Low-dose metronomic chemotherapy as an efficient treatment option in metastatic breast cancer-results of an exploratory case-control study.

PURPOSE: There is growing interest in low-dose metronomic chemotherapy (LDMC) in metastatic breast cancer (MBC). In this retrospective case-control analysis, we compared the efficacy of LDMC and conventional chemotherapy (CCT) in MBC. METHODS: Each LDMC patient receiving oral cyclophosphamide (CTX) (50 mg daily) and methotrexate (MTX) (2.5 mg every other day) was matched with two controls who received CCT. Age, number of chemotherapy lines and metastatic sites as well as hormone receptor (HR) status were considered as matching criteria. Primary endpoint was disease control rate longer than 24 weeks (DCR). Secondary endpoints were progression-free survival (PFS), duration of response (DoR) and subgroup analyses using the matching criteria. RESULTS: 40 cases and 80 controls entered the study. 30.0% patients with LDMC and 22.5% patients with CCT showed DCR (p = 0.380). The median PFS was 12.0 weeks in both groups (p = 0.218) and the median DoR was 31.0 vs. 20.5 weeks (p = 0.383), respectively. Among younger patients, DCR was 40.0% in LDMC vs. 25.0% in the CCT group (p = 0.249). DCR was achieved in 33.3% vs. 26.2% non-heavily pretreated patients (p = 0.568) and in 36.0% vs. 18.0% patients without multiple metastases (p = 0.096), respectively. In the HR-positive group, 30.0% LDMC vs. 28.3% CCT patients showed DCR (p = 1.000). Among triple-negative patients, DCR was achieved in 30.0% LDMC and 5.0% CCT patients (p = 0.095). CONCLUSIONS: We demonstrated a similar efficacy of LDMC compared to CCT in the treatment of MBC. Thus, LDMC may be a valuable treatment option in selected MBC patients.

Prostate Cancer Nodal Staging: Using Deep Learning to Predict 68Ga-PSMA-Positivity from CT Imaging Alone.

Lymphatic spread determines treatment decisions in prostate cancer (PCa) patients. 68Ga-PSMA-PET/CT can be performed, although cost remains high and availability is limited. Therefore, computed tomography (CT) continues to be the most used modality for PCa staging. We assessed if convolutional neural networks (CNNs) can be trained to determine 68Ga-PSMA-PET/CT-lymph node status from CT alone. In 549 patients with 68Ga-PSMA PET/CT imaging, 2616 lymph nodes were segmented. Using PET as a reference standard, three CNNs were trained. Training sets balanced for infiltration status, lymph node location and additionally, masked images, were used for training. CNNs were evaluated using a separate test set and performance was compared to radiologists' assessments and random forest classifiers. Heatmaps maps were used to identify the performance determining image regions. The CNNs performed with an Area-Under-the-Curve of 0.95 (status balanced) and 0.86 (location balanced, masked), compared to an AUC of 0.81 of experienced radiologists. Interestingly, CNNs used anatomical surroundings to increase their performance, "learning" the infiltration probabilities of anatomical locations. In conclusion, CNNs have the potential to build a well performing CT-based biomarker for lymph node metastases in PCa, with different types of class balancing strongly affecting CNN performance.

Only strongly enhanced residual FDG uptake in early response PET (Deauville 5 or qPET ≥ 2) is prognostic in pediatric Hodgkin lymphoma: Results of the GPOH-HD2002 trial.

PURPOSE: In 2014, we published the qPET method to quantify fluorodeoxyglucose positron emission tomography (FDG-PET) responses. Analysis of the distribution of the quantified signals suggested that a clearly abnormal FDG-PET response corresponds to a visual Deauville score (vDS) of 5 and high qPET values ≥ 2. Evaluation in long-term outcome data is still pending. Therefore, we analyzed progression-free survival (PFS) by early FDG-PET response in a subset of the GPOH-HD2002 trial for pediatric Hodgkin lymphoma (PHL). PATIENTS/METHODS: Pairwise FDG-PET scans for initial staging and early response assessment after two cycles of chemotherapy were available in 93 PHL patients. vDS and qPET measurement were performed and related to PFS. RESULTS: Patients with a qPET value ≥ 2.0 or vDS of 5 had 5-year PFS rates of 44%, respectively 50%. Those with qPET values < 2.0 or vDS 1 to 4 had 5-year PFS rates of 90%, respectively 80%. The positive predictive value of FDG-PET response assessment increased from 18% (9%; 33%) using a qPET threshold of 0.95 (vDS ≤ 3) to 30% (13%; 54%) for a qPET threshold of 1.3 (vDS ≤ 4) and to 56% (23%; 85%) when the qPET threshold was ≥ 2.0 (vDS 5). The negative predictive values remained stable at ≥92% (CI: 82%; 98%). CONCLUSION: Only strongly enhanced residual FDG uptake in early response PET (vDS 5 or qPET ≥ 2, respectively) seems to be markedly prognostic in PHL when treatment according to the GPOH-HD-2002 protocol is given.

