| 1. |
- 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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| 2. |
- 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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| 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. |
- Bolsi, Alessandra, et al.
(författare)
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Practice patterns of image guided particle therapy in Europe : A 2016 survey of the European Particle Therapy Network (EPTN)
- 2018
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 128:1, s. 4-8
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Image guidance is critical in achieving accurate and precise radiation delivery in particle therapy, even more than in photon therapy. However, equipment, quality assurance procedures and clinical workflows for image-guided particle therapy (IGPT) may vary substantially between centres due to a lack of standardization. A survey was conducted to evaluate the current practice of IGPT in European particle therapy centres.Material and methods: In 2016, a questionnaire was distributed among 19 particle therapy centres in 12 European countries. The questionnaire consisted of 30 open and 37 closed questions related to image guidance in the general clinical workflow, for moving targets, current research activities and future perspectives of IGPT.Results: All centres completed the questionnaire. The IGPT methods used by the 10 treating centres varied substantially. The 9 non-treating centres were in the process to introduce IGPT. Most centres have developed their own IGPT strategies, being tightly connected to their specific technical implementation and dose delivery methods.Conclusions: Insight into the current clinical practice of IGPT in European particle therapy centres was obtained. A variety in IGPT practices and procedures was confirmed, which underlines the need for harmonisation of practice parameters and consensus guidelines.
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| 5. |
- Daşu, Alexandru, et al.
(författare)
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Dose-effect models for risk - relationship to cell survival parameters
- 2005
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:8, s. 829-835
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Tidskriftsartikel (refereegranskat)abstract
- There is an increased interest in estimating the induction of cancers following radiotherapy as the patients have nowadays a much longer life expectancy following the treatment. Clinical investigations have shown that the dose response relationship for cancer induction following radiotherapy has either of two main characteristics: an increase of the risk with dose to a maximum effect followed by a decrease or an increase followed by a levelling-off of the risk. While these behaviours have been described qualitatively, there is no mathematical model that can explain both of them on mechanistic terms. This paper investigates the relationship between the shape of the dose-effect curve and the cell survival parameters of a single risk model. Dose response relationships were described with a competition model which takes into account the probability to induce DNA mutations and the probability of cell survival after irradiation. The shape of the curves was analysed in relation to the parameters that have been used to obtain them. It was found that the two main appearances of clinical data for the induction of secondary cancer following radiotherapy could be the manifestations of the particular sets of parameters that describe the induction of mutations and cell kill for fractionated irradiations. Thus, the levelling off appearance of the dose response curve could be either a sign of moderate to high inducible repair effect in cell survival (but weak for DNA mutations) or the effect of heterogeneity, or both. The bell-shaped appearance encompasses all the other cases. The results also stress the importance of taking into account the details of the clinical delivery of dose in radiotherapy, mainly the fractionated character, as the findings of our study did not appear for single dose models. The results thus indicate that the shapes of clinically observed dose response curves for the induction of secondary cancers can be described by using one single competition model. It was also found that data for cancer induction may be linked to in vivo cell survival parameters that may be used for other modelling applications.
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| 6. |
- Dasu, Alexandru, et al.
(författare)
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Dose painting by numbers - do the practical limitations of the technique decrease or increase the probability of controlling tumours?
- 2013
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Ingår i: IFMBE Proceedings. - Berlin, Heidelberg : Springer Berlin/Heidelberg. - 1680-0737 .- 1433-9277. ; 39, s. 1731-1734, s. 1731-1734
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Tidskriftsartikel (refereegranskat)abstract
- One of the important questions regarding the feasibility of dose-painting-by-numbers approaches for treatment planning concerns the influence of the averaging of the imaging techniques used and the resolution of the planned and achieved dose distributions. This study investigates the impact of these aspects on the probability of controlling dynamic tumours. The effectiveness of dose painting approaches to target tumour hypoxia has been investigated in terms of the predicted tumour control probabilities (TCP) for tumours with dynamic oxygenations. Several levels of resolution for the resistance of the tumour or the planned dose distributions have been investigated. A very fine heterogeneous dose distribution ideally calculated at voxel level for a high target TCP would fail to control a tumour with dynamic oxygenation during the course of fractionated radiotherapy as mismatches between hotspots in the dose distribution and resistant hypoxic foci would lead to a significant loss in TCP. Only adaptive treatment would lead to reasonably high TCP. A coarse resolution for imaging or for dose distributions might compensate microscale mismatches in dynamic tumours, but the resulting tumour control could still be below the target levels. These results indicate that there is a complex relationship between the resolution of the dose-painting-by-numbers approaches and the dynamics of tumour oxygenation. Furthermore, the clinical success of hypoxia targeting strategies in the absence of adaptive approaches might be explained by changes in tumour radiation resistance through reoxygenation.
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| 7. |
- Dasu, Alexandru, et al.
(författare)
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Impact of increasing irradiation time on the treatment of prostate cancers
- 2015
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Ingår i: World Congress on Medical Physics and Biomedical Engineering, June 7-12, 2015, Toronto, Canada. - Cham : Springer. - 9783319193861 - 9783319193878 ; 51, s. 490-493
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Konferensbidrag (refereegranskat)abstract
- This study aimed to investigate the expected impact of intrafraction repair during increasing irradiation times for the treatment of prostate cancers. Lengthy sessions are indeed expected for some advanced irradiation techniques capable to deliver the large fractional doses required by the increased fractionation sensitivity of the prostates. For this purpose, clinically-derived parameters characterizing repair rates and dose response curves for prostate tumors have been used to calculate the expected loss of effectiveness when increasing the irradiation time. The results have shown that treatment sessions lasting more than about 20 to 40 minutes could reduce the probability of biochemical control of prostate tumors by more than 20 to 30 percentage points. These results are in agreement with some observed clinical results and therefore they suggest that treatment durations in prostate radiation therapy should be carefully recorded in order to explicitly account for intrafraction repair, especially when irradiation techniques make use of multiple beams and imaging sessions. Failure to do so might overestimate the expected effectiveness of the treatment and could lead to disappointing clinical results precisely from the demanding treatment modalities expected to increase the therapeutic gain in prostate radiotherapy.
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| 8. |
- 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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| 9. |
- Daşu, Alexandru, et al.
(författare)
-
In response to Dr. Karger et al.
- 2008
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 70:5, s. 1614-1615
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Dasu, Alexandru, et al.
(författare)
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Long-term effects and secondary tumors
- 2014
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Ingår i: Comprehensive biomedical physics. - Amsterdam : Elsevier. - 9780444536327 ; , s. 223-233, s. 223-233
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Bokkapitel (refereegranskat)abstract
- The issue of secondary tumours as long-term effects of radiation therapy has gained increased importance as the life expectancy of cancer patients has increased due to improvements in detecting and treating their primary tumours. Current knowledge indicates that radiotherapy leads to a small but significant risk of inducing cancers which is often referred to as the price to pay for the effectiveness of this treatment modality. Nevertheless, the levels of incidence for the long-term effects of radiation therapy may be influenced by many factors that could be both treatment-related and patient-related and therefore proposals have been made to include risk estimations in the process of treatment optimisation. This chapter summarises the current knowledge concerning the induction of secondary cancers after radiotherapy and discusses their consequences for the therapeutic use of ionising radiation.
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| 11