Search

The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase III trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy.A clinical-grade whole-transcriptome assay was carried out on radical prostatectomy samples obtained from patients enrolled in Swiss Group for Clinical Cancer Research (SAKK) 09/10, a phase III trial of 350 men with biochemical recurrence after radical prostatectomy randomized to 64 Gy versus 70 Gy without concurrent hormonal therapy or pelvic nodal RT. A prespecified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, postradical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks.The analytic cohort of 226 patients was representative of the overall trial, with a median follow-up of 6.3 years (interquartile range 6.1-7.2 years). The GC (high versus low-intermediate) was independently associated with biochemical progression [subdistribution hazard ratio (sHR) 2.26, 95% confidence interval (CI) 1.42-3.60; P0.001], clinical progression (HR 2.29, 95% CI 1.32-3.98; P = 0.003), and use of hormone therapy (sHR 2.99, 95% CI 1.55-5.76; P = 0.001). GC high patients had a 5-year freedom from biochemical progression of 45% versus 71% for GC low-intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower versus higher GC scores.This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. These data confirm the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting.

Purpose & Objective A clinical study (PRIMA) regarding the potential of range verification in proton therapy by prompt-gamma imaging (PGI) is carried out at our institution. As a step towards the automatic evaluation of the measured PGI data, we present an approach to detect anatomical changes in prostate cancer patients from realistically simulated PGI data using convolutional neural networks (CNNs). Materials & Methods In-room control CTs (cCTs) were acquired in treatment position before monitoring 146 field deliveries of 10 hypo-fractioned (3Gy/fraction) prostate cancer patients with a PGI slit camera (range: 8-18 fields/patient). After manual CT registration and dose recalculation, spot-wise shifts of integrated depth-dose (IDD) profiles between cCTs and planning CTs were extracted at the 80% distal falloff position and used for ground-truth classification. Treatment fields were considered to be affected by relevant anatomical changes of the patient if >0.1% of all spots (with at least 0.1% of the total monitor units per field) had absolute IDD shifts above 5 mm. These parameters lead to a field-wise IDD ground-truth classification in optimal agreement with a prior manual field-wise classification based on dose difference maps. Based on the cCTs, we simulated realistic PGI profiles, including Poisson noise and a positioning uncertainty of the PGI slit camera, and extracted spot-wise range shifts by comparison with the expected reference profiles for the planning CT. Spots with reliable PGI information (inside field-of-view and >5E7 protons), were considered with their Bragg peak position for generating two independent 3D spatial maps of 161616 voxels (0.740.740.66 cm3): (1) The PGI-determined range shift in each voxel is the weighted average taking the spot-wise proton number into account. (2) The proton number in each voxel is summed over all respective spots and normalized per field (Fig. 1). With these maps and the IDD classification, 3D-CNNs (6 convolutional & 2 downsampling layers) were trained using patient-wise 10-fold cross-validation on the binary task to detect anatomical changes. Results The CNNs achieved a mean training and validation accuracy of 0.85 (range: 0.77-0.91) and 0.83 (0.70-0.93), respectively (Fig. 2). Based on the validation results, anatomical changes were detected with a sensitivity of 0.88 and a specificity of 0.76. Conclusion Our work shows that CNNs can reliably detect anatomical changes in prostate cancer patients from realistically simulated PGI data of clinical irradiations. While a validation on measured PGI data is the next step, this study highlights the potential of an automatic interpretation of PGI data, which is highly desired for routine clinical application and required for the inclusion of PGI in an automated feedback loop for online adaptive proton therapy.

