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Title: Oesophageal Cancer : strategies to improve outcomes, and identify novel immunological biomarkers and targets
Author: Noble, Fergus
ISNI:       0000 0004 6348 6028
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2014
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Oesophageal cancer is the most rapidly increasing cancer in the western world, the 6th most common cause of cancer death and is associated with a 5-year survival of less than 15%. This thesis aims to address current clinical issues in the management of patients with oesophageal cancer in an attempt to improve outcomes. We have assessed the impact of recent innovations in staging and minimally invasive surgery, and suggest potential novel immunological targets and biomarkers to predict response to chemotherapy, morbidity following surgery, and survival. The impact of positron emission tomography - computed tomography in staging was observed in a multi-centre United Kingdom setting and found an additional 9% of occult distant metastases compared to traditional staging methods, justifing its use by reducing the radical treatment of patients with metastatic disease. Minimally invasive oesophagectomy has been recently introduced into practice in a few specialist centres and we compare minimally invasive with open Ivor Lewis oesophagectomy showing there to be no detriment when compared directly for short and medium term outcomes. With regard to improving morbidity we developed and prospectively validated a novel scoring system, based on markers of the systemic inflammatory response, to predict major complications and anastomotic leak earlier than standard postoperative care. Both neoadjuvant chemotherapy and oesophagectomy are associated with significant morbidity. To improve outcomes further we firstly define what represents a significant immunopathological response to neoadjuvant chemotherapy, suggesting that both the response in the tumour and lymph node is adopted as a method to evaluate tumour regression, as it is these patients that have a significant benefit. We highlight immunonutritional blood-borne markers that predict both long-term survival and response to neoadjuvant chemotherapy. In terms of novel treatments for oesophageal cancer, immunotherapy remains attractive. Current immunotherapies have not delivered significant results in solid tumours, the reasons for this being multifactorial but include the ability of the tumour to evade the immune response. We define the local tumour inflammatory environment and specific target tumour antigens, cancer testis antigens, as potential cancer vaccine targets and biomarkers in oesophageal adenocarcinoma.
Supervisor: Sahota, Surinder ; Ottensmeier, Christian ; Bateman, Andrew Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available