Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Results of a prospective phase II study.

PURPOSE: Dose escalations above 60 Gy based on MRI have not led to prognostic benefits in glioblastoma patients yet. With positron emission tomography (PET) using [(18)F]fluorethyl-L-tyrosine (FET), tumor coverage can be optimized with the option of regional dose escalation in the area of viable tumor tissue. METHODS AND MATERIALS: In a prospective phase II study (January 2008 to December 2009), 22 patients (median age 55 years) received radiochemotherapy after surgery. The radiotherapy was performed as an MRI and FET-PET-based integrated-boost intensity-modulated radiotherapy (IMRT). The prescribed dose was 72 and 60 Gy (single dose 2.4 and 2.0 Gy, respectively) for the FET-PET- and MR-based PTV-FET((72 Gy)) and PTV-MR((60 Gy)). FET-PET and MRI were performed routinely for follow-up. Quality of life and cognitive aspects were recorded by the EORTC-QLQ-C30/QLQ Brain20 and Mini-Mental Status Examination (MMSE), while the therapy-related toxicity was recorded using the CTC3.0 and RTOG scores. RESULTS: Median overall survival (OS) and disease-free survival (DFS) were 14.8 and 7.8 months, respectively. All local relapses were detected at least partly within the 95% dose volume of PTV-MR((60 Gy)). No relevant radiotherapy-related side effects were observed (excepted alopecia). In 2 patients, a pseudoprogression was observed in the MRI. Tumor progression could be excluded by FET-PET and was confirmed in further MRI and FET-PET imaging. No significant changes were observed in MMSE scores and in the EORTC QLQ-C30/QLQ-Brain20 questionnaires. CONCLUSION: Our dose escalation concept with a total dose of 72 Gy, based on FET-PET, did not lead to a survival benefit. Acute and late toxicity were not increased, compared with historical controls and published dose-escalation studies.

[Use of amino acid PET in the Diagnostic and Treatment Management of cerebral gliomas]. / Anwendung der Aminosäure-PET in der Diagnostik und Therapie von zerebralen Gliomen.

Structural as well as functional imaging methods are of special importance in neurooncology. Improvements of radionuclide and magnetic resonance-based imaging modalities over the past decade have enabled clinicians to non-invasively assess the dynamics of disease-specific processes at the molecular level in patients with malignant gliomas. To date, a range of complementary imaging parameters have been established in the diagnostic work-up of patients with brain tumours. Magnetic resonance imaging (MRI) provides morphological information as well as functional information such as vascular permeability, cell density, tumour perfusion, and metabolic information by using magnetic resonance spectroscopy. The use of radiolabelled amino acids for positron emission tomography (PET) allows a better delineation of tumour margins and improves targeting of biopsy and radiotherapy, and planning surgery. In addition, amino acid imaging appears useful in distinguishing tumour recurrence from non-specific post-therapeutic scar tissue, in predicting prognosis in low-grade gliomas, and in monitoring metabolic response during treatment. Taken together, MRI and PET provide complementary information about tumour biology and activity, thereby resulting in an improved understanding of the kinetics of tumour growth and therefore allow new insights into the pathophysiology of malignant brain tumours. However, multimodal imaging studies comparing the value of amino acid PET and functional methods of MRI (e. g., perfusion and diffusion weighted imaging) are needed. From these studies, surrogate MRI and PET imaging techniques need to be derived to gain complementary structural and functional information of brain tumours that can be placed into common clinical practice which will optimise the clinical management of patients with malignant gliomas.

[German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids]. / PET- und SPECT-Untersuchungen von Hirntumoren mit radioaktiv markierten Aminosäuren.

For the primary diagnosis of brain tumours, morphological imaging by means of magnetic resonance imaging (MRI) is the current method of choice. The complementary use of functional imaging by positron emitting tomography (PET) and single photon emitting computerized tomography (SPECT) with labelled amino acids can provide significant information on some clinically relevant questions, which are beyond the capacity of MRI. These diagnostic issues affect in particular the improvement of biopsy targeting and tumour delineation for surgery and radiotherapy planning. In addition, amino acid labelled PET and SPECT tracers are helpful for the differentiation between tumour recurrence and non-specific post-therapeutic tissue changes, in predicting prognosis of low grade gliomas, and for metabolic monitoring of treatment response. The application of dynamic PET examination protocols for the assessment of amino acid kinetics has been shown to enable an improved non-invasive tumour grading. The purpose of this guideline is to provide practical assistance for indication, examination procedure and image analysis of brain PET/SPECT with labelled amino acids in order to allow for a high quality standard of the method. After a short introduction on pathobiochemistry and radiopharmacy of amino acid labelled tracers, concrete and detailed information is given on the several indications, patient preparation and examination protocols as well as on data reconstruction, visual and quantitative image analysis and interpretation. In addition, possible pitfalls are described, and the relevant original publications are listed for further information.

Multimodal target point assessment for stereotactic biopsy in children with diffuse bithalamic astrocytomas.

