Stability and reproducibility of 6013 deep inspiration breath-holds in left-sided breast cancer.

PURPOSE: Patients with left-sided breast cancer frequently receive deep inspiration breath-hold (DIBH) radiotherapy to reduce the risk of cardiac side effects. The aim of the present study was to analyze intra-breath-hold stability and inter-fraction breath-hold reproducibility in clinical practice. MATERIAL AND METHODS: Overall, we analyzed 103 patients receiving left-sided breast cancer radiotherapy using a surface-guided DIBH technique. During each treatment session the vertical motion of the patient was continuously measured by a surface guided radiation therapy (SGRT) system and automated gating control (beam on/off) was performed using an audio-visual patient feedback system. Dose delivery was automatically triggered when the tracking point was within a predefined gating window. Intra-breath-hold stability and inter-fraction reproducibility across all fractions of the entire treatment course were analyzed per patient. RESULTS: In the present series, 6013 breath-holds during beam-on time were analyzed. The mean amplitude of the gating window from the baseline breathing curve (maximum expiration during free breathing) was 15.8 mm (95%-confidence interval: [8.5-30.6] mm) and had a width of 3.5 mm (95%-CI: [2-4.3] mm). As a measure of intra-breath-hold stability, the median standard deviation of the breath-hold level during DIBH was 0.3 mm (95%-CI: [0.1-0.9] mm). Similarly, the median absolute intra-breath-hold linear amplitude deviation was 0.4 mm (95%-CI: [0.01-2.1] mm). Reproducibility testing showed good inter-fractional reliability, as the maximum difference in the breathing amplitudes in all patients and all fractions were 1.3 mm on average (95%-CI: [0.5-2.6] mm). CONCLUSION: The clinical integration of an optical surface scanner enables a stable and reliable DIBH treatment delivery during SGRT for left-sided breast cancer in clinical routine.

[A German version of the Cambridge examination for mental disorders of older people with Down's syndrome and others with intellectual disabilities : A diagnostic procedure for detecting dementia in people with Down's syndrome]. / Eine deutsche Fassung der Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities : Ein Diagnoseverfahren zur Erfassung von Demenz bei Menschen mit einem Down-Syndrom.

BACKGROUND: Although people with Down's syndrome (DS) are at a high risk of developing an Alzheimer type dementia (AD) due to a triplication of the amyloid precursor gene, there are practically no internationally available test procedures to detect cognitive deficits in this at risk population in the German language. OBJECTIVE: The aim was to provide a German translation and intercultural adaptation of the Cambridge examination for mental disorders of older people with Down's syndrome and others with intellectual disabilities (CAMDEX-DS), which is available in English and Spanish. This instrument for diagnostics and monitoring consists of a psychological test examination (CAMCOG-DS) and a caregiver interview. METHODS: The translation and adaptation of the CAMDEX-DS were achieved through a multistep translation process, whereby two independent forward and back translations were provided by professional translators and a consensus version was finalized and tested. The final version of the caregiver interview was applied to 11 subjects and the CAMCOG-DS was conducted with 28 patients. RESULTS: The German version of the CAMDEX-DS proved to be easily administered. The CAMCOG-DS could be fully administered to 21 out of 28 patients (75%). The CAMCOG-DS values were much lower for older patients aged ≥45 years than for younger patients (46/109 vs. 73.5/109; p = 0.033). DISCUSSION: The German version of the CAMDEX-DS provides an internationally recognized tool for the diagnostics and monitoring of cognitive decline in Down's syndrome. Furthermore, the German version can standardize medical care of these patients. In particular it provides a means of participation in international research trials for this at risk population.

Optical Surface Scanning for Patient Positioning in Radiation Therapy: A Prospective Analysis of 1902 Fractions.

