scholarly journals Relationship between Mesenteric and Peripheral Blood Levels of CA 19-9 in Patients with Colorectal Cancer

2001 ◽  
Vol 16 (1) ◽  
pp. 27-30 ◽  
Author(s):  
N. M. Forones ◽  
M. Tanaka ◽  
D. Matos
Keyword(s):  
Colorectal Cancer ◽  
Clinical Stage ◽  
Elevated Serum ◽  
Stage Iv ◽  
Close Correlation ◽  
Serum Levels ◽  
Stage I ◽  
Blood Levels ◽  
Peripheral Vein ◽  
Mesenteric Vein

Introduction CA19-9 is one of the most important tumor markers used in patients with colorectal cancer, mainly in radical surgery follow-up. Aim: The purpose of this study was to evaluate the preoperative CA19-9 level obtained from a peripheral vein (PV) and compare it to the level obtained from the mesenteric vein (MV). Materials and methods Blood was collected from a PV of the arm and from the MV of 59 patients with colorectal cancer before primary surgery. Of these 59 patients fourteen had stage I disease, 10 stage II, 22 stage III, and 13 stage IV. CA19-9 was determined in serum by immunoenzymatic assay (Abbott Diagnostica). Results Fifteen patients (24%) had elevated serum levels of CA19-9 in the MV and 13 (22%) in the PV. None of the stage I or II patients had elevated serum levels of CA19-9. There were no differences between marker levels in blood collected from the MV or PV, independent of clinical stage. The CA19-9 values obtained from the MV differed significantly in the different stages of the disease according to the Kruskal-Wallis analysis (p=0.026); this difference was not statistically significant (p=0.08) in serum from the PV. There was no correlation between venous infiltration by the tumor and positivity of CA19-9 serum levels collected from the mesenteric vein. We observed a close correlation between the serum levels of CA19-9 collected from the PV and from the MV (r=0.9). Conclusion The current study demonstrates a close correlation between the serum levels of CA19-9 collected from a peripheral vein and from the mesenteric vein. Our results confirmed the poor sensitivity of serum CA19-9 at diagnosis, independent of the collection site.

The impact of the COVID-19 pandemic on stage at diagnosis of breast and colorectal cancers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6501-6501
Author(s):  
Jade Zhou ◽  
Shelly Kane ◽  
Celia Ramsey ◽  
Melody Ann Akhondzadeh ◽  
Ananya Banerjee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
Cancer Screening ◽  
Late Stage ◽  
Stage Iv ◽  
Stage I ◽  
Screening Programs ◽  
Stage Distribution ◽  
Number Of Patients ◽  
The Impact

6501 Background: Effective cancer screening leads to a substantial increase in the detection of earlier stages of cancer, while decreasing the incidence of later stage cancer diagnoses. Timely screening programs are critical in reducing cancer-related mortality in both breast and colorectal cancer by detecting tumors at an early, curable stage. The COVID-19 pandemic resulted in the postponement or cancellation of many screening procedures, due to both patient fears of exposures within the healthcare system as well as the cancellation of some elective procedures. We sought to identify how the COVID-19 pandemic has impacted the incidence of early and late stage breast and colorectal cancer diagnoses at our institution. Methods: We examined staging for all patients presenting to UCSD at first presentation for a new diagnosis of malignancy or second opinion in 2019 and 2020. Treating clinicians determined the stage at presentation for all patients using an AJCC staging module (8th edition) in the electronic medical record (Epic). We compared stage distribution at presentation in 2019 vs 2020, both for cancers overall and for colorectal and breast cancer, because these cancers are frequently detected by screening. Results: Total numbers of new patient visits for malignancy were similar in 2019 and 2020 (1894 vs 1915 pts), and stage distribution for all cancer patients was similar (stage I 32% in 2019 vs 29% in 2020; stage IV 26% in both 2019 and 2020). For patients with breast cancer, we saw a lower number of patients presenting with stage I disease (64% in 2019 vs 51% in 2020) and a higher number presenting with stage IV (2% vs 6%). Similar findings were seen in colorectal cancer (stage I: 22% vs 16%; stage IV: 6% vs 18%). Conclusions: Since the COVID-19 pandemic, there has been an increase in incidence of late stage presentation of colorectal and breast cancer, corresponding with a decrease in early stage presentation of these cancers at our institution. Cancer screening is integral to cancer prevention and control, specifically in colorectal and breast cancers which are often detected by screening, and the disruption of screening services has had a significant impact on our patients. We plan to continue following these numbers closely, and will present data from the first half of 2021 as it becomes available.

