The biology of colorectal peritoneal malignancy and its prognostic significance.

Hallam, Sally ORCID: 0000-0002-7937-0711 (2021). The biology of colorectal peritoneal malignancy and its prognostic significance. University of Birmingham. Ph.D.

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Abstract

Peritoneal metastasis, (CPM) develop in 15% of colorectal cancers. Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS & HIPEC) aims to achieve macroscopic tumour resection and ablation of microscopic disease. However, 5-year survival varies widely and morbidity and mortality are relatively high. There is a need to improve patient selection and a paucity of research concerning CPM disease biology. Prognostic classifiers have been developed in a number of cancers, though none in CPM. I aimed to identify a multi-dimensional classifier to improve patient selection for CRS & HIPEC and to further the understanding of CPM disease biology.

Firstly, clinical prognostic factors for patients with CPM undergoing CRS & HIPEC were identified by systematic review. Secondly, comprehensive molecular profiling of the transcriptome, epigenome and genome of CPM was performed to develop a prognostic multidimensional classifier. Finally, a potential biomarker of tumour recurrence following CRS & HIPEC was examined using circulating tumour DNA.

This study has identified clinical and molecular features capable of predicting poor prognosis CPM and has potential applications in improved patient selection for treatment and the development of novel personalised treatments.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
Supervisor(s):
Supervisor(s)EmailORCID
Beggs, AndrewUNSPECIFIEDorcid.org/0000-0003-0784-2967
Youssef, HaneyUNSPECIFIEDUNSPECIFIED
Youssef, PeterUNSPECIFIEDUNSPECIFIED
Licence: All rights reserved
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: Institute of Cancer and Genomic Sciences
Funders: Cancer Research UK, Other
Other Funders: Royal college of surgeons, University Hospitals Birmingham hospital charity
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RD Surgery
R Medicine > RM Therapeutics. Pharmacology
URI: http://etheses.bham.ac.uk/id/eprint/11133

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