A comparison of dose-response characteristics of four NTCP models using outcomes of radiation-induced optic neuropathy and retinopathy

<p>Abstract</p> <p>Background</p> <p>Biological models are used to relate the outcome of radiation therapy to dose distribution. As use of biological models in treatment planning expands, uncertainties associated with the use of specific models for predicting outcomes should be understood and quantified. In particular, the question to what extent model predictions are data-driven or dependent on the choice of the model has to be explored.</p> <p>Methods</p> <p>Four dose-response models--logistic, log-logistic, Poisson-based and probit--were tested for their ability and consistency in describing dose-response data for radiation-induced optic neuropathy (RION) and retinopathy (RIRP). Dose to the optic nerves was specified as the minimum dose, <it>D_min</it>, received by any segment of the organ to which the damage was diagnosed by ophthalmologic evaluation. For retinopathy, the dose to the retina was specified as the highest isodose covering at least 1/3 of the retinal surface (<it>D_33%</it>) that geometrically covered the observed retinal damage. Data on both complications were modeled separately for patients treated once daily and twice daily. Model parameters <it>D₅₀</it>and <it>γ </it>and corresponding confidence intervals were obtained using maximum-likelihood method.</p> <p>Results</p> <p>Model parameters were reasonably consistent for RION data for patients treated once daily, <it>D₅₀</it>ranging from 94.2 to 104.7 Gy and <it>γ </it>from 0.88 to 1.41. Similar consistency was seen for RIRP data which span a broad range of complication incidence, with <it>D₅₀</it>from 72.2 to 75.0 Gy and <it>γ </it>from 1.51 to 2.16 for patients treated twice daily; 72.2-74.0 Gy and 0.84-1.20 for patients treated once daily. However, large variations were observed for RION in patients treated twice daily, D₅₀from 96.3 to 125.2 Gy and <it>γ </it>from 0.80 to 1.56. Complication incidence in this dataset in any dose group did not exceed 20%.</p> <p>Conclusions</p> <p>For the considered data sets, the log-logistic model tends to lead to larger <it>D₅₀</it>and lower <it>γ </it>compared to other models for all datasets. Statements regarding normal tissue radiosensitivity and steepness of dose-response, based on model parameters, should be made with caution as the latter are not only model-dependent but also sensitive to the range of complication incidence exhibited by clinical data.</p

Dosimetric comparison study between intensity modulated radiation therapy and three-dimensional conformal proton therapy for pelvic bone marrow sparing in the treatment of cervical cancer.

The objective was to compare intensity-modulated radiation therapy (IMRT) with 3D conformal proton therapy (3DCPT) in the treatment of cervical cancer. In particular, each technique's ability to spare pelvic bone marrow (PBM) was of primary interest in this study. A total of six cervical cancer patients (3 postoperative and 3 intact) were planned and analyzed. All plans had uniform 1.0 cm CTV-PTV margin and satisfied the 95% PTV with 100% isodose (prescription dose = 45 Gy) coverage. Dose-volume histograms (DVH) were analyzed for comparison. The overall PTV and PBM volumes were 1035.9 ± 192.2 cc and 1151.4 ± 198.3 cc, respectively. In terms of PTV dose conformity index (DCI) and dose homogeneity index (DHI), 3DCPT was slightly superior to IMRT with 1.00 ± 0.001, 1.01 ± 0.02, and 1.10 ± 0.02, 1.13 ± 0.01, respectively. In addition, 3DCPT demonstrated superiority in reducing lower doses (i.e., V30 or less) to PBM, small bowel and bladder. Particularly in PBM, average V10 and V20 reductions of 10.8% and 7.4% (p = 0.001 and 0.04), respectively, were observed. However, in the higher dose range, IMRT provided better sparing (&gt; V30). For example, in small bowel and PBM, average reductions in V45 of 4.9% and 10.0% (p = 0.048 and 0.008), respectively, were observed. Due to its physical characteristics such as low entrance dose, spread-out Bragg peak and finite particle range of protons, 3DCPT illustrated superior target coverage uniformity and sparing of the lower doses in PBM and other organs. Further studies are, however, needed to fully exploit the benefits of protons for general use in cervical cancer

Predicting Persistent Opioid Use, Abuse, and Toxicity Among Cancer Survivors.

