Alexander Haug

Evaluation of fatty acid synthase in prostate cancer recurrence: SUV of [(11) C]acetate PET as a prognostic marker.

High levels of fatty acid synthase have shown to correlate with the aggressiveness of prostate cancer. As [11C]acetate exhibits a close correlation with the level of fatty acid synthase, we aimed to assess whether the SUV in [11C]acetate PET serves as a suitable prognostic marker in patients with recurrent prostate cancer.

Radioembolization with Yttrium-90 Microspheres (SIRT) in Pancreatic Cancer Patients with Liver Metastases: Efficacy, Safety and Prognostic Factors

Objective: To analyze the clinical efficacy of 90Y radioembolization in liver metastases from pancreatic cancer, to describe treatment toxicities and to identify biomarkers as predictors of outcome. Methods: Data from 19 pancreatic cancer patients (9 females/10 males) who had received 90Y radioembolization for metastatic liver disease between 06/2004 and 01/2011 were analyzed retrospectively. Results: The median age at 90Y radioembolization was 63 years (range 43-77). In 16 patients, previous palliative gemcitabine-based chemotherapy was given for metastatic disease. Objective response in the liver after 90Y radioembolization was 47%. Median local progression-free survival in the liver was 3.4 months (range 0.9-45.0). Median overall survival (OS) was 9.0 months (range 0.9-53.0) and 1-year survival was 24%. Cox regression models for baseline biomarkers at 90Y radioembolization revealed correlations of increased carbohydrate antigen 19-9 (p = 0.02) and C-reactive protein (p = 0.03) with shorter OS. Short-term adverse events (nausea, vomiting, fatigue, fever and abdominal pain) did not exceed grade 3. As long-term adverse events, liver abscesses, gastroduodenal ulceration, cholestasis and cholangitis, ascites and spleen infarction were observed. Conclusion:90Y radioembolization is able to induce an encouraging local response rate of liver metastases of pancreatic cancer patients. Most short-term toxicities are manageable; however, patients should be followed up carefully for severe long-term toxicities.

Prognostic value of volumetric PET parameters in unresectable and metastatic esophageal cancer

PURPOSE To assess the prognostic value of volumetric parameters measured with PET/CT in patients with advanced or metastatic esophageal cancer (EC). MATERIALS AND METHODS We identified 71 patients (33 adenocarcinoma [AC] and 38 squamous cell carcinoma [ESCC]) with unresectable or metastatic EC who had PET/CT prior to palliative treatment. Volumetric parameters (metabolic tumor volume [MTV], total lesion glycolysis [TLG], tumor length [TL]) as well as maximum and mean standardized uptake (SUVmax, SUVmean) were obtained from (18)F-FDG PET/CT studies. The correlation between overall survival (OS) and established clinical parameters was assessed using a Cox proportional hazards model. RESULTS ESCC patients had higher SUVmax and SUVmean compared to AC (p=0.002 and p<0.001, respectively). There was an association of lower SUVmax and SUVmean with metastatic compared to locally advanced tumors (e.g., median SUVmax stage IV: 14.9, 95% confidence interval [95% CI 4.4-35.5] vs. stage IIIA-C: 23.3 [9.2-40.6], p=0.017). TL, MTV and TLG showed an association to OS for all patients and for the subgroup of AC patients (AC; TL: Hazard ratio [HR] 3.23, [95% CI 1.03-10.11], p=0.044; MTV: HR 3.16, [95% CI 1.08-9.23], p=0.035). There was no correlation between PET parameters and survival in ESCC patients. Clinical nodal status was the only clinical variable associated to OS (HR 2.45 [95% CI 1.26-4.75], p=0.008) in AC patients. In a multivariate analysis, nodal status and MTV remained as independent factors associated to OS (N: HR 9.98, [95% CI 1.28-78.11], p=0.028; MTV: HR 1.02, [95% CI 1.01-1.03], p=0.003). CONCLUSIONS MTV predicted poor OS in patients with advanced AC. No PET parameters were associated to OS in ESCC patients.

