| 1. |
- Raptis, Apostolos, et al.
(författare)
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Cancer risk after breast proton therapy considering physiological and radiobiological uncertainties
- 2020
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Ingår i: Physica medica (Testo stampato). - : Elsevier BV. - 1120-1797 .- 1724-191X. ; 76, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Background: The reduced normal tissue dose burden from protons can reduce the risk of second cancer for breast cancer patients. Breathing motion and the impact of variable relative biological effectiveness (RBE) are however concerns for proton dose distributions. This study aimed to quantify the impact of these factors on risk predictions from proton and photon therapy.Materials and methods: Twelve patients were planned in free breathing with protons and photons to deliver 50 Gy (RBE) in 25 fractions (assuming RBE = 1.1 for protons) to the left breast. Second cancer risk was evaluated with several models for the lungs, contralateral breast, heart and esophagus as organs at risk (OARs). Plans were recalculated on CT-datasets acquired in extreme phases to account for breathing motion. Proton plans were also recalculated assuming variable RBE for a range of radiobiological parameters.Results: The OARs received substantially lower doses from protons compared to photons. The highest risks were for the lungs (average second cancer risks of 0.31% and 0.12% from photon and proton plans, respectively). The reduced risk with protons was maintained, even when breathing and/or RBE variation were taken into account. Furthermore, while the total risks from the photon plans were seen to increase with the integral dose, no such correlation was observed for the proton plans.Conclusions: Protons have an advantage over the photons with respect to the induction of cancer. Uncertainties in physiological movements and radiobiological parameters affected the absolute risk estimates, but not the general trend of lower risk associated with proton therapy.
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| 2. |
- Romero-Expósito, Maite, et al.
(författare)
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Determining out-of-field doses and second cancer risk from proton therapy in young patients : an overview
- 2022
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Proton therapy has the potential to provide survival and tumor control outcomes comparable and frequently superior to photon therapy. This has led to a significant concern in the medical physics community on the risk for the induction of second cancers in all patients and especially in younger patients, as they are considered more radiosensitive than adults and have an even longer expected lifetime after treatment. Thus, our purpose is to present an overview of the research carried out on the evaluation of out-of-field doses linked to second cancer induction and the prediction of this risk. Most investigations consisted of Monte Carlo simulations in passive beam facilities for clinical scenarios. These works established that equivalent doses in organs could be up to 200 mSv or 900 mSv for a brain or a craniospinal treatment, respectively. The major contribution to this dose comes from the secondary neutrons produced in the beam line elements. Few works focused on scanned-beam facilities, but available data show that, for these facilities, equivalent doses could be between 2 and 50 times lower. Patient age is a relevant factor in the dose level, especially for younger patients (by means of the size of the body) and, in addition, in the predicted risk by models (due to the age dependence of the radiosensitivity). For risks, the sex of the patient also plays an important role, as female patients show higher sensitivity to radiation. Thus, predicted risks of craniospinal irradiation can range from 8% for a 15-year-old male patient to 58% for a 2-year-old female patient, using a risk model from a radiological protection field. These values must be taken with caution due to uncertainties in risk models, and then dosimetric evaluation of stray radiation becomes mandatory in order to complement epidemiological studies and be able to model appropriate dose-response functions for this dose range. In this sense, analytical models represent a useful tool and some models have been implemented to be used for young patients. Research carried out so far confirmed that proton beam therapy reduces the out-of-field doses and second cancer risk. However, further investigations may be required in scanned-beam delivery systems.
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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
- 2023
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Ingår i: Medical physics (Lancaster). - 0094-2405.
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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. |
- Sandström, Helena, et al.
