Neuroprotection in radiotherapy of brain metastases: A pattern-of-care analysis in Germany, Austria and Switzerland by the German Society for radiation Oncology - working group Neuro-Radio-Oncology (DEGRO AG-NRO).

Background and purpose: Many patients with solid tumors develop brain metastases (BM). With more patients surviving long-term, preservation of neurocognitive function gains importance. In recent years, several methods to delay cognitive deterioration have been tested in clinical trials. However, knowledge on the extent to which these neuroprotective strategies have been implemented in clinical practice is missing. Materials and methods: We performed an online survey regarding treatment patterns of BM in German-speaking countries, focused on the use of neuroprotective approaches. The survey was distributed among radiation oncologists (ROs) registered within the database of the German Society for Radiation Oncology (DEGRO). Results: Physicians of 78 centers participated in the survey. Whole brain radiotherapy (WBRT) is still preferred by 70 % of ROs over stereotactic radiotherapy (SRT) in patients with 6-10 BM. For 4-5 BM WBRT is preferred by 23 % of ROs. The fraction of ROs using hippocampal sparing (HS) in WBRT has increased to 89 %, although the technique is used on a regular basis only by a minority (26 %). The drug memantine is not widely prescribed (14% of ROs). A trend was observed for university hospitals to implement neuroprotective approaches more frequently. Conclusion: There is considerable heterogeneity regarding the treatment of BM in German-speaking countries and a general standard of care is lacking. Neuroprotective strategies are not yet standard approaches in daily clinical routine, although usage is increasing. Further clinical trials, as well as improvement of technical opportunities and reimbursement, might further shift the treatment landscape towards neuroprotective radiation treatments in the future.

Efficacy and safety of high-dose chemotherapy as the first or subsequent salvage treatment line in patients with relapsed or refractory germ cell cancer: an international multicentric analysis.

BACKGROUND: In relapsed or refractory (RR) metastatic germ cell cancer (GCC), high-dose (HD) chemotherapy (CTX) plus autologous stem cell transplantation is considered the standard of care. Limited data exist regarding the efficacy of HD-CTX following conventionally dosed salvage regimens (CDRs). This analysis explores and contrasts the efficacy of HD-CTX as the first or subsequent salvage regimen. PATIENTS AND METHODS: Data were retrospectively collected to explore the efficacy of HD-CTX administered as the first (group A) or subsequent salvage CTX (group B) after a CDR. The primary endpoint was OS from the time of HD-CTX. Associations of survival, overall response rate (ORR), and toxicity with clinical characteristics were explored using stratified Kaplan-Meier and Cox regression models. RESULTS: Overall, 283 patients with GCC were included from 11 international centers, with 159 patients (56%) in group A and 124 patients (44%) in group B. The first salvage treatment was administered between 1998 and 2022, with a median follow-up of 27.0 [standard deviation (SD) 46.2] months for group A and 17.0 (SD 48.5) months for group B. The median OS from HD-CTX treatment initiation was not reached in group A, compared with 25 months in group B (P = 0.00027), associated with 2- and 5-year OS rates of 74% and 63% (group A) versus 53% and 37% (group B), respectively. When administered as the first salvage treatment, HD-CTX was associated with a higher ORR (79% versus 60%; P = 0.013) and lower nonhematologic grade ≥3 toxicity rate (78% versus 97%; P < 0.001). Concerning risk factor analysis for the total cohort, the International Prognostic Factors Study Group score was the only independent predictor of OS in multivariable analysis (P = 0.006). CONCLUSIONS: When administered as the initial salvage treatment or after CDR, HD-CTX exhibits curative potential for patients with RR GCC. The efficacy and safety outcomes were more favorable when HD-CTX was conducted as the first salvage treatment line.

Long-term survival in patients with brain metastases-clinical characterization of a rare scenario.

