Date of Award

2018

Degree Name

Master of Science (Medicine)

Schools and Centres

Medicine

First Supervisor

Dr Paul Cohen

Second Supervisor

Dr Aime Powell

Third Supervisor

Professor Jim Codde

Abstract

High-grade serous tubo-ovarian carcinoma (HGSOC) is the most common tubal/ovarian malignant tumour and is usually diagnosed at an advanced stage. Historically, primary debulking surgery followed by adjuvant platinum-based chemotherapy was the recommended management of these patients. However, since two randomised controlled phase III trials (1, 2) both demonstrated non-inferior survival after neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) compared to primary debulking surgery, there has been an increasing trend to treat HGSOC patients with NACT. (3, 4)

Evidence supporting the change in practice is mounting, with the findings of a recent meta-analysis of 1,607 women showing that NACT is associated with superior rates of optimal surgical cytoreduction, lower peri-operative mortality as well as postsurgical mortality, and better quality of life compared to primary surgery in patients with advance ovarian cancer. (5) A cross-sectional analysis that included more than 6000 women treated for advanced epithelial ovarian cancer in the United States, reported that adoption of NACT resulted in a sizable reduction in mortality within three years of diagnosis. (3)

Opinion, however, remains divided with calls for better methods of patient selection and improved efficacy of NACT. (6, 7) While histopathological scoring of tissue removed at IDS has been routinely used to measure the response to antineoplastic treatment for many solid tumours such as breast, (8-10) rectum (11, 12) and oesophagus, (13, 14) until recently, there has been no accepted system for HGSOC due to studies having small sample size, based on a single site, utilising differing classification systems and lacking in validation or reproducibility. (15-18)

Following a publication by Böhm at al., (15) who developed, tested and validated a three-tier ‘Chemotherapy Response Score’ (CRS) that was reported to be reproducible and easy for pathologists to use, the International Collaboration on Cancer Reporting (ICCR) recently recommended the adoption of this grading system, whilst calling for further studies to confirm its relevance. (19)

In response to the above, the purpose of this thesis was to test the hypothesis that the CRS score was independently associated with the survival outcomes of patients with advanced high-grade serous ovarian cancer undergoing NACT-IDS.

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