(författare)
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Simultaneous truth and performance level estimation method for evaluation of target contouring in radiosurgery
- 2021
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 41:1, s. 279-288
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: The problem of lack of standardisation in target delineation and herewith the variability of target contours in Gamma Knife radiosurgery is as severe as in linac-based radiotherapy in general. The first aim of this study was to quantify the contouring variability for a group of five radiosurgery targets and estimate their true-volume based on multiple delineations using the Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm. The second aim was to assess the robustness of the STAPLE method for the assessment of the true-volume, with respect to the number of contours available as input. Patients and Methods: A multicentre analysis of the variability in contouring of five cases was performed. Twelve contours were provided for each case by experienced planners for Gamma Knife. To assess the robustness of the STAPLE method with respect to the number of contours used as input, sets of contours were randomly selected in the analysis. Results: A high similarity was observed between the STAPLE generated true-volume and the 50%-agreement volume when all 12 available contours were used as input (90-100%). Lower similarity was observed with smaller sets of contours (10-70%). Conclusion: If a high number of input contours is available, the STAPLE method provides a valuable tool in the estimation of the true volume of a target based on multiple contours as well as the sensitivity and specificity for each input contour relative to the true volume of that structure. The robustness of the STAPLE method for rendering the true target volume depends on the number of contours provided as input and their variability with respect to shape, size and position.
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| 5. |
- Santacroce, Antonio, et al.
(författare)
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Proton beam radiation therapy for vestibular schwannomas-tumor control and hearing preservation rates : a systematic review and meta-analysis
- 2023
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Ingår i: Neurosurgical review. - : Springer Nature. - 0344-5607 .- 1437-2320. ; 46:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective Proton beam therapy is considered, by some authors, as having the advantage of delivering dose distributions more conformal to target compared with stereotactic radiosurgery (SRS). Here, we performed a systematic review and metaanalysis of proton beam for VSs, evaluating tumor control and cranial nerve preservation rates, particularly with regard to facial and hearing preservation.Methods We reviewed, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) articles published between 1968 and September 30, 2022. We retained 8 studies reporting 587 patients.Results Overall rate of tumor control (both stability and decrease in volume) was 95.4% (range 93.5–97.2%, p heterogeneity= 0.77, p<0.001). Overall rate of tumor progression was 4.6% (range 2.8–6.5%, p heterogeneity < 0.77, p<0.001). Overall rate of trigeminal nerve preservation (absence of numbness) was 95.6% (range 93.5–97.7%, I2 = 11.44%, p heterogeneity= 0.34, p<0.001). Overall rate of facial nerve preservation was 93.7% (range 89.6–97.7%, I2 = 76.27%, p heterogeneity<0.001, p<0.001). Overall rate of hearing preservation was 40.6% (range 29.4–5 International Stereotactic Radiosurgery 1.8%, I2 = 43.36%, p heterogeneity= 0.1, p<0.001).Conclusion Proton beam therapy for VSs achieves high tumor control rates, as high as 95.4%. Facial rate preservation overall rates are 93%, which is lower compared to the most SRS series. Compared with most currently reported SRS techniques, proton beam radiation therapy for VSs does not ofer an advantage for facial and hearing preservation compared to most of the currently reported SRS series.
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| 6. |
- Toma-Dasu, Iuliana, et al.
(författare)
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RBE for proton radiation therapy – a Nordic view in the international perspective
- 2020
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 59:10, s. 1151-1156
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Tidskriftsartikel (refereegranskat)abstract
- Background: This paper presents an insight into the critical discussions and the current strategies of the Nordic countries for handling the variable proton relative biological effectiveness (RBE) as presented at The Nordic Collaborative Workshop for Particle Therapy that took place at the Skandion Clinic on 14th and 15th of November 2019.Material and methods: In the current clinical practice at the two proton centres in operation at the date, Skandion Clinic, and the Danish Centre for Particle Therapy, a constant proton RBE of 1.1 is applied. The potentially increased effectiveness at the end of the particle range is however considered at the stage of treatment planning at both places based on empirical observations and knowledge. More elaborated strategies to evaluate the plans and mitigate the problem are intensely investigated internationally as well at the two centres. They involve the calculation of the dose-averaged linear energy transfer (LETd) values and the assessment of their distributions corroborated with the distribution of the dose and the location of the critical clinical structures.Results: Methods and tools for LETd calculations are under different stages of development as well as models to account for the variation of the RBE with LETd, dose per fraction, and type of tissue. The way they are currently used for evaluation and optimisation of the plans and their robustness are summarised. A critical but not exhaustive discussion of their potential future implementation in the clinical practice is also presented.Conclusions: The need for collaboration between the clinical proton centres in establishing common platforms and perspectives for treatment planning evaluation and optimisation is highlighted as well as the need of close interaction with the research academic groups that could offer a complementary perspective and actively help developing methods and tools for clinical implementation of the more complex metrics for considering the variable effectiveness of the proton beams.
