Navigator-based motion compensation for liver BOLD measurement with five-echo SAGE EPI and breath-hold task.

PURPOSE: The purpose of this work is to apply multi-echo spin- and gradient-echo (SAGE) echo-planar imaging (EPI) combined with a navigator-based (NAV) prospective motion compensation method for a quantitative liver blood oxygen level dependent (BOLD) measurement with a breath-hold (BH) task. METHODS: A five-echo SAGE sequence was developed to quantitatively measure T2 and T2* to depict function with sufficient signal-to-noise ratio, spatial resolution and sensitivity to BOLD changes induced by the BH task. To account for respiratory motion, a navigator was employed in the form of a single gradient-echo projection readout, located at the diaphragm along the inferior-superior direction. Prior to each transverse imaging slice of the spin-echo EPI-based readouts, navigator acquisition and fat suppression were incorporated. Motion data was obtained from the navigator and transmitted back to the sequence, allowing real-time adjustments to slice positioning. Six healthy volunteers and three patients with liver carcinoma were included in this study. Quantitative T2 and T2* were calculated at each time point of the BH task. Parameters of t value from first-level analysis using a general linear model and hepatovascular reactivity (HVR) of Echo1, T2 and T2* were calculated. RESULTS: The motion caused by respiratory activity was successfully compensated using the navigator signal. The average changes of T2 and T2* during breath-hold were about 1% and 0.7%, respectively. With the help of NAV prospective motion compensation whole liver t values could be obtained without motion artifacts. The quantified liver T2 (34.7 ± 0.7 ms) and T2* (29 ± 1.2 ms) values agreed with values from literature. In healthy volunteers, the distribution of statistical t value and HVR was homogeneous throughout the whole liver. In patients with liver carcinoma, the distribution of t value and HVR was inhomogeneous due to metastases or therapy. CONCLUSIONS: This study demonstrates the feasibility of using a NAV prospective motion compensation technique in conjunction with five-echo SAGE EPI for the quantitative measurement of liver BOLD with a BH task.

[Imaging in immunotherapy for tumor diseases]. / Bildgebung bei Immuntherapie bei Tumorerkrankungen.

Immunotherapeutic agents and in particular immune checkpoint inhibitors (ICI) have opened up extensive new therapeutic possibilities in oncology over the last decade. For numerous entities these substances have improved the clinical outcome, sometimes as monotherapy but also in combination with cytostatic or targeted treatment. In routine clinical practice the type of radiological response often differs from what is seen under cytostatic treatment: a mixed response of individual lesions is more frequently observed and occasionally also a response after an initial progress (so-called pseudoprogression). Furthermore, there is a diverse spectrum of toxicity in the form of immune-related adverse events (irAE), which is observed in large temporal variability to the application. Therefore, early detection and rapid side effect management are essential.

Pulmonary magnetic resonance-guided online adaptive radiotherapy of locally advanced: the PUMA trial.

BACKGROUND: Patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) are often ineligible for surgery, so that definitive chemoradiotherapy (CRT) represents the treatment of choice. Nevertheless, long-term tumor control is often not achieved. Intensification of radiotherapy (RT) to improve locoregional tumor control is limited by the detrimental effect of higher radiation exposure of thoracic organs-at-risk (OAR). This narrow therapeutic ratio may be expanded by exploiting the advantages of magnetic resonance (MR) linear accelerators, mainly the online adaptation of the treatment plan to the current anatomy based on daily acquired MR images. However, MR-guidance is both labor-intensive and increases treatment times, which raises the question of its clinical feasibility to treat LA-NSCLC. Therefore, the PUMA trial was designed as a prospective, multicenter phase I trial to demonstrate the clinical feasibility of MR-guided online adaptive RT in LA-NSCLC. METHODS: Thirty patients with LA-NSCLC in stage III A-C will be accrued at three German university hospitals to receive MR-guided online adaptive RT at two different MR-linac systems (MRIdian Linac®, View Ray Inc. and Elekta Unity®, Elekta AB) with concurrent chemotherapy. Conventionally fractioned RT with isotoxic dose escalation up to 70 Gy is applied. Online plan adaptation is performed once weekly or in case of major anatomical changes. Patients are followed-up by thoracic CT- and MR-imaging for 24 months after treatment. The primary endpoint is twofold: (1) successfully completed online adapted fractions, (2) on-table time. Main secondary endpoints include adaptation frequency, toxicity, local tumor control, progression-free and overall survival. DISCUSSION: PUMA aims to demonstrate the clinical feasibility of MR-guided online adaptive RT of LA-NSCLC. If successful, PUMA will be followed by a clinical phase II trial that further investigates the clinical benefits of this approach. Moreover, PUMA is part of a large multidisciplinary project to develop MR-guidance techniques. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05237453 .

