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A dose calculation algorithm for radiosurgery treatment room shielding optimization

MEDICAL PHYSICS 2023年第6期50卷 3852-3861页

作者： Nygren, Nelly Nordstrom, Hakan da Silva, Joakim Elekta Instrument AB Stockholm Sweden Elekta Instrument AB Kungstensgatan 18Box 7593 SE-10393 Stockholm Sweden

BackgroundMethods described in the literature for designing shielding for treatment rooms for radiotherapy systems often involve assumptions that lead to overestimations of the wall thicknesses required to meet dose rate constraints outside the room. The Leksell Gamma Knife (LGK) has built-in shielding that results in primarily scattered photons leaking into the room. The field of leakage radiation, therefore, has a wide spectrum of energies, up to the primary energies of cobalt-60, and is highly anisotropic, making standard site planning methods difficult to adapt to the LGK. Monte Carlo (MC) simulations are an alternative for dose calculations but are computationally expensive. PurposeThe aim was to develop a dose calculation algorithm for fast estimations of dose rates outside the barriers of a treatment room. The algorithm could then be employed in iterative methods to optimize treatment room parameters such as wall thicknesses and position of the LKG unit. MethodsThe algorithm uses pre-calculated MC simulation data in two steps. First, it uses phase spaces that describe single photons in the radiation field around the LGK. Using each photon's position and direction, they are raytraced to the outside of the room. Based on their energy, angle of incidence to the barrier, and the barrier's thickness, a depth-dose profile is sampled from a pre-calculated library of profiles. The contribution from each photon is added to the space outside the barriers, giving the total dose distribution. The barrier thicknesses are optimized by iteratively running the algorithm and finding the minimum thickness required to keep the resulting maximum dose rate outside below a given upper limit. ResultsComparisons between dose distributions from the dose algorithm and full MC simulations of two typical rooms show good agreement, with the maximum dose rate outside each barrier being estimated within what represents a 2 cm error in concrete barrier thickness. The algorithm is successful

关键词： dose algorithm gamma knife shielding optimization

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Comparison of Maintenance dose Predictions by Warfarin Dosing algorithms Based on Chinese and Western Patients

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JOURNAL OF CLINICAL PHARMACOLOGY 2023年第5期63卷 569-582页

作者： Deng, Jiexin Wang, Yi An, Xiaokang Henan Univ Sch Nursing & Hlth Kaifeng Peoples R China Henan Univ Dept Thorac & Cardiovasc Surg Huaihe Hosp Kaifeng Peoples R China Henan Univ Affiliated Hosp 1 Dept Thorac Surg Kaifeng Peoples R China Henan Univ Jinming CampusJinming Rd North Kaifeng Henan Peoples R China

Warfarin has a long record of safe and effective clinical use, and it remains one of the most commonly prescribed drugs for the prevention and treatment of thromboembolic conditions even in the era of direct oral anticoagulants. To address its large interindividual variability and narrow therapeutic window, the Clinical Pharmacogenetics Implementation Consortium has recommended using pharmacogenetic dosing algorithms, such as the ones developed by the International Warfarin Pharmacogenetics Consortium (IWPC) and by Gage et al, to dose warfarin when genotype information is available. In China, dosing algorithms based on local patient populations have been developed and evaluated for predictive accuracy of warfarin maintenance doses. In this study, percentage deviations of doses predicted by 15 Chinese dosing algorithms from that by IWPC and Gage algorithms were systematically evaluated to understand the differences between Chinese and Western algorithms. In general, dose predictions by Chinese dosing algorithms tended to be lower than those predicted by IWPC or Gage algorithms for the most prevalent VKORC1 and CYP2C9 genotypes in the Chinese population. The extent of negative prediction deviation appeared to be largest in the younger age group with smaller body weight. Our findings are consistent with previous reports that Asians have a higher sensitivity to warfarin and require lower doses than Western populations.