BackgroundAlthough opioids play a critical role in the management of cancer pain, the ongoing opioid epidemic has raised concerns regarding their persistent use and abuse. We lack data-driven tools in oncology to understand the risk of adverse opioid-related outcomes. This project seeks to identify clinical risk factors and create a risk score to help identify patients at risk of persistent opioid use and abuse.MethodsWithin a cohort of 106 732 military veteran cancer survivors diagnosed between 2000 and 2015, we determined rates of persistent posttreatment opioid use, diagnoses of opioid abuse or dependence, and admissions for opioid toxicity. A multivariable logistic regression model was used to identify patient, cancer, and treatment risk factors associated with adverse opioid-related outcomes. Predictive risk models were developed and validated using a least absolute shrinkage and selection operator regression technique.ResultsThe rate of persistent opioid use in cancer survivors was 8.3% (95% CI = 8.1% to 8.4%); the rate of opioid abuse or dependence was 2.9% (95% CI = 2.8% to 3.0%); and the rate of opioid-related admissions was 2.1% (95% CI = 2.0% to 2.2%). On multivariable analysis, several patient, demographic, and cancer and treatment factors were associated with risk of persistent opioid use. Predictive models showed a high level of discrimination when identifying individuals at risk of adverse opioid-related outcomes including persistent opioid use (area under the curve [AUC] = 0.85), future diagnoses of opioid abuse or dependence (AUC = 0.87), and admission for opioid abuse or toxicity (AUC = 0.78).ConclusionThis study demonstrates the potential to predict adverse opioid-related outcomes among cancer survivors. With further validation, personalized risk-stratification approaches could guide management when prescribing opioids in cancer patients

Farsighted Risk Mitigation of Lateral Movement Using Dynamic Cognitive Honeypots

Lateral movement of advanced persistent threats has posed a severe security challenge. Due to the stealthy and persistent nature of the lateral movement, defenders need to consider time and spatial locations holistically to discover latent attack paths across a large time-scale and achieve long-term security for the target assets. In this work, we propose a time-expanded random network to model the stochastic service links in the user-host enterprise network and the adversarial lateral movement. We design cognitive honeypots at idle production nodes and disguise honey links as service links to detect and deter the adversarial lateral movement. The location of the honeypot changes randomly at different times and increases the honeypots' stealthiness. Since the defender does not know whether, when, and where the initial intrusion and the lateral movement occur, the honeypot policy aims to reduce the target assets' Long-Term Vulnerability (LTV) for proactive and persistent protection. We further characterize three tradeoffs, i.e., the probability of interference, the stealthiness level, and the roaming cost. To counter the curse of multiple attack paths, we propose an iterative algorithm and approximate the LTV with the union bound for computationally efficient deployment of cognitive honeypots. The results of the vulnerability analysis illustrate the bounds, trends, and a residue of LTV when the adversarial lateral movement has infinite duration. Besides honeypot policies, we obtain a critical threshold of compromisability to guide the design and modification of the current system parameters for a higher level of long-term security. We show that the target node can achieve zero vulnerability under infinite stages of lateral movement if the probability of movement deterrence is not less than the threshold

Oral and dermal toxicity of alkenones extracted from Isochrysis species

Author Posting. © Bioscience Research Institute, 2020. This article is posted here by permission of Bioscience Research Institute for personal use, not for redistribution. The definitive version was published in McIntosh, K., Sarver, J., Mell, K., Terrero, D. J., Ashby, C. R., Reddy, C., O’Neil, G., Ramapuram, J. B., & Tiwari, A. K. Oral and dermal toxicity of alkenones extracted from Isochrysis species. Frontiers in Bioscience-Landmark, 25(5), (2020): 817–837, https://doi.org/10.2741/4836.Isochrysis is commercially available marine algae used for animal feed, human nutrient supplements, and biodiesel. The Isochrysis species is one of five genera of haptophytes that produces unique, long-chain lipids known as alkenones that are promising new ingredients for green cosmetics, personal care products and pharmaceutical delivery. However, there is a lack of toxicity data for alkenones in animals, thus limiting their use in humans. In this study, we performed acute oral, acute dermal, and repeated 28-day dermal toxicity studies, using female SAS Sprague Dawley Rats. Our behavioral studies indicated that the specific alkenones had no overt behavioural effects at oral doses up to 4000 mg/kg. In the acute and chronic dermal toxicity studies, the alkenones produced less irritation and did not significantly damage the skin based on the Draize skin reaction scale and trans-epidermal water loss readings compared to the positive control, 1% sodium lauryl sulfate. Overall, our results indicated that alkenones are safe in Sprague Dawley rats, suggesting that they could be used for both oral and dermal formulations, although additional studies will be required.This work was supported by the Marine Biological Laboratory Woods Hole Oceanographic Institute (WHOI) under grant (N-126665-01, 2017), Washington Research Foundation, and University of Toledo start-up funding under a grant (F110760) to A.K.T. The authors declare no conflict of interest

Cost-effectiveness of genotype-guided and dual antiplatelet therapies in acute coronary syndrome.

