reviewed gene alterations, recently described in the literature, as promising potential biomarkers that may be specifically used in liquid biopsy tests.

Impact of colonoscopy screening on individuals at high risk of hereditary nonpolyposis colorectal cancer (HNPCC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 384-384
Author(s):  
C. Guillen-Ponce ◽  
C. Martinez-Sevila ◽  
R. Jover ◽  
R. Perea ◽  
M. Molina-Garrido ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Early Stage ◽  
Colorectal Adenomas ◽  
Medical Documentation ◽  
Synchronous Tumors ◽  
Colonoscopy Screening ◽  
Amsterdam Criteria ◽  
The Impact

384 Background: Colonoscopy screening reduces the incidence of, and mortality from, colorectal cancer (CRC) in individuals with HNPCC. The aim of this study was to determine the impact of colonoscopic follow-up in individuals at high risk of HNPCC, in terms of detection of precursor lesions (adenomas) or cancer. Methods: Between 2005-2008, 163 individuals with HNPCC were advised to undergo regular follow-up colonoscopy. Compliance and results of the scans were evaluated annually and were verified with medical documentation. Results: Of the 125 individuals who underwent at least one colonoscopy during the follow-up period of colonoscopy screening, in 33 subjects (26%) at least one colonic adenoma was detected. The median number of adenomas detected per colonoscopy in individuals with polyps was 2. The number of colonoscopies with polyps did not differ between women and men. However, the number of polyps removed by colonoscopy and the total number of polyps removed during the follow-up period was significantly higher in men (p = 0.005, p = 0.05 bilateral, respectively). 5 individuals (4%) were diagnosed with CRC, one of whom had two synchronous tumors. Of these, four individuals had properly followed the screening recommendations with the recommended frequency. In the case where two synchronous tumors were detected, it was the first colonoscopy screening that had been performed on the individual. None had had cancer previously, they were healthy relatives of an index case. All except one belonged to families that fulfilled the Amsterdam criteria I / II. All the tumors were diagnosed at an early stage, except two, which exhibited positive nodes. Conclusions: Colonoscopy screening is effective in diagnosing colorectal adenomas and cancer in individuals with HNPCC. Men with HNPCC have a greater number of colorectal adenomas. Screening allows the detection of colorectal cancer at an early stages. Funded by a young researcher's grant from the Spanish Society of Medical Oncology 2006. No significant financial relationships to disclose.

Tumor-informed assessment of molecular residual disease and its incorporation into practice for patients with early and advanced-stage colorectal cancer (CRC-MRD Consortia).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4108-4108 ◽  
Author(s):  
Pashtoon Murtaza Kasi ◽  
Farshid Dayyani ◽  
Van K. Morris ◽  
Scott Kopetz ◽  
Aparna Raj Parikh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Disease ◽  
Residual Disease ◽  
Early Stage ◽  
Circulating Tumor Dna ◽  
Response To Treatment ◽  
Chi Square ◽  
Multiplex Pcr Assay ◽  
Crc Management ◽  
First Time

4108 Background: Circulating tumor DNA (ctDNA) testing can be used for the assessment of molecular residual disease (MRD) in patients with early-stage or advanced colorectal cancer (CRC). Prospective evaluation of this methodology in clinical practice has been limited to-date. Methods: A personalized and tumor-informed multiplex PCR assay (Signatera 16-plex bespoke mPCR NGS assay) was used for the detection and quantification of ctDNA for MRD assessment. We analyze and present results from an ongoing early adopter program of ctDNA testing across the spectrum of CRC management. Results: Here we present a total of 250 patients with colon (n=200), rectal (n=40), and other lower gastrointestinal cancers (n =10; anal, appendiceal, small bowel). MRD positivity rates and ctDNA quantification (mean tumor molecules/mL) are shown in Table. ctDNA detection was significantly associated with stage of disease (p<0.0001 Chi-square: 70.33). Additionally, in patients with radiologically measurable active metastatic disease, ctDNA detection rate was 100%. On the contrary, patients with advanced/metastatic disease who had partial response to treatment or no evidence of disease (NED) showed 28.5% and 19.2% of ctDNA-positivity, respectively. Conclusions: This is the first large, real-world study reporting on the results from a clinically validated MRD assay. For the first time we delineate MRD rates and quantify ctDNA concentration in patients with early-stage and advanced CRC. Furthermore, we provide an initial readout that effective ongoing treatment in patients with CRC may be correlated with ctDNA clearance. Ongoing analysis expanded to a cohort of 1200 clinical cases including correlation with genomic and serial testing will be presented. [Table: see text]

scholarly journals 91P Liquid biopsy for detection of minimal residual disease after liver metastasectomy in stage IV colorectal cancer

