Towards offline PET monitoring of proton therapy at MedAustron

The characteristic depth-dose profile of protons traveling through material is the main advantage of proton therapy over conventional radiotherapy with photons or electrons. However, uncertainties regarding the range of the protons in human tissue prevent to exploit the full potential of proton therapy. Therefore, a non-invasive in-vivo dose monitoring is desired. At the ion beam center MedAustron in Wiener Neustadt/Austria, patient treatment with proton beams started in December 2016. A PET/CT is available in close vicinity of the treatment rooms, exclusively dedicated to offline PET monitoring directly after the therapeutic irradiation. Preparations for a patient study include workflow tests under realistic clinical conditions using two different phantoms, irradiated with protons prior to the scan in the PET/CT. GATE simulations of the C-11 production are used as basis for the prediction of the PET measurement. We present results from the workflow tests in comparison with simulation results, and by this, we demonstrate the applicability of the PET monitoring at the MedAustron facility.     

Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives

Biliary tract cancers (BTCs) are a group of invasive neoplasms, with increasing incidence and dismal prognosis. In advanced disease, the standard of care is represented by first-line chemotherapy with cisplatin and gemcitabine. In subsequent lines, no clear recommendations are currently available, highlighting the need for novel therapeutic approaches.The PI3K/AKT/mTOR pathway is a core regulator of cell metabolism, growth and survival, and is involved in BTCs carcinogenesis and progression. Mutations, gene copy number alterations and aberrant protein phosphorylation of PI3K, AKT, mTOR and PTEN have been thoroughly described in BTCs and correlate with poor survival outcomes.Several pre-clinical evidences state the efficacy of PI3K/AKT/mTOR pathway inhibitors in BTCs, both in vitro and in vivo. In the clinical setting, initial studies with rapamycin analogs have shown interesting activity with an acceptable toxicity profile. Novel strategies evaluating AKT and PI3K inhibitors have risen serious safety concerns, pointing out the need for improved patient selection and increased target specificity for the clinical development of these agents, both alone and in combination with chemotherapy.This review extensively describes the role of the PI3K/AKT/mTOR pathway in BTCs and examines the rationale of its targeting in these tumors, with particular focus on clinical activity, toxicities and perspectives on further development of PI3K/AKT/mTOR pathway inhibitors.     

An Interactive RADIANCE Toolkit for Customizable CT Dose Monitoring and Reporting

The need for tools to monitor imaging-related radiation has grown dramatically in recent years. RADIANCE, a freely available open-source dose-monitoring tool, was developed in response to the need for an informatics solution in this realm. A number of open-source as well as commercial solutions have since been developed to enable radiology practices to monitor radiation dose parameters for modalities ranging from computed tomography to radiography to fluoroscopy. However, it is not sufficient to simply collect this data; it is equally important to be able to review it in the appropriate context. Most of the currently available dose-monitoring solutions have some type of reporting capability, such as a real-time dashboard or a static report. Previous versions of RADIANCE have included a real-time dashboard with pre-set screens that plot effective dose estimates according to different criteria, as well as monthly scorecards to summarize dose estimates for individuals within a radiology practice. In this work, we present the RADIANCE toolkit, a customizable reporting solution that allows users to generate reports of interest to them, summarizing a variety of metrics that can be grouped according to useful parameters. The output of the toolkit can be used for real-time dose monitoring or scheduled reporting, such as to a quality assurance committee. Making dose parameter data more accessible and more meaningful to the user promotes dose reduction efforts such as regular protocol review and optimization, and ultimately improves patient care by decreasing unnecessary radiation exposure.     

Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment

1,4-Dioxane is found in consumer products and is used as a solvent in manufacturing. Studies in rodents show liver tumors to be consistently reported after chronic oral exposure. However, there were differences in the reporting of non-neoplastic lesions in the livers of rats and mice. In order to clarify these differences, a reread of mouse liver slides from the 1978 NCI bioassay on 1,4-dioxane in drinking water was conducted. This reread clearly identified dose-related non-neoplastic changes in the liver; specifically, a dose-related increase in the hypertrophic response of hepatocytes, followed by necrosis, inflammation and hyperplastic hepatocellular foci. 1,4-Dioxane does not cause point mutations, DNA repair, or initiation. However, it appears to promote tumors and stimulate DNA synthesis. Using EPA Guidelines (2005), the weight of the evidence suggests that 1,4-dioxane causes liver tumors in rats and mice through cytotoxicity followed by regenerative hyperplasia. Specific key events in this mode of action are identified. A Reference Dose (RfD) of 0.05 mg/kg day is proposed to protect against regenerative liver hyperplasia based on a benchmark dose (BMD) approach. Based on this RfD, a maximum contaminant level goal of 350 μg/L is proposed using a default relative source contribution for water of 20%.     

Glutathione S-transferase A1 (GSTA1) release,an early indicator of acute hepatic injury in mice

Three acute hepatic injury models (a CCl₄-induced model, APAP-induced model and ethanol-induced model) in mice were used to study the importance of GSTA1 in acute hepatic injury by comparison with a standard enzyme marker, alanine aminotransferase (ALT). GSTA1 release was demonstrated to be an earlier and more sensitive indicator of hepatotoxicity than was ALT. Significant increases in GSTA1 were detected at 2 h after CCl₄ exposure, while ALT was undetected at this time. GSTA1 was also a more sensitive indicator of hepatotoxicity than ALT after 6 h. In the APAP and ethanol models, GSTA1 was markedly increased earlier than ALT, at 2 h post exposure. The release of GSTA1 was significantly increased at a dose of 12.5 mg/kg (CCl₄ model), 100 mg/kg (APAP model) and 10 ml/kg (ethanol model), the lowest exposure concentration for each model. In contrast, AST release was not statistically significant. These results suggest that GSTA1 can be detected at low concentrations during the early stages of acute hepatic injury and that GSTA1 is a more sensitive and more accurate indicator than ALT.     

Évaluation et choix des protocoles d’imagerie sur le système de tomographie conique de basse énergie XVI® d’Elekta

PurposeThis work proposes an evaluation of the Elekta XVI^® kilovoltage cone-beam computed tomography imaging system. The average dose delivered for each acquisition protocol proposed by default by the manufacturer was measured with several detectors and compared to theoretical dose values given by Elekta. At the same time, an evaluation of image quality for pelvic protocols correlated to dose measurements in homogeneous and heterogeneous mediums allowed to optimize the use of the XVI^® system.Materials and methodsThe dose was measured for each acquisition protocol (varying filters, FOV and collimations) with four detectors (CT pencil ion chamber, 0.3 and 0.125 cm³ cylindrical ion chambers, radiothermoluminescent dosimeters) in a CTDI phantom. The dose evaluation in a heterogeneous medium was performed in an experimental anthropomorphic phantom simulating a male pelvis. Image quality was assessed with a Catphan^® 600 phantom.ResultsThe average dose measured in a homogeneous medium was about 17 mGy and 25 mGy per acquisition for Pelvis and Prostate protocols and about 17 mGy and 1 mGy for Lung and Head protocols. The study performed with different detectors showed that doses obtained were of the same order of magnitude (± 10%) and agreed with those supplied by the manufacturer. The evaluation of image quality correlated to the average dose measured allowed to optimize the use of XVI^® acquisition protocols. Measurement results in a heterogeneous medium showed a dose decrease by a factor 1.5 for bone and by a factor 2 for titanium.ConclusionThe study showed that theoretical values proposed by the manufacturer could be used to estimate the average dose delivered to the patient by the kV-CBCT imaging system. The analysis of all the results led to the implementation of a procedure allowing to optimize and account for the dose delivered to the patient by the CBCT imaging system and to report it in the patient folder.     

