Prognostic significance of cancer within 1 mm of the circumferential resection margin in oesophageal cancer patients following neo-adjuvant chemotherapy.

Department of Upper GI Surgery, St James's University Hospital, Leeds, UK.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery (Impact Factor: 2.4). 06/2012; DOI: 10.1093/ejcts/ezs331
Source: PubMed

ABSTRACT OBJECTIVES: The prognostic significance of the circumferential resection margin (CRM) status in oesophageal cancer patients treated with neo-adjuvant chemotherapy and radical resection is controversial. Furthermore, it is currently unclear whether patients with cancer located at the CRM have a prognosis different from that of those with cancer within 1 mm of the CRM. This is the first study aiming to establish the optimal tumour-free distance from the CRM of an oesophagectomy in patients who have undergone neo-adjuvant chemotherapy. METHODS: The clinicopathological data of 232 oesophageal cancer patients from two UK centres were analysed. The CRM status was classified as Group A (cancer at the CRM), Group B (cancer within 1 mm but not at the CRM) and Group C (no cancer within 1 mm from the CRM). The relationship between the CRM status and patient survival was investigated. RESULTS: Thirty-eight specimens were classified as Group A, 89 as Group B and 105 as Group C. CRM status was related to the depth of tumour invasion (P < 0.001) and lymph node status (P < 0.001). The prognoses of the Group A and the Group B patients were similar. Both were poorer than that of the Group C patients (P = 0.008). Lymph node status was the only independent prognostic marker in multivariate analysis. CONCLUSIONS: Oesophageal cancer patients treated with pre-operative chemotherapy with cancer cells at the CRM or within 1 mm of the CRM of the resected specimen have a significantly worse survival than patients with no cancer cells within 1 mm of the margin. However, this study suggests that the overall prognostic significance of the CRM status is limited in this cohort and the post-operative lymph node status is the most important prognostic factor in oesophageal cancer patients treated with neo-adjuvant chemotherapy and surgery.

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    ABSTRACT: BACKGROUND: The prognostic role and definition of circumferential resection margin (CRM) involvement in operable oesophageal cancer remain controversial. The College of American Pathologists (CAP) and Royal College of Pathologists (RCP) define CRM involvement as tumour found at the cut resection margin and within 1 mm of the cut margin respectively. This systematic review and meta-analysis was performed to determine the influence of CRM involvement on survival in operable oesophageal cancer. METHODS: PubMed, MEDLINE and the Cochrane Library (January 1990 to June 2012) were searched for studies correlating CRM involvement with 5-year mortality. Statistical analysis of dichotomous variables was performed using the odds ratio (OR) as the summary statistic. RESULTS: Fourteen studies involving 2433 patients with oesophageal cancer who had undergone potentially curative oesophagectomy were analysed. Rates of CRM involvement were 15·3 per cent (173 of 1133) and 36·5 per cent (889 of 2433) according to the CAP and RCP criteria respectively. Overall 5-year mortality rates were significantly higher in patients with CRM involvement compared with CRM-negative patients according to both CAP (OR 4·02, 95 per cent confidence interval (c.i.) 2·25 to 7·20; P < 0·001) and RCP (OR 2·52, 1·96 to 3·25; P < 0·001) criteria. CRM involvement between 0·1 and 1 mm was associated with a significantly higher 5-year mortality rate than CRM-negative status (involvement more than 1 mm from CRM) (OR 2·05, 95 per cent c.i. 1·41 to 2·99; P < 0·001). CONCLUSION: CRM involvement is an important predictor of poor prognosis. CAP criteria differentiate a higher-risk group than RCP criteria, but overlook a patient group with similar poor outcomes. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
    British Journal of Surgery 01/2013; · 4.84 Impact Factor
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    ABSTRACT: Background:The optimum multimodal treatment for oesophageal cancer, and the prognostic significance of histopathological tumour involvement of the circumferential resection margin (CRM+) are uncertain. The aims of this study were to determine the prognostic significance of CRM+ after oesophagectomy and to identify endosonographic (endoluminal ultrasonography (EUS)) features that predict a threatened CRM+.Methods:Two hundred and sixty-nine consecutive patients underwent potentially curative oesophagectomy (103 surgery alone, 124 neoadjuvant chemotherapy (CS) and 42 chemoradiotherapy (CRTS)). Primary outcome measures were disease-free survival (DFS) and overall survival (OS).Results:CRM+ was reported in 98 (38.0%) of all, and in 90 (62.5%) of pT3 patients. Multivariate analysis of pathological factors revealed: lymphovascular invasion (HR 2.087, 95% CI 1.396-3.122, P<0.0001), CRM+ (HR 1.762, 95% CI 1.201-2.586, P=0.004) and lymph node metastasis count (HR 1.563, 95% CI 1.018-2.400, P=0.041) to be independently and significantly associated with DFS. Lymphovascular invasion (HR 2.160, 95% CI 1.432-3.259, P<0.001) and CRM+ (HR 1.514, 95% CI 1.000-2.292, P=0.050) were also independently and significantly associated with OS. Multivariate analysis revealed EUS T stage (T3 or T4, OR 24.313, 95% CI 7.438-79.476, P<0.0001) and use or not of CRTS (OR 0.116, 95% CI 0.035-0.382, P<0.0001) were independently and significantly associated with CRM+.Conclusion:A positive CRM was a better predictor of DFS and OS than standard pTNM stage.British Journal of Cancer advance online publication, 20 November 2012; doi:10.1038/bjc.2012.511
    British Journal of Cancer 11/2012; · 5.08 Impact Factor
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    ABSTRACT: Accurate selection of patients for radical treatment of esophageal cancer is essential to avoid early recurrence and death (ERD) after surgery. We sought to evaluate a large series of consecutive resections to assess factors that may be associated with this poor outcome. This was a cohort study including 680 patients operated for esophageal cancer between 2000 and 2010. The poor outcome group comprised 100 patients with tumor recurrence and death within 1 year of surgery. The comparison group comprised 267 long-term survivors, defined as those surviving more than 3 years from surgery. Pathological characteristics associated with poor outcome were analyzed using logistic regression to determine odds ratios (OR) and 95% confidence intervals (CI). On the adjusted model T stage and N stage predicted poor survival, with the greatest risk being patients with locally advanced tumors and three or more involved lymph nodes (OR 10.6, 95% CI 2.8-40.0). Poor differentiation (OR 2.8, 95% CI 1.4-5.5), chemotherapy response (OR 3.6, 95% CI 1.2-10.6), and involved resection margins (OR 2.7, 95% CI 1.2-6.0) were all significant independent prognostic markers in the multivariable model. There was a trend toward worse survival with lymphovascular invasion (OR 2.0, 95% CI 0.9-4.2) and low albumin (OR 1.9, 95% CI 0.8-4.4) but not of statistical significance in the adjusted model. Esophageal cancer patients with poorly differentiated tumors and three or more involved lymph nodes have a particularly high risk of ERD after surgery. Accurate risk stratification of patients may identify a group who would be better served by alternative oncological treatment strategies. J. Surg. Oncol. © 2013 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 12/2013; · 2.64 Impact Factor


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