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  • 1
    Keywords: DENSITY ; POSITRON-EMISSION-TOMOGRAPHY ; CRITERIA ; RECIST ; DUAL-ENERGY CT ; MULTIKINASE INHIBITOR SORAFENIB ; TUMOR-RESPONSE
    Abstract: OBJECTIVES: To investigate the volumetric iodine-uptake (VIU) changes by dual-energy CT (DECT) in assessing the response to sorafenib treated hepatocellular carcinoma (HCC) patients, compared with AASLD (American Association for the Study of Liver Diseases) and Choi criteria. MATERIALS AND METHODS: Fifteen patients with HCC receiving sorafenib, monitored with contrast-enhanced DECT scans at baseline and a minimum of one follow-up (8-12 weeks) were retrospectively evaluated. 30 target lesions in total were analyzed for tumor response according to VIU and adapted Choi criteria and compared with the standard AASLD. RESULTS: According to AASLD criteria, 67% target lesions showed disease control: partial response (PR) in 3% and stable disease (SD) in 63%. 33% lesions progressed (PD). Disease control rate presented by VIU (60%) was similar to AASLD (67%) and Choi (63%) (P〉0.05). For disease control group, change in mean VIU was from 149.5+/-338.3mg to 108.5+/-284.1mg (decreased 19.1+/-42.9%); and for progressive disease group, change in mean VIU was from 163.7+/-346.7mg to 263.9+/-537.2mg (increased 230.5+/-253.1%). Compared to AASLD (PR, 3%), VIU and Choi presented more PR (33% and 30%, respectively) in disease control group (P〈0.05). VIU has moderate consistency with both AASLD (kappa=0.714; P〈0.005) and Choi (kappa=0.648; P〈0.005), while VIU showed a better consistency and correlation with AASLD (kappa=0.714; P〈0.005; r=0.666, P〈0.005) than Choi with AASLD (kappa=0.634, P〈0.005; r=0.102, P=0.296). CONCLUSION: VIU measurements by DECT can evaluate the disease control consistent with the current standard AASLD. Measurements are semi-automatic and therefore easy and robust to apply. As VIU reflects vital tumor burden in HCC, it is likely to be an optimal tumor response biomarker in HCC.
    Type of Publication: Journal article published
    PubMed ID: 23246016
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  • 2
    Keywords: radiotherapy ; liver ; radiation ; PROTON-BEAM
    Abstract: PURPOSE: Photon-based radiation therapy does currently not play a major role as local ablative treatment for hepatocellular carcinoma (HCC). Carbon ions offer distinct physical and biological advantages. Due to their inverted dose profile and the high local dose deposition within the Bragg peak, precise dose application and sparing of normal tissue is possible. Furthermore, carbon ions have an increased relative biological effectiveness (RBE) compared to photons. METHODS AND MATERIALS: A total of six patients with one or more HCC-lesions were treated with carbon ions delivered by the raster-scanning technique according to our clinical trial protocol. Diagnosis of HCC was confirmed by histology or two different imaging modalities (CT and MRI) according to the AASLD-guidelines. Applied fractionation scheme was 4 x 10 Gy(RBE). Correct dose application was controlled by in-vivo PET measurement of beta + -activity in the irradiated tissue shortly after treatment. RESULTS: Patients were observed for a median time period of 11.0 months (range, 3.4 - 12.7 months). Imaging studies showed a partial response in 4/7 lesions and a stable disease in 3/7 lesions in follow-up CT- and MRI scans. Local control was 100%. One patient with multifocal intrahepatic disease underwent liver transplantation 3 months after carbon ion therapy. During radiotherapy and the follow-up period no severe adverse events have occurred. CONCLUSIONS: We report the first clinical results of patients with HCC undergoing carbon ion therapy using the rasterscanning technique at our institution. All patients are locally controlled and experienced no higher toxicities in a short follow-up period. Further patients will be included in our prospective Phase-I clinical trial PROMETHEUS-01 (NCT01167374).
