Employer-Based Stool DNA (sDNA) Colorectal Cancer (CRC) Screening Leads to Identification of Early-Stage Disease

419 Background: Early detection of colorectal cancer (CRC) has been shown to decrease mortality, although compliance to CRC screening is low. Availability of a blood-based test is expected to improve CRC screening compliance. Specific detection of CRC using the Septin9 biomarker (mSEPT9) in a large prospective trial of an average-risk CRC screening population exhibited 67% sensitivity for CRC with 88% specificity. Laboratory-developed tests detecting mSEPT9 in plasma are now available in North America and a 2nd generation molecular diagnostic blood test for mSEPT9 is available as a CE-marked kit in Europe. The current research evaluated the clinical performance of the 2nd generation mSEPT9 assay. Methods: Bisulfite-converted DNA (bisDNA) was prepared from 3.5 mL human plasma using the 2ndgeneration plasma DNA preparation kit. Resulting bisDNA was analyzed in triplicate on the ABI7500 Fast Dx (Life Technologies, Inc.) using proprietary HeavyMethyl real-time PCR technology for mSEPT9 and the 2nd generation real-time PCR kit. In a case – control design, plasma from 98 CRC patients (n = 87 stages I - III) and 99 age-matched, colonoscopy-verified normal individuals were processed with the mSEPT9 assay. In addition, plasma from 150 prospectively enrolled average risk individuals scheduled for screening colonoscopy was tested. mSEPT9 was qualitatively analyzed such that any detection of mSEPT9 in a PCR was called “positive”. Results: The revised mSEPT9 assay exhibited 95% sensitivity (95% CI: 89-98%) for CRC. Sensitivity for stage I was 89% (95% CI: 72-96%, n = 27) and sensitivity for stage II was 93% (95% CI: 78-98%, n = 29). The control group was positive at a rate of 16% (95% CI: 10-25%). Specificity of the mSEPT9 assay in the screening cohort was 85% (95% CI: 78-89%). Conclusions: The 2nd generation mSEPT9 assay demonstrated improved sensitivity for CRC without significant impact on specificity. The enhanced design and robustness of the assay will further facilitate its standardized use in routine laboratory settings. Finally, the increased sensitivity of the revised mSEPT9 assay improves the detection of early stage disease and demonstrates the feasibility of a blood-based CRC screening technology.

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Novel Biomarker-Targeted Therapies for Metastatic Colorectal Cancer

Digestive Disease Interventions ◽

10.1055/s-0041-1727225 ◽

2021 ◽

Author(s):

Shimoli V. Barot ◽

Suneel D. Kamath

Keyword(s):

Colorectal Cancer ◽

Growth Factor ◽

Metastatic Disease ◽

Targeted Therapies ◽

Early Stage ◽

Growth Factor Receptor ◽

Precision Oncology ◽

Dynamic Heterogeneity ◽

Early Stage Disease ◽

Stage Disease

AbstractColorectal cancer (CRC) is one of the most common and fatal malignancies worldwide. Screening, surgery, and adjuvant therapy have proved efficacious in improving outcomes for early-stage disease. Despite decades of research efforts, cytotoxic chemotherapy has been the mainstay of treatment for metastatic disease and the prognosis remains unsatisfactory. Compelling evidence suggests that a fundamental reason for the limited success is the cancer's inherent dynamic heterogeneity, which is more predominant in late-stage disease. As our understanding of this molecular blueprint of CRC has evolved, a new avenue of targeted therapies has emerged. Beginning with epidermal growth factor receptor and vascular endothelial growth factor inhibitors, numerous targeted agents have been developed and investigated in large, multicenter, prospective clinical trials. Testing for mutations in RAS (KRAS and NRAS), BRAF, and HER2 and for mismatch repair/microsatellite instability and NTRK fusions has now been incorporated in the management guidelines, with additional biomarkers rapidly surfacing. As we enter the latest paradigm of precision oncology in CRC, this article will provide an overview of the different molecular subsets of CRC and the current biomarker-targeted therapies in the management of metastatic disease.

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L1CAM expression in colorectal cancer identifies patients prone to metastasis already in early-stage disease

Annals of Oncology ◽

10.1093/annonc/mdz155.217 ◽

2019 ◽

Vol 30 ◽

pp. iv60

Author(s):

A. Tampakis ◽

E. Tampaki ◽

A. Nonni ◽

E. Patsouris ◽

M. von Flüe ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Stage ◽

Early Stage Disease ◽

Stage Disease ◽

L1cam Expression

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Prognostic Significance of DNA Aneuploidy and p21ras Oncoprotein Expression in Colorectal Cancer and Their Role in the Determination of Treatment Modalities

The International Journal of Biological Markers ◽

10.1177/172460080101600203 ◽

2001 ◽

Vol 16 (2) ◽

pp. 97-104 ◽

Cited By ~ 5

Author(s):

N.H. Karelia ◽

D.D. Patel ◽

N.S. Desai ◽

H.V. Mehta ◽

P.K. Yadav ◽

...

