Computed tomography imaging parameters for inhomogeneity correction in radiation treatment planning

Modern treatment planning systems provide accurate dosimetry in heterogeneous media (such as a patient' body) with the help of tissue characterization based on computed tomography (CT) number. However, CT number depends on the type of scanner, tube voltage, field of view (FOV), reconstruction algorithm including artifact reduction and processing filters. The impact of these parameters on CT to electron density (ED) conversion had been subject of investigation for treatment planning in various clinical situations. This is usually performed with a tissue characterization phantom with various density plugs acquired with different tube voltages (kilovoltage peak), FOV reconstruction and different scanners to generate CT number to ED tables. This article provides an overview of inhomogeneity correction in the context of CT scanning and a new evaluation tool, difference volume dose-volume histogram (DVH), dV-DVH. It has been concluded that scanner and CT parameters are important for tissue characterizations, but changes in ED are minimal and only pronounced for higher density materials. For lungs, changes in CT number are minimal among scanners and CT parameters. Dosimetric differences for lung and prostate cases are usually insignificant (<2%) in three-dimensional conformal radiation therapy and < 5% for intensity-modulated radiation therapy (IMRT) with CT parameters. It could be concluded that CT number variability is dependent on acquisition parameters, but its dosimetric impact is pronounced only in high-density media and possibly in IMRT. In view of such small dosimetric changes in low-density medium, the acquisition of additional CT data for financially difficult clinics and countries may not be warranted

Acute toxicity in comprehensive head and neck radiation for nasopharynx and paranasal sinus cancers: cohort comparison of 3D conformal proton therapy and intensity modulated radiation therapy.

Background: To evaluate acute toxicity endpoints in a cohort of patients receiving head and neck radiation with proton therapy or intensity modulated radiation therapy (IMRT). Methods: Forty patients received comprehensive head and neck radiation including bilateral cervical nodal radiation, given with or without chemotherapy, for tumors of the nasopharynx, nasal cavity or paranasal sinuses, any T stage, N0-2. Fourteen received comprehensive treatment with proton therapy, and 26 were treated with IMRT, either comprehensively or matched to proton therapy delivered to the primary tumor site. Toxicity endpoints assessed included g-tube dependence at the completion of radiation and at 3 months after radiation, opioid pain medication requirement compared to pretreatment normalized as equivalent morphine dose (EMD) at completion of treatment, and at 1 and 3 months after radiation. Results: In a multivariable model including confounding variables of concurrent chemotherapy and involved nodal disease, comprehensive head and neck radiation therapy using proton therapy was associated with a lower opioid pain requirement at the completion of radiation and a lower rate of gastrostomy tube dependence by the completion of radiation therapy and at 3 months after radiation compared to IMRT. Proton therapy was associated with statistically significant lower mean doses to the oral cavity, esophagus, larynx, and parotid glands. In subgroup analysis of 32 patients receiving concurrent chemotherapy, there was a statistically significant correlation with a greater opioid pain medication requirement at the completion of radiation and both increasing mean dose to the oral cavity and to the esophagus. Conclusions: Proton therapy was associated with significantly reduced radiation dose to assessed non-target normal tissues and a reduced rate of gastrostomy tube dependence and opioid pain medication requirements. This warrants further evaluation in larger studies, ideally with patient-reported toxicity outcomes and quality of life endpoints

Impact of proton beam availability on patient treatment schedule in radiation oncology