A proof-of-concept pipeline to guide evaluation of tumor tissue perfusion by dynamic contrast-agent imaging: Direct simulation and inverse tracer-kinetic procedures.

Dynamic contrast-enhanced (DCE) perfusion imaging has shown great potential to non-invasively assess cancer development and its treatment by their characteristic tissue signatures. Different tracer kinetics models are being applied to estimate tissue and tumor perfusion parameters from DCE perfusion imaging. The goal of this work is to provide an in silico model-based pipeline to evaluate how these DCE imaging parameters may relate to the true tissue parameters. As histology data provides detailed microstructural but not functional parameters, this work can also help to better interpret such data. To this aim in silico vasculatures are constructed and the spread of contrast agent in the tissue is simulated. As a proof of principle we show the evaluation procedure of two tracer kinetic models from in silico contrast-agent perfusion data after a bolus injection. Representative microvascular arterial and venous trees are constructed in silico. Blood flow is computed in the different vessels. Contrast-agent input in the feeding artery, intra-vascular transport, intra-extravascular exchange and diffusion within the interstitial space are modeled. From this spatiotemporal model, intensity maps are computed leading to in silico dynamic perfusion images. Various tumor vascularizations (architecture and function) are studied and show spatiotemporal contrast imaging dynamics characteristic of in vivo tumor morphotypes. The Brix II also called 2CXM, and extended Tofts tracer-kinetics models common in DCE imaging are then applied to recover perfusion parameters that are compared with the ground truth parameters of the in silico spatiotemporal models. The results show that tumor features can be well identified for a certain permeability range. The simulation results in this work indicate that taking into account space explicitly to estimate perfusion parameters may lead to significant improvements in the perfusion interpretation of the current tracer-kinetics models.

Quantification and reduction of cross-vendor variation in multicenter DWI MR imaging: results of the Cancer Core Europe imaging task force.

OBJECTIVES: In the Cancer Core Europe Consortium (CCE), standardized biomarkers are required for therapy monitoring oncologic multicenter clinical trials. Multiparametric functional MRI and particularly diffusion-weighted MRI offer evident advantages for noninvasive characterization of tumor viability compared to CT and RECIST. A quantification of the inter- and intraindividual variation occurring in this setting using different hardware is missing. In this study, the MRI protocol including DWI was standardized and the residual variability of measurement parameters quantified. METHODS: Phantom and volunteer measurements (single-shot T2w and DW-EPI) were performed at the seven CCE sites using the MR hardware produced by three different vendors. Repeated measurements were performed at the sites and across the sites including a traveling volunteer, comparing qualitative and quantitative ROI-based results including an explorative radiomics analysis. RESULTS: For DWI/ADC phantom measurements using a central post-processing algorithm, the maximum deviation could be decreased to 2%. However, there is no significant difference compared to a decentralized ADC value calculation at the respective MRI devices. In volunteers, the measurement variation in 2 repeated scans did not exceed 11% for ADC and is below 20% for single-shot T2w in systematic liver ROIs. The measurement variation between sites amounted to 20% for ADC and < 25% for single-shot T2w. Explorative radiomics classification experiments yield better results for ADC than for single-shot T2w. CONCLUSION: Harmonization of MR acquisition and post-processing parameters results in acceptable standard deviations for MR/DW imaging. MRI could be the tool in oncologic multicenter trials to overcome the limitations of RECIST-based response evaluation. KEY POINTS: • Harmonizing acquisition parameters and post-processing homogenization, standardized protocols result in acceptable standard deviations for multicenter MR-DWI studies. • Total measurement variation does not to exceed 11% for ADC in repeated measurements in repeated MR acquisitions, and below 20% for an identical volunteer travelling between sites. • Radiomic classification experiments were able to identify stable features allowing for reliable discrimination of different physiological tissue samples, even when using heterogeneous imaging data.

