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  • 1. Høye, Ellen Marie
    et al.
    Skyt, Peter S.
    Balling, Peter
    Muren, Ludvig P.
    Taasti, Vicki T.
    Swakoń, Jan
    Mierzwińska, Gabriela
    Rydygier, Marzena
    Bassler, Niels
    Stockholm University, Faculty of Science, Department of Physics. Aarhus University, Denmark.
    Petersen, Jørgen B. B.
    Chemically tuned linear energy transfer dependent quenching in a deformable, radiochromic 3D dosimeter2017In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 62, no 4, p. N73-N89Article in journal (Refereed)
    Abstract [en]

    Most solid-state detectors, including 3D dosimeters, show lower signal in the Bragg peak than expected, a process termed quenching. The purpose of this study was to investigate how variation in chemical composition of a recently developed radiochromic, silicone-based 3D dosimeter influences the observed quenching in proton beams. The dependency of dose response on linear energy transfer, as calculated through Monte Carlo simulations of the dosimeter, was investigated in 60 MeV proton beams. We found that the amount of quenching varied with the chemical composition: peak-to-plateau ratios (1 cm into the plateau) ranged from 2.2 to 3.4, compared to 4.3 using an ionization chamber. The dose response, and thereby the quenching, was predominantly influenced by the curing agent concentration, which determined the dosimeter's deformation properties. The dose response was found to be linear at all depths. All chemical compositions of the dosimeter showed dose-rate dependency; however this was not dependent on the linear energy transfer. Track-structure theory was used to explain the observed quenching effects. In conclusion, this study shows that the silicone-based dosimeter has potential for use in measuring 3D-dose-distributions from proton beams.

  • 2. Nielsen, Steffen
    et al.
    Bassler, Niels
    Stockholm University, Faculty of Science, Department of Physics.
    Grzanka, Leszek
    Swakon, Jan
    Olko, Pawel
    Andreassen, Christian Nicolaj
    Overgaard, Jens
    Alsner, Jan
    Singers Sørensen, Brita
    Differential gene expression in primary fibroblasts induced by proton and cobalt-60 beam irradiation2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 11, p. 1406-1412Article in journal (Refereed)
    Abstract [en]

    Introduction: Proton beam therapy delivers a more conformal dose distribution than conventional radiotherapy, thus improving normal tissue sparring. Increasing linear energy transfer (LET) along the proton track increases the relative biological effectiveness (RBE) near the distal edge of the Spread-out Bragg peak (SOBP). The severity of normal tissue side effects following photon beam radiotherapy vary considerably between patients.

    Aim: The dual study aim was to identify gene expression patterns specific to radiation type and proton beam position, and to assess whether individual radiation sensitivity influences gene expression levels in fibroblast cultures irradiated in vitro.

    Methods: The study includes 30 primary fibroblast cell cultures from patients previously classified as either radiosensitive or radioresistant. Cells were irradiated at three different positions in the proton beam profile: entrance, mid-SOBP and at the SOBP distal edge. Dose was delivered in three fractions × 3.5 Gy(RBE) (RBE 1.1). Cobalt-60 (Co-60) irradiation was used as reference. Real-time qPCR was performed to determine gene expression levels for 17 genes associated with inflammation response, fibrosis and angiogenesis.

    Results: Differences in median gene expression levels were observed for multiple genes such as IL6, IL8 and CXCL12. Median IL6 expression was 30%, 24% and 47% lower in entrance, mid-SOBP and SOBP distal edge groups than in Co-60 irradiated cells. No genes were found to be oppositely regulated by different radiation qualities. Radiosensitive patient samples had the strongest regulation of gene expression; irrespective of radiation type.

    Conclusions: Our findings indicate that the increased LET at the SOBP distal edge position did not generally lead to increased transcriptive response in primary fibroblast cultures. Inflammatory factors were generally less extensively upregulated by proton irradiation compared with Co-60 photon irradiation. These effects may possibly influence the development of normal tissue damage in patients treated with proton beam therapy.

