scholarly journals Adjuvant chemotherapy use and outcomes of patients with high-risk versus low-risk stage II colon cancer

Cancer ◽  
2014 ◽  
Vol 121 (4) ◽  
pp. 527-534 ◽  
Author(s):  
Aalok Kumar ◽  
Hagen F. Kennecke ◽  
Daniel J. Renouf ◽  
Howard J. Lim ◽  
Sharlene Gill ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Low Risk ◽  
Stage Ii ◽  
Stage Ii Colon Cancer

Development and validation of a robust prognostic and predictive signature for colorectal cancer (CRC) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4036-4036
Author(s):  
A. M. Glas ◽  
P. Roepman ◽  
R. Salazar ◽  
G. Capella ◽  
V. Moreno ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Gene Signature ◽  
Low Risk ◽  
Stage Ii ◽  
Significant Difference ◽  
Independent Cohort

4036 Background: Between 25 and 35% of stage II CRC patients will experience a recurrence of their disease and may benefit from adjuvant chemotherapy. Official guidelines give suggestions but no clear recommendation for best risk stratification. Here we describe the development a robust signature that predicts disease relapse and can assist in treatment decisions. Methods: Fresh frozen tumor tissues from 180 patients with stage I, II and III colorectal cancer undergoing surgery were analyzed using high density Agilent 44K oligonucleotide arrays. Median FU was 70.2 months; 85% of patients did not receive adjuvant chemotherapy. Unsupervised hierarchical clustering based on full-genome gene expression measurement indicated the existence of 3 main colon molecular subclasses. Survival analysis of the 3 classes showed that subtype C (n= 27) had a poor outcome and subtype A (n= 48) good outcome. Only the intermediate group B (n=104) was used to develop a signature by using a cross validation procedure to score all genes for their association with 5-yr distant metastasis free survival (DMFS) and subsequently applied to all samples (n=180). The obtained gene signature was further validated on an independent cohort of 178 stage II + III colon samples. Results: A set of 38 prognosis related gene probes showed robust DMFS association in over 50% of all iterations in the Training Set of 180 samples. The gene signature was validated on an independent cohort of 178 samples from stage II + III colon cancer patients. The profile classified 61% of the validation samples as low-risk and 39% as high-risk. The low- and high-risk samples showed a significant difference in DMFS with a HR of 3.19 (P= 8.5e-4). Five-year DMFS rates were 89% (95%CI 83–95) for low-risk and 62% (95%CI 50–77) for high-risk samples. Moreover, the profile showed a significant performance within stage II (P=0.0058) and III (P=0.036) only samples. The performance of the profile was significant for both untreated (P=0.0082) and treated patients (P=0.016) suggesting that its power is independent of treatment benefits. Conclusions: ColoPrint is able to predict the prognosis of stage II and III colon cancer patients and facilitates the identification of patients who would benefit from adjuvant 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

American Society of Clinical Oncology Recommendations on Adjuvant Chemotherapy for Stage II Colon Cancer

2004 ◽  
Vol 22 (16) ◽  
pp. 3408-3419 ◽  
Author(s):  
Al B. Benson ◽  
Deborah Schrag ◽  
Mark R. Somerfield ◽  
Alfred M. Cohen ◽  
Alvaro T. Figueredo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Clinical Oncology ◽  
Meta Analysis ◽  
Indirect Evidence ◽  
Stage Ii ◽  
Prognostic Features ◽  
American Society ◽  
Stage Ii Colon Cancer

Purpose To address whether all medically fit patients with curatively resected stage II colon cancer should be offered adjuvant chemotherapy as part of routine clinical practice, to identify patients with poor prognosis characteristics, and to describe strategies for oncologists to use to discuss adjuvant chemotherapy in practice. Methods An American Society of Clinical Oncology Panel, in collaboration with the Cancer Care Ontario Practice Guideline Initiative, reviewed pertinent information from the literature through May 2003. Results A literature-based meta-analysis found no evidence of a statistically significant survival benefit of adjuvant chemotherapy for stage II patients. Recommendations The routine use of adjuvant chemotherapy for medically fit patients with stage II colon cancer is not recommended. However, there are populations of patients with stage II disease that could be considered for adjuvant therapy, including patients with inadequately sampled nodes, T4 lesions, perforation, or poorly differentiated histology. Conclusion Direct evidence from randomized controlled trials does not support the routine use of adjuvant chemotherapy for patients with stage II colon cancer. Patients and oncologists who accept the relative benefit in stage III disease as adequate indirect evidence of benefit for stage II disease are justified in considering the use of adjuvant chemotherapy, particularly for those patients with high-risk stage II disease. The ultimate clinical decision should be based on discussions with the patient about the nature of the evidence supporting treatment, the anticipated morbidity of treatment, the presence of high-risk prognostic features on individual prognosis, and patient preferences. Patients with stage II disease should be encouraged to participate in randomized trials.

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.