    Type of Publication: Journal article published
    PubMed ID: 23497349
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  • 3
    Keywords: GROWTH ; PATIENT ; RESPONSES ; SIMULATION ; FLOW ; VELOCITY ; thrombus ; RUPTURE ; WALL SHEAR-STRESS
    Abstract: Objectives: To evaluate hemodynamic changes during aneurysmal dilatation in chronic type B aortic dissections compared to hemodynamic parameters in the healthy aorta with the use of computational fluid dynamics (CFD). Methods: True lumen (TL)/false lumen (FL) dimensional changes, changes in total pressure (TP), and wall shear stress (WSS) were evaluated at follow-up (FU) compared to initial examination (IE) with transient CFD simulation with geometries derived from clinical image data and inflow boundary conditions from magnetic resonance images. The TL/FL pressure gradient between ascending and descending aorta (DAo) and maximum WSS at the site of largest dilatation was compared to values for the healthy aorta. Results: Hemodynamic changes at site of largest FL dilatation included 77% WSS reduction and 69% TP reduction. Compared to the healthy aorta, pressure gradient between ascending and DAo was a factor of 1.4 higher in the TL and a factor of 1.5 in the FL and increased at FU (1.6 and 1.7, respectively). Maximum WSS at the site of largest dilatation was a factor of 3 lower than that for the healthy aorta at IE and decreased by more than a factor of 2 at FU. Conclusions: The FL dilatation at FU favorably reduced TP. In contrast, unfavorable increase in pressure gradient between ascending and DAo was observed with higher values than in the healthy aorta. Maximum WSS was reduced at the site of largest dilation compared to healthy aorta.
    Type of Publication: Journal article published
    PubMed ID: 24048257
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  • 4
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    Radiologe 52 (4), 330-337 
    Keywords: CT ; TUMORS ; COMPLEX ; LYMPHOMA ; monitoring ; positron emission tomography (PET) ; RESPONSE CRITERIA ; Cheson criteria
    Abstract: CLINICAL/METHODICAL ISSUE: A proven criterion for assessing tumor response is the increase in tumor size. Unlike most tumors, lymph nodes are normal anatomical structures and can be measured even when benign. The International Working Group (IWG) criteria for lymphomas therefore combine morphological with functional (positron emission tomography PET) and biopsy (bone marrow biopsy) parameters. The IWG criteria have been established as the standard in clinical trials and take nodal involvement, spleen, liver involvement as well as bone marrow involvement into account, which makes the response evaluation complex. STANDARD RADIOLOGICAL METHODS: This involves an investigator-dependent, non-standardized and poorly reproducible estimation of tumor response to therapy. METHODICAL INNOVATIONS: The formulation of standardized response categories for malignant lymphomas. PERFORMANCE: The aim was to produce uniform and standardized criteria for application in medication studies. ACHIEVEMENTS: Established as the standard for medication studies but too time-consuming for practical application. PRACTICAL RECOMMENDATIONS: An improved practicability can be achieved by incorporating a computer-assisted evaluation program.
    Type of Publication: Journal article published
    PubMed ID: 22418972
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  • 5
    Keywords: PATHWAY ; TUMORS ; TRENDS ; B-RAF ; cell proliferation ; RAS MUTATIONS ; VEMURAFENIB
    Abstract: Purpose: Targeted therapy can lead to considerable tumor reduction and may result initially in altered tissue at constant tumor size. In this setting, Response Evaluation Criteria in Solid Tumors (RECIST) can be inadequate for assessing early treatment response. Choi-criteria combine both size and density measurements. Our purpose was to evaluate computed tomography (CT) images of melanoma patients under BRAF-inhibitor therapy according to Choi-criteria which were adapted to our study (aChoi). Material and Methods: Twelve patients (four male, eight female, mean age 49) with stage IV melanoma treated with a BRAF inhibitor were included. Response was assessed according to RECIST for 39 lesions in contrast-enhanced CT. Target volumes are semiautomatically segmented to calculate mean density for aChoi-criteria, thus using a two-dimensional nonstandardized region of interest could be prevented. Results: Eight patients are RECIST responders. aChoi-criteria indicate therapy response earlier compared to RECIST in five of eight patients. In seven cases, tumor density in CT had decreased 8 weeks after therapy start, whereas in some cases tumor size diminished less or even increased. Response according to aChoi was diagnosed in seven patients who showed in RECIST-evaluation stable disease in five and partial response in two cases. Fifteen weeks after therapy start almost all patients within the aChoi responders were RECIST responders, too. Only one aChoi responder showed still stable disease in RECIST. Conclusion: Our initial data indicate that aChoi-criteria can reflect response to vemurafenib earlier compared to RECIST. This is of clinical significance as BRAF-inhibitors are cost-intensive targeted therapies and can cause severe side effects, so criteria for early therapy response have to be evaluated.
