Performance comparison of the methylated BCAT1/IKZF1 ctDNA test (COLVERA) with the CEA assay for detection of recurrent colorectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3589-3589 ◽  
Author(s):  
Erin L. Symonds ◽  
Susanne Kartin Pedersen ◽  
David Murray ◽  
Susan E Byrne ◽  
Paul Hollington ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Blood Test ◽  
Treatment Options ◽  
Roc Curves ◽  
Circulating Tumor Dna ◽  
Performance Comparison ◽  
Ct Scans ◽  
Recurrent Colorectal Cancer ◽  
Current Standard

3589 Background: Early detection of recurrent colorectal cancer (CRC) will improve treatment options, but the current standard blood test of carcinoembryonic-antigen (CEA) has suboptimal sensitivity for recurrence. This study compared performance of a quantitative circulating tumor DNA (ctDNA) assay for methylated BCAT1 and IKZF1 (COLVERA) with that of CEA. Methods: 301 patients were monitored for recurrence after clearance of primary CRC. Blood was collected at scheduled intervals and concentrations of CEA and ctDNA were measured using the LIAISON CEA test (Diasorin) and the COLVERA ctDNA test (Clinical Genomics). Surveillance for recurrent disease was examined using regular CT scans. Sensitivity of each blood test for recurrence was assessed in the sample collected closest to the time of imaging confirming recurrence status. Absence of recurrence was defined as at least two consecutive clear CT scans. Receiver operator characteristic (ROC) analyses were used to determine optimal positivity threshold for Colvera. Results: 131 patients underwent satisfactory assessment for recurrence and had blood testing performed within 12 months of determining recurrence status (61.8% male, mean age 62.6 ±.12.2(SD)y). Of the 47 recurrence cases, 37 (74%) were distant. The areas under the ROC curves were 0.7761 and 0.8188 for CEA and COLVERA, respectively (each p < 0.001). An optimal cut-off of 12.8pg/sample was determined for COLVERA and the standard 5ng/mL cut-off was selected for CEA. COLVERA had a significantly higher sensitivity for detecting recurrence as compared to CEA (68.1% vs 31.9%, p < 0.001) with a similar specificity (97.6% Vs 96.4%, p = 0.6547). A multivariate analysis determined COLVERA to be a predictor of recurrence independent of CEA with positive COLVERA samples being 66.4 times (95%CI 14.0-315.8) more likely to have recurrence confirmed within the study timeframe, whereas CEA was not a significant predictor of recurrence (p = 0.228). Conclusions: These findings indicate that COLVERA, reporting in quantitative mode, is a more sensitive test than CEA. It provides a viable alternative for sensitive and early detection of recurrent CRC. Clinical trial information: 12611000318987.

Biomarkers for Early Detection of Colitis-associated Colorectal Cancer - Current Concepts, Future Trends

2020 ◽  
Vol 22 (1) ◽  
pp. 137-145
Author(s):  
Tomasz Mackiewicz ◽  
Aleksander Sowa ◽  
Jakub Fichna
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Cancer Development ◽  
Sporadic Colorectal Cancer ◽  
Future Trends ◽  
Significant Progress ◽  
Current Standard ◽  
Risk Of Cancer ◽  
Histological Testing ◽  
Made In

: Colitis-associated colorectal cancer (CAC) remains a critical complication of ulcerative colitis (UC) with mortality of approximately 15%, which makes early CAC diagnosis crucial. The current standard of surveillance, with repetitive colonoscopies and histological testing of biopsied mucosa samples is burdensome and expensive, and therefore less invasive methods and reliable biomarkers are needed. Significant progress has been made thanks to continuous extensive research in this field, however no clinically relevant biomarker has been established so far. This review of the current literature presents the genetic and molecular differences between CAC and sporadic colorectal cancer and covers progress made in the early detection of CAC carcinogenesis. It focuses on biomarkers under development, which can be easily tested in samples of body fluids or breath and, once made clinically available, will help to differentiate between progressors (UC patients who will develop dysplasia) from non-progressors and enable early intervention to decrease the risk of cancer development.