scholarly journals Malignant Extracranial Germ Cell Tumours: A First Report by the South African Children’s Cancer Study Group

2021 ◽  
Author(s):  
Marc Hendricks ◽  
Annibale Cois ◽  
Jennifer Geel ◽  
Jan du Plessis ◽  
Mairi Bassingthwaighte ◽  
...  
Keyword(s):  
Germ Cell ◽  
South African ◽  
Economic Status ◽  
Clinical Stage ◽  
Elevated Serum ◽  
Treatment Protocol ◽  
Stage Iv ◽  
Germ Cell Tumours ◽  
Advanced Clinical Stage ◽  
Risk Of Death

OBJECTIVE  To determine the overall survival (OS) and prognostic factors influencing outcomes in children and adolescents with malignant extracranial germ cell tumours (MEGCTs) in preparation for the development of a harmonised national treatment protocol.METHODS A retrospective folder review was undertaken at nine South African paediatric oncology units to document patient profiles, tumour and treatment-related data and outcomes for all children with biopsy proven MEGCTs from birth up to and including 16 years of age. RESULTS Between 1 January 2000 and 31 December 2015, 218 patients were diagnosed with MEGCTs. Female sex (HR 0.284 p=0.037) and higher socio-economic status (SES) (HR 0.071; p=0.039) were associated with a significantly lower risk of death. Advanced clinical stage at diagnosis significantly affected 5-year OS: stage I -96%; stage II - 94.3%; stage III -75.5%; (p=0.017) and stage IV (60.1%; p<0.001). There was a significant association between earlier stage at presentation and higher SES (p=0.03). Patients with a serum AFP level of more than 33,000 ng/ml at diagnosis had significantly poorer outcomes (p=0.002). The use of chemotherapy significantly improved survival, irrespective of the regimen used (p<0.001). CONCLUSIONS The cohort demonstrated a 5-year OS of 80.3% with an EFS of 75.3%. Stage, the use of chemotherapy and an elevated serum AFP level of more than 33,000ng/ml were independently predictive of outcome. The relationship between SES and outcome is important as the implementation of the new national protocol hopes to standardise care across the socio-economic divide.

scholarly journals Clinical Significance of Fibroblast Growth Factor (FGF) Expression in Colorectal Cancer

2014 ◽  
Vol 99 (5) ◽  
pp. 493-499 ◽  
Author(s):  
Norie Jibiki ◽  
Noboru Saito ◽  
Shingo Kameoka ◽  
Makio Kobayashi
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Stage Iv ◽  
Serum Levels ◽  
Lymphatic Invasion ◽  
Fibroblast Growth ◽  
Clinicopathological Factors

Abstract In this study, we serologically and pathologically examined the clinical significance of fibroblast growth factor (FGF) expression in patients with colorectal cancer. Serum basic FGF (bFGF) levels in 92 surgical colorectal cancer patients and 31 controls were measured, and the relationship between those levels and clinicopathological factors were examined. Immunohistochemical study was also conducted on specimens from 51 cancer patients, and the association between bFGF staining and serum levels were investigated. An examination of clinicopathological factors revealed significant differences in bFGF levels between stage 0-IIIb and stage IV cancers (P = 0.013). Lymphatic invasion was one factor that differed significantly. Patients with a tumor 30 mm or smaller had a bFGF level of 7.65 ± 1.11 pg/ml while patients with a tumor 31 mm or larger had a bFGF level of 8.53 ± 3.22 pg/ml; significant differences in these bFGF levels were noted (P &lt; 0.05). Patients with a tumor that had no lymphatic invasion (ly0) had a bFGF level of 7.25 ± 0.66 pg/ml, those with a tumor that had minimal lymphatic invasion (ly1) had a bFGF level of 7.99 ± 1.68 pg/ml, and those with a tumor that had moderate lymphatic invasion (ly2) had a bFGF level of 9.17 ± 4.23 pg/ml. bFGF levels differed significantly for tumors with no/minimal lymphatic invasion (ly0-ly1) and those with moderate lymphatic invasion (ly2) (P &lt; 0.0001). Serological examination of bFGF levels during the proliferation of colorectal cancer revealed that moderate lymphatic invasion can be readily distinguished.

