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

2017 ◽  
Vol 32 (3) ◽  
pp. 267-273 ◽  
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.

Tumor Budding as an Index to Identify High-Risk Patients with Stage II Colon Cancer

2008 ◽  
Vol 51 (5) ◽  
pp. 568-572 ◽  
Author(s):  
Takatoshi Nakamura ◽  
Hiroyuki Mitomi ◽  
Hideki Kanazawa ◽  
Yasuo Ohkura ◽  
Masahiko Watanabe
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Stage Ii ◽  
Tumor Budding ◽  
High Risk Patients ◽  
Risk Patients ◽  
Stage Ii Colon Cancer

scholarly journals Redefining high-risk patients with stage II colon cancer by risk index and microRNA-21: results from a population-based cohort

2014 ◽  
Vol 111 (7) ◽  
pp. 1285-1292 ◽  
Author(s):  
T F Hansen ◽  
S Kjær-Frifeldt ◽  
R D Christensen ◽  
S Morgenthaler ◽  
T Blondal ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Risk Index ◽  
Population Based ◽  
Stage Ii ◽  
High Risk Patients ◽  
Risk Patients ◽  
Stage Ii Colon Cancer

Independent validation of a prognostic genomic profile (ColoPrint) for stage II colon cancer (CC) patients.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 358-358 ◽  
Author(s):  
R. Rosenberg ◽  
M. Maak ◽  
I. Simon ◽  
U. Nitsche ◽  
T. Schuster ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Distant Metastasis ◽  
Stage Ii ◽  
Genomic Profile ◽  
High Risk Patients ◽  
Independent Validation ◽  
Risk Patients ◽  
Stage Ii Colon Cancer

358 Background: Adjuvant therapy is not routinely recommended for stage II CC patients but may be considered for high-risk patients. In this study we aim to independently validate a genomic profile that was developed to identify high-risk patients and can assist in treatment decisions. Methods: An 18-gene profile had been developed using gene expression data from whole genome Agilent 44K oligonucleotide arrays and was validated in samples from an independent cohort of 206 CC patients and in in-silico datasets (Salazar et al. JCO 2010 in press). The profile was translated into a robust diagnostic test (ColoPrint) using customized 8-pack arrays. For this study, 233 patients who underwent curative resection (R0) for colon cancer stages II or III at the Klinikum rechts der Isar from 1987 to 2003 were selected. Fresh frozen tissues, clinical parameters and follow-up data for all patients were available. The samples were hybridized and the ColoPrint index was determined for all samples blinded from the clinical data. Results: Patients in this study had a median age of 64 years and median follow-up of 97 months. The median number of resected lymph nodes was 21, giving an indirect measure of the quality of surgery. In the 135 stage II patients, ColoPrint identified most patients (73%) as low risk. The 5-year distant-metastasis free survival was 95% for low-risk patients and 80% for high-risk patients. In the univariate analysis, ColoPrint was the only significant parameter to predict the development of distant metastasis with a HR of 4.1 (95% CI 1.31-13.01, p=0.009). Using clinical parameters from the ASCO recommendation (T4, perforation, less than 12 LN assessed and/ or high grade) for the identification of high-risk patients was not significant (HR 2.3; 95% CI 0.68-7.53, p=0.18) and did not add power to the ColoPrint classification. These results are in good agreement with results from the first independent validation. Conclusions: ColoPrint is able to predict the development of distant metastasis of stage II colon cancer patients and facilitates the identification of patients who may be safely managed without chemotherapy. [Table: see text]

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

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 378-378 ◽  
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

Identification of risk factors for stage II colon cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 375-375
Author(s):  
Sho Sawazaki ◽  
Manabu Shiozawa ◽  
Koji Numata ◽  
Masakatsu Numata ◽  
Teni Godai ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Disease Free Survival ◽  
Lymphatic Invasion ◽  
Clinicopathological Features ◽  
Stage Ii ◽  
Tumor Diameter ◽  
Free Survival ◽  
Stage Ii Colon Cancer ◽  
Disease Free

375 Background: The use of adjuvant chemotherapy remains controversial in Stage II colon cancer. However, patients with specific clinicopathological features are thought to have high risk for recurrence. The aim of this study was to identify the subgroup of patients at great risk, by investigating the clinicopathological features associated with poor survived in Stage II. Methods: A total of 282 patients with Stage II colon cancer who underwent curative resection from January 1990 to September 2007 at Kanagawa Cancer Center were enrolled. Then, the clinicopathological data of the patients were retrospectively evaluated. Disease-free survival rates were calculated by the Kaplan-Meier method, and survival curves were compared by the log-rank test. Cox’s regression analysis was used for multivariate analyses. P values <0.05 were considered to be statistically significant. Results: The median follow up was 62.5 months. The 5-year disease-free survival was 92.2% in the study group as a whole. Among the recurrent patients (n=23), the most recurrent site was the liver (n=11, 44%), followed by lung (n=6, 24%), and peritoneum (n=5, 20%). Univariate analysis for 5-year disease-free survival identified two factors; tumor diameter (>5cm vs…5cm, p=0.018), and lymphatic invasion (p=0.009). Multivariate analysis for 5-year disease-free survival identified two independent factors; tumor diameter (hazard ratio [HR], 4.82; 95% CI, 1.55-15.0; p=0.006), and lymphatic invasion (HR, 4.15; 95% CI, 1.68-10.2; p=0.002). The 5-year disease-free survival differed significantly among patients with neither of these prognostic factors (98.6%), those with only 1 factor (93.3%), and those with 2 factors (76.6%, p=0.000). Conclusions: Patients with stage II colon cancer who have both 5cm in diameter and lymphatic invasion are at high risk for recurrence. The use of adjuvant chemotherapy should be considered in this subgroup of patients.

