Effect of folate supplementation on mucosal cell proliferation in high risk patients for colon cancer

Background High-risk patients with stage II colon cancer may benefit from adjuvant chemotherapy, but identifying this patient population can be difficult. We assessed the prognosis value for predicting tumor progression in patients with stage II colon cancer, of a panel of 2 biomarkers for colon cancer: tumor budding and preoperative carcinoembryonic antigen (CEA). Methods Consecutive patients (N = 134) with stage II colon cancer who underwent curative surgery from 2000 to 2007 were included. Multivariate analysis was used to evaluate the association of CEA and tumor budding grade with 5-year disease-free survival (DFS). The prognostic accuracy of CEA, tumor budding grade and the combination of both (CEA-budding panel) was determined. Results The study found that both CEA and tumor budding grade were associated with 5-year DFS. The prognostic accuracy for disease progression was higher for the CEA-budding panel (82.1%) than either CEA (70.9%) or tumor budding grade (72.4%) alone. Conclusions The findings indicate that the combination of CEA levels and tumor budding grade has greater prognostic value for identifying patients with stage II colon cancer who are at high-risk for disease progression, than either marker alone.

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Genomic classifiers (ColoPrint/MSI-Print) predict outcome and chemotherapy benefit in stage II and III colon cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.378 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 378-378 ◽

Cited By ~ 2

Author(s):

Scott Kopetz ◽

Zhi-Qin Jiang ◽

Michael J. Overman ◽

Christa Dreezen ◽

Sun Tian ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Additional Treatment ◽

Low Risk ◽

Stage Ii ◽

High Risk Patients ◽

Risk Patients

378 Background: Although the benefit of chemotherapy in stage II and III colon cancer patients is significant, many patients might not need adjuvant chemotherapy because they have a good prognosis even without additional treatment. ColoPrint is a gene expression classifier that distinguish patients with low or high risk of disease relapse. It was developed using whole genome expression data and has been validated in public datasets, independent European patient cohorts and technical studies (Salazar 2011 JCO, Maak 2012 Ann Surg). Methods: In this study, the commercial ColoPrint test was validated in stage II (n=96) and III patients (n=95) treated at the MD Anderson Cancer Center from 2003 to 2009. Frozen tissue specimen, clinical parameters, MSI-status and follow-up data (median follow-up 64 months) were available. The 64-gene MSI-signature developed to identify patients with deficient mismatch repair system (Tian 2012 J Path) was evaluated for its accuracy to identify MSI patients and also for prognosis. Results: In this cohort, ColoPrint classified 56% of stage II and III patients as being at low risk. The 3-year Relapse-Free-Survival (RFS) was 90.6% for Low Risk and 78.4% for High Risk patients with a HR of 2.33 (p=0.025). In uni-and multivariate analysis ColoPrint and stage were the only significant factors to predict outcome. The MSI-signature classified 47 patients (24.6%) as MSI-H and most MSI-H patients were ColoPrint low risk (81%). Patients who were ColoPrint low risk and MSI-H by signature had the best outcome with a 3-year RFS of 95% while patients with ColoPrint high risk had a worse outcome independently of the MSI-status. Low risk ColoPrint patients had a good outcome independent of stage or chemotherapy treatment (90.1% 3-year RFS for treated patients, 91.4% for untreated patients) while ColoPrint high risk patients treated with adjuvant chemotherapy had 3-year RFS of 84%, compared to 70.1% 3-year RFS in untreated patients (p=0.026). Conclusions: The combination of ColoPrint and MSI-Print improves the prognostic accuracy in stage II and stage III patients and may help the identification of patients at higher risk who are more likely to benefit from additional treatment

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6070 POSTER Non Elective Colon Cancer Resections in the Dutch Surgical Colorectal Audit, a Scoring System to Identify High Risk Patients

European Journal of Cancer ◽

10.1016/s0959-8049(11)71715-4 ◽

2011 ◽

Vol 47 ◽

pp. S412

Author(s):

N. Kolfschoten ◽

M.W.J.M. Wouters ◽

G.A. Gooiker ◽

E.H. Eddes ◽

J. Kievit ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Scoring System ◽

High Risk Patients ◽

Risk Patients ◽

Elective Colon

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Presence of a High Amount of Stroma and Downregulation of SMAD4 Predict for Worse Survival for Stage I–II Colon Cancer Patients

Analytical Cellular Pathology ◽

10.1155/2009/214085 ◽

2009 ◽

Vol 31 (3) ◽

pp. 169-178

Author(s):

Wilma E. Mesker ◽

Gerrit-Jan Liefers ◽

Jan M. C. Junggeburt ◽

Gabi W. van Pelt ◽

Paola Alberici ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Disease Free Survival ◽

