Expanding the role of positron emission tomography-computed tomography and its utility in the management of oesophageal cancer
Citation:MALIK, VINOD, Expanding the role of positron emission tomography-computed tomography and its utility in the management of oesophageal cancer, Trinity College Dublin.School of Medicine.SURGERY, 2018
FINAL PHD THESIS (Vinny 30th March 2018).pdf (PDF) 4.150Mb
Purpose: 18F-fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET-CT) is an established diagnostic tool in the management of oesophageal cancer. The role of 18F-FDG PET-CT in assessing tumour response to multimodal regimens, the effect of detecting synchronous neoplasms, the impact of negative FDG tumours, the identification of robust prognostic factors at staging, it?s comparability to other diagnostic tools and it?s economic merit in the clinical management of oesophageal cancer are some areas where it?s utility is still not demonstrated and is the endeavour of this PhD undertaking. Material and methods: From 1st January 2003 to 31st December 2010 patients with newly diagnosed biopsy-proven carcinoma of the oesophagus or gastro-esophageal junction were evaluated with staging 18F-FDG PET (N=100) and PET-CT (N=650) and considered for the various studies being investigated. Patients being evaluated for tumour response underwent pre-treatment and intra-treatment 18FDG-PET scans in the second week of a 6-week course of neoadjuvant chemoradiotherapy and 3-4 weeks after treatment. Additional investigations as appropriate were undertaken, and histopathological verification was obtained where possible to validate the suspected synchronous neoplasm identified on 18F-FDG PET and PET-CT. Endoscopic ultrasound sound (N=150) and whole body magnetic resonance imaging (WBMRI) (n=50) were evaluated for T stage (T1-T4), regional lymph node metastases (N0 or N+), systemic distant metastasis and for the identification of prognostic factors. RESULTS: Kaplan-Meier survival analysis of 18FDG-PET responders (>26.4% reduction in SUV) compared with 18FDG-PET non-responders (<26.4% reduction in SUV) revealed no survival benefit for responders (P = 0.6812). A synchronous neoplasm was suspected on 18F-FDG PET and PET-CT in 55 (9.3%) of 591 patients, predominantly at sites in the colon (26) and head and neck (21). Additional investigations in 43 cases revealed malignant neoplasms in 8 (18.6%), pre-malignant in 9 (20.9%) and benign lesions in 26 (60.5%) cases. The management plan was altered in 8 patients, 1.4% overall. The total cost of added tests was $27,482.57 (?21,024) with the decision to treat the oesophageal cancer deferred by a mean of 10.7 days. When 18F-FDG PET-CT and EUS were simultaneously performed, independent significant prognostic factors of overall survival at staging were 18F-FDG PET-CT metabolic tumour volume (MTV) <7.5 cm3 (p=0.0006), EUS T stage (p=0.01) and EUS N stage (p=0.01). When 18F-FDG PET-CT and WBMRI were simultaneously performed the primary tumour was identified in 46/49 (94%) and 48/49 (98%) patients respectively. Distant metastases were identified in two patients on both imaging modalities. WBMRI missed three colonic neoplasms identified by 18F-FDG PET-CT. Expression of epithelial GLUT 3, PKM2 and stromal HK II all revealed significant association with FDG uptake but only PKM2 was an independent predictor of survival. CONCLUSION: In contrast to published data on neoadjuvant chemotherapy, % change in standard uptake value (SUV) between pre-treatment and intra-treatment 18F-FDG PET-CT did not correlate either with histopathologic response or survival, the combination of chemotherapy with radiation runs counter to its prediction efficacy, perhaps through radiation ? induced inflammation leading to false negative responses. 18F-FDG uptake concerning for synchronous neoplasms is evident in approximately one in ten cases, and of these a minority will represent a malignant neoplasm that significantly impacts on treatment. The overall added costs per patient are relatively modest and the treatment delay within acceptable limits of clinical practice. Combined anatomic-functional WBMRI has similar accuracy to 18F-FDG PET-CT in detecting the primary tumour, nodal deposits and for exclusion of systemic metastatic disease. MTV, a volumetric parameter of 18F-FDG PET-CT is a valuable prognostic factor in oesophageal cancer, more so than SUV and when used in conjunction with EUS T stage and EUS N stage can predict survival with the potential to facilitate selection of patients to treatment regimens with the benefit of enhanced clinical outcomes. FDG uptake and subsequent PET detectability can be associated with expression of other forms of GLUT with them also predicting survival.
Author: MALIK, VINOD
Publisher:Trinity College Dublin. School of Medicine. Discipline of Surgery
Type of material:Thesis
Availability:Full text available