Visual and semiquantitative 11C-methionine PET: an independent prognostic factor for survival of newly diagnosed and treatment-naïve gliomas

Background Few data exist regarding the prognostic value of L-[S-methyl-11C]methionine (MET) PET for treatment-naïve gliomas. Methods A total of 160 glioma patients (89 men, 71 women; mean age: 45, range 18-84 y) underwent a MET PET prior to any therapy. The PET scans were evaluated visually and semiquantitatively by tumor-to-background (T/N) ratio thresholds chosen by analysis of receiver operating characteristics. Additionally, isocitrate dehydrogenase 1-R132H (IDH1-R132H) immunohistochemistry was performed. Survival analysis was done using Kaplan-Meier estimates and the Cox proportional hazards model. Results Significantly shorter mean survival times (7.2 vs 8.6 y; P = 0.024) were seen in patients with amino acid avid gliomas (n = 137) compared with visually negative tumors (n = 33) in MET PET. T/N ratio thresholds of 2.1 and 3.5 were significantly associated with survival (10.3 vs 7 vs 4.3 y; P < 0.001). Mean survival differed significantly using the median T/N ratio of 2.4 as cutoff, independent of histopathology (P < 0.01; mean survival: 10.2 ± 0.8 y vs 5.5 ± 0.6 y). In the subgroup of 142 glioma patients characterized by IDH1-R132H status, METT/N ratio demonstrated a significant prognostic impact in IDH1-R132H wildtype astrocytomas and glioblastoma (P = 0.001). Additionally, multivariate testing revealed semiquantitative MET PET as an independent prognostic parameter for treatment-naïve glioma patients without (P = 0.031) and with IDH1-R132H characterization of gliomas (P = 0.024; odds ratio 1.57). Conclusion This retrospective analysis demonstrates the value of MET PET as a prognostic parameter on survival in treatment-naïve glioma patients.

Reduced task durations in functional PET imaging with [18F]FDG approaching that of functional MRI

Introduction: The brains energy budget can be non‐invasively assessed with different imaging modalities such as functional MRI (fMRI) and PET (fPET), which are sensitive to oxygen and glucose demands, respectively. The introduction of hybrid PET/MRI systems further enables the simultaneous acquisition of these parameters. Although a recently developed method offers the quantification of task‐specific changes in glucose metabolism (CMRGlu) in a single measurement, direct comparison of the two imaging modalities is still difficult because of the different temporal resolutions. Thus, we optimized the protocol and systematically assessed shortened task durations of fPET to approach that of fMRI. Methods: Twenty healthy subjects (9 male) underwent one measurement on a hybrid PET/MRI scanner. During the scan, tasks were completed in four blocks for fMRI (4×30s blocks) and fPET: participants tapped the fingers of their right hand repeatedly to the thumb while watching videos of landscapes. For fPET, subjects were randomly assigned to groups of n=5 with varying task durations of 10, 5, 2 and 1min, where task durations were kept constant within a measurement. The radiolabeled glucose analogue [18F]FDG was administered as 20% bolus plus constant infusion. The bolus increases the signal‐to‐noise ratio and leaves sufficient activity to detect task‐related effects but poses additional challenges due to a discontinuity in the tracer uptake. First, three approaches to remove task effects from the baseline term were evaluated: (1) multimodal, based on the individual fMRI analysis, (2) atlas‐based by removing presumably activated regions and (3) model‐based by fitting the baseline with exponential functions. Second, we investigated the need to capture the arterial input function peak with automatic blood sampling for the quantification of CMRGlu. We finally compared the task‐specific activation obtained from fPET and fMRI qualitatively and statistically. Results: CMRGlu quantified only with manual arterial samples showed a strong correlation to that obtained with automatic sampling (r=0.9996). The multimodal baseline definition was superior to the other tested approaches in terms of residuals (p<0.001). Significant task‐specific changes in CMRGlu were found in the primary visual and motor cortices (tM1=18.7 and tV1=18.3). Significant changes of fMRI activation were found in the same areas (tM1=16.0 and tV1=17.6) but additionally in the supplementary motor area, ipsilateral motor cortex and secondary visual cortex. Post‐hoc t‐tests showed strongest effects for task durations of 5 and 2min (all p<0.05 FWE corrected), whereas 1min exhibited pronounced unspecific activation. Percent signal change (PSC) was higher for CMRGlu (˜18%–27%) compared to fMRI (˜2%). No significant association between PSC of task‐specific CMRGlu and fMRI was found (r=0.26). Conclusion: Using a bolus plus constant infusion protocol, the necessary task duration for reliable quantification of task‐specific CMRGlu could be reduced to 5 and 2min, therefore, approaching that of fMRI. Important for valid quantification is a correct baseline definition, which was ideal when task‐relevant voxels were determined with fMRI. The absence of a correlation and the different activation pattern between fPET and fMRI suggest that glucose metabolism and oxygen demand capture complementary aspects of energy demands. HIGHLIGHTSQuantification of task‐specific CMRGlu with 20% bolus plus constant infusion.Functional PET task durations down to 1min were evaluated.Active primary regions overlap between BOLD and CMRGlu.No significant correlation between BOLD and CMRGlu.

