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Title: Novel radiotherapy treatment approaches for locally advanced pancreatico- biliary tumours
Author: Rembielak, Agata Izabela
ISNI:       0000 0004 2688 2216
Awarding Body: The University of Manchester
Current Institution: University of Manchester
Date of Award: 2009
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Background: The mortality of pancreatico-biliary tumours (PBT) is high. The majority of patients present with advanced disease and poor performance status; thus palliative treatment plays a very important role. There is no standard palliative approach for PBT. The role of chemotherapy (CHT) and/or radiotherapy (RT) and/or molecular agents remains to be established in clinical trials. Molecular analysis of tumours may help to predict in whom the disease will remain localised for a significant time. With functional imaging techniques, it may be possible to assess response to anti-cancer drugs. These approaches could help triage patients for single or combined modality therapy. Aims: 1) To evaluate the results of treatment with concurrent cetuximab and RT in locally advanced pancreatic cancer (LAPC) patients in the PACER trial. 2) To develop a quality assurance (QA) strategy for RT in PACER. 3) To determine the feasibility of obtaining and processing skin biopsies and blood samples in the PACER-TRANS molecular sub-study. 4) To assess the value of dynamic PET imaging as a predictive factor in patients with pancreatic cancer. 5) To assess current practice in the management of cholangiocarcinoma (CCA) at The Christie NHS Foundation Trust. 6) To develop a clinical trial for patients with locally advanced CCA (LACCA). Materials and methods: 1) To date ten patients have been recruited to the PACER study. 2) The QA strategy for PACER was developed. 3) Five patients consented to give blood and skin biopsies. RNA was extracted from the skin samples using the Trizol method. Blood was centrifuged and plasma aliquots were frozen for further proteomics studies. 4) C50]H20 scans of two pancreatic cancer patients were used to calculate perfusion parameters. 5) Case notes of 132 CCA patients registered at The Christie between 2000-2004 were reviewed. 6) A protocol for a phase 1/11 trial for patients with LACCA was written with the help of experts in molecular biology and pharmacology. Findings: 1) Cetuximab and RT was generally we" tolerated (one episode of grade 3 hypomagnesaemia). At 6-month follow up, one patient had a partial response, two stable disease and six progression; one patient died before the 6-month follow-up. At the time of analysis, five patients survived. The 6-month survival was 75% (Kaplan-Meier method). 2) A QA strategy was implemented involving treatment and patient questionnaires and dummy runs. 3) High quality RNA for further downstream analysis has been successfully extracted from skin samples. 4) It is feasible to calculate perfusion parameters (blood flow and Vd) in patients with pancreatic cancer using [150]H20 PET. 5) The CCA review showed that patients generally had advanced disease, CHT was the predominant treatment and median survival was poor regardless of treatment type. 6) The protocol for BRACE, a phase 1/11 clinical trial of capecitabine, erlotinib and RT in patients with LACCA, was completed and it is hoped to set up the trial in early 2010. Conclusion: Novel RT treatment approaches appear promising
Supervisor: Not available Sponsor: Not available
Qualification Name: MD Qualification Level: Doctoral
EThOS ID:  DOI: Not available