Background The analysis aimed to compare the radiotracers [68Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 intraindividually in terms of malignant lesions, mi(molecular-imaging)TNM staging and presumable unspecific lesions retrospectively as used in routine clinical practice. Methods A retrospective analysis of 46 prostate cancer patients (median age: 71 years) who underwent consecutive [18Ga]-Ga-PSMA-11- and [18F]-F-PSMA-1007-PET/CT or PET/MRI within a mean of 12 ± 8.0 days was performed. MiTNM staging was performed in both studies by two nuclear medicine physicians who were blinded to the results of the other tracer. After intradisciplinary and interdisciplinary consensus with two radiologists was reached, differences in both malignant and presumable nonspecific tracer accumulation were analyzed. Results Differences in terms of miTNM stages in both studies occurred in nine of the 46 patients (19.6%). The miT stages differed in five patients (10.9%), the miN stages differed in three patients (6.5%), and different miM stages occurred only in one patient who was upstaged in [18F]-F-PSMA-1007 PET. Concordant miTNM stages were obtained in 37 patients (80.4%). There was no significant difference between [18F]-F-PSMA-1007 and [68Ga]-Ga-PSMA-11 in the SUVmax locally (31.5 vs. 32.7; p = 0.658), in lymph node metastases (28.9 vs. 24.9; p = 0.30) or in bone metastases (22.9 vs. 27.6; p = 0.286). In [18F]-F-PSMA-1007 PET, more patients featured presumable unspecific uptake in the lymph nodes (52.2% vs. 28.3%; p: 18F]-F-PSMA-1007-positive lesions mainly occurred in the ribs (58.7%), axillary lymph nodes (39.1%) and cervical ganglia (28.3%). Conclusion In terms of miTNM staging, both tracers appeared widely exchangeable, as no tracer relevantly outperformed the other. The differences between the two tracers were far more common in presumable unspecific lesions than in malignant spots. A routinely performed two-tracer study could not be shown to be superior. Since it seems at least challenging for most nuclear medicine departments to provide both [18F]-F-PSMA-1007 and [68Ga]-Ga-PSMA-11, it appears reasonable to choose the PSMA radiotracer depending on local availability with attention to the greater occurrence of nonspecific bone findings with [18F]-F-PSMA-1007.

Introduction We present results of the worldwide first systematic study on the sensitivity of prompt-gamma-imaging (PGI) to detect anatomical changes in proton therapy for the ongoing evaluation in prostate-cancer treatments. Materials&Methods Spot-wise range shifts were monitored with a PGI-slit-camera during 40 fractions of hypo-fractionated prostate-cancer treatments (5 patients, 2 fields, each 1.5GyE). In-room CTs were acquired for these fractions and range shifts of spot-wise integrated depth-dose (IDD) profiles serve as ground-truth. For both PGI and IDD data, spots were clustered based on Bragg-peak position and proton number to mitigate statistical uncertainty in the PGI measurement using a low-dose spot cut-off at 5e7 protons, a minimum number of 3e9 protons per cluster, and a minimum/maximum cluster volume of 1cm3/8cm3. Clusters with absolute range shift ≥5mm were classified as relevant anatomical changes. Results A strong correlation (rPearson=0.72) was found between ground-truth IDD and PGI range shifts per cluster with an average absolute deviation of 1.3mm over all fractions. In total, 245/7143 (3.4%) clusters (found within 24/72 fields) contained relevant IDD-based range shifts. PGI detected these changes with a sensitivity of 68%, specificity of 96%, and accuracy of 95%. The results might be affected by potential intra-fractional changes between in-room CT acquisition and treatment delivery. A higher sensitivity is also expected for a gantry-mounted camera system with decreased positioning uncertainty. Conclusion Our systematic investigation on the sensitivity of a PGI-slit-camera with a first quantitative comparison of range shifts from PGI and IDD profiles demonstrates the capability to locally detect relevant anatomical changes in patients.

Introduction: Anatomical changes during proton therapy can cause severe dosimetric deviation. Treatment verification is thus highly desirable. Here, we present the first systematic evaluation of the sensitivity of a Prompt-Gamma-Imaging (PGI) based range verification system to detect anatomical changes in prostate-cancer treatments. Materials and Methods: Spot-wise range deviations were monitored with a PGI slit camera during in total 16 fractions of hypo-fractionated Pencil-Beam-Scanning (PBS) prostate-cancer treatments (2 patients, 2 fields, each 1.5GyE). For all monitored fractions, in-room control-CT scans were acquired, serving as ground-truth reference for the identification and scoring of anatomical changes (strong/moderate/light). The sensitivity to detect these changes was determined for both, clinically measured and simulated PGI-data, respectively: For distal PBS spots, expected shifts, determined from line-dose profiles (planning-CT vs. control-CT), were manually compared with PGI-derived spot-wise shifts (Fig.1). Furthermore, a simple two-parametric model was established to classify each monitored field into scenarios of global, local and no-clinically-relevant anatomical changes. Results: Overall 66% (84%) of the 64 detected anatomical changes were identified from measured (simulated) PGI-data (Fig.2a). All strong changes (14/64) were identified correctly. The first attempt for automated field-wise classification was able to correctly classify most global changes (9/11). However, differentiation between non-relevant from local changes seemed more difficult (4/6 and 7/14 fields classified correctly, respectively); but even ground-truth classification was often borderline in those cases (Fig.2b). Conclusion: In the first systematic investigation of the sensitivity of clinical PGI-based treatment verification, its capability to detect strong anatomical changes has been clearly demonstrated. Moving towards automated interpretation of PGI-data, a simple two-parametric model already showed encouraging results.

37th European Photovoltaic Solar Energy Conference and Exhibition; 621-626, Bifacial CIGSe solar cells with ITO back contacts and with absorber thicknesses ranging from 300 to 1020 nm were studied by measuring J-V-characteristics and EQE with illumination from front and rear side, respectively. Compared to simultaneously processed samples with Mo back contacts, increased open circuit voltages occured with ITO back contacts. This effect was more pronounced with decreasing absorber thickness and can be related to a possible hole extraction barrier. Systematic electrical simulations were employed to determine the back contact recombination velocity at the CIGSe/ITO interface, resulting in a value of the order of 105 cm/s.

Objective: To improve the accuracy of range verification with prompt-gamma-ray imaging (PGI), enabling the validation of CT-based stopping-power prediction in patients. Material & Methods: A PGI-slit-camera system was modified to enhance its positioning accuracy, now using a floor-based docking station. The camera position is calibrated with orthogonal X-rays and its reproducibility was validated with X-ray measurements at two different days with ten repositioning iterations each. To determine the PGI simulation accuracy, the camera position derived with the X-Ray system and PGI-based range shift determination in a PMMA phantom (measured vs. simulated PGI profiles) was correlated. Subsequently, the PGI system was clinically applied to monitor absolute proton ranges for a 1.5Gy field during eight fractions of a hypo-fractionated prostate-cancer treatment using pencil beam scanning (Fig.1). For all monitored fractions, in-room control CT scans were acquired in treatment position, enabling PGI-based range analysis for the actual patient anatomy. Results: The reproducibility of the camera position in beam direction was ±0.55mm (1σ) over different days. A 1.1mm offset in absolute range determination was found. It can be directly identified as simulation accuracy and is corrected in subsequent clinical application. The overall PGI range measurement uncertainty of about 2mm (averaging over multiple spots for global-shift determination) is well below the range prediction uncertainty (3.5%∙Range+2mm). Evaluation of the clinical slit-camera application and the verification of the applied stopping-power prediction using dual-energy CT is ongoing. Conclusion: The accuracy of PGI-based range verification was improved to enable the verification of CT-based stopping-power prediction in patients, potentially allowing for a future reduction of currently used range uncertainties.

Introduction Currently, the uncertainty in CT-based range prediction is substantially impairing the accuracy of particle therapy. Improvements like a determination of stopping-power ratio (SPR) from dual-energy CT (DECT) have been proposed. However, a validation of range prediction in patients has not been achieved by any means. Here, we present the first verification of proton range prediction in patients, using Prompt-Gamma-Imaging (PGI). Materials & Methods A PGI-slit-camera system was modified to enhance its positioning accuracy using a floor-based docking station. Its accuracy and positioning reproducibility were determined with x-ray and PGI measurements. The PGI system was clinically applied to monitor absolute proton ranges for a 1.5Gy field during eight fractions of hypo-fractionated treatment of two prostate-cancer patients using pencil beam scanning (Fig.1). For all monitored fractions, in-room control-CT scans were acquired in treatment position enabling PGI-based spot-by-spot range analysis for the actual patient anatomy. The PG measurements were compared to simulations of the expected PGI signal using either a standard CT-number-to-SPR conversion (HLUT) or a HLUT optimized with patient-specific DECT-derived SPR information (DECT-HLUT), respectively. Results The accuracy and precision for global range verification (averaging over multiple spots) was determined to be 0.6mm and 1.3mm (both 2σ-level), respectively. The precision is limited by remaining uncertainties in image registration and positioning reproducibility (1mm,2σ). To verify range prediction in patients, the histogram of range shifts was analyzed concerning its Gaussian mean (Fig. 2) as surrogate for the accuracy of the respective range prediction method, independent from random uncertainty contributions (e.g. positioning, statistical uncertainty in shift determination). The mean deviation for the DECT-HLUT and standard HLUT were -0.6mm and 1.3mm, respectively. Conclusion The accuracy of PGI-based range verification was improved to enable the verification of CT-based stopping-power prediction in patients for the first time. First data evaluation suggests a slight superiority of DECT-based range prediction.

In prostate cancer, disease progression after primary treatment and subsequent androgen deprivation therapy is common. Intensification of systemic treatment is the standard of care. Recently, 68[16_TD$DIFF]Ga prostate-specific membrane antigen positron emission tomography (PSMA-PET) imaging was introduced to identify oligometastatic prostate cancer patients. In this retrospective, exploratory study, we report on the efficacy of PSMA-PET-guided local ablative radiotherapy (aRT) in 15 oligometastatic castrationresistant prostate cancer (CRPC) patients, selected from our prospective institutional database and treated between 2013 and 2016. After multidisciplinary discussion, aRT was delivered with two different schedules. Androgen deprivation therapy remained unchanged. Prostate-specific antigen (PSA) response and time to PSA progression were analysed. For comparison, individual time to PSA progression without aRT was estimated by individual PSA doubling time (PSADT). PSA response was observed in 11 patients (73%). Mean time to PSA progression or last follow-up was 17.9 mo, as opposed to 2.9 mo estimated from the PSADT without aRT (p 12 mo.

Purpose: Retrospective proton dose calculation based on a unique dataset of daily CT images to confirm our prostate patient positioning and immobilization protocol for counterbalancing interfractional motion. Material/Methods: For 12 prostate cancer patients treated to 74GyE with double-scattered lateral or anterior oblique proton fields, daily (27-37, median 32) in-room control CTs (cCT) were acquired. Patient preparation includes a drink protocol, water-filled endorectal balloon insertion, bony anatomy alignment by orthogonal X-Ray imaging, and CT-based verification of prostate location via implanted fiducial marker positions. Fraction doses were calculated on all manually delineated cCTs and accumulated on the planning CT by a deformable image registration (DIR) in RayStation 5.99. DVH parameters of iCTVs, bladder, rectum, femoral heads, bladder and rectal wall were analyzed fractionwise prior and after DIR and values from the cumulated and planned dose distributions were compared. Results: Fig.1 shows the fractionwise assessed DVH parameters for one patient. 275 fraction doses were analyzed in total without finding trends for improving or worsening DVH parameters over treatment time. Intended target coverage, D98%(iCTV)>95%, was missed in 29 cCTs (10.5%) due to suboptimal bladder filling, endorectal balloon position or delineation variation. No overdosage was observed (D2%(iCTV)

Bacteria are able to translocate over surfaces using different types of active and passive motility mechanisms. Sliding is one of the passive types of movement since it is powered by the pushing force of dividing cells and additional factors facilitating the expansion over surfaces. In this review, we describe the sliding proficient bacteria that were previously investigated in details highlighting the sliding facilitating compounds and the regulation of sliding motility. Besides surfactants that reduce the friction between cells and substratum, other compounds including exopolysaccharides, hydrophobic proteins, or glycopeptidolipids where discovered to promote sliding. Therefore, we present the sliding bacteria in three groups depending on the additional compound required for sliding. Despite recent accomplishments in sliding research there are still many open questions about the mechanisms underlying sliding motility and its regulation in diverse bacterial species.

