Reduced splenic uptake on 68Ga-Pentixafor-PET/CT imaging in multiple myeloma - a potential imaging biomarker for disease prognosis

Beyond being a key factor for tumor growth and metastasis in human cancer, C-X-C motif chemokine receptor 4 (CXCR4) is also highly expressed by a number of immune cells, allowing for non-invasive read-out of inflammatory activity. With two recent studies reporting on prognostic implications of the spleen signal in diffusion-weighted magnetic resonance imaging in patients with plasma cell dyscrasias, the aim of this study was to correlate splenic (68)Ga-Pentixafor uptake in multiple myeloma (MM) with clinical parameters and to evaluate its prognostic impact. METHODS: Eighty-seven MM patients underwent molecular imaging with (68)Ga-Pentixafor-PET/CT. Splenic CXCR4 expression was semi-quantitatively assessed by peak standardized uptake values (SUV(peak)) and corresponding spleen-to-bloodpool ratios (TBR) and correlated with clinical and prognostic features as well as survival parameters. RESULTS: (68)Ga-Pentixafor-PET/CT was visually positive in all MM patients with markedly heterogeneous tracer uptake in the spleen. CXCR4 expression determined by (68)Ga-Pentixafor-PET/CT corresponded with advanced disease and was inversely associated with the number of previous treatment lines as compared to controls or untreated smouldering multiple myeloma patients (SUV(peak)Spleen 4.06 ± 1.43 vs. 6.02 ± 1.16 vs. 7.33 ± 1.40; (P5.79 ((P<) 0.001). Multivariate Cox analysis confirmed SUV(peak)Spleen as an independent predictor of survival (HR 0.75;P= 0.009). CONCLUSION: These data suggest that splenic (68)Ga-Pentixafor uptake might provide prognostic information in pre-treated MM patients similar to what was reported for diffusion-weighted magnetic resonance imaging. Further research to elucidate the underlying biologic implications is warranted

Tetramodal therapy with transurethral resection followed by chemoradiation in combination with hyperthermia for muscle-invasive bladder cancer: early results of a multicenter phase IIB study.

BACKGROUND Transurethral resection of bladder tumor (TUR-BT) followed by chemoradiation (CRT) is a valid treatment option for patients with muscle-invasive bladder cancer (MIBC). This study aimed to investigate the efficacy of a tetramodal approach with additional regional hyperthermia (RHT). METHODS Patients with stages T2-4 MIBC were recruited at two institutions. Treatment consisted of TUR-BT followed by radiotherapy at doses of 57-58.2 Gy with concurrent weekly platinum-based chemotherapy and weekly deep RHT (41-43 °C, 60 min) within two hours of radiotherapy. The primary endpoint was a complete response six weeks after the end of treatment. Further endpoints were cystectomy-free rate, progression-free survival (PFS), local recurrence-free survival (LRFS), overall survival (OS) and toxicity. Quality of life (QoL) was assessed at follow-up using the EORTC-QLQ-C30 and QLQ-BM30 questionnaires. Due to slow accrual, an interim analysis was performed after the first stage of the two-stage design. RESULTS Altogether 27 patients were included in the first stage, of these 21 patients with a median age of 73 years were assessable. The complete response rate of evaluable patients six weeks after therapy was 93%. The 2-year cystectomy-free rate, PFS, LRFS and OS rates were 95%, 76%, 81% and 86%, respectively. Tetramodal treatment was well tolerated with acute and late G3-4 toxicities of 10% and 13%, respectively, and a tendency to improve symptom-related quality of life (QoL) one year after therapy. CONCLUSION Tetramodal therapy of T2-T4 MIBC is promising with excellent local response, moderate toxicity and good QoL. This study deserves continuation into the second stage

A Maintenance-Oriented Fault Model for the DECOS Integrated Diagnostic Architecture

The increasing use of electronics in the automotive and avionic domain has lead to dramatic improvements with respect to functionality, safety, and cost. However, with this growth of electronics the likelihood of failures due to faults originating from electronic equipment also increases. In order to tackle prevalent diagnostic problems such as the reduction of the fault-not-found ratio, a maintenance-oriented fault model is needed that serves as the basis for the classification of experienced failures

Evaluation of Fault Handling of the Time-Triggered Architecture with Bus and Star Topology

Arbitrary faults of a single node In a time-triggered architecture (TTA) bus topology system may cause error propagation to correct nodes and may lead to inconsistent system states. This has been observed in validation work using software implemented fault injection (SWIFI) and heavy-ion fault injection techniques in a TTA cluster. In a TTA system, the membership and the clique avoidance algorithms detect state inconsistencies and force the nodes that do not have the same state with the state of majority of nodes, to restart. Changing the interconnection structure of the cluster to a star topology allows the use of star couplers that will isolate faults of a node, thus guaranteeing consistency, even in the presence of arbitrary node failures. The same SWIFI and heavy-ion fault injection experiments that caused error propagation in bus-based TTA clusters, were performed in the star configuration. No error propagation was observed in a TTA system with the star topology during the execution of SWIFI and heavy-ion experiments