BackgroundThe choice of antiplatelet therapy after acute coronary syndrome (ACS) is complicated: Ticagrelor and prasugrel are novel alternatives to clopidogrel, patients with some genotypes may not respond to clopidogrel, and low-cost generic formulations of clopidogrel are available.ObjectiveTo determine the most cost-effective strategy for dual antiplatelet therapy after percutaneous coronary intervention for ACS.DesignDecision-analytic model.Data sourcesPublished literature, Medicare claims, and life tables.Target populationPatients having percutaneous coronary intervention for ACS.Time horizonLifetime.PerspectiveSocietal.InterventionFive strategies were examined: generic clopidogrel, prasugrel, ticagrelor, and genotyping for polymorphisms of CYP2C19 with carriers of loss-of-function alleles receiving either ticagrelor (genotyping with ticagrelor) or prasugrel (genotyping with prasugrel) and noncarriers receiving clopidogrel.Outcome measuresDirect medical costs, quality-adjusted life years(QALYs), and incremental cost-effectiveness ratios (ICERs).Results of base-case analysisThe clopidogrel strategy produced$179 301 in costs and 9.428 QALYs. Genotyping with prasugrel was superior to prasugrel alone, with an ICER of$35 800 per QALY relative to clopidogrel. Genotyping with ticagrelor was more effective than genotyping with prasugrel ($30 200 per QALY relative to clopidogrel). Ticagrelor was the most effective strategy($52 600 per QALY relative to genotyping with ticagrelor).Results of sensitivity analysisStronger associations between genotype and thrombotic outcomes rendered ticagrelor substantially less cost-effective ($104 800 per QALY). Genotyping with prasugrel was the preferred therapy among patients who could not tolerate ticagrelor.LimitationNo randomized trials have directly compared genotyping strategies or prasugrel with ticagrelor.ConclusionGenotype-guided personalization may improve the cost-effectiveness of prasugrel and ticagrelor after percutaneous coronary intervention for ACS, but ticagrelor for all patients may bean economically reasonable alternative in some settings

Incidence of Long-Term Esophageal Dilation With Various Treatment Approaches in the Older Head and Neck Cancer Population

Purpose: Treatments for locoregionally advanced head and neck cancer (LAHNC) negatively impact swallowing function, but the long-term incidence of severe toxicity requiring esophageal dilation is not well-documented in the population. The aim of this study was to compare the incidence of long-term esophageal dilation across varying treatments for LAHNC.Methods and Materials: We identified 5,223 patients with LAHNC diagnosed from 2000 to 2009 in the SEER-Medicare database. We compared the incidence of esophageal dilation for surgery alone vs. surgery plus adjuvant radiotherapy (RT) and chemoradiotherapy (CRT) vs. definitive RT or CRT.Results: The cumulative incidence of esophageal dilation for all sites at 10 years, according to treatment group were as follows: CRT, 14% (95% confidence interval (CI), 12–17%); definitive RT, 13% (95% CI, 10–16%); surgery alone, 5% (95% CI, 3–7%); surgery and CRT, 15% (95% CI, 11–19%); surgery and adjuvant RT: 10% (95% CI, 8–13%). There was no significant difference in the incidence of esophageal dilation between surgery plus adjuvant RT/CRT or definitive RT/CRT (p = 0.37), but the incidence was significantly increased in both groups compared to surgery alone (p = 0.003). On multivariable analysis, chemotherapy was associated with significantly increased incidence of esophageal dilation (HR 2.9, 95% CI 1.5–5.5, p &lt; 0.001) in oropharyngeal cancers.Conclusions: The incidence of esophageal dilation is similar in LAHNC patients undergoing RT with or without surgery. Chemoradiotherapy increases the long-term risk of esophageal dilation events over surgery alone

Comparison of model-predicted and measured moment arms for the rotator cuff muscles

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.clinbiomech.2007.02.001. © 2007. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Background The ability of mathematical models of the shoulder to accurately replicate physiological muscle moment arms is unknown. The purpose of this study was to compare model-predicted and experimentally measured moment arms for the rotator cuff muscles during arm elevation. Methods Moment arms obtained from six mathematical models and seven experimental studies were compared for the supraspinatus, infraspinatus, teres minor, and subscapularis for elevation in the scapular plane. Results All of the included models generated moment arms that generally fell within the range of experimentally measured data. Interpretation The quantitative agreement between model-predicted and experimentally measured moment arms supports the use of the included models for biomechanical shoulder analyses.National Institute of Healt

Hybrid cloud computing architecture based on open source technology

The advance of technologies such as distributed computing, Internetand grid computing, have enabled Cloud Computing to become part of a new model of computing and business. Cloud Computing is transforming the traditional ways in which companies use and acquire Information Technology (IT) resources. After an initial boom in Public Cloud, companies begun to mount hybrid Clouds that offer the advantages of Cloud Computing in addition to the privacy of data they consider strategic. A hybrid Cloud solution allows the integration of both systems. Leading companies in cloud solutions have understood this evolution and begun to offer hybrid solutions. Moreover, many of these companies are taking the next step by offering solutions based on open source standards that allow a high degree of interoperability and portability