Advanced treatment planning: robust optimization and proton RBE

This thesis aims to improve the way uncertainties are incorporated in the treatment planning process of radiotherapy treatments.By using robust optimization instead of the more commonly used PTV-optimization the effects of movement on the radiation dose to the target can be calculated more accurately. This thesis describes the expected benefits of robust optimization are for head and neck cancer patients treated with photons. Additionally, an estimate is made of the magnitude of shifts that need to be accounted for during robust optimization of head and neck cancer patients treated with proton therapy.The biological effect of proton therapy dose is higher than that of equal photon therapy dose. This is caused by the higher linear energy transfer (LET) of protons compared to photons. In clinical practice this is compensated by multiplying proton therapy dose with a constant relative biological effectiveness (RBE) factor of 1.1 when it needs to be compared to photon therapy dose. In reality, the LET is variable which is expected to result in a variable RBE. In this thesis, measurements are described of LET calculations with which the RBE can be calculated for clinical patients. Additionally, two RBE models are compared to simplified models to better understand them. Lastly, a simulation is used to show that the effects of variable RBE for patients cannot be observed directly using patient toxicities, even though it is expected to have an effect on it

Can the mean linear energy transfer of organs be directly related to patient toxicities for current head and neck cancer intensity-modulated proton therapy practice?

BACKGROUND AND PURPOSE: The relative biological effectiveness (RBE) of proton therapy is predicted to vary with the dose-weighted average linear energy transfer (LETd). However, RBE values may substantially vary for different clinical endpoints. Therefore, the aim of this study was to assess the feasibility of relating mean D⋅LETd parameters to patient toxicity for HNC patients treated with proton therapy. MATERIALS AND METHODS: The delivered physical dose (D) and the voxel-wise product of D and LETd (D⋅LETd) distributions were calculated for 100 head and neck cancer (HNC) proton therapy patients using our TPS (Raystation v6R). The means and covariance matrix of the accumulated D and D⋅LETd of all relevant organs-at-risk (OARs) were used to simulate 2.500 data sets of different sizes. For each dataset, an attempt was made to add mean D⋅LETd parameters to a multivariable NTCP model based on mean D parameters of the same OAR for xerostomia, tube feeding and dysphagia. The likelihood of creating an NTCP model with statistically significant parameters (i.e. power) was calculated as a function of the simulated sample size for various RBE models. RESULTS: The sample size required to have a power of at least 80% to show an independent effect of mean D⋅LETd parameters on toxicity is over 15000 patients for all toxicities. CONCLUSION: For current clinical practice, it is not feasible to directly model NTCP with both mean D and mean D⋅LETd of OARs. These findings should not be interpreted as a contradiction of previous evidence for the relationship between RBE and LETd

Assessment of residual geometrical errors of clinical target volumes and their impact on dose accumulation for head and neck radiotherapy

Purpose: To assess the residual geometrical errors (dr) and their impact on the clinical target volumes (CTV) dose coverage for head and neck cancer (HNC) proton therapy patients.Methods: We analysed 28 HNC patients treated with 70 Gy (RBE) and 54.25 Gy (RBE) to the therapeutic CTV70 and prophylactic CTV54.25, respectively. Daily cone beam CTs were converted to high quality synthetic CTs (sCTs). The CTVs from the nominal CT were propagated to the corresponding sCTs using a hybrid deformable image registration (propagated CTVs) in RayStation 11B. For 11 patients, all propagated CTVs were reviewed by our HNC radiation oncologist (physician corrected CTVs).The residual geometrical error dr was quantified as a function of the daily CTVs volume overlap with the nominal plan CTV. The errors dr(propagated CTVs) and dr(physician corrected CTVs) and the difference in dice similarity coefficients (ΔDSC) were determined. Using clinical plans, dose coverage and the tumor control probability (TCP) for the nominal, accumulated and voxel-wise minimum scenarios were determined.Results: The difference in the residual geometrical error dr (propagated CTVs – physician corrected CTVs) and mean DSC (|ΔDSC|mean) were minor: Δdr(CTV70) = 0.16 mm, Δdr(CTV54.25) = 0.26 mm, |ΔDSC|mean &lt; 0.9%. For all 28 patients, dr(CTV70) = 1.91 mm and dr(CTV54.25) = 1.90 mm. However, CTV54.25 above and below the cricoid cartilage differed substantially (1.00 mm c.f. 3.93 mm). The CTV54.25 coverage below the cricoid was then almost always lower, although the TCP of the accumulated dose was higher than the TCP of the voxel-wise minimum dose.Conclusions: Setup uncertainty setting of 2 mm is possible. The feasibility of using propagated CTVs for error determination is demonstrated.</p