[18F]FDG-PET/CT and MRI for initial pelvic lymph node staging in patients with cervical carcinoma: The potential usefulness of [18F]FDG-PET/MRI

The current study aimed to determine the optimum diagnostic imaging technique out of magnetic resonance imaging (MRI), 18F-fludeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT, otherwise known as PET/CT) and [18F]FDG-PET/MRI (otherwise known as PET/MRI) for the pelvic lymph node staging (N-staging) of untreated cervical carcinoma (CC). A total of 27 patients were included in the present study. All patients had undergone pre-treatment with PET/CT and MRI ≤45 days prior to undergoing a lymphadenectomy. The results from PET (separated from PET/CT), MRI and the statistically combined results of (virtual) PET/MRI were compared to those from histological analyses (the gold standard). A per-patient-based analysis of the detection of pelvic lymph node metastases indicated that PET/MRI had a sensitivity of 64%. The specificity of PET/CT and MRI were 69 and 62%, respectively. The positive predictive value (PPV) was 69 and 64% for PET/CT and MRI, respectively. The negative predictive value (NPV) was 64 and 62% for PET/CT and MRI, respectively. The sensitivity of the PET-guided PET/MRI and the MRI-guided PET/MRI was 64% for both. The specificity of the PET-guided PET/MRI and the MRI-guided PET/MRI was 77 and 62%, respectively. The PPV was 75% for PET-guided PET/MRI and 64% for MRI-guided PET/MRI, and the NPV was 67 and 62%, respectively. PET/CT and the virtual PET/MRI exhibited the same low sensitivity (64%). PET/MRI exhibited slightly better results than PET/CT regarding specificity (77 vs. 69%, respectively), PPV (75 vs. 69%, respectively) and NPV (67 vs. 64%, respectively). The results of the present study suggested that PET/CT and MRI are not optimal diagnostic modalities, and that PET/MRI does not necessarily lead to better results than PET/CT, in the pelvic N-staging of CC.

Does elevated glucose metabolism correlate with higher cell density in Neurofibromatosis type 1 associated peripheral nerve sheath tumors

Purpose To investigate whether elevated glucose metabolism in neurofibroma, determined by [F18]-FDG-PET, is correlated with cell density in MRI, as expressed through the apparent diffusion coefficient. Materials and methods Patients diagnosed with neurofibromatosis type 1 and peripheral nerve sheath tumors (PNST) were enrolled in this prospective, IRB-approved study. After a single [F18]-FDG injection, patients consecutively underwent [F18]-FDG-PET/CT and [F18]-FDG-PET/MRI on the same day. Maximum and mean standardized uptake values (SUVmax, SUVmean) on [F18]-FDG-PET/CT and [F18]-FDG-PET/MRI were compared, and correlated with minimum and mean apparent diffusion coefficients (ADCmean, ADCmin). Results A total of 12 (6 male/6 female, mean age was 16.2 ± 5.2 years) patients were prospectively included and analyzed on a per-lesion (n = 39) basis. The SUVmean of examined PNST showed a moderate negative correlation with the ADCmean (r = -.441) and ADCmin (r = -.477), which proved to be statistically significant (p = .005 and p = .002). The SUVmax of the respective lesions, however, showed a weaker negative correlation for ADCmean (r: -.311) and ADCmin (r: -.300) and did not reach statistical significance (p = .054 and p = .057). Lesion-based correlation between [F18]-FDG-PET/MRI and [F18]-FDG-PET/CT showed a moderate correlation for SUVmax (r = .353; p = .027) and a strong one for SUVmean (r = .879; p = .001)). Patient-based liver uptake (SUVmax and mean) of [F18]-FDG-PET/MRI and [F18]-FDG-PET/CT were strongly positively correlated (r = .827; p < .001 and r = .721; p < .001) but differed significantly (p < .001). Conclusions We found a statistically significant, negative correlation between glucose metabolism and cell density in PNST. Thus, ADCmean and ADCmin could possibly add complimentary information to the SUVmax and SUVmean and may serve as a potential determinant of malignant transformation of PNST.

Appearances are often deceptive (Reply: High impact of angiographic parameters on MAA and 90Y loaded microsphere uptake correlation)

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