Evaluation of Fault Handling of the Time-Triggered Architecture with Bus and Star Topology

Arbitrary faults of a single node In a time-triggered architecture (TTA) bus topology system may cause error propagation to correct nodes and may lead to inconsistent system states. This has been observed in validation work using software implemented fault injection (SWIFI) and heavy-ion fault injection techniques in a TTA cluster. In a TTA system, the membership and the clique avoidance algorithms detect state inconsistencies and force the nodes that do not have the same state with the state of majority of nodes, to restart. Changing the interconnection structure of the cluster to a star topology allows the use of star couplers that will isolate faults of a node, thus guaranteeing consistency, even in the presence of arbitrary node failures. The same SWIFI and heavy-ion fault injection experiments that caused error propagation in bus-based TTA clusters, were performed in the star configuration. No error propagation was observed in a TTA system with the star topology during the execution of SWIFI and heavy-ion experiments

A tunable add-on diagnostic protocol for time-triggered systems

We present a tunable diagnostic protocol for generic time-triggered (TT) systems to detect crash and send/receive omission faults. Compared to existing diagnostic and membership protocols for TT systems, it does not rely on the single-fault assumption and tolerates malicious faults. It runs at the application level and can be added on top of any TT system (possibly as a middleware component) without requiring modifications at the system level. The information on detected faults is accumulated using a penalty/reward algorithm to handle transient faults. After a fault is detected, the likelihood of node isolation can be adapted to different system configurations, including those where functions with different criticality levels are integrated. Using actual automotive and aerospace parameters, we experimentally demonstrate the transient fault handling capabilities of the protocol. © 2007 IEEE

cpmViz : A Web-Based Visualization Tool for Uncertain Spatiotemporal Data

The goal of the VAST challenge 2019 Mini Challenge 2 was to visualize radioactive contaminations measured by mobile and static sensors and their changes over time, allowing city officials to determine the severity of the leakage at the city's nuclear power plant. We propose cpmViz, a web-based tool that allows for interactive data exploration of the sensor readings in both of the spatial and temporal dimensions. The tool consists out of three views that are connected via linking and scrolling. We visualize static sensor uncertainty by introducing Voronoi cells to illustrate how much space is covered by an individual measurement unit. For mobile sensors, we showcase their activity periods and introduce the concept of sensor streaks as periods of uninterrupted recordings as a temporal uncertainty measure. As for spatial uncertainty, we color individual districts based on the amount of data that was recorded inside the user's selected time window. Using our system, we were able to easily spot major events like the city's initial earthquake in the sensor readings. Certain southern districts are clearly visible as areas of concern that we consider in need of more static sensors. Furthermore, we were also able to identify static as well as moving contaminations.publishe

Radiotherapy combined with deep regional hyperthermia in elderly and frail patients with muscle-invasive bladder cancer: quality analysis of hyperthermia and impact on clinical results

AbstractPurpose: Radiotherapy (RT) in combination with deep regional hyperthermia (HT) after transurethral removal of bladder tumor (TURBT) can be offered to elderly and frail patients with muscle-invasive bladder cancer (MIBC).Methods: In total, 21 patients (mean age 84 years) with unifocal or multifocal MIBC received radiation to a dose of 48–50 Gy/16–20 fractions with weekly HT. The primary endpoint was the variation in temperature metrics, thermal dose expressed as cumulative equivalent minutes at 43 °C when the measured temperature is T90 (CEM43T90) and net power applied in target volume per each HT session. Secondary endpoints were three-year overall survival (OS), disease-free survival (DFS), local progression-free survival (LPFS) and toxicity.Results: The temperature metrics, CEM43T90, mean and maximum net power applied did not differ significantly among the HT sessions of the 21 patients. With a median follow-up of 65 months, 52% (95% CI 32–72%) of patients had died 3 years after treatment. The three-year DFS and LPFS rates were 62% (95%CI 41–79%) and 81% (95%CI 60–92%), respectively. The three-year bladder preservation rate was 100%. Three out of four patients with local failure received a thermal dose CEM43T90 below a median of 2.4 min. The rates of acute and late grade-3 toxicities were 10% and 14%, respectively.Conclusion: The reproducibility of HT parameters between sessions was high. A moderately high CEM43T90 (> 2.4 min) for each HT session seems to be preferable for local control. RT combined with HT is a promising organ-preservation therapy for elderly and frail MIBC patients