| 1. |
- Dasu, Alexandru, et al.
(författare)
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Impact of variable RBE on proton fractionation
- 2013
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Ingår i: Medical physics (Lancaster). - : Wiley. - 0094-2405 .- 2473-4209. ; 40:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To explore the impact of variable proton RBE on dose fractionation for clinically-relevant situations. A generic RBE=1.1 is generally used for isoeffect calculations, while experimental studies showed that proton RBE varies with tissue type, dose and LET.Material and methods: An analytical expression for the LET and α/β dependence of the LQ model has been used for proton simulations in parallel with the assumption of a generic RBE=1.1. Calculations have been performed for ranges of LET values and fractionation sensitivities to describe clinically-relevant cases, like the treatment of H&N and prostate tumors. Isoeffect calculations were compared with predictions from a generic RBE value and reported clinical results.Results: The generic RBE=1.1 appears to be a reasonable estimate for the proton RBE of rapidly growing tissues irradiated with low LET radiation. However, the use of a variable RBE predicts larger differences for tissues with low α/β (both tumor and normal) and at low doses per fraction. In some situations these differences may appear in contrast to the findings from photon studies highlighting the importance of accurate accounting for the radiobiological effectiveness of protons. Furthermore, the use of variable RBE leads to closer predictions to clinical results. Conclusions: The LET dependence of the RBE has a strong impact on the predicted effectiveness of fractionated proton radiotherapy. The magnitude of the effect is modulated by the fractionation sensitivity and the fractional dose indicating the need for accurate analyses both in the target and around it. Care should therefore be employed for changing clinical fractionation patterns or when analyzing results from clinical studies for this type of radiation.
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| 2. |
- Kjellsson Lindblom, Emely, et al.
(författare)
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Impact of SBRT fractionation in hypoxia dose painting - accounting for heterogeneous and dynamic tumour oxygenation
- 2019
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Ingår i: Medical physics (Lancaster). - : Wiley. - 0094-2405 .- 2473-4209. ; 46:5, s. 2512-2521
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTumor hypoxia, often found in nonsmall cell lung cancer (NSCLC), implies an increased resistance to radiotherapy. Pretreatment assessment of tumor oxygenation is, therefore, warranted in these patients, as functional imaging of hypoxia could be used as a basis for dose painting. This study aimed at investigating the feasibility of using a method for calculating the dose required in hypoxic subvolumes segmented on 18F‐HX4 positron emission tomography (PET) imaging of NSCLC.MethodsPositron emission tomography imaging data based on the hypoxia tracer 18F‐HX4 of 19 NSCLC patients were included in the study. Normalized tracer uptake was converted to oxygen partial pressure (pO2) and hypoxic target volumes (HTVs) were segmented using a threshold of 10 mmHg. Uniform doses required to overcome the hypoxic resistance in the target volumes were calculated based on a previously proposed method taking into account the effect of interfraction reoxygenation, for fractionation schedules ranging from extremely hypofractionated stereotactic body radiotherapy (SBRT) to conventionally fractionated radiotherapy.ResultsGross target volumes ranged between 6.2 and 859.6 cm3, and the hypoxic fraction < 10 mmHg between 1.2% and 72.4%. The calculated doses for overcoming the resistance of cells in the HTVs were comparable to those currently prescribed in clinical practice as well as those previously tested in feasibility studies on dose escalation in NSCLC. Depending on the size of the HTV and the distribution of pO2, HTV doses were calculated as 43.6–48.4 Gy for a three‐fraction schedule, 51.7–57.6 Gy for five fractions, and 59.5–66.4 Gy for eight fractions. For patients in whom the HTV pO2 distribution was more favorable, a lower dose was required despite a bigger volume. Tumor control probability was lower for single‐fraction schedules, while higher levels of tumor control probability were found for schedules employing several fractions.ConclusionsThe method to account for heterogeneous and dynamic hypoxia in target volume segmentation and dose prescription based on 18F‐HX4‐PET imaging appears feasible in NSCLC patients. The distribution of oxygen partial pressure within HTV could impact the required prescribed dose more than the size of the volume.
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| 3. |
- Romero-Expósito, Maite, et al.