Thiourea derivatives as chelating agents for bioconjugation of rhenium and technetium.

Potential tetradentate thiocarbamoylbenzamidine derivatives H4L have been synthesized from the corresponding benzimidoyl chlorides and triglycine. They are suitable chelating agents for the oxidotechnetium(v) and oxidorhenium(v) cores and form stable, neutral [MO(HL)] complexes with an equatorial SN3 coordination sphere and an additional, uncoordinated carboxylic group, which can be used for bioconjugation. Representatives of the rhenium and 99Tc products have been isolated and analyzed with spectroscopic methods and X-ray diffraction. Bioconjugates of these complexes with angiotensin-II have been synthesized and structurally characterized. Analogous 99mTc complexes have been produced and tested in vitro and in vivo. The experiments confirm a considerable stability for the [99mTc(HL)] product as well as for its bioconjugate and recommend this class of compounds for further bioconjugation studies towards clinical applications.

Evaluation of bone viability in patients after girdlestone arthroplasty: comparison of bone SPECT/CT and MRI.

PURPOSE: To test the diagnostic performance of bone SPECT/CT and MRI for the evaluation of bone viability in patients after girdlestone-arthroplasty with histopathology used as gold standard. MATERIALS AND METHODS: In this cross-sectional study, patients after girdlestone-arthroplasty were imaged with single-photon-emission-computed-tomography/computed-tomography (SPECT/CT) bone-scans using 99mTc-DPD. Additionally, 1.5 T MRI was performed with turbo-inversion-recovery-magnitude (TIRM), contrast-enhanced T1-fat sat (FS) and T1-mapping. All imaging was performed within 24 h prior to revision total-hip-arthroplasty in patients with a girdlestone-arthroplasty. In each patient, four standardized bone-tissue-biopsies (14 patients) were taken intraoperatively at the remaining acetabulum superior/inferior and trochanter major/minor. Histopathological evaluation of bone samples regarding bone viability was used as gold standard. RESULTS: A total of 56 bone-segments were analysed and classified as vital (n = 39) or nonvital (n = 17) by histopathology. Mineral/late-phase SPECT/CT showed a high sensitivity (90%) and specificity (94%) to distinguish viable and nonviable bone tissue. TIRM (sensitivity 87%, specificity 88%) and contrast-enhanced T1-FS (sensitivity 90%, specificity 88%) also achieved a high sensitivity and specificity. T1-mapping achieved the lowest values (sensitivity 82%, specificity 82%). False positive results in SPECT/CT and MRI resulted from small bone fragments close to metal artefacts. CONCLUSIONS: Both bone SPECT/CT and MRI allow a reliable differentiation between viable and nonviable bone tissue in patients after girdlestone arthroplasty. The findings of this study could also be relevant for the evaluation of bone viability in the context of avascular bone necrosis.

Subtype-specific prognostic impact of different immune signatures in node-negative breast cancer.