2021 ◽  
Vol 32 ◽  
pp. S395-S396
Author(s):  
M.A. Gouda ◽  
M.J. Overman ◽  
H.J. Huang ◽  
J. Thomas ◽  
N.A. Dasari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Minimal Residual Disease ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Stage Iv ◽  
Stage Iv Colorectal Cancer ◽  
Minimal Residual

scholarly journals Liquid Biopsy in Early Breast Cancer: A Preliminary Report

2020 ◽  
pp. 1-8
Author(s):  
Antonio Rulli ◽  
Antognelli Cinzia ◽  
Antonio Rulli ◽  
Covarelli Piero ◽  
Izzo Luciano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Early Stage ◽  
Dynamic Monitoring ◽  
Molecular Profile ◽  
Precision Oncology ◽  
Surgical Biopsy ◽  
Post Surgery ◽  
Genetic Landscape

Background: Liquid biopsy (LB) is a technique that utilizes circulating biomarkers from cancer patients to provide information regarding the genetic landscape of the cancer. LB is emerging as an alternative and complementary diagnostic and prognostic tool to surgical biopsy and is expected to provide the tool for the implementation of precision oncology in clinical settings. In fact, it may contribute to enhance understanding of tumor heterogeneity and permitting the dynamic monitoring of treatment responses and genomic variations. Thus, LB is a promising method for the management of cancer, including breast cancer (BC), whose incidence in Italy is progressively increasing. Previous studies focused mainly on patients with advanced-stage BC. In the present study we evaluated the number of circulating tumor cells (CTCs), the quantity of cell free tumor DNA (cftDNA) and the analysis of the mutational profile of DNA from CTCs (ctcDNA) and cftDNA in early stage BC patients. Methods: Matched pre- and post-surgery blood samples were collected from 47 early stage BC patients. CTCs enumeration was done using Isoflux system, molecular profile of ctcDNA and cftDNA was performed with the Spotlight 59 Panels kit on a MiSeq Illumina instrument. Results: Eighty percent of samples was CTCs-positive, while healthy controls were all CTCs-negative. Forty-four patients provided a pre-surgery and 21 post-surgery sample. By comparing the number of CTCs post-surgery with that of pre-surgery, we found that 66% of patients showed a decreased number of CTCs, 14% of patients continued to have the same number of CTCs, while, interestingly, 19% of patients showed an increased number of CTCs. Next Generation Sequencing (NGS) of ctcDNA and cftDNA showed that 52% of samples had mutations in 9 genes (TP53, CDKN2A, FBXW7, PTPN11, KRAS, NRAS, BRAF, IDH1, ALK) and in 5 genes (PIK3CA, APC ALK, KRAS, TSC1), respectively, with KRAS and ALK overlapping and TP53 being the most frequently mutated gene in ctcDNA analysis. Conclusions: LB could facilitate early detection of minimal residual disease, aiding in the initiation of adjuvant therapy to prevent recurrence and progression towards metastasis, enhance individualized treatment and longitudinal screening, thus improving the clinical management and outcome of patients with early BC.

scholarly journals Exosomal Non Coding RNA in LIQUID Biopsies as a Promising Biomarker for Colorectal Cancer

2020 ◽  
Vol 21 (4) ◽  
pp. 1398 ◽  
Author(s):  
Amro Baassiri ◽  
Farah Nassar ◽  
Deborah Mukherji ◽  
Ali Shamseddine ◽  
Rihab Nasr ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Sensitivity And Specificity ◽  
Liquid Biopsy ◽  
Early Stage ◽  
Noncoding Rnas ◽  
Predictive Biomarkers ◽  
Carbohydrate Antigen ◽  
Combination Regimen ◽  
Liquid Biopsies ◽  
Diagnostic Potential