Adapting Imaging Protocols for PET-CT and PET-MRI for Immunotherapy Monitoring.

Hybrid imaging with positron emission tomography (PET) in combination with computer tomography (CT) is a well-established diagnostic tool in oncological staging and restaging. The combination of PET with magnetic resonance imaging (MRI) as a clinical scanner was introduced approximately 10 years ago. Although MRI provides superb soft tissue contrast and functional information without the radiation exposure of CT, PET-MRI is not as widely introduced in oncologic imaging as PET-CT. One reason for this hesitancy lies in the relatively long acquisition times for a PET-MRI scan, if the full diagnostic potential of MRI is exploited. In this review, we discuss the possible advantages of combined imaging protocols of PET-CT and PET-MRI, within the context of staging and restaging of patients under immunotherapy, in order to achieve "multi-hybrid imaging" in one single patient visit.

Phase 2 Trial of Oncolytic H-1 Parvovirus Therapy Shows Safety and Signs of Immune System Activation in Patients With Metastatic Pancreatic Ductal Adenocarcinoma.

PURPOSE: To investigate the safety, clinical efficacy, virus pharmacokinetics, shedding, and immune response after administration of an oncolytic parvovirus (H-1PV, ParvOryx) to patients with metastatic pancreatic ductal adenocarcinoma (PDAC) refractory to first-line therapy. PATIENTS AND METHODS: This is a noncontrolled, single-arm, open-label, dose-escalating, single-center clinical trial. Seven patients with PDAC and at least one liver metastasis were included. ParvOryx was administered intravenously on 4 consecutive days and as an intralesional injection, 6 to 13 days thereafter. Altogether, three escalating dose levels were investigated. In addition, gemcitabine treatment was initiated on day 28. RESULTS: ParvOryx showed excellent tolerability with no dose-limiting toxicities. One patient had a confirmed partial response and one patient revealed an unconfirmed partial response according to RECIST criteria. Both patients showed remarkably long surivial of 326 and 555 days, respectively. Investigation of pharmacokinetics and virus shedding revealed dose dependency with no excretion of active virus particles in saliva or urine and very limited excretion in feces. H-1PV nucleic acids were detected in tumor samples of four patients. All patients showed T-cell responses to viral proteins. An interesting immunologic pattern developed in tumor tissues and in blood of both patients with partial response suggesting immune activation after administration of ParvOryx. CONCLUSIONS: The trial met all primary objectives, revealed no environmental risks, and indicated favorable immune modulation after administration of ParvOryx. It can be considered a good basis for further systematic clinical development alone or in combination with immunomodulatory compounds.

Joint Imaging Platform for Federated Clinical Data Analytics.

PURPOSE: Image analysis is one of the most promising applications of artificial intelligence (AI) in health care, potentially improving prediction, diagnosis, and treatment of diseases. Although scientific advances in this area critically depend on the accessibility of large-volume and high-quality data, sharing data between institutions faces various ethical and legal constraints as well as organizational and technical obstacles. METHODS: The Joint Imaging Platform (JIP) of the German Cancer Consortium (DKTK) addresses these issues by providing federated data analysis technology in a secure and compliant way. Using the JIP, medical image data remain in the originator institutions, but analysis and AI algorithms are shared and jointly used. Common standards and interfaces to local systems ensure permanent data sovereignty of participating institutions. RESULTS: The JIP is established in the radiology and nuclear medicine departments of 10 university hospitals in Germany (DKTK partner sites). In multiple complementary use cases, we show that the platform fulfills all relevant requirements to serve as a foundation for multicenter medical imaging trials and research on large cohorts, including the harmonization and integration of data, interactive analysis, automatic analysis, federated machine learning, and extensibility and maintenance processes, which are elementary for the sustainability of such a platform. CONCLUSION: The results demonstrate the feasibility of using the JIP as a federated data analytics platform in heterogeneous clinical information technology and software landscapes, solving an important bottleneck for the application of AI to large-scale clinical imaging data.

