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Title: Assessment of histopathological methods of evaluating response to neoadjuvant therapy in oesophageal and gastric adenocarcinoma
Author: George Hanna, Akram Ramsis
ISNI:       0000 0004 2693 8646
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2010
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Upper gastrointestinal tract (GIT) cancers usually receive neoadjuvant therapy prior to surgery. The histological assessment of this response and if this can be predicted on the pre-treatment biopsy are the subject of this thesis. The first study assessed the inter- and intra-observer variation amongst pathologists in evaluating the degree of regression using the Mandard scoring system. The results showed that the reproducibility of this system was only fair to moderate in both cases of inter- and intra-observer testing. The second study examined the levels of expression of selected tumour markers before and after neoadjuvant chemotherapy. These included markers monitoring apoptosis (p53 and bcl-2), proliferation (Ki-67), angio- and lymphangio-genesis (VEGF, CD-31 and LYVE-1). The levels of expression in these markers were measured in the pre-treatment biopsies, to monitor if they could predict the response to neoadjuvant therapy. It was found that when the panel of chosen markers being used together, delivered a much higher power of prediction rather than adopting only one marker, where the collective power of prediction was 80.6%, whereas individually, the power of prediction ranged between 24.6% (VEGF) and 60.7% (Ki-67). The third study explored the use of digital image analysis in assessing the response to neoadjuvant therapy. It was found that while this technique paralleled the Mandard scoring system, it delivered a more objective and reproducible assessment. On the basis of these results I suggest that image analysis should be used to assess tumour regression especially in the context of clinical trials. In this retrospective study it has been shown that the pre-treatment biopsy can predict the degree of regression.
Supervisor: Goldin, Robert Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral