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Objectives Standardized measures for assessing neurological patients needing palliative care remain scarce. The Integrated Palliative care Outcome Scale for neurological patients in its short form (IPOS Neuro-S8) helps assess and identify patients’ symptom burden and needs early but has not yet been validated in German. The aim was to culturally adapt and translate the IPOS Neuro-S8 into the German health-care context and evaluate its face and content validity. Methods Cultural adaptation study following the first 6 out of 8 phases of the Palliative care Outcome Scale measures manual: (1) conceptual definition, (2) forward translation to German, (3) backward translation to English, (4) expert review, (5) cognitive debriefing, (6) proofreading. Neurological patients needing palliative care and clinical staff of the Department of Palliative Medicine or Neurology of the University Hospital of Cologne were included. Data were analyzed using thematic content analysis and descriptive statistics. Results A total of 13 patients and 16 clinical staff participated in this study. The expert review panel (phase 4) consisted of 11 additional members. While patients (n = 9) and clinical staff (n = 11) confirmed that the IPOS Neuro-S8 is an intelligible tool that is well accepted (phase 5), some linguistic and cultural differences were found between the original English and German versions. These mainly concerned the items mouth problems and spasms. Significance of results The German version of the IPOS Neuro-S8 has demonstrated face and content validity and captures relevant symptoms of neurological patients needing palliative care. Its psychometric properties, including construct and criterion validity, will be investigated next.

Care and case management (CCM) aims to provide optimal care for patients and their caregivers on an individual and superordinate level of health care providers and authorities. To facilitate a clear and systematic CCM process as part of a clinical study intervention, a semistructured manual is the prerequisite.The ongoing COCOS-MS (Communication, Coordination and Security for People with Multiple Sclerosis) study is a randomized controlled Phase II clinical intervention study. The CCM manual is being tested on the intervention group consisting of severely affected individuals with multiple sclerosis (MS; Expanded Disability Status Scale [EDSS]5) and their caregivers receiving CCM for 12 months in addition to standard care. The intervention comprises monthly personal visits and weekly telephone calls during which the CCM manual is applied.The CCM manual has been developed on the basis of previous literature and well-established questionnaires following theoretical aspects and prior scientific work covering individual domains of life of people with MS. Within the COCOS-MS study, its feasibility is being tested meticulously. It allows for a standardized assessment while being tailored to the individual. At the end of the intervention period, it will be analyzed statistically and qualitatively. Consequently, conclusions can be drawn as to whether the CCM manual is feasible or has to be adapted for use in standard care after analyzation.The CCM manual serves as a tool for the continuous, long-term, cross-sectoral care for patients suffering from severe MS and their caregivers. The manual provides guidance in adequately addressing patients' complex symptoms, problems, and needs, as well as assessing existing resources both at the individual patient level and at a superordinate level.

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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

IntroductionPatients with multiple sclerosis (MS) have complex needs that range from organising one’s everyday life to measures of disease-specific therapy monitoring to palliative care. Patients with MS are likely to depend on multiple healthcare providers and various authorities, which are often difficult to coordinate. Thus, they will probably benefit from comprehensive cross-sectoral coordination of services provided by care and case management (CCM). Though studies have shown that case management improves quality of life (QoL), functional status and reduces service use, such benefits have not yet been investigated in severely affected patients with MS. In this explorative phase ll clinical trial, we evaluated a CCM with long-term, cross-sectoral and outreaching services and, in addition, considered the unit of care (patients and caregivers).Methods and analysisEighty patients with MS and their caregivers will be randomly assigned to either the control (standard care) or the intervention group (standard care plus CCM (for 12 months)). Regular data assessments will be done at baseline and then at 3-month intervals. As primary outcome, we will evaluate patients’ QoL. Secondary outcomes are patients’ treatment-related risk perception, palliative care needs, anxiety/depression, use of healthcare services, caregivers’ burden and QoL, meeting patients’ and caregivers’ needs, and evaluating the CCM intervention. We will also evaluate CCM through individual interviews and focus groups. The sample size calculation is based on a standardised effect of 0.5, and one baseline and four follow-up assessments (with correlation 0.5). Linear mixed models for repeated measures will be applied to analyse changes in quantitative outcomes over time. Multiple imputation approaches are taken to assess the robustness of the results. The explorative approach (phase ll clinical trial) with embedded qualitative research will allow for the development of a final design for a confirmative phase lll trial.Ethics and disseminationThe trial will be conducted under the Declaration of Helsinki and has been approved by the Ethics Commission of Cologne University’s Faculty of Medicine. Trial results will be published in an open-access scientific journal and presented at conferences.Trial registration numberGerman Register for Clinical Studies (DRKS) (DRKS00022771).

