Magnetic resonance imaging-guided radiation therapy using animal models of glioblastoma

Glioblastoma is the most aggressive and most common malignant primary brain tumour in adults and has a high mortality and morbidity. Because local tumour control in glioblastoma patients is still elusive in the majority of patients, there is an urgent need for alternative treatment strategies. However, to implement changes to the existing clinical standard of care, research must be conducted to develop alternative treatment strategies. A novel approach in radiotherapy is the introduction of pre-clinical precision image-guided radiation research platforms. The aim of this review is to give a brief overview of the efforts that have been made in the field of radiation research using animal models of glioblastoma. Because MRI has become the reference imaging technique for treatment planning and assessment of therapeutic responses in glioblastoma patients, we will focus in this review on small animal radiotherapy combined with MRI

Cost-effectiveness of [18F] fluoroethyl-L-tyrosine for temozolomide therapy assessment in patients with glioblastoma

Background and Purpose: Glioblastomas are the most aggressive of all gliomas. The prognosis of these gliomas, which are classified as grade IV tumors by the World Health Organization (WHO), is poor. Combination therapy, including surgery, radiotherapy, and chemotherapy has variable outcomes and is expensive. In light of rising healthcare costs, there are societal demands for the justification of medical expenses. Therefore, we calculated the cost-effectiveness of follow-up [F-18] fluoroethyl-L-tyrosine ([F-18] FET) positron emission tomography (PET) scans performed on patients with glioblastoma after surgery and before commencing temozolomide maintenance treatment. Materials and Methods: To determine the cost-effectiveness of follow-up [F-18] FET PET procedures, we examined published clinical data and calculated the associated costs in the context of Belgian healthcare. We subsequently performed one-way deterministic sensitivity analysis and Monte Carlo analysis on the calculated ratios. Results: The decision tree based on overall survival rates showed that the number of non-responders identified using PET was 57.14% higher than the number of non-responders identified using conventional MRI. Further, the decision tree based on progression-free survival rates revealed a comparable increase of 57.50% non-responders identified. The calculated cost of two required PET scans per patient during the follow-up treatment phase was 780.50 euros. Two cost-effectiveness ratios were determined for overall survival and progression-free survival rates. Both of these calculations yielded very similar results: incremental cost-effectiveness ratios of 1,365.86 and 1,357.38 euros, respectively, for each identified non-responder. The findings of the sensitivity analysis supported the calculated results, confirming that the obtained data were robust. Conclusion: Our comparative study of conventional MRI and [F-18] FET PET revealed that the latter is a valuable tool for predicting the treatment responses of patients with glioblastomas to follow-up temozolomide maintenance treatment while considering its cost-effectiveness. Thus, [F-18] FET PET scans enable clinical outcomes to be predicted accurately and at a low cost. Moreover, given the robustness of the data in the sensitivity analyses, the level of certainty of this outcome is acceptable

In vitro 2-deoxy-2-[18F]fluoro-D-glucose uptake: practical considerations

In oncology 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]-FDG), a glucose analogue, is the most used positron emission tomography (PET) tracer. There are however some limitations due to low metabolic activity or high surrounding physiological uptake in several tumors or regions. Investigating new tracers or methods is expensive and elaborative when animal experiments or phase I clinical trials are used. In vitro experiments can overcome these limitations. We analyzed the influence of incubation time, cell medium conditions, administered activity, and cell density on [F-18]-FDG uptake in six different cell cultures. Glucose transporter 1 (GLUT1)- and hexokinase 2 (HK2)-expression at high and low cell density was analyzed using immunocytochemistry. FDG-uptake increases over time and absence of glucose in the incubation medium increases uptake. By increasing the administered activity, uptake per protein also increases and tracer uptake per protein is lower at higher cell densities. Immunocytochemical analysis reveals a lower expression of both GLUT1 and HK2 at higher cell concentrations. All investigated parameters influenced FDG uptake and therefore we can conclude it is of utmost importance to keep administered activity, incubation medium, and time constant and to correct uptake when cell density changes due to environmental conditions, such as therapy

Differentiation between peri-anastomotic inflammatory changes and local recurrence following neoadjuvant radiochemotherapy surgery for colorectal cancer using visual and semiquantitative analysis of PET-CT data

Aim. The aim of this study was to evaluate the usefulness of visual and semiquantitative [F-18]fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) data for the diagnosis of peri-anastomotic colorectal cancer recurrence, taking into account the time period between surgery and [F-18]FDG PET-CT scanning. Methods. The study population consisted of 70 patients who had prior preoperative radiochemotherapy and surgical resection of the primary tumor and who underwent whole body [F-18]FDG PET-CT scanning for the detection of recurrent disease. Visual and semiquantitative (SUVmax) analysis of [F-18]FDG uptake at the peri-anastomosis was performed. The final diagnosis was based on pathological proof or clinical and/or imaging follow-up data. Results. On visual reading, 27 patients exhibited increased [F-18]FDG uptake at the peri-anastomosis. Of these, 11 (41%) patients had a local tumor recurrence and 16 (59%) had no recurrent tumor. Among the 43 patients without increased [F-18]FDG uptake at the peri-anastomosis, none had local tumor recurrence. On semiquantitation, SUVmax in patients with and without a local recurrence overlapped. However, when the time period between surgery and [F-18]FDG PET-CT scanning was taken into account, overlap of SUVmax was mainly observed within a postoperative period of <= 12 months; thereafter, a threshold SUVmax of 3.2 discriminated between benign and malignant lesions in all but one patient. Conclusion. In our series, visually increased [F-18]FDG uptake at the peri-anastomosis was 100% sensitive but non-specific (73% specificity) for the diagnosis of local tumor recurrence. On the other hand, normal [F-18]FDG uptake at the peri-anastomosis precluded a local tumor recurrence (a negative predictive value of 100%). In addition, semiquantitative (SUVmax) analysis of [F-18]FDG uptake at the peri-anastomosis may increase specificity (up to 97%), while preserving maximum sensitivity, if the postoperative period is >12 months