BACKGROUND: The role of different subtypes of immune cells is still a matter of debate. METHODS: We compared the prognostic relevance for metastasis-free survival (MFS) of a B-cell signature (BS), a T-cell signature (TS), and an immune checkpoint signature (CPS) in node-negative breast cancer (BC) using mRNA expression. Microarray-based gene-expression data were analyzed in six previously published cohorts of node-negative breast cancer patients not treated with adjuvant therapy (n = 824). The prognostic relevance of the individual immune markers was assessed using univariate analysis. The amount of independent prognostic information provided by each immune signature was then compared using a likelihood ratio statistic in the whole cohort as well as in different molecular subtypes. RESULTS: Univariate Cox regression in the whole cohort revealed prognostic significance of CD4 (HR 0.66, CI 0.50-0.87, p = 0.004), CXCL13 (HR 0.86, CI 0.81-0.92, p < 0.001), CD20 (HR 0.76, CI 0.64-0.89, p = 0.001), IgκC (HR 0.81, CI 0.75-0.88, p < 0.001), and CTLA-4 (HR 0.67, CI 0.46-0.97, p = 0.032). Multivariate analyses of the immune signatures showed that both TS (p < 0.001) and BS (p < 0.001) showed a significant prognostic information in the whole cohort. After accounting for clinical-pathological variables, TS (p < 0.001), BS (p < 0.05), and CPS (p < 0.05) had an independent effect for MFS. In subgroup analyses, the prognostic effect of immune cells was most pronounced in HER2+ BC: BS as well as TS showed a strong association with MFS when included first in the model (p < 0.001). CONCLUSION: Immune signatures provide subtype-specific additional prognostic information over clinical-pathological variables in node-negative breast cancer.

Prognostic significance of interferon regulating factor 4 (IRF4) in node-negative breast cancer.

PURPOSE: The transcription factor IRF4 regulates immunoglobulin class switch recombination as well as plasma cell differentiation. We examined the prognostic significance of IRF4 expression in node-negative breast cancer (BC). METHODS: IRF4 expression was evaluated by immunostaining in a cohort of 197 node-negative BC patients not treated in adjuvant setting, referred to as Mainz cohort. The prognostic significance of immunohistochemically determined IRF4 expression for metastasis-free survival (MFS) was examined by Kaplan-Meier survival analysis as well as univariate and multivariate Cox analysis adjusted for age, pT stage, histological grade, ER, and HER2 status. For verification of immunohistochemical results, IRF4 mRNA expression was evaluated using microarray-based gene expression profiling in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) consisting of 824 node-negative breast cancer patients in total, who were not treated with adjuvant therapy. The prognostic significance of IRF4 mRNA expression on metastasis-free survival (MFS) was examined by univariate and multivariate Cox analysis in the Mainz cohort and by a meta-analysis of all node-negative BC patients and different molecular subtypes. IRF4 mRNA levels were compared to immunohistochemically determined IRF4 expression in 140 patients of the Mainz cohort using Spearman correlation. RESULTS: Immunohistochemically determined high IRF4 expression was associated with higher MFS in univariate Cox regression (HR 0.178, 95% CI 0.070-0.453, p < 0.001). IRF4 maintained its significance independently of established clinical factors for MFS (HR 0.088, 95% CI 0.033-0.232, p < 0.001). Immunohistochemically, determined IRF4 correlated moderately with IRF4 mRNA expression (ρ = 0.589). Higher expression of IRF4 was associated with better MFS in a meta-analysis of the total cohort (HR 0.438, 95% CI 0.307-0.623, p < 0.001). Prognostic significance was more pronounced in the HER2+ molecular subtype (HR 0.215, 95% CI 0.090-0.515, p = 0.001) as compared to the luminal A (HR 0.549, 95% CI 0.248-1.215, p = 0.139), luminal B (HR 0.444, 95% CI 0.215-0.916, p = 0.028), and basal-like subtypes (HR 0.487, 95% CI 0.269-0.883, p = 0.018). Further, IRF4 expression showed independent prognostic significance in a multivariate analysis of the Mainz cohort (HR 0.236, 95% CI 0.105-0.527, p < 0.001). CONCLUSIONS: IRF4 had independent prognostic significance in node-negative BC. Higher expression of IRF4 was associated with improved outcome. The prognostic impact differed between diverse molecular subtypes and was most pronounced in HER2+ breast cancer.

[Intradermal metal deposits in an industrial worker]. / Intradermale Metalleinsprengungen bei einem Industriearbeiter.

CASE REPORT: We describe a 75-year-old patient with asymptomatic grey pigmentation on the face and fingers. He had worked over two decades in cutting high-voltage cables. The cutting procedures were performed without a face shield or protection gloves. The patient presented with gray punctate lesions beside some homogeneously stained zones. DIAGNOSTICS: Histologically, the deposits presented in the dermal tissue in a horse-shoe, oval, or splinter-like shape. The foreign body material was embedded by a few CD68-positive macrophages. Undyed histological sections were investigated via two-dimensional micro-synchrotron X-ray fluorescence analysis (SRXRF). The deposits were identified as zinc (Zn), copper (Cu), nickel (Ni), and strontium (Sr), which were strongly associated with maximal sulfur (S) concentrations. This association is presumably induced by complex binding between thiol groups and metal ions such as Zn, Ni etc. However, the iron (Fe) distribution patterns were quite different to those of Zn, Cu, or Ni. These heavy metals are major components of the metal wires that the patient worked with in his profession. CONCLUSION: To the best of our knowledge, this is the first case report in the dermatological literature of intradermal metal deposits identified via SRXRF analysis.