The goal of this study was to compare the value of contrast-enhanced MRI and O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) PET for response assessment in glioma patients after adjuvant temozolomide chemotherapy (TMZ). Methods: After biopsy or resection and completion of radiotherapy with concomitant TMZ, 41 newly diagnosed and histomolecularly characterized glioma patients (glioblastoma, 90%; age range, 20-79 y) were subsequently treated with adjuvant TMZ. MR and 18F-FET PET imaging were performed at baseline and after the second cycle of adjuvant TMZ. We obtained 18F-FET metabolic tumor volumes (MTVs) as well as mean and maximum tumor-to-brain ratios (TBRmean and TBRmax, respectively). Threshold values of 18F-FET PET parameters to predict outcome were established by receiver-operating-characteristic analyses using a median progression-free survival (PFS) of ≥ 9 mo and overall survival (OS) of ≥ 15 mo as reference. MRI response assessment was based on the Response Assessment in Neuro-Oncology (RANO) working group criteria. The predictive value of changes of 18F-FET PET and MRI parameters on survival was evaluated subsequently using univariate and multivariate survival estimates. Results: After 2 cycles of adjuvant TMZ chemotherapy, a treatment-induced reduction of MTV and TBRmax predicted a significantly longer PFS and OS (both P ≤ 0.03; univariate survival analyses) whereas RANO criteria were not significant (P > 0.05). Multivariate survival analysis revealed that TBRmax changes predicted a prolonged PFS (P = 0.012) and changes of MTV a prolonged OS (P = 0.005) independent of O6-methylguanine-DNA-methyltransferase promoter methylation and other strong prognostic factors. Conclusion: Changes of 18F-FET PET parameters appear to be helpful for identifying responders to adjuvant TMZ early after treatment initiation.

The goal of this study was to compare the value of contrast-enhanced MRI and O-(2-[

The goal of this prospective study was to compare the value of both conventional MRI and O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET for response evaluation in glioblastoma patients treated with bevacizumab plus lomustine (BEV/LOM) at first progression. After chemoradiation with concomitant and adjuvant temozolomide, 21 IDH wild-type glioblastoma patients at first progression (age range, 33–75 years; MGMT promoter unmethylated, 81%) were treated with BEV/LOM. Contrast-enhanced MRI and FET-PET scans were performed at baseline and after 8–10 weeks. We obtained FET metabolic tumor volumes (MTV) and tumor/brain ratios. Threshold values of FET-PET parameters for treatment response were established by ROC analyses using the post-progression overall survival (OS) ≤/>9 months as the reference. MRI response assessment was based on RANO criteria. The predictive ability of FET-PET thresholds and MRI changes on early response assessment was evaluated subsequently concerning OS using uni- and multivariate survival estimates. Early treatment response as assessed by RANO criteria was not predictive for an OS>9 months (P = 0.203), whereas relative reductions of all FET-PET parameters significantly predicted an OS>9 months (P

