Adjuvant Therapy for Stage II Colon Cancer: A Systematic Review From the Cancer Care Ontario Program in Evidence-Based Care’s Gastrointestinal Cancer Disease Site Group

Purpose To develop a systematic review that would address the following question: Should patients with stage II colon cancer receive adjuvant therapy? Methods A systematic review was undertaken to locate randomized controlled trials comparing adjuvant therapy to observation. Results Thirty-seven trials and 11 meta-analyses were included. The evidence for stage II colon cancer comes primarily from a trial of fluorouracil plus levamisole and a meta-analysis of 1,016 patients comparing fluorouracil plus folinic acid versus observation. Neither detected an improvement in disease-free or overall survival for adjuvant therapy. A recent pooled analysis of data from seven trials observed a benefit for adjuvant therapy in a multivariate analysis for both disease-free and overall survival. The disease-free survival benefits appeared to extend to stage II patients; however, no P values were provided. A meta-analysis of chemotherapy by portal vein infusion has also shown a benefit in disease-free and overall survival for stage II patients. A meta-analysis was conducted using data on stage II patients where data were available (n = 4,187). The mortality risk ratio was 0.87 (95% CI, 0.75 to 1.01; P = .07). Conclusion There is preliminary evidence indicating that adjuvant therapy is associated with a disease-free survival benefit for patients with stage II colon cancer. These benefits are small and not necessarily associated with improved overall survival. Patients should be made aware of these results and encouraged to participate in active clinical trials. Additional investigation of newer therapies and more mature data from the presently available trials should be pursued.

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Cochrane systematic review and meta-analysis of adjuvant chemotherapy for stage II colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.3548 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 3548-3548

Author(s):

Brandon Matthew Meyers ◽

Humaid Obaid Al-Shamsi ◽

Alvaro Tell Figueredo

Keyword(s):

Colon Cancer ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Meta Analysis ◽

Disease Free Survival ◽

Stage Ii ◽

Cochrane Systematic Review ◽

Free Survival ◽

Stage Ii Colon Cancer ◽

Disease Free

3548 Background: Colon cancer is potentially curable by surgery in the early stages of the disease. Adjuvant chemotherapy improves disease-free and overall survival in patients with stage III disease, but the magnitude of benefit in stage II colon cancer is less clear. A previous Cochrane systematic review and meta-analysis (SR/MA) found improved disease-free, but not overall survival (Figueredo et al., 2008). An updated SR/MA was performed to determine the effects of adjuvant chemotherapy on disease-free and overall survival in patients with stage II colon cancer. Methods: Relevant databases (MEDLINE, EMBASE, and Cochrane) were independently searched by all authors, using the same search strategy employed in the original study (1/1988 to 9/2012). Randomized trials containing data on stage II colon cancer patients undergoing adjuvant 5-fluorouracil (5FU) chemotherapy versus observation were included. Pooled results were expressed as hazard ratios (HR) whenever possible, or risk ratios (RR), with 95% confidence intervals (95%CI) using a random effects model. Results: Seven studies were identified, and included in the final SR/MA. Six of the 7 studies were included in the disease-free survival analysis (n=4587). Adjuvant 5FU was associated with better disease-free survival (RR 0.84 (95%CI 0.75-0.94)). All 7 studies (n=5353) were included in the overall survival analysis showing an improvement with adjuvant 5FU (HR 0.87 (95%CI 0.78-0.97)). There was no evidence of heterogeneity across the studies (I2 = 0% for all analyses). Conclusions: In stage II colon cancer, adjuvant 5FU chemotherapy statistically improves both disease-free and overall survival. Our SR/MA demonstrates, for the first time, an overall survival advantage with adjuvant chemotherapy in stage II colon cancer.

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Association of Bevacizumab Plus Oxaliplatin-Based Chemotherapy With Disease-Free Survival and Overall Survival in Patients With Stage II Colon Cancer

JAMA Network Open ◽

10.1001/jamanetworkopen.2020.20425 ◽

2020 ◽

Vol 3 (10) ◽

pp. e2020425 ◽

Cited By ~ 2

Author(s):

Benoist Chibaudel ◽

Julie Henriques ◽

Manel Rakez ◽

Baruch Brenner ◽

Tae Won Kim ◽

...

