Potentials of on-line repositioning based on implanted fiducial markers and electronic portal imaging in prostate cancer radiotherapy

<p>Abstract</p> <p>Background</p> <p>To evaluate the benefit of an on-line correction protocol based on implanted markers and weekly portal imaging in external beam radiotherapy of prostate cancer. To compare the use of bony anatomy versus implanted markers for calculation of setup-error plus/minus prostate movement. To estimate the error reduction (and the corresponding margin reduction) by reducing the total error to 3 mm once a week, three times per week or every treatment day.</p> <p>Methods</p> <p>23 patients had three to five, 2.5 mm Ø spherical gold markers transrectally inserted into the prostate before radiotherapy. Verification and correction of treatment position by analysis of orthogonal portal images was performed on a weekly basis. We registered with respect to the bony contours (setup error) and to the marker position (prostate motion) and determined the total error. The systematic and random errors are specified. Positioning correction was applied with a threshold of 5 mm displacement.</p> <p>Results</p> <p>The systematic error (1 standard deviation [SD]) in left-right (LR), superior-inferior (SI) and anterior-posterior (AP) direction contributes for the setup 1.6 mm, 2.1 mm and 2.4 mm and for prostate motion 1.1 mm, 1.9 mm and 2.3 mm. The random error (1 SD) in LR, SI and AP direction amounts for the setup 2.3 mm, 2.7 mm and 2.7 mm and for motion 1.4 mm, 2.3 mm and 2.7 mm. The resulting total error suggests margins of 7.0 mm (LR), 9.5 mm (SI) and 9.5 mm (AP) between clinical target volume (CTV) and planning target volume (PTV). After correction once a week the margins were lowered to 6.7, 8.2 and 8.7 mm and furthermore down to 4.9, 5.1 and 4.8 mm after correcting every treatment day.</p> <p>Conclusion</p> <p>Prostate movement relative to adjacent bony anatomy is significant and contributes substantially to the target position variability. Performing on-line setup correction using implanted radioopaque markers and megavoltage radiography results in reduced treatment margins depending on the online imaging protocol (once a week or more frequently).</p

CNG und LNG aus biogenen Reststoffen – ein Konzept zur ressourcenschonenden Kraftstoffproduktion

Es wurde ein Verfahren entwickelt, das die Umwandlung von Reststoffen zu methanbasierten Kraftstoffen unter höchstmöglichem Erhalt des biogenen Kohlenstoffs mithilfe von elektrischer Energie aus erneuerbaren Quellen ermöglicht. Waldrestholz, Stroh und Klärschlamm wurden als besonders relevante Einsatzstoffe identifiziert. Durch die hochintegrierte Kopplung von Vergasung, Hochtemperaturelektrolyse und Methanisierung wird der biogene Kohlenstoff aus den Edukten nahezu vollständig in das Produkt Methan überführt. Die Gestehungskosten sind dabei mit denen gegenwärtig eingesetzter Technologien vergleichbar und liegen bei Großanlagen im Bereich üblicher Werte der Biomethanerzeugung

A non-randomised, single-centre comparison of induction chemotherapy followed by radiochemotherapy versus concomitant chemotherapy with hyperfractionated radiotherapy in inoperable head and neck carcinomas

BACKGROUND: The application of induction chemotherapy failed to provide a consistent benefit for local control in primary treatment of advanced head and neck (H&N) cancers. The aim of this study was to compare the results of concomitant application of radiochemotherapy for treating locally advanced head-and-neck carcinoma in comparison with the former standard of sequential radiochemotherapy. METHODS: Between 1987 and 1995 we treated 122 patients with unresectable (stage IV head and neck) cancer by two different protocols. The sequential protocol (SEQ; 1987–1992) started with two courses of neoadjuvant chemotherapy (cisplatin [CDDP] + 120-h continuous infusions (c.i.) of folinic acid [FA] and 5-fluorouracil [5-FU]), followed by a course of radiochemotherapy using conventional fractionation up to 70 Gy. The concomitant protocol (CON; since 1993) combined two courses of FA/5-FU c.i. plus mitomycin (MMC) concomitantly with a course of radiotherapy up to 30 Gy in conventional fractionation, followed by a hyperfractionated course up to 72 Gy. Results from the two groups were compared. RESULTS: Patient and tumor characteristics were balanced (SEQ = 70, CON = 52 pts.). Mean radiation dose achieved (65.3 Gy vs. 71.6 Gy, p = 0.00), response rates (67 vs. 90 % for primary, p = 0.02), and local control (LC; 17.6% vs. 41%, p = 0.03), were significantly lower in the SEQ group, revealing a trend towards lower disease-specific (DSS; 19.8% vs. 31.4%, p = 0.08) and overall (14.7% vs. 23.7%, p = 0.11) survival rates after 5 years. Mucositis grades III and IV prevailed in the CON group (54% versus 44%). Late toxicity was similar in both groups. CONCLUSION: Concurrent chemotherapy seemed more effective in treating head and neck tumors than induction chemotherapy followed by chemoradiation, resulting in better local control and a trend towards improved survival