BACKGROUND: The goal of this prospective study was to compare the value of conventional MRI and O-(2-(18)F-fluoroethyl)-L-tyrosine (FET) PET for response assessment in patients with malignant glioma treated with first-line adjuvant temozolomide chemotherapy (TMZ). METHODS: After biopsy/resection and completion of radiotherapy with concomitant temozolomide, 34 malignant glioma patients (glioblastoma, n=31; IDH-wildtype anaplastic astrocytoma, n=2; H3K27-mutated midline glioma, n=1) (age range, 20–66 years) were subsequently treated with adjuvant TMZ (5/28). FET-PET scans were performed at baseline and after 10–12 weeks. The first follow-up MRI after radiotherapy (9 ± 3 weeks) was compared with the early postoperative MRI. We obtained FET metabolic tumor volumes (MTV) and tumor/brain ratios (TBR). Threshold values of FET-PET parameters for treatment response were established by ROC analyses using the progression-free survival (PFS) ≤/>9 months as reference. MRI response assessment was based on RANO criteria. The predictive ability of FET-PET thresholds and MRI changes on early response assessment was evaluated subsequently concerning PFS using univariate survival estimates. RESULTS: Relative TBR changes were not predictive for a PFS>9 months (P>0.05), whereas the absolute MTV at follow-up significantly predicted a PFS>9 months (P=0.016; threshold, 14.5 ml). The relative MTV change enabled the most significant PFS prediction. Responders defined by relative MTV changes (threshold, ≤0%) had a significantly 2-fold longer PFS than non-responders (16 vs. 8 months, P=0.003). RANO criteria at the first follow-up MRI after radiotherapy were not predictive for a PFS>9 months (P=0.260). CONCLUSIONS: FET-PET appears to be useful for identifying responders to adjuvant TMZ early after treatment initiation.

Novel therapeutic targets in malignant glioma patients are urgently needed. Point mutations of the v-Raf murine sarcoma viral oncogene homolog B (BRAF) gene occur predominantly in melanoma patients, but may also occur in gliomas. Thus, this is a target of great interest for this group of patients. In a nine-year-old male patient, an anaplastic astrocytoma in the left temporoparietal region was diagnosed histologically. After first- and second-line treatment, a malignant progression to a secondary glioblastoma was observed ten years after the initial diagnosis. Within the following seven years, all other conventional treatment options were exhausted. At this time point, recurrent tumor histology revealed an epithelioid glioblastoma, without a mutation in the isocitrate dehydrogenase gene (IDH wild-type). In order to identify a potential target for an experimental salvage therapy, mutational tumor analysis showed a BRAF V600E mutation. Consecutively, dabrafenib treatment was initiated. The patient remained clinically stable, and follow-up magnetic resonance images (MRI) were consistent with “Stable Disease” according to the Response Assessment in Neuro-Oncology Working Group (RANO) criteria for the following ten months until tumor progression was detected. The patient died 16 months after dabrafenib treatment initiation. Particularly in younger glioma patients as well as in patients with an epithelioid glioblastoma, screening for a V600E BRAF mutation is promising since, in these cases, targeted therapy with BRAF inhibitors seems to be a useful salvage treatment option.

The implementation of self-reported outcome measurements into clinical routine was tested to help facilitate early access to palliative care (PC) for glioblastoma (GBM)-patients. Measures detail PC symptoms and concerns and caregiver burden. Between January 2014 and December 2016, a total of 337 GBM-patients were discussed during meetings of the neuro-oncology tumor board to examine further treatment options. Each patient, along with their caregivers, was requested to participate in self-assessment using the palliative outcome scale (POS) and the Zarit Burden Interview (ZBI). Analyses encompassed summary statistics, non-parametric tests, visual graphic analysis, content analysis and assessing the utilization of the specialized PC consulting service (SPCCS). Ninety-five (28%) GBM-patients and 71 (21%) caregivers completed the self-assessment. Of these, 20 patients and 12 caregivers repeated the assessment at least once more during follow-up. POS total scores were similar in the group of patients with initial diagnosis [10 (0-31)] and those with later disease stages like recurrent diagnosis [9 (0-25)], but ZBI total scores differed [14 (0-51) vs. 24 (2-62)]. Single item analysis demonstrated that anxiety and worries about the future predominated. Caregivers were torn between high engagement in caring and feeling overburdened. Still, requests for the SPCCS showed no increase. Actual implementation of measures like POS and ZBI for detecting PC concerns and caregiver burden with GBM-patients in the field remains challenging as indicated by the limited response rate and lack of increased requests for the SPCCS. Modified clinical routines including strengthening awareness of PC, and allowing proxy-assessment might help to overcome barriers.