Keyword(s):

Colon Cancer ◽

Overall Survival ◽

Disease Free Survival ◽

Stage Ii ◽

Free Survival ◽

Stage Ii Colon Cancer ◽

Disease Free

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Predictive Prognostic Value of Tissue-Based MicroRNA Expression in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-analysis

Journal of Dental Research ◽

10.1177/0022034518762090 ◽

2018 ◽

Vol 97 (7) ◽

pp. 759-766 ◽

Cited By ~ 27

Author(s):

G. Troiano ◽

F. Mastrangelo ◽

V.C.A. Caponio ◽

L. Laino ◽

N. Cirillo ◽

...

Keyword(s):

Systematic Review ◽

Overall Survival ◽

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Mirna Expression ◽

Prognostic Value ◽

Meta Analysis ◽

Disease Free Survival ◽

Free Survival ◽

Disease Free

Oral squamous cell carcinoma (OSCC) is a common type of cancer characterized by a low survival rate, mostly due to local recurrence and metastasis. In view of the importance of predicting tumor behavior in the choice of treatment strategies for OSCC, several studies have attempted to investigate the prognostic value of tissue biomarkers, including microRNA (miRNA). The purpose of this study was to perform a systematic review and meta-analysis to evaluate the relationship between miRNA expression and survival of OSCC patients. Studies were identified by searching on MEDLINE/PubMed, SCOPUS, Web of Science, and Google Scholar. Quality assessment of studies was performed with the Newcastle-Ottawa Scale. Data were collected from cohort studies comparing disease-free survival and overall survival in patients with high miRNA expression compared to those with low expression. A total of 15 studies featuring 1,200 OSCC samples, predominantly from Asia, met the inclusion criteria and were included in the meta-analysis. Poor prognosis correlated with upregulation of 9 miRNAs (miR-21, miR-455-5p, miiR-155-5p, miR-372, miR-373, miR-29b, miR-1246, miR-196a, and miR-181) and downregulation of 7 miRNAs (miR-204, miR-101, miR-32, miR-20a, miR-16, miR-17, and miR-125b). The pooled hazard ratio values (95% confidence interval) related to different miRNA expression for overall survival and disease-free survival were 2.65 (2.07–3.39) and 1.95 (1.28–2.98), respectively. The results of this meta-analysis revealed that the expression levels of specific miRNAs can robustly predict prognosis of OSCC patients.

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TP1.2.3Oncological Outcomes of Organ Preservation Strategies - Local Excision Procedures and ‘Watchful Waiting’ In Management of Low Rectal Cancers – A Systematic Review And Meta-Analysis

British Journal of Surgery ◽

10.1093/bjs/znab362.002 ◽

2021 ◽

Vol 108 (Supplement_7) ◽

Author(s):

A R Aspari ◽

V Ramesh ◽

G Kumar ◽

S N Narayanasamy ◽

A O Gumber ◽

...

Keyword(s):

Systematic Review ◽

Overall Survival ◽

Local Recurrence ◽

Organ Preservation ◽

Meta Analysis ◽

Disease Free Survival ◽

Distant Metastases ◽

Free Survival ◽

Rectal Cancers ◽

Disease Free

Abstract Objective To evaluate local recurrence, metastases, and survival outcomes of `wait and watch’ (WW) strategy and local excision (LE) of tumours, in comparison to the present standard practice of total mesorectal excision (TME) for locally advanced rectal cancers. Data Sources MEDLINE, EMBASE, PubMed databases, and sources of Grey literature. Study Selection Randomised and non-randomised prospective studies, retrospective studies with propensity-score-matched analyses. Data Extraction and Synthesis These were carried out independently by two reviewers. A random-effects methodology was used for meta-analyses. Data was presented keeping with the 27-item PRISMA checklist. Main Outcomes The primary outcomes of interest were local recurrence, distant metastases, disease-free-survival and overall-survival, which were assessed in comparison to those associated with radical surgeries (TME). Results 7 of the 16 studies in the systematic review were included for the quantitative synthesis and meta-analysis. Local recurrence rates were comparable amongst patients in WW group and LE group to those undergoing TME. [Risk ratio (RR) 3.07/1.41; 95% Confidence Interval (CI) 0.86-10.95/0.66-3.01; P = 0.08/P=0.89 respectively]. Rates of distant metastases in the WW group and LE group were comparable to those undergoing TME [RR = 0.71/0.94; 95% CI 0.22-2.30/0.55-1.61; P = 0.56/ P = 0.83 respectively]. The median 3-year disease-free survival among patients undergoing WW, LE procedure, and TME were 88%, 80%, and 78.2% respectively; and the median 3-year overall survival among the three groups were 96%, 93%, and 89.5% respectively. Conclusions and Relevance Organ-preservation strategies appear to be a viable treatment option in the management of rectal-cancers. Further research is warranted to provide stronger levels of evidence on organ-preservation strategies.

