Assessment of Brain Tumour Perfusion Using Early-Phase 18F-FET PET: Comparison with Perfusion-Weighted MRI.

PURPOSE: Morphological imaging using MRI is essential for brain tumour diagnostics. Dynamic susceptibility contrast (DSC) perfusion-weighted MRI (PWI), as well as amino acid PET, may provide additional information in ambiguous cases. Since PWI is often unavailable in patients referred for amino acid PET, we explored whether maps of relative cerebral blood volume (rCBV) in brain tumours can be extracted from the early phase of PET using O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET). PROCEDURE: Using a hybrid brain PET/MRI scanner, PWI and dynamic 18F-FET PET were performed in 33 patients with cerebral glioma and four patients with highly vascularized meningioma. The time interval from 0 to 2 min p.i. was selected to best reflect the blood pool phase in 18F-FET PET. For each patient, maps of MR-rCBV, early 18F-FET PET (0-2 min p.i.) and late 18F-FET PET (20-40 min p.i.) were generated and coregistered. Volumes of interest were placed on the tumour (VOI-TU) and normal-appearing brain (VOI-REF). The correlation between tumour-to-brain ratios (TBR) of the different parameters was analysed. In addition, three independent observers evaluated MR-rCBV and early 18F-FET maps (18F-FET-rCBV) for concordance in signal intensity, tumour extent and intratumoural distribution. RESULTS: TBRs calculated from MR-rCBV and 18F-FET-rCBV showed a significant correlation (r = 0.89, p < 0.001), while there was no correlation between late 18F-FET PET and MR-rCBV (r = 0.24, p = 0.16) and 18F-FET-rCBV (r = 0.27, p = 0.11). Visual rating yielded widely agreeing findings or only minor differences between MR-rCBV maps and 18F-FET-rCBV maps in 93 % of the tumours (range of three independent raters 91-94%, kappa among raters 0.78-1.0). CONCLUSION: Early 18F-FET maps (0-2 min p.i.) in gliomas provide similar information to MR-rCBV maps and may be helpful when PWI is not possible or available. Further studies in gliomas are needed to evaluate whether 18F-FET-rCBV provides the same clinical information as MR-rCBV.

The effect of surveillance for differentiated thyroid carcinoma in childhood cancer survivors on survival rates: a decision-tree-based analysis.

Background: Childhood cancer survivors (CCS) who received radiation therapy exposing the thyroid gland are at increased risk of developing differentiated thyroid cancer (DTC). Therefore, the International Guideline Harmonization Group (IGHG) on late effects of childhood cancer therefore recommends surveillance. It is unclear whether surveillance reduces mortality. Aim: The aim of this study was to compare four strategies for DTC surveillance in CCS with the aim of reducing mortality: Strategy-1, no surveillance; Strategy-2, ultrasound alone; Strategy-3, ultrasound followed by fine-needle biopsy (FNB); Strategy-4, palpation followed by ultrasound and FNB. Materials and methods: A decision tree was formulated with 10-year thyroid cancer-specific survival as the endpoint, based on data extracted from literature. Results: It was calculated that 12.6% of CCS will develop DTC. Using Strategy-1, all CCS with DTC would erroneously not be operated upon, but no CCS would have unnecessary surgery. With Strategy-2, all CCS with and 55.6% of CCS without DTC would be operated. Using Strategy-3, 11.1% of CCS with DTC would be correctly operated upon, 11.2% without DTC would be operated upon and 1.5% with DTC would not be operated upon. With Strategy-4, these percentages would be 6.8, 3.9 and 5.8%, respectively. Median 10-year survival rates would be equal across strategies (0.997). Conclusion: Different surveillance strategies for DTC in CCS all result in the same high DTC survival. Therefore, the indication for surveillance may lie in a reduction of surgery-related morbidity rather than DTC-related mortality. In accordance with the IGHG guidelines, the precise strategy should be decided upon in a process of shared decision-making.

Assessment of the lymphatic system by indirect lymphography in patients with post-thrombotic syndrome.

OBJECTIVE: Alterations in lower extremity lymph drainage caused by chronic venous obstruction (CVO) have not been well studied, partially because of a lack of standardized imaging modalities to assess the quality of lymphatic drainage in the lower extremities of patients with post-thrombotic syndrome (PTS). However, these changes are likely to have an impact on the severity of the disease and clinical outcomes of interventions. In the present study, we investigated the feasibility and diagnostic value of preintervention indirect lymphography in patients with CVO and their pre- and postintervention Villalta scores. METHODS: A total of 17 patients (21 limbs) with iliofemoral and caval CVO were included in the study between 2017 and 2018. The deep and superficial lymphatic vessels in both legs were assessed before venous recanalization and stenting. The quality of lymphatic flow was compared between the legs with CVO and healthy legs. Moreover, the correlation between the lymphatic changes and clinical severity of PTS was evaluated using the Villalta score and CEAP (Clinical, Etiology, Anatomy, and Pathophysiology) classification. RESULTS: The mean patient age was 44 ± 12 years, and 10 patients (59%) were women. The patients had undergone treatment at a mean of 25 ± 6 months after their first episode of deep vein thrombosis. Five patients (29%) had had recurrent deep vein thrombosis. The mean pre- and postinterventional Villalta score was 10.5 ± 1.46 and 9.27 ± 1.12, respectively (P = .0096). Using the CEAP classification, four legs were class 5, seven were class 4, and three each were class 3 and 2. The primary and secondary patency rate was 70.5% and 82.5% after a mean follow-up of 18 months, respectively. Indirect lymphography of the superficial and deep lymphatic systems was completed before intervention in both legs for all 17 patients (21 legs). According to the qualitative criteria, abnormal lymphatic vessel function was found in 35.2% of the superficial and 58.8% of the deep lymphatic vessels of the affected legs. Further analysis revealed abnormal function of the deep lymphatic vessels in all patients with moderate to severe PTS according to the Villalta score. CONCLUSIONS: Indirect lymphography is a feasible diagnostic tool to use for the evaluation of the function of lymphatic vessels. Impaired drainage of the deep lymphatic system was found in all our patients with moderate to severe PTS. The clinical significance of these lymphatic changes is not clear; however, an association between clinical severity and outcomes is possible.

Cost Effectiveness of 18F-FET PET for Early Treatment Response Assessment in Glioma Patients After Adjuvant Temozolomide Chemotherapy.

In light of increasing health-care costs, higher medical expenses should be justified socioeconomically. Therefore, we calculated the effectiveness and cost effectiveness of PET using the radiolabeled amino acid O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) compared with conventional MRI for early identification of responders to adjuvant temozolomide chemotherapy. A recently published study in isocitrate dehydrogenase wild-type glioma patients suggested that 18F-FET PET parameter changes predicted a significantly longer survival already after 2 cycles whereas MRI changes were not significant. Methods: To determine the effectiveness and cost effectiveness of serial 18F-FET PET imaging, we analyzed published clinical data and calculated the associated costs from the perspective of the German Statutory Health Insurance system. Based on a decision-tree model, the effectiveness of 18F-FET PET and MRI was calculated-that is, the probability to correctly identify a responder as defined by an overall survival of at least 15 mo. To determine the cost effectiveness, the incremental cost effectiveness ratio (ICER) was calculated-that is, the cost for each additionally identified responder by 18F-FET PET who would have remained undetected by MRI. The robustness of the results was tested by deterministic and probabilistic Monte Carlo sensitivity analyses. Results: Compared with MRI, 18F-FET PET increased the rate of correctly identified responders to chemotherapy by 26%; thus, 4 patients needed to be examined by 18F-FET PET to identify 1 additional responder. Considering the respective costs for serial 18F-FET PET and MRI, the ICER resulted in €4,396.83 for each additional correctly identified responder by 18F-FET PET. Sensitivity analyses confirmed the robustness of the results. Conclusion: In contrast to conventional MRI, the model suggests that 18F-FET PET is cost-effective in terms of ICER values. Considering the high cost of temozolomide, the integration of 18F-FET PET has the potential to avoid premature chemotherapy discontinuation at reasonable cost.

O-(2-18F-fluoroethyl)-L-tyrosine PET for evaluation of brain metastasis recurrence after radiotherapy: an effectiveness and cost-effectiveness analysis.