PURPOSE: This study aimed to assess clinical, treatment, and prognostic features in patients with brain metastases (BM) from solid tumors achieving long-term survival (LTS). Further, the accuracy of diagnosis-specific Graded Prognostic Assessment scores (ds-GPA) to predict LTS was evaluated. METHODS: Patients admitted for radiotherapy of BM between 2010 and 2020 at a large tertiary cancer center with survival of at least 3 years from diagnosis of BM were included. Patient, tumor, treatment characteristics and ds-GPA were compiled retrospectively. RESULTS: From a total of 1248 patients with BM, 61 (4.9%) survived ≥ 3 years. In 40 patients, detailed patient charts were available. Among LTS patients, median survival time from diagnosis of BM was 51.5 months. Most frequent primary tumors were lung cancer (45%), melanoma (20%), and breast cancer (17.5%). At the time of diagnosis of BM, 11/40 patients (27.5%) had oligometastatic disease. Estimated mean survival time based on ds-GPA was 19.7 months (in 8 cases estimated survival < 12 months). Resection followed by focal or whole-brain radiotherapy (WBRT) was often applied (60%), followed by primary stereotactic radiotherapy (SRT) (20%) or WBRT (20%). 80% of patients received systemic treatment, appearing particularly active in specifically altered non-small lung cancer (NSCLC), melanoma, and HER2-positive breast cancer. Karnofsky performance score (KPS) and the presence of oligometastatic disease at BM diagnosis were persisting prognostic factors in LTS patients. CONCLUSION: In this monocentric setting reflecting daily pattern of care, LTS with BM is heterogeneous and difficult to predict. Effective local treatment and modern systemic therapies often appear crucial for LTS. The impact of concomitant diseases and frailty is not clear.

Increased incidence of immune thrombocytopenia (ITP) in 2021 correlating with the ongoing vaccination campaign against COVID-19 in a tertiary center - A monocentric analysis.

Immune thrombocytopenia (ITP) was reported as a rare complication of COVID-19 vaccines. We conducted a retrospective single-center analysis of all ITP cases detected in 2021 and compared the quantity with the pre-vaccination years, from 2018 to 2020. In 2021, a two-fold increase in ITP cases was identified compared to previous years; 11 of 40 cases (27.5%) were considered COVID-19-vaccine related. Our study highlights an increase in ITP cases at our institution, probably related to COVID-19 vaccinations. Further studies are needed to investigate this finding globally.

Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial.

PURPOSE: In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population. METHODS: Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the concomitant phase of chemotherapy. RESULTS: HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was similar between treatment arms (CCNU/TMZ 11.5; TMZ 13 days). Chemotherapy was more often discontinued due to HAE in CCNU/TMZ than in TMZ (19.7 vs. 6.3%, p = 0.036). The occurrence of HAE was not associated with survival differences (p = 0.76). Regression analysis confirmed older age (OR 1.08) and female sex (OR 2.47), but not treatment arm, as predictors of HAE. CONCLUSION: Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures. TRIAL REGISTRATION: NCT01149109.

[Skull base metastases with cranial nerve deficits : Clinical profile of a severe disease]. / Schädelbasismetastasen mit Hirnnervenaffektionen : Klinischer Steckbrief einer schwerwiegenden Erkrankung.

BACKGROUND AND PURPOSE: Skull base metastases are a severe complication of various malignant tumors. If cranial nerves are involved even small lesions can cause significant symptoms. Specific clinical characteristics like neurological symptoms, associated primary tumors, prognosis and optimal treatment are poorly defined and are systematically described in this article. METHODS: In a monocentric retrospective study patients with skull base metastases and cranial nerve deficits who received treatment between 2006 and 2018 were analyzed concerning clinical characteristics at initial diagnosis, treatment and course of the disease. RESULTS: In this study 45 patients with skull base metastases and cranial nerve deficits were included. The most frequent primary tumors were prostate cancer (27%), breast cancer (22%) and multiple myeloma (16%). The most involved cranial nerves were trigeminal nerve (42%), oculomomotor nerve (33%) and facial nerve (27%). Of the patients 84% had additional bone metastases outside the skull base. Dural infiltration or meningeal carcinomatosis were each observed in 13% of the patients. After radiotherapy cranial nerve deficits remained stable in 61% of all cases and in 22% symptoms improved. Median overall survival from treatment was 8 months (range 0.4-51 months). Patients with dose-escalated radiotherapy appeared to live longer (16.4 months vs. 4.7 months). This effect persisted in a multivariate analysis including the Karnofsky index, number of metastases, primary tumor and radiation dose (HR 0.37, p = 0.02). CONCLUSION: Skull base metastases with cranial nerve deficits are complex diseases with poor prognosis. Precise diagnosis and treatment are required. Further research is needed to improve treatment.

How we treat medulloblastoma in adults.