(författare)
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Range shifter contribution to neutron exposure of patients undergoing proton pencil beam scanning
- 2024
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Ingår i: Medical physics (Lancaster). - : John Wiley & Sons. - 0094-2405. ; 51:7, s. 5099-5108
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Tidskriftsartikel (refereegranskat)abstract
- Background: Superficial targets require the use of the lowest energies within the available energy range in proton pencil-beam scanning (PBS) technique. However, the lower efficiency of the energy selection system at these energies and the requirement of a greater number of layers may represent disadvantages for this approach. The alternative is to use a range shifter (RS) at nozzle exit. However, one of the concerns of using this beamline element is that it becomes an additional source of neutrons that could irradiate organs situated far from the target.Purpose: The purpose of this study is to assess the increase in neutron dose due to the RS in proton PBS technique. Additionally, an analytical model for the neutron production is tested.Methods: Two clinical plans, designed to achieve identical target coverage, were created for an anthropomorphic phantom. These plans consisted of a lateral field delivering an absorbed dose of 60 Gy (RBE) to the target. One of the plans employed the RS. The MCNP code was used to simulate the plans, evaluating the distribution of neutron dose equivalent (Hn) and the equivalent dose in organ. In the plan with the RS plan, neutron production from both the patient and the RS were assessed separately. Hn values were also fitted versus the distance to field edge using a Gaussian function.Results: Hn per prescription dose, in the plan using the RS, ranged between 1.4 and 3.7 mSv/Gy at the field edge, whereas doses at 40 cm from the edge ranged from 9.9 to 32 μSv/Gy. These values are 1.2 to 10 times higher compared to those obtained without the RS. Both this factor and the contribution of neutrons originating from the RS increases with the distance from field edge. A triple-Gaussian function was able to reproduce the equivalent dose in organs within a factor of 2, although underestimating the values.Conclusions: The dose deposited in the patient by the neutrons originating from the RS predominantly affects areas away from the target (beyond approximately 25 cm from field edge), resulting in a neutron dose equivalent of the order of mSv. This indicates an overall low neutron contribution from the use of RS in PBS.
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| 4. |
- Ödén, Jakob, et al.
(författare)
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Spatial correlation of linear energy transfer and relative biological effectiveness with treatment related toxicities following proton therapy for intracranial tumors
- 2020
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Ingår i: Medical physics (Lancaster). - : Wiley. - 0094-2405 .- 2473-4209. ; 47:2, s. 342-351
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The enhanced relative biological effectiveness (RBE) at the end of the proton range might increase the risk of radiation-induced toxicities. This is of special concern for intracranial treatments where several critical organs at risk (OARs) surround the tumor. In the light of this, a retrospective analysis of dose-averaged linear energy transfer (LETd) and RBE-weighted dose (DRBE) distributions was conducted for three clinical cases with suspected treatment related toxicities following intracranial proton therapy. Alternative treatment strategies aiming to reduce toxicity risks are also presented.Methods: The clinical single-field optimized (SFO) plans were recalculated for 81 error scenarios with a Monte Carlo dose engine. The fractionation DRBE was 1.8 Gy (RBE) in 28 or 30 fractions assuming a constant RBE of 1.1. Two LETd- and α/β-dependent variable RBE models were used for evaluation, including a sensitivity analysis of the α/β parameter. Resulting distributions of DRBE and LETd were analyzed together with normal tissue complication probabilities (NTCPs). Subsequently, four multi-field optimized (MFO) plans, with an additional beam and/or objectives penalizing protons stopping in OARs, were created to investigate the potential reduction of LETd, DRBE and NTCP.Results: The two variable RBE models agreed well and predicted average RBE values around 1.3 in the toxicity volumes, resulting in increased near-maximum DRBE of 7-11 Gy (RBE) compared to RBE=1.1 in the nominal scenario. The corresponding NTCP estimates increased from 0.8%, 0.0% and 3.7% (RBE=1.1) to 15.5%, 1.8% and 45.7% (Wedenberg RBE model) for the three patients, respectively. The MFO plans generally allowed for LETd, DRBE and NTCP reductions in OARs, without compromising the target dose. Compared to the clinical SFO plans, the maximum reduction of the near-maximum LETd was 56%, 63% and 72% in the OAR exhibiting the toxicity for the three patients, respectively.Conclusions: Although a direct causality between RBE and toxicity cannot be established here, high LETd and DRBE correlated spatially with the observed toxicities, whereas setup and range uncertainties had a minor impact. Individual factors, which might affect the patient-specific radiosensitivity, were however not included in these calculations. The MFO plans using both an additional beam and proton track-end objectives allowed the largest reductions in LETd, DRBE and NTCP, and might be future tools for similar cases.
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| 5. |
- Dasu, Alexandru, et al.
(författare)
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Vascular oxygen content and the tissue oxygenation--a theoretical analysis.
- 2008
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Ingår i: Med Phys. - : American Association of Physicists in Medicine (AAPM). - 0094-2405. ; 35:2, s. 539-45
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Several methods exist for evaluating tumor oxygenation as hypoxia is an important prognostic factor for cancer patients. They use different measuring principles that highlight various aspects of oxygenation. The results could be empirically correlated, but it has been suspected that there could be discordances in some cases. This study describes an analysis of the relationship between vascular and tissue oxygenations. Theoretical simulation has been employed to characterize tissue oxygenations for a broad range of distributions of intervessel distances and vascular oxygenations. The results were evaluated with respect to the implications for practical measurements of tissue oxygenations. The findings showed that although the tissue oxygenation is deterministically related to vascular oxygenation, the relationship between them is not unequivocal. Variability also exists between the fractions of values below the sensitivity thresholds of various measurement methods which in turn could be reflected in the power of correlations between results from different methods or in the selection of patients for prognostic studies. The study has also identified potential difficulties that may be encountered at the quantitative evaluation of the results from oxygenation measurements. These could improve the understanding of oxygenation measurements and the interpretation of comparisons between results from various measurement methods.
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