Tissue engineered pre-vascularized buccal mucosa equivalents utilizing a primary triculture of epithelial cells, endothelial cells and fibroblasts.

Artificial generated buccal mucosa equivalents are a promising approach for the reconstruction of urethral defects. Limiting in this approach is a poor blood vessel supply after transplantation, resulting in increased morbidity and necrosis. We generated a pre-vascularized buccal mucosa equivalent in a tri-culture of primary buccal epithelial cells, fibroblasts and microvascular endothelial cells, using a native collagen membrane as a scaffold. A successful pre-vascularization and dense formation of capillary-like structures at superficial areas was demonstrated. The lumen size of pre-formed blood vessels corresponded to the capillary size in vivo (10-30 µm). Comparing native with a highly cross-linked collagen membrane we found a distinct higher formation of capillary-like structures on the native membrane, apparently caused by higher secretion of angiogenic factors such as PDGF, IL-8 and angiopoietin by the cells. These capillary-like structures became functional blood vessels through anastomosis with the host vasculature after implantation in nude mice. This in vitro method should result in an accelerated blood supply to the biomaterial with cells after transplantation and increase the succes rates of the implant material.

[Perioperative Outcomes in Correlation to the Learning Curve for Robotic Assisted Partial Nephrectomy: The First 109 Cases of our Clinic]. / Perioperatives Outcome in Korrelation zur Lernkurve bei robotisch assistierter partieller Nephrektomie: Die ersten 109 Fälle unserer Klinik.

BACKGROUND: In contrast to conventional laparoscopic partial nephrectomy, the approach of robot-assisted partial nephrectomy (RAPN) shows a steep learning curve with shorter warm ischaemia times (WIT) and comparable postoperative outcomes. Therefore RAPN is considered a good minimally-invasive surgical procedure for patients presenting with a renal cell carcinoma in clinical stage cT1a. The aim of the presented study was to evaluate the perioperative outcomes of our patients after RAPN and to illustrate the learning curve based on characteristic perioperative parameters such as WIT. MATERIAL AND METHODS: The data of 109 patients treated by RAPN in our clinic between January 2010 and April 2015 were retrospectively analysed regarding perioperative, laboratory and oncological outcomes. Postoperative complications until 30 days after surgery were documented. We analysed the data of the largest patient population treated by a single urologist, comparing WIT, operating time, blood loss and decline of the glomerular filtration rate between the first and the second 30 consecutive cases. RESULTS: Mean WIT was 18.4 min (SD±10.2), mean operating time was 199 min (SD±20), and mean estimated blood loss was 657 millilitres (SD±715 ml). Mean loss of GFR was reported to be 4.99 mg/dl/1.73 m (2) (SD±15.44). 83 (76%) malignant lesions were removed. 11 patients (10%) had a R1 resection, one patient had a R2 resection and in 2 cases the resection status was Rx. 22% of patients developed postoperative complications. Intraoperative complications were documented in 2 cases. According to the Clavien-Dindo Classification, 6% of patients had grade 1 and 2 complications and 13% developed grade 3 and 4 complications. WIT was significantly lower after 30 consecutive cases treated by one urologist. Regarding operating time, GFR or blood loss no significant correlation was found. CONCLUSION: Our data is in line with the surgical outcomes described in the literature. RAPN is a safe surgical technique with a steep learning curve. In our experience, 30 surgical cases provide a urologist with sufficient expertise to achieve good perioperative results. Weaknesses of this report include the retrospective design and insufficient documentation in some cases.

[Prevascularization of an in vitro buccal mucosa equivalent for regeneration of the urethra]. / Prävaskularisierung eines In-vitro-Mundschleimhautäquivalents zur Regeneration der Urethra.