Medulloblastoma is a rare tumour in postpubertal patients and adults that is potentially curable. Several subgroups have been defined that are associated with clinical features, have different prognoses, and in some cases offer personalized treatment options. In adults, the sonic hedgehog (SHH) subtype is the most common subtype, followed by the wingless (WNT) and group 4 subtypes. Multimodal therapies allow 5-year overall survival rates of up to 70%. However, in adults, therapeutic evidence from prospective randomized trials is largely lacking. Therefore, regardless of individual risk, most patients are currently treated uniformly with craniospinal chemoradiation with a boost to the tumour bed, followed by maintenance chemotherapy, usually with alkylating agents. In Europe, the so-called Packer regimen, together with cisplatin-etoposide regimens, is the most commonly used chemotherapy option. Targeted treatment approaches have not yet been implemented, although tumour biology is well understood and offers personalized approaches, especially for the SHH subgroup. At relapse, rapid resistance occurs frequently, necessitating repositioning of these agents in an earlier treatment phase. Due to the good to intermediate prognosis, patients with medulloblastoma require structured long-term clinical follow-up including MRI of the brain, monitoring of side effects, and psychosocial and fertility counselling. Recently, clinical trials have been initiated with the aim of de-escalating treatment to reduce toxicity and adding targeted therapies to increase efficacy, with the main goal of therapy to cure the tumour while maintaining the physical and psychosocial integrity of affected patients. This article summarizes our opinion on the diagnosis and treatment of medulloblastoma in adults.

Theoretical and numerical analysis of nano-actuators based on grafted polyelectrolytes in an electric field.

We analyze, theoretically and by means of molecular dynamics (MD) simulations, the generation of mechanical force by a polyelectrolyte (PE) chain grafted to a plane and exposed to an external electric field; the free end of the chain is linked to a deformable target body. Varying the field, one can alter the length of the non-adsorbed (bulk) part of the chain and hence the deformation of the target body and the arising force. We focus on the impact of added salt on the magnitude of the generated force, which is especially important for applications. In particular, we develop a simple variational theory for the double layer formed near electrodes to compute the electric field acting on the bulk part of the chain. Our theoretical predictions agree well with the MD simulations. Next, we study the effectiveness of possible PE-based nano-vices, comprised of two clenching planes connected by PEs exposed to an external electric field. We analyze a novel phenomenon - two-dimensional diffusion of a nano-particle, clenched between two planes, and introduce a quantitative criterion for clenching efficiency, the clenching coefficient. It is defined as a logarithm of the ratio of the diffusion coefficients of a free and clenched particle. Using first a microscopic counterpart of the Coulomb friction model, and then a novel microscopic model based on surface phonons, with the vibration direction normal to the surface, we calculate the clenching coefficient as a function of the external electric field. Our results demonstrate a dramatic decrease of the diffusion coefficient of a clenched nano-particle for the range of parameters relevant for applications; this proves the effectiveness of the PE-based nano-vices.

The uncertainty in the radon hazard classification of areas as a function of the number of measurements.

The administration in many countries demands a classification of areas concerning their radon risk taking into account the requirements of the EU Basic Safety Standards. The wide variation of indoor radon concentrations in an area which is caused by different house construction, different living style and different geological situations introduces large uncertainties for any classification scheme. Therefore, it is of importance to estimate the size of the experimental coefficient of variation (relative standard deviation) of the parameter which is used to classify an area. Besides the time period of measurement it is the number of measurements which strongly influences this uncertainty and it is important to find a compromise between the economic possibilities and the needed confidence level. Some countries do not use pure measurement results for the classification of areas but use derived quantities, usually called radon potential, which should reduce the influence of house construction, living style etc. and should rather represent the geological situation of an area. Here, radon indoor measurements in nearly all homes in three municipalities and its conversion into a radon potential were used to determine the uncertainty of the mean radon potential of an area as a function of the number of investigated homes. It could be shown that the coefficient of variation scales like 1/√n with n the number of measured dwellings. The question how to deal with uncertainties when using a classification scheme for the radon risk is discussed and a general procedure is proposed.

Indoor radon, geogenic radon surrogates and geology - Investigations on their correlation.

The indoor radon concentration was measured in most houses in a couple of municipalities in Austria. At the same time the activity concentration of radium in soil, the soil gas radon concentration, the permeability of the ground and the ambient dose equivalent rate were also measured and the geological situations (geological units) were recorded too. From the indoor radon concentration and different house and living parameters a radon potential (Austrian radon potential) was derived which should represent the radon concentration in a standard room. Another radon potential (Neznal radon potential) was calculated from the soil gas radon concentration and the permeability. The aim of the investigation was to correlate all the different variables and to test if the use of surrogate data (e.g. geological information, ambient dose equivalent rate, etc.) can be used to judge the radon risk for an area without performing numerous indoor measurements.