Development and clinical validation of a blood test for early detection of colorectal adenomas and cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 50-50
Author(s):  
Shai Friedland ◽  
Jennifer Y. Pan ◽  
Drew Watson ◽  
Yu Chen ◽  
Ashish Nimgaonkar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Blood Test ◽  
High Specificity ◽  
Colorectal Adenomas ◽  
Prior History ◽  
Disease Category ◽  
Screening Guidelines ◽  
Advanced Neoplasia ◽  
Screening And Surveillance

50 Background: Many of the 50,000 annual colorectal cancer (CRC) deaths can be attributed to 1/3 eligible Americans not following screening guidelines or approximately 1/2 of the population not adherent to the follow-up post-polypectomy guidelines. The new understanding of the natural history and shared etiology of adenomas and CRC inform integration of clinically relevant biomarkers. The two objectives of CRC screening and surveillance are early detection to improve survival and prevention of CRC through removal of adenomas using colonoscopy. Adenomas account for 98% of actionable colonoscopies. Stool tests have low sensitivity for advanced adenomas (AA, 24-42%). Methods: A prospective, blinded study was conducted at the VA Palo Alto Health Care System. Patients had blood drawn prior to colonoscopy. The test analyzes two biomarkers: circulating gastrointestinal epithelial cells and somatic mutations of cell-free DNA. The probability of advanced neoplasia was obtained by ordinal/nominal logistic regression methods together with SEER-incidence rate and prior history of AA on a training set of 346 subjects. The cutpoint for the quantitative score was fixed and the remaining 112 subjects were tested. Results: Interim results for 458 patients with no prior diagnosis of colorectal cancer (CRC) are presented. The cohort included both screening (239) and surveillance (219) subjects. Indications for colonoscopy were 86% asymptomatic and 14% with symptoms or positive-FIT. Balanced distribution of roughly 3/4th subjects in each disease category were randomly selected for training and algorithm development and the remaining 1/4th subjects were used for validation. A cutpoint was selected to obtain a test specificity (non-neoplastic finding or negative colonoscopy) of 90% resulting in a sensitivity of 100% and 80.0% for detection of CRC and advanced neoplasia (AN = CRC+AA), respectively, on the training subjects. The area under the ROC curve is 0.91. Validation using the fixed cutpoint and 112 test subjects achieved 91.4% specificity and 100% and 75.0% sensitivity for CRC and AN. Conclusions: This blood test has high sensitivity for colorectal advanced neoplasia while retaining high specificity. The quantitative nature of the score has the potential to enable stratification of patients for screening or post-polypectomy surveillance colonoscopy. [Table: see text]

Early detection of colorectal cancer with faecal occult blood test screening

2010 ◽  
Vol 97 (10) ◽  
pp. 1567-1571 ◽  
Author(s):  
H. Paimela ◽  
N. Malila ◽  
T. Palva ◽  
T. Hakulinen ◽  
H. Vertio ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Blood Test ◽  
Occult Blood ◽  
Faecal Occult Blood Test ◽  
Occult Blood Test ◽  
Faecal Occult Blood ◽  
Faecal Occult

scholarly journals The role of the family doctor in the early diagnosis of colorectal cancer

2021 ◽  
Vol 16 (3) ◽  
pp. 307-313
Author(s):  
Mihaela Adela IANCU ◽  
◽  
Gabriela GANEA ◽  
Ramona Dorotea CĂLIN ◽  
Irina Anca EREMIA ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Family History ◽  
Early Detection ◽  
Treatment Options ◽  
Family Doctor ◽  
Tobacco Consumption ◽  
Individual Risk ◽  
The Family

The incidence of colorectal cancer is increasing. It is currently the third most common cancer, after lung and breast cancer. Despite the increased incidence, recent advances in early detection, performing the screening according to the recommendations and treatment options have reduced colorectal cancer mortality. The role of the family doctor is to advise and to identify non-modifiable risk factors (age, male sex, race, family history, inflammatory bowel disease) as well as modifiable ones (tobacco consumption, low-fiber, high-fat and high carbohydrate diet, a sedentary lifestyle, obesity), in order to avoid these risk factors by developing a personalized plan for the prevention and early detection of colorectal cancer depending on the individual risk. Genetic testing and a more comprehensive family history documentation by the family doctor can enable those with a hereditary predisposition for the colorectal cancer to take preventive measures. Applying evidence-based prevention strategies reduces the prognosis of colorectal cancer and reduces mortality. Colorectal cancer has an increased survival rate if diagnosed early and treated properly.