Keyword(s):

Colorectal Cancer ◽

Dna Ploidy ◽

Early Stage ◽

Prognostic Significance ◽

S Phase ◽

Response To Therapy ◽

Phase Fraction ◽

Treatment Modalities ◽

Early Stage Disease ◽

Stage Disease

The purpose of the present study was to investigate the prognostic significance of DNA ploidy, S-phase fraction and p21ras oncoprotein expression in patients with colorectal cancer and to correlate these factors with the clinical behavior of the tumors and their response to therapy. Of 79 patients with colorectal cancer 57% (45/79) had early stage disease. Forty-one percent (32/79) had aneuploid tumors while 30% (24/79) of the tumors had a high (>10%) S-phase fraction. p21ras oncoprotein expression was detected in 38% (30/79) of tumors. Patients with aneuploid tumors had a worse prognosis than patients with diploid tumors (p=0.0002). Similarly, patients with high S-phase fraction tumors had a shorter survival than those with low S-phase fraction tumors (p=0.005). No such difference was found between p21ras-positive and p21ras-negative tumor subgroups. In early stage colorectal cancer, aneuploidy was closely correlated with disease outcome (p=0.029). Early stage patients with diploid tumors who received radiotherapy and chemotherapy had a better prognosis than patients with aneuploid tumors. In conclusion, DNA ploidy is a significant and independent prognostic factor in colorectal cancer. Aneuploidy and genetic alteration of the p21ras oncoprotein are important in determining the biological aggressiveness of colorectal cancer. Furthermore, DNA ploidy may identify those subgroups of patients with early stage disease who may benefit from more aggressive treatment.

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L1CAM expression in colorectal cancer identifies a high-risk group of patients with dismal prognosis already in early-stage disease

Acta Oncologica ◽

10.1080/0284186x.2019.1667022 ◽

2019 ◽

Vol 59 (1) ◽

pp. 55-59 ◽

Cited By ~ 1

Author(s):

Athanasios Tampakis ◽

Ekaterini Christina Tampaki ◽

Afroditi Nonni ◽

Gerasimos Tsourouflis ◽

Alberto Posabella ◽

...

Keyword(s):

Colorectal Cancer ◽

High Risk ◽

Risk Group ◽

Early Stage ◽

High Risk Group ◽

Early Stage Disease ◽

Dismal Prognosis ◽

Stage Disease ◽

L1cam Expression

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MAP17 Expression in Colorectal Cancer Is a Prognostic Factor for Disease Recurrence and Dismal Prognosis Already in Early Stage Disease

Oncology ◽

10.1159/000515596 ◽

2021 ◽

pp. 1-11

Author(s):

Athanasios Tampakis ◽

Ekaterini Christina Tampaki ◽

Afroditi Nonni ◽

Michael Kontos ◽

Gerasimos Tsourouflis ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Cancer Cells ◽

Early Stage ◽

Progression Free Survival ◽

Disease Recurrence ◽

Morbidity And Mortality ◽

Early Stage Disease ◽

Free Survival ◽

Stage Disease

Background: Disease recurrence in colorectal cancer constitutes a major cause of significant cancer-associated morbidity and mortality. MAP17 is a small protein, and its overexpression in malignant tumors has been correlated with aggressive tumor phenotypes. The aim of the present study was to investigate the expression patterns of MAP17 in colorectal cancer specimens and to assess its clinical significance. Patients and Methods: Surgical specimens of 111 patients with primary resectable colorectal cancer constituted the study population. Expression of MAP17 was assessed by immunohistochemistry, and the results were correlated with clinical and survival data. Results: MAP17 was expressed in cancer cells and endothelial cells of tumor blood vessels. Expression of MAP17 more than 10% was correlated with advanced disease stage (p < 0.001), higher T classification (p = 0.007), the presence of lymph node metastasis (p < 0.001), vascular (p = 0.013) and perineural invasion (p = 0.012). Patients exhibiting MAP17 expression of more than 30% in cancer cells compared to those expressing MAP17 less than 10% demonstrated a significantly worse 3-year progression-free survival (35.2 vs. 91%, p < 0.001) and 5-year overall survival (40.8 vs. 91%, p < 0.001). Cox regression analysis confirmed MAP17 expression of more than 30% as a prognostic marker of progression free survival (HR 0.136, 95% CI = 0.056–0.329, p < 0.001) and overall survival (HR 0.144 [95% CI) = 0.049–0.419, p < 0.001) independent of other clinicopathological characteristics. Statistically significantly worse 3-year progression-free survival and 5-year overall survival was demonstrated in the subgroup analysis of patients with early stage cancer only and high expression of MAP17. Conclusions: High MAP17 expression in patients with colorectal cancer is a significant risk factor for cancer-associated morbidity and mortality already in early stage disease.