INTRODUCTION: Diffuse glial tumors with bithalamic involvement are rare in children. Diagnostic assessment can be difficult as the radiological findings can be unspecific. MATERIALS AND METHODS: In order to enhance the diagnostic yield metabolic imaging with MRS and PET using FET ( O-(2-[(18)F]fluoroethyl)- L-tyrosine) was performed in two children (2 and 10 years of age). Co-registered images were used for image-guided biopsy, which was planned with neuronavigation and stereotaxy simultaneously. RESULTS: Biopsies from the right thalamus were planned, but locations were changed in both cases after metabolic imaging was available. MRS (thalamic voxel) was typical for a glial tumor in one child. In the older girl FET-PET revealed an unexpected lesion in the left cerebellar hemisphere, with a tumor-to-cortex ratio of 3.8, as against 1.7 in the thalamus. Accordingly, a stereotactic biopsy specimen was taken from the left cerebellar hemisphere, and a final diagnosis of anaplastic astrocytoma was made. The other patient showed a higher uptake (tumor-to-cortex ratio 1.6) in the left dorsal thalamus, compared with bilateral homogeneous hyperintensity of the thalamus structures on MRI. Stereotactic biopsy revealed a low-grade diffuse astrocytoma. CONCLUSION: Stereotactic biopsy using metabolic imaging and image fusion can enhance the diagnostic yield in cases of diffuse pediatric gliomas disclosing unexpected 'hot spots'.

Monitoring isotretinoin therapy in thyroid cancer using 18F-FDG PET.

Treatment with isotretinoin (13-cis-retinoic acid, 13-cis-RA) is a recent additional option in advanced, otherwise intractable differentiated thyroid cancers. The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the prediction and the monitoring of response to 13-cis-RA therapy. Twenty-one patients with advanced differentiated thyroid cancers were investigated using 18F-FDG PET and iodine-131 whole-body scans before and 3, 6 and 9 months after initiation of 13-cis-RA therapy. After 9 months, 13-cis-RA treatment was discontinued and imaging procedures repeated 3 months later. Average 18F-FDG uptake (SUV) decreased significantly during 13-cis-RA therapy but subsequently increased in five of eight patients after withdrawal of 13-cis-RA. 18F-FDG uptake (SUV) 3 months after onset of 13-cis-RA therapy was significantly lower in patients who developed increased 131I uptake in their tumour sites than in patients with no subsequent increase in 131I uptake. There was no relationship between serum thyroglobulin level on the one hand and simultaneously measured 131I or 18F-FDG uptake on the other hand. There was a tendency towards lower 18F-FDG uptake in tumour manifestations with a better outcome. Therefore, 18F-FDG PET at 3 months after the start of treatment promises to differentiate between those patients who will eventually benefit from 13-cis-RA and those who will not. In conclusion, these data indicate that 18F-FDG PET is a useful tool for the evaluation and monitoring of adjuvant therapy with 13-cis-RA in thyroid cancer.

The influence of image resolution on the positron emission tomographic measurement of caudate glucose consumption.

The aim of this study was to investigate the influence of image resolution on (a) relative and absolute values of caudate glucose consumption (rCMRGlc) determined by positron emission tomography (PET), and (b) the detection of significant differences in these metabolic values between groups of subjects. For this purpose, raw data of cerebral accumulation of fluorine-18 fluorodeoxyglucose (FDG) obtained in 11 normal subjects and in nine patients with unilateral thalamic infarction were reconstructed using filtered backprojection with four different cut-off frequencies (CFs), yielding images with a transaxial resolution of 5.7, 7.1, 8.9 and 11 mm (full-width at half-maximum; FWHM). Absolute values of caudate rCMRGlc decreased significantly by more than 30% over the range of image resolutions studied. Bilateral ratios of caudate rCMRGlc were insensitive to variations in image resolution. Levels of significance assessing the differences in mean metabolic values between patients and controls were all below 0.01. They were, however, slightly better at image resolutions of 7.1 and 8.9 mm than at a resolution of 5.7 mm. These data indicate (a) that relative values of rCMRGlc are better suited to compare quantitative results from different PET cameras than are absolute values, and (b) that the CF used for the filtered back-projection exerts a small but not negligible influence on levels of significance assessing differences in metabolic values between groups of subjects.

Stereotactic laser therapy in cerebral gliomas.

The 1.06 micron Nd:YAG laser and a new fiberoptic delivery system, the Interstitial Thermo-Therapy (ITT) laser fibre, allows stereotactic interstitial irradiation of cerebral tumours. In experimental rat brain studies we found typical laser-tissue effects with a central necrosis and a sharply demarcated oedema towards the normal brain. The size of the lesion depended on the energy and exposure time applied. In a pilot series we treated 5 patients with cerebral gliomas WHO grade II-III in functionally important regions and monitored the therapeutic effects by MR imaging and PET scan. Early post-operative results showed irreversible necrotic changes in the tumour centre and reversible oedematous changes at the tumour margin. Long-term results will show if stereotactic interstitial laser therapy is a useful supplementary method in the treatment of malignant cerebral tumours.

Changed pattern of regional glucose metabolism during yoga meditative relaxation.

Using positron emission tomography (PET), measurements of the regional cerebral metabolic rate of glucose (rCMRGlc) are able to delineate cerebral metabolic responses to external or mental stimulation. In order to examine possible changes of brain metabolism due to Yoga meditation PET scans were performed in 8 members of a Yoga meditation group during the normal control state (C) and Yoga meditative relaxation (YMR). Whereas there were intraindividual changes of the total CMRGlc, the alterations were not significant for intergroup comparison; specific focal changes or changes in the interhemispheric differences in metabolism were also not seen; however the ratios of frontal vs. occipital rCMRGlc were significantly elevated (p less than 0.05) during YMR. These altered ratios were caused by a slight increase of frontal rCMRGlc and a more pronounced reduction in primary and secondary visual centers. These data indicate a holistic behavior of the brain metabolism during the time of altered state of consciousness during YMR.