| 1. |
- Antonovic, Laura, et al.
(författare)
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Clinical oxygen enhancement ratio of tumors in carbon ion radiotherapy : the influence of local oxygenation changes
- 2014
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Ingår i: Journal of radiation research. - : Oxford University Press (OUP). - 0449-3060 .- 1349-9157. ; 55:5, s. 902-911
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Tidskriftsartikel (refereegranskat)abstract
- The effect of carbon ion radiotherapy on hypoxic tumors has recently been questioned because of low linear energy transfer (LET) values in the spread-out Bragg peak (SOBP). The aim of this study was to investigate the role of hypoxia and local oxygenation changes (LOCs) in fractionated carbon ion radiotherapy. Three-dimensional tumors with hypoxic subvolumes were simulated assuming interfraction LOCs. Different fractionations were applied using a clinically relevant treatment plan with a known LET distribution. The surviving fraction was calculated, taking oxygen tension, dose and LET into account, using the repairable–conditionally repairable (RCR) damage model with parameters for human salivary gland tumor cells. The clinical oxygen enhancement ratio (OER) was defined as the ratio of doses required for a tumor control probability of 50% for hypoxic and well-oxygenated tumors. The resulting OER was well above unity for all fractionations. For the hypoxic tumor, the tumor control probability was considerably higher if LOCs were assumed, rather than static oxygenation. The beneficial effect of LOCs increased with the number of fractions. However, for very low fraction doses, the improvement related to LOCs did not compensate for the increase in total dose required for tumor control. In conclusion, our results suggest that hypoxia can influence the outcome of carbon ion radiotherapy because of the non-negligible oxygen effect at the low LETs in the SOBP. However, if LOCs occur, a relatively high level of tumor control probability is achievable with a large range of fractionation schedules for tumors with hypoxic subvolumes, but both hyperfractionation and hypofractionation should be pursued with caution.
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| 2. |
- Antonovic, Laura, et al.
(författare)
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Radiobiological description of the LET dependence of the cell survival of oxic and anoxic cells irradiated by carbon ions
- 2013
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Ingår i: Journal of radiation research. - : Oxford University Press (OUP). - 0449-3060 .- 1349-9157. ; 54:1, s. 18-26
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Tidskriftsartikel (refereegranskat)abstract
- Light-ion radiation therapy against hypoxic tumors is highly curative due to reduced dependence on the presence of oxygen in the tumor at elevated linear energy transfer (LET) towards the Bragg peak. Clinical ion beams using spread-out Bragg peak (SOBP) are characterized by a wide spectrum of LET values. Accurate treatment optimization requires a method that can account for influence of the variation in response for a broad range of tumor hypoxia, absorbed doses and LETs. This paper presents a parameterization of the Repairable Conditionally-Repairable (RCR) cell survival model that can describe the survival of oxic and hypoxic cells over a wide range of LET values, and investigates the relationship between hypoxic radiation resistance and LET. The biological response model was tested by fitting cell survival data under oxic and anoxic conditions for V79 cells irradiated with LETs within the range of 30 – 500 keV/μm. The model provides good agreement with experimental cell survival data for the range of LET investigated, confirming the robustness of the parameterization method. This new version of the RCR model is suitable for describing the biological response of mixed populations of oxic and hypoxic cells and at the same time taking into account the distribution of doses and LETs in the incident beam and its variation with depth in tissue. The model offers a versatile tool for the selection of LET and dose required in the optimization of the therapeutic effect, without severely affecting normal tissue in realistic tumors presenting highly heterogeneous oxic and hypoxic regions.
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| 3. |
- Antonovic, Laura, 1982-, et al.
(författare)
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Relative clinical effectiveness of carbon ion radiotherapy: theoretical modelling for H&N tumours
- 2015
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Ingår i: Journal of radiation research. - : Oxford University Press (OUP). - 0449-3060 .- 1349-9157. ; 56:4, s. 639-645
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Tidskriftsartikel (refereegranskat)abstract
- Comparison of the efficiency of photon and carbon ion radiotherapy (RT) administered with the same number of fractions might be of limited clinical interest, since a wide range of fractionation patterns are used clinically today. Due to advanced photon treatment techniques, hypofractionation is becoming increasingly accepted for prostate and lung tumours, whereas patients with head and neck tumours still benefit from hyperfractionated treatments. In general, the number of fractions is considerably lower in carbon ion RT. A clinically relevant comparison would be between fractionation schedules that are optimal within each treatment modality category. In this in silico study, the relative clinical effectiveness (RCE) of carbon ions was investigated for human salivary gland tumours, assuming various radiation sensitivities related to their oxygenation. The results indicate that, for hypoxic tumours in the absence of reoxygenation, the RCE (defined as the ratio of D50 for photons to carbon ions) ranges from 3.5 to 5.7, corresponding to carbon ion treatments given in 36 and 3 fractions, respectively, and 30 fractions for photons. Assuming that interfraction local oxygenation changes take place, results for RCE are lower than that for an oxic tumour if only a few fractions of carbon ions are used. If the carbon ion treatment is given in more than 12 fractions, the RCE is larger for the hypoxic than for the well-oxygenated tumour. In conclusion, this study showed that in silico modelling enables the study of a wide range of factors in the clinical considerations and could be an important step towards individualisation of RT treatments.