Generation of mechanical force by grafted polyelectrolytes in an electric field: application to polyelectrolyte-based nano-devices.

We analyse theoretically and by means of molecular dynamics (MD) simulations the generation of mechanical force by a polyelectrolyte (PE) chain grafted to a plane. The PE is exposed to an external electric field that favours its adsorption on the plane. The free end of the chain is linked to a deformable target body. By varying the field, one can alter the length of the non-adsorbed part of the chain. This entails variation of the deformation of the target body and hence variation of the force arising in the body. Our theoretical predictions for the generated force are in very good agreement with the MD data. Using the theory developed for the generated force, we study the effectiveness of possible PE-based nano-vices, composed of two clenching planes connected by PEs and exposed to an external electric field. We exploit the Cundall-Strack solid friction model to describe the friction between a particle and the clenching planes. We compute the diffusion coefficient of a clenched particle and show that it drastically decreases even in weak applied fields. This demonstrates the efficacy of the PE-based nano-vices, which may be a possible alternative to the existing nanotube nano-tweezers and optical tweezers.This article is part of the themed issue 'Multiscale modelling at the physics-chemistry-biology interface'.

Generation of mechanical force by grafted polyelectrolytes in an electric field.

We study theoretically and by means of molecular dynamics (MD) simulations the generation of mechanical force by grafted polyelectrolytes in an external electric field, which favors its adsorption on the grafting plane. The force arises in deformable bodies linked to the free end of the chain. Varying the field, one controls the length of the nonadsorbed part of the chain and hence the deformation of the target body, i.e., the arising force too. We consider target bodies with a linear force-deformation relation and with a Hertzian one. While the first relation models a coiled Gaussian chain, the second one describes the force response of a squeezed colloidal particle. The theoretical dependences of generated force and compression of the target body on an applied field agree very well with the results of MD simulations. The analyzed phenomenon may play an important role in future nanomachinery, e.g., it may be used to design nanovices to fix nanosized objects.

Diffusion of macromolecules in a polymer hydrogel: from microscopic to macroscopic scales.

To gain insight into the fundamental processes determining the motion of macromolecules in polymeric matrices, the dynamical hindrance of polymeric dextran molecules diffusing as probe through a polyacrylamide hydrogel is systematically explored. Three complementary experimental methods combined with Brownian dynamics simulations are used to study a broad range of dextran molecular weights and salt concentrations. While multi-parameter fluorescence image spectroscopy (MFIS) is applied to investigate the local diffusion of single molecules on a microscopic length scale inside the hydrogel, a macroscopic transmission imaging (MTI) fluorescence technique and nuclear magnetic resonance (NMR) are used to study the collective motion of dextrans on the macroscopic scale. These fundamentally different experimental methods, probing different length scales of the system, yield long-time diffusion coefficients for the dextran molecules which agree quantitatively. The measured diffusion coefficients decay markedly with increasing molecular weight of the dextran and fall onto a master curve. The observed trends of the hindrance factors are consistent with Brownian dynamics simulations. The simulations also allow us to estimate the mean pore size for the herein investigated experimental conditions. In addition to the diffusing molecules, MFIS detects temporarily trapped molecules inside the matrix with diffusion times above 10 ms, which is also confirmed by anisotropy analysis. The fraction of bound molecules depends on the ionic strength of the solution and the charge of the dye. Using fluorescence intensity analysis, also MTI confirms the observation of the interaction of dextrans with the hydrogel. Moreover, pixelwise analysis permits to show significant heterogeneity of the gel on the microscopic scale.

Does the onset of bone metastasis in sunitinib-treated renal cell carcinoma patients impact the overall survival?