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| 7. |
- Tuleasca, Constantin, et al.
(författare)
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Impact of the Mean Cochlear Biologically Effective Dose on Hearing Preservation After Stereotactic Radiosurgery for Vestibular Schwannoma: A Retrospective Longitudinal Analysis
- 2024
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Ingår i: Neurosurgery. - 0148-396X .- 1524-4040. ; 94:1, s. 174-182
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) is a useful alternative for small- to medium-sizedvestibular schwannoma. To evaluate whether biologically effective dose (BEDGy2.47), calculated for mean (BEDGy2.47 mean)and maximal (BEDGy2.47 max) cochlear dose, is relevant for hearing preservation. METHODS: This is a retrospective longitudinal single-center study. Were analyzed 213 patients with useful baselinehearing. Risk of hearing decline was assessed for Gardner–Robertson classes and pure tone average (PTA) loss. The meanfollow-up period was 39 months (median 36, 6-84).RESULTS: Hearing decline (Gardner–Robertson class) 3 years after SRS was associated with higher cochlear BEDGy2.47 mean(odds ratio [OR] 1.39, P = .009). Moreover, BEDGy2.47 mean was more relevant as compared with BEDGy2.47 max (OR 1.13, P = .04).Risk of PTA loss (continuous outcome, follow-up minus baseline) was significantly corelated with BEDGy2.47 mean at 24 (betacoefficient 1.55, P = .002) and 36 (beta coefficient 2.01, P = .004) months after SRS. Risk of PTA loss (>20 dB vs ≤) was associatedwith higher BEDGy2.47 mean at 6 (OR 1.36, P = .002), 12 (OR 1.36, P = .007), and 36 (OR 1.37, P = .02) months. Risk of hearingdecline at 36 months for the BEDGy2.47 mean of 7–8, 10, and 12 Gy2.47 was 28%, 57%, and 85%, respectively. CONCLUSION: Cochlear BEDGy2.47 mean is relevant for hearing decline after SRS and more relevant as compared withBEDGy2.47 max. Three years after SRS, this was sustained for all hearing decline evaluation modalities. Our data suggestthe BEDGy2.47 mean cut-off of ≤8 Gy2.47 for better hearing preservation rates.
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| 8. |
- Tuleasca, Constantin, et al.
(författare)
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The Relevance of Biologically Effective Dose for Hearing Preservation After Stereotactic Radiosurgery for Vestibular Schwannomas : A Retrospective Longitudinal Study
- 2023
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Ingår i: Neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 0148-396X .- 1524-4040. ; 92:6, s. 1216-1226
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Stereotactic radiosurgery has become a common treatment approach for small-to-medium size vestibular schwannomas.OBJECTIVE: To evaluate relationship between time (beam-on and treatment) and risk of hearing decline after stereotactic radiosurgery for vestibular schwannomas in patients with Gardner–Robertson (GR) baseline classes I and II.METHODS: This retrospective longitudinal single-center study included 213 patients with GR I and II treated between June 2010 and December 2019. Risk of passing from GR classes I and II (coded 0) to other classes III, IV, and V (coded 1) and the increase in pure tone average (continuous outcome) were evaluated using a mixed-effect regression model. Biologically effective dose (BED) was further assessed for an alpha/beta ratio of 2.47 (Gy2.47).RESULTS: Binary outcome analysis revealed sex, dose rate, integral dose, time [beam-on time odds ratio 1.03, P = .03, 95% CI 1.00-1.06; treatment time (P = .02) and BED (P = .001) as relevant. Fitted multivariable model included the sex, dose rate, and BED. Pure tone average analysis revealed age, integral dose received by tumor, isocenter number, time (beam-on time odds ratio 0.20, P = .001, 95% CI 0.083-0.33) and BED (P = .005) as relevant.CONCLUSION: Our analysis showed that risk of hearing decline was associated with male sex, higher radiation dose rate (cutoff 2.5 Gy/minute), higher integral dose received by the tumor, higher beam-on time ≥20 minutes, and lower BED. A BED between 55 and 61 was considered as optimal for hearing preservation.