Magnetic resonance imaging, computed tomography, and 68Ga-DOTATOC positron emission tomography for imaging skull base meningiomas with infracranial extension treated with stereotactic radiotherapy - a case series

<p>Abstract</p> <p>Introduction</p> <p>Magnetic resonance imaging (MRI) and computed tomography (CT) with ⁶⁸Ga-DOTATOC positron emission tomography (⁶⁸Ga-DOTATOC-PET) were compared retrospectively for their ability to delineate infracranial extension of skull base (SB) meningiomas treated with fractionated stereotactic radiotherapy.</p> <p>Methods</p> <p>Fifty patients with 56 meningiomas of the SB underwent MRI, CT, and ⁶⁸Ga-DOTATOC PET/CT prior to fractionated stereotactic radiotherapy. The study group consisted of 16 patients who had infracranial meningioma extension, visible on MRI ± CT (MRI/CT) <it>or </it>PET, and were evaluated further. The respective findings were reviewed independently, analyzed with respect to correlations, and compared with each other.</p> <p>Results</p> <p>Within the study group, SB transgression was associated with bony changes visible by CT in 14 patients (81%). Tumorous changes of the foramen ovale and rotundum were evident in 13 and 8 cases, respectively, which were accompanied by skeletal muscular invasion in 8 lesions. We analysed six designated anatomical sites of the SB in each of the 16 patients. Of the 96 sites, 42 had infiltration that was delineable by MRI/CT and PET in 35 cases and by PET only in 7 cases. The mean infracranial volume that was delineable in PET was 10.1 ± 10.6 cm³, which was somewhat larger than the volume detectable in MRI/CT (8.4 ± 7.9 cm³).</p> <p>Conclusions</p> <p>⁶⁸Ga-DOTATOC-PET allows detection and assessment of the extent of infracranial meningioma invasion. This method seems to be useful for planning fractionated stereotactic radiation when used in addition to conventional imaging modalities that are often inconclusive in the SB region.</p

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Positioning accuracy and setup variability of target volume in marker-based image-guided percutaneous radiotherapy of localized prostate cancer and strategies for increasing the precision