PURPOSE/OBJECTIVE: Reproducible patient positioning remains one of the major challenges in modern radiation therapy. Recently, optical surface scanners have been introduced into clinical practice in addition to well-established positioning systems, such as room laser and skin marks. The aim of this prospective study was to evaluate setup errors of the optical surface scanner Catalyst HD (C-RAD AB) in different anatomic regions. MATERIAL/METHODS: Between October 2016 and June 2017 a total of 1902 treatment sessions in 110 patients were evaluated. The workflow of this study included conventional setup procedures using laser-based positioning with skin marks and an additional registration of the 3-dimensional (3D) deviations detected by the Catalyst system. The deviations of the surface-based method were then compared to the corrections of cone beam computed tomography alignment which was considered as gold standard. A practical Catalyst setup error was calculated between the translational deviations of the surface scanner and the laser positioning. Two one-sided t tests for equivalence were used for statistical analysis. RESULTS: Data analysis revealed total deviations of 0.09 mm ± 2.03 mm for the lateral axis, 0.07 mm ± 3.21 mm for the longitudinal axis, and 0.44 mm ± 3.08 mm vertical axis for the Catalyst system, compared to -0.06 ± 3.54 mm lateral, 0.53 ± 3.47 mm longitudinal, and 0.19 ± 3.49 mm vertical for the laser positioning compared to cone beam computed tomography. The lowest positional deviations were found in the cranial region, and larger deviations occurred in the thoracic and abdominal sites. A statistical comparison using 2 one-sided t tests showed a general concordance of the 2 methods ( P ≤ 0.036), excluding the vertical direction of the abdominal region ( P = 0.198). CONCLUSION: The optical surface scanner Catalyst HD is a reliable and feasible patient positioning system without any additional radiation exposure. From the head to the thoracic and abdominal region, a decrease in accuracy was observed within a comparable range for Catalyst and laser-assisted positioning.

Real-time intra-fraction motion management in breast cancer radiotherapy: analysis of 2028 treatment sessions.

BACKGROUND: Intra-fraction motion represents a crucial issue in the era of precise radiotherapy in several settings, including breast irradiation. To date, only few data exist on real-time measured intra-fraction motion in breast cancer patients. Continuous surface imaging using visible light offers the capability to monitor patient movements in three-dimensional space without any additional radiation exposure. The aim of the present study was to quantify the uncertainties of possible intra-fractional motion during breast radiotherapy. MATERIAL AND METHODS: One hundred and four consecutive patients that underwent postoperative radiotherapy following breast conserving surgery or mastectomy were prospectively evaluated during 2028 treatment sessions. During each treatment session the patients' motion was continuously measured using the Catalyst™ optical surface scanner (C-RAD AB, Sweden) and compared to a reference scan acquired at the beginning of each session. The Catalyst system works through an optical surface imaging with light emitting diode (LED) light and reprojection captured by a charge coupled device (CCD) camera, which provide target position control during treatment delivery with a motion detection accuracy of 0.5 mm. For 3D surface reconstruction, the system uses a non-rigid body algorithm to calculate the distance between the surface and the isocentre and using the principle of optical triangulation. Three-dimensional deviations and relative position differences during the whole treatment fraction were calculated by the system and analyzed statistically. RESULTS: Overall, the maximum magnitude of the deviation vector showed a mean change of 1.93 mm ± 1.14 mm (standard deviation [SD]) (95%-confidence interval: [0.48-4.65] mm) and a median change of 1.63 mm during dose application (beam-on time only). Along the lateral and longitudinal axis changes were quite similar (0.18 mm ± 1.06 mm vs. 0.17 mm ± 1.32 mm), on the vertical axis the mean change was 0.68 mm ± 1.53 mm. The mean treatment session time was 154 ± 53 (SD) seconds and the mean beam-on time only was 55 ± 16 s. According to Friedman's test differences in the distributions of the three possible directions (lateral, longitudinal and vertical) were significant (p < 0.01), in post-hoc analysis there were no similarities between any two of the three directions. CONCLUSION: The optical surface imaging system is an accurate and easy tool for real-time motion management in breast cancer radiotherapy. Intra-fraction motion was reported within five millimeters in all directions. Thus, intra-fraction motion in our series of 2028 treatment sessions seems to be of minor clinical relevance in postoperative radiotherapy of breast cancer.

[Amyloid positron-emission-tomography with [18 F]-florbetaben in the diagnostic workup of dementia patients]. / Amyloid-Positronenemissionstomographie mit [18 F]-Florbetaben in der Demenzdiagnostik.

