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Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer.

ABSTRACT: Tumour budding is a histological finding in epithelial cancers indicating an unfavourable phenotype. Previous studies have demonstrated that it is a negative prognostic indicator in colorectal cancer (CRC), and has been proposed as an additional factor to incorporate into staging protocols.A systematic review of papers until March 2016 published on Embase, Medline, PubMed, PubMed Central and Cochrane databases pertaining to tumour budding in CRC was performed. Study end points were the presence of lymph node metastases, recurrence (local and distal) and 5-year cancer-related death.A total of 7821 patients from 34 papers were included, with a mean rate of tumour budding of 36.8±16.5%. Pooled analysis suggested that specimens exhibiting tumour budding were significantly associated with lymph node positivity (OR 4.94, 95% CI 3.96-6.17, P<0.00001), more likely to develop disease recurrence over the time period (OR 5.50, 95% CI 3.64-8.29, P<0.00001) and more likely to lead to cancer-related death at 5 years (OR 4.51, 95% CI 2.55-7.99, P<0.00001).Tumour budding in CRC is strongly predictive of lymph node metastases, recurrence and cancer-related death at 5 years, and its incorporation into the CRC staging algorithm will contribute to more effective risk stratification.

SUBMITTER: Rogers AC

PROVIDER: S-EPMC5046217 | biostudies-other | 2016 Sep

REPOSITORIES: biostudies-other

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Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer.

Rogers A C AC Winter D C DC Heeney A A Gibbons D D Lugli A A Puppa G G Sheahan K K

British journal of cancer 20160906 7

<h4>Background</h4>Tumour budding is a histological finding in epithelial cancers indicating an unfavourable phenotype. Previous studies have demonstrated that it is a negative prognostic indicator in colorectal cancer (CRC), and has been proposed as an additional factor to incorporate into staging protocols.<h4>Methods</h4>A systematic review of papers until March 2016 published on Embase, Medline, PubMed, PubMed Central and Cochrane databases pertaining to tumour budding in CRC was performed. ...[more]

PMID: 27599041

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Project description:BACKGROUND:Myosteatosis has been reported to be a novel biomarker that could predict survival outcomes in patients with colorectal cancer. However, results have been conflicting. This systematic review and meta-analysis aimed to evaluate the long-term impact of myosteatosis on the survival of these patients. METHODS:A systematic search of PubMed, Embase, and Cochrane up to 27 November 2019 generated 7022 records. Studies that reported hazard ratio (HR) for overall survival, cancer-specific survival, or disease-free survival based on myosteatosis or radiodensity were included. A total of 110 full-text articles were considered for inclusion, and 14 were selected for qualitative analysis. Inverse variance method was used with random effects model for data analysis. RESULTS:The total number of enrolled patients included in the meta-analysis was 6518 for univariate and 8572 for multivariate HR analysis, from 12 and 10 studies, respectively. Patients with myosteatosis had a significant increase in overall mortality compared with non-myosteatosis patients by both univariate analysis [HR 1.38, 95% confidence interval (CI) 1.21 to 1.58, P < 0.00001] and multivariate analysis (HR 1.55, 95% CI 1.23 to 1.96, P < 0.00001). In subgroup analysis based on studies that reported HRs of both sarcopenia and myosteatosis, the negative effect of myosteatosis on overall survival was independent of sarcopenia using univariate values (sarcopenia HR 1.48, 95% CI 1.14 to 1.91, P = 0.003 vs. myosteatosis HR 1.51, 95% CI 1.17 to 1.96, P = 0.002) and multivariate values (sarcopenia HR 1.28, 95% CI 1.09 to 1.49, P = 0.002 vs. myosteatosis HR 1.38, 95% CI 1.07 to 1.80, P = 0.001). CONCLUSIONS:This meta-analysis demonstrates that myosteatosis is associated with worse overall survival in patients with colorectal cancer. More investigation is needed to standardize the measurement protocol for myosteatosis and to further optimize its prognostic power for colorectal cancer patients.

Project description:In 2011, the Tumour Node Metastasis (TNM) staging system still remains the gold standard for stratifying colorectal cancer (CRC) patients into prognostic subgroups, and is considered a solid basis for treatment management. Nevertheless, there is still a challenge with regard to therapeutic strategy; stage II patients are not typically selected for postoperative adjuvant chemotherapy, although some stage II patients have a comparable outcome to stage III patients who, themselves do receive such treatment. Consequently, there has been an inundation of 'prognostic biomarker' studies aiming to improve the prognostic stratification power of the TNM staging system. Most proposed biomarkers are not implemented because of lack of reproducibility, validation and standardisation. This problem can be partially resolved by following the REMARK guidelines. In search of novel prognostic factors for patients with CRC, one might glance at a table in the book entitled 'Prognostic Factors in Cancer' published by the International Union against Cancer (UICC) in 2006, in which TNM stage, L and V classifications are considered 'essential' prognostic factors, whereas tumour grade, perineural invasion, tumour budding and tumour-border configuration among others are proposed as 'additional' prognostic factors. Histopathology reports normally include the 'essential' features and are accompanied by tumour grade, histological subtype and information on perineural invasion, but interestingly, the tumour-border configuration (i.e., growth pattern) and especially tumour budding are rarely reported. Although scoring systems such as the 'BRE' in breast and 'Gleason' in prostate cancer are solidly based on histomorphological features and used in daily practice, no such additional scoring system to complement TNM staging is available for CRC. Regardless of differences in study design and methods for tumour-budding assessment, the prognostic power of tumour budding has been confirmed by dozens of study groups worldwide, suggesting that tumour budding may be a valuable candidate for inclusion into a future prognostic scoring system for CRC. This mini-review therefore attempts to present a short and concise overview on tumour budding, including morphological, molecular and prognostic aspects underlining its inter-disciplinary relevance.

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Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer.

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Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer.

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