Improving outcomes in patients with a diagnosis of pancreatic cancer

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with high resistance to chemotherapy. Many clinical trials with novel treatment combinations have failed to increase survival for patients with advanced disease, and consequently, it is currently one of the deadliest cancers globally. This PhD thesis aimed to identify areas within the management framework of PDAC that, with appropriate interventions, could lead to improved patient outcomes. As such, I addressed two clinical entities highly prevalent but often overlooked in patients with PDAC, to determine whether improvements in these areas could lead to improved outcomes. A specifically-designed and populated large retrospective data collection of patients with PDAC (all stages), demonstrated for the first time that high GlucMin (defined as the lowest plasma glucose measured per patient ever) confers a worse OS; and that antidiabetic treatment use in patients with high baseline glucose leads to better OS. Thus, these results give the first signal that better antidiabetic control in patients with PDAC could lead to longer OS. Whilst confirmation and validation of these results are needed from prospective studies, I also showed that hyperglycaemia is a widespread issue in patients with PDAC, with almost 2/3 of patients having abnormal glucose levels, but only 29% were known to be diabetic. Conventional survival-based outcomes were then challenged by assessing clinician and patient perceptions on "clinically-meaningful" outcomes in the setting of a poor-prognosis malignancy, with modestly-effective treatment options. For this purpose, a prospective investigator-designed longitudinal questionnaire study was developed comprising of purposely built survey; and two validated tools measuring quality of life. Results from this study revealed that there is a mismatch between patient and physician views about the aims, priorities and expected benefit from the treatment of advanced PDAC. The main findings were that patients significantly overestimated the expected length of time extension that chemotherapy would offer, and when making decisions about treatment options: patients prioritised length of survival, while physicians thought that patients would prioritise the best balance between side-effects and survival. Overall, patients in this study had significantly higher hopes for treatment leading to life extension, compared to their physicians, and also had a lot of fear and worry about the future and poor symptom scores and quality of life. These findings highlight that there are currently some important improvements that could be made in management of hyperglycaemia and diabetes, quality of life and symptoms, and patient expectations in patients with PDAC. Given the poor outcomes in PDAC, these potential advancements should not be overlooked.

Date of Award	1 Aug 2021
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Juan Valle (Supervisor) & Mairead Mcnamara (Supervisor)