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.

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.

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.

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.

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.