BACKGROUND: Conventional MRI is the standard method to diagnose recurrence of brain metastases after radiation. However, following radiation therapy, reactive transient blood-brain barrier alterations with consecutive contrast enhancement can mimic brain metastasis recurrence. Recent studies have suggested that O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET improves the correct differentiation of brain metastasis recurrence from radiation injury. Based on published evidence and clinical expert opinion, we analyzed effectiveness and cost-effectiveness of the use of FET PET in addition to MRI compared with MRI alone for the diagnosis of recurrent brain metastases. METHODS: A decision-tree model was designed to compare the 2 diagnostic strategies from the perspective of the German Statutory Health Insurance (SHI) system. Effectiveness was defined as correct diagnosis of recurrent brain metastasis and was compared between FET PET with MRI and MRI alone. Costs were calculated for a baseline scenario and for a more expensive scenario. Robustness of the results was tested using sensitivity analyses. RESULTS: Compared with MRI alone, FET PET in combination with MRI increases the rate of correct diagnoses by 42% (number needed to diagnose of 3) with an incremental cost-effectiveness ratio of €2821 (baseline scenario) and €4014 (more expensive scenario) per correct diagnosis. The sensitivity analyses confirmed the robustness of the results. CONCLUSIONS: The model suggests that the additional use of FET PET with conventional MRI for the diagnosis of recurrent brain metastases may be cost-effective. Integration of FET PET has the potential to avoid overtreatment with corresponding costs as well as unnecessary side effects.

Diagnostic accuracy of diffusion-weighted magnetic resonance imaging versus positron emission tomography/computed tomography for early response assessment of liver metastases to Y90-radioembolization.

OBJECTIVES: Patients with hepatic metastases who are candidates for Y90-radioembolization (Y90-RE) usually have advanced tumor stages with involvement of both liver lobes. Per current guidelines, these patients have usually undergone several cycles of potentially hepatotoxic systemic chemotherapy before Y90-RE is at all considered, requiring split (lobar) treatment sessions to reduce hepatic toxicity. Assessing response to Y90-RE early, that is, already after the first lobar session, would be helpful to avoid an ineffective and potentially hepatotoxic second lobar treatment. We investigated the accuracy with which diffusion- weighted magnetic resonance imaging (DWI-MRI) and positron emission tomography/computed tomography (PET/CT) can provide this information. METHODS: An institutional review board-approved prospective intraindividual comparison trial on 35 patients who underwent fluorodeoxyglucose PET/CT and DWI-MRI within 6 weeks before and 6 weeks after Y90-RE to treat secondary-progressive liver metastases from solid cancers (20 colorectal, 13 breast, 2 other) was performed. An increase of minimal apparent diffusion coefficient (ADCmin) or decrease of maximum standard uptake value (SUVmax) by at least 30% was regarded as positive response. Long-term clinical and imaging follow-up was used to distinguish true- from false-response classifications. RESULTS: On the basis of long-term follow-up, 23 (66%) of 35 patients responded to the Y90 treatment. No significant changes of metastases size or contrast enhancement were observable on pretreatment versus posttreatment CT or magnetic resonance images.However, overall SUVmax decreased from 8.0 ± 3.9 to 5.5 ± 2.2 (P < 0.0001), and ADCmin increased from 0.53 ± 0.13 × 10(-3) mm2/s to 0.77 ± 0.26 × 10(-3) mm2/s (P < 0.0001). Pretherapeutic versus posttherapeutic changes of ADCmin and SUVmax correlated moderately (r = -0.53). In 4 of the 35 patients (11%), metastases were fluorodeoxyglucose-negative such that no response assessment was possible by PET. In 25 (71%) of the 35 patients, response classification by PET and DWI-MRI was concordant; in 6 (17%) of the 35, it was discordant. In 5 of the 6 patients with discordant classifications, follow-up confirmed diagnoses made by DWI. The positive predictive value to predict response was 22 (96%) of 23 for MRI and 15 (88%) of 17 for PET. The negative predictive value to predict absence was 11 (92%) of 12 for MRI and 10 (56%) of 18 for PET. Sensitivity for detecting response was significantly higher for MRI (96%; 22/23) than for PET (65%; 15/23) (P < 0.02). CONCLUSIONS: Diffusion-weighted magnetic resonance imaging appears superior to PET/CT for early response assessment in patients with hepatic metastases of common solid tumors. It may be used in between lobar treatment sessions to guide further management of patients who undergo Y90-RE for hepatic metastases.

