Sharma, Bhupinder (2022) Imaging assessment of haematopoietic and lymphoid tumours; advancing methodologies and applications. (PhD thesis), Kingston University, .
Abstract
Haematological malignancies are a burden being the fifth most common cancer and the second leading cause of cancer mortality on a global scale. Their presentation is complex due to disparate patterns of biological behaviour and anatomical involvement. Accurate detection of disease and precise assessment of treatment response is critical for optimal patient management. However, the appropriate use of imaging tests requires awareness of their strengths and limitations and appreciation of the myriad biological behaviours of haematological malignancies. This thesis presents research undertaken to enhance the imaging assessment of haematological malignancies. Four key themes of concern were identified and addressed. Firstly, general reporting of haematological malignancies lacked standardisation in staging, response, and prognostication assessment across all imaging studies: computed tomography (CT), positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI). A multimodality imaging report with a multidisciplinary team meeting (MDTM) style conclusion needs to be issued at each relevant timepoint in the patient pathway. The aim was to reduce imaging ‘error’ rates by using template reports, produce comparative datasets from different centres, and improve patient outcomes. Analogous to UK developments in pathology reporting, a robust and adaptable methodology, termed ‘Specialist Integrated Haematological Malignancy Imaging Reporting’ (SIHMIR), was formulated. Secondly, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) imaging guidance varied widely. There was no detailed analysis of the strengths and weaknesses of the numerous imaging tests used, and patient data was prone to misinterpretation. No comprehensive imaging guidance was available for the distinct types of BIA-ALCL, a ‘cascade’ of investigations being performed. An assessment of the strengths and limitations of all anatomical and functional imaging investigations in BIA-ALCL was undertaken, and patient imaging pathways were developed. Thirdly, a prompt diagnosis of Richter’s transformation (RT) from chronic lymphocytic leukaemia (CLL) was needed. The selection of a biopsy target to diagnose RT was a particular challenge in clinical practice. A PET-CT driven decision-making pathway to decide whether biopsy was required and, if so, to select a representative biopsy site in the era of novel therapies was developed. Lastly, MRI, used for central nervous system lymphoma (CNSL) imaging, was unable to differentiate disease activity from benign post-biopsy and inflammatory change and did not provide prognostic information. Two imaging applications for this purpose were developed: (i) the theoretical concept and clinical use of contrast clearance analysis (CCA), with its ability to differentiate viable CNSL from benign enhancement, and (ii) 18F-choline radiotracer (FCH) cranial PET-CT for staging, response-assessment, and prognostication. This thesis advances the imaging assessment in haematopoietic and lymphoid tumours, most notably with a standardised reporting framework (SIHMIR), guidance in both BIA-ALCL and CLL RT, and two CNSL imaging applications. The disease-histology specific approach to the use of imaging tests has been endorsed by the UK National Institute of Health and Care Excellence (NICE) Guidelines and UK Medicines and Healthcare products Regulatory Agency (MHRA) Guidelines. The new methodologies and tools described, particularly the two new tools for CNSL assessment, have the capacity to change global clinical and research trial practice.
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