Proton beam therapy offers unique physical properties with potential for reduced toxicity and better patient care. There is an increased interest in radiation oncology centers to acquire proton therapy capabilities. The operation of a proton treatment center is quite different than a photon-based clinic because of the more complex technology involved, as well as the single proton beam source serving multiple treatment rooms with no backup source available. There is limited published data which investigates metrics that can be used to determine the performance of a proton facility. The purpose of this study is to evaluate performance metrics of Indiana University Cyclotron Operations (IUCO), including availability, mean time between failures, and mean time to repair, and to determine how changes in these metrics impact patient treatments. We utilized a computerized maintenance management system to log all downtime occurrences and servicing operations for the facility. These data were then used to calculate the availability as well as the mean time between failures and mean time to repair. Impact on patient treatments was determined by analyzing delayed and missed treatments, which were recorded in an electronic medical record and database maintained by the therapists. The availability of the IUCO proton beam has been increasing since beginning of operation in 2003 and averaged 96.9% for 2009 through 2011. The mean time between failures and mean time to repair were also determined and correlated with improvements in the maintenance and operating procedures of the facility, as well as environmental factors. It was found that events less than 15 minutes in duration have minimal impact on treatment delays, while events lasting longer than one hour may result in missed treatments. The availability of the proton beam was more closely correlated with delayed than with missed treatments, demonstrating the utility and limitations of the availability metric. In conclusion, we suggest that the availability metric and other performance parameters, such as the mean time between failures and the mean time to repair, should be used in combination with downtime impact on patient treatments in order to adequately evaluate the operational success of a proton therapy facility

The Expectation Monad in Quantum Foundations

The expectation monad is introduced abstractly via two composable adjunctions, but concretely captures measures. It turns out to sit in between known monads: on the one hand the distribution and ultrafilter monad, and on the other hand the continuation monad. This expectation monad is used in two probabilistic analogues of fundamental results of Manes and Gelfand for the ultrafilter monad: algebras of the expectation monad are convex compact Hausdorff spaces, and are dually equivalent to so-called Banach effect algebras. These structures capture states and effects in quantum foundations, and also the duality between them. Moreover, the approach leads to a new re-formulation of Gleason's theorem, expressing that effects on a Hilbert space are free effect modules on projections, obtained via tensoring with the unit interval.Comment: In Proceedings QPL 2011, arXiv:1210.029

A model of population dynamics of TB in a prison system and application to South Africa

BACKGROUND: Tuberculosis (TB) continues to spread in South African prisons in particular, as prisons are over-capacitated and have poor ventilation. The awaiting trial detainees are not screened on admission and are at high risk of getting infected with TB. RESULTS: We propose a compartmental model to describe the population dynamics of TB disease in prisons. Our model considers the inflow of susceptible, exposed and TB infectives into the prison population. Removal of individuals out of the prison population can be either by death or by being released from prison, as compared to a general population in which removal is only by death. We describe conditions, including non-inflow of infectives into the prison, which will ensure that TB can be eradicated from the prison population. The model is calibrated for the South African prison system, by using data in existing literature. The model can be used to make quantitative projections of TB prevalence and to measure the effect of interventions. Illustrative simulations in this regard are presented. The model can be used for other prison populations too, if data is available to calculate the model parameters. CONCLUSIONS: Various simulations generated with our model serve to illustrate how it can be utilized in making future projections of the levels of prevalence of TB, and to quantify the effect of interventions such as screening, treatment or reduction of transmission parameter values through improved living conditions for inmates. This makes it particularly useful as there are various targets set by the World Health Organization and by governments, for reduction of TB prevalence and ultimately its eradication. Towards eradication of TB from a prison system, the theorem on global stability of the disease-free state is a useful indicator

Tumor-Stromal Interactions Influence Radiation Sensitivity in Epithelial- versus Mesenchymal-Like Prostate Cancer Cells

HS-27a human bone stromal cells, in 2D or 3D coultures, induced cellular plasticity in human prostate cancer ARCaPE and ARCaPM cells in an EMT model. Cocultured ARCaPE or ARCaPM cells with HS-27a, developed increased colony forming capacity and growth advantage, with ARCaPE exhibiting the most significant increases in presence of bone or prostate stroma cells. Prostate (Pt-N or Pt-C) or bone (HS-27a) stromal cells induced significant resistance to radiation treatment in ARCaPE cells compared to ARCaPM cells. However pretreatment with anti-E-cadherin antibody (SHEP8-7) or anti-alpha v integrin blocking antibody (CNT095) significantly decreased stromal cell-induced radiation resistance in both ARCaPE- and ARCaPM-cocultured cells. Taken together the data suggest that mesenchymal-like cancer cells reverting to epithelial-like cells in the bone microenvironment through interaction with bone marrow stromal cells and reexpress E-cadherin. These cell adhesion molecules such as E-cadherin and integrin alpha v in cancer cells induce cell survival signals and mediate resistance to cancer treatments such as radiation