PURPOSE: To evaluate the impact of bone metastasis (BM) onset toward prognosis in metastatic renal cell carcinoma (mRCC) patients treated with sunitinib. METHODS: mRCC patients with BM and sunitinib as first targeted therapy between May 2005 and December 2012 were retrospectively analyzed. Patients with synchronous (s) BM or metachronous (m) BM were compared with regard to treatment and outcome [time to clinical progression (TTcP), overall survival (OS), skeletal-related events (SRE)]. Descriptive statistics, Kaplan-Meier estimation of TTcP and OS, Cox regression analyses, and a landmark analysis were administered. RESULTS: BM was identified in 127 mRCC patients; thereof, 82 sunitinib-treated patients were analyzed [sBM n = 57 (69.5 %), mBM n = 25 (30.5 %)]. Higher tumor grading (p = 0.029), male predominance (p = 0.02), and less second-line therapy (p = 0.001) were detected in sBM compared to mBM. SRE remained similar between subgroups (p = 0.462). TTcP during sunitinib was similar [median sBM 8.1 (95 % CI 3.9-12.3) vs. mBM 8.7 (95 % CI 2.7-14.8) months, p = 0.903]. OS remained significantly inferior in sBM patients compared to mBM [median sBM 21.1 (95 % CI 16-26.2) months vs. mBM 38.5 (95 % CI 15-62) months, p = 0.001], which was confirmed by landmark analyses at 1.5, 3, 6, 9, and 12 months. However, OS after occurrence of BM was similar in both groups [median sBM 24.2 (95 % CI 17.3-31.1) months vs. mBM 17.2 (95 % CI 8.4-26) months, p = 0.519]. CONCLUSIONS: mBM is associated with an improved OS compared to sBM in mRCC with sunitinib treatment, despite similar efficacy of sunitinib treatment in both groups of patients.

Analysis of frequency of deep white matter metastasis on cerebral MRI.

Supratentorial white matter is an important part of the brain and a major site of detrimental effects after whole brain radiotherapy (WBRT). It is not known if prevalence of metastases in white matter justifies standard inclusion of white matter in whole brain treatment. In this retrospective analysis we examined the frequency of metastasis in supratentorial deep cerebral white matter with cerebral magnetic resonance imaging (MRI). Deep white matter (DWM) was defined as white matter in corpus callosum with forceps anterior and posterior and centrum semiovale. Lesions extending from grey matter, gyrus or ventricles into white matter were not classified as DWM metastases. Brain MRI of 198 patients from two centres were analyzed. In total 1330 metastases were counted and only 4.6% were located in DWM. Metastases in DWM were small (median diameter 6 mm). Only 1/41 patients (2%) with a singular metastasis had a DWM metastasis, 2/35 patients (6%) with 2 metastases had a DWM metastasis, 14/79 patients (18%) with 3-9 metastases and 12/43 patients (28%) with >9 metastases had a single or more DWM metastases (p = 0.003). There appeared to be tumor related differences with renal cell carcinoma showing significantly more DWM metastasis (6/17, 35%), than NSCLC (11/85, 13%, p = 0.024), breast cancer (1/20, 5%, p = 0.019) or colorectal cancer (0/10, 0%, p = 0.033). Overall, relevant preservation of DWM from metastases, especially in oligometastatic disease, was shown. This implies that DWM in patients with only few brain metastases is unnecessarily damaged by conventional WBRT.

MRI characteristics of ependymoblastoma: results from 22 centrally reviewed cases.

BACKGROUND AND PURPOSE: Ependymoblastoma is a malignant embryonal tumor that develops in early childhood and has a dismal prognosis. Categorized by the World Health Organization as a subgroup of CNS-primitive neuroectodermal tumor, ependymoblastoma is histologically defined by "ependymoblastic rosettes." Because it is so rare, little is known about specific MR imaging characteristics of ependymoblastoma. We systematically analyzed and discussed MR imaging features of ependymoblastoma in a series of 22 consecutive patients. MATERIALS AND METHODS: Ependymoblastoma cases were obtained from the database of the German multicenter HIT trials between 2002 and 2013. All cases within this study were centrally reviewed for histopathology, MR imaging findings, and multimodal therapy. For systematic analysis of initial MR imaging scans at diagnosis, we applied standardized criteria for reference image evaluation of pediatric brain tumors. RESULTS: Ependymoblastomas are large tumors with well-defined tumor margins, iso- to hyperintense signal on T2WI, and diffusion restriction. Contrast enhancement is variable, with a tendency to mild or moderate enhancement. Subarachnoid spread is common in ependymoblastoma but can be absent initially. There was a male preponderance (1.75:1 ratio) for ependymoblastoma in our cohort. Mean age at diagnosis was 2.1 years. CONCLUSIONS: With this study, we add the largest case collection to the limited published database of MR imaging findings in ependymoblastoma, together with epidemiologic data. However, future studies are needed to systematically compare MR imaging findings of ependymoblastoma with other CNS-primitive neuroectodermal tumors and ependymoma, to delineate imaging criteria that might help distinguish these pediatric brain tumor entities.