33rd European Photovoltaic Solar Energy Conference and Exhibition; 1088-1092, We study the light induced degradation of bare Cu(In,Ga)Se2 (CIGSe) surfaces by means of time-resolved photoluminescence (TRPL) measurements. Illumination with 1 sun equivalent white light in air causes a severe reduction of the measured minority carrier lifetime. We assign this to strong recombination at the CIGSe surface. No degradation is observed, when the CIGSe layers were exposed to air without illumination or illumination without air. X-ray photoelectron spectroscopy reveals a correlation between illumination time and concentrations of sodium and oxygen on the CIGSe surface. In comparison to non-illuminated absorber layers, solar cells with light exposed absorber layers show an up to 10% reduction of open circuit voltage, fill factor, and efficiency. However, upon light soaking at 85°C of the complete solar cell, a recovery of J-V parameters for devices with illuminated absorbers is achieved. Both effects, the degradation of bare absorbers and the parameter recovery of complete solar cells, are related to a light induced segregation of Na at the surface/interface.

External beam proton therapy (EBPT) treats cancer by delivering small daily fractions of ionizing radiation to a target volume. For prostate cancer, the target undergoes day-to-day geometrical variations in position, volume, and shape. Accurate treatment delivery requires management of daily variations. (Water-filled) Endorectal balloons (ERBs) can be used to limit these variations. However, patterns of variations for patients with ERB have not yet been investigated. We used point set non-rigid registration and statistical modeling to extract and model patterns of geometrical variations for patients with EBRs. Non-rigid registration was optimized to ensure high accuracy.

Objectives: We report the quality of life (QoL) and the impact of dose-volume-parameters on the gastrointestinal (GI) and genitourinary (GU) toxicities in localized/locally advanced prostate cancer patients treated with definitive normo-fractionated (74-76Gy) proton therapy (PT). Methods: Twenty-five patients treated in the context of an approved clinical study (Proto-R-Prostata) were selected. Three intraprostatic fiducial markers were placed for daily position verification. A water-filled endo-rectal balloon was placed prior to each fraction. Toxicity and QoL were collected prospectively. The first were graded according to CTCAE v4, the latter by EORTC C30 and PR25 QoL questionnaires. The organs at risk (OARs; rectal wall, whole rectum, whole bladder, bladder wall, anterior and posterior bladder wall) were re-contoured. The dose (Gy) to 5-95% of the volume of OARs (D5-D95%) was reported in 5 % increments, as the volume (cc) receiving an absolute dose of 5-75 Gy (V5-V75Gy). Correlations between dose-volume-parameters to the OARs and toxicities were modelled by logistic regression. Results: Based on the EORTC-C30, physical functioning and social functioning had a slight worsening after PT, but they improved 3 months after PT, whereas the emotional functioning increased slightly during PT and significantly 3 month after PT (p=0.035). Role functioning showed a statistically significant decrease at the end of PT (p=0.017), but also a subsequent improvement. A correlation was found between GU toxicities during PT and the functional and symptom scale based on the EORTC-PR25 (pain, urinary symptoms and hormonal treatment related symptoms, respectively). Dose-volume parameters V5-V20Gy to the anterior bladder wall and V60–V70Gy to the posterior bladder wall were significantly related to cystitis. V5Gy, V15Gy to the posterior bladder wall and V15-V20Gy to the anterior bladder wall had significant impact on urinary incontinence and urinary frequency, respectively. Conclusions: QoL during/after PT was reported to be good. The estimated dosimetric parameters can be useful to further plan optimization and to find adequate constraints to PT.