Improving radiologic communication in oncology: a single-centre experience with structured reporting for cancer patients.

OBJECTIVES: Our aim was to develop a structured reporting concept (structured oncology report, SOR) for general follow-up assessment of cancer patients in clinical routine. Furthermore, we analysed the report quality of SOR compared to conventional reports (CR) as assessed by referring oncologists. METHODS: SOR was designed to provide standardised layout, tabulated tumour burden documentation and standardised conclusion using uniform terminology. A software application for reporting was programmed to ensure consistency of layout and vocabulary and to facilitate utilisation of SOR. Report quality was analysed for 25 SOR and 25 CR retrospectively by 6 medical oncologists using a 7-point scale (score 1 representing the best score) for 6 questionnaire items addressing different elements of report quality and overall satisfaction. A score of ≤ 3 was defined as a positive rating. RESULTS: In the first year after full implementation, 7471 imaging examinations were reported using SOR. The proportion of SOR in relation to all oncology reports increased from 49 to 95% within a few months. Report quality scores were better for SOR for each questionnaire item (p < 0.001 each). Averaged over all questionnaire item scores were 1.98 ± 1.22 for SOR and 3.05 ± 1.93 for CR (p < 0.001). The overall satisfaction score was 2.15 ± 1.32 for SOR and 3.39 ± 2.08 for CR (p < 0.001). The proportion of positive ratings was higher for SOR (89% versus 67%; p < 0.001). CONCLUSIONS: Department-wide structured reporting for follow-up imaging performed for assessment of anticancer treatment efficacy is feasible using a dedicated software application. Satisfaction of referring oncologist with report quality is superior for structured reports.

Granulomatous Reaction to Cosmetic Soft Tissue Filler with Late-onset Inflammatory Response.

is missing (Short communication).

INFORM2 NivEnt: The first trial of the INFORM2 biomarker driven phase I/II trial series: the combination of nivolumab and entinostat in children and adolescents with refractory high-risk malignancies.

BACKGROUND: Pediatric patients with relapsed or refractory disease represent a population with a desperate medical need. The aim of the INFORM (INdividualized Therapy FOr Relapsed Malignancies in Childhood) program is to translate next generation molecular diagnostics into a biomarker driven treatment strategy. The program consists of two major foundations: the INFORM registry providing a molecular screening platform and the INFORM2 series of biomarker driven phase I/II trials. The INFORM2 NivEnt trial aims to determine the recommended phase 2 dose (RP2D) of the combination treatment of nivolumab and entinostat (phase I) and to evaluate activity and safety (phase II). METHODS: This is an exploratory non-randomized, open-label, multinational and multicenter seamless phase I/II trial in children and adolescents with relapsed / refractory or progressive high-risk solid tumors and CNS tumors. The phase I is divided in 2 age cohorts: 12-21 years and 6-11 years and follows a 3 + 3 design with two dose levels for entinostat (2 mg/m2 and 4 mg/m2 once per week) and fixed dose nivolumab (3 mg/kg every 2 weeks). Patients entering the trial on RP2D can seamlessly enter phase II which consists of a biomarker defined four group basket trial: high mutational load (group A), high PD-L1 mRNA expression (group B), focal MYC(N) amplification (group C), low mutational load and low PD-L1 mRNA expression and no MYC(N) amplification (group D). A Bayesian adaptive design will be used to early stop cohorts that fail to show evidence of activity. The maximum number of patients is 128. DISCUSSION: This trial intends to exploit the immune enhancing effects of entinostat on nivolumab using an innovative biomarker driven approach in order to maximize the chance of detecting signs of activity. It prevents exposure to unnecessary risks by applying the Bayesian adaptive design for early stopping for futility. The adaptive biomarker driven design provides an innovative approach accelerating drug development and reducing exposure to investigational treatments in these vulnerable children at the same time. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03838042. Registered on 12 February 2019.

Interdisciplinary approach allows minimally invasive, nerve-sparing removal of retroperitoneal peripheral nerve sheath tumors.