88 Objectives To determine if 18F-FDG (FDG) could replace 67Ga (Ga) for differentiating acute interstitial nephritis (AIN) from acute tubular necrosis (ATN). Methods 50 rats were divided into 3 groups: Controls (10), AIN (20) & ATN (20). Half of the animals in each group were studied with FDG & half with Ga. AIN animals were imaged 14 days after a single injection of 150 mg/kg puromycin aminonucleoside. ATN animals were imaged 8 days after intraperitoneal injection of 6 mg/kg cisplatin. FDG imaging was performed on a micro-PET system 45 min after tail vein injection of 7.4 MBq FDG. Kidney SUV’s were determined. After imaging, organs were removed & kidney/spine tissue counting ratios generated. Renal tissue samples were evaluated by a pathologist for evidence of cellular infiltration. Ga imaging was performed 48 hr after tail vein injection of 3.7 MBq Ga. Static images were acquired at maximum magnification (zoom = 2.19, 5.9 mm/pixel) with a pinhole collimator for 10 min. Regions of interest were drawn around kidneys & adjacent lumbar spine; kidney:spine image count ratios were generated. An experienced Nuclear physician interpreted all images visually. Results For FDG, AIN & ATN SUV’s were significantly higher than Control SUVs, but similar to each other (Table). Tissue analysis results were similar. The reader could distinguish FDG AIN & ATN from Controls, but not from each other. For Ga, kidney:spine ratios were significantly higher for AIN than ATN & Controls, which were similar to each other. Tissue analysis results were similar. The reader could differentiate AIN from ATN & Controls, but not ATN from Controls. Cellular infiltration was predominantly mononuclear, & was significantly higher in AIN than in ATN & Controls (2.3±0.5 versus 0.6±0.5 cells, p=0.002). Conclusions The results indicate that FDG-PET cannot replace Ga for differentiating acute interstitial nephritis from acute tubular necrosis.

The follow-up of glioblastoma patients after radiochemotherapy with conventional MRI can be difficult since reactive alterations to the blood–brain barrier with contrast enhancement may mimic tumour progression (i.e. pseudoprogression, PsP). The aim of this study was to assess the clinical value of O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) PET in the differentiation of PsP and early tumour progression (EP) after radiochemotherapy of glioblastoma. A group of 22 glioblastoma patients with new contrast-enhancing lesions or lesions showing increased enhancement (>25 %) on standard MRI within the first 12 weeks after completion of radiochemotherapy with concomitant temozolomide (median 7 weeks) were additionally examined using amino acid PET with 18F-FET. Maximum and mean tumour-to-brain ratios (TBRmax, TBRmean) were determined. 18F-FET uptake kinetic parameters (i.e. patterns of time–activity curves, TAC) were also evaluated. Classification as PsP or EP was based on the clinical course (no treatment change at least for 6 months), follow-up MR imaging and/or histopathological findings. Imaging results were also related to overall survival (OS). PsP was confirmed in 11 of the 22 patients. In patients with PsP, 18F-FET uptake was significantly lower than in patients with EP (TBRmax 1.9 ± 0.4 vs. 2.8 ± 0.5, TBRmean 1.8 ± 0.2 vs. 2.3 ± 0.3; both P

Background Despite an increasing number of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET studies in supratentorial gliomas, studies regarding the usefulness of 18F-FET PET in brainstem and spinal cord gliomas to date remain scarce. Methods Thirty-six 18F-FET PET scans were performed in 29 patients with brainstem (n = 29 scans) or spinal cord glioma (n = 7 scans). In 32 of 36 PET scans, a dynamic acquisition was performed. Fifteen scans in 15 patients were performed to assess newly diagnosed lesions, and 21 scans were obtained during follow-up: for diagnosing tumor progression (n = 15 scans in 14 patients) as well as for treatment monitoring (n = 6 scans in 3 patients). Four patients underwent additional serial scans (range, 1-2), and 3 of these 4 patients were examined for more than one indication. Maximum and mean tumor/brain ratios (TBRmax/mean) of 18F-FET uptake (20-40 min post injection) as well as kinetic 18F-FET uptake parameters were determined. Final diagnoses were confirmed histologically (54%) or by clinical follow-up (46%). Results In all newly diagnosed high-grade (n = 3 patients) and in 5 of 11 patients with low-grade gliomas, 18F-FET uptake was increased (TBRmax ≥2.5 and/or TBRmean ≥1.9). In 2 patients with newly diagnosed gliomas without MR contrast enhancement, 18F-FET PET nevertheless showed increased metabolism. At suspected progression, the combination of TBRs with kinetic 18F-FET parameters correctly identified presence or absence of progressive disease in 9 of 11 patients (82%). Conclusions This preliminary study suggests that 18F-FET PET adds valuable diagnostic information in brainstem and spinal cord glioma, particularly when the diagnostic information derived from MRI is equivocal.

