Surgery (Austin & Northern Health) - Theses

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    18F-fluorodeoxyglucose positron emission tomography as a biomarker for colorectal cancer liver metastases
    Lau, Lawrence F. ( 2017)
    Background: Colorectal cancer is the second most common cause of cancer-related death in Australia. The majority of patients with colorectal cancer develop liver metastases but only those amenable for surgical resection have a possibility of long term survival. Recent advances in achieving macroscopic resectability of colorectal liver metastases needs to be balanced urgently, by an ability to assess systemic micrometastatic disease. Tumour staging by 18F-fluorodeoxyglucose positron emission tomography (PET) is a non-invasive tool already in routine use. Aim: To explore metabolic characteristics assessed by PET as biomarkers for colorectal cancer liver metastases. Methods / Results: Four studies were performed, each addressing separate aspects regarding the utility of tumour metabolic assessment. The first three studies were performed on retrospective cohorts while the fourth study was a prospective study. The studies and main novel findings are summarized below: 1) The Prognostic Impact of Tumour Metabolism an a Single PET Scan after Preoperative Chemotherapy Various parameters that characterize and quantify tumour metabolism were assessed for their prognostic ability. These parameters were compared to clinical and pathological features as well as previously verified prognostic scoring systems. The metabolic parameters corresponding to metabolic tumour burden were found to be most prognostic on a single PET scan following preoperative chemotherapy. 2) The Prognostic Impact of Tumour Metabolic Response to Preoperative Chemotherapy The prognostic ability of metabolic response to preoperative chemotherapy was assessed using the serial assessment of various metabolic parameters. In comparison, tumour size shrinkage on computed tomography and pathological response, the current gold standards of chemotherapy response evaluation, were assessed. Metabolic response to preoperative chemotherapy was shown to be the best prognostic indicator. 3) Metabolic Response Correlated to Biological Mechanisms The biological mechanisms underlying the prognostic impact of metabolic response was explored. Immunohistochemical analysis of six tumour biomarkers showed an inverse correlation between metabolic response and the expression of Ki-67, a marker of cellular proliferation; and a direct correlation between metabolic response and the expression of p16, a tumour suppressor. 4) Early Metabolic Response Assessment The use of early tumour metabolic response after only the first cycle of preoperative chemotherapy was assessed for the ability to predict eventual metabolic response. Early tumour metabolic response after one cycle of chemotherapy did not predict eventual metabolic response or clinical outcome. Conclusion: This thesis showed tumour metabolism to be a powerful prognostic indicator for patients with colorectal cancer liver metastases. In particular, it reveals the burden of disease as well as the sensitivity of the metastases to systemic chemotherapy. PET assessment of tumour metabolic response to chemotherapy should be routinely performed, particularly in patients undergoing complex liver surgery.