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| 4. |
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| 5. |
- Böhlen, Till Tobias, et al.
(författare)
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A Monte Carlo-based treatment-planning tool for ion beam therapy
- 2013
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Ingår i: Journal of radiation research. - : Oxford University Press (OUP). - 0449-3060 .- 1349-9157. ; 54, s. 77-81
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Tidskriftsartikel (refereegranskat)abstract
- Ion beam therapy, as an emerging radiation therapy modality, requires continuous efforts to develop and improve tools for patient treatment planning (TP) and research applications. Dose and fluence computation algorithms using the Monte Carlo (MC) technique have served for decades as reference tools for accurate dose computations for radiotherapy. In this work, a novel MC-based treatment-planning (MCTP) tool for ion beam therapy using the pencil beam scanning technique is presented. It allows single-field and simultaneous multiple-fields optimization for realistic patient treatment conditions and for dosimetric quality assurance for irradiation conditions at state-of-the-art ion beam therapy facilities. It employs iterative procedures that allow for the optimization of absorbed dose and relative biological effectiveness (RBE)-weighted dose using radiobiological input tables generated by external RBE models. Using a re-implementation of the local effect model (LEM), the MCTP tool is able to perform TP studies using ions with atomic numbers Z < 8. Example treatment plans created with the MCTP tool are presented for carbon ions in comparison with a certified analytical treatment-planning system. Furthermore, the usage of the tool to compute and optimize mixed-ion treatment plans, i.e. plans including pencil beams of ions with different atomic numbers, is demonstrated. The tool is aimed for future use in research applications and to support treatment planning at ion beam facilities.
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| 6. |
- Nakamura, Ayumi, et al.
(författare)
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Application of cell sorting for enhancing the performance of the cytokinesis-block micronucleus assay
- 2016
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Ingår i: Journal of radiation research. - : Oxford University Press (OUP). - 0449-3060 .- 1349-9157. ; 57:2, s. 121-126
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Tidskriftsartikel (refereegranskat)abstract
- Among the numerous methods available to assess genotoxicity, the cytokinesis-block micronucleus (CBMN) assay is very popular due its relative simplicity and power to detect both clastogenic and aneugenic compounds. A problem with the CBMN assay is that all DNA damaging agents also inhibit the ability of cells to progress through mitosis, leading to a low number of binucleated cells (BNCs). One method to resolve this issue is to ensure a sufficient proportion of BNCs in the samples. In the current study, the applicability of a cell sorting system capable of isolating cell fractions containing abundant BNCs was investigated. Furthermore, to investigate the relationship between the cell division delay due to radiation exposure and the generation of BNCs and micronuclei (MN), we assessed a series of lag times between radiation exposure and addition of cytochalasin-B (Cyt-B). Cells from the human chronic myelogenous leukemia cell line K562 were exposed to X-rays (2 Gy and 4 Gy), and Cyt-B was subsequently added at 0, 6 and 12 h following irradiation. After treatment with Cyt-B for 24 h, the percentage of BNCs, the MN frequency and the cell cycle distribution were analyzed. In addition, cells displaying the DNA contents corresponding to BNCs were isolated and analyzed. The results indicate that applying the cell sorter to the CBMN assay increased the percentage of BNCs compared with the standard method. Thus, this technique is a promising way of enhancing the capacity of the CBMN assay.
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| 7. |
- Ploc, Ondrej, et al.
(författare)
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Poster session 11: Space dosimetry and environment dosimetry measurements using timepix in mixed radiation fields induced by heavy ions; comparison with standard dosimetry methods
- 2014
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Ingår i: Journal of Radiation Research. - : Oxford University Press (OUP). - 0449-3060 .- 1349-9157. ; 55, s. i141-i142
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Tidskriftsartikel (refereegranskat)abstract
- Objective of our research was to explore capabilities of Timepix for its use as a single dosemeter and LET spectrometer in mixed radiation fields created by heavy ions. We exposed it to radiation field (i) at heavy ion beams at HIMAC, Chiba, Japan, (ii) in the CERN's high-energy reference field (CERF) facility at Geneva, France/Switzerland, (iii) in the exposure room of the proton therapy laboratory at JINR, Dubna, Russia, and (iv) onboard aircraft. We compared the absolute values of dosimetric quantities obtained with Timepix and with other dosemeters and spectrometers like tissue-equivalent proportional counter (TEPC) Hawk, silicon detector Liulin, and track-etched detectors (TEDs). © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Therapeutic Radiology and Oncology.
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