Colorectal cancer (CRC) is one of the most common cancers worldwide, with a high mortality rate, especially in those that are diagnosed in late stages of the disease. The current screening blood-based markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), have low sensitivity and specificity. Meanwhile, other modalities are either expensive or invasive. Therefore, recent research has shifted towards a minimally invasive test, namely, liquid biopsy. Exosomes are favorable molecules sought in blood samples, since they are abundant, stable in circulation, and harbor genetic information and other biomolecules that could serve as biomarkers or even therapeutic targets. Furthermore, exosomal noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, have demonstrated the diagnostic potential to detect CRC at an early stage with a higher sensitivity and specificity than CEA and CA19-9 alone. Moreover, they have prognostic potential that is TNM stage specific and could serve as predictive biomarkers for the most common chemotherapeutic drug and combination regimen in CRC, which are 5-FU and FOLFOX, respectively. Therefore, in this review, we focus on the role of these exosomal noncoding RNAs as diagnostic, prognostic, and predictive biomarkers. In addition, we discuss the advantages and challenges of exosomes as a liquid biopsy target.

Circulating Tumor DNA as a Biomarker for Outcomes Prediction in Colorectal Cancer Patients

2020 ◽  
Vol 21 ◽  
Author(s):  
Angelica Petrillo ◽  
Massimiliano Salati ◽  
Dario Trapani ◽  
Michele Ghidini
Keyword(s):  
Colorectal Cancer ◽  
Residual Disease ◽  
Early Stage ◽  
Recurrence Risk ◽  
Early Response ◽  
Circulating Tumor Dna ◽  
Response To Treatment ◽  
Molecular Profile ◽  
Liquid Biopsies ◽  
Tissue Biopsy

Abstract:: Circulating tumour DNA (ctDNA) is a novel tool that has being investigated in several types of tumours, includ-ing colorectal cancer (CRC). In fact, the techniques based on liquid biopsies are proposed as appealing non-invasive alter-natives to tissue biopsy, adding more insights into tumour molecular profile, heterogeneity and for cancer detection and monitoring. Additionally, some analysis showed that in CRC patients ctDNA seems to act as biomarker able to predict the outcome (prognostic role) and the response to treatments (predictive role). In particular, in the early stage CRC (stage I-III) it could represent a time marker of adjuvant therapy benefit as well as a marker of minimal residual disease and recurrence risk in addition to the already recognized risk factors. In metastatic CRC, the analysis of molecular tumour profile by ctDNA has shown to have high concordance with the tissue biopsy at diagnosis. Additionally, some studies demonstrated that ctDNA level during the treatment was linked with early response to treatment and prognosis. Finally, the quantitative anal-ysis of ctDNA and copy number alterations may be useful in order to detect resistance to therapy at the time of progression of disease and to help in finding new therapeutic targets.

Impact of a novel decision counseling program on treatment knowledge, decisional conflict, and choice in men with early-stage, low-risk prostate cancer.

2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 9-9
Author(s):  
Jean H. Hoffman-Censits ◽  
Anett Petrich ◽  
Anna Quinn ◽  
Amy Leader ◽  
Leonard G. Gomella ◽  
...  
Keyword(s):  
Decision Making ◽  
Early Stage ◽  
Treatment Decision ◽  
Decisional Conflict ◽  
Counseling Program ◽  
Treatment Decision Making ◽  
Treatment Knowledge ◽  
Risk Prostate Cancer ◽  
Low Risk Prostate Cancer