Tumor Stroma ◽

High Risk Group ◽

Stage I ◽

Prognostic Information ◽

Mesenchymal Transition ◽

High Risk Patients ◽

Risk Patients

Background: For stage I–II colon cancer a significant number (5–25%) of patients has recurrent disease within 5 years. There is need to identify these high-risk patients as they might benefit from additional treatment.Stroma-tissue surrounding the cancer cells plays an important role in the tumor behavior. The proportion of intra-tumor stroma was evaluated for the identification of high-risk patients. In addition, protein expression of markers involved in pathways related to stroma production and epithelial-to-mesenchymal transition (EMT) was analyzed: β-catenin, TGF-β-R2 and SMAD4.Methods: In a retrospective study of 135 patients with stage I–II colon cancer, the amount of stroma was estimated on routine haematoxylin–eosin stained histological sections. Sections were also immunohistochemically stained for β-catenin, TGF-β-R2 and SMAD4.Results: Of 135 analyzed patients 34 (25.2%) showed a high proportion of stroma (stroma-high) and 101 (74.8%) a low proportion (stroma-low). Significant differences in overall-survival and disease-free-survival were observed between the two groups, with stroma-high patients showing poor survival (OS p < 0.001, HZ 2.73, CI 1.73–4.30; DFS p < 0.001, HZ 2.43, CI 1.55–3.82). A high-risk group was identified with stroma-high and SMAD4 loss (OS p = 0.008, HZ 7.98, CI 4.12–15.44, DFS p = 0.005, HZ 6.57, CI 3.43–12.56); 12 of 14 (85.7%) patients died within 3 years. In a logistic-regression analysis a high proportion of stroma and SMAD4 loss were strongly related (HZ 5.42, CI 2.13–13.82, p < 0.001).Conclusion: Conventional haematoxylin–eosin stained tumor slides contain more prognostic information than previously fathomed. This can be unleashed by assessing the tumor–stroma ratio. The combination of analyzing the tumor–stroma ratio and staining for SMAD4 results in an independent parameter for confident prediction of clinical outcome.

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OC.04.3 GENETIC PREDISPOSITION TO COLON CANCER IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: NGS APPROACH TO IDENTIFY HIGH RISK PATIENTS

Digestive and Liver Disease ◽

10.1016/s1590-8658(19)30155-0 ◽

2019 ◽

Vol 51 ◽

pp. e87

Author(s):

G. Biscaglia ◽

O. Palmieri ◽

A. Latiano ◽

S. Castellana ◽

F. Bossa ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Colon Cancer ◽

High Risk ◽

Genetic Predisposition ◽

Bowel Disease ◽

High Risk Patients ◽

Risk Patients ◽

Inflammatory Bowel

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Prognostic analysis and beneficiary identification of adjuvant external beam radiotherapy for stage pT4b sigmoid colon cancer

Scientific Reports ◽

10.1038/s41598-021-91172-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yaobin Lin ◽

Lei Wang ◽

Lingdong Shao ◽

Xueqing Zhang ◽

Huaqin Lin ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Risk Stratification ◽

Sigmoid Colon ◽

External Beam Radiotherapy ◽

Sigmoid Colon Cancer ◽

High Risk Patients ◽

Risk Patients ◽

Stratification System ◽

Risk Stratification System

AbstractThe clinical efficacy of adjuvant radiotherapy in sigmoid colon cancer remains questioned. To evaluate the clinical efficacy of adjuvant external beam radiotherapy (EBRT) for patients with pathologic stage T4b sigmoid colon cancer. Patients with stage pT4b sigmoid colon cancer receiving adjuvant EBRT or not followed by surgery between 2004 and 2016 were extracted from the Surveillance, Epidemiology, and End Results database. Analysis of overall survival (OS) was performed using Kaplan–Meier curves and prognostic factors were identified using Cox proportional hazards regression models with 95% confidence intervals within the entire cohort. A risk-stratification system was then developed based on the β regression coefficient. Among 2073 patients, 284 (13.7%) underwent adjuvant EBRT. The median OS in the group receiving adjuvant EBRT was significantly longer than that in the non-radiotherapy group (p < 0.001). Age, serum carcinoembryonic antigen (CEA) level, perineural invasion, lymph node dissection (LND) number, and adjuvant EBRT were independent factors associated with OS. A risk‐stratification system was generated, which showed that low‐risk patients had a higher 5-year survival rate than high-risk patients (75.6% vs. 42.3%, p < 0.001). Adjuvant EBRT significantly prolonged the 5-year survival rate of high-risk patients (62.6% vs. 38.3%, p = 0.009) but showed no survival benefit among low‐risk patients (87.7% vs. 73.2%, p = 0.100). Our risk‐stratification model comprising age, serum CEA, perineural invasion, and LND number predicted the outcomes of patients with stage pT4b sigmoid colon cancer based on which subgroup of high-risk patients should receive adjuvant EBRT.

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