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Title: Planning treatment and predicting outcomes in low rectal cancer
Author: Battersby, Nicholas John
ISNI:       0000 0004 7427 7002
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Introduction: Low rectal cancer management presents a unique challenge. On one hand more radical measures are required to address poor oncological outcomes and on the other hand there is a need to avoid unacceptably high permanent colostomy rates and suboptimal post-treatment function. This thesis investigates radiological, surgical, pathological and quality of life factors in low rectal cancer, in order to predict outcomes and provide a patient-tailored approach to low rectal cancer management. Methods: The majority of data presented within this thesis will be from the ongoing Low Rectal Cancer Study (MERCURY II). This multidisciplinary study prospectively collected surgical, radiological, pathological and QoL data in consecutive patients undergoing treatment for low rectal cancer. In addition, a multicentre crosssectional quality of life study was performed. This was designed to evaluate post-operative bowel function using patient reported outcome measures (PROMs). Results: Analysis from 279 low rectal cancer patients from the MERCURY II study suggested that MRI assessment of the low rectal plane (mrLRP) guided selection for pre-operative therapy and for restorative resection. MRI assessment contributed to the low (9%, 25/279) pathological circumferential resection margin (pCRM) involvement; significantly lower than the pre-stated target of ≤15% and lower than published studies. Multivariate analysis identified three other predictors for pCRM involvement: tumour ≤4cm from the anal verge; anterior quadrant tumour invasion; and MRI evidence of EMVI. This thesis also validates the English translation of a Danish PROM (LARS score). This data was also used to predict for post-operative bowel-related quality of life (BQoL) impairment following a restorative anterior resection. Finally, the UK LARS data was used to develop a model that predicts post-operative bowel dysfunction (POLARS) with external validation with Danish data. Future Work: The predictors for pCRM involvement require external validation. Future studies should also explore the relationship between these predictors and long-term survival. The POLARS and the LARS score should be used in clinical practice to identify patients who may benefit from additional support for postoperative bowel dysfunction. The value of the post-treatment MRI requires further investigation and the TRIGGER trial has been designed for this purpose.
Supervisor: Brown, Gina Sponsor: Pelican Cancer Foundation
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral