Real-World Data for Lenvatinib in Radioiodine-Refractory Differentiated Thyroid Cancer (RELEVANT): A Retrospective Multicentric Analysis of Clinical Practice in Austria.

BACKGROUND: Lenvatinib has proven efficacy in progressive, radioiodine- (RAI-) refractory thyroid cancer (TC). Dose reductions are commonly performed due to decreased tolerability and adverse effects. This retrospective multicenter study analyzed overall survival (OS) and progression-free survival (PFS) and tolerability in the Austrian patient population treated with lenvatinib. METHODS: Clinical data of 43 patients (25 males and 18 females) with a median age of 70 years (range: 39-91 years) and RAI-refractory TC with metastases to the lymph nodes (74%), lungs (86%), bone (35%), liver (16%), and brain (12%) were analyzed. The mean duration of treatment with lenvatinib was 26.6 ± 15.4 months with dosage reductions required in 39 patients (91%). RESULTS: PFS after 24 months was 71% (95% CI: 56-87), and overall survival (OS) was 74% (95% CI: 60-88), respectively. OS was significantly shorter (p=0.048) in patients with a daily maintenance dosage ≤ 10 mg (63%) (95% CI: 39-86) as compared to patients on ≥ 14 mg lenvatinib (82%) (95% CI: 66-98) daily. Dose reduction was noted in 39 patients (91%). Grade ≥3 toxicities (hypertension, diarrhea, weight loss, and palmar-plantar erythrodysesthesia syndrome) were most common leading to discontinuation of lenvatinib in 7 patients (16%). CONCLUSION: Lenvatinib showed sustained clinical efficacy in patients with metastatic RAI-refractory TC even with reduced maintenance dosages over years. The effects were comparable to the registration trial, although patients had a higher median age and, more commonly, dose reductions.

The impact of 18F-FDOPA-PET/MRI image fusion in detecting liver metastasis in patients with neuroendocrine tumors of the gastrointestinal tract.

BACKGROUND: This study assesses the value of image fusion using 18F-fluoro-L-DOPA (18F-DOPA) positron emission tomography (PET) and magnetic resonance imaging (MRI) for examining patients with neuroendocrine tumors (NETs) and a suspicion of metastasis of the liver. METHODS: Eleven patients (five women and six men aged between 20 and 81, with a mean age of 54.6 years) were included in the study. All patients underwent whole-body 18F-DOPA PET examinations and contrast-enhanced MRI with diffusion-weighted sequences (DWS). Image fusion was performed using a semiautomatic voxel-based algorithm. Images obtained using PET and MRI were assessed separately. Side-by-side evaluations of fused PET/MRI images were also performed. RESULTS: In total, 55 liver lesions (52 liver metastases and 3 benign lesions) were detected in the 11 patients. Sensitivity detection for liver lesions was higher when using PET/CT than when using contrast-enhanced MRI without DWSs and lower than using MRI with DWSs. The sensitivity of PET/MRI image fusion in the detection of liver metastasis was significantly higher than that of MRI with DWSs (P < 0.05). CONCLUSION: Images of the liver obtained using PET and MRI in patients with NETs exhibited characteristic features. These findings suggest that an appropriate combination of available imaging modalities can optimize patient evaluations.

Sarcopenia and osteoporosis are interrelated in geriatric inpatients.

BACKGROUND: Sarcopenia and osteoporosis share an underlying pathology and reinforce each other in terms of negative outcomes. OBJECTIVE: To evaluate the extent of concomitance of sarcopenia as defined by the European Working Group on Sarcopenia in Older People (EWGSOP) and osteoporosis as defined by the World Health Organization (WHO) in geriatric inpatients and their relationship to nutritional and functional status. MATERIAL AND METHODS: A cross-sectional analysis of geriatric inpatients from the sarcopenia in geriatric elderly (SAGE) study. Measurements included dual X­ray absorptiometry for bone mineral density and appendicular muscle mass; gait speed and hand grip strength, the Barthel index, body mass index (BMI) and the mini nutritional assessment short form (MNA-SF). RESULTS: Of the 148 patients recruited for SAGE, 141 (84 women, 57 men; mean age 80.6 ± 5.5 years) had sufficient data to be included in this ancillary investigation: 22/141 (15.6%) were only osteoporotic, 19/141 (13.5%) were only sarcopenic and 20/141 (14.2%) osteosarcopenic (i.e. both sarcopenia and osteoporosis). The prevalence of osteoporosis was higher in sarcopenic than in non-sarcopenic individuals (51.3% vs. 21.6%, p < 0.001). Sarcopenic, osteoporotic and osteosarcopenic subjects had a lower BMI, MNA-SF, handgrip and gait speed (p < 0.05) than the reference group (those neither osteoporotic nor sarcopenic, n = 80). The Barthel index was lower for sarcopenic and osteosarcopenic (p < 0.05) but not for osteoporotic (p = 0.07) subjects. The BMI and MNA-SF were lower in osteosarcopenia compared to sarcopenia or osteoporosis alone (p < 0.05) while there were no differences in functional criteria. CONCLUSION: Osteoporosis and sarcopenia are linked to nutritional deficits and reduced function in geriatric inpatients. Co-occurrence (osteosarcopenia) is common and associated with a higher degree of malnutrition than osteoporosis or sarcopenia alone.

Consequences of applying the new EWGSOP2 guideline instead of the former EWGSOP guideline for sarcopenia case finding in older patients.

INTRODUCTION: we examined the consequences of applying the new EWGSOP2 algorithm for sarcopenia screening instead of the former EWGSOP algorithm (EWGSOP1) in geriatric inpatients. METHODS: the dataset of our formerly published Sarcopenia in Geriatric Elderly (SAGE) study includes 144 geriatric inpatients (86 women, 58 men, mean age 80.7±5.6 years) with measurements of gait speed, handgrip strength and appendicular muscle mass by dual x-ray absorptiometry (DXA). We analysed the agreement between EWGSOP and EWGSOP2 algorithms in identifying patients as sarcopenic/non-sarcopenic. Differences in the distribution sarcopenic vs. non-sarcopenic were assessed by Chi²-test. RESULTS: sarcopenia prevalence according to EWGSOP1 (41 (27.7%)) was significantly higher than with EWGSOP2 (26(18.1%), p<0.05). The sex-specific sarcopenia prevalence was 22.1% (EWGSOP1) and 17.4% (EWGSOP2), respectively, for women (difference not significant) and 37.9% vs. 19.4% for men (p<0.05%). The overall agreement in classifying subjects as sarcopenic/non-sarcopenic was 81.25% (81.4% for women, 81.0% for men). However, among the 41 sarcopenia cases identified by EWGSOP1, only 20 (48.8%) were diagnosed with sarcopenia by EWGSOP2 (9/19 w (47.4%), 11/22 m (50.0%)). Ten of 19 women (52.6%) and 11 of 22 men (50.0%) diagnosed with sarcopenia by EWGSOP1 were missed by EWGSOP2, while 6 of 15 women (40.0%) and 0 of 11 men (0.0%) were newly diagnosed. DISCUSSION: there is a substantial mismatch in sarcopenia case finding according to EWGSOP1 and EWGSOP2. The overall prevalence and the number of men diagnosed with sarcopenia are significantly lower in EWGSOP2. While the absolute number of women identified as sarcopenic remains relatively constant, the overlap of individual cases between the two definitions is low.

Quantifying appendicular muscle mass in geriatric inpatients: Performance of different single frequency BIA equations in comparison to dual X-ray absorptiometry.

BACKGROUND: Quantification of skeletal muscle mass is mandatory for diagnosing sarcopenia, a highly prevalent geriatric syndrome. While dual energy X-ray absorptiometry (DXA) is the reference method in a clinical context, bioimpedance analysis (BIA) is more readily applicable on a broad scale. Recently BIA equations for the prediction of appendicular skeletal muscle mass in higher age groups have been published, but data on their performance in geriatric inpatients are lacking. METHODS: In 144 geriatric inpatients (86 women and 58 men, mean age 80.7 ± 5.6 years) appendicular skeletal muscle mass was predicted by 4 different BIA equations and measured by DXA. Results were compared by linear regression analysis and Bland Altmann plots. The agreement with DXA in classifying subjects to have normal or reduced muscle mass was calculated for the BIA based approaches. RESULTS: The 4 BIA equations showed only minor differences in regression analysis, but major differences in mean error (range -0.98 kg to + 0.19 kg in women and -2.47 kg to -0.58 kg in men). Considering regression parameters and mean error, the equation of Scafoglieri et al. performed best, resulting in an agreement with DXA of more than 83%. Sensitivity to detect subjects with reduced muscle mass was <70% in the whole group for all BIA equations. CONCLUSION: The BIA equation of Scafoglieri et al. performs best in geriatric inpatients, with more than 83% of subjects classified correctly as having normal or reduced muscle mass compared to DXA. Low sensitivity to detect subjects with reduced muscle mass in geriatric inpatients remains a limitation of BIA.

32nd International Austrian Winter Symposium : Zell am See, the Netherlands. 20-23 January 2016.

TABLE OF CONTENTS: A1 68Ga-PSMA PET/CT in staging and restaging of Prostate Cancer Patients: comparative study with 18F-Choline PET/CTW Langsteger, A Rezaee, W Loidl, HS Geinitz, F Fitz, M Steinmair, G Broinger, L Pallwien-Prettner, M BeheshtiA2 F18 Choline PET - CT: an accurate diagnostic tool for the detection of parathyroid adenoma?L Imamovic, M Beheshti, G Rendl, D Hackl, O Tsybrovsky, M Steinmair, K Emmanuel, F Moinfar, C Pirich, W LangstegerA3 [18F]Fluoro-DOPA-PET/CT in the primary diagnosis of medullary thyroid carcinomaA Bytyqi, G Karanikas, M Mayerhöfer, O Koperek, B Niederle, M HartenbachA4 Variations of clinical PET/MR operations: An international survey on the clinical utilization of PET/MRIT Beyer, K Herrmann, J CzerninA5 Standard Dixon-based attenuation correction in combined PET/MRI: Reproducibility and the possibility of Lean body mass estimationI Rausch, P Rust, MD DiFranco, M Lassen, A Stadlbauer, ME Mayerhöfer, M Hartenbach, M Hacker, T BeyerA6 High resolution digital FDG PET/MRI imaging for assessment of ACL graft viabilityK Binzel, R Magnussen, W Wei, MU Knopp, DC Flanigan, C Kaeding, MV KnoppA7 Using pre-existing hematotoxicity as predictor for severe side effects and number of treatment cycles of Xofigo therapyA Leisser, M Nejabat, M Hartenbach, G Kramer, M Krainer, M Hacker, A HaugA8 QDOSE - comprehensive software solution for internal dose assessmentWencke Lehnert, Karl Schmidt, Sharok Kimiaei, Marcus Bronzel, Andreas KlugeA9 Clinical impact of Time-of-Flight on next-generation digital PET imaging of Yttrium-90 radioactivity following liver radioembolizationCL Wright, K Binzel, J Zhang, Evan Wuthrick, Piotr Maniawski, MV KnoppA10 Snakes in patients! Lessons learned from programming active contours for automated organ segmentationM Blaickner, E Rados, A Huber, M Dulovits, H Kulkarni, S Wiessalla, C Schuchardt, RP Baum, B Knäusl, D GeorgA11 Influence of a genetic polymorphism on brain uptake of the dual ABCB1/ABCG2 substrate [11C]tariquidarM Bauer, B Wulkersdorfer, W Wadsak, C Philippe, H Haslacher, M Zeitlinger, O LangerA12 Outcome prediction of temporal lobe epilepsy surgery from P-glycoprotein activity. Pooled analysis of (R)-[11C]-verapamil PET data from two European centresM Bauer, M Feldmann, R Karch, W Wadsak, M Zeitlinger, MJ Koepp, M-C Asselin, E Pataraia, O LangerA13 In-vitro and in-vivo characterization of [18F]FE@SNAP and derivatives for the visualization of the melanin concentrating hormone receptor 1M Zeilinger, C Philippe, M Dumanic, F Pichler, J Pilz, M Hacker, W Wadsak, M MitterhauserA14 Reducing time in quality control leads to higher specific radioactivity of short-lived radiotracersL Nics, B Steiner, M Hacker, M Mitterhauser, W WadsakA15 In vitro 11C-erlotinib binding experiments in cancer cell lines with epidermal growth factor receptor mutationsA Traxl, Thomas Wanek, Kushtrim Kryeziu, Severin Mairinger, Johann Stanek, Walter Berger, Claudia Kuntner, Oliver LangerA16 7-[11C]methyl-6-bromopurine, a PET tracer to measure brain Mrp1 function: radiosynthesis and first PET evaluation in miceS Mairinger, T Wanek, A Traxl, M Krohn, J Stanek, T Filip, M Sauberer, C Kuntner, J Pahnke, O LangerA17 18F labeled azidoglucose derivatives as "click" agents for pretargeted PET imagingD Svatunek, C Denk, M Wilkovitsch, T Wanek, T Filip, C Kuntner-Hannes, J Fröhlich, H MikulaA18 Bioorthogonal tools for PET imaging: development of radiolabeled 1,2,4,5-TetrazinesC Denk, D Svatunek, T Wanek, S Mairinger, J Stanek, T Filip, J Fröhlich, H Mikula, C Kuntner-HannesA19 Preclinical evaluation of [18F]FE@SUPPY- a new PET-tracer for oncologyT Balber, J Singer, J Fazekas, C Rami-Mark, N Berroterán-Infante, E Jensen-Jarolim, W Wadsak, M Hacker, H Viernstein, M MitterhauserA20 Investigation of Small [18F]-Fluoroalkylazides for Rapid Radiolabeling and In Vivo Click ChemistryC Denk, D Svatunek, B Sohr, H Mikula, J Fröhlich, T Wanek, C Kuntner-Hannes, T FilipA21 Microfluidic 68Ga-radiolabeling of PSMA-HBED-CC using a flow-through reactorS Pfaff, C Philippe, M Mitterhauser, M Hartenbach, M Hacker, W WadsakA22 Influence of 24-nor-ursodeoxycholic acid on hepatic disposition of [18F]ciprofloxacin measured with positron emission tomographyT Wanek, E Halilbasic, M Visentin, S Mairinger, B Stieger, C Kuntner, M Trauner, O LangerA23 Automated 18F-flumazenil production using chemically resistant disposable cassettesP Lam, M Aistleitner, R Eichinger, C ArtnerA24 Similarities and differences in the synthesis and quality control of 177Lu-DOTA-TATE, 177Lu -HA-DOTA-TATE and 177Lu-DOTA-PSMA (PSMA-617)H Eidherr, C Vraka, A Haug, M Mitterhauser, L Nics, M Hartenbach, M Hacker, W WadsakA25 68Ga- and 177Lu-labelling of PSMA-617H Kvaternik, R Müller, D Hausberger, C Zink, RM AignerA26 Radiolabelling of liposomes with 67Ga and biodistribution studies after administration by an aerosol inhalation systemU Cossío, M Asensio, A Montes, S Akhtar, Y te Welscher, R van Nostrum, V Gómez-Vallejo, J LlopA27 Fully automated quantification of DaTscan SPECT: Integration of age and gender differencesF VandeVyver, T Barclay, N Lippens, M TrochA28 Lesion-to-background ratio in co-registered 18F-FET PET/MR imaging - is it a valuable tool to differentiate between low grade and high grade brain tumor?L Hehenwarter, B Egger, J Holzmannhofer, M Rodrigues-Radischat, C PirichA29 [11C]-methionine PET in gliomas - a retrospective data analysis of 166 patientsN Pötsch, I Rausch, D Wilhelm, M Weber, J Furtner, G Karanikas, A Wöhrer, M Mitterhauser, M Hacker, T Traub-WeidingerA30 18F-Fluorocholine versus 18F-Fluorodeoxyglucose for PET/CT imaging in patients with relapsed or progressive multiple myeloma: a pilot studyT Cassou-Mounat, S Balogova, V Nataf, M Calzada, V Huchet, K Kerrou, J-Y Devaux, M Mohty, L Garderet, J-N TalbotA31 Prognostic benefit of additional SPECT/CT in sentinel lymph node mapping of breast cancer patientsS Stanzel, G Pregartner, T Schwarz, V Bjelic-Radisic, B Liegl-Atzwanger, R AignerA32 Evaluation of diagnostic value of TOF-18F-FDG PET/CT in patients with suspected pancreatic cancerS Stanzel, F Quehenberger, RM AignerA33 New quantification method for diagnosis of primary hyperpatahyroidism lesions and differential diagnosis vs thyropid nodular disease in dynamic scintigraphyA Koljevic Markovic, Milica Jankovic, V Miler Jerkovic, M Paskas, G Pupic, R Dzodic, D PopovicA34 A rare case of diffuse pancreatic involvement in patient with merkel cell carcinoma detected by 18F-FDGMC Fornito, D FamiliariA35 TSH-stimulated 18F-FDG PET/CT in the diagnosis of recurrent/metastatic radioiodine-negative differentiated thyroid carcinomas in patients with various thyroglobuline levelsP Koranda, H Polzerová, I Metelková, L Henzlová, R Formánek, E Buriánková, M KamínekA36 Breast Dose from lactation following I131 treatmentWH Thomson, C LewisA37 A new concept for performing SeHCAT studies with the gamma cameraWH Thomson, J O'Brien, G James, A NotghiA38 Whole body F-18-FDG-PET and tuberculosis: sensitivity compared to x-ray-CTH Huber, I Stelzmüller, R Wunn, M Mandl, F Fellner, B Lamprecht, M GabrielA39 Emerging role 18F-FDG PET-CT in the diagnosis and follow-up of the infection in heartware ventricular assist system (HVAD)MC Fornito, G LeonardiA40 Validation of Poisson resampling softwareWH Thomson, J O'Brien, G JamesA41 Protection of PET nuclear medicine personnel: problems in satisfying dose limit requirementsJ Hudzietzová, J Sabol, M Fülöp.

Added value of semi-quantitative breast-specific gamma imaging in the work-up of suspicious breast lesions compared to mammography, ultrasound and 3-T MRI.

OBJECTIVE: To prospectively analyse the diagnostic value of semi-quantitative breast-specific gamma imaging (BSGI) in the work-up of suspicious breast lesions compared with that of mammography (MG), breast ultrasound and MRI of the breast. METHODS: Within a 15-month period, 67 patients with 92 breast lesions rated as Category IV or V according to the breast imaging reporting and data system detected with MG and/or ultrasound were included into the study. After the injection of 740-1110 MBq of Technetium-99m ((99m)Tc) SestaMIBI intravenously, scintigrams were obtained in two projections comparable to MG. The BSGI was analysed visually and semi-quantitatively by calculating a relative uptake factor (X). With the exception of two patients with cardiac pacemakers, all patients underwent 3-T breast MRI. Biopsy results were obtained as the reference standard in all patients. Sensitivity, specificity, positive- and negative-predictive values, accuracy and area under the curve were calculated for each modality. RESULTS: Among the 92 lesions, 67 (72.8%) were malignant. 60 of the 67 cancers of any size were detected by BSGI with an overall sensitivity of 90%, only exceeded by ultrasound with a sensitivity of 99%. The sensitivity of BSGI for lesions <1 cm declined significantly to 60%. Overall specificity of ultrasound was only 20%. Specificity, accuracy and positive-predictive value were the highest for BSGI (56%, 80% and 85%, respectively). X was significantly higher for malignant lesions (mean, 4.27) and differed significantly between ductal types (mean, 4.53) and the other histopathological entities (mean, 3.12). CONCLUSION: Semi-quantitative BSGI with calculation of the relative uptake factor (X) can help to characterize breast lesions. BSGI negativity may obviate the need for biopsy of breast lesions >1 cm with low or intermediate prevalence for malignancy. ADVANCES IN KNOWLEDGE: Compared with morphological imaging modalities, specificity, positive-predictive value for malignancy and accuracy were the highest for BSGI in our study. BSGI negativity may support the decision not to biopsy in selected lesions with a low or low-to-moderate pre-test probability for malignancy.

[Treatment of patients with radioiodine refractory, differentiated thyroid carcinoma. A Consensus Statement]. / Therapie des Patienten mit Radioiod-refraktärem, differenziertem Schilddrüsenkarzinom. Ein Konsensusstatement.

There is no clear standard therapy for patients with radioactive iodine (131I)-refractory locally advanced or metastatic differentiated thyroid cancer. The therapeutic options for this indication have expanded with the recently approved multiple kinase inhibitor sorafenib. Recommendations for the definition and the management of iodine refractory patients were worked up by an interdisciplinary expert panel, consisting of endocrine surgeons, medical oncologists and nuclear medicine specialists.

99mTc tetrofosmin myocardial perfusion scintigraphy in CAD. Performance with early and standard delayed acquisition and fractional flow reserve.

AIM: Early stress imaging (15 min after injection of the radiopharmaceutical) in 99mTc tetrofosmin myocardial perfusion scintigraphy (MPS) has been shown feasible in comparison to standard imaging after 45 minutes, but the effects on image quality and diagnostic accuracy ask for further evaluation. PATIENTS, METHODS: 97 patients (61 men, 36 women, age 69 ± 11 years) underwent both early (EA) and standard (SA) acquisition (after 14 ± 4 min and 43 ± 6 min, respectively) using 99mTc tetrofosmin gated SPECT with iterative reconstruction. Sub-diaphragmatic tracer activity and image quality was scored in a 4-point scale by blinded observers. Semiquantitative myocardial perfusion analysis was performed on a 17-segment model using standard cardiac quantification SPECT software (4 DM-SPECT). Stenoses of indeterminate haemodynamic significance were validated by measurement of fractional flow reserve (FFR). RESULTS: Extra-cardiac tracer activity was more commonly found in EA (43%) than in SA (38%), but without any diagnostic impact in > 95% of the patients. The mean summed stress score was significantly higher for early than standard imaging (6.4 ± 6.3 vs. 5.6 ± 6.1, p = 0.009). The amount of ischaemic area was not significantly different (EA: 9.1 ± 6.7 % vs. SA: 7.8 ± 6.9 %). The mean stress ejection fraction was 52 ± 11% (EA) compared to 55 ± 11 % (SA) (p = ns). FFR was inversely related to SDS at early (r = -0.704, p < 0.05) and standard (r = -0.678, p < 0.05) acquisition. All patients with a FFR < 0.8 (considered as hemodynamically significant stenoses) revealed a positive scan. CONCLUSION: Stress 99mTc tetrofosmin MPS with early acquisition is feasible and at least equally accurate when iterative reconstruction is applied.

Prolonged back pain attributed to suspected spondylodiscitis. The value of ¹8F-FDG PET/CT imaging in the diagnostic work-up of patients.

OBJECTIVE: This study aimed at investigating the diagnostic value of ¹8F-FDG PET/CT in cases of suspected spondylodiscitis after inconclusive results in initial diagnostic imaging. PATIENTS, METHODS: We analysed 38 consecutive cases of suspected spondylodiscitis (mean age: 67 ± 14 years) with chronic back pain referred to our Department during a four-year-period after inconclusive results in MRI or other conventional modalities. Clinical histories were retrospectively worked up and results of ¹8F-FDG PET/CT and MRI were analysed and related to the results of biopsy, blood culture and a one-year clinical follow-up. ¹8F-FDG PET/CT was analysed qualitatively by visual analysis and quantitatively. We measured the maximum standardized uptake value (SUV(max)) in the region of back pain and in a corresponding reference region (RR) in each patient and calculated a SUV(max-ratio). RESULTS: 22/38 patients had confirmed spondylodiscitis, while 16 were negative. ¹8F-FDG PET/CT established a correct diagnosis in 34 out of 38 patients by visual analysis. ¹8F-FDG PET/CT reached a sensitivity, specificity and accuracy of 81.8%, 100%, 89.5% and a PPV and NPV of 100% and 80%. MRI, performed in 27 patients reached a sensitivity, specificity and accuracy of 75%, 71.4%, 74.1% and a PPV and NPV of 88.2% and 50%. Patients with confirmed spondylodiscitis showed a significantly (p < 0.05) higher SUV(max) of 5.1 ± 1.9 and SUV(max)-ratio of 1.9 ± 0.8 than patients without it (SUV(max) (3.8 ± 1.5), SUV(max-ratio) (1.2 ± 0.3). CONCLUSION: ¹8F-FDG PET/CT provided diagnostic information in most patients with chronic back pain and suspected spondylodiscitis. It was helpful in establishing a correct diagnosis in challenging cases of spondylodiscitis with mostly unclear findings in previous MRI.

The impact of PET and PET/CT on treatment planning and prognosis of patients with NSCLC treated with radiation therapy.