The study presents the first series of daily in-room CT images acquired from the first 12 prostate cancer patients after proton-specific immobilization and positioning procedures and followed by actual proton radiotherapy at the University Proton Therapy Dresden. Based on this unique dataset, the actually delivered proton dose is calculated retrospectively for each fraction, analyzed for inter-fractional variability and accumulated to a total dose for comparison with the treatment plan. Introduction: The steep dose gradients and small number of treatment fields require reproducible anatomical geometry and positioning in proton therapy to secure an accurate dose delivery. Prostate cancer is known to be subjected to inter-fractional variation due to day-to-day variation in bowel, rectum and bladder filling. Adequate positioning and treatment protocols were investigated prior the start of proton therapy to prostate cancer patients in our institute [1]. The presented study analyzes the suitability of these protocols by means of a retrospective evaluation of actually delivered proton dose in comparison to the treatment plan. Material and Methods: Inter-fractional motion in prostate cancer patients treated at the University Proton Therapy Dresden is counteracted by water-filled endorectal ballon and bladder filling protocol. Patient positioning is based on bony anatomy match utilizing orthogonal X-Ray imaging. Stability of implanted fiducial markers and anatomy were checked in the first 12 patients by daily scheduled in-room control CT (cCT) after immobilization and positioning. Typical plans (XiO, Elekta Instruments AB, Stockholm) for 74 Gy(RBE) sequential boost treatment in 37 fractions include two series of opposing lateral double-scattered proton beams covering the respective internal clinical target volume (iCTV). In RayStation 4.6 (RaySearch Laboritories AB, Stockholm), all cCTs are delineated retrospectively and the treatment plans were recalculated on the planning CT and the registered cCTs. All fraction doses were accumulated on the planning CT after deformable registration. Parameters of delivered dose to iCTV (D98% > 95%, D2% < 107%), bladder (V75Gy < 15%, V70Gy < 25%, V65Gy < 30%), rectum (V70Gy < 10%, V50Gy < 40%) and femoral heads (V50Gy < 5%) are compared to those in the treatment plan. Intra-therapy variation is represented in DVH bands. Result: Due to CT maintenance, physician’s decision and initial workflow optimization, the median number of actually acquired cCTs within 37 fractions was 32 (range: 27-37). Seven patients received the sequential boost series prior the nominal series due to concerns that anatomy might change noticeably during six weeks of therapy and then margin concepts might be insufficient. One patient received a nominal plan of 37 fractions to an iCTV excluding seminal vesicles. First intra-therapy variability analysis in 5 patients showed no time-dependent parameter drift and revealed strongest variability for bladder dose. In some fractions, iCTV coverage (D98%) and rectum V70Gy was missed. An illustration of the dosimetric evaluation is shown for an exemplary patient in Figure 1. No alarming differences (cp. Table 1) were observed between planned and retrospectively accumulated dose for all 12 patients: iCTV constraints were met, except for one patient (D98% = 94.4% in non-boosted iCTV). Considered bladder and femoral head dosimetric values were below the limits. Rectum V70Gy was slightly exceeded (

Purpose: Retrospective calculation of the delivered proton dose in prostate cancer patients based on a unique dataset of daily CT images. Methods: Inter-fractional motion in prostate cancer patients treated at our proton facility is counteracted by water-filled endorectal ballon and bladder filling protocol. Typical plans (XiO, Elekta Instruments AB, Stockholm) for 74 Gy(RBE) sequential boost treatment in 37 fractions include two series of opposing lateral double-scattered proton beams covering the respective iCTV. Stability of fiducial markers and anatomy were checked in 12 patients by daily scheduled in-room control CT (cCT) after immobilization and positioning according to bony anatomy utilizing orthogonal X-ray. In RayStation 4.6 (RaySearch Laboritories AB, Stockholm), all cCTs are delineated retrospectively and the treatment plans were recalculated on the planning CT and the registered cCTs. All fraction doses were accumulated on the planning CT after deformable registration. Parameters of delivered dose to iCTV (D98%>95%, D2%75Gy70Gy65Gy70Gy50Gy50Gy98%=94.6% in non-boosted iCTV). Considered bladder and femoral head values were below the limits. Rectum V70Gy was slightly exceeded (98%) and rectum V70Gy was missed. Conclusion: Double scattered proton plans are accurately delivered to prostate cancer patients due to fractionation effects and the applied precise positioning and immobilization protocols. As a result of rare interventions after daily 3D imaging of the first 12 patients, in-room CT frequency for prostate cancer patients was reduced. The presented study supports this decision.