Tumor-associated macrophages as predictive biomarkers for postoperative adjuvant chemotherapy in patients with stage II colon cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 620-620
Author(s):  
Jianmin Xu ◽  
Qingyang Feng ◽  
Wenju Chang ◽  
Ye Wei ◽  
Li Ren ◽  
...  
Keyword(s):  
Risk Factors ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Stage Ii ◽  
Tumor Associated Macrophages ◽  
Postoperative Adjuvant Chemotherapy ◽  
Patient Counselling ◽  
High Risk Factors ◽  
Stage Ii Colon Cancer

620 Background: For stage II colon cancer, the effect of postoperative adjuvant chemotherapy is still controversial. It is well known that tumor-associated macrophages (TAMs) play an important role in tumor progression. The aim of this study is to determine the effect of TAMs as predictor for adjuvant chemotherapy for stage II colon cancer. Methods: From July 2009 to June 2012, 521 patients with pathological stage II colon cancer were included. TAMs were detected using tissue microarray and immunohistochemistry (all TAMs detected by CD68; M2 subtype detected by CD206). The density of CD68+ TAMs, CD206+ TAMs and the ratio of CD206+ TAMs / CD68+ TAMs (CD206 / CD68 ratio) were calculated. The cut-off values were defined using X-Tile software. Results: High CD206+ TAMs density and high CD206 / CD68 ratio were significantly associated with reduced disease-free survival (DFS, P < 0.001 and P < 0.001, respectively) and overall survival (OS, P < 0.001 and P < 0.001, respectively). And CD206 / CD68 ratio had a better prognostic power. Furthermore, for patients with low CD206 / CD68 ratio, adjuvant chemotherapy made no benefit. But for high CD206 / CD68 ratio, adjuvant chemotherapy significantly improved DFS and OS (as shown in Table 1). In subgroup analysis, for T3 with high-risk factors or T4 tumors, CD206 / CD68 ratio was also a significant predictor for adjuvant chemotherapy (interaction P = 0.024 in DFS). Conclusions: For stage II colon cancer, CD206 / CD68 ratio was a good prognostic and predictive biomarker for adjuvant chemotherapy. Together with clinicopathological high-risk factors, it might facilitate patient counselling and individualise management. [Table: see text]

Clinical utility of the systemic inflammatory response (SIR) in identifying high-risk stage II colon cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 220-220
Author(s):  
Allan Matthew Golder ◽  
Donald C. McMillan ◽  
David Mansouri ◽  
Paul G. Horgan ◽  
Campbell SD Roxburgh
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Stage Ii ◽  
Margin Involvement ◽  
Nodal Harvest ◽  
T Stage ◽  
Emergency Presentation ◽  
Stage Ii Colon Cancer

220 Background: Surgery for TNM Stage II colon cancer is considered curative however approximately 20% of patients will have recurrence of their disease. A number of high risk pathological features guide the use of adjuvant chemotherapy. More recently the preoperative SIR has been consistently shown to have prognostic value but to date has not been utilised clinically as a high risk feature. The present study compared the influence of the SIR versus established high-risk clinical features on overall/cancer specific survival (OS/CSS). Methods: Patients in the West of Scotland undergoing curative resection for Stage II colon cancer from 2011-2015 were identified with survival updated until December 2018. Additional data was obtained from online records. Through uni/multivariate analysis (UVA/MVA) we compared the effect on survival of the SIR measured using the modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) when entered individually into a multivariate model alongside established high-risk features. Results: 982 patients were identified having had a curative resection of Stage II colon cancer. Median follow up was 61 months and there were 307 deaths during follow up. For OS: emergency presentation, T stage, adjuvant chemotherapy, nodal harvest, margin involvement, mGPS, LMR, NLR (all p≤0.001) and EMVI (p < 0.05) were significant on UVA. On MVA: age (HR 1.51), T stage (HR 1.59), nodal harvest (HR 1.67), margin involvement (HR 1.94), adjuvant chemotherapy (HR 0.47), mGPS (HR 1.38), NLR (HR 1.35) and LMR (HR 1.50) remained significant (all p < 0.05). For CSS: age, emergency presentation, T stage, margin involvement, mGPS, NLR, LMR (all p < 0.001), nodal harvest and adjuvant chemotherapy (both p < 0.05) remained significant on UVA. On MVA emergency presentation (HR 1.88), T stage (HR 2.02), margin involvement (HR 2.98), adjuvant chemotherapy (HR 0.51) and mGPS (HR 1.34) remained significant (all p < 0.05). Conclusions: The present study suggests that the SIR is an independent predictor of worse OS/CSS in Stage II colon cancer and should be considered a high risk feature in future prospective studies.

Kolonkarzinom: Was und wem nützt die Chemotherapie?

2018 ◽  
Vol 50 (03) ◽  
pp. 120-123
Keyword(s):  
Risk Factors ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Stage Ii ◽  
High Risk Factors ◽  
Stage Ii Colon Cancer

Verhoeff SR, van Erning FN, Lemmens V et al. Adjuvant chemotherapy is not associated with improved survival for all high-risk factors in stage II colon cancer. Int J Cancer 2016; 139: 187–193. doi:10.1002/ijc.30053

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