11. The analysis of doses in the tumour and in critical tissues in the brachytherapy of malignant melanoma localised in eyes

Brachytherapy is known and used procedure in the treatment of tumours localised in eyes, especially recommended when avoiding of enucleation accompany the long term cure.AimThe aim of this paper was to compare the doses delivered to the tumour and critical tissues during the treatment of the group of patients treated with Ru-106 applicator.PatientsBetween 1994 and 2000, 67 patients (dgn. melanoma malignum in eye) underwent brachytherapy. At 51 patients the tumour was localized in the back of eye, at 15 equatorially and at one in the front section of the eyeball. The median of the patients’ age was 56.3 years. The CCB type applicator was applied for 56 patients, the COB for 7 and the ROA for 4 patients.MethodIrradiation – Prescribed dose of 60 Gy was normalized to the top of the tumour, it decreased by 50%—10% per millimetre with the distance from applicator. The isotope producer determined the dose-rate accuracy for +/−30%. This caused that therapeutic dose had to be calculated taking account for the minimal dose-rate, while the doses in critical organs for maximal dose-rate possible.AnalysisAll patients were divided into three subgroups: 8 patients into 1st, 19 into 2nd and 40 into 3rd. The inclusion criterion was size of tumour: up to 3 mm of height (1st group), 3–5 mm (2nd), and larger than 5 mm (3rd) respectively.ResultsTable presents mean doses in the tumour, sclera and lens (calculated at it's middle) for each group of patients.[[tgroup cols="4"]][[colspec colname="col1"/]][[colspec colname="col2"/]][[colspec colname="col3"/]][[colspec colname="col4"/]][[tbody]][[row]][[entry morerows="1" rowsep="1" align="center"]]Tumour size [mm][[/entry]][[entry namest="col2" nameend="col4" rowsep="1" align="center"]]Doses [Gy][[/entry]][[/row]][[row]][[entry rowsep="1" align="center"]]Tumour[[/entry]][[entry rowsep="1" align="center"]]Sclera[[/entry]][[entry rowsep="1" align="center"]]lens[[/entry]][[/row]][[row]][[entry rowsep="1" align="center"]]5[[/entry]][[entry align="center"]]268.2[[/entry]][[entry align="center"]]974.9[[/entry]][[entry align="center"]]840.6[[/entry]][[/row]][[/tbody]][[/tgroup]]ConclusionsMean doses in tumour varied from 102.9 Gy to 268.2 Gy depending on the tumour size. Doses in sclera and lens did not exceed the tolerance levels in all three groups of patients

58 Porównanie zamierzonych współczynników TAR i SAR dla źródła 60Co – Theratron 780 z danymi literaturowymi

WprowadzenieWspółczynnik TAR i SAR pozwalają na obliczenie dawek dla pól nieregularnych lub zawierających osłony poprzez podzielenie ich na wiele pól i policzenie wkładu do całkowitej dawki.MetodaPomiarów na Theratronie 780E dokonano za pomocą fantomu wodnego PTW z oprogramowaniem Mephysto. Pomiary rozpoczęto od najmniejszego pola 5×5 cm i od powierzchni wody. Komora jonizacyjna typu 2271 (0,6 mm) była połączona z dawkomierzem firmy Nuclear Enterprise. Pomiary w wodzie zakończono na największym polu 35×35 cm. Głębokość maksymalna 30 cm. Następnie dokonano w tych samych warunkach pomiarów w powietrzu. Zachowano tę samą geometrię pomiarów. Pomiarów dokonano z nasadką build up, aby zachować równowagę elektronową.WynikiZamierzone współczynniki TAR i SAR dla źródła 60Co porównano z danymi literaturowymi. Dla małych pól, do 10 cm i na głębokości 0,5 cm uzyskano zgodność w granicach 1%. Dla pól większych różnice wzrosły do 3%. Wraz ze wzrostem głębokości pomiaru zgodność malała. Przy dużych głębokościach, powyżej 15 cm rozbieżności w wynikach osiągnęły 40°f. Uzyskane dawki dla tej samej głębokości i pól od pola zerowego do pola 35×35 cm zachowują charakterystykę zgodną z danymi literaturowymi.WnioskiWykonane pomiary były zgodne z literaturowymi. Krzywe opisujące zależność TAR i SAR od wielkości pola, osiągają dla dużych pól charakterystyczne plateau. Z analizy wyników wynika, że coraz bardziej uwidaczniają się różnice dla większych głębokości. Okazało się, że zbliżając się z komorą jonizacyjną do dna fantomu, coraz więcej promieniowania rozproszonego od jego dna i stołu terapeutycznego docierało do dozymetru. Dane literaturowe nie uwzględniają tych przyczynków. Promieniowanie pochodzące od stołu powinno być uwzględnione, gdyż w praktyce medycznej pacjent leży na stole terapeutycznym

