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Title: The role of surgery in the management of oesophageal cancer : an assessment of staging and multi-modality treatment over ten years
Author: Davies, Andrew Richard
ISNI:       0000 0004 5368 4530
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2015
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Introduction : Oesophageal cancer represents a formidable challenge to both patients and clinicians. Due to its propensity for early systemic dissemination, the majority of patients are not eligible for curative treatment. In the minority of patients suitable for surgical resection, there remain many controversies in management. Good prospective data from high volume centres is vital in attempting to improve staging algorithms and management strategies. Methods : A large prospectively collected database was utilised, the result of a research collaboration between two high volume oesophageal cancer centres (St Thomas’ hospital and Royal Marsden hospital) in London, UK. The database consisted of consecutive patients undergoing surgery for oesophageal or oesophago-gastric junction (type 1 and 2) tumours between 2000 and 2010. The database was rigorously cross-referenced to ensure accuracy. Data were analysed independently at an aligned academic unit by an experienced bio-statistician. The aim was to assess factors predicting early recurrence and death after oesophagectomy (study 1), the influence of surgical radicality on outcomes (study 2), and the down-staging effects of neo-adjuvant chemotherapy (study 3). Each of these was to be presented as a scientific article, accepted for peer-review publication. Results : Of the 680 patients included, the median age was 64 years with a male preponderance (81%). The majority of patients had adenocarcinoma (82%), although patients with squamous cell carcinoma (14%) and high grade dysplasia (4%) were also included in the database. Multivariable analysis showed T and N stage (T3-4 N2-3 OR 10.6; 95% CI 2.8-40.0), poor differentiation (OR 2.8; 95% CI 1.4-5.5), involved resection margins (OR 2.7; 95% CI 1.2-6.0) and poor response to pre-operative chemotherapy (OR 3.2; 95% CI 1.1-8.8) to independently predict early recurrence and death after surgery. The predominant mode of recurrence was with distant metastases. Surgical approach, comparing transhiatal with transthoracic oesophagectomy, had no impact on overall survival (HR 1.07, 95% CI 0.84 – 1.36) or tumour recurrence (HR 0.99, 95% CI 0.76 – 1.29) when adjusted for potential confounding factors. In patients undergoing neo-adjuvant chemotherapy, outcome was determined by tumour stage after chemotherapy rather than that of initial presentation. This may have a significant impact on staging algorithms with a shift in focus to assessment of tumour stage after chemotherapy in order to improve clinical decision making and predict outcome. The three studies were published in the Journal of Surgical Oncology, British Journal of Surgery and Journal of Clinical Oncology respectively. Conclusions : Predictive models that could guide individualised patient management are achievable. These could include selecting patients for specific neo-adjuvant treatment strategies, guiding surgical approach in patients deemed suitable for resection and improved selection of patients who are most likely to benefit from surgery.
Supervisor: Lagergren, Jesper Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available