  • 3. Singers Sørensen, Brita
    et al.
    Bassler, Niels
    Stockholm University, Faculty of Science, Department of Physics.
    Nielsen, Steffen
    Horsman,, Michael R.
    Grzanka, Leszek
    Spejlborg, Harald
    Swakoń, Jan
    Olko, Paweł
    Overgaard, Jens
    Relative biological effectiveness (RBE) and distal edge effects of proton radiation on early damage in vivo2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 11, p. 1387-1391Article in journal (Refereed)
    Abstract [en]

    Introduction: The aim of the present study was to examine the RBE for early damage in an in vivo mouse model, and the effect of the increased linear energy transfer (LET) towards the distal edge of the spread-out Bragg peak (SOBP).

    Method: The lower part of the right hind limb of CDF1 mice was irradiated with single fractions of either 6 MV photons, 240 kV photons or scanning beam protons and graded doses were applied. For the proton irradiation, the leg was either placed in the middle of a 30-mm SOBP, or to assess the effect in different positions, irradiated in 4 mm intervals from the middle of the SOBP to behind the distal dose fall-off. Irradiations were performed with the same dose plan at all positions, corresponding to a dose of 31.25 Gy in the middle of the SOBP. Endpoint of the study was early skin damage of the foot, assessed by a mouse foot skin scoring system.

    Results: The MDD50 values with 95% confidence intervals were 36.1 (34.2–38.1) Gy for protons in the middle of the SOBP for score 3.5. For 6 MV photons, it was 35.9 (34.5–37.5) Gy and 32.6 (30.7–34.7) Gy for 240 kV photons for score 3.5. The corresponding RBE was 1.00 (0.94–1.05), relative to 6 MV photons and 0.9 (0.85–0.97) relative to 240 kV photons. In the mice group positioned at the SOBP distal dose fall-off, 25% of the mice developed early skin damage compared with 0–8% in other groups. LETd,z = 1 was 8.4 keV/μm at the distal dose fall-off and the physical dose delivered was 7% lower than in the central SOBP position, where LETd,z =1 was 3.3 keV/μm.

    Conclusions: Although there is a need to expand the current study to be able to calculate an exact enhancement ratio, an enhanced biological effect in vivo for early skin damage in the distal edge was demonstrated.

  • 4.
    Thomas, Henry
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Bassler, Niels
    Stockholm University, Faculty of Science, Department of Physics.
    Ureba, Ana
    Stockholm University, Faculty of Science, Department of Physics.
    Tsubouchi, Toshiro
    Valdman, Alexander
    Siegbahn, Albert
    Stockholm University, Faculty of Science, Department of Physics.
    Development of an interlaced-crossfiring geometry for proton grid therapy2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 11, p. 1437-1443Article in journal (Refereed)
    Abstract [en]

    Background: Grid therapy has in the past normally been performed with single field photon-beamgrids. In this work, we evaluated a method to deliver grid therapy based on interlacing and crossfiringgrids of mm-wide proton beamlets over a target volume, by Monte Carlo simulations.

    Material and methods: Dose profiles for single mm-wide proton beamlets (1, 2 and 3 mm FWHM) inwater were simulated with the Monte Carlo code TOPAS. Thereafter, grids of proton beamlets weredirected toward a cubic target volume, located at the center of a water tank. The aim was to deliver anearly homogeneous dose to the target, while creating high dose heterogeneity in the normal tissue,i.e., high gradients between valley and peak doses in the grids, down to the close vicinity of thetarget.

    Results: The relative increase of the beam width with depth was largest for the smallest beams(þ6.9mm for 1 mm wide and 150MeV proton beamlets). Satisfying dose coverage of the cubic targetvolume (r< ±5%) was obtained with the interlaced-crossfiring setup, while keeping the grid pattern ofthe dose distribution down to the target (valley-to-peak dose ratio<0.5 less than 1 cm before the tar-get). Center-to-center distances around 7–8 mm between the beams were found to give the best com-promise between target dose homogeneity and low peak doses outside of the target.

    Conclusions: A nearly homogeneous dose distribution can be obtained in a target volume by crossfir-ing grids of mm-wide proton-beamlets, while maintaining the grid pattern of the dose distribution atlarge depths in the normal tissue, close to the target volume. We expect that the use of this methodwill increase the tumor control probability and improve the normal tissue sparing in grid therapy.

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