9 Background: Active surveillance (AS - serial follow-up PSA, exam, and biopsy) is an option for men with early stage, low risk prostate cancer (LRPca). While data show comparable survival for AS vs active treatment (AT - surgery or radiation), currently most men with LRPca undergo AT. A pilot Decision Counseling Program (DCP) to assist men in making an informed, shared LRPca treatment decision was implemented. Methods: Men with LRPca seen at the Jefferson Genitourinary Multidisciplinary Cancer Center (JGUMDCC) were consented. A nurse educator (NE) reviewed risks/benefits of AS and AT; had the participant identify factors influencing treatment decision making and specify decision factor weights; entered data into an online DCP; and generated a report of participant treatment preference and decision factors. The report was used by the participant and clinicians in shared treatment decision making. A follow-up survey was administered 30 days after the visit, with treatment status assessed. Change in treatment-related knowledge and decisional conflict were measured using baseline and 30-day survey data. Results: Baseline decision counseling preference of 16 participants: 4 - AS, 8 equal for AS and AT, 4 - AT. At 30 days, 12 participants initiated AS, 4 chose AT; participant mean treatment knowledge scores (8-point scale) increased (+1.13 points); decisional conflict subscale scores (strongly disagree = 1, strongly agree = 5) decreased (uncertain: -1.15, uninformed: -1.36, unclear: -1.12; and unsupported: -1.15). Conclusions: Decision counseling and shared decision making helped participants become better informed about treatment choices and reduced uncertainty in treatment decision making. The combined intervention resulted in most participants choosing AS. Ongoing study recruitment, data collection, and analyses are planned.

Use of circulating tumor DNA in colorectal cancer patients to assess tumor burden and response to therapy: An observational study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3528-3528
Author(s):  
Erin L. Symonds ◽  
Susanne Kartin Pedersen ◽  
Bernita Hui Li Yeo ◽  
Hiba Al Naji ◽  
Susan E. Byrne ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Size ◽  
Residual Disease ◽  
Early Stage ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Post Treatment ◽  
Response To Therapy ◽  
Maximum Diameter ◽  
Curative Intent

3528 Background: Residual disease after treatment for colorectal cancer (CRC) poses a risk for recurrence but imaging and CEA are limited in their capacity to detect residual disease. A simple test is needed for assessing treatment response. This study determined whether levels of methylated BCAT1/IKZF1 DNA in blood correlate with tumor burden and whether post-treatment levels inform efficacy of different treatments for CRC. Methods: Patients with primary CRC had blood collected prior to treatment (n = 282, 59.9% males, median age 68.5y). Cell free DNA (cfDNA) was extracted from plasma and assayed for methylation in BCAT1 and IKZF1. Detection of methylation in either gene deemed a sample positive; levels were expressed as %methylation (average methylation/average cfDNA). Positive patients had additional samples collected post-treatment for early stage CRC (surgery, n = 31), advanced/metastatic CRC (surgery + adjuvant chemotherapy, n = 15), and rectal cancer (neoadjuvant therapy, surgery +/- chemotherapy, n = 6), or following mid-therapy suspension of treatment in advanced CRC (n = 24). Tumor size was expressed as the maximum diameter of the primary (assessed surgically or by MRI). Results: Pretreatment results increased with CRC stage. Positivity by stage was: I, 23.7% (14/59); II, 62.1% (54/87); III, 68.6% (70/102); IV, 85.3% (29/34). Level by stage: I, 0.0%; II, 0.06%; III, 0.07%; IV, 4.07%, p < 0.001). Pretreatment levels correlated significantly with tumor size (r = 0.372, p < 0.001). Post-treatment blood was collected a median 2.4mo (IQR 1.7-3.9) after therapy completion. Positivity decreased after completing treatment (Table), with 88.4% of cases (46/52) becoming ctDNA negative. All cases with complete treatment had a reduction in biomarker levels, whereas in those with incomplete therapy, 54.5% (12/22) remained positive and the pre- and post-treatment levels were not significantly different. Of those positive after treatment, 13 had a further blood sample: 8 had become ctDNA negative and all but one remained disease free. Five remained positive and all had further suspected or confirmed disease. Conclusions: Levels of methylated BCAT1 and IKZF1 DNA in blood correlated with tumor burden; levels became undetectable in the majority of patients following completion of planned curative intent treatment. The methylated ctDNA blood test aids monitoring of responses to therapy and identification of those cases with residual cancer who might benefit from ongoing therapy.[Table: see text]

