The PEGASUS Trial in Stage III and High-risk Stage II Colon Cancer Patients

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.

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PRODIGE 50 - ASPIK French: French double blind randomised study of aspirin versus placebo in resected stage III or high risk stage II colon cancer with PIK3CA mutation

Annals of Oncology ◽

10.1093/annonc/mdx393.134 ◽

2017 ◽

Vol 28 ◽

pp. v206

Author(s):

P. Michel ◽

T. André ◽

V. Boige ◽

T. Aparicio ◽

E. Maillard ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Pik3ca Mutation ◽

Stage Ii ◽

Stage Iii ◽

Double Blind ◽

Randomised Study ◽

Resected Stage ◽

Stage Ii Colon Cancer

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Aspirin versus placebo in stage III or high-risk stage II colon cancer with PIK3CA mutation: A French randomised double-blind phase III trial (PRODIGE 50-ASPIK)

Digestive and Liver Disease ◽

10.1016/j.dld.2017.12.023 ◽

2018 ◽

Vol 50 (3) ◽

pp. 305-307 ◽

Cited By ~ 4

Author(s):

Pierre Michel ◽

Valerie Boige ◽

Thierry Andre ◽

Thomas Aparicio ◽

Jean Baptiste Bachet ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Pik3ca Mutation ◽

Stage Ii ◽

Phase Iii ◽

Stage Iii ◽

Double Blind ◽

Phase Iii Trial ◽

Stage Ii Colon Cancer

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Adjuvant systemic chemotherapy for stages II and III colon cancer after complete resection: a clinical practice guideline

Current Oncology ◽

10.3747/co.23.3330 ◽

2016 ◽

Vol 23 (6) ◽

pp. 418 ◽

Cited By ~ 15

Author(s):

B.M. Meyers ◽

R. Cosby ◽

F. Quereshy ◽

D. Jonker

Keyword(s):

Colon Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Practice Guideline ◽

Stage Ii ◽

Stage Iii ◽

Cochrane Library ◽

Stage Iii Colon Cancer ◽

Resected Stage ◽

Stage Ii Colon Cancer

Background Updated practice guidelines on adjuvant chemotherapy for completely resected colon cancer are lacking. In 2008, Cancer Care Ontario’s Program in Evidence-Based Care developed a guideline on adjuvant therapy for stages ii and iii colon cancer. With newer regimens being assessed in this patient population and older agents being either abandoned because of non-effectiveness or replaced by agents that are more efficacious, a full update of the original guideline was undertaken.Methods Literature searches (January 1987 to August 2015) of medline, embase, and the Cochrane Library were conducted; in addition, abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress were reviewed (the latter for January 2007 to August 2015). A practice guideline was drafted that was then scrutinized by internal and external reviewers whose comments were incorporated into the final guideline.Results Twenty-six unique reports of eighteen randomized controlled trials and thirteen unique reports of twelve meta-analyses or pooled analyses were included in the evidence base. The 5 recommendations developed included 3 for stage ii colon cancer and 2 for stage iii colon cancer.Conclusions Patients with completely resected stage iii colon cancer should be offered adjuvant 5-fluorouracil (5fu)–based chemotherapy with or without oxaliplatin (based on definitive data for improvements in survival and disease-free survival). Patients with resected stage ii colon cancer without “high-risk” features should not receive adjuvant chemotherapy. For patients with “high-risk” features, 5fu-based chemotherapy with or without oxaliplatin should be offered, although no clinical trials have been conducted to conclusively demonstrate the same benefits seen in stage iii colon cancer.

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Sidedness influences prognosis in stage III but not in stage II colon cancer patients receiving an adjuvant therapy: A GISCAD analysis from three randomized trials including 5234 patients

Annals of Oncology ◽

10.1093/annonc/mdx393.008 ◽

2017 ◽

Vol 28 ◽

pp. v161

Author(s):

S. Cascinu ◽

D. Poli ◽

A. Zaniboni ◽

R. Labianca ◽

A. Sobrero ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Therapy ◽

Cancer Patients ◽

Randomized Trials ◽

Stage Ii ◽

Stage Iii ◽

Stage Ii Colon Cancer

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Deletion of Chromosome 4q Predicts Outcome in Stage II Colon Cancer Patients

Analytical Cellular Pathology ◽

10.1155/2010/161608 ◽

2010 ◽

Vol 33 (2) ◽

pp. 95-104 ◽

Cited By ~ 5

Author(s):

R. P. M. Brosens ◽

E. J. T. H. Belt ◽

J. C. Haan ◽

T. E. Buffart ◽

B. Carvalho ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Cancer Patients ◽

Copy Number ◽

Multiple Testing ◽

Stage Ii ◽

Comparative Genomic ◽

Multiple Testing Correction ◽

Dna Copy Number ◽

Stage Ii Colon Cancer

Background: Around 30% of all stage II colon cancer patients will relapse and die of their disease. At present no objective parameters to identify high-risk stage II colon cancer patients, who will benefit from adjuvant chemotherapy, have been established. With traditional histopathological features definition of high-risk stage II colon cancer patients is inaccurate. Therefore more objective and robust markers for prediction of relapse are needed. DNA copy number aberrations have proven to be robust prognostic markers, but have not yet been investigated for this specific group of patients. The aim of the present study was to identify chromosomal aberrations that can predict relapse of tumor in patients with stage II colon cancer.Materials and Methods: DNA was isolated from 40 formaldehyde fixed paraffin embedded stage II colon cancer samples with extensive clinicopathological data. Samples were hybridized using Comparative Genomic Hybridization (CGH) arrays to determine DNA copy number changes and microsatellite stability was determined by PCR. To analyze differences between stage II colon cancer patients with and without relapse of tumor a Wilcoxon rank-sum test was implemented with multiple testing correction.Results: Stage II colon cancers of patients who had relapse of disease showed significantly more losses on chromosomes 4, 5, 15q, 17q and 18q. In the microsatellite stable (MSS) subgroup (n=28), only loss of chromosome 4q22.1–4q35.2 was significantly associated with disease relapse (p < 0.05, FDR < 0.15). No differences in clinicopathological characteristics between patients with and without relapse were observed.Conclusion: In the present series of MSS stage II colon cancer patients losses on 4q22.1–4q35.2 were associated with worse outcome and these genomic alterations may aid in selecting patients for adjuvant therapy.

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