关键词： cardiopharmacology dose algorithm ethnic sensitivity PK PD warfarin

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Estimation of RF and ELF dose by anatomical location in the brain from wireless phones in the MOBI-Kids study

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ENVIRONMENT INTERNATIONAL 2022年 163卷 107189页

作者： Calderon, Carolina Castano-Vinyals, Gemma Maslanyj, Myron Wiart, Joe Lee, Ae-Kyoung Taki, Masao Wake, Kanako Abert, Alex Badia, Francesc Hadjem, Abdelhamid Kromhout, Hans de Llobet, Patricia Varsier, Nadege Conil, Emmanuelle Choi, Hyung-Do Sim, Malcolm R. Cardis, Elisabeth UK Hlth Secur Agcy Chem Radiat & Environm Hazards Didcot OX11 0RQ Oxon England Barcelona Inst Global Hlth ISGlobal 88 Doctor Aiguader E-08003 Barcelona Spain Univ Pompeu Fabra Barcelona Spain CIBER Epidemiol & Salud Publ Madrid Spain IMIM Hosp del Mar Med Res Inst Barcelona Spain WHIST Lab Common Lab Orange Labs R&D Issy Les Moulineaux France Inst Mines Telecom Issy Les Moulineaux France Inst Polytech Paris Telecom Paris LTCI F-91120 Palaiseau France Elect & Telecommun Res Inst ETRI Radio Technol Res Dept Daejeon South Korea Tokyo Metropolitan Univ Grad Sch Engn Dept Elect Engn Tokyo Japan Natl Inst Informat & Commun Technol Radio Res Inst Electromagnet Stand Res Ctr Electromagnet Compatibil Lab Koganei Tokyo Japan Univ Autonoma Barcelona Barcelona Spain Univ Utrecht Inst Risk Assessment Sci IRAS Utrecht Netherlands Agence Natl FRequences ANFR Maisons Alfort France Monash Univ Alfred Ctr Sch Publ Hlth & Prevent Med Fac Med Nursing & Hlth Sci Commercial Rd Melbourne Vic 3004 Australia

Wireless phones (both mobile and cordless) emit not only radiofrequency (RF) electromagnetic fields (EMF) but also extremely low frequency (ELF) magnetic fields, both of which should be considered in epidemiological studies of the possible adverse health effects of use of such devices. This paper describes a unique algorithm, developed for the multinational case-control MOBI-Kids study, that estimates the cumulative specific energy (CSE) and the cumulative induced current density (CICD) in the brain from RF and ELF fields, respectively, for each subject in the study (aged 10-24 years old). Factors such as age, tumour location, self-reported phone models and usage patterns (laterality, call frequency/duration and hands-free use) were considered, as was the prevalence of different communication systems over time. Median CSE and CICD were substantially higher in GSM than 3G systems and varied considerably with location in the brain. Agreement between RF CSE and mobile phone use variables was moderate to null, depending on the communication system. Agreement between mobile phone use variables and ELF CICD was higher overall but also strongly dependent on communication system. Despite ELF dose distribution across the brain being more diffuse than that of RF, high correlation was observed between RF , ELF dose. The algorithm was used to systematically estimate the localised RF and ELF doses in the brain from wireless phones, which were found to be strongly dependent on location and communication system. Analysis of car-tographies showed high correlation across phone models and across ages, however diagonal agreement between these cartographies suggest these factors do affect dose distribution to some level. Overall, duration and number of calls may not be adequate proxies of dose, particularly as communication systems available for voice calls tend to become more complex with time.

关键词： ELF-EMF RF-EMF Mobile phones dose algorithm Exposure assessment Brain tumour

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Acuros(R)dose verification of ultrasmall lung lesions with EBT-XD film in a homogeneous and heterogeneous anthropomorphic phantom setup

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MEDICAL PHYSICS 2020年第11期47卷 5829-5837页

作者： Ollers, Michel C. Swinnen, Ans C. C. Verhaegen, Frank Maastricht Univ GROW Sch Oncol Dept Radiat Oncol Maastro Med Ctr Maastricht Netherlands