BACKGROUND We evaluated the diagnostic value of static and dynamic O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) PET parameters in patients with progressive or recurrent glioma. METHODS We retrospectively analyzed 132 dynamic (18)F-FET PET and conventional MRI scans of 124 glioma patients (primary World Health Organization grade II, n = 55; grade III, n = 19; grade IV, n = 50; mean age, 52 ± 14 y). Patients had been referred for PET assessment with clinical signs and/or MRI findings suggestive of tumor progression or recurrence based on Response Assessment in Neuro-Oncology criteria. Maximum and mean tumor/brain ratios of (18)F-FET uptake were determined (20-40 min post-injection) as well as tracer uptake kinetics (ie, time to peak and patterns of the time-activity curves). Diagnoses were confirmed histologically (95%) or by clinical follow-up (5%). Diagnostic accuracies of PET and MR parameters for the detection of tumor progression or recurrence were evaluated by receiver operating characteristic analyses/chi-square test. RESULTS Tumor progression or recurrence could be diagnosed in 121 of 132 cases (92%). MRI and (18)F-FET PET findings were concordant in 84% and discordant in 16%. Compared with the diagnostic accuracy of conventional MRI to diagnose tumor progression or recurrence (85%), a higher accuracy (93%) was achieved by (18)F-FET PET when a mean tumor/brain ratio ≥2.0 or time to peak

Antiangiogenic treatment using bevacizumab in brain tumor patients may cause difficulties in the diagnosis of tumor progression (ie, nonenhancing tumor progression). Newly defined criteria for treatment assessment and diagnosis of tumor progression (ie, RANO [Response Assessment in Neuro-Oncology] criteria) have implemented signal alterations on T2/fluid-attenuated inversion recovery (FLAIR) sequences to changes in contrast enhancement. However, T2/FLAIR hyperintensity may be influenced by other causes (eg, radiation-induced leukoencephalopathy, peritumoral edema, gliosis). Positron emission tomography using the radiolabeled amino acid O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET-PET) may help detect the metabolically active tumor extent. We present 18F-FET-PET imaging findings in a glioblastoma patient during bevacizumab treatment suggesting an earlier diagnosis of tumor progression than magnetic resonance imaging changes, which are based on the RANO criteria.

The purpose of this positron emission tomography (PET) study was to compare the prognostic value of pretreatment volume of ¹¹C]-methionine (MET) uptake and semiquantitative MET uptake ratio in patients with malignant glioma. The study population comprised 40 patients with malignant glioma. Pretreatment magnetic resonance imaging (MRI) and MET-PET imaging were performed before the initiation of glioma treatment in all patients. The pretreatment MET uptake ratios and volumes were assessed. To create prognostically homogeneous subgroups, patients' pretreatment prognostic factors were stratified according to the six classes of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA). Univariate and multivariate analyses were performed to determine significant prognostic factors. Survival analyses identified the pretreatment volume of MET uptake and a higher RTOG RPA class as significant predictors. In contrast, pretreatment maximum areas of contrast enhancement on MRI and semiquantitative MET uptake ratios could not be identified as significant prognostic factors. The patients' outcomes and Karnofsky Performance Scale scores were significantly correlated with pretreatment volume of MET uptake but not with semiquantitative MET uptake ratio. The data suggest that pretreatment volumetry of MET uptake but not the semiquantitative MET uptake ratio is a useful biologic prognostic marker in patients with malignant glioma.

In patients with World Health Organization (WHO) grade III glioma with a lack of or minimal (1 cm3) magnetic resonance imaging (MRI) contrast enhancement, the volume of the metabolically active part of the tumor was assessed by [¹¹C]-methionine positron emission tomography (MET-PET). Eleven patients with WHO grade III gliomas underwent MET-PET and MRI (contrast-enhanced T1- and T2-weighted images). To calculate the volumes in cubic centimeters, threshold-based volume of interest analyses of the metabolically active tumor (MET uptake index ≥ 1.3), contrast enhancement, and the T2 lesion were performed after coregistration of all images. In all patients, the metabolically active tumor volume was larger than the volume of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhancement (20.8 ± 18.8 vs 0.29 ± 0.25 cm3; p.001). With the exception of one patient, the volumes of contrast enhancement were located within the metabolically active tumor volume. In contrast, in the majority of patients, MET uptake overlapped with the T2 lesion and reached beyond it (in 10 of 12 MRIs/MET-PET scans). The present data suggest that in patients with WHO grade III glioma with minimal or a lack of contrast enhancement, MET-PET delineates metabolically active tumor tissue. These findings support the use of combined PET-MRI with radiolabeled amino acids (eg, MET) for the delineating of the true extent of active tumor in the diagnosis and treatment planning of patients with gliomas.