PURPOSE: En bloc resection of retroperitoneal peripheral nerve sheath tumors (PNST) is advocated by a variety of surgical disciplines. Yet, microsurgical, nerve-sparing tumor resection might be better suited to improve symptoms and maintain neurological function, especially in cases where patients present with preoperative neurological deficits. However, neurosurgeons, versed in nerve-sparing techniques to remove PNST, are generally unfamiliar with the visceral approaches to retroperitoneal PNST. METHODS: We retrospectively evaluate a series of 16 patients suffering from retroperitoneal PNST. Patients were treated by a unique interdisciplinary approach, combining the visceral surgeon's skills to navigate the complex anatomy of the retroperitoneal space and the neurosurgeon's familiarity with microsurgical, nerve-sparing tumor removal. Specifically, we assess whether our interdisciplinary approach is suited to improve preoperative symptoms and maintain neurological function and study whether oncological outcome, surgical morbidity, and operative times are comparable to those reported for "classical" retroperitoneal PNST resection. In addition, we study two cases of suspected PNST that were diagnosed as malignant peripheral nerve sheath tumors (MPNST) after surgery. RESULTS: Total macroscopic tumor resection was achieved in 14/16 PNST patients. Mean intraoperative blood loss was 680.6 ml (95% CI, 194.3-1167.0 ml) and mean operative time was 162.5 min (95% CI, 121.6-203.4 min). We did not record any major postoperative surgical or neurological complications. A total of 8/11 patients with preoperative pain symptoms reported long-lasting improvement of their symptoms. In terms of oncological outcome, all patients that had been subjected to total tumor removal and for whom follow-up was available, were tumor-free after a mean follow-up of 761.9 days (95% CI, 97.6-1426.0 days). One of the two MPNST patients, who presented with tumor progress 15 months after initial surgery, was subjected to radical re-resection. CONCLUSIONS: Interdisciplinary, nerve-sparing removal of retroperitoneal PNST is well suited to improve preoperative symptoms and maintain neurological function, while achieving an oncological outcome and a surgical morbidity similar to previously reported results for radical retroperitoneal PNST resection. Radical re-resection was feasible in a patient with post hoc MPNST diagnosis.

Macroangiopathy is a positive predictive factor for response to immunotherapy.

Immunotherapies demand for predictive biomarkers to avoid unnecessary adverse effects and costs. Analytic morphomics is the technique to use body composition measures as imaging biomarkers for underlying pathophysiology to predict prognosis or outcome to therapy. We investigated different body composition measures to predict response to immunotherapy. This IRB approved retrospective analysis encompassed 147 patients with ipilimumab therapy. Degree of macroangiopathy was quantified with the newly defined total plaque index (TPI), i.e. the body height corrected sum of the soft and hard plaque volume of the infrarenal aorta on portalvenous CT scans. Furthermore, mean psoas density (MPD), different adipose tissue parameters as well as degree of cerebral microangiopathy were extracted from the imaging data. Subsequent multivariate Cox regression analysis encompassed TPI, MPD, serum LDH, S100B, age, gender, number of immunotherapy cycles as well as extent of distant metastases. TPI and MPD correlated positively with PFS in multivariate analysis (p = 0.03 and p = 0.001, respectively). Furthermore, single visceral organ and/or soft tissue involvement significantly decreased progression risk (p = 0.01), whereas increased S100B level showed a trend towards PFS shortening (p = 0.05). In conclusion, degree of macroangiopathy and sarcopenia were independent predictors for outcome to immunotherapy and of equivalent significance compared to other clinical biomarkers.

Tumor Cell Load and Heterogeneity Estimation From Diffusion-Weighted MRI Calibrated With Histological Data: an Example From Lung Cancer.