Purpose Modern type 'c' dose calculation algorithms like Acuros(R)can predict dose for lung tumors larger than approximately 4 cm(3)with a relative uncertainty up to 5%. However, increasingly better tumor diagnostics are leading to the detection of very small early-stage lung tumors that can be treated with stereotactic body radiotherapy (SBRT) for inoperable patients. This raises the question whether dose algorithms like Acuros(R)can still accurately predict dose within 5% for challenging conditions involving small treatment fields. Current recommendations for Quality Assurance (QA) and dose verification in SBRT treatments are to use phantoms that are as realistic as possible to the clinical situation, although water-equivalent phantoms are still largely used for dose verification. In this work we aim to demonstrate that existing dose verification methods are inadequate for accurate dose verification in very small lung tumors treated with SBRT. Method The homogeneous PTW Octavius4D phantom with the Octavius 1000 SRS detector ("Octavius4D phantom") and the heterogeneous CIRS Dynamic Thorax phantom ('CIRS phantom') were used for dose measurements. The CIRS phantom contained different lung-equivalent film-holding cylindrical phantom inserts ("film inserts") with water-equivalent spherical targets with diameters 0.5, 0.75, 1, 2, and 3 cm. Plans were calculated for 6 and 10 MV for each spherical target in the CIRS phantom, resulting in 14 treatment plans. The plans were delivered to both Octavius4D and CIRS phantom to compare measured dose in a commonly used homogeneous and more realistic heterogeneous phantom setup. In addition, treatment plans of seven clinical lung cancer patients with lung tumors below approximately 1.0 cm(3)were irradiated in the heterogeneous CIRS phantom. The actual tumor size within the clinical treatment plans determined the choice of the spherical target size, such that both measurement geometry and clinical target volumes match as closely as

关键词： Acuros anthropomorphic phantom dose algorithm EBT film small-field dosimetry

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Assessment of warfarin algorithms for hospitalized adults: searching for a safe dosing strategy

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JOURNAL OF THROMBOSIS AND THROMBOLYSIS 2019年第4期48卷 570-579页

作者： Cohen, Jessica L. Thompson, Elena Sinvani, Liron Kozikowski, Andrzej Qiu, Guang Pekmezaris, Renee Spyropoulos, Alex C. Wang, Jason J. Northwell Hlth Div Hosp Med Dept Med 300 Community Dr Manhasset NY 11030 USA Northwell Hlth Donald & Barbara Zucker Sch Med Hofstra Northwell Manhasset NY 11030 USA Northwell Hlth Div Hlth Serv Res Ctr Heath Innovat & Outcomes Res Dept Med Manhasset NY 11030 USA Northwell Hlth Syst Lenox Hill Hosp Dept Med Anticoagulat & Clin Thrombosis Serv New York NY 10075 USA

This study evaluates three warfarin dosing algorithms (Kimmel, Dawson, High dose >= 2.5 mg) for hospitalized older adults. A random selection of 250 patients with overshoots (INR >= 5 after 48 h of hospitalization) and 250 patients without overshoots were accessed from a database of 12,107 inpatients >= 65 years treated with chronic warfarin during hospitalization between January 1, 2014 and June 30, 2016. algorithms were retrospectively applied to patients 2 days prior to overshoots in the overshoot group, and 2 days prior to the maximum INR reached after 48 h of hospitalization in the non-overshoot group. Patients were categorized as overdosed or not overdosed and compared using descriptive statistics. Logistic regression modeling determined predictors for overshoots. There was no significant difference between overdose and non-overdose groups for progressing to overshoots by the Kimmel (51.0% vs. 48.7%, p = 0.67) or Dawson (48.5 vs. 57.9%, p = 0.19) algorithms. The Low dose Group (<= 2.5 mg) was significantly more likely to experience an overshoot than the High dose Group (56.6% vs. 45.5%, p = 0.04). The Low dose Group was more likely to be older (81.4% vs. 71.1%, p = 0.02), female (63.5% vs. 49.8%, p = 0.02), weigh less (71.3 +/- 21.9 vs. 79 +/- 23.1, p = 0.002), and be prescribed amiodarone (16.6% vs. 8.1%, p = 0.01). While none of the algorithms predicted overshoots in logistic regression modeling, weight over 70 kg and black race remained protective. The High dose algorithm revealed that providers appropriately gave lower doses to patients at highest risk for warfarin sensitivity. Future studies are needed to investigate tools for inpatient warfarin dosing in older adults.

