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Title: CT-PET guided target delineation in head and neck cancer and implications for improved outcome
Author: Moule, R. N.
ISNI:       0000 0004 2727 7413
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2010
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Aim: Fifty percent of patients with squamous cell carcinoma of the Head and Neck develop loco-regional recurrence after treatment. Factors leading to this failure are most likely altered intra-tumoural glucose metabolism and increased hypoxia. Tissue glucose utilisation and the degree of hypoxia can be visualised by CTPET imaging with 18FDG and hypoxic radio-nuclides. This thesis has investigated 18FDG CT-PET guided target volume delineation methods and attempted to validate 64Cu-ATSM as a hypoxic radio-nuclide in patients with squamous cell carcinoma of the Head and Neck. Materials and Methods: Eight patients with locally advanced disease underwent 18FDG CT-PET imaging before and during curative radiotherapy or chemo-radiotherapy. Fixed (SUV cut off and percentage threshold of the SUVmax) and adaptive thresholds were investigated. The functional volumes automatically delineated by these methods and SUVmax were compared at each point, and between thresholds. Four patients with locally advanced disease, two to seven days prior to surgery, underwent 3D dynamic CT-PET imaging immediately after injection of 64Cu- ATSM. Two patients were also imaged 18 hours after injection, and two underwent a dynamic contrast-enhanced CT to evaluate intra-tumoural perfusion. All patients received pimonidazole before surgery. The pimonidazole, GLUT1, CAIX, and HIF1a immuno-histochemical hypoxic fractions were defined. Staining was correlated with the retention pattern of 64Cu-ATSM at 3 time points. Hypoxic target volumes were delineated according to tumour to muscle, blood and background ratios. Results: 18FDG primary and lymph node target volumes significantly reduced with radiation dose by the SUV cut off method and correlated with the reduction in the SUVmax within the volume. Volume reduction was also found between thresholds by the same delineation method. The volumes delineated by the other methods were not significantly reduced (except the lymph node functional volume when defined by the adaptive threshold). 64Cu-ATSM correlated with hypoxic immuno-histochemical staining but not with blood flow. Tumour ratios increased with time after injection, which influenced the delineated hypoxic target volume. Conclusion: Dose-escalated image-guided radiotherapy strategies using these CT-PET guided functional volumes have the potential to improve loco-regional control in patients with squamous cell carcinoma of the Head and Neck. CT-PET 18FDG volume delineation is intricately linked to the method and threshold of delineation and the timing of the imaging. 64Cu-ATSM is promising as a hypoxic radio-nuclide and warrants further investigation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available