Diffusion-weighted magnetic resonance imaging (DWI) is a key non-invasive imaging technique for cancer diagnosis and tumor treatment assessment, reflecting Brownian movement of water molecules in tissues. Since densely packed cells restrict molecule mobility, tumor tissues produce usually higher signal (a.k.a. less attenuated signal) on isotropic maps compared with normal tissues. However, no general quantitative relation between DWI data and the cell density has been established. In order to link low-resolution clinical cross-sectional data with high-resolution histological information, we developed an image processing and analysis chain, which was used to study the correlation between the diffusion coefficient (D value) estimated from DWI and tumor cellularity from serial histological slides of a resected non-small cell lung cancer tumor. Color deconvolution followed by cell nuclei segmentation was performed on digitized histological images to determine local and cell-type specific 2d (two-dimensional) densities. From these, the 3d cell density was inferred by a model-based sampling technique, which is necessary for the calculation of local and global 3d tumor cell count. Next, DWI sequence information was overlaid with high-resolution CT data and the resected histology using prominent anatomical hallmarks for co-registration of histology tissue blocks and non-invasive imaging modalities' data. The integration of cell numbers information and DWI data derived from different tumor areas revealed a clear negative correlation between cell density and D value. Importantly, spatial tumor cell density can be calculated based on DWI data. In summary, our results demonstrate that tumor cell count and heterogeneity can be predicted from DWI data, which may open new opportunities for personalized diagnosis and therapy optimization.

A non-controlled, single arm, open label, phase II study of intravenous and intratumoral administration of ParvOryx in patients with metastatic, inoperable pancreatic cancer: ParvOryx02 protocol.

BACKGROUND: Metastatic pancreatic cancer has a dismal prognosis, with a mean six-month progression-free survival of approximately 50% and a median survival of about 11 months. Despite intensive research, only slight improvements of clinical outcome could be achieved over the last decades. Hence, new and innovative therapeutic strategies are urgently required. ParvOryx is a drug product containing native parvovirus H-1 (H-1PV). Since H-1PV was shown to exert pronounced anti-neoplastic effects in pre-clinical models of pancreatic cancer, the drug appears to be a promising candidate for treatment of this malignancy. METHODS: ParvOryx02 is a non-controlled, single arm, open label, dose-escalating, single center trial. In total seven patients with pancreatic cancer showing at least one hepatic metastasis are to be treated with escalating doses of ParvOryx according to the following schedule: i) 40% of the total dose infused intravenously in equal fractions on four consecutive days, ii) 60% of the total dose injected on a single occasion directly into the hepatic metastasis at varying intervals after intravenous infusions. The main eligibility criteria are: age ≥ 18 years, disease progression despite first-line chemotherapy, and at least one hepatic metastasis. Since it is the second trial within the drug development program, the study primarily explores safety and tolerability after further dose escalation of ParvOryx. The secondary objectives are related to the evaluation of certain aspects of anti-tumor activity and clinical efficacy of the drug. DISCUSSION: This trial strongly contributes to the clinical development program of ParvOryx. The individual hazards for patients included in the current study and the environmental risks are addressed and counteracted adequately. Besides information on safety and tolerability of the treatment after further dose escalation, thorough evaluations of pharmacokinetics and intratumoral spread as well as proof-of-concept (PoC) in pancreatic cancer will be gained in the course of the trial. TRIAL REGISTRATION: ClinicalTrials.gov-ID: NCT02653313 , Registration date: Dec. 4th, 2015.

Morpho-Functional 1H-MRI of the Lung in COPD: Short-Term Test-Retest Reliability.