AIM: 18F fluoro-deoxy-glucose (FDG) positron emission tomography (PET)-imaging improves the diagnostic accuracy in staging non small cell lung cancer (NSCLC) with possible impact on survival. This prospective study aimed to investigate the impact of PET and PET/CT on treatment planning and prognosis in patients with NSCLC treated with radiation therapy. METHODS: From October 2003 to January 2008, 91 consecutive patients with proven NSCLC stage T1-4N0-3M0 (clinical stages: I-IIIb) underwent accelerated, twice daily radiation therapy in target splitting technique. 70 patients received chemotherapy before radiation therapy (76%). All patients underwent PET or PET/CT-imaging and were followed up for a median time of 30 months. Imaging findings were interpreted visually and a SUV cut-off of 2.5 was applied for delineation of tumor borders. Changes in staging and planning treatment volumes (PTV) due to PET or PET/CT-imaging and survival were defined as primary study endpoints. The impact of tumor-type, stage, age, gender, weight loss and FDG-uptake in PET imaging as measured by the standardized uptake value (SUV) on survival were analysed as secondary endpoints. RESULTS: PET imaging provided additional diagnostic information over CT alone in 20% (N.=18) of our study population, leading to upstaging in 17% of them, respectively. In 5 patients (5.5% of 91) atelectasis could be separated from tumor tissue, PTV was altered in 9% (N.=8). 39 patients (43%) died during the observation period, mean overall survival was 32.3 months (95% Confidence intervalI 27.6-37.1) and tumor specific survival was 36.9 months (95 % CI 32.0-42.0), respectively. One- and two year survival rates reached 90.1% and 67.7%, respectively. Multivariate analysis did not reveal any significant prognostic impact of tumor-type, stage, age, gender or FDG-uptake as given by SUVmax (mean 13.6±6.8) or SUVmean (mean 5.5±1.6). CONCLUSION: The use of FDG-PET- and PET/CT-imaging provided incremental information relevant for treatment-planning in about 10 % of patients with NSCLC undergoing accelerated radiation therapy with curative intent. This prospective trial did not provide evidence for the assumption that the SUV might be an independent predictor of outcome.

Effect of alpine skiing training on tendon mechanical properties in older men and women.

Strain is one of the parameters determining tendon adaptation to mechanical stimuli. The aim of this study was to test whether the patellar tendon strain induced during recreational alpine skiing would affect tendon mechanical properties in older individuals. Twenty-two older males and females (67 ± 2 years) were assigned to a 12-week guided skiing programme (IG) and 20 aged-matched volunteers served as controls (CG). Patellar tendon mechanical properties and cross-sectional area (CSA) were measured before and after training, with combined dynamometry and ultrasonography scanning. None of the variables changed significantly in the CG after training. In the IG, tendon stiffness and Young's modulus were increased (respectively, 14% and 12%, P<0.01), without any significant change in tendon CSA. In addition, changes in tendon stiffness were blunted in women (9%) compared with men (19%). Serum IGF-1 concentration tended to be lower in women (-19%, P=0.07). These results demonstrate that the mechanical stimulus induced by alpine skiing is sufficient to elicit adaptive changes in patellar tendon mechanical and material properties in older subjects. Furthermore, the present sex-specific adaptations are consistent with previous reports of lower collagen metabolic responsiveness in women and may be underpinned by anthropometric and metabolic differences.

Glucose homeostasis and cardiovascular disease biomarkers in older alpine skiers.

Alpine skiing and ski training involves elements of static and dynamic training, and may therefore improve insulin sensitivity. Healthy men and women who where beginners/intermediate level of alpine skiing, were studied before (Pre) and immediately after (Post) 12 weeks of alpine ski training. After an additional 8 weeks a third test (retention study, Ret) was performed. The subjects were randomized into an intervention group (IG, n=22, age=66.6 ± 0.4 years) or a control group (CG, n=20, age=67.0 ± 1.0 years). Plasma glucose decreased (P<0.05) in CG, but increased (P<0.05) again at Ret, while a continued decrease was seen in IG (Ret vs Post, P<0.05). Plasma insulin decreased (P<0.05) with training in IG, while no effect was seen in CG. HOMA2 index for insulin resistance decreased (P<0.05) from 0.80 ± 0.08 to 0.71 ± 0.09 in IG. The value at Ret (0.57 ± 0.08) tended (P=0.067) to be different from Post. In CG the corresponding values were 0.84 ± 0.09, 0.81 ± 0.12 and 0.70 ± 0.09, respectively. Total cholesterol and LDL decreased in both IC and CG, a result, interpreted as seasonal variation. Biomarkers for endothelial function and low-grade inflammation were not elevated and similar in IG and CG, and did not change. Alpine ski training improves glucose homeostasis and insulin sensitivity in healthy, elderly individuals.

Lymphoscintigraphy in breast cancer patients after neoadjuvant chemotherapy. Diagnostic value and the work-up of sentinel node negative patients.