19. Does in vivo dosimetry improve quality of radiotherapy: evaluation of 1000 patient's checks

Radiotherapy is a part of a complex treatment administered to patients with cancer. It uses a radiation which is generated and processed by specialized and sophisticated equipment.Since the beginning of the 20th century the main idea of radiotherapy remained unchanged. It is based on a proven interaction between radiation and human tissues resulting in their partial or total damage. Over the years more knowledge has been gained, especially on fractionation, doses and the reactions of different tissues and organs. The new sources of radiation have begun to be used, including high energy photon end electron beam accelerators. It became evident that major advance in clinical results might be achieved by limitation of the dose strictly to the target volume (tumour) and by sparing normal tissues.The issue of critical importance was the execution of the prescribed treatment. When treatment planning with the accuracy expressed in milimmitres became possible it it had to be proved that subsequent treatments would make it possible to assure such accuracy. In-vivo dosimetry was believed to be of help in increasing the accuracy in radiotherapy. Since its aim was not to modify the treatment but only to execute it according to a prescribed schedule dosimetry should bring about only benefits when implemented in the routine workHowever, being an extensive procedure, dosimetry consumed a lot of effort. In regular work, it is difficult to imagine that each beam could be measured in-vivo for each fraction. Measurements at more than one point for one beam were only considered for special and rare procedures such as mantle fields.In the practice of radiotherapy as carried out at the Greatpoland Cancer Centre routine in-vivo dosimetry was started in 1999, first applied to the patient's head and neck, and then extended to all patients. At least two measurements for each patient were made during the whole treatment. Whenever discrepancy occurred, exceeding 10% between the calculated and measured dose, the search for its cause was initiated. The very first problem involving the implementation of our method to the routine, was the number of dosimeters required. Transporting the dosimeter from one unit to another when dosimetry was requested involved a larger error due to the instability of the detecting unit. Another problem was the staff required. At first, physicists took care of dosimetry, but then technologists were trained who are now making the majority of measurements. A protocol from each measurement is included in the patient's record and is shown for approval to the physician.For the evaluation of our method a group of 1123 patients were analysed: 850 patients with head and neck cancer, 228 with breast cancer and 45 with lung cancer. The number of measurements was at least twice as large because each patient was irradiated from more than one beam.The mean percent differences between the calculated doses and those measured in-vivo were −1.5% (Standard Deviation, SD of 7.8) for the head and neck, +3.4% (SD=4.9) for breast, and −2.4% (4.3) for the lungs.The estimation of the error usinf a total differential method for a single measurement gives the value of more than 10% (upper limit of error). However, the statistical analysis of the measurements on the whole group with nearly a normal distribution provided a more realistic error of about 6%.ConclusionsIn-vivo dosimetry is a standard procedure in conformal radiotherapy. It does not help to avoid casual and even large errors since it is not done for all beams every time. It makes it possible to reduce the mean error in whole group of patients, which in effect should lead to more effective radiotherapy

Effect of irradiation on interleukin 6 and soluble interleukin 6 receptor modified melanoma genetic vaccine