Impact of BRAF mutations on prognosis and immunotherapy response in microsatellite instability/mismatch repair deficient metastatic colorectal cancer: A systematic review and meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3557-3557
Author(s):  
Robin Park ◽  
Laércio Lopes da Silva ◽  
Sunggon Lee ◽  
Anwaar Saeed
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Braf Mutation ◽  
Meta Analysis ◽  
Stage Iv ◽  
Stage I ◽  
Prognostic Impact ◽  
Braf Mutations ◽  
Mutation Status ◽  
The Impact

3557 Background: Mismatch repair deficient/microsatellite instability high (dMMR/MSI-H) colorectal cancer (CRC) defines a molecular subtype with distinct clinicopathologic characteristics including an excellent response to immunotherapy. Although BRAF mutations are established as a negative prognostic marker in CRC, whether they retain their negative prognostic impact in or alter the response to immunotherapy in dMMR/MSI-H CRC remains unknown. Herein, we present a systematic review and meta-analysis of the impact of BRAF mutations on the overall survival (OS) and immune checkpoint inhibitor (ICI) response in dMMR/MSI-H CRC. Methods: Studies published from inception to 26 January 2021 were searched in PubMed, Embase, and major conference proceedings (AACR, ASCO, and ESMO). Eligible studies included the following: 1) observational studies reporting outcomes based on BRAF mutation status in dMMR/MSI-H CRC patients and 2) experimental studies of ICI reporting outcomes based on BRAF mutation status in dMMR/MSI-H CRC patients. A summary hazard ratio (HR) was calculated for OS in BRAF mutated ( BRAFmut) vs. BRAF wild type ( BRAFwt) patients (pts) with the random effects meta-analysis (REM). A summary odds ratio (OR) was calculated for objective response rate (ORR) in BRAFmut vs. BRAFwt pts treated with ICI with the REM. Results: Database search conducted according to PRISMA guidelines found 4221 studies in total. Initial screening identified 30 studies and after full-text review, 9 studies (N = 4158 pts) were included for the meta-analysis of prognosis (analysis A) and 3 studies (N = 178 pts) were included for the meta-analysis of ICI response (analysis B). The outcome measures are summarized in the table below. Analysis A showed that in stage I-IV dMMR/MSI-H CRC pts, BRAFmut was associated with worse OS than BRAFwt (HR 1.57, 1.23-1.99). The heterogeneity was low (I2 = 21%). Subgroup analysis showed no significant difference in the prognostic impact of BRAF mutation status between stage IV only and stage I-IV CRC pts. Analysis B showed no difference in ORR (OR 1.04, 0.48-2.25) between BRAFmut vs. BRAFwt dMMR/MSI-H pts who received ICI. The heterogeneity was low (I2 = 0%). Conclusions: BRAF mutations retain their negative prognostic impact in dMMR/MSI-H stage I-IV and stage IV CRC but are not associated with differential ICI response. Limitations include the following: analysis A was based on retrospective studies; also, the impact of BRAF status on the survival outcome of ICI could not be assessed due to limited number of studies.[Table: see text]

Tumor Markers in Serum of Patients with Primary Squamous Cell Carcinoma of the Esophagus

1989 ◽  
Vol 75 (5) ◽  
pp. 489-493 ◽  
Author(s):  
Massimo Gion ◽  
Carlo Tremolada ◽  
Riccardo Mione ◽  
Paolo della Palma ◽  
Ruggero Dittadi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Cell Carcinoma ◽  
Tumor Markers ◽  
Squamous Cell ◽  
Clinical Stage ◽  
Stage Iv ◽  
Blood Levels ◽  
Primary Squamous Cell Carcinoma ◽  
Carcinoma Of The Esophagus