UNLABELLED: The AIM of this study was to evaluate the diagnostic value of lymphatic mapping by lymphoscintigraphy in breast cancer patients undergoing neoadjuvant chemotherapy (NCTX). We assessed the association between clinicopathological factors and nonvisualized sentinel nodes during preoperative lymphoscintigraphy. As secondary aims, we analyzed whether post NCTX axillary ultrasonography and fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (F18-FDG-PET/CT) might be useful for staging in case of nonvisualized sentinel nodes. PATIENTS, METHODS: 61 patients with newly diagnosed, invasive breast cancer potentially eligible for NCTX were included in this substudy of a prospective trial on the monitoring of NCTX with ¹8F-FDG PET/CT. In all patients, lymphoscintigraphy was performed prior to sentinel lymph node biopsy (SLNB). 42 patients received neoadjuvant chemotherapy. 19 patients did not receive NCTX. After SLNB, mastectomy or lumpectomy (breast-conserving surgery) combined with level I and II axillary lymph node dissection were performed. Cases of nonvisualized sentinel nodes were analyzed with respect to tumour and patient characteristics and the results of ultrasonography and ¹8F-FDG-PET/CT before and after NCTX. RESULTS: Lymphoscintigram successfully identified at least one sN in 55 patients (i.e. identification rate of 90%). The risk of failure to identify the sN was associated statistically with a positive clinical nodal status prior to NCTX (p = 0.021). There was no statistical difference between patients with visualized and nonvisualized sN with respect to age, tumour grade, tumour size, pathological lymph node status or tumour histology. In patients without NCTX the sN identification rate was 100% versus 86% in patients with NCTX (n.s.). The FNR of patients with NCTX was 9.1%. Post NCTX axillary ultrasonography or FDG-PET/CT did not provide accurate information about the lymph node status in case of failing lymphatic mapping. CONCLUSION: On the basis of our findings, SLNB can not yet be recommended as a reliable staging method in breast cancer patients undergoing neoadjuvant chemotherapy. Patients with clinically positive axillary lymph nodes have a higher chance of unsuccessful lymphatic mapping by lymphoscintigraphy. Performing SLNB before NCTX in clinically node-negative patients may identify the subset of patients in whom axillary lymph node dissection can be omitted. Post NCTX axillary ultrasonography and ¹8F-FDG-PET/CT can not be suggested as valid axillary staging methods in case of a failed lymphatic mapping.

Long-term prognosis of medullary thyroid carcinoma.

OBJECTIVE: The clinical course of patients with medullary thyroid carcinoma (MTC) is variable, even in the subgroup of patients after surgery with curative intent and postoperatively persistent elevated calcitonin levels. This study aimed to evaluate the long-term prognosis of survival in patients with MTC. PATIENTS: Long-term survival was analysed in 32 patients with MTC being treated in an endocrine centre over a 40-year period. Patients were classified as having sporadic MTC, familial MTC (FMTC), multiple endocrine neoplasia (MEN) IIA or MEN IIB. RESULTS: Seventeen patients had sporadic MTC (53.1%), eight had MEN IIA (25%) and three had MEN IIB (9.4%); the remaining four patients (12.5%) had not undergone genetic analysis until now. The overall average age at diagnosis was 42.0 years, and the median follow-up time was 9.5 years (range 0.5-39 years). Mortality due to progressive MTC was 15.6%. The 5-year survival rate was 96% (95% CI 89-100), the 10-year survival rate 91% (95% CI 79-100), and the 15-year survival rate 85% (95% CI 78-100). The estimated mean survival time after initial diagnosis was 31 years (95% CI 26.7-37.0). There is a significant difference in survival time between patients achieving complete remission compared with patients with biochemical persistent disease (P = 0.038) or metastasis (P = 0.0003). In five patients, advanced imaging with positron emission tomography/computed tomography (PET/CT) identified additional sites of tumour load. Eight more lymph node metastases were found in four patients and one local tumour recurrence in one patient by PET/CT. CONCLUSION: The overall prognosis of MTC is favourable, even if the rate of biochemical cure is lower in MTC than in differentiated types of thyroid cancer. This is also true for patients with biochemically persistent disease. Whether the identification of further tumour sites by advanced imaging procedures such as PET/CT translates into a better prognosis in patients with persistently elevated calcitonin levels remains to be investigated.

13N-ammonia rest/stress PET: folic acid improves global coronary vasoreactivity in coronary artery disease patients with normal or elevated homocysteine levels.

AIM: Hyperhomocysteinaemia (Hhcy) is known to be an independent risk factor for vascular disease. Coronary flow reserve (CFR) measured by positron emission tomography (PET) is a sensitive method to monitor the effects of pharmacologic interventions in Hhcy. We assessed coronary vascular reactivity by PET in patients with coronary artery disease (CAD) dependent on their homocysteine (Hcy) levels before and under high dose folic acid supplementation therapy (FAST). PATIENTS, METHODS: Twelve patients with CAD underwent rest/adenosine (13) N-ammonia PET for quantification of myocardial blood flow (MBF) and CFR before and after nine weeks FAST (10 mg/day). RESULTS: Folate levels increased from 21 +/- 6 to 210 +/- 34 microg/l (+900%, p < 0.0001) while Hcy levels decreased from 12.1 +/- 3.6 to 9.1 +/- 3.1 micromol/l ( - 25%; p < 0.01). Global resting MBF remained nearly unchanged after FAST, while stress MBF (from 2.61 +/- 0.93 to 3.25 +/- 1.15 ml/g/min; p = 0.05) and CFR (from 3.00 +/- 0.76 to 3.72 +/- 0.93 ml/g/min; p < 0.05; +24%) significantly increased in patients with normal and elevated Hcy levels (cut off 12 micromol/l). An inverse relation was found between Hcy and CFR (R = - 0.53; p = 0.08) and between Hcy and MBF at rest (R = - 0.62; p < 0.05) at baseline conditions, not persisting after FAST. CONCLUSION: Coronary vascular reactivity can be improved by FAST in patients with CAD and normal or elevated Hcy levels. FAST might lower an increased cardiovascular risk in CAD patients possibly by mechanisms that are not related to Hcy.

FDG gamma camera PET equipped with one inch crystal and XCT. Assessment of myocardial viability.