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121 MicroRNA-21 is expressed in stroma of colorectal cancers and high levels identified by image analysis predict short disease-free survival in stage II colon cancer patients

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(10)70929-0 ◽

2010 ◽

Vol 8 (5) ◽

pp. 32

Author(s):

B.S. Nielsen ◽

S. Jorgensen ◽

J. Fog ◽

I.J. Christensen ◽

U. Hansen ◽

...

Keyword(s):

Colon Cancer ◽

Image Analysis ◽

Cancer Patients ◽

Disease Free Survival ◽

Stage Ii ◽

Colorectal Cancers ◽

Free Survival ◽

Stage Ii Colon Cancer ◽

Disease Free ◽

Short Disease Free Survival

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Endpoints in adjuvant trials: A systematic review of the literature in colon cancer and proposed definitions for future trials

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4018 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4018-4018

Author(s):

M. E. Buyse ◽

K. J. Punt ◽

C. H. Köhne ◽

P. Hohenberger ◽

R. Labianca ◽

...

Keyword(s):

Systematic Review ◽

Colon Cancer ◽

Overall Survival ◽

Disease Free Survival ◽

Review Of The Literature ◽

Free Survival ◽

Medical Oncologists ◽

Starting Point ◽

Definition Of ◽

Disease Free

4018 Background: Disease-free survival (DFS) is the primary endpoint of most trials testing adjuvant treatments. However many other endpoints are used. There is much confusion about these endpoints since different definitions were used among trials, or no definitions were provided at all. Moreover there is no consensus on either the definition of each endpoint or on the most relevant among these endpoints. This creates difficulties when comparing the results of various trials. Methods: Adjuvant trials in colon cancer were used as a model. A systematic review was performed on published adjuvant studies in colon cancer from 1997–2006, and the definitions of endpoints other than overall survival (OS) were recorded. A panel of medical oncologists, surgical oncologists, and a statistician, all with expertise in randomised trials in colorectal cancer, aimed to reach consensus on the definition of the various endpoints as well as to select the most relevant among these. Results: A total of 52 studies were identified. In addition to overall survival 8 other endpoints were used, and both the definition of these endpoints as well as the starting point differed considerably among these studies. No definition was provided for the endpoint in 19 (37%) studies and for the starting point in 30 (58%) studies. The panel reached consensus on the definition of each endpoint ( table ), and agreed that DFS, defined as the time from randomisation to any event irrespective of cause was considered to be the most relevant endpoint for adjuvant studies. The date of randomisation was considered to be the most appropriate starting point. Conclusions: The proposed guideline will help in the design of future adjuvant studies in colon cancer, and will achieve the uniformity required to facilitate cross-study comparisons. It may serve as a model for adjuvant studies in other solid tumors. [Table: see text] No significant financial relationships to disclose.

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Overall survival (OS) and updated disease-free survival (DFS) results of the NSABP C-08 trial assessing bevacizumab (B) in stage II and III colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.3508 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 3508-3508 ◽

Cited By ~ 3

Author(s):

C. J. Allegra ◽

G. A. Yothers ◽

M. J. O'Connell ◽

S. Sharif ◽

N. J. Petrelli ◽

...

Keyword(s):

Colon Cancer ◽

Overall Survival ◽

Disease Free Survival ◽

Stage Ii ◽

Free Survival ◽

Disease Free

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Identification of risk factors for stage II colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.375 ◽

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.

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