Thyroid nodules with indeterminate cytology: molecular imaging with 99mTc-methoxyisobutylisonitrile (MIBI) is more cost-effective than the Afirma gene expression classifier.

PURPOSE: To compare the cost-effectiveness of (99m)Tc-methoxyisobutylisonitrile (MIBI) thyroid scintigraphy and the Afirma gene expression classifier for the assessment of cytologically indeterminate thyroid nodules. METHODS: A decision tree model was used. Costs were calculated from the perspective of the German health insurance system. The robustness of the results was assessed with probabilistic sensitivity analyses using a Monte Carlo simulation. RESULTS: Life expectancy was 34.3 years (estimated costs per patient €1,459 - €2,224) for the MIBI scan and 34.1 years (estimated costs €3,560 - €4,071) for the molecular test. These results were confirmed by the Monte Carlo simulation. CONCLUSION: MIBI thyroid scintigraphy is more cost-effective than the gene expression classifier.

The use of O-(2-18F-fluoroethyl)-L-tyrosine PET for treatment management of bevacizumab and irinotecan in patients with recurrent high-grade glioma: a cost-effectiveness analysis.

UNLABELLED: To date, the use of structural MR imaging (including contrast-enhanced and T2-weighted or fluid-attenuated inversion recovery-weighted images) is the standard method to diagnose tumor progression and to assess antiangiogenic treatment effects. However, several studies have suggested that O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET adds valuable clinical information to the information derived from structural MR imaging alone. We evaluated the effectiveness and cost-effectiveness of the addition of (18)F-FET PET to structural MR imaging for the management of treatment with bevacizumab and irinotecan (BEV/IR) in patients with recurrent high-grade glioma compared with MR imaging alone from the perspective of the German Statutory Health Insurance. METHODS: To evaluate the incremental cost-effectiveness of the additional use of (18)F-FET PET, a decision tree model was used. Effectiveness of (18)F-FET PET was defined as correct identification of both tumor progression before BEV/IR treatment initiation and BEV/IR treatment response and was evaluated for the combination of (18)F-FET PET and MR imaging compared with MR imaging alone. Costs were estimated for a baseline scenario and for a more expensive scenario. The robustness of the results was tested using deterministic and probabilistic sensitivity analyses. RESULTS: The use of (18)F-FET PET resulted in a number needed to diagnose of 2.4, that is, 3 additional patients have to be diagnosed to avoid 1 wrong diagnosis. The incremental cost-effectiveness ratio of (18)F-FET PET/MR imaging compared with MR imaging alone was €5,725 (€1 ≈ $1.30) for the baseline scenario and €8,145 for the more expensive scenario per additional correct diagnosis. The probabilistic sensitivity analysis confirmed the robustness of the results. CONCLUSION: The model suggests that the additional use of (18)F-FET PET in the management of patients with recurrent high-grade glioma treated with BEV/IR may be cost-effective. Integration of (18)F-FET PET has the potential to avoid overtreatment and corresponding costs, as well as unnecessary side effects to the patient.

Cost-effectiveness analysis of FET PET-guided target selection for the diagnosis of gliomas.

PURPOSE: Several diagnostic trials have indicated that the combined use of (18)F-fluoroethyl-L: -tyrosine (FET) PET and MRI may be superior to MRI alone in selecting the biopsy site for the diagnosis of gliomas. We estimated the cost-effectiveness of the use of amino acid PET compared to MRI alone from the perspective of the German statutory health insurance. METHODS: To evaluate the incremental cost-effectiveness of the use of amino acid PET, a decision tree model was built. The effectiveness of FET PET was determined by the probability of a correct diagnosis. Costs were estimated for a baseline scenario and for a more expensive scenario in which disease severity was considered. The robustness of the results was tested using deterministic and probabilistic sensitivity analyses. RESULTS: The combined use of PET and MRI resulted in an increase of 18.5% in the likelihood of a correct diagnosis. The incremental cost-effectiveness ratio for one additional correct diagnosis using FET PET was €6,405 for the baseline scenario and €9,114 for the scenario based on higher disease severity. The probabilistic sensitivity analysis confirmed the robustness of the results. CONCLUSION: The model indicates that the use of amino acid PET may be cost-effective in patients with glioma. As a result of several limitations in the data used for the model, further studies are needed to confirm the results.