UNLABELLED: Metabolic imaging with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) is actually considered as the best method to detect and quantitatively assess myocardial tissue viability. The aim of this study was to investigate the accuracy of FDG gamma camera positron emission tomography (GCPET) imaging equipped with one inch NaI crystals in comparison to FDG dedicated PET (dPET) imaging as a "gold standard" in phantom and clinical studies. PATIENTS, METHODS: Nineteen patients with coronary artery disease (CAD) underwent both imaging modalities. Phantom and clinical GCPET imaging were performed with a dual-headed, coincidence based gamma camera equipped with 1 inch thick NaI crystals and an x-ray tube (XCT) for attenuation correction (AC), as well as with a dedicated PET scanner with AC. (99m)Tc tetrofosmin single-photon emission tomography (SPET) studies were performed for assessment of myocardial perfusion, with AC. RESULTS: Phantom studies showed a significant relation in segmental activity between FDG imaging with AC using GCPET and dPET (r = 0.91, p < 0.001). In clinical studies with AC correlation coefficients of mean segmental FDG uptake and regional defect size were r = 0.87 (p < 0.0001) and r = 0.83 (p < 0.0001), respectively. In regional analysis close agreement was even found in the most attenuated regions of the heart if AC was used in GCPET imaging. The overall agreement for detection of viable myocardium was 81% between FDG-dPET (AC) and FDG-GCPET (AC) and 74% between FDG-dPET (AC) and FDG-GCPET (NC). CONCLUSION: This study suggests that the assessment of myocardial metabolism by means of FDG is feasible with a coincidence based gamma camera equipped with 1 inch thick NaI crystals if AC is performed. The results reveal a close concordance and agreement between FDG-dPET (AC) and FDG-GCPET (AC) as compared to FDG-GCPET (NC).

Myocardial perfusion in patients with typical chest pain and normal angiogram.

BACKGROUND: Approximately 10-30% of patients with typical chest pain present normal epicardial coronaries. In a proportion of these patients, angina is attributed to microvascular dysfunction. Previous studies investigating whether angina is the result of abnormal resting or stress perfusion are controversial but limited by varying inclusion criteria. Therefore, we investigated whether microvascular dysfunction in these patients is associated with perfusion abnormalities at rest or at stress. PATIENTS AND METHODS: In 58 patients (39 female, 19 male, mean age 58+/-10 years) with angina and normal angiogram as well as 10 control patients with atypical chest pain and normal coronaries (six female, four male, mean age 53+/-11 years) myocardial blood flow (MBF) was measured at rest and under dipyridamole using 13N-ammonia PET. Resting MBF and coronary flow reserve (CFR) as the ratio of hyperaemic to resting MBF were corrected for rate-pressure-product (RPP): normalized resting MBF (MBFn)=MBFx10,000/RPP and CFRn=CFRxRPP/10,000. RESULTS: Sixteen/58 patients had a normal CFRn (=2.5; group I; CFRn: 3.1+/-0.88); the same as the controls (CFRn: 3.3+/-0.74). Forty-two/58 patients presented a reduced CFRn (group II; CFRn: 1.78+/-0.57). Group II had both a higher MBFn (group II: 1.30+/-0.33 vs. Group I: 1.03+/-0.26; P<0.05 and vs. controls: 1.07+/-0.19; P<0.01) and a lower hyperaemic MBF (group II: 2.25+/-0.76 mL g-1 min-1 vs. Group I: 3.07+/-0.78 mL g-1 min-1; P<0.001 and vs. controls: 3.41+/-0.94 mL g-1 min-1; P<0.0001). CONCLUSION: Impaired CFRn in patients with typical angina and normal angiogram is owing to both an increased resting and reduced hyperaemic MBF. Therefore, PET represents a prerequisite for further studies to optimize treatment in individuals with anginal pain and normal coronary angiogram.

Should lidocaine be avoided for local anesthesia in radiation synovectomy?

AIM: Leakage is of major concern when performing radiation synovectomy. Although post-treatment immobilization was provided, extra-articular leakage of radioactivity has occasionally been observed in patients receiving local anesthesia in the course of radiation synovectomy. This study was performed to uncover any unfavourable effect of lidocaine on stability of (166)Ho-FHMA (ferrum hydroxide macroaggregate). METHODS: The radiopharmaceutical was investigated in bovine serum albumin (BSA) solutions (5, 10 mg/ml) at pH 6, 7 and 8. Furthermore, the tracer was incubated for 0, 2, 24, 48 and 120 hours in synovial fluid. In both series the influence of lidocaine-HCl 2% (500, 1000 microl) has been evaluated. RESULTS: In BSA test solutions, amount of lidocaine added [df(2), F=7.82, p-level: 0.00] and pH [df(2), F=7.82, p-level: 0.00] significantly influenced in vitro stability of (166)Ho labeled FHMA (n=72). This finding was confirmed in synovial fluid [df(2), F=3.82, p-level: 0.03] (n=60). CONCLUSION: In an experimental design mimicking normal and inflammatory conditions in the joint, addition of a few milliliters of lidocaine-HCl followed by a shift towards lower pH-values in synovial fluid may endanger stability of the carrier-tracer complex (166)Ho-FHMA and thereby enhance extra-articular leakage.