For reconstructive interventions on the urethra the use of autologous buccal mucosa has a proven value. The aim of this study was to generate an in vitro preparation which is already infiltrated by capillary-like structures and is more rapidly incorporated after implantation. Commercially available collagen matrices which have been approved for use in humans were used as the substrate. Application possibilities of such artificial tissue in addition to reconstruction of the urethra include coverage of large defects in the oral, neck, nasal and aural areas, in gynecology and in ophthalmology.

Ventilation/perfusion SPECT/CT in patients with pulmonary emphysema. Evaluation of software-based analysing.

UNLABELLED: The purpose of this study was to evaluate the reproducibility of a new software based analysing system for ventilation/perfusion single-photon emission computed tomography/computed tomography (V/P SPECT/CT) in patients with pulmonary emphysema and to compare it to the visual interpretation. PATIENTS, MATERIAL AND METHODS: 19 patients (mean age: 68.1 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. Data were analysed by two independent observers in visual interpretation (VI) and by software based analysis system (SBAS). SBAS PMOD version 3.4 (Technologies Ltd, Zurich, Switzerland) was used to assess counts and volume per lung lobe/per lung and to calculate the count density per lung, lobe ratio of counts and ratio of count density. VI was performed using a visual scale to assess the mean counts per lung lobe. Interobserver variability and association for SBAS and VI were analysed using Spearman's rho correlation coefficient. RESULTS: Interobserver agreement correlated highly in perfusion (rho: 0.982, 0.957, 0.90, 0.979) and ventilation (rho: 0.972, 0.924, 0.941, 0.936) for count/count density per lobe and ratio of counts/count density in SBAS. Interobserver agreement correlated clearly for perfusion (rho: 0.655) and weakly for ventilation (rho: 0.458) in VI. CONCLUSIONS: SBAS provides more reproducible measures than VI for the relative tracer uptake in V/P SPECT/CTs in patients with pulmonary emphysema. However, SBAS has to be improved for routine clinical use.

[Bone metastasis by renal cell carcinoma. Importance of calcium and calcium-sensing receptor]. / Knochenmetastasierung des Nierenzellkarzinoms. Die Bedeutung von Calcium und calciumsensitivem Rezeptor.

Bone tissue is one of the main locations of metastases in renal cell carcinoma (RCC). In bone tissue the concentration of calcium ions is very high. Cells recognize extracellular calcium by the calcium-sensing receptor (CaSR). To investigate the role of calcium in bone metastases, the CaSR was quantified in tumor tissue and primary tumor cells of patients who were free of metastases or developed bone or lung metastases during a time period of 5 years after nephrectomy. In tissue specimens and primary cells of patients developing bone metastases, CaSR expression was clearly enhanced. Functionally, analyses showed a higher sensitivity in bone metastasizing cells concerning proliferation and chemotactical migration. These effects were caused by enhanced activity of the downstream targets of CaSR, namely AKT, PLCg, JNK and p38, analyzed in a phospho-kinase array and western blot analysis. The extent to which CaSR is suitable as a new marker for bone-specific metastases from renal cancer must be examined further.

Detection of pancreatic neuroendocrine tumors (PNET) using semi-quantitative [68Ga]DOTATOC PET in combination with multiphase contrast-enhanced CT.

AIM: Pancreatic neuroendocrine tumors (PNETs) pose a diagnostic challenge with respect to the physiologic somatostatin receptor expression in the uncinate process representing a potential pitfall for receptor imaging with PET/CT. METHODS: We identified 49 PNETs from a total of 316 consecutive [68Ga]DOTATOC PET/CT examinations for whom the detections rates of PET and multiphase contrast enhanced (CE-) CT could be retrospectively compared and 38 PNETs for which SUVmax and SUVmax target-to-liver ratios could be calculated for the tumors and the uncinate process. RESULTS: The detection rate of PET (83.7%) was higher than of the different CT phases (arterial: 59.2%, P=0.017; portal-venous: 38.8%, P<0.001; venous: 46.9%, P=0.001; multiphase: 71.4%, P=0.286). Compared to the other method PET revealed 28.6% additional lesions and multiphase CE-CT 16.3%. The portal-venous phase revealed only lesions that were also detected in the arterial or venous phase. The detection rate for PNETs in the uncinate process (N.=9) was 66.7% for PET versus 55.6% for multiphase CE-CT. SUVmax and SUVmax target-to-liver ratios differed significantly (P<0.001) for PNETs (mean, range: SUVmax, 14.6, 1.4-69.3; SUVmax target-to-liver ratio, 3.2, 0.69-23.1) and uncinate process (4.32, 0.8-13.5; 0.94, 0.51-1.56), however with a wide overlap. CONCLUSION: Patients with PNETs should undergo [68Ga]DOTATOC PET/CT with at least an arterial and venous phase CT scan. SUVmax and SUVmax target-to-liver ratios provide additional information but do no reliably separate PNETs from normal tracer uptake in the uncinate process.