Improving the Students\u27 Writing Competence in a Second Language Acquisition Through the Implementation of Lesson Study

Writing is the most difficult skill for second language learners. It can be seen, for example, they always make ageneralization, simplification, less of knowing vocabularies, punctuation, spelling, and grammar. This paper will describe improving the students\u27 writing competence in second language acquisition through the implementation of lesson study in faculty of language education of Indraprasta PGRI University of Jakarta. This research uses qualitative approach and the data taken from the students who are studying writing in the class. In applying lesson study, lecturer model explains about the materials based on the syllabus of the subject. The students are also given tasks in their groups. The observers watch and write about the students and assist them. After doing this, the observers discuss about the class with the lecturer model. By doing the implementation of Lesson Study, the students can work in group together, the class is so inspiring, they feel satisfied with the explanation of the lecturer model and havegood impact to improve the students\u27 writing competence

School functioning in 8- to 18-year-old children born after in vitro fertilization

The aim of this study was to examine the school functioning of 8- to 18-year-old children born after in vitro fertilization (IVF). We compared 233 children born after IVF to 233 matched control children born spontaneously from parents with fertility problems on measures of education level, general cognitive ability, school performance (need for extra help, repeating a grade, special education), and rates of learning and developmental disorders. No differences were found between IVF and control children on these measures of school functioning. More than 60% of adolescents at secondary school attended high academic levels (with access to high school or university). We conclude that children and adolescents born after IVF show good academic achievement and general cognitive ability. They do not experience any more educational limitations than the naturally conceived children and adolescents of the control group. The tendency of reassuring school functioning already found in younger IVF children has been shown to continue at secondary school age

Validation of the proton range accuracy and optimization of CT calibration curves utilizing range probing

Proton therapy is affected by range uncertainty, which is partly caused by an ambiguous conversion from x-ray attenuation to proton stopping power. CT calibration curves, or Hounsfield look-up tables (HLUTs), are institution-specific and may be a source of systematic errors in treatment planning. A range probing method to verify, optimize and validate HLUTs for proton treatment is proposed. An initial HLUT was determined according to the stoichiometric approach. For HLUT validation, three types of animal tissue phantoms were prepared: a pig's head, 'thorax' and femur. CT scans of the phantoms were taken and a structure, simulating a water slab, was added on the scan distal to the phantoms to mimic the detector used for integral depth-dose measurements. The CT scans were imported into the TPS to calculate individual pencil beams directed through the phantoms. The phantoms were positioned at the therapy system isocenter using x-ray imaging. Shoot-through pencil beams were delivered, and depth-dose profiles were measured using a multi-layer ionization chamber. Measured depth-dose curves were compared to the calculated curves and the range error per spot was determined. Based on the water equivalent path length (WEPL) of individual spot, a range error margin was defined. Ratios between measured error and theoretical margin were calculated per spot. The HLUT optimization was performed by identifying systematic shifts of the mean range error per phantom and minimizing the ratios between range errors and uncertainty margins. After optimization, the ratios of the actual range error and the uncertainty margin over the complete data set did not exceed 0.75 (1.5 SD), indicating that the actual errors are covered by the theoretical uncertainty recipe. The feasibility of using range probing to assess range errors was demonstrated. The theoretical uncertainty margins in the institution-specific setting potentially may be reduced by ∼25%

Analisis Kesalahan Berbahasa Indonesia Dalam Karangan Eksposisi Siswa Sekolah Menengah Atas

: The purpose of this research is : (1) to describes the error of Indonesian language in exposition text by the students at class X of SMA Negeri in Karanganyar in the academic year 2011/2012; (2) causes of error, and (3) the effort which is done by the teacher and student to solve the error. This research is a qualitative descriptive research with a sample student text SMA Negeri 1 Karanganyar and SMA Negeri Kebakkramat. The sampling technique used was purposive sampling. Data collection techniques used were in-depth interviews and document analysis. Data analysis technique used is the interactive analytical model that includes four components, namely data collection, data reduction, data presentation, and verification. The conclusions of this study are as follows. Firstly, the linguistic elements of language errors that often occur in the student text is divided into four errors : spelling error, diction, sentence, and paragraph. Secondly, language errors that often occur in a student text exposition caused by several factors, among others: is inadequate of language mastery, lack of examples by the teachers, the influence of foreign language, lack of writing peactice, and lack of writing time. Thirdly, the efforts have been made to minimize errors include: improving students\u27 language mastery, having more practices in writing, implementing appropriate correction technique, and implementing a process approach to teaching writing