Cost-effectiveness analysis of amino acid PET-guided surgery for supratentorial high-grade gliomas.

UNLABELLED: High-grade gliomas are brain tumors associated with a devastating prognosis. Recent studies have indicated that the combined use of amino acid PET and MRI is superior to MRI alone to plan the surgical resection of high-grade gliomas. The aim of the study was to analyze the cost-effectiveness of the use of amino acid PET for the surgical resection of high-grade gliomas, compared with MRI alone, from the perspective of the national health insurance in Germany. METHODS: A decision-tree model was set up to compare 2 strategies: the use of MRI alone and the combined use of MRI and PET for surgical resection of high-grade gliomas. For the analysis, 2 scenarios were calculated: a baseline scenario and a more expensive scenario, accounting for disease severity. To test the robustness of the results, probabilistic sensitivity analyses using Monte Carlo simulation were calculated. RESULTS: Compared with MRI alone, the combined use of MRI and PET showed an incremental cost-effectiveness ratio of €2,948 (€1 ~ U.S.$1.3)per life-year gained for the baseline scenario and an incremental cost-effectiveness ratio of €4,105 per life-year gained for the admissible-charge-rate scenario. In the probabilistic sensitivity analysis in about 60% of the iterations, the combined use of PET and MRI was superior to MRI alone when assuming a willingness-to-pay threshold of €30,000. CONCLUSION: The model indicates that the combined use of MRI and PET may be cost-effective. The results of this analysis have to be considered carefully because there was only limited empiric evidence for several input parameters.

Assessment of large-vessel involvement in giant cell arteritis with 18F-FDG PET: introducing an ROC-analysis-based cutoff ratio.

UNLABELLED: In the diagnosis of giant cell arteritis (GCA) with aortic involvement, (18)F-FDG PET has been demonstrated to be a powerful tool. No other imaging method is able to directly detect acute inflammation within the aortic wall. However, because GCA is a rare PET indication, the assessment of GCA with (18)F-FDG PET remains difficult and highly dependent on the experience of the investigator. This study aimed to semiquantify the relationship between aortic and liver uptake and to introduce a receiver operating characteristic (ROC)-based cutoff ratio to allow investigator- and experience-independent GCA diagnosis with optimal sensitivity and specificity. Ratios of aortic wall uptake versus liver uptake were calculated in a group of GCA patients and a control group. These data were assessed in an ROC analysis, and finally, a cutoff-ratio-optimizing strategy was applied. METHODS: Twenty-three patients with initially suspected GCA (18 positive for GCA criteria, 5 negative) and 36 matched controls were included. The control subjects underwent PET for oncologic diagnostics. None had intrathoracic or hepatic disease or therapy-related tracer accumulation. Additionally, physiologic liver metabolism was ensured by the presence of normal liver enzymes. After defining regions of interest over the thoracic aorta and the liver, we calculated maximal standardized uptake value ratios. Sensitivities and specificities for cutoff ratios from 0.1 to 2.5 were estimated and were ultimately used to assess an optimal cutoff ratio for separating GCA patients from controls. To further investigate the usefulness of the resulting cutoff ratio, we tested it in a second control group with changed hepatic metabolism and elevated liver enzymes. RESULTS: ROC analysis revealed optimal selectivity for a cutoff ratio of 1.0. This ratio led to a sensitivity of 88.9%, a specificity of 95.1%, and an accuracy of 94.4%. When this aorta-to-liver ratio was applied to the control group with pathologic liver metabolism, the resulting specificity was 95.6%. CONCLUSION: The (18)F-FDG PET region-of-interest analysis with aorta-to-liver maximal standardized uptake value ratios is a reliable, investigator-independent indicator of GCA not affected by minor inflammation-associated changes in hepatic metabolism. Our results for a cutoff ratio of 1.0 prove that (18)F-FDG PET is a method of high sensitivity and specificity for GCA-related large-vessel inflammation.