Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.582135
Title: On the prediction of response to neo-adjuvant chemotherapy for primary oesophageal adenocarcinoma
Author: Saha, Arin Kumar
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2011
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Abstract:
Management of oesophageal cancer is associated with poor outcomes and it has become apparent that surgery alone is not sufficient to effect genuine long term survival. In the UK, it is standard practice to treat oesophageal adenocarcinoma with neo-adjuvant chemotherapy (no radiation) and surgery. One problem with this approach is the issue of those patients who do not respond. The aim of this study was to investigate biomarkers which might predict response to chemotherapy. Methods A retrospective audit was carried out on post-operative outcome after oesophagectomy from 2000 to 2006 and results compared with those from previous similar audits. Patients who received neo-adjuvant chemotherapy were identified and pre-treatment oesophageal biopsies were obtained. Immunohistochemistry was used to analyse expression ofthymidylate synthase, excision cross-complementation group 1, vascular endothelial growth factor, hypoxia-inducible factor 1 and carbonic anhydrase IX. Expression was compared with histopathological evidence of response to chemotherapy after surgical resection. In a separate prospective study from 2007 to 2008 the single-cell gel electrophoresis (comet) assay was used to measure DNA damage in response to in vivo exposure to 5-fluorouracil (5FU) and compared with subsequent response to chemotherapy. Results Post-operative mortality after oesophagectomy improved from 27% in the 1970s and 80s to less than 3% in the 2000s. At the same time, 5-year survival increased from 7% to 55%. Low expression of thymidylate synthase, VEGF and ERCC 1 was significantly associated with . good response to chemotherapy. High VEGF expression was significantly associated with nodal metastases. VB Baseline levels of DNA damage were higher in cancer cells compared to adjacent Barrett's and normal oesophageal epithelium. Response to chemotherapy was predicted by high levels of DNA damage induced by in vivo exposure to 5FU. Conclusions Methods of measuring these biomarkers should be considered and developed to aid individualised treatment plans for patients with oesophageal adenocarcinoma and predict response to chemotherapy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.582135  DOI: Not available
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