    Type of Publication: Journal article published
    PubMed ID: 23498982
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  • 6
    Keywords: POSITRON-EMISSION-TOMOGRAPHY ; METASTATIC MALIGNANT-MELANOMA ; RANDOMIZED PHASE-III ; QUALITY-OF-LIFE ; HIGH-RISK MELANOMA ; STAGE-IV MELANOMA ; SENTINEL LYMPH-NODES ; HEPATIC ARTERIAL CHEMOEMBOLIZATION ; VS. 3-DIMENSIONAL HISTOLOGY ; SERUM LACTATE-DEHYDROGENASE
    Type of Publication: Journal article published
    PubMed ID: 23721604
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  • 7
    Keywords: POSITRON-EMISSION-TOMOGRAPHY ; ISOLATED LIMB PERFUSION ; RANDOMIZED PHASE-III ; QUALITY-OF-LIFE ; COOPERATIVE-ONCOLOGY-GROUP ; AMERICAN-JOINT-COMMITTEE ; HIGH-RISK MELANOMA ; STAGE-IV MELANOMA ; SENTINEL LYMPH-NODE ; PRIMARY CUTANEOUS MELANOMA
    Abstract: This first German evidence-based guideline for cutaneous melanoma was developed under the auspices of the German Dermatological Society (DDG) and the Dermatologic Cooperative Oncology Group (DeCOG) and funded by the German Guideline Program in Oncology. The recommendations are based on a systematic literature search, and on the consensus of 32 medical societies, working groups and patient representatives. This guideline contains recommendations concerning diagnosis, therapy and follow-up of melanoma. The diagnosis of primary melanoma based on clinical features and dermoscopic criteria. It is confirmed by histopathologic examination after complete excision with a small margin. For the staging of melanoma, the AJCC classification of 2009 is used. The definitive excision margins are 0.5 cm for in situ melanomas, 1 cm for melanomas with up to 2 mm tumor thickness and 2 cm for thicker melanomas, they are reached in a secondary excision. From 1 mm tumor thickness, sentinel lymph node biopsy is recommended. For stages II and III, adjuvant therapy with interferon-alpha should be considered after careful analysis of the benefits and possible risks. In the stage of locoregional metastasis surgical treatment with complete lymphadenectomy is the treatment of choice. In the presence of distant metastasis mutational screening should be performed for BRAF mutation, and eventually for CKIT and NRAS mutations. In the presence of mutations in case of inoperable metastases targeted therapies should be applied. Furthermore, in addition to standard chemotherapies, new immunotherapies such as the CTLA-4 antibody ipilimumab are available. Regular follow-up examinations are recommended for a period of 10 years, with an intensified schedule for the first three years.
    Type of Publication: Journal article published
    PubMed ID: 24028775
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  • 8
    Keywords: CANCER ; THERAPY ; GUIDELINES ; PHASE-II ; GASTROINTESTINAL STROMAL TUMORS ; MALIGNANT-LYMPHOMA ; RECIST ; WORKING GROUP ; ADVANCED HEPATOCELLULAR-CARCINOMA ; RESPONSE EVALUATION CRITERIA
    Abstract: PURPOSE: Thanks to advances in cancer therapy, the diagnosis of "incurable cancer" is increasingly able to be changed to a chronic disease that is manageable over long periods, resulting in a change in the clinical management of cancer patients with solid tumors. New parameters are needed to measure the success of targeted therapy in clinical trials. MATERIALS AND METHODS: Review article on the basis of selective literature research. RESULTS: In order to assess how well solid tumors respond to treatment, size-based criteria called RECIST (Response Evaluation Criteria in Solid tumors) have been defined. These criteria have been validated in large oncology trials and are currently used most frequently. New molecular therapies often do not - or at least do not immediately - reduce the size of a tumor. Therefore, RECIST evaluation should be critically assessed especially in the case of modern therapies. Any additional available tumor biology information should be considered. In radiology new methods and developments of RECIST have been introduced to better assess the success of targeted therapy. CONCLUSION: Assessment according to RECIST has been proven for the follow-up of classic tumor therapy. For the monitoring of targeted therapies, new parameters are often required. Therefore, some specific tumor- and therapy-adapted criteria have already been defined to better evaluate treatment success in clinical trials.
    Type of Publication: Journal article published
    PubMed ID: 24563412
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