Ability of the National Surgical Quality Improvement Program Risk Calculator to Predict Complications Following Total Laryngectomy

Importance The accuracy of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) risk calculator has been assessed in multiple surgical subspecialties; however, there have been no publications doing the same in the head and neck surgery literature. Objective To evaluate the accuracy of the calculator’s predictions in a single institution’s total laryngectomy (TL) population. Design, Setting, and Participants Total laryngectomies performed between 2013 and 2014 at a tertiary referral academic center were evaluated using the risk calculator. Predicted 30-day outcomes were compared with observed outcomes for return to operating room, surgical site infection, postoperative pneumonia, length of stay, and venous thromboembolism. Main Outcomes and Measures Comparison of the NSQIP risk calculator’s predicted postoperative complication rates and length of stay to what occurred in this patient cohort using percent error, Brier scores, area under the receiver operating characteristic curve, and Pearson correlation analysis. Results Of 49 patients undergoing TL, the mean (SD) age at operation was 59 (9.3) years, with 67% male. The risk calculator had limited efficacy predicting perioperative complications in this group of patients undergoing TL with or without free tissue reconstruction or preoperative chemoradiation or radiation therapy with a few exceptions. The calculator overestimated the occurrence of pneumonia by 165%, but underestimated surgical site infection by 7%, return to operating room by 24%, and length of stay by 13%. The calculator had good sensitivity and specificity of predicting surgical site infection for patients undergoing TL with free flap reconstruction (area under the curve, 0.83). For all other subgroups, however, the calculator had poor sensitivity and specificity for predicting complications. Conclusions and Relevance The risk calculator has limited utility for predicting perioperative complications in patients undergoing TL. This is likely due to the complexity of the treatment of patients with head and neck cancer and factors not taken into account when calculating a patient’s risk

Ascaroside Expression in Caenorhabditis elegans Is Strongly Dependent on Diet and Developmental Stage

Background: The ascarosides form a family of small molecules that have been isolated from cultures of the nematode Caenorhabditis elegans. They are often referred to as “dauer pheromones” because most of them induce formation of long-lived and highly stress resistant dauer larvae. More recent studies have shown that ascarosides serve additional functions as social signals and mating pheromones. Thus, ascarosides have multiple functions. Until now, it has been generally assumed that ascarosides are constitutively expressed during nematode development. Methodology/Principal Findings: Cultures of C. elegans were developmentally synchronized on controlled diets. Ascarosides released into the media, as well as stored internally, were quantified by LC/MS. We found that ascaroside biosynthesis and release were strongly dependent on developmental stage and diet. The male attracting pheromone was verified to be a blend of at least four ascarosides, and peak production of the two most potent mating pheromone components, ascr#3 and asc#8 immediately preceded or coincided with the temporal window for mating. The concentration of ascr#2 increased under starvation conditions and peaked during dauer formation, strongly supporting ascr#2 as the main population density signal (dauer pheromone). After dauer formation, ascaroside production largely ceased and dauer larvae did not release any ascarosides. These findings show that both total ascaroside production and the relative proportions of individual ascarosides strongly correlate with these compounds' stage-specific biological functions. Conclusions/Significance: Ascaroside expression changes with development and environmental conditions. This is consistent with multiple functions of these signaling molecules. Knowledge of such differential regulation will make it possible to associate ascaroside production to gene expression profiles (transcript, protein or enzyme activity) and help to determine genetic pathways that control ascaroside biosynthesis. In conjunction with findings from previous studies, our results show that the pheromone system of C. elegans mimics that of insects in many ways, suggesting that pheromone signaling in C. elegans may exhibit functional homology also at the sensory level. In addition, our results provide a strong foundation for future behavioral modeling studies