PURPOSE: Non-invasive end-points for interventional trials and tailored treatment regimes in chronic obstructive pulmonary disease (COPD) for monitoring regionally different manifestations of lung disease instead of global assessment of lung function with spirometry would be valuable. Proton nuclear magnetic resonance imaging (1H-MRI) allows for a radiation-free assessment of regional structure and function. The aim of this study was to evaluate the short-term reproducibility of a comprehensive morpho-functional lung MRI protocol in COPD. MATERIALS AND METHODS: 20 prospectively enrolled COPD patients (GOLD I-IV) underwent 1H-MRI of the lung at 1.5T on two consecutive days, including sequences for morphology, 4D contrast-enhanced perfusion, and respiratory mechanics. Image quality and COPD-related morphological and functional changes were evaluated in consensus by three chest radiologists using a dedicated MRI-based visual scoring system. Test-retest reliability was calculated per each individual lung lobe for the extent of large airway (bronchiectasis, wall thickening, mucus plugging) and small airway abnormalities (tree in bud, peripheral bronchiectasis, mucus plugging), consolidations, nodules, parenchymal defects and perfusion defects. The presence of tracheal narrowing, dystelectasis, pleural effusion, pulmonary trunk ectasia, right ventricular enlargement and, finally, motion patterns of diaphragma and chest wall were addressed. RESULTS: Median global scores [10(Q1:8.00;Q3:16.00) vs.11(Q1:6.00;Q3:15.00)] as well as category subscores were similar between both timepoints, and kappa statistics indicated "almost perfect" global agreement (ĸ = 0.86, 95%CI = 0.81-0.91). Most subscores showed at least "substantial" agreement of MRI1 and MRI2 (ĸ = 0.64-1.00), whereas the agreement for the diagnosis of dystelectasis/effusion (ĸ = 0.42, 95%CI = 0.00-0.93) was "moderate" and of tracheal abnormalities (ĸ = 0.21, 95%CI = 0.00-0.75) "fair". Most MRI acquisitions showed at least diagnostic quality at MRI1 (276 of 278) and MRI2 (259 of 264). CONCLUSION: Morpho-functional 1H-MRI can be obtained with reproducible image quality and high short-term test-retest reliability for COPD-related morphological and functional changes of the lung. This underlines its potential value for the monitoring of regional lung characteristics in COPD trials.

Efficacy of targeted treatment beyond third-line therapy in metastatic kidney cancer: retrospective analysis from a large-volume cancer center.

INTRODUCTION/BACKGROUND: Currently, 7 agents are approved for the first- and second-line therapy for metastatic renal cell carcinoma. In contrast, data supporting their use beyond second line are limited. Here we summarize our experience in patients treated with more than 4 lines of therapy. METHODS: We retrospectively assessed the outcome of 24 patients treated at our institution with at least 4 lines of therapy. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier estimates. RESULTS: Median OS from the initiation of first-line therapy for the whole cohort is 64.7 months. Up to 96% of the patients received a tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitor (mTOR-I) within the first 3 lines of treatment. In the fourth or following lines, patients were treated with TKI, mTOR-I, bevacizumab/interferon, or experimental drugs. Seven patients continued treatment with a sixth-line agent; one has been treated up to the ninth line. Sixteen percent of the patients receiving fourth-line therapy and 13% receiving fifth-line therapy experienced a partial remission, which was independent from response to previous therapies. Median OS from fourth and fifth line was 30.8 and 26.2 months, respectively. Median PFS for fourth-line therapy was 5.8 months. No significant difference in PFS was observed for patients with disease that responded or did not respond to first-line therapy. CONCLUSION: Despite the limitations of a retrospective analysis, our study suggests that selected patients benefit from multiple lines of treatment, independent of response to first-line therapy. However, the optimal sequence of treatment with regard to later lines remains to be determined.

Automatic lung segmentation method for MRI-based lung perfusion studies of patients with chronic obstructive pulmonary disease.

PURPOSE: A novel fully automatic lung segmentation method for magnetic resonance (MR) images of patients with chronic obstructive pulmonary disease (COPD) is presented. The main goal of this work was to ease the tedious and time-consuming task of manual lung segmentation, which is required for region-based volumetric analysis of four-dimensional MR perfusion studies which goes beyond the analysis of small regions of interest. METHODS: The first step in the automatic algorithm is the segmentation of the lungs in morphological MR images with higher spatial resolution than corresponding perfusion MR images. Subsequently, the segmentation mask of the lungs is transferred to the perfusion images via nonlinear registration. Finally, the masks for left and right lungs are subdivided into a user-defined number of partitions. Fourteen patients with two time points resulting in 28 perfusion data sets were available for the preliminary evaluation of the developed methods. RESULTS: Resulting lung segmentation masks are compared with reference segmentations from experienced chest radiologists, as well as with total lung capacity (TLC) acquired by full-body plethysmography. TLC results were available for thirteen patients. The relevance of the presented method is indicated by an evaluation, which shows high correlation between automatically generated lung masks with corresponding ground-truth estimates. CONCLUSION: The evaluation of the developed methods indicates good accuracy and shows that automatically generated lung masks differ from expert segmentations about as much as segmentations from different experts.