BACKGROUND: We compared prospectively MRI response assessment based on RANO criteria with metabolic O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET response evaluation during bevacizumab plus lomustine (BEV/LOM) treatment in glioblastoma patients at first recurrence. METHODS: Patients at first recurrence of a primary glioblastoma after radiotherapy with concomitant and adjuvant temozolomide chemotherapy were treated accordingly to the BELOB trial with LOM 90 mg/m2 every 6 weeks and BEV 10 mg/kg every 2 weeks. Dynamic FET PET and standard MRI scans were performed at baseline and after 8-10 weeks. FET PET metabolic tumor volumes (MTV), maximum and mean tumor/brain ratios (TBRmax/mean) as well as dynamic FET PET parameters were obtained. The predictive ability of FET PET parameters and standard MRI on treatment response assessment was evaluated with regard to PFS and OS after starting of treatment. Using receiver-operating characteristic curve analyses, threshold values for FET PET parameter changes were obtained. MRI changes consistent with “Stable Disease”, “Partial Response” and “Complete Response” were considered as treatment response. Subsequently, Kaplan-Meier survival analyses were performed to assess their predictive power for survival. RESULTS: Nineteen patients were included. Fifteen of 19 patients (age range, 34-75 years; MGMT promoter not methylated, 87%; IDH wild type, 100%) were eligible for data evaluation. Treatment response as assessed by standard MRI based on RANO criteria was not predictive for a significant longer PFS (P = 0.23) and OS (P = 0.07), respectively. In contrast, FET PET changes predicted a longer PFS (MTV decrease > 25%, P = 0.01; TBRmax decrease > 12%, P = 0.02) and OS (MTV decrease > 10%, P = 0.04), respectively. Interestingly, absolute MTV at the first follow-up scan provides the most significant prediction for increased PFS (P = 0.006) as well as OS (P = 0.003). However, both TBRmean and dynamic FET PET parameters were not predictive for treatment response. CONCLUSIONS: FET PET appears to be helpful to identify treatment responders to BEV/LOM early after initiation of treatment.

BACKGROUND: Experience regarding the use of dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) PET in children and adolescents with brain tumors is limited. METHODS: Sixty-nine 18F-FET PET scans of 49 patients (median age, 13 years; range, 1-18 years) were analyzed retrospectively. Patients had been referred for: (A) assessment of newly diagnosed cerebral lesions (26 scans in 26 patients), (B) diagnosing tumor progression/recurrence (24 scans in 18 patients), (C) monitoring of chemotherapy effects (8 scans in 4 patients), and (D) the detection of residual tumor tissue after resection (11 scans in 10 patients). Maximum and mean tumor/brain ratios (TBRmax/mean) of 18F-FET uptake were determined (20-40 min p.i.) and time-activity curves were generated and assigned to one of the following patterns: (1) constantly increasing uptake, (2) uptake peaking at a midway point (>20-40 min) followed by a plateau, and (3) uptake peaking early (≤20 min) followed by a constant descent. The diagnostic values of TBRs and kinetic parameters to detect neoplastic tissue or diagnose tumor progression/recurrence were assessed using ROC analyses. Diagnoses were confirmed histologically and/or by clinical course. RESULTS: In patients with newly diagnosed cerebral lesions, highest accuracy (77%) to detect neoplastic tissue (7 of 26 patients) was obtained when TBRmax was >1.7 (AUC, 0.80 ± 0.09; sensitivity, 79%; specificity, 71%, PPV, 88%; P = 0.02). For diagnosing tumor progression/recurrence, highest accuracy (82%) was obtained when curve patterns 2 or 3 were present (AUC, 0.80 ± 0.11; sensitivity, 75%; specificity, 90%, PPV, 90%; P = 0.02). During chemotherapy, a decrease of TBRs was associated with a stable clinical course at least for 6 months. In patients after complete tumor resection (2 of 10 patients), 18F-FET PET detected metabolically active tumor (TBRmax ≥ 1.7). CONCLUSIONS: Our findings suggest that 18F-FET PET can add valuable information for clinical decision-making in pediatric brain tumor patients.