The lower saxony bank of health. rationale, principles, services, organization and architectural framework.

INTRODUCTION: This article is part of a Focus Theme of METHODS of Information in Medicine on Health Record Banking. BACKGROUND: Poor communication of health care information between health care providers (HCP) is still a major problem. One recent approach is the concept of Health Record Banking. OBJECTIVES: With this report we want to introduce the Lower Saxony Bank of Health (LSBH) to the international community. The main objective of this paper is to report and explain: 1) why this organization has been founded, 2) which basic principles have been set, 3) which services will be provided, 4) which type of organization has been chosen, and 5) which architectural framework has been selected. METHODS: To report and discuss how we plan to achieve the intended objectives. RESULTS: The LSBH was founded as an entrepreneurial company, regarding itself as a neutral third-party information broker. The bank does not store medical documents on its central servers but offers a document registry with links to documents stored at participating health care providers. Subject to valid patient consent, the LSBH grants access to these documents to authorized health care providers. To implement our services, we chose the established technical frameworks of the Integrating the Healthcare Enterprise (IHE) initiative using cross-enterprise document sharing (XDS). CONCLUSIONS: Different approaches to establish health information exchange (HIE) are in early stages and some have failed in the past. Health Record Banking can address major challenges described in the literature about HIE. The future will show if our provider-sponsored business model is sustainable. After reaching a stable network, we intend to add additional HCPs, e.g., care homes or ambulance services, to the network.

Authentication systems for securing clinical documentation workflows. A systematic literature review.

CONTEXT: Integration of electronic signatures embedded in health care processes in Germany challenges health care service and supply facilities. The suitability of the signature level of an eligible authentication procedure is confirmed for a large part of documents in clinical practice. However, the concrete design of such a procedure remains unclear. OBJECTIVE: To create a summary of usable user authentication systems suitable for clinical workflows. DATA SOURCE: A Systematic literature review based on nine online bibliographic databases. Search keywords included authentication, access control, information systems, information security and biometrics with terms user authentication, user identification and login in title or abstract. Searches were run between 7 and 12 September 2011. Relevant conference proceedings were searched manually in February 2013. Backward reference search of selected results was done. SELECTION: Only publications fully describing authentication systems used or usable were included. Algorithms or purely theoretical concepts were excluded. Three authors did selection independently. DATA EXTRACTION AND ASSESSMENT: Semi-structured extraction of system characteristics was done by the main author. Identified procedures were assessed for security and fulfillment of relevant laws and guidelines as well as for applicability. Suitability for clinical workflows was derived from the assessments using a weighted sum proposed by Bonneau. RESULTS: Of 7575 citations retrieved, 55 publications meet our inclusion criteria. They describe 48 different authentication systems; 39 were biometric and nine graphical password systems. Assessment of authentication systems showed high error rates above European CENELEC standards and a lack of applicability of biometric systems. Graphical passwords did not add overall value compared to conventional passwords. Continuous authentication can add an additional layer of safety. Only few systems are suitable partially or entirely for use in clinical processes. CONCLUSIONS: Suitability strongly depends on national or institutional requirements. Four authentication systems seem to fulfill requirements of authentication procedures for clinical workflows. Research is needed in the area of continuous authentication with biometric methods. A proper authentication system should combine all factors of authentication implementing and connecting secure individual measures.

Tumour shrinkage measured with first treatment evaluation under VEGF-targeted therapy as prognostic marker in metastatic renal cell carcinoma (mRCC).

BACKGROUND: The aim of our analysis is to further characterise the prognostic relevance of early tumour shrinkage (TS) during VEGF-targeted therapy in mRCC, in order to explore whether this could define a group of patients with long-term survivorship. METHODS: A hundred patients were stratified into five subgroups according to their change of tumour size with first treatment evaluation: -100% to -60%; -59% to -30% and -29% to 0% TS or gain of tumour size from 1% to 19% and ≤20% or occurrence of new lesions (i.e., progressive disease). RESULTS: The median PFS and OS were 10.4 months and 28.2 months, respectively. The median OS stratified according to the subgroups as described above was 77.4, 33.5, 26.9, 30.0 and 14.3 months, respectively. Multivariate analysis revealed early TS as a prognostic marker (P=0.021; HR 1.624). CONCLUSION: The extent of TS defines a small proportion of patients with an excellent prognosis. Larger studies are warranted to define the relationship of long-term survivorship and extent of TS with targeted therapies.