Consumer Participation in Identifying Research and Development Priorities for Power Wheelchair Input Devices and Controllers

A focus group comprised of persons who use power wheelchairs and professionals working in the field were asked to participate in a brainstorming session to determine priorities for the development and application of power mobility input devices and control concepts. The group consensus was that durability and reliability are the most important criteria. Essentially, the expectation is that a power wheelchair must work everyday in the way a person needs it and wants it. At the same time, there is a desire to enhance and advance the features of input devices and control systems. Many would say these changes constitute designing “smarter” power wheelchairs, such as systems that can independently detect obstacles and can provide users with more feedback. This paper presents the rationale behind forming this focus group and details of the results of a brainstorming session where ideas were generated and prioritized. The five most important issues as determined by the group are discussed in depth.     

The Effect of Dose Grid Resolution on Dose Volume Histograms for Slender Organs at Risk during Pelvic Intensity-modulated Radiotherapy

PurposeThere are enduring uncertainties regarding the optimal dose grid resolution for use with pelvic intensity-modulated radiotherapy (IMRT) plans in which the adjacent organs at risk are slender and transect the field edge. Therefore, this study evaluated the effect of dose grid resolution on bladder wall dose-volume histogram (DVH) calculations for prostate IMRT plans.Materials and MethodsThe planning computed tomography scans and clinical plans from 15 prostate cancer patients were included in this analysis. For each study computed tomography, the entire inner and outer bladder surfaces were delineated. Nine versions of the clinical plan were created, varying interval between the dose grid calculation points uniformly in three dimensions, whereas all other plan parameters were kept constant. The dose grid increments tested were 1–10 mm. The plans were recalculated and the bladder wall DVH compared against the study benchmark (1 mm grid).ResultsAll the dose grid increments evaluated resulted in a systematic overestimation of the bladder wall volume receiving low doses and an underestimation of the volume receiving high doses. Grid increments <2.5 mm all resulted in mean volume differences less than 1 cm³ across the whole DVH. Grid increments >5.0 mm resulted in mean volume differences greater than 2 cm³. Individual patient analysis revealed that only the 1.5 mm increment resulted in maximum volume differences ≤1 cm³ for every patient across the full length of the DVH curve. Bladder wall thickness ranged from 1.7 to 4.4 mm and displayed no correlation with the magnitude of the dose grid effect.ConclusionsFor an accurate DVH calculation for bladder wall during IMRT planning for prostate cancer, a 1.5 mm dose grid increment is recommended. This finding was unaffected by a normal range in bladder wall thickness. It is suggested that the application of any new treatment planning technique or organ delineation method be accompanied with an evaluation of optimal dose grid resolution.     

High dose rate brachytherapy with customized applicators for malignant facial skin lesions

PurposeBrachytherapy is a well-known treatment in the management of skin tumors. For facial or scalp lesions, applicators have been developed to deliver non-invasive treatment. We present cases treated with customized applicators with high dose rate system.Material and methodsPatients with poor performance status treated for malignant skin lesions of the scalp or the facial skin between 2011 and 2014 were studied. Afterloading devices were chosen between Freiburg^® Flap, silicone-mold or wax applicators. The clinical target volume (CTV) was created by adding margins to lesions (10 mm to 20 mm). The dose schedules were 25 Gy in five fractions for postoperative lesions, 30 Gy in six fractions for exclusive treatments and a single session of 8 Gy could be considered for palliative treatments.ResultsIn 30 months, 11 patients received a treatment for a total of 12 lesions. The median age was 80 years. The median follow-up was 17 months and the 2-year local control rate was 91%. The mean CTV surface was 41.1 cm² with a mean thickness of 6.1 mm. We conceived three wax applicators, used our silicone-mold eight times and the Freiburg^® Flap one time. We observed only low-grade radiodermitis (grade I: 50%, grade II: 33%), and no high-grade skin toxicity.ConclusionHigh dose rate brachytherapy with customized applicators for facial skin and scalp lesions is efficient and safe. It is a good modality to treat complex lesions in patients unfit for invasive treatment.