Hintergrund: In einer früheren Planungsstudie an Patienten mit NSCLC wurde untersucht, ob mittels einer FDG-PET/CT während einer fraktionierten Strahlentherapie eine Verkleinerung des Zielvolumens und damit eine Dosiseskalation der Dosis über 66 Gy möglich ist. Es zeigte sich, dass die Tumorvolumina während der Therapie abnahmen. Doch bei 6/10 Patienten war eine Therapie mit einer Dosis von 78 Gy selbst dann nicht möglich, wenn das Bestrahlungsvolumen nach 66 Gy auf die Tumorausdehnung des PET/CT 5-6 Wochen nach Beginn der RT (PET/CT w5-6) reduziert wurde (Radiother Oncol, in press). In der vorliegenden Untersuchung soll geprüft werden, ob eine optimierte inverse Therapieplanung für eine intensitätsmodulierte Strahlentherapie (IMRT) zu einer Reduktion der Normalgewebsbelastung führt und in diesen Fällen eine Dosiseskalation bis 78 Gy ermöglicht. Patienten und Methodik: 10 Patienten mit einem NSCLC im Stadium III wurden in Bestrahlungsposition vor und während einer fraktionierten Strahlentherapie (66 Gy in 33 Fraktionen) mittels FDG-PET/CT (Biograph 16) untersucht. Die Konturierung des GTV in PET und CT erfolgte durch den Strahlentherapeuten (GC) und wurde durch einen Radiologen (NA) bzw. Nuklearmediziner (KZ) überprüft. Das PTV ergab sich durch einen Sicherheitsabstand von 1,5 cm um das GTV-PET/CT ohne prophylaktische Bestrahlung des Mediastinums. Die Strahlentherapie wurde mit einer Zieldosis von 78 Gy (Bestrahlung auf das Ausgangsvolumen oder Feldverkleinerung ab 66 Gy auf PTV-PET/CT w5-6) geplant (Pinnacle, Phillips). Die Vorgaben für die Normalgewebsbelastung waren: Myelon max. 45 Gy , mittlere Lungendosis (MLD) £20 Gy, Lungenvolumen 20 Gy (V20) £37%, Ösophagusvolumen 60 Gy (V60) £30 %, Herzbelastung 1/3 £60 Gy, 2/3 £50 Gy und 3/3 £40 Gy. Für 6/10 Patienten, bei denen diese Vorgaben mit 3D-konformaler Planung nicht eingehalten werden konnten (5/10 Pat. V60 >30%; 3/10 Pat. V20>37% bzw. MLD>20 Gy), wurde eine IMRT geplant. Hierbei sollten die Minima im CTV (GTV+7 mm) ³95% sein, eine geringe Unterdosierung im PTV wurde akzeptiert. Ergebnisse: Eine Reduktion der Belastung kritischer Organe (Lunge, Ösophagus) konnte bei 5 der 6 Patienten durch eine IMRT-Planung erreicht werden. Allerdings führte nur in 2 Fällen die IMRT zu einer Unterschreitung der vorgegebenen Dosisgrenzen und ermöglichte damit eine Dosiseskalation bis 78 Gy. Eine Reduktion des Bestrahlungsvolumens nach 66 Gy brachte dabei keinen entscheidenden Vorteil. Bei einem Patienten war eine inverse Planung mit einer akzeptablen Dosisverteilung nicht möglich. In 5/6 Fällen führte die IMRT-Planung zu einer inhomogeneren Erfassung des PTV und CTV mit geringen Minima im PTV. Schlussfolgerung: In ausgewählten Fällen kann für Patienten mit NSCLC, für die mittels konventioneller Planung das Risiko der Normalgewebstoxizität zu hoch ist, durch eine IMRT-Planung eine Dosiseskalation bis 78 Gy möglich werden. Gefördert durch das BMBF (03ZIK042)