BACKGROUND: The follow-up of glioblastoma patients may be difficult with conventional MRI since reactive blood-brain barrier alterations with contrast enhancement can mimick tumor progression (“pseudoprogression”), especially early after completion of radiochemotherapy. PATIENTS AND METHODS: Twenty-six glioblastoma patients with newly appearance or an increase of enhancing lesions (>25%) on standard MRI with gadolinium-based contrast agents within the first 12 weeks after completion of radiochemotherapy with concomitant temozolomide (median time, 7 weeks) were additionally examined by amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) (n = 22) or 11C-methyl-L-methionine (11C-MET) (n = 4). Median duration between MR and amino acid PET imaging was 7 d. Maximum and mean tumor/brain ratios (TBRmax, TBRmean) of 18F-FET and 11C-MET uptake were determined. Furthermore, 18F-FET uptake kinetic parameters (i.e., time-to-peak and patterns of the time-activity curves (TAC)) were evaluated. The presence of pseudoprogression/early tumor progression was based on the clinical course (progression-free survival (PFS) >/≤ 6 mo) and/or histopathological findings. Imaging results were also related to overall survival (OS). RESULTS: Pseudoprogression was confirmed in 14 of 26 patients. TBRmax and TBRmean of 18F-FET/11C-MET uptake were significantly higher in patients with early tumor progression (n = 12) than in patients with pseudoprogression (TBRmax, 3.6 ± 0.8 vs. 2.4 ± 0.4; TBRmean, 2.5 ± 0.3 vs. 1.8 ± 0.2; both P < 0.001). Furthermore, patterns of TAC were significantly different in both groups (P = 0.04) and presence of MGMT promoter methylation was significantly higher in patients with pseudoprogression (P = 0.02). Receiver-operating-characteristic analysis yielded a TBRmax of 2.9 as an optimal cut-off to identify early tumor progression (sensitivity, 92%; specificity, 93%; accuracy, 92%; area under the curve, 0.96 ± 0.04; P < 0.001). Univariate survival analyses revealed that a TBRmax < 2.9 predicted both a significantly longer PFS (median PFS, 21 vs. 5 months; P < 0.001) and OS (median OS, 33 vs. 12 months; P = 0.007). CONCLUSION: Amino acid PET contributes significantly in diagnosing pseudoprogression.

Antiangiogenic treatment using bevacizumab in brain tumor patients may cause difficulties in the diagnosis of tumor progression (ie, nonenhancing tumor progression). Newly defined criteria for treatment assessment and diagnosis of tumor progression (ie, RANO [Response Assessment in Neuro-Oncology] criteria) have implemented signal alterations on T2/fluid-attenuated inversion recovery (FLAIR) sequences to changes in contrast enhancement. However, T2/FLAIR hyperintensity may be influenced by other causes (eg, radiation-induced leukoencephalopathy, peritumoral edema, gliosis). Positron emission tomography using the radiolabeled amino acid O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET-PET) may help detect the metabolically active tumor extent. We present 18F-FET-PET imaging findings in a glioblastoma patient during bevacizumab treatment suggesting an earlier diagnosis of tumor progression than magnetic resonance imaging changes, which are based on the RANO criteria.

The purpose of this positron emission tomography (PET) study was to compare the prognostic value of pretreatment volume of ¹¹C]-methionine (MET) uptake and semiquantitative MET uptake ratio in patients with malignant glioma. The study population comprised 40 patients with malignant glioma. Pretreatment magnetic resonance imaging (MRI) and MET-PET imaging were performed before the initiation of glioma treatment in all patients. The pretreatment MET uptake ratios and volumes were assessed. To create prognostically homogeneous subgroups, patients' pretreatment prognostic factors were stratified according to the six classes of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA). Univariate and multivariate analyses were performed to determine significant prognostic factors. Survival analyses identified the pretreatment volume of MET uptake and a higher RTOG RPA class as significant predictors. In contrast, pretreatment maximum areas of contrast enhancement on MRI and semiquantitative MET uptake ratios could not be identified as significant prognostic factors. The patients' outcomes and Karnofsky Performance Scale scores were significantly correlated with pretreatment volume of MET uptake but not with semiquantitative MET uptake ratio. The data suggest that pretreatment volumetry of MET uptake but not the semiquantitative MET uptake ratio is a useful biologic prognostic marker in patients with malignant glioma.