We have designed phase I/II human melanoma gene therapy clinical protocol. The aim of the study was to actively immunize HLA-A1 and/or HLA-A2-positive patients with melanoma with an admixture of irradiated autologous tumor cells and allogeneic melanoma cells genetically engineered to secrete IL-6 and sIL-6R in order to elicit or enhance specific and nonspecific anti-melanoma immune responses to autologous tumor cells to eradicate distant melanoma lesions. Irradiation of autologous and allogeneic tumor cells is a key step in preparation of cellular vaccine because of two major reasons, (i) it inhibits cell proliferation which is crucial in the case of autologous cells which may form a tumor; (ii) it increases melanoma vaccine immunogenicity. The aim of the study was to estimate the optimal dose of ionizing radiation which will provide sterilization of both autologous and allogeneic melanoma cells and will ensure cytokine secretion.Human melanoma cells (Mich-1) were transduced with IL-6 and sIL-6R cDNA using double copy bicistronic retroviral vector. Parental and transduced cells were seeded at in six-well tissue culture plates and were irradiated with 10, 50, 100 and 200 Gy. Secretion of both recombinant proteins into culture was analyzed before and 24, 48, 72, 96 h and 6, 7, 10 and 12 days following irradiation. At the same time adherent cells were enumerated, evaluated for viability and proliferation. At 24, 48, 72 and 96 h postirradiation specific IL-6 and sIL-6R mRNA levels were analyzed.Irradiation of gene modified cells inhibited their proliferation in the dose dependant manner. Dose of 50 Gy sufficiently affected cell proliferation, however, for safety reasons we decided to use the dose of 100 Gy for vaccine preparation. Irradiation did not inhibit secretion of IL-6 and sIL-6R. In contrary, on a per cell basis it significantly increased their secretion which lasted 12 days postirradiation. Interestingly, we did not observe dose or time dependent differences in specific mRNA cellular levels suggesting that increased secretion of both proteins is regulated not on the transcriptional but rather on the posttranscriptional level. Taking all these facts into account we concluded that irradiation of tumor cells may provide an effective and safe approach for gene-modified vaccine preparation

Effect of irradiation on interleukin 6 and soluble interleukin 6 receptor modified melanoma genetic vaccine

We have designed phase I/II human melanoma gene therapy clinical protocol. The aim of the study was to actively immunize HLA-A1 and/or HLA-A2-positive patients with melanoma with an admixture of irradiated autologous tumor cells and allogeneic melanoma cells genetically engineered to secrete IL-6 and sIL-6R in order to elicit or enhance specific and nonspecific antimelanoma immune responses to autologous tumor cells to eradicate distant melanoma lesions. Irradiation of autologous and allogeneic tumor cells is a key step in preparation of cellular vaccine because of two major reasons, (i) it inhibits cell proliferation which is crucial in the case of autologous cells which may form a tumor; (ii) it increases melanoma vaccine immunogenicity. The aim of the study was to estimate the optimal dose of ionizing radiation which will provide sterilization of both autologous and allogeneic melanoma cells and will ensure cytokine secretion.Human melanoma cells (Mich-1) were transduced with IL-6 and sIL-6R cDNA using double copy bicistronic retroviral vector. Parental and transduced cells were seeded at in six-well tissue culture plates and were irradiated with 10, 50, 100 and 200 Gy. Secretion of both recombinant proteins into culture was analyzed before and 24, 48,72,96 h and 6, 7, 10 and 12 days following irradiation. At the same time adherent cells were enumerated, evaluated’ for viability and proliferation. At 24, 48, 72 and 96 h postirradiation specific IL-6 and sIL-6R mRNA levels were analyzed.Irradiation of gene modified cells inhibited their proliferation in the dose dependant manner. Dose of 50 Gy sufficiently affected cell proliferation, however, for safety reasons we decided to use the dose of 100 Gy for vaccine preparation. Irradiation did not inhibit secretion of IL-6 and sIL-6R. In contrary, on a per cell basis it significantly increased their secretion which lasted 12 days postirradiation. Interestingly, we did not observe dose or time dependent differences in specific mRNA cellular levels suggesting that increased secretion of both proteins is regulated not on the transcriptional but rather on the posttranscriptional level. Taking all these facts into account we concluded that irradiation of tumor cells may provide an effective and safe approach for gene-modified vaccine preparation

Low-Rank Subspace Override for Unsupervised Domain Adaptation

Current supervised learning models cannot generalize well across domain boundaries, which is a known problem in many applications, such as robotics or visual classification. Domain adaptation methods are used to improve these generalization properties. However, these techniques suffer either from being restricted to a particular task, such as visual adaptation, require a lot of computational time and data, which is not always guaranteed, have complex parameterization, or expensive optimization procedures. In this work, we present an approach that requires only a well-chosen snapshot of data to find a single domain invariant subspace. The subspace is calculated in closed form and overrides domain structures, which makes it fast and stable in parameterization. By employing low-rank techniques, we emphasize on descriptive characteristics of data. The presented idea is evaluated on various domain adaptation tasks such as text and image classification against state of the art domain adaptation approaches and achieves remarkable performance across all tasks

