Tumour budding in preoperative biopsy specimens is a useful prognostic index for identifying high-risk patients in early-stage (pN0) colon cancer

Abstract Follicular lymphoma is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. The natural history of FL appears to have been favorably impacted by the introduction of rituximab after randomized clinical trials demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival. Yet, the disease is biologically and clinically heterogeneous with wide variations in outcomes for individual patients. The ability to accurately risk-stratify patients and then tailor therapy to the individual is an area of ongoing research. Historically, tumor grade, tumor burden, and the FL international prognostic index (version 1 and version 2) have been used to distinguish low-risk from high-risk patients. Biologic factors such as mutations in key genes can identify patients at high risk for poor outcomes to first-line therapy (mutational status of 7 genes [EZH2, ARID1A, MEF2B, EP300, FOX01, CREBBP, and CARD11] with Follicular Lymphoma International Prognostic Index). More recently, the quality of the response to initial therapy, as measured by either PET imaging or by remission duration, has been show to identify individuals at high risk. However, several unmet needs remain, including a better ability to identify high-risk patients at diagnosis, the development of predictive biomarkers for targeted agents, and strategies to reduce the risk of transformation.

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Outcomes After Surgery in High-Risk Patients With Early Stage Lung Cancer

The Annals of Thoracic Surgery ◽

10.1016/j.athoracsur.2015.08.088 ◽

2016 ◽

Vol 101 (3) ◽

pp. 1043-1051 ◽

Cited By ~ 14

Author(s):

Manu S. Sancheti ◽

John N. Melvan ◽

Rachel L. Medbery ◽

Felix G. Fernandez ◽

Theresa W. Gillespie ◽

...

Keyword(s):

Lung Cancer ◽

High Risk ◽

Early Stage ◽

Early Stage Lung Cancer ◽

High Risk Patients ◽

Risk Patients ◽

Stage Lung Cancer

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Use of a Combination of CEA and Tumor Budding to Identify High-risk Patients with Stage II Colon Cancer

The International Journal of Biological Markers ◽

10.5301/jbm.5000255 ◽

2017 ◽

Vol 32 (3) ◽

pp. 267-273 ◽

Cited By ~ 3

Author(s):

Changzheng Du ◽

Weicheng Xue ◽

Fangyuan Dou ◽

Yifan Peng ◽

Yunfeng Yao ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Disease Progression ◽

Disease Free Survival ◽

Stage Ii ◽

Tumor Budding ◽

High Risk Patients ◽

Prognostic Accuracy ◽

Risk Patients ◽

Stage Ii 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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Effect of calcium supplementation on mucosal cell proliferation in high risk patients for colon cancer.

Gut ◽

10.1136/gut.30.3.376 ◽

1989 ◽

Vol 30 (3) ◽

pp. 376-382 ◽

Cited By ~ 58

Author(s):

R C Gregoire ◽

H S Stern ◽

K S Yeung ◽

J Stadler ◽

S Langley ◽

...

Keyword(s):

Colon Cancer ◽

Cell Proliferation ◽

High Risk ◽

Calcium Supplementation ◽

Mucosal Cell ◽

High Risk Patients ◽

Risk Patients ◽

Mucosal Cell Proliferation

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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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O124 A BLOOD-BASED 3-GENE SIGNATURE WITH SUFFICIENT SENSITIVITY AND SPECIFICITY TO DETECT EARLY STAGE HUMAN HEPATOCELLULAR CARCINOMA IN HIGH-RISK PATIENTS WITH CHRONIC HEPATITIS AND CIRRHOSIS

Journal of Hepatology ◽

10.1016/s0168-8278(14)60126-4 ◽

2014 ◽

Vol 60 (1) ◽

pp. S52

Author(s):

K. Hui

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

High Risk ◽

Sensitivity And Specificity ◽

Early Stage ◽

Gene Signature ◽

Human Hepatocellular Carcinoma ◽

High Risk Patients ◽

Risk Patients

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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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