BACKGROUND: To this day the definite diagnosis of Alzheimer's disease still relies on post-mortem histopathological detection of neurofibrillary tangles and beta-amyloid deposits. Amyloid positron emission tomography (PET) is a new diagnostic tool that enables the in vivo quantification of pathological beta-amyloid deposits. The aim of the current study was to evaluate to what extent 18F-florbetaben-PET (FBB-PET) influences the diagnosis of patients with dementia. MATERIAL AND METHODS: Imaging with FBB-PET was performed on 33 patients from our outpatient department for cognitive neurology. Beforehand all patients underwent a comprehensive clinical, neuropsychiatric and laboratory examination as well as imaging by means of magnetic resonance imaging (MRI) and fluorodeoxyglucose-PET. The working diagnoses before and after FBB-PET imaging were compared. RESULTS: 17 out of 33 patients were scored as FBB-PET positive. In four cases the initial diagnosis had to be changed to Alzheimer's disease (three cases) and cerebral amyloid angiopathy (one case) due to the positive FBB-PET scan. 16 patients showed a negative FBB-PET scan. In three patients the initial diagnosis of Alzheimer's disease could be ruled out due to the negative FBB-PET scan. Overall, in 7 out of 33 examined patients the initial diagnosis had to be changed because of the findings of the FBB-PET scan. In 24 patients the initial diagnosis was confirmed by the results of the FBB-PET scan. CONCLUSION: Amyloid-PET is currently no standard procedure in the diagnosis of dementia; however, it can be a helpful additional diagnostic tool when used according to the "Appropriate Use Criteria" and the S3 guidelines on dementia in cases of unclear clinical presentation, atypically early age of onset as well as in patients with persistent or progressive unexplained mild cognitive impairment. By facilitating early diagnosis amyloid-PET imaging allows patient selection for therapeutic drug trials.

Treatment planning and evaluation of gated radiotherapy in left-sided breast cancer patients using the CatalystTM/SentinelTM system for deep inspiration breath-hold (DIBH).

BACKGROUND: There is a potential for adverse cardiovascular effects in long-term breast cancer survivors following adjuvant radiotherapy (RT). For this purpose, the deep inspiration breath-hold technique (DIBH) has been introduced into clinical practice, to maximally reduce the radiation dose to the heart. However, there are a variety of DIBH delivery techniques, patient positioning and visual patient feedback mechanisms. The aim of the present study was to evaluate the application of radiotherapy in DIBH using the CatalystTM/SentinelTM system, with a special emphasis on treatment planning and dosimetric plan comparison in free breathing (FB) and DIBH. PATIENTS AND METHODS: A total of 13 patients with left-sided breast cancer following breast conserving surgery were included in this prospective clinical trial. For treatment application the CatalystTM/SentinelTM system (C-RAD AB, Uppsala, Sweden) was used and gating control was performed by an audio-visual patient feedback system. CT and surface data were acquired in FB and DIBH and dual treatment plans were created using Pencil Beam and Collapsed Cone Convolution. Dosimetric output parameters of organs at risk were compared using Wilcoxon signed-rank test. Central lung distance (CLD) was retrieved from iViewTM portal images during treatment delivery. RESULTS: The system contains a laser surface scanner (SentinelTM) and an optical surface scanner (CatalystTM) interconnected to the LINAC systems via a gating interface and allows for a continuous and touchless surface scanning. Overall, 225 treatment fractions with audio-visual guidance were completed without any substantial difficulties. Following initial patient training and treatment setup, radiotherapy in DIBH with the CatalystTM/SentinelTM system was time-efficient and reliable. Following dual treatment planning for all patients, nine of 13 patients were treated in DIBH. In these patients, the reduction of the mean heart dose for DIBH compared to FB was 52 % (2.73 to 1.31 Gy; p = 0.011). The maximum doses to the heart and LAD were reduced by 59 % (47.90 to 19.74 Gy; p = 0.008) and 75 % (38.55 to 9.66 Gy; p = 0.008), respectively. In six of the nine patients the heart completely moved out of the treatment field by DIBH. The standard deviation of the CLD varied between 0.12 and 0.29 cm (mean: 0.16 cm). CONCLUSION: The CatalystTM/SentinelTM system enabled a fast and reliable application and surveillance of DIBH in daily clinical routine. Furthermore, the present data show that using the DIBH technique during RT could significantly reduce high dose areas and mean doses to the heart. TRIAL REGISTRATION: DRKS: DRKS00010929 registered on 5. August 2016.

Reduction of cardiac and coronary artery doses in irradiation of left-sided breast cancer during inspiration breath hold : A planning study.