关键词： Warfarin Inpatients International normalized ratio dose algorithm

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Warfarin Pharmacogenetics Reevaluated Subgroup Analysis Reveals a Likely Underestimation of the Maximum Pharmacogenetic Benefit by Clinical Trials

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AMERICAN JOURNAL OF CLINICAL PATHOLOGY 2016年第5期145卷 671-686页

作者： Stack, Gary Maurice, Carleta B. VA Connecticut Healthcare Syst Pathol & Lab Med Serv West Haven CT 06516 USA Yale Univ Sch Med Dept Lab Med New Haven CT 06510 USA

Objectives: Various patient subgroups were examined to determine which ones obtain the largest pharmacogenetic improvements in warfarin dose accuracy. Subgrouping schemes of recent clinical trials were analyzed for comparison. Methods: The accuracy of a pharmacogenetic dose algorithm was determined retrospectively in comparison to that of a clinical algorithm in subgroups of the International Warfarin Pharmacogenetics Consortium (IWPC) patient database (n = 2,274) and of newly studied clinic patients (n = 146). Results: White patients with low-dose genotypes (*1*3/AA, *2*2/AA, *2*3/GA, *2*3/AA, *3*3/GG, *3*3/GA, and *3*3/AA) achieved the largest pharmacogenetic improvements in warfarin dose accuracy. Mean absolute dosing error (MAE) in this subgroup of IWPC and newly studied patients was reduced 75.7% and 89.7%, respectively. White IWPC patients with >2 variants or >= 2 mg/day absolute difference between pharmacogenetic and clinical dose predictions obtained MAE reductions of 71.1% and 65.3%, respectively. By comparison, unstratified populations and subgroups of a major clinical trial, when replicated in IWPC patients, obtained smaller MAE reductions of 31.8% to 48.2%. Blacks and Asians obtained substantially smaller dose accuracy improvements overall than whites. Conclusions: Patient subgroups were identified that obtained the largest pharmacogenetic improvements in warfarin dose accuracy. These subgroups have not been analyzed in clinical trials to date, likely resulting in underestimation of the pharmacogenetic benefit.

关键词： Warfarin Oral anticoagulant Pharmacogenetics Genotype CYP2C9 VKORC1 Subgroup dose algorithm

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A multi-factorial analysis of response to warfarin in a UK prospective cohort

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GENOME MEDICINE 2016年第1期8卷 1-12页

作者： Bourgeois, Stephane Jorgensen, Andrea Zhang, Eunice J. Hanson, Anita Gillman, Matthew S. Bumpstead, Suzannah Toh, Cheng Hock Williamson, Paula Daly, Ann K. Kamali, Farhad Deloukas, Panos Pirmohamed, Munir Wellcome Trust Sanger Inst Hinxton CB10 1SA Cambs England Univ Liverpool Liverpool L69 3GE Merseyside England Newcastle Univ Newcastle Upon Tyne NE1 7RU Tyne & Wear England Royal Liverpool & Broadgreen Univ Hosp NHS Trust Liverpool L7 8XP Merseyside England Queen Mary Univ London Barts & London Sch Med & Dent William Harvey Res Inst London EC1M 6BQ England Univ Liverpool Inst Translat Med Wolfson Ctr Personalised Med Liverpool L69 3GL Merseyside England

Background: Warfarin is the most widely used oral anticoagulant worldwide, but it has a narrow therapeutic index which necessitates constant monitoring of anticoagulation response. Previous genome-wide studies have focused on identifying factors explaining variance in stable dose, but have not explored the initial patient response to warfarin, and a wider range of clinical and biochemical factors affecting both initial and stable dosing with warfarin. Methods: A prospective cohort of 711 patients starting warfarin was followed up for 6 months with analyses focusing on both non-genetic and genetic factors. The outcome measures used were mean weekly warfarin dose (MWD), stable mean weekly dose (SMWD) and international normalised ratio (INR) > 4 during the first week. Samples were genotyped on the Illumina Human610-Quad chip. Statistical analyses were performed using Plink and R. Results: VKORC1 and CYP2C9 were the major genetic determinants of warfarin MWD and SMWD, with CYP4F2 having a smaller effect. Age, height, weight, cigarette smoking and interacting medications accounted for less than 20 % of the variance. Our multifactorial analysis explained 57.89 % and 56.97 % of the variation for MWD and SMWD, respectively. Genotypes for VKORC1 and CYP2C9*3, age, height and weight, as well as other clinical factors such as alcohol consumption, loading dose and concomitant drugs were important for the initial INR response to warfarin. In a small subset of patients for whom data were available, levels of the coagulation factors VII and IX (highly correlated) also played a role. Conclusion: Our multifactorial analysis in a prospectively recruited cohort has shown that multiple factors, genetic and clinical, are important in determining the response to warfarin. VKORC1 and CYP2C9 genetic polymorphisms are the most important determinants of warfarin dosing, and it is highly unlikely that other common variants of clinical importance influencing warfarin dosage will be found. Both