Global scaling for semi-quantitative analysis in FP-CIT SPECT.

UNLABELLED: Semi-quantitative characterization of dopamine transporter availability from single photon emission computed tomography (SPECT) with 123I-ioflupane (FP-CIT) is based on uptake ratios relative to a reference region. The aim of this study was to evaluate the whole brain as reference region for semi-quantitative analysis of FP-CIT SPECT. The rationale was that this might reduce statistical noise associated with the estimation of non-displaceable FP-CIT uptake. PATIENTS, METHODS: 150 FP-CIT SPECTs were categorized as neurodegenerative or non-neurodegenerative by an expert. Semi-quantitative analysis of specific binding ratios (SBR) was performed with a custom-made tool based on the Statistical Parametric Mapping software package using predefined regions of interest (ROIs) in the anatomical space of the Montreal Neurological Institute. The following reference regions were compared: predefined ROIs for frontal and occipital lobe and whole brain (without striata, thalamus and brainstem). Tracer uptake in the reference region was characterized by the mean, median or 75th percentile of its voxel intensities. The area (AUC) under the receiver operating characteristic curve was used as performance measure. RESULTS: The highest AUC of 0.973 was achieved by the SBR of the putamen with the 75th percentile in the whole brain as reference. The lowest AUC for the putamen SBR of 0.937 was obtained with the mean in the frontal lobe as reference. CONCLUSION: We recommend the 75th percentile in the whole brain as reference for semi-quantitative analysis in FP-CIT SPECT. This combination provided the best agreement of the semi-quantitative analysis with visual evaluation of the SPECT images by an expert and, therefore, is appropriate to support less experienced physicians.

Combined measurement of tumor perfusion and glucose metabolism for improved tumor characterization in advanced cervical carcinoma. A PET/CT pilot study using [15O]water and [18F]fluorodeoxyglucose.

BACKGROUND AND PURPOSE: The aim of this pilot study was (1) to evaluate the combination of [(18)F]fluorodeoxyglucose (FDG) and [(15)O]water for detection of flow-metabolism mismatch in advanced cervical carcinomas, i.e., increased glycolysis at low blood flow, as a possible parameter for prediction of response to treatment, and (2) to propose a method for automated quantification of its spatial extent. PATIENTS AND METHODS: The study retrospectively included 10 women with advanced cervical carcinoma in whom PET with both FDG and [(15)O]water had been performed prior to therapy. The metabolically active tumor volume was delineated automatically in the FDG images. For computation of the regional blood flow in the tumor, a recovery corrected image-derived arterial input function was used. A tumor voxel was classified as mismatched when the voxel SUV of FDG was larger than the median tumor SUV and the voxel perfusion (K1) was smaller than the median perfusion. The absolute mismatch volume (aMMV) was defined as the volume of all mismatched voxels in ml, and the relative mismatch volume (rMMV) as the ratio of the aMMV to the metabolic tumor volume in percent. RESULTS: The tumors were quite heterogeneous with respect to both FDG uptake and perfusion. The aMMV clustered into 2 groups: "large aMMV" ≥ 10 ml in 40 % of patients and "small aMMV" ≤ 5 ml in 60 % of patients. The rMMV ranged from 12.7-24.9 %. There was no correlation between rMMV and metabolic tumor volume. There was a tendency (p = 0.126) for an association between rMMV and histological grading, rMMV being about 20 % higher in G3 than in G2 tumors. rMMV did not correlate with SUV or perfusion. CONCLUSION: These results suggest that combined PET with FDG and [(15)O]water allows detection and quantitative characterization of flow-metabolism mismatch in advanced cervical carcinomas.

Detection of pancreatic neuroendocrine tumors (PNET) using semi-quantitative [68Ga]DOTATOC PET in combination with multiphase contrast-enhanced CT.