3D time series analysis of cell shape using Laplacian approaches

Background: Fundamental cellular processes such as cell movement, division or food uptake critically depend on cells being able to change shape. Fast acquisition of three-dimensional image time series has now become possible, but we lack efficient tools for analysing shape deformations in order to understand the real three-dimensional nature of shape changes. Results: We present a framework for 3D+time cell shape analysis. The main contribution is three-fold: First, we develop a fast, automatic random walker method for cell segmentation. Second, a novel topology fixing method is proposed to fix segmented binary volumes without spherical topology. Third, we show that algorithms used for each individual step of the analysis pipeline (cell segmentation, topology fixing, spherical parameterization, and shape representation) are closely related to the Laplacian operator. The framework is applied to the shape analysis of neutrophil cells. Conclusions: The method we propose for cell segmentation is faster than the traditional random walker method or the level set method, and performs better on 3D time-series of neutrophil cells, which are comparatively noisy as stacks have to be acquired fast enough to account for cell motion. Our method for topology fixing outperforms the tools provided by SPHARM-MAT and SPHARM-PDM in terms of their successful fixing rates. The different tasks in the presented pipeline for 3D+time shape analysis of cells can be solved using Laplacian approaches, opening the possibility of eventually combining individual steps in order to speed up computations

The SERRATE protein is involved in alternative splicing in <em>Arabidopsis thaliana</em>

Howalternative splicing (AS) is regulated in plants has not yet been elucidated. Previously, we have shown that the nuclear cap-binding protein complex (AtCBC) is involved in AS in Arabidopsis thaliana. Here we show that both subunits of AtCBC (AtCBP20 and AtCBP80) interact with SERRATE (AtSE), a protein involved in the microRNA biogenesis pathway. Moreover, using a high-resolution reverse transcript-ase-polymerase chain reaction AS system we have found that AtSE influences AS in a similar way to the cap-binding complex (CBC), preferentially affecting selection of 50 splice site of first introns. The AtSE protein acts in cooperation with AtCBC: many changes observed in the mutant lacking the correct SERRATE activity were common to those observed in the cbp mutants. Interestingly, significant changes in AS of some genes were also observed in other mutants of plant microRNA biogenesis pathway, hyl1-2 and dcl1-7, but a majority of them did not cor-respond to the changes observed in the se-1mutant. Thus, the role of SERRATE in AS regulation is distinct from that of HYL1andDCL1, and is similar to the regu-lation of AS in which CBC is involved

Active target TPC for study of photonuclear reactions at astrophysical energies

A setup designed to study photonuclear reactions at astrophysical energies - an active target Time Projection Chamber was developed and constructed at the Faculty of Physics, University of Warsaw. The device was successfully employed in two experiments at the Institute of Nuclear Physics Polish Academy of Sciences in Cracow, in which {\gamma}- and neutron-induced reactions with CO2 gas target were measured. The reaction products were detected and their momenta reconstructed. Preliminary results are shown.Comment: Presented at Zakopane Conference on Nuclear Physics 202

A finite strain fibre-reinforced viscoelasto-viscoplastic model of plant cell wall growth

A finite strain fibre-reinforced viscoelasto-viscoplastic model implemented in a finite element (FE) analysis is presented to study the expansive growth of plant cell walls. Three components of the deformation of growing cell wall, i.e. elasticity, viscoelasticity and viscoplasticity-like growth, are modelled within a consistent framework aiming to present an integrative growth model. The two aspects of growth—turgor-driven creep and new material deposition—and the interplay between them are considered by presenting a yield function, flow rule and hardening law. A fibre-reinforcement formulation is used to account for the role of cellulose microfibrils in the anisotropic growth. Mechanisms in in vivo growth are taken into account to represent the corresponding biologycontrolled behaviour of a cell wall. A viscoelastic formulation is proposed to capture the viscoelastic response in the cell wall. The proposed constitutive model provides a unique framework for modelling both the in vivo growth of cell wall dominated by viscoplasticity-like behaviour and in vitro deformation dominated by elastic or viscoelastic responses. A numerical scheme is devised, and FE case studies are reported and compared with experimental data