BACKGROUND AND PURPOSE: The radiation dose received by the heart during adjuvant left-sided breast irradiation plays a crucial role in development of late toxicity. Although the absolute risk of cardiotoxicity can be reduced with modern irradiation techniques, cardiotoxic chemotherapy increases the risk of late damage. Thus, the radiation dose to the heart should be minimized. This study evaluated the influence of different amplitudes of inspiration breath hold (IBH) during simulated left-sided breast irradiation on cardiac doses compared to free breathing (FB). PATIENTS AND METHODS: CT data of 11 lung cancer patients were retrospectively used as left-sided pseudo-breast cancer cases. Two CT scans were used, one during IBH and one during FB, and two treatment plans were generated. Relevant heart, lung, and left anterior descending artery (LAD) parameters were derived from dose-volume histograms. The normal tissue complication probabilities (NTCPs) for the heart were calculated based on the relative seriality model. Inspiration depth was quantified using chest volume and diameter, and correlated thereafter to a possible sparing of heart tissue. RESULTS: Mean reduction of heart dose for IBH compared to FB was 40 % (1.65 vs. 0.99 Gy; p = 0.007). Maximum dose to the heart and LAD could be decreased by 33 % (p = 0.011) and 43 % (p = 0.024), respectively. The mean anteroposterior shift was 5 mm (range 0.9-9.5 mm). Significant negative correlations between the relative change in LAD mean dose and the mean thoracic diameter and volume change, as well as with the absolute change in thoracic diameter were seen. The NTCP for cardiac mortality could be decreased by about 78 % (p = 0.017). CONCLUSION: For left-sided breast cancer patients, cardiac doses can be significantly decreased with tangential irradiation and IBH.

[A Pair of Siblings with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis and a Novel Thr462Lysfs Mutation in the TBK1 Gene]. / Ein Geschwisterpaar mit frontotemporaler Lobärdegeneration und amyotropher Lateralsklerose und einer neuen Mutation im TBK1-Gen (Thr462Lysfs).

We report on a pair of siblings with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) and a novel Thr462Lysfs mutation in the TANK-binding kinase 1 (TBK1) gene identified through the European Early-Onset Dementia Consortium. The patients presented at the age of 77 and 75 years and displayed dementia and bulbar symptoms as well as progressive paresis. After a progressive course, both of them died only a few months after diagnosis. Most recently, TBK1 mutations were identified in patients with FTD and ALS. A loss of expression of the mutant allele, leading to 50 % reduced TBK1 protein levels, seems to be causative. The occurrence of TBK1 mutations in FTD and ALS underlines the fact that FTD and ALS are part of the same disease spectrum. For future therapeutic trials, characterization of TBK1 mutation carriers in presymptomatic cohorts, such as the genetic frontotemporal dementia initiative (GENFI), is of great importance.

Human Islets Exhibit Electrical Activity on Microelectrode Arrays (MEA).

This study demonstrates for the first time that the microelectrode array (MEA) technique allows analysis of electrical activity of islets isolated from human biopsies. We have shown before that this method, i.e., measuring beta cell electrical activity with extracellular electrodes, is a powerful tool to assess glucose responsiveness of isolated murine islets. In the present study, human islets were shown to exhibit glucose-dependent oscillatory electrical activity. The glucose responsiveness could be furthermore demonstrated by an increase of insulin secretion in response to glucose. Electrical activity was increased by tolbutamide and inhibited by diazoxide. In human islets bursts of electrical activity were markedly blunted by the Na(+) channel inhibitor tetrodotoxin which does not affect electrical activity in mouse islets. Thus, the MEA technique emerges as a powerful tool to decipher online the unique features of human islets.Additionally, this technique will enable research with human islets even if only a few islets are available and it will allow a fast and easy test of metabolic integrity of islets destined for transplantation.

Surface parameters of ferritic iron-rich Fe-Cr alloy.

Using first-principles density functional theory in the implementation of the exact muffin-tin orbitals method and the coherent potential approximation, we studied the surface energy and the surface stress of the thermodynamically most stable surface facet (100) of the homogeneous disordered body-centred cubic iron-chromium system in the concentration interval up to 20 at.% Cr. For the low-index surface facets of Fe and Cr, the surface energy of Cr is slightly larger than that of Fe, while the surface stress of Cr is considerably smaller than that of Fe. We find that Cr addition to Fe generally increases the surface energy of the Fe-Cr alloy; however, an increase of the bulk amount of Cr also increases the surface stress. As a result of this unexpected trend, the (100) surface of Fe-Cr becomes more stable against reconstruction with increasing Cr concentration. We show that the observed trends are of magnetic origin. In addition to the homogeneous alloy case, we also investigated the impact of surface segregation on both surface parameters.