Specific activity of cyclin dependent kinase 1 as a novel predictor of recurrence risk in stage II colon cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 402-402
Author(s):  
M. Maak ◽  
E. Zeestraten ◽  
M. Shibayama ◽  
T. Schuster ◽  
H. Friess ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Specific Activity ◽  
Risk Group ◽  
Tumor Resection ◽  
Recurrence Risk ◽  
High Risk Group ◽  
Stage Ii ◽  
Stage Ii Colon Cancer

402 Background: Altered cell cycle dynamics and check points are typical features of solid tumors, and cyclin dependent kinases (CDKs) play pivotal roles in these processes. Previously we have demonstrated that CDK-based analysis, composed of CDK1 and CDK2, is useful in the prediction of outcomes in early breast cancer patients (Ann Oncol. 19(1):68-72, 2008, Br J Cancer. 100(3):494-500, 2009). Clinically, there is a need for risk stratification in patients with stage II colon cancer who have a recurrence risk of 20 to 30%. Therefore we investigated the use of CDK-based analysis for recurrence prediction of stage II colon cancer patients. Methods: Fresh frozen tissue samples of 254 patients with histologically confirmed adenocarcinoma of the colon, UICC stage II, who received primary tumor resection in Munich (217 cases), and Leiden (37 cases) were used. Protein expression and activity of CDK1 and CDK2 were determined by in vitro assays as previously described. Specific activity (SA) of CDKs was calculated as kinase activity in relation to its corresponding mass concentration. Results: Development of distant metastasis was observed in 27 patients (10.6%) after a median follow up of 86 months. We found that predictive performance of CDK1SA, but not CDK2SA, for the metastasis was substantial and almost constant for long-term event prediction (average area under the curve (AUC) = 0.69). Tumor recurrence risk analysis in association with CDK1SA identified a low- (41% of population) and high- risk group (59%). Cox proportional hazard model analysis retained the CDK-based patient classification as an independent prognostic factor for distant metastases-free survival (low vs. high-risk group: Hazard ratio = 6.2, 95% CI: 1.45 to 26.9, p=0.0049). Clinical parameters such as grading, T-categories, age, and sex were excluded as confounding factors for CDK1SA-risk. Conclusions: CDK1SA allows stratification of different risk subgroups of stage II colon cancer patients. CDK1SA-based analysis is useful for predicting patients with high risk of distant recurrence, who should be treated with chemotherapy. No significant financial relationships to disclose.

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

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS10632-TPS10632
Author(s):  
Ramon Salazar ◽  
John Marshall ◽  
Jaume Capdevila ◽  
Bengt Glimelius ◽  
Jan Willem de Waard ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Colon Cancer ◽  
High Risk ◽  
Prospective Study ◽  
Cancer Patients ◽  
Relapse Rate ◽  
Recurrence Risk ◽  
Low Risk ◽  
Stage Ii ◽  
Stage Ii Colon Cancer

TPS10632 Background: An 18-gene expression profile, ColoPrint, has been developed for identifying colon cancer patients more likely to develop recurrent disease and who would be candidates for adjuvant chemotherapy. The gene signature was validated in public datasets and independent patient cohorts (stage II and III patients). Uni-and multivariate analysis was performed on the pooled stage II patient set (n=320) (median follow-up 70 months). ColoPrint classifies 65% of stage II patients as Low Risk. The 3-year RFS was 91% for Low Risk and 74% for High Risk patients with a HR of 2.9 (p=0.001). ColoPrint was the only significant prognostic marker in the subgroup of patients with T3-MSS phenotype (Tabernero, ASCO GI 2012). Methods: A blinded prospective trial, PARSC (Prospective study for the Assessment of Recurrence risk in Stage II colon cancer 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. (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 (blinded for ColoPrint result). The trial started in Sept. 2008 with currently 32 participating sites in 11 countries. Thus far, 340 eligible stage II and 280 stage III patients have been enrolled. The aim is to enroll 575 stage II patients. Clinical trial registry number: NCT00903565.

Stage II high-risk colon cancer: A retrospective analysis of the benefit of chemotherapy in patient subgroups based on the risk factor.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16068-e16068
Author(s):  
Linu Abraham Jacob
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Risk Group ◽  
Disease Free Survival ◽  
High Risk Group ◽  
Stage Ii ◽  
Resected Stage ◽  
Stage Ii Colon Cancer ◽  
Patient Subgroups

e16068 Background: Adjuvant chemotherapy is routinely recommended for patients with high risk stage II colon cancer. However the risk conferred by each high risk feature (HRF) may be different. This study was done to analyze the magnitude of benefit of chemotherapy in individual HRF patient subgroups. Methods: Resected stage II colon cancer patients during the period January 2012 to March 2018 were retrospectively analyzed for risk features, chemotherapy treatment and survival. Statistical analysis was done with SPSS 16.0. Results: A total of 41 patients were identified as having pathological stage II colon cancer during the study period - 63.4% were males and 36.6%, females. 68.3% had left sided tumor while 31.7% had right sided tumor. 29.3% had none of the high risk features and received no adjuvant chemotherapy. 70.7% patients had at least one of the high risk features and received adjuvant chemotherapy with fluoropyrimidine ± oxaliplatin. 90.2%, 7.3% and 2.5% had stage IIA, IIB and IIC disease respectively. 36.6%, 43.9% and 19.5% had grade I, II and III tumors respectively. Lymphovascular invasion (LVI) and perineural invasion (PNI) were present in 14.6% and 19.5% patients respectively. 29.3% had inadequate lymph node dissection. 22.0% patients had elevated CEA prior to surgery and 4.9% patients had presented with intestinal obstruction. After a minimum follow up period of 20 months the median disease free survival (DFS) was 26 months for the entire cohort. Left sided tumors had significantly prolonged median DFS compared to the right sided tumors (31 vs 26 months; p = 0.05). Median DFS was 24 months for the high risk group compared to 33 months for the low risk group (p = 0.002). On subset analysis T4 HRF subgroup had superior DFS, while LVI HRF subgroup had inferior DFS both of which were statistically significant. Conclusions: Magnitude of chemotherapy benefit was highest in the T4 subgroup, while it was lowest in the LVI subgroup in resected stage II high risk colon cancer [Table: see text]

12-Gene Recurrence Score Assay Stratifies the Recurrence Risk in Stage II/III Colon Cancer With Surgery Alone: The SUNRISE Study

2016 ◽  
Vol 34 (24) ◽  
pp. 2906-2913 ◽  
Author(s):  
Takeharu Yamanaka ◽  
Eiji Oki ◽  
Kentaro Yamazaki ◽  
Kensei Yamaguchi ◽  
Kei Muro ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Risk Group ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
High Risk Group ◽  
Stage Ii ◽  
Stage Iii ◽  
Stage Iiia ◽  
Resected Stage ◽  
Stage Ii Colon Cancer

Purpose The 12-gene Recurrence Score assay has been validated in resected stage II colon cancer treated with or without chemotherapy and resected stage III disease treated with chemotherapy. This study evaluated the 12-gene Recurrence Score assay for stage II and III colon cancer without chemotherapy to reveal the natural course of recurrence risk in stage III disease. Methods A cohort-sampling design was used. From 1,487 consecutive patients with stage II to III disease who had surgery alone, 630 patients were sampled for inclusion with a 1:2 ratio of recurrence and nonrecurrence. Sampling was stratified by stage (II v III). The assay was performed on formalin-fixed, paraffin-embedded primary cancer tissue. Association of the Recurrence Score result with recurrence-free interval (RFI) was assessed by using weighted Cox proportional hazards regression. Results Overall, 597 of 630 patients were analyzable—247 patients had stage II, and 350 had stage III colon cancer. The continuous Recurrence Score was significantly associated with RFI after adjustment for disease stage (hazard ratio for a 25-unit increase in Recurrence Score, 2.05; 95% CI, 1.47 to 2.86; P < .001). With respect to prespecified subgroups, as defined by low (< 30), intermediate (30 to 40), and high (≥ 41) Recurrence Score risk groups, patients with stage II disease in the high-risk group had a 5-year risk of recurrence similar to patients with stage IIIA to IIIB disease in the low-risk group (19% v 20%), whereas patients with stage IIIA to IIIB disease in the high-risk group had a recurrence risk similar to that of patients with stage IIIC disease in the low-risk group (approximately 38%). Conclusion To our knowledge, this study provides the first validation of the 12-gene Recurrence Score assay in stage III colon cancer without chemotherapy and showed the heterogeneity of recurrence risks in stage III as well as in stage II colon cancer.

Abstract CT263: Post-surgical liquid biopsy-guided treatment of stage III and high-risk stage II colon cancer patients: The PEGASUS trial

2020 ◽  
Author(s):  
Elena Elez ◽  
Filippo Pietrantonio ◽  
Andrea Sartore-Bianchi ◽  
Clara Montagut ◽  
Andres Cervantes ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Stage Ii ◽  
Stage Iii ◽  
Stage Ii Colon Cancer

Identifying High-Risk Stage II Colon Cancer Patients: A Three-MicroRNA-Based Score as a Prognostic Biomarker

2016 ◽  
Vol 15 (4) ◽  
pp. e175-e182 ◽  
Author(s):  
Oriol Caritg ◽  
Alfons Navarro ◽  
Isabel Moreno ◽  
Francisco Martínez-Rodenas ◽  
Anna Cordeiro ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Prognostic Biomarker ◽  
Stage Ii ◽  
Stage Ii Colon Cancer