Serum levels of several tumor markers were studied in 96 patients with untreated primary squamous cell carcinoma of the esophagus. Three markers specific for digestive tract malignancies - CEA, CA19.9 and CA50 - and two non organ specific indicators of malignancy - ferritin and TPA - were evaluated. Positivity rates of CAI9.9 and CA50 were very low (4.4 % and 8.6 % respectively); the markers were therefore considered ineffective in the disease. CEA, TPA and ferritin showed a fair positivity rate (27.1 %, 28.1 %, 33.7% respectively); CEA and TPA were directly related to clinical stage, CEA levels being significantly higher in stage IV than in stage III cases (p = 0.016). TPA preoperatory levels were also directly related to a lower survival probability (p = 0.004). CEA showed significantly lower levels in tumors of lower than in those of middle (p = 0.03) and upper esophagus (p = 0.004). TPA showed a similar behaviour with lower levels in tumors of lower than of middle esophagus (p = 0.03). These findings could be due to a bulky metabolism of tumor markers drained via portail vein in the liver. From our data the following conclusions may be drawn: 1) CEA and TPA may be useful in the staging of esophageal cancer as an ancillary tool to assess the extent of the disease; 2) tumor location is an important variable when evaluating blood levels of tumor markers in patients with esophageal cancer.

Limited-Stage Mantle Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5330-5330 ◽  
Author(s):  
Ritsuro Suzuki ◽  
Dai Chihara ◽  
Naoko Asano ◽  
Ken Ohmachi ◽  
Tomohiro Kinoshita ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
Clinical Stage ◽  
Stage Iv ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Advanced Stage ◽  
Limited Stage ◽  
Stage Disease

Abstract [Background] Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma, characterized by the overexpression of cyclin D1 derived from t(11;14)(q13;q32) and poor prognosis. Most MCLs show nodal presentation, but also accompany extranodal involvement, such as bone marrow, peripheral blood or gastrointestinal tract. As a result, many MCLs present with advanced stage disease. Since only a small portion of patients show limited-stage disease, minimal data exist on treatment of patients diagnosed with limited stage disease. Nevertheless, the treatment strategy of MCL is recommended according to the clinical stage of limited- (stage I or non-bulky II) vs. advanced-stage, as well as other types of lymphoma. [Patients and methods] We recently collected 633 patient data of MCL (Chihara, et al. Ann Oncol 2015). Information of clinical stage was available in 626 patients. The patient data were retrospectively analyzed the by the clinical stage at initial presentation. [Results] The clinical stage was I in 24 patients (4%), II in 33 (5%), III in 70 (11%), and IV in 499 (80%). Only one patient presented with bulky stage II. Detailed demographic information by the clinical stage are listed in Table. Age and sex were not significantly different by clinical stage. Limited stage patients were associated with better performance status (PS), less B symptoms, no extranodal involvement, and lower lactate dehydrogenase (LDH) level and white blood cell (WBC) count. Most patients in any stage were treated with cytotoxic chemotherapy, but more patients in limited stage received radiotherapy. The proportion of high-dose cytarabine (HDCA)-containing regimen over CHOP/CHOP-like was higher in advanced stage patients. Complete and overall response rates were 92% and 96% in stage I, 58% and 94% in stage II, 66% and 86% in stage III, and 52% and 82% in stage IV, respectively (P = 0.02). However, the higher response rate in limited stage patients did not translate into better prognosis. The median survival was 11.0 years in stage I, 13.4 years in stage II, 11.5 years in stage III, and 5.6 years in stage IV (Figure). The prognosis was not significantly different among patients with stage I, II, and III (P = 0.33). [Conclusion] Prognosis of limited-stage MCL was almost similar to that of stage III MCL. Although the present study includes several limitations including a retrospective nature and limited number of patients, prognosis of patients with limited-stage MCL was not satisfactory. The significance of radiotherapy, as well as the optimal choice of chemotherapy, for limited-stage MCL needs re-evaluation. Table Table. Figure Figure. Disclosures Suzuki: Chugai: Honoraria; Kyowa Hakko kirin: Honoraria; Bristol-Myers Squibb: Honoraria. Asano:Jannsen: Honoraria; Chugai: Honoraria. Kinoshita:Ono: Research Funding; Gilead: Research Funding; Zenyaku: Honoraria, Research Funding; Takeda: Research Funding; Chugai: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Solasia: Research Funding; Janssen: Honoraria; Kyowa Kirin: Honoraria. Suzumiya:Chugai: Honoraria, Research Funding; Astellas: Research Funding; Eisai: Honoraria, Research Funding; Takeda: Honoraria; Toyama Chemical: Research Funding; Kyowa Hakko kirin: Research Funding. Ogura:SymBio Pharmaceuticals: Consultancy, Honoraria; Celltrion, Inc.: Consultancy, Honoraria.