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Body composition measured by computed tomography is associated with colorectal cancer survival, also in early-stage disease

Acta Oncologica ◽

10.1080/0284186x.2020.1744716 ◽

2020 ◽

Vol 59 (7) ◽

pp. 799-808 ◽

Cited By ~ 1

Author(s):

Mona Shirdel ◽

Fredrick Andersson ◽

Robin Myte ◽

Jan Axelsson ◽

Martin Rutegård ◽

...

Keyword(s):

Colorectal Cancer ◽

Computed Tomography ◽

Body Composition ◽

Cancer Survival ◽

Early Stage ◽

Early Stage Disease ◽

Colorectal Cancer Survival ◽

Stage Disease

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COLLISION TUMORS OF THE CERVIX IN AN EARLY STAGE DISEASE. A CASE REPORT

10.26226/morressier.5770e29ad462b80290b4b9f3 ◽

2016 ◽

Author(s):

Jimmy Billod

Keyword(s):

Case Report ◽

Early Stage ◽

Early Stage Disease ◽

Collision Tumors ◽

Stage Disease

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Novel approaches to improve prostate cancer diagnosis and management in early-stage disease

BJU International ◽

10.1111/j.1464-410x.2011.10870.x ◽

2012 ◽

Vol 109 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

Michael Marberger ◽

Jelle Barentsz ◽

Mark Emberton ◽

Jonas Hugosson ◽

Stacy Loeb ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Diagnosis ◽

Early Stage ◽

Early Stage Disease ◽

Prostate Cancer Diagnosis ◽

Diagnosis And Management ◽

Stage Disease ◽

Novel Approaches ◽

Improve Prostate Cancer

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Colorectal cancer screening using a stool DNA-based SDC2 methylation test: a multicenter, prospective trial

BMC Gastroenterology ◽

10.1186/s12876-021-01759-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chang Woo Kim ◽

Hyunjin Kim ◽

Hyoung Rae Kim ◽

Bong-Hyeon Kye ◽

Hyung Jin Kim ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Early Detection ◽

Prospective Trial ◽

Screening Colonoscopy ◽

Quantitative Detection ◽

Screening Programs ◽

Crc Screening ◽

Stool Dna ◽

Dna 2

Abstract Background Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low. Syndecan-2 (SDC2) is a stool-based DNA methylation marker used for early detection of CRC. Using the EarlyTect™-Colon Cancer test, the sensitivity and specificity of SDC2 methylation in stool DNA for detecting CRC were previously demonstrated to be greater than 90%. Therefore, a larger trial to validate its use for CRC screening in asymptomatic populations is now required. Methods All participants will collect their stool (at least 20 g) before undergoing screening colonoscopy. The samples will be sent to a central laboratory for analysis. Stool DNA will be isolated using a GT Stool DNA Extraction kit, according to the manufacturer’s protocol. Before performing the methylation test, stool DNA (2 µg per reaction) will be treated with bisulfite, according to manufacturer’s instructions. SDC2 and COL2A1 control reactions will be performed in a single tube. The SDC2 methylation test will be performed using an AB 7500 Fast Real-time PCR system. CT values will be calculated using the 7500 software accompanying the instrument. Results from the EarlyTect™-Colon Cancer test will be compared against those obtained from colonoscopy and any corresponding diagnostic histopathology from clinically significant biopsied or subsequently excised lesions. Based on these results, participants will be divided into three groups: CRC, polyp, and negative. The following clinical data will be recorded for the participants: sex, age, colonoscopy results, and clinical stage (for CRC cases). Discussion This trial investigates the clinical performance of a device that allows quantitative detection of a single DNA marker, SDC2 methylation, in human stool DNA in asymptomatic populations. The results of this trial are expected to be beneficial for CRC screening and may help make colonoscopy a selective procedure used only in populations with a high risk of CRC. Trial registration: This trial (NCT04304131) was registered at ClinicalTrials.gov on March 11, 2020 and is available at https://clinicaltrials.gov/ct2/show/NCT04304131?cond=NCT04304131&draw=2&rank=1.

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