GCC expression in lymph nodes (LNs) as a significant determinant of recurrence in stage II colon cancer (CC) patients (pts).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 369-369 ◽  
Author(s):  
D. J. Sargent ◽  
Q. Shi ◽  
B. M. Bot ◽  
M. B. Resnick ◽  
M. O. Meyers ◽  
...  
Keyword(s):  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cox Regression ◽  
Risk Group ◽  
Recurrence Risk ◽  
High Risk Group ◽  
Stage Ii ◽  
Significant Determinant ◽  
Recurrence Rates ◽  
The Relationship

369 Background: A multi-center prospectively specified retrospective study Validating Indicators to Associate Recurrence (VITAR) is assessing the relationship between guanylyl cyclase C (GCC) gene expression in formalin fixed LNs and recurrence risk in stage II CC pts not treated with adjuvant chemotherapy. Here we report the preplanned initial analysis performed with 241 pts. Methods: GCC mRNA was quantified by RT-qPCR using FFPE LNs tissues from untreated stage II CC pts diagnosed from 1999-2006 with at least 10 LN examined blinded to clinical outcomes. Cox regression models examined the relationship between GCC nodal status and the prespecified primary endpoint of recurrence risk. Results: Twenty-ninepts (12%) had a disease recurrence or cancer death, median follow-up was 60 months and median LNs examined was 15. The ratio of the number of GCC+ LNs over the total number of informative LNs (LNR) significantly predicted higher recurrence risk for 84 pts classified as high risk (HR, 2.38; p=0.02). The estimated 5-yr recurrence rates were 10% and 27% for the low and high risk group, respectively. After adjusting for age, T stage, number of LNs assessed, and MMR status, the significant association remained (HR, 2.61; 95% CI, 1.17-5.83; p=0.02). In a subset of 181 pts with negative margin, T3 tumor only and ≥12 LN examined, the GCC LNR had a HR for recurrence of 5.06 (95% CI 1.61-15.91, p=0.003), translating into 5-yr recurrence rates of 4% among low risk pts and 27% for the high-risk group. Conclusions: Our results suggest that GCC expression in LNs is a significant determinant of recurrence in appropriately staged CC pts not treated with adjuvant chemotherapy. The validation component of the study is ongoing. [Table: see text] [Table: see text]

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.

KRAS Mutation is Associated with Worse Prognosis in Stage III or High-risk Stage II Colon Cancer Patients Treated with Adjuvant FOLFOX

2014 ◽  
Vol 22 (1) ◽  
pp. 187-194 ◽  
Author(s):  
Dae-Won Lee ◽  
Kyung Ju Kim ◽  
Sae-Won Han ◽  
Hyun Jung Lee ◽  
Ye Young Rhee ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Kras Mutation ◽  
Stage Ii ◽  
Stage Iii ◽  
Stage Ii Colon Cancer ◽  
Worse Prognosis

scholarly journals Effect of adjuvant chemotherapy on stage II colon cancer: Analysis of Korean national data.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 798-798
Author(s):  
Minki KIM ◽  
Daeyoun Won ◽  
Seong Taek Oh ◽  
In Kyu Lee
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Quality Assessment ◽  
Cancer Patients ◽  
Risk Group ◽  
Low Risk ◽  
Stage Ii ◽  
Current Status ◽  
National Quality ◽  
Stage Ii Colon Cancer

798 Background: Debates exist regarding the effectiveness of adjuvant chemotherapy for stage II colon cancer. This study aimed to investigate the current status of adjuvant chemotherapy and its impact on survival for Korean stage II colon cancer patients by analyzing the National Quality Assessment data. Methods: A total of 7880 patients who underwent curative resection for stage II colon adenocarcinoma between Jan 2011 and Dec 2014 in Korea were selected randomly as evaluation subjects for the quality assessment. The factors that influenced overall survival were identified. The high-risk group was defined as having at least one of the following: perforation/obstruction, lymph node harvest less than 12, lymphovascular/perineural invasion, positive resection margin, poor differentiation, or pathologic T4 stage. Results: The median follow-up period was 38 (1-63) months. Chemotherapy was a favorable prognostic factor for either the high- (HR 0.50 [0.40-0.62], p < 0.001) or low-risk group (HR 0.74 [0.61-0.89], p = 0.002) in multivariate analysis. This was also the case in patients over 70 years of age. The hazard ratio was significantly increased as the number of involved risk factors was increased in patients who didn’t receive chemotherapy. However, there was no survival difference between low-risk group patients and patients who only had 1 risk factor among patients who received adjuvant chemotherapy (HR 1.19 [0.93-1.52], p = 0.165). Adding oxaliplatin showed no difference in survival (HR 1.36 [0.91-2.03], p = 0.132). Conclusions: Adjuvant chemotherapy can be recommended for stage II colon cancer patients, but the addition of oxaliplatin to the regimen must be selective.

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