关键词： Warfarin International Normalise Ratio Warfarin dose Index Visit dose algorithm

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Individualized recombinant human folliclestimulating hormone dosing using the CONSORT calculator in assisted reproductive technology: a large, multicenter, observational study of routine clinical practice

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DRUG HEALTHCARE AND PATIENT SAFETY 2015年 7卷 69-76页

作者： Naether, Olaf G. J. Tandler-Schneider, Andreas Bilger, Wilma MVZ Fertil Ctr Hamburg Reprod Endocrinol Speersort 4 D-20095 Hamburg Germany Fertil Ctr Berlin Ctr Reprod Med Berlin Germany Merck Serono GmbH Med Affairs Fertil Endocrinol & Gen Med Darmstadt Germany

Purpose: This postmarketing surveillance survey was conducted to investigate the utility of the CONsistency in r-FSH Starting doses for individualized tReatmenT (CONSORT) calculator for individualizing recombinant human follicle-stimulating hormone (r-hFSH) starting doses for controlled ovarian stimulation (COS) in routine clinical practice. Methods: This was a 3-year, open-label, observational study evaluating data from women undergoing COS for assisted reproductive technology at 31 German fertility centers. Physicians stated their recommended r-hFSH starting dose, then generated a CONSORT-recommended r-hFSH starting dose. Physicians could prescribe any r-hFSH starting dose. The primary objective was to compare the r-hFSH starting dose recommended by the physician with the CONSORTcalculated dose and that prescribed. Statistical analyses were conducted post hoc. Results: Data were collected from 2,579 patients;the mean (standard deviation [SD]) age was 30.5 (2.93) years (range: 19-40 years). The mean (SD) CONSORT-calculated r-hFSH starting dose was significantly lower than the physician-recommended dose (134.5 [38.0] IU versus 164.6 [47.1] IU;P, 0.0001);the mean (SD) starting dose prescribed was 162.2 (48.4) IU. CONSORT-calculated doses were prescribed for 27.3% (number [n] = 677) of patients, and non-CONSORT-calculated doses prescribed for 72.7% (n= 1,800). The mean (SD) number of oocytes retrieved per patient was 10.6 (6.15) and 11.4 (6.66) in the CONSORT and non-CONSORT groups, respectively;the mean (SD) number of embryos transferred per patient was 1.98 (0.41) and 2.03 (0.45), respectively. Clinical pregnancy rates per COS cycle were 38.8% (CONSORT) and 34.8% (non-CONSORT) (P= 0.142);clinical pregnancy rates per embryos transferred were 45.0% and 39.5%, respectively (P= 0.049). Miscarriage occurred in 14.8% of all clinical pregnancies (CONSORT: 12.5%;non-CONSORT: 15.3%). The rate of grade 3 ovarian hyperstimulation syndrome (OHSS) was 0.3% (n= 2) in the CONSORT

关键词： controlled ovarian stimulation dose algorithm follitropin alfa postmarketing product surveillance

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Comparison between Acuros XB and Brainlab Monte Carlo algorithms for photon dose calculation

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STRAHLENTHERAPIE UND ONKOLOGIE 2012年第7期188卷 599-605页

作者： Misslbeck, M. Kneschaurek, P. Tech Univ Munich Klinikum Rechts Isar Klin & Poliklin Strahlentherapie & Radiol Onkol D-81675 Munich Germany