Aim: Pancreatic neuroendocrine tumors (PNETs) pose a diagnostic challenge with respect to the physiologic somatostatin receptor expression in the uncinate process representing a potential pitfall for receptor imaging with PET/CT. Methods: We identified 49 PNETs from a total of 316 consecutive [68Ga]DOTATOC PET/CT examinations for whom the detections rates of PET and multiphase contrast enhanced (CE-) CT could be retrospectively compared and 38 PNETs for which SUV max and SUV max target-to-liver ratios could be calculated for the tumors and the uncinate process. Results: The detection rate of PET (83.7%) was higher than of the different CT phases (arterial: 59.2%, P=0.017; portal-venous: 38.8%, P<0.001; venous: 46.9%, P=0.001; multiphase: 71.4%, P=0.286). Compared to the other method PET revealed 28.6% additional lesions and multiphase CE-CT 16.3%. The portal-venous phase revealed only lesions that were also detected in the arterial or venous phase. The detection rate for PNETs in the uncinate process (N.=9) was 66.7% for PET versus 55.6% for multiphase CE-CT. SUV max and SUV max target-to-liver ratios differed significantly (P<0.001) for PNETs (mean, range: SUV max,14.6, 1.4-69.3; SUV max target-to-liver ratio, 3.2, 0.69-23.1) and uncinate process (4.32, 0.8-13.5; 0.94, 0.51-1.56), however with a wide overlap. Conclusion: Patients with PNETs should undergo [68Ga]DOTATOC PET/CT with at least an arterial and venous phase CT scan. SUV max and SUV max target-to-liver ratios provide additional information but do no reliably separate PNETs from normal tracer uptake in the uncinate process.

[Bone scintigraphy. German Guideline S1]. / Skelettszintigraphie. DGN-Handlungsempfehlung (S1-Leitlinie).

The purpose of this guideline is to provide comprehensive state-of-the-art information about indication and how to perform and analyze bone scintigraphy. Based upon pathophysiology and pharmacology current acquisition techniques including new methodologies are summarized followed by a detailed list of indications. In the main part all relevant practical aspects such as patient preparation, anamnestic information, appropriate choice and dosage of the radiopharmaceutical, and data acquisition including interventions are discussed. Data processing and analysis, interpretation, reporting and documentation are described in the next chapters. Quality control, typical pitfalls and a short outlook to future developments complete the guideline.

SDF1ß expression in renal cell carcinoma correlates with grading and infiltration by CD8+ T-cells.

For several tumor entities, a significant correlation between the chemokine stromal cell-derived factor 1 (SDF1) and its receptor C-X-C chemokine receptor type 4 (CXCR4), metastasis and tumor proliferation, as well as prognosis, has been described. In this study, a series of 105 renal cell carcinoma patients were analyzed in terms of expression of SDF1α and SDF1ß and infiltration by CD4+ and CD8+ T-cells and the data correlated with TNM category, grading and survival. While the splice variant SDF1α had no impact on tumor grading, T-cell invasion or overall survival, expression of SDF1ß showed a significant correlation with tumor grading and also suggested a correlation with metastasis, as well as CD8+ T-cell invasion. These results indicate a potential T-cell-mediated antitumor response induced by SDF1ß up-regulation. Therefore targeting the SDF1ß-CXCR4 signaling pathway may be a promising means for new therapeutic strategies in advanced tumor stages.

FDG PET/CT in cancer therapy monitoring: computer-assisted analysis of baseline together with up to two follow-ups.

OBJECTIVES: We developed and tested a software tool for computer-assisted analysis of FDG-PET/CT in cancer therapy monitoring. The tool provides automatic semi-quantitative analysis of a baseline scan together with up to two follow-up scans (standardized uptake values, glycolytic volume). The tool also supports visual analysis by local spatial registration which allows display of tumor lesions with the same orientation in all scans. The tool's stability and accuracy was tested at typical everyday image quality. PATIENTS, METHODS: Ten unselected cancer patients in whom three FDG PET/CT scans had been performed were included. A total of 18 lesions were analyzed. RESULTS: Automatic lesion tracking worked properly in all lesions but one. In this lesion local coregistration had to be adjusted manually which, however, is easily performed with the tool. Semi-automatic lesion segmentation and fully automatic semi-quantitative analysis worked properly in all cases. Computer-assisted analysis was significantly less time consuming than manual analysis. CONCLUSIONS: The novel software tool appears useful for analysis of FDG-PET/CT in cancer therapy monitoring in clinical routine patient care.