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The Circumferential Resection Margin Is a Prognostic Predictor in Colon Cancer.

ABSTRACT: Objective: This study aimed to investigate the potential value of circumferential resection margin (CRM) in colon cancer prognostics. Summary Background Data: CRM has been extensively studied as an important prognostic factor in rectal and esophageal cancer, but not in colon cancer. Methods: Data from 6,681 CRM-positive patients and 25,908 CRM-negative patients diagnosed with colon cancer in 2010-2015 were obtained from the Surveillance, Epidemiology, and End Results database. Statistical analysis methods utilized included the chi-square test, Kaplan-Meier estimates, Cox proportional, and X-tile software analyses. Results: After propensity score matching, CRM positivity was found to be negatively related with survival (P < 0.001). X-tile software identified 0 and 30 mm as optimal cutoff values (P < 0.001) for prognosis, which was applicable only in stage II-IV patients. A 20 and 33% risk decrease were observed in patients with CRM between 0 and 30 mm [95% confidence interval (CI) = 0.76-0.84], and larger than 30 mm (95% CI = 0.62-0.71), respectively. Chemotherapy strongly benefited prognosis with a hazard ratio of 0.36 (95% CI = 0.34-0.38) for overall survival (OS). Patients with a CRM value of 0-30 mm seemed to benefit most from chemotherapy compared with other groups. CRM and number of regional lymph nodes are independent risk factors, and the latter is a good substitute for CRM in AJCC stage I patients. Conclusion: CRM positivity is a strong unfavorable survival indicator for colon cancer patients. A better outcome is expected with CRM values larger than 30 mm. This cutoff value only applied to stage II-IV patients. For stage I patients, number of regional lymph nodes is a good substitute to predict survival. Chemotherapy was another favorable prognostic factor, especially for patients with a CRM value between 0 and 30 mm.

SUBMITTER: Tang XY

PROVIDER: S-EPMC7332859 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Circumferential Resection Margin Is a Prognostic Predictor in Colon Cancer.

Tang Xin-Yi XY Huang Meng-Xi MX Han Si-Qi SQ Chang Yue Y Li Zhi-Ping ZP Kao Xiao-Ming XM Chen Yan-Yan YY Liu Chao C Huang Ya-Di YD Chen Yi-Tian YT Lei Zeng-Jie ZJ Chu Xiao-Yuan XY

Frontiers in oncology 20200626

Objective: This study aimed to investigate the potential value of circumferential resection margin (CRM) in colon cancer prognostics. Summary Background Data: CRM has been extensively studied as an important prognostic factor in rectal and esophageal cancer, but not in colon cancer. Methods: Data from 6,681 CRM-positive patients and 25,908 CRM-negative patients diagnosed with colon cancer in 2010-2015 were obtained from the Surveillance, Epidemiology, and End Results databas ...[more]

PMID: 32670875

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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.

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:BACKGROUND:Colon adenocarcinoma (COAD) is one of the most lethal cancers. It is particularly important to accurately predict prognosis and to provide individualized treatment. Several lines of evidence suggest that genetic factors and clinicopathological characteristics are related to cancer onset and progression. The aim of this study was to identify potential prognostic genes and to develop a nomogram to predict survival and recurrence of COAD. METHODS:To identify potential prognostic genes in COAD, microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained from GEO2R. Venn diagram was drawn to select those genes that were overexpressed in all datasets, and survival analyses were performed to determine the prognostic values of the selected genes. New nomograms were developed based on the genes that were significantly associated with prognosis. Clinicopathological data were obtained from The Cancer Genome Atlas (TCGA). Finally, the new nomograms were compared head-to-head comparison with the TNM nomogram. RESULTS:From GSE21510, GSE110223, GSE113513 and GSE110224, a total of 834, 218, 236 and 613 overexpressed DEGs were screened out, respectively. The Venn diagram revealed that 12 genes appeared in all four profiles. After survival analyses, only INHBA expression was associated with both overall survival (OS) and disease-free survival (DFS). Multivariate analyses revealed that age, pathological N and pathological M were significant independent risk factors for OS. Age, pathological N, pathological M and INHBA were significant independent risk factors for DFS. Two prediction models predicted the probability of 3-year survival and 5-year survival for OS and DFS, respectively. The concordance indexes were 0.785 for 3-year overall survival, 0.759 for 5-year overall survival, 0.789 for 3-year disease-free survival and 0.757 for 5-year disease-free survival. The head-to-head comparison according to time-dependent ROC curves indicated that the new models had higher predictive accuracy. Decision curve analyses (DCA) indicated that the clinical value of the new models were higher than TNM models for predicting disease-free survival. CONCLUSION:The combination of INHBA expression with a clinical nomogram improves prognostic power in colon adenocarcinoma, especially for predicting recurrence.

Dataset Information

The Circumferential Resection Margin Is a Prognostic Predictor in Colon Cancer.

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The Circumferential Resection Margin Is a Prognostic Predictor in Colon Cancer.

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