MicroRNA signatures from FFPE tissue distinguish patients with colorectal cancer of UICC stage I from those with metastatic disease of stage IV.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. e14055-e14055
Author(s):  
T. Mayr ◽  
P. Pechanska ◽  
K. Ridwelski ◽  
R. Mantke ◽  
M. Pross ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Disease ◽  
Stage Iv ◽  
Ffpe Tissue ◽  
Stage I ◽  
Uicc Stage

Serum-based multiplex protein assay for early detection of colorectal cancer and precancerous lesions in a FIT positive population.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16145-e16145
Author(s):  
Herbert A. Fritsche ◽  
Jason Lee Liggett ◽  
Hong Zhang ◽  
Linnea Ferm ◽  
Ib Jarle Christensen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Stage Iv ◽  
Stage I ◽  
Stage Ii ◽  
Supervised Machine Learning ◽  
Stage Iii ◽  
Screening Programs ◽  
Medium Risk ◽  
Validation Set

e16145 Background: Colorectal cancer (CRC) is the second leading cancer worldwide in terms of incidence, 5-year prevalence and mortality for both women and men ages 45 years old and up. The current screening method for many countries with organized screening programs is the FIT test for fecal occult blood; however, this test can result in false positive rates as high as 65%. A FIT reflex test could reduce unnecessary colonoscopies while reducing wait times for those patients that need confirmatory colonoscopies the most. Methods: Danish FIT positive colonoscopy confirmed serum samples (n = 1,499) were divided into training and validation sets maintaining approximately equivalent percentages of clean colonoscopy (40%), low risk adenomas (16%), medium risk adenomas (19%), high risk adenomas (13%), stage I CRC (5%), stage II CRC (2%), stage III CRC (4%), and stage IV CRC (0.5%). Proteins were quantified by custom 16-plex immunoassays utilizing the Luminex xMAP platform. A support vector machine supervised machine learning algorithm was trained with the 16 biomarkers plus age and FIT concentration using 1,291 samples for the outcome medium risk adenoma, high risk adenoma, and CRC. Then this algorithm was tested on a blind 208 sample validation set. Results: The training set was 90% sensitive and 27% specific (AUC = 0.68) and the validation set was 93% sensitive and 21% specific (AUC = 0.63). The sensitivities of the validation by risk/stage was as follows: medium risk adenoma 91%, high risk adenomas 92%, stage I CRC 100%, stage II CRC 100%, stage III CRC 100%, stage IV CRC 93%. Conclusions: This study demonstrates feasibility of a novel blood-based multiplex protein immunoassay for use as a reflex to FIT positive results in population wide screening. It detected nearly all adenomas and carcinomas while reducing FIT false positives and thus unnecessary colonoscopies by more than 20%. A FIT reflex test could alleviate endoscopy burden experienced in countries with organized cancer screening programs, while providing better patient outcomes by detecting polyps and early-stage CRC with high sensitivity.

Prognostication based on TNM staging for socioeconomically disadvantaged colorectal cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19036-e19036
Author(s):  
Yan Lu ◽  
Aaron Gehr ◽  
Jolonda Bullock ◽  
Bassam Ghabach ◽  
Latha Sri Neerukonda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Stage Iv ◽  
Safety Net ◽  
Stage I ◽  
Socioeconomically Disadvantaged ◽  
Pathologic Stage ◽  
Eligible Population ◽  
Prognostic Groups ◽  
Colorectal Cancer Patients