BACKGROUND AND PURPOSE: To test a new contrast-specific sonography imaging method that offers visualization of the intracranial vasculature in a manner similar to that seen on angiography. MATERIALS AND METHODS: Thirty patients (35 sonography studies total) were included in the study after they provided written informed consent. The patients were scanned through the temporal bone window from both sides after intravenous injection of an ultrasound contrast agent (UCA; perflexane lipid microspheres [Imagent]). The goal was to visualize the intracranial arteries, including the middle (M1–M3), anterior (A1 and A2), and posterior (P1–P3) cerebral arteries, using an axial scanning plane. The studies were performed using a contrast-specific imaging mode, based on a phase inversion technique (transcranial ultrasound angiography [tUSA]). For sensitivity, the results were compared with x-ray angiography as the “gold standard.” For interobserver reliability, 24 of 35 sonography studies were evaluated by 2 physicians with little training in transcranial sonography and by a seasoned sonographer. RESULTS: The sensitivity of tUSA ranged between 0.778 (95% confidence interval [CI] of 0.577–0.914) and 0.963 (95% CI of 0.810–0.999). The sensitivities were similar among physicians with little training in transcranial sonography and the seasoned sonographer, indicating high inter-rater reliability. Overall, tUSA provided high anatomic resolution and vascular delineation even of small vessels in the millimeter range. At peak intensity, no UCA-related artifacts were observed. CONCLUSION: tUSA provides images of the intracranial arteries similar to those obtained at angiography with high anatomic resolution, reasonable sensitivity, and interobserver reliability.

Aims: To detect a reduction in disease volume during radical radiotherapy for non-small cell lung cancer (NSCLC) using PET-CT and to determine whether this would facilitate dose escalation. Methods: Ten patients with localised inoperable NSCLC were prospectively enrolled. Each received conformally planned radiotherapy to a dose of 66Gy/33# over 6.5 weeks using 6-15MV photons and prescribed to the 100% isodose. PET-CT imaging was performed just prior to and following 50 or 60Gy. Target volume definition was performed by one senior radiation oncologist with the help of a senior radiologist and nuclear medicine physician. For all patients and at both time points CT and PET-delineated gross tumour volumes were generated (GTVCT, GTVPET). A composite GTV was then created (GTVCT+PET) and 15mm added in all planes to form the planning target volume (PTV). No correction for organ movement was incorporated and no elective nodal irradiation performed. Each of the different volumes were compared before and after 50-60 Gray. Two plans were then created and compared: 78Gy delivered to the initial PTV and 66Gy to the initial PTV with a 12Gy boost to the post 50/60Gy PTV. Results: All patients (mean age 64 years) had stage III disease (4 IIIA and 6 IIIB). There were 4 squamous cell and 6 adeno-carcinomas. After 50/60 Gray the GTVCT, GTVPET, GTVCT+PET and PTV reduced by a mean of 22%, 43%, 30% and 22% respectively. The delivery of 78 Gray to the initial PTV could have been safely achieved in 4/10 patients. Of these delivering treatment in two phases would have substantially spared normal tissue in 2 patients. In the remaining 6 patients, delivering 78 Gray to the initial PTV would have exceeded normal tissue constraints and no benefit was seen when planned in 2 phases. Conclusions: The PTV, consequent on changes seen on PET-CT, reduces during a course of radical radiotherapy for NSCLC. Such a reduction permits dose escalation in a subset of patients and may lead to improved therapeutic outcomes.