Saudi Cultural Missions Theses & Dissertations
Permanent URI for this communityhttps://drepo.sdl.edu.sa/handle/20.500.14154/10
Browse
2 results
Search Results
Item Restricted The Utility of Post-Treatment FDG PET/CT Metrics In the Evaluation of Head And Neck Squamous Cell Carcinoma(Saudi Digital Library, 2023-11-24) Althubaiti, Reem; Mehanna, Hisham; Nankivell, Paul; Sanghera, Bal18F-Fluorodeoxyglucose (FDG) positron-emission tomography–computed tomography (PET/CT) imaging is a valuable imaging procedure for tumour staging, restaging, assessing the response to therapy, and in follow-up surveillance among patients diagnosed with head and neck squamous cell carcinoma (HNSCC). While qualitatively assessing PET/CT images has become widely adopted, quantitative analyses have also been introduced to overcome several limitations of visual analysis, enabling a more objective and easier examination of inter- and intra-patient variations. This thesis presents research to investigate the role of FDG PET/CT quantitative metrics in HNSCC. A systematic review and three retrospective studies were undertaken to assess the utility of PET/CT quantitative metrics, including maximum standardised uptake value (SUVmax) and peak standardised uptake value (SUVpeak) derived at three months following the completion of chemoradiotherapy (CRT) in HNSCC. These studies confirmed the continuous use of the SUVmax in post-treatment HNSCC and developed further insights regarding the diagnostic and prognostic value of these metrics in this setting. It also provided more insight into the impact of utilising different body size metrics as well as relative metrics in SUV normalisation. Specifically, the systematic review aimed to evaluate the evidence base in the literature on the diagnostic performance and prognostic value of post-treatment FDG PET/CT metrics derived from primary tumour and lymph node sites to discriminate residual disease and predict survival outcomes in patients with HNSCC. This review revealed inconsistent results, requiring further investigation to determine the value of these metrics in the post-treatment setting. The first study aimed to identify the normalisation method that is least sensitive to body size measurements when reporting PET/CT parameters in patients with HNSCC. It was found that variations in body size might have a limited impact on those metrics; therefore, the use of any body size factors appears to be acceptable when analysing post-treatment FGD PET/CT quantitative metrics in HNSCC. The second study sought to assess the diagnostic performance of these quantitative metrics for distinguishing HNSCC residual disease. It was found that all metrics could discriminate between residual disease at the primary and nodal sites at certain thresholds. It was also found that the use of lean body mass (LBM) and body surface area (BSA), as well as a second normalisation of the FDG uptake in the background regions, did not improve their performance. Lastly, the third study investigated the prognostic utility of these quantitative metrics in predicting survival outcomes, as well as the effect of human papilloma virus (HPV) status on their prognostic value. Regardless of HPV status, post-treatment primary tumour and lymph node SUV metrics were found to be significant prognostic factors for predicting three-year progression-free survival (PFS). However, the analysis of five-year overall survival (OS) showed inconclusive findings. Overall, it was concluded that the use of either total body weight, LBM, or BSA in SUV normalisation is suitable for analysing post-treatment scans of HNSCC. This includes the evaluation of quantitative metrics for prognostication and discriminatory ability. Importantly, an increase in post-treatment SUVmax and SUVpeak values higher than the thresholds presented in this thesis, could potentially signify an augmented likelihood of disease progression. Patients with lesions exhibiting SUVmax and SUVpeak values that surpass the specified thresholds should thus be closely monitored.15 0Item Restricted Repurposing Approved-Chemotherapeutics for Head and Neck Squamous Cell Carcinoma(Saudi Digital Library, 2022) Alkurdi, Khlood; Tappuni, Anwar; Muy, Teck- TehThe advancement in head and neck squamous cell carcinoma (HNSCC) therapy necessitates the acquisition of a superior understanding of cancer molecular biology and the capability to use this knowledge to adapt the therapy to achieve best patient outcome. HNSCC is heterogeneous in its basis, mechanism, and behaviour, and its biomarkers are considered greatly important in identifying the tumorigenesis mechanism that is involved in therapy resistance to increase patient survival. Resistance to chemotherapy is a major cause of treatment failure in HNSCC patients; the long-term assessment of a patient’s compliance with chemotherapy is key to overcoming treatment resistance and controlling cancer. FOXM1 is a known oncogene and plays an important role in conferring chemoresistance. The objective of the current study was to investigate candidate approved-chemotherapeutic drugs to inhibit FOXM1 in HNSCC cells in the aim to counteract chemoresistance. Methods: Dose-response assay was performed to investigate the potency of 16 candidate drugs using crystal violet cell viability assay in 11 human cell lines consisting of normal oral keratinocytes, oral fibroblasts, normal skin keratinocytes, premalignant oral buccal mucosa and 7 HNSCC cell lines. The most potent drugs with least toxicity towards normal control cells were selected to investigate their effect on FOXM1 gene expression using reverse transcription quantitative PCR. Results: Vincristine, lanatoside A and topotecan were found to be the most potent drugs with least toxicity across the 11 cell lines. Lanatoside A was the only effective drug for a paclitaxel resistant cell line (CaLH2-PTX). All three drugs significantly suppressed FOXM1 gene expression levels in all 7 HNSCC cell lines. Conclusion: This study identified 3 existing candidate approved chemotherapeutic drugs demonstrating potent anti-proliferation effects against a panel of HNSCC cell lines and with low toxicity towards normal cells. Further investigations are needed to understand their mechanisms and their effects on FOXM1 in HNSCC cells.7 0