Clinical, pathologic, and demographic characteristics of colorectal cancer in patients under age 50 in a third level Mexican cancer center.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15592-e15592
Author(s):  
Omar Serrano Villamayor ◽  
Benigno Rodriguez ◽  
Diana Alejandra Villegas Osorno ◽  
Geovani Amador ◽  
Raul Alejandro Andrade Moreno ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Early Stage ◽  
Medical Center ◽  
Target Therapy ◽  
Age At Diagnosis ◽  
Cancer Center ◽  
First Line ◽  
Kras Mutations

e15592 Background: Colorectal cancer (CRC) is the most common gastrointestinal neoplasia, with 1.36 million cases worldwide, representing the third cause of death due to cancer. Commonly affects people after the 6th decade of life, but recently the diagnosis in patients below 50 years is increasing. Methods: We conducted an observational, retrospective, longitudinal analysis based on medical records of patients diagnosed with colorectal cancer treated in the ABC Medical Center. Information was collected between January 2016 and January 2021. Descriptive statistics were utilized regarding data analysis. Results: We identified 289 patients with CRC, of which 23 (8.2%) patients were less than 50 years of age at diagnosis. Gender distribution reflected slightly more feminine patients (56%). The median age at diagnosis was 43 years, oncologic family history in first- or second-degree family members was documented in 31.4% of patients. At diagnosis, 22% of patients presented with an early-stage neoplasm, 31% had locoregional disease and 50% had advanced disease. Left sided disease was present in 78% of patients, 8% on the right colon and 13% were in rectum. Adenocarcinoma was found in 95% of patients. Mucinous pattern was present in 39% of patients studied, intestinal tumors in 21%, singlet ring cells in 4.3%. Histologic grade was G2: 69%. Molecular analysis was conducted in 86% of tissue biopsies. Regarding RAS mutations, 15% were positive (Gly12asp, K117N and Gly13Asp), but none in NRAS. BRAF mutation was studied in 43% of patients, no mutations were found. The search for microsatellite instability was conducted in all tumors, finding it present in only one patient (5%). At median follow up of 31.8 months, 91.4% remainded alive. Patients with early stage cancer were given adjuvant therapy in 69%. mean RFS was 40 months. All patients diagnosed in stage IV disease received systemic therapy, with a medium PFS of 10 months. First line treatment was FOLFOX in 58% of patients. Target therapy with anti-EGFR and anti-VEGF was prescribed in 83.3% and 8.3% of patients in the first line respectively. Conclusions: We found that patients under 50 years with dignosis of colorectal cancer, have a family history of cancer in up to a third of patients, the most frecuent histology reported was adenocarcinoma with mucinous pattern. We observed a low frecuency of KRAS mutations compared with literature reports. A longer follow-up is requiered to asses overall survival.

scholarly journals Colorectal Cancer Screening: Video-Reviewed Flexible Sigmoidoscopy by Nurse Endoscopists — A Canadian Community-Based Perspective

2001 ◽  
Vol 15 (7) ◽  
pp. 441-445 ◽  
Author(s):  
TF Shapero ◽  
PE Alexander ◽  
J Hoover ◽  
E Burgis ◽  
R Schabas
Keyword(s):  
Colorectal Cancer ◽  
Flexible Sigmoidoscopy ◽  
Screening Program ◽  
Early Stage ◽  
Community Setting ◽  
Average Risk ◽  
Crc Screening ◽  
Asymptomatic Patients ◽  
Incident Cancer

BACKGROUND: Colorectal cancer (CRC) is the third most common incident cancer and the second most fatal cancer in Canada. Flexible sigmoidoscopy (FS) is one of the modalities under consideration for CRC screening. The present series reports on a screening program of FS performed by nonphysician endoscopists in a Canadian community setting, with video review of procedures by physicians and recommendation of follow-up colonoscopy where polyps are identified.RESULTS: Five hundred twenty-five, average-risk, asymptomatic patients were examined. After exclusion of inappropriate referrals, 488 remained for analysis. The duration and extent of examination were comparable with those of previous studies elsewhere. Compliance with suggested follow-up was 97.3%. Polyps were identified at FS in 15.4% of examinees. In 8.2% of patients, the polyps were neoplastic at subsequent histology. Four malignant lesions were detected, all at an early stage. There were no complications of FS.INTERPRETATION: This report shows that FS can be carried out safely and effectively by nonphysician personnel in a community setting in Canada. The manpower cost for nonphysician operators is considerably less than that for specialist physician endoscopists. This approach deserves consideration in cost effectiveness analyses of CRC screening.

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