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| 9. |
- Ureba, Ana, et al.
(författare)
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Assessment of the probability of tumour control for prescribed doses based on imaging of oxygen partial pressure
- 2021
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Ingår i: Oxygen Transport to Tissue XLII. - Cham : Springer. - 9783030482367 - 9783030482381 ; 1269, s. 185-190
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Bokkapitel (refereegranskat)abstract
- In radiotherapy, hypoxia is a known negative factor, occurring especially in solid malignant tumours. Nitroimidazole-based positron emission tomography (PET) tracers, due to their selective binding to hypoxic cells, could be used as surrogates to image and quantify the underlying oxygen distributions in tissues. The spatial resolution of a clinical PET image, however, is much larger than the cellular spatial scale where hypoxia occurs. A question therefore arises regarding the possibility of quantifying different hypoxia levels based on PET images, and the aim of the present study is the prescription of corresponding therapeutic doses and its exploration.A tumour oxygenation model was created consisting of two concentric spheres with different oxygen partial pressure (pO2) distributions. In order to mimic a PET image of the simulated tumour, given the relation between uptake and pO2, fundamental effects that limit spatial resolution in a PET imaging system were considered: the uptake distribution was processed with a Gaussian 3D filter, and a re-binning to reach a typical PET image voxel size was performed. Prescription doses to overcome tumour hypoxia and predicted tumour control probability (TCP) were calculated based on the processed images for several fractionation schemes. Knowing the underlying oxygenation at microscopic scale, the actual TCP expected after the delivery of the calculated prescription doses was evaluated. Results are presented for three different dose painting strategies: by numbers, by contours and by using a voxel grouping-based approach.The differences between predicted TCP and evaluated TCP indicate that careful consideration must be taken on the dose prescription strategy and the selection of the number of fractions, depending on the severity of hypoxia.
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| 10. |
- Zubatkina, Irina, et al.
(författare)
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Clinically Driven Alpha/Beta Ratios for Melanoma Brain Metastases and Investigation of Biologically Effective Dose as a Predictor for Local Control After Radiosurgery : A Proof of Concept in a Retrospective Longitudinal Series of 274 Consecutive Lesions
- 2024
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Ingår i: Neurosurgery. - : Wolters Kluwer. - 0148-396X .- 1524-4040. ; 94:2, s. 423-430
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Brain metastases (BM) develop in nearly half of the patients with advanced melanoma. The aim of this retrospective historical cohort study was to analyze radiological response of melanoma BM to single-fraction Gamma Knife radiosurgery (GKRS), in relation to biologically effective dose (BED) for various alpha/beta ratios.METHODS: Included in the study were 274 lesions. Primary outcome was local control (LC). Mean marginal dose was 21.6 Gy (median 22, range 15-25). Biologically effective dose was calculated for an alpha/beta ratio of 3 (Gy3), 5 (Gy10), 10 (Gy10), and 15 (Gy15).RESULTS: Receiver operating characteristic value for LC and BED was 85% (most statistically significant odds ratio 1.14 for BED Gy15, P = .006), while for LC and physical dose was 79% (P = .02). When comparing equality of 2 receiver operating characteristic areas, this was statistically significant (P = .02 and .03). Fractional polynomial regression revealed BED (Gy10 and Gy15) as statistically significant (P = .05) with BED of more than 63 Gy10 or 49 Gy15 as relevant, also for higher probability of quick decrease in volume first month after GKRS and lower probability of radiation necrosis. Shorter irradiation time was associated with better LC (P = .001), particularly less than 40 minutes (LC below 90%, P = .05).CONCLUSION: BED Gy10 and particularly Gy15 were more statistically significant than physical dose for LC after GKRS for radioresistant melanoma BM. Irradiation time (per lesion) longer than 40 minutes was predictive for lower rates of LC. Such results need to be validated in larger cohorts.
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