A novel 2-gene blood test for colorectal cancer recurrence.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 495-495
Author(s):  
Susanne Kartin Pedersen ◽  
Erin L Symonds ◽  
Scott Mansfield ◽  
Susan Byrne ◽  
Libby Bambacas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Blood Test ◽  
Residual Disease ◽  
Cancer Recurrence ◽  
Distant Recurrence ◽  
Primary Diagnosis ◽  
Clinical Findings ◽  
Ct Scans ◽  
Monitoring Methods ◽  
Gene Test

495 Background: Annual computed tomography (CT) scans and periodic carcinoembryonic antigen (CEA) testing are monitoring methods for colorectal cancer (CRC) recurrence. We have previously described a 2-gene blood test for CRC (methylated BCAT1 and IKZF1) that may indicate tumour DNA shedding into the blood. The aim was to compare the 2-gene and CEA blood tests at detecting recurrence in CRC surveillance patients. Methods: Methylated BCAT1/IKZF1and CEA (positive ≥5ng/mL) were measured in patients previously diagnosed with CRC (excluding those undergoing active treatment). McNemar’s test was used for statistical analyses, using clinical findings including CT to diagnose recurrence. Results: At study midpoint, 340 patients were enrolled (64% men, average 64yr at diagnosis), including 59 patients with blood testing done pre- and post-resection, and 105 with CT surveillance scans (median 18 months after primary diagnosis). Following resection (median 2.3 months), 91% of patients who were 2-gene positive prior to treatment showed either no detectable methylated BCAT1/IKZF1(26/35) or significantly reduced levels in blood (6/35). Residual disease was found in two patients (2/3) who remained gene positive post treatment. Recurrence was identified in 30/105 (29%) patients with surveillance CT scans. Of these, 67% and 27% were 2-gene and CEA positive, respectively, with 8 (27%) cases positive by both tests (Table 1, p<0.001). In 13 cases with local recurrence, 54% were 2-gene positive, with only 1 (8%) positive by both tests (p=0.03). In 17 cases with distant recurrence, respective 76% and 41% were 2-gene and CEA positive (p=0.03). In patients with no evident disease, 20% were positive for one test but not the other (2-gene test, 16%; CEA, 4%; p = 0.04). Conclusions: Following resection, most patients had either reduced or no methylated BCAT1/IKZF1 in blood, indicating a correlation with the presence of cancer. Two-gene positivity correlated with local (54%) and distant (76%) recurrence with 2.5-fold more recurrence cases detected than with CEA. The 2-gene test may be better than CEA for recurrence monitoring. [Table: see text]

The potential in artificial intelligence-driven radiomic signature to predict survival in patients with metastatic colorectal cancer treated with cetuximab-based therapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 247-247
Author(s):  
Laurent Dercle ◽  
Lin Lu ◽  
Lawrence Howard Schwartz ◽  
Min Qian ◽  
Sabine Tejpar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Tumor Imaging ◽  
Roc Curves ◽  
Standard Of Care ◽  
Treatment Quality ◽  
Ct Scans ◽  
Imaging Features ◽  
Data Set ◽  
Mutational Status

247 Background: This analysis was undertaken to forecast survival and enhance treatment decisions for patients (pts) with colorectal cancer (CRC) with liver metastases sensitive to folinic acid, fluorouracil and irinotecan (FOLFIRI) alone [F] or in combination with cetuximab [FC] using simple quantitative radiomic changes between CT scans at baseline and 8 weeks. Methods: We retrospectively analyzed 667 pts with KRAS-unselected metastatic CRC in NCT00154102 treated with F and FC. CT quality was classified as high (HQ) or standard (SQ), and four data sets were created and named by treatment quality. Pts were randomly assigned 1:2 to training or validation sets: FCHQ, 38/78 pts; FCSQ, 62/124 pts; FHQ, 51/78 pts; FSQ, 78/158 pts. A machine-learning signature was trained using data set FCHQ to classify pts as treatment-sensitive or treatment-insensitive using just 4 of 3,499 potential radiomic imaging features. Performance was calibrated/validated using ROC curves. Hazard ratios (HRs) and Cox regression models were used to evaluate association with overall survival (OS). Results: The signature used decrease in tumor heterogeneity plus boundary infiltration to successfully predict sensitivity to FC (FCHQ: AUC, 0.80; FCSQ: AUC, 0.72) but failed with non-cetuximab regimens (FHQ: AUC, 0.59; FSQ: AUC, 0.55). The radiomic signature outperformed existing biomarkers ( KRAS mutational status and tumor shrinkage by RECIST 1.1) for sensitivity to cetuximab-based therapy and was strongly associated with OS in the cetuximab-containing sets FCHQ (HR, 44.3; p = 0.0001) and FCSQ (HR, 6.5; p = 0.005). Conclusions: This signature, derived from simple radiomic analysis of tumor imaging phenotype using only standard-of-care CT scans, appeared to be treatment-specific and was superior to all tested prognostic biomarkers. The signature provided early prediction of sensitivity and survival and could be used to guide treatment continuation decisions.

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