The AcurosA (R) XB dose calculation algorithm by Varian and the Monte Carlo algorithm XVMC by Brainlab were compared with each other and with the well-established AAA algorithm, which is also from Varian. First, square fields to two different artificial phantoms were applied: (1) a "slab phantom" with a 3 cm water layer, followed by a 2 cm bone layer, a 7 cm lung layer, and another 18 cm water layer and (2) a "lung phantom" with water surrounding an eccentric lung block. For the slab phantom, depth-dose curves along central beam axis were compared. The lung phantom was used to compare profiles at depths of 6 and 14 cm. As clinical cases, the CTs of three different patients were used. The original AAA plans with all three algorithms using open fields were recalculated. There were only minor differences between Acuros and XVMC in all artificial phantom depth doses and profiles;however, this was different for AAA, which had deviations of up to 13% in depth dose and a few percent for profiles in the lung phantom. These deviations did not translate into the clinical cases, where the dose-volume histograms of all algorithms were close to each other for open fields. Only within artificial phantoms with clearly separated layers of simulated tissue does AAA show differences at layer boundaries compared to XVMC or Acuros. In real patient CTs, these differences in the dose-volume histogram of the planning target volume were not observed.

关键词： dose algorithm Acuros Monte Carlo AAA

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Validation of the acenocoumarol EU-PACT algorithms: similar performance in the Rotterdam Study cohort as in the original study

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PHARMACOGENOMICS 2012年第11期13卷 1239-1245页

作者： van Schie, Rianne M. F. el Khedr, Nadia Verhoef, Talitha I. Teichert, Martina Stricker, Bruno H. Hofman, Albert Buhre, Peter N. Wessels, Judith A. M. Schalekamp, Tom le Cessie, Saskia van der Meer, Felix J. M. Rosendaal, Frits R. de Boer, Anthonius Maitland-van der Zee, Anke-Hilse Visser, Loes E. Univ Utrecht Div Pharmacoepidemiol & Clin Pharmacol Utrecht Inst Pharmaceut Sci NL-3508 TB Utrecht Netherlands Royal Dutch Pharmacists Assoc R&D Dept The Hague Netherlands Radboud Univ Nijmegen Sci Inst Qual Healthcare IQ Healthcare NL-6525 ED Nijmegen Netherlands Erasmus MC Dept Epidemiol Rotterdam Netherlands Erasmus MC Dept Internal Med Rotterdam Netherlands Erasmus MC Dept Med Informat Rotterdam Netherlands Inspectorate Hlth Care The Hague Netherlands Star Med Diagnost Ctr Rotterdam Netherlands Leiden Univ Dept Clin Pharm & Toxicol Med Ctr Leiden Netherlands Leiden Univ Med Ctr Dept Med Stat & Bioinformat Leiden Netherlands Leiden Univ Dept Clin Epidemiol Med Ctr Leiden Netherlands Leiden Univ Dept Thrombosis & Hemostasis Med Ctr Leiden Netherlands Med Diagnost Labs Hoofddorp Netherlands Erasmus MC Dept Hosp Pharm Rotterdam Netherlands

Aim: To evaluate the performance of the European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) acenocoumarol dose algorithms in an independent data set. The EU-PACT trial investigates the added value of pretreatment genotyping for use of warfarin, phenprocoumon and acenocoumarol. Patients & methods: External validation was performed in the Rotterdam Study cohort using information about 707 acenocoumarol users. R-2, which measures the strength of correlation between the predicted and observed acenocoumarol dose, mean absolute error and mean squared error were calculated to evaluate the performance of the original algorithm. Results: Validation resulted in a R-2 of 52.7 and 12.9% compared with an R-2 of 52.6 and 17.8% in the original study for the genotype-guided and nongenotype-guided dose algorithm, respectively. For the genotype-guided dose algorithm, the mean absolute error was 0.48 mg/day and the mean squared error was 0.38 (mg/day)(2). For the nongenotype-guided dose algorithm, the mean absolute error was 0.62 mg/day and the mean squared error was 0.63 (mg/day)2. Conclusion: The EU-PACT acenocoumarol algorithm performs just as accurately in this study as in the original study, which implies applicability in various populations.

关键词： acenocoumarol CYP2C9 dose algorithm validation VKORC1

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