e19036 Background: The TNM classification system is the global standard for staging solid tumors, but the ability of TNM to differentiate prognostic groups may vary between settings because of differences in case-mix and treatments. Little information is available about prognostication using TNM in safety-net health systems, which provide care for socioeconomically disadvantaged individuals and have limited resources. Therefore, we aimed to assess the ability of TNM to differentiate prognostic groups for colorectal cancer patients in an urban safety-net cancer center. Methods: We used institutional registry data from the JPS Oncology and Infusion Center (Fort Worth, TX), which is a Comprehensive Community Cancer Program. Our eligible population included adults who were diagnosed with first primary colorectal cancer between 2008 and 2017, had TNM pathologic stage I – IV, and received at least part of the first course treatment at JPS. Our outcome of interest was 5-year all-cause mortality and our exposure of interest was TNM pathologic stage. Patients were followed from cancer diagnosis until death, loss to follow up, or end of study (December 31, 2018), whichever occurred first. We used a pseudo-observation approach and generalized linear models with log link to estimate risk ratios (RR) and corresponding 95% confidence limits (CL) comparing 5-year mortality between TNM stages, where stage I was the reference category. Results: Our eligible population comprised 655 colorectal cancer survivors, of whom 85% were aged < 65 years, 54% were male, 60% were racial/ethnic minorities, and 65% were uninsured at time of diagnosis. Stage IV patients had 4.4 times higher risk of 5-year mortality compared with stage I (RR = 4.4, 95% CL: 2.9, 6.6). Stage III patients had 2.1 times higher risk of 5-year mortality compared with stage I (RR = 2.1, 95% CL: 1.3, 3.2). Stage II patients had 1.4 times higher risk of 5-year mortality compared with stage I (RR = 1.4, 95% CL: 0.81, 2.3). Conclusions: Our findings suggest that TNM stages do not adequately differentiate colorectal cancer prognostic groups in a socioeconomically disadvantaged population. Stage IV is distinct, but stages I – III have limited differentiation and notable overlap. The use of TNM stages for colorectal cancer prognostication may be misleading for socioeconomically disadvantaged individuals. Factors beyond TNM should be considered for better prognostication in this population.

An improved method for detection of methylated circulating tumor DNA in colorectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15120-e15120 ◽  
Author(s):  
Nicky Boulter ◽  
Gregor Tevz ◽  
Betty Yu ◽  
Michelle Chan ◽  
David Murray ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stage Iv ◽  
Circulating Tumor Dna ◽  
Qpcr Assay ◽  
Stage I ◽  
Stage Ii ◽  
Detection Methods ◽  
Assay Sensitivity ◽  
Crc Screening ◽  
Tumor Dna

e15120 Background: Assays detecting methylated circulating tumor DNA (ctDNA) hold promise for colorectal cancer (CRC) screening, but there is a need to develop more accurate assays for early stages. In this study, we examined modifications to COLVERA (an IKZF1 and BCAT1 methylation marker qPCR assay) that added a third biomarker (IRF4) as well as introducing double stranded detection. Methods: Bisulfite converted DNA extracted from plasma collected from subjects undergoing diagnosis for CRC was assayed using either a double-stranded (ds) specific multiplexed qPCR for BCAT1 and IKZF1 detection (Assay 1) and/or a single-stranded (ss) specific BCAT1/IRF4, ds-specific IKZF1 multiplexed qPCR (Assay 2). The unmodified COLVERA test (Clinical Genomics) was used for comparison. Detection of any marker was considered positive. Results: Assay 1 performance evaluated against COLVERA on bisulfite converted DNA from 1453 samples showed an improved sensitivity for CRC detection (93/134 (69.4%) vs 79/134 (59.0%) COLVERA, p = 0.02), but specificity was suboptimal (no neoplasia: 861/1023 (84.2%) vs 946/1023 (92.5%) COLVERA, p < 0.0001). The decrease in specificity resulted primarily from modifications in the BCAT1 assay component (1023 no neoplasia: 60 positive with ss- BCAT1 vs 146 positive with ds- BCAT1, p < 0.0001). Thus, a novel configuration, Assay 2 (ss- BCAT1, ss- IRF4 and ds- IKZF1) was compared to Assay 1 using 189 previously untested specimens. Assay 2 showed a notable improvement in specificity (99/104 (95.2%) vs 93/104 (89.4%) Assay 1; p = 0.0351). Both assays exhibited comparable sensitivities for CRC (41/49 (83.7%) vs 39/49 (79.6%), Assay 1, p = 0.3633). Assay 2 was positive in: adenomas, 9/36 (25.0%); Stage I, 3/7 (42.9%); Stage II, 17/19 (89.5%); Stage III, 6/6 (100%); Stage IV, 7/7 (100%) and 8/10 (80%) unstaged CRCs. Prior COLVERA sensitivity estimates were 9% adenoma, 41% Stage I and 76% Stage II. Conclusions: Targeting both of the non-complementary bisulfite converted strands of selective regions of interest markedly improve ctDNA assay sensitivity for cancer including early lesions while achieving good specificity. Prospective evaluation in a true CRC screening population is now underway. Clinical trial information: 12611000318987.

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