In patients with World Health Organization (WHO) grade III glioma with a lack of or minimal (< 1 cm3) magnetic resonance imaging (MRI) contrast enhancement, the volume of the metabolically active part of the tumor was assessed by [ 11 C]-methionine positron emission tomography (MET-PET). Eleven patients with WHO grade III gliomas underwent MET-PET and MRI (contrast-enhanced T1-and T2-weighted images). To calculate the volumes in cubic centimeters, threshold-based volume of interest analyses of the metabolically active tumor (MET uptake index ≥ 1.3), contrast enhancement, and the T2 lesion were performed after coregistration of all images. In all patients, the metabolically active tumor volume was larger than the volume of gadolinium–diethylenetriamine pentaacetic acid (Gd-DTPA) enhancement (20.8 ± 18.8 vs 0.29 ± 0.25 cm3; p < .001). With the exception of one patient, the volumes of contrast enhancement were located within the metabolically active tumor volume. In contrast, in the majority of patients, MET uptake overlapped with the T2 lesion and reached beyond it (in 10 of 12 MRIs/MET-PET scans). The present data suggest that in patients with WHO grade III glioma with minimal or a lack of contrast enhancement, MET-PET delineates metabolically active tumor tissue. These findings support the use of combined PET-MRI with radiolabeled amino acids (eg, MET) for the delineating of the true extent of active tumor in the diagnosis and treatment planning of patients with gliomas.

BACKGROUND: The follow-up of glioblastoma patients may be difficult with conventional MRI since reactive blood-brain barrier alterations with contrast enhancement can mimick tumor progression (“pseudoprogression”), especially early after completion of radiochemotherapy. PATIENTS AND METHODS: Twenty-six glioblastoma patients with newly appearance or an increase of enhancing lesions (>25%) on standard MRI with gadolinium-based contrast agents within the first 12 weeks after completion of radiochemotherapy with concomitant temozolomide (median time, 7 weeks) were additionally examined by amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) (n = 22) or 11C-methyl-L-methionine (11C-MET) (n = 4). Median duration between MR and amino acid PET imaging was 7 d. Maximum and mean tumor/brain ratios (TBRmax, TBRmean) of 18F-FET and 11C-MET uptake were determined. Furthermore, 18F-FET uptake kinetic parameters (i.e., time-to-peak and patterns of the time-activity curves (TAC)) were evaluated. The presence of pseudoprogression/early tumor progression was based on the clinical course (progression-free survival (PFS) >/≤ 6 mo) and/or histopathological findings. Imaging results were also related to overall survival (OS). RESULTS: Pseudoprogression was confirmed in 14 of 26 patients. TBRmax and TBRmean of 18F-FET/11C-MET uptake were significantly higher in patients with early tumor progression (n = 12) than in patients with pseudoprogression (TBRmax, 3.6 ± 0.8 vs. 2.4 ± 0.4; TBRmean, 2.5 ± 0.3 vs. 1.8 ± 0.2; both P < 0.001). Furthermore, patterns of TAC were significantly different in both groups (P = 0.04) and presence of MGMT promoter methylation was significantly higher in patients with pseudoprogression (P = 0.02). Receiver-operating-characteristic analysis yielded a TBRmax of 2.9 as an optimal cut-off to identify early tumor progression (sensitivity, 92%; specificity, 93%; accuracy, 92%; area under the curve, 0.96 ± 0.04; P < 0.001). Univariate survival analyses revealed that a TBRmax < 2.9 predicted both a significantly longer PFS (median PFS, 21 vs. 5 months; P < 0.001) and OS (median OS, 33 vs. 12 months; P = 0.007). CONCLUSION: Amino acid PET contributes significantly in diagnosing pseudoprogression.