Pusat Informasi Pariwisata dan Kebudayaan Kalimantan Timur di Samarinda

Samarinda sekarang merupakan ibukota dari Kalimantan Timur yang didalamnya memiliki potensi pariwisata dan kebudayaan. Hadirnya fasilitas pusat informasi ini bertujuan untuk memenuhi kebutuhan kota atas potensi dan penjawaban salah satu permasalahan kota yang ada. Pusat Informasi ini di desain untuk memberikan informasi serta pemasaran tentang pariwisata dan kebudayaan yang ada di wilayah Kalimantan Timur. tidak hanya berupa data saja tetapi dari fasilitas gallery, workshop, ampitheatre, perpustakaan sampai informasi yang berupa kuliner dari resotran yang di desain.informasi juga dipaparkan lewat puisi semiotika yaitu pada ekspresi bangunan yang menggunakan pendekatan simbolik dengan tema “Genesis of East Borneo Culture”. Tidak semata-mata mentah mengambil bentuk dari arsitektur Kalimantan Timur tetapi dimodernisasikan mengikuti perkembangan dunia arsitektur disertai dengan Kubahan bentuk melalui proses simbolik

Basic design and simulation of a SPECT microscope for in vivo stem cell imaging

The need to understand the behavior of individual stem cells at the various stages of their differentiation and to assess the resulting reparative action in pre-clinical model systems, which typically involves laboratory animals, provides the motivation for imaging of stem cells in vivo at high resolution. Our initial focus is to image cells and cellular events at single cell resolution in vivo in shallow tissues (few mm of intervening tissue) in laboratory mice and rates. In order to accomplish this goal we are building a SPECT-based microscope. We based our design on earlier theoretical work with near-field coded apertures and have adjusted the components of the system to meet the real-world demands of instrument construction and of animal imaging. Our instrumental design possesses a reasonable trade-off between field-of-view, sensitivity, and contrast performance (photon penetration). A layered gold aperture containing 100 pinholes and intended for use in coded aperture imaging application has been designed and constructed. A silicon detector connected to a TimePix readout from the CERN collaborative group was selected for use in our prototype microscope because of its ultra-high spatial and energy resolution capabilities. The combination of the source, aperture, and detector has been modeled and the coded aperture reconstruction of simulated sources is presented in this work

Head and neck IMPT probabilistic dose accumulation:Feasibility of a 2 mm setup uncertainty setting

OBJECTIVE: To establish optimal robust optimization uncertainty settings for clinical head and neck cancer (HNC) patients undergoing 3D image-guided pencil beam scanning (PBS) proton therapy. METHODS: We analyzed ten consecutive HNC patients treated with 70 and 54.25 GyRBE to the primary and prophylactic clinical target volumes (CTV) respectively using intensity-modulated proton therapy (IMPT). Clinical plans were generated using robust optimization with 5 mm/3% setup/range uncertainties (RayStation v6.1). Additional plans were created for 4, 3, 2 and 1 mm setup and 3% range uncertainty and for 3 mm setup and 3%, 2% and 1% range uncertainty. Systematic and random error distributions were determined for setup and range uncertainties based on our quality assurance program. From these, 25 treatment scenarios were sampled for each plan, each consisting of a systematic setup and range error and daily random setup errors. Fraction doses were calculated on the weekly verification CT closest to the date of treatment as this was considered representative of the daily patient anatomy. RESULTS: Plans with a 2 mm/3% setup/range uncertainty setting adequately covered the primary and prophylactic CTV (V95≥ 99% in 98.8% and 90.8% of the treatment scenarios respectively). The average organ-at-risk dose decreased with 1.1 GyRBE/mm setup uncertainty reduction and 0.5 GyRBE/1% range uncertainty reduction. Normal tissue complication probabilities decreased by 2.0%/mm setup uncertainty reduction and by 0.9%/1% range uncertainty reduction. CONCLUSION: The results of this study indicate that margin reduction below 3 mm/3% is possible but requires a larger cohort to substantiate clinical introduction