Clinical indications for 4D-PET/CT in lung cancer diagnosis and radiation therapy

Abstract

Over the past decade PET/CT scanning has become an invaluable tool in the evaluation of many oncologic processes. A lesion seen on a PET scan will become blurred if affected by respiratory motion, an effect similar to that created when a person moves while a photograph is taken with a slow shutter speed in low-light conditions. The compounding effects of blurring and mis-registration in whole body PET/CT imaging make accurate characterization of disease in areas of high respiratory motion challenging. A scanning technique known as respiratory gated or 4D-PET/CT scanning is a tool that can control for the effects for respiratory motion. This thesis comprises of a series of studies investigating the clinical application of 4D-PET/CT in lung cancer diagnosis and therapy. This thesis begins by presenting a review of the literature in chapter two. This chapter is a published review of the literature, performed by the candidate, which encompasses the literature up until the commencement of this thesis. The review is then updated in the second part of chapter two which reports on the progress of 4D-PET/CT in the literature during the preparation of this thesis. The first stage in the management of lung cancer is a correct diagnosis. The study presented in chapter three investigates the added value of 4D-PET/CT in correctly classifying a lung nodule as either benign of malignant. In a series of 20 patients it was found that an additional 4D-PET/CT scan only influenced the final diagnosis when the standard whole body scan was of indeterminate aetiology. These results show that use of 4D-PET/CT scanning isn’t necessary in every case but that it can be a valuable tool to aid in the timely diagnosis of lung cancer for indeterminate nodules. The use of 4D-PET/CT scanning in the treatment of known lung cancer is covered in chapters four and five. A malignant lung lesion that is unable to be resected is most likely to be treated with a course of radical radiation therapy. This involves the delivery of a prescribed dose of radiation to a target volume defined on imaging. The delineation of internal target volumes (ITV) in radiotherapy of lung tumours is currently performed using either a free-breathing (FB) FDG-PET/CT or a 4D-CT maximum intensity projection (MIP). In chapter four of this thesis I present our validation of a 4D-PET-MIP, equivalent to a 4D-CT-MIP, for the delineation of target volumes in both a phantom and in patients. In the study comparing 4D-PET and CT MIPs we were able to confirm that a 4D-PET-MIP produces volumes with high concordance with 4D-CT-MIP across multiple breathing patterns and lesion sizes in both a phantom and among patients. This can be achieved without the additional radiation exposure for a separate planning 4D-CT scan. Chapter five presents our study analysing the consequences of only using 3D-PET/CT for target volume delineation. The purpose was to investigate geographic miss of lung tumours due to respiratory motion for target volumes defined on a standard 3D-PET/CT scan when compared to target volumes defined on a 4D-PET/CT scan. In this study it was found that without any form of motion suppression the current standard of a 3D- PET/CT and 15mm PTV margin employed for lung lesions has an increasing risk of significant geographic miss in particular when tumour motion increases. Chapter six presents our study investigating the effects of respiratory motion on VQ-PET/CT scanning and determine if 4D imaging will improve co-registration between PET and CT modalities enabling more accurate ability to quantify regional lung function to allow monitoring of the effect of radiation therapy on the normal lung. In this study we were able to show for the first time that ⁶⁸Ga-VQ 4D PET/CT is feasible and the blurring caused by respiratory motion is well corrected with 4D acquisition. The results presented in this thesis show that 4D-PET/CT can have a clinical impact on the management of patients with lung cancer from the point of diagnosis to their treatment and the monitoring of the effects of radiation therapy. The use of 4D-PET/CT is now establishing itself as routine clinical tool that will likely improve outcomes for patient with highly mobile lung tumours.