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

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.

The PARSC trial, a prospective study for the assessment of recurrence risk in stage II colon cancer (CC) patients using ColoPrint.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 678-678 ◽  
Author(s):  
Ramon Salazar ◽  
Jan Willem de Waard ◽  
Bengt Glimelius ◽  
John Marshall ◽  
Joost Klaase ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Colon Cancer ◽  
High Risk ◽  
Prospective Study ◽  
Relapse Rate ◽  
Recurrence Risk ◽  
Low Risk ◽  
Stage Ii ◽  
Risk Patients ◽  
Stage Ii Colon Cancer

678 Background: An 18-gene expression profile, ColoPrint, has been developed for identifying CC patients more likely to develop recurrent disease and who would be candidates for adjuvant chemotherapy. The gene signature was validated in in-silico datasets and independent patient cohorts of stage II and III patients. Uni-and multivariate analysis was performed on the pooled stage II patient set (n=320) who had a median follow-up of 70 months. ColoPrint identified two-third of the stage II patients (209/320) as low risk. The 3-year relapse-free survival was 94% for Low Risk patients and 79% for High Risk patients with a HR of 2.74 (95% CI 1.54 - 4.88; p=0.006). Moreover, the profile stratified patients independent of ASCO clinical risk factors. Methods: A prospective trial, PARSC (Prospective study for the Assessment of Recurrence risk in Stage II CC patients) using ColoPrint has been initiated. Objectives are: (1) to validate the performance of ColoPrint in estimating the 3-year relapse rate in patients with stage II colon cancer; (2) to compare the risk assessment in stage II patients using the ColoPrint profile vs. a clinical risk assessment based on Investigator’s assessment of risk and ASCO high-risk recommendations; (3) to investigate therapy as a potential confounding factor for ColoPrint results; and (4) to assess the performance of ColoPrint in estimating the 3-year relapse rate in patients with stage III colon cancer. Inclusion criteria: age ≥ 18 years, adenocarcinoma of the colon, stage II and III, no prior neo-adjuvant therapy, no synchronous tumors, fresh tumor sample, and written informed consent. The treatment of the patient is at the discretion of the physician adhering to National Comprehensive Cancer Network (NCCN)-approved regimens or a recognized alternative. Results: The trial started in Sept. 2008 with currently 30 participating sites in 11 countries. Thus far, 288 eligible stage 2 and 251 stage 3 patients have been enrolled. Conclusions: The aim is to enroll 575 stage II patients to differentiate between 3 year RFS predicted by ColoPrint and clinical factors.

Impact of high-risk features on disease-free survival (DFS) in patients (pts) with high-risk stage II colon cancer (CC) in ACHIEVE-2 trial as part of the IDEA collaboration.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4011-4011
Author(s):  
Dai Manaka ◽  
Manabu Shiozawa ◽  
Masahito Kotaka ◽  
Makio Gamoh ◽  
Akio Shiomi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Vascular Invasion ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Nodal Harvest ◽  
Poorly Differentiated ◽  
Stage Ii Colon Cancer ◽  
Disease Free

4011 Background: The IDEA collaboration for high-risk stage 2 colorectal cancer patients (pts) demonstrated that for CAPOX, 3 months was non-inferior to 6 months treatment, while for FOLFOX, 6 months was superior to 3 months treatment. We investigated the impact of high risk features on disease-free survival (DFS). Methods: ACHIEVE-2, one of the 4 IDEA studies (SCOT, TOSCA, ACHIEVE-2, HORG), was an open-label, multicenter randomized trial for high-risk stage II colon cancer. High risk features are defined as one or more: T4, inadequate nodal harvest < 12, poorly differentiated, clinical sign of obstruction and perforation or vascular invasion. The association of high risk features with DFS were measured by Cox regression analyses. Results: Between 2014 and 2017, ACHIEVE-2 enrolled 525 pts, out of whom 514 pts were the modified ITT (mITT) population; 432 received CAPOX (84.0%) and 82 did mFOLFOX6 (16.0%). High-risk features included 35.8% of T4, 12.8% of inadequate nodal harvest, 11.5% of poorly differentiated, 19.3% of obstruction, 6.4% of perforation and 87.5% of vascular invasion; 47.3% had one features, 35.2% had two, 14.6% had three, and 2.9% had four or more. With a median follow-up of 36.1 months, 3-year DFS rates were 88% in both arms, with a hazard ratio (HR) of 1.12 (95% CI, 0.67-1.87, p=0.67). In multivariate analysis, T4 (HR 3.77 [2.18-6.53], p< 0.0001) and inadequate nodal harvest (HR 2.98 [1.59-5.59], p= 0.0006) remained independent significant negative prognostic factors. The 3-year DFS rates in T4 and Non-T4 diseases were 78% and 94% (p<0.0001), while 3-year DFS rate in pts with inadequate and adequate nodal harvest were 77% and 90% (p=0.0059). No interaction was observed between treatment duration and T4 or inadequate nodal harvest. Conclusions: Our findings indicated the relative impact of high risk features on DFS varies across factors; T4 and inadequate nodal harvest < 12 were more significant than the others. Our results must be interpreted within the combined analysis as well as within the reproducibility of results across the 4 trials. Clinical trial information: 000013036 .

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