Die Behandlung von Patienten mit Prostatakarzinomen kann derzeit in einem früheren Risikostadium beginnen und mit vergleichsweise höherer Wahrscheinlichkeit zur Kuration führen. Die angestrebte langfristige PSA- Kontrolle des Prostatakarzinoms erfordert die Anwendung hoher Strahlendosen, die jedoch durch die Dosisbelastung der Nachbarorgane limitiert werden. Ein wesentlicher Parameter ist der Sicherheitsabstand zwischen PTV und CTV. Dieser wiederum kann durch eine hochpräzise Positionierungstechnik reduziert werden. Insbesondere bildgestützte Bestrahlungsverfahren sind dazu geeignet und genügen dadurch den modernen Ansprüchen einer dosiseskalierten nebenwirkungsarmen Behandlungsmethode. Dabei ist die Lagerungsgenauigkeit des Patienten alleine häufig nicht ausreichen, weil auch die Prostatabewegung signifikant zu Ungenauigkeiten beiträgt. An der Klinik für Strahlenheilkunde der Charité sollte ein Protokoll zur Lagerungskontrolle implementiert werden, um dessen Anwendbarkeit und Sicherheit zu prüfen und die institutionsspezifische Positionierungsgenauigkeit zu bestimmen. In einer Gruppe von Patienten mit lokalisiertem Prostatakarzinom, die mit 3D-konformer Strahlentherapie behandelt wurden, implantierten wir dazu intraprostatische Goldmarker. Die Bildführung erfolgte mittels MV-Portal-Imaging. Wir konnten die problemlose Durchführbarkeit der gewählten Methodik aufzeigen. Für den unkorrigierten Gesamtfehler berechneten wir die notwendige CTV-PTV Sicherheitssäume von 7,0 mm (LR), 9,5 mm (SI) und 9,5 mm (AP). Durch wöchentliche Korrektur ließen sich die die Sicherheitsabstände auf 6,7, 8,2 und 8,7 mm reduzieren. Für simulierte tägliche Kontrollen könnten diese darüber hinaus bis auf 4,9, 5,1 und 4,8 mm gesenkt werden. Analysen einer weiteren Patientenkohorte erfolgten nach täglicher vor Bestrahlungsbeginn Online vorgenommener Repositionierung anhand interner Marker über ein implementiertes röntgenbasiertes automatisiertes Repositionierungssystem (ET/NB). Dadurch ließ sich der Restfehler auf <2 mm verringern. Der verbleibende Restfehler entsteht durch intrafraktionelle Bewegung der Prostata sowie durch verbleibende Ungenauigkeiten wie geometrische / mechanische Unsicherheiten, Drehfehler und Ungenauigkeiten der Bildverarbeitung. Unsere Analyse der Restfehler zeigte, dass diese individualisiert (Patientenabhängig / Institutsabhängig) auftreten können. Die vorliegende Arbeit ermöglichte eine Reevaluation der Sicherheitsabstände und konsekutiv deren deutliche Verringerung. Drehfehler können komplizierend hinzu. Diese folgen in der untersuchten Patientenkohorte annähernd einer Standardverteilung und korrelierten nicht signifikant mit Verschiebungsfehlern. Anhand unserer Messungen konnten wir einen, durch das verwendete Positionierungssystem induzierten systematischen Fehler ausschließen, der zunächst in der Literatur vermutet worden war. Die in unserer Institution als Standard implementierte bildgestützte dosiseskalierte intensitätsmodulierte Strahlentherapie des lokalisierten Prostatakarzinoms erfordert Behandlungszeiten von etwa 15 min. und die Rolle der intrafraktionellen Beweglichkeit gewann Bedeutung. Wir untersuchten in einer weiteren Patientengruppe die intrafraktionell auftretenden Fehler. Diese entstehen nach initialer Korrektur der Verschiebungs- und Drehfehler, betragen etwa 2 mm, und weisen wesentliche individuelle Unterschiede auf. Dieser Fehler lässt sich nur aufwendig, z.B. durch Trackingmethoden oder robotassistierte hypofraktionierte Bestrahlungstechniken korrigieren und muss durch Anpassung der Sicherheitssäume ausgeglichen werden. Die Lage des Zielorgans der Prostata und dessen Verschiebung hängen von der Position der umgebenden Organe ab, die in hohem Masse von Füllung oder Dehnung, insbesondere des Mastdarms und in einen geringen Grad der Blase beeinflusst wird. Theoretisch könnte die Verlagerung der Prostata reduziert werden kann und an Bedeutung verlieren, wenn eine konstante und reproduzierbare Organfüllung aufrechterhalten werden könnte. Wir etablierten durch sorgfältige Patienteninstruktion eine gut definierte Referenzsituation von entleertem Mastdarm und reproduzierbarer Blasenfüllung von einigen hundert Milliliter. In der Literatur zur IGRT der Prostata werden diese patientenabhängigen Faktoren häufig nicht angegeben, damit fehlen Daten zur Abhängigkeit der Prostataverschiebung von der Patientenvorbereitung. Unter klinischen Bedingungen ist die Markerimplantation nicht nur ein zusätzliches invasives Verfahren (mit zusätzlichem Risiko), sondern auch zeitaufwendig und teuer. Wir untersuchten deshalb in einer nächsten Arbeit die die Frage, ob und in welchem Umfang die Prostatabewegung durch entsprechende Anleitung der Patienten reduziert werden kann. Wir berechneten die Sicherheitsabstände für bildgestützte Bestrahlung alleinig anhand der knöchernen Beckenstrukturen auf 2 mm in RL, 4 mm in AP, und 5 mm in SI. Dieses Verfahren erwies sich damit als beinahe so erfolgreich wie die markerbasierte Führung. Weitere markerbasierte Studien sind erforderlich, um die optimale Strategie zur Minimierung der inter-und intrafraktionellen Bewegung und die Rolle der IGRT zu klären und Methoden oder Technologien zur Verbesserung der klinischen Ergebnisse zu entwickeln. Zusammenfassend erlaubt die bildgestützte Bestrahlungsmethode mittels intensitätsmodulierter Strahlentherapie dosiseskalierte Schemata bei geringeren Sicherheitsabständen. Der Nachweis signifikanter Unterschiede bezüglich des biochemische Rezidivfreiheit oder der Spättoxizität stehen noch aus.The treatment of patients with prostate cancer currently starts in an earlier risk stage and leads with a relatively higher probability to curation. The targeted long-term PSA control of prostate cancer requires the application of high doses of radiation, which, however, are limited due to the dose loading of