Dataset Information

Meta-analysis of the influence of a positive circumferential resection margin in oesophageal cancer.

ABSTRACT:

Background

The evidence regarding the prognostic impact of a positive circumferential resection margin (CRM) in oesophageal cancer is conflicting, and there is global variability in the definition of a positive CRM. The aim of this study was to determine the impact of a positive CRM on survival in patients undergoing oesophagectomy for oesophageal cancer.

Methods

A systematic review and meta-analysis was performed. PubMed and Embase databases were searched for articles to May 2018 examining the effect of a positive CRM on survival. Cohort studies written in English were included. Meta-analyses of univariable and multivariable hazard ratios (HRs) were performed using both Royal College of Pathologists (RCP) and College of American Pathologists (CAP) criteria. Risk of bias was assessed using the Newcastle-Ottawa Scale. Egger regression, and Duval and Tweedie trim-and-fill statistics were used to assess publication bias.

Results

Of 133 studies screened, 29 incorporating 6142 patients were finally included for analysis. Pooled univariable HRs for overall survival in patients with a positive CRM were 1·68 (95 per cent c.i. 1·48 to 1·91; P?P?P?P?ConclusionA positive CRM is associated with a worse prognosis regardless of classification system, T category, tumour type or neoadjuvant therapy.

SUBMITTER: Evans R

PROVIDER: S-EPMC6773635 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Meta-analysis of the influence of a positive circumferential resection margin in oesophageal cancer.

Evans R R Bundred J R JR Kaur P P Hodson J J Griffiths E A EA

BJS open 20190625 5

<h4>Background</h4>The evidence regarding the prognostic impact of a positive circumferential resection margin (CRM) in oesophageal cancer is conflicting, and there is global variability in the definition of a positive CRM. The aim of this study was to determine the impact of a positive CRM on survival in patients undergoing oesophagectomy for oesophageal cancer.<h4>Methods</h4>A systematic review and meta-analysis was performed. PubMed and Embase databases were searched for articles to May 2018 ...[more]

PMID: 31592511

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Project description:Background:A positive circumferential resection margin (CRM) has been associated with higher rates of locoregional recurrence and worse survival in oesophageal cancer. The aim of this study was to establish if clinicopathological and radiological variables might predict CRM positivity in patients who received neoadjuvant chemotherapy before surgery for oesophageal adenocarcinoma. Methods:Multivariable analysis of clinicopathological and CT imaging characteristics considered potentially predictive of CRM was performed at initial staging and following neoadjuvant chemotherapy. Prediction models were constructed. The area under the curve (AUC) with 95% confidence intervals (c.i.) from 1000 bootstrapping was assessed. Results:A total of 223 patients were included in the study. Poor differentiation (odds ratio (OR) 2·84, 95 per cent c.i. 1·39 to 6·01) and advanced clinical tumour status (T3-4) (OR 2·93, 1·03 to 9·48) were independently associated with an increased CRM risk at diagnosis. CT-assessed lack of response (stable or progressive disease) following chemotherapy independently corresponded with an increased risk of CRM positivity (OR 3·38, 1·43 to 8·50). Additional CT evidence of local invasion and higher CT tumour volume (14 cm3) improved the performance of a prediction model, including all the above parameters, with an AUC (c-index) of 0·76 (0·67 to 0·83). Variables associated with significantly higher rates of locoregional recurrence were pN status (P = 0·020), lymphovascular invasion (P = 0·007) and poor response to chemotherapy (Mandard score 4-5) (P = 0·006). CRM positivity was associated with a higher locoregional recurrence rate, but this was not statistically significant (P = 0·092). Conclusion:The presence of advanced cT status, poor tumour differentiation, and CT-assessed lack of response to chemotherapy, higher tumour volume and local invasion can be used to identify patients at risk of a positive CRM following neoadjuvant chemotherapy.

Project description:Negative circumferential resection margins (CRM) are the cornerstone for the curative treatment of locally advanced rectal cancer (LARC). However, in up to 18.6% of patients, tumor-positive resection margins are detected on histopathology. In this proof-of-concept study, we investigated the feasibility of optical molecular imaging as a tool for evaluating the CRM directly after surgical resection to improve tumor-negative CRM rates. Methods: LARC patients treated with neoadjuvant chemoradiotherapy received an intravenous bolus injection of 4.5 mg of bevacizumab-800CW, a fluorescent tracer targeting vascular endothelial growth factor A, 2-3 d before surgery (ClinicalTrials.gov identifier: NCT01972373). First, for evaluation of the CRM status, back-table fluorescence-guided imaging (FGI) of the fresh surgical resection specimens (n = 8) was performed. These results were correlated with histopathology results. Second, for determination of the sensitivity and specificity of bevacizumab-800CW for tumor detection, a mean fluorescence intensity cutoff value was determined from the formalin-fixed tissue slices (n = 42; 17 patients). Local bevacizumab-800CW accumulation was evaluated by fluorescence microscopy. Results: Back-table FGI correctly identified a tumor-positive CRM by high fluorescence intensities in 1 of 2 patients (50%) with a tumor-positive CRM. For the other patient, low fluorescence intensities were shown, although (sub)millimeter tumor deposits were present less than 1 mm from the CRM. FGI correctly identified 5 of 6 tumor-negative CRM (83%). The 1 patient with false-positive findings had a marginal negative CRM of only 1.4 mm. Receiver operating characteristic curve analysis of the fluorescence intensities of formalin-fixed tissue slices yielded an optimal mean fluorescence intensity cutoff value for tumor detection of 5,775 (sensitivity of 96.19% and specificity of 80.39%). Bevacizumab-800CW enabled a clear differentiation between tumor and normal tissue up to a microscopic level, with a tumor-to-background ratio of 4.7 ± 2.5 (mean ± SD). Conclusion: In this proof-of-concept study, we showed the potential of back-table FGI for evaluating the CRM status in LARC patients. Optimization of this technique with adaptation of standard operating procedures could change perioperative decision making with regard to extending resections or applying intraoperative radiation therapy in the case of positive CRM.

Dataset Information

Meta-analysis of the influence of a positive circumferential resection margin in oesophageal cancer.

Background

Methods

Results

Publications

Meta-analysis of the influence of a positive circumferential resection margin in oesophageal cancer.

Similar Datasets

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