neighboring organs. An essential parameter is the safety distance between PTV and CTV, which can be reduced by high-precision positioning technology. In particular, image-based Irradiation methods are suitable for this purpose and thereby satisfy the modern claims of a dose-escalated treatment with low side effects. The positioning accuracy of the patient alone is often insufficient, because the prostate movement also contributes significantly to inaccuracies. At the Medical Hospital for Radiotherapy of Charité, a protocol should be implemented with respect to its applicability and safety. Furthermore, the institution-specific positioning accuracy should be determinated. In a group of patients with localized prostate cancer, who were treated using 3-dimensional Radiotherapy and implanted intraprostatic Gold markers. The image guidance was carried out by means of MV portal imaging. We could demonstrate the feasibility of the chosen methodology. Without correction, we calculated margins of 7.0 mm (LR), 9.5 mm (SI) and 9.5 mm (AP). By weekly corrections, the safety distances could be reduced to 6.7, 8.2 and 8.7 mm. For simulated daily controls, these could be lowered up to 4.9, 5.1 and 4.8 mm. Analyzes of another cohort of patients were performed daily start of irradiation Online repositioning using internal markers via an implemented x-ray based automated repositioning system (ET / NB). This allowed the residual error to be reduced to <2 mm. The remaining residual error is caused by intrafractional movement of the prostate and by remaining inaccuracies such as geometric / mechanical uncertainties, rotation errors and inaccuracies of image processing. Our analysis of residual errors showed that these occur in an individualized way (depending on the patient / institution-dependent) The present work allowed a re - evaluation of the safety distances and consecutively their significant reduction. Rotational errors can be complicated. These follow in the examined patient cohort approximates a standard distribution and does not correlate significantly with shift errors. Based on our measurements, we were able to to rule out that the used positioning system induced systematic errors, which was initially suspected in the literature. The image-based dose-scale implemented in our institution as a standard requires intensity-modulated radiotherapy of localized prostate cancer Treatment times of about 15 min. and the role of intrafractional mobility gained importance. We examined the patients in another patient group intrafractionally occurring errors. These arise after initial correction of the displacement and rotation errors amount to about 2 mm, and have substantial individual differences. This error can only be corrected costly, e.g. by tracking methods or robot-assisted hypofractionated radiation techniques and must be compensated by adjusting the safety margins. The location of the target organ of the prostate and its displacement depend on the position of the surrounding organs, which depends to a great extent on filling or stretching, especially of the rectum and in a small degree of the bladder. Theoretically, the displacement of the prostate gland could be reduced and loose meaning when a constant and reproducible organ filling could be maintained. We established through careful patient instruction bladder filling of a few hundred milliliters. In the literature on the IGRT of the prostate these patient-dependent factors are often not indicated, thus missing data on the dependence of prostate displacement on patient preparation. In clinical conditions, the marker implantation is not just an additional one invasive procedure (with additional risk), but also time consuming and expensive. Therefore, in a next work we examined the question of whether and in which scope the prostate movement can be reduced by appropriate guidance of patients. We calculated the safety margins for image-guided irradiation solely based on the bony pelvic structures on 2 mm in RL, 4 mm in AP, and 5 mm in SI. This process proved to be almost as successful as the marker-based leadership. Further marker-based studies are needed to complete the optimal strategy for minimizing inter- and intrafractional movement and the role of the IGRT to clarify methods or technologies to improve the clinical results. In summary, the image-based irradiation method allows dose-escaled intensity-modulated radiation therapy schemes at lower safety distances. The detection of significant differences in biochemical recurrence or late toxicity stand still out

A Braille Conversion Service Using GPU and Human Interaction by Computer Vision: Paper - iPRES 2011 - Singapore

Scalable systems and services for preserving digital content became important technologies with increasing volumes of digitized data. This paper presents a new Braille converter service that is a sample implementation of scalable service for preserving digital content. The converter service facilitates complex conversion problems regarding Braille code. Braille code is a method which allows visually impaired people to read and write tactile text. Using a GPU with the CUDA architecture allows the creation of a parallel processing service with enhanced scalability. The Braille converter is a web service that provides automatic conversion from the older BRF to the newer PEF Braille format. This service can manage a large number of objects. Speedups on the order of magnitude of 5000 to 6900 (depending on the size of the object) were achieved using a GPU (GTX460 graphics card) with respect to a CPU implementation. An extension involving an image processing system is used for human interaction. Optical pattern recognition allows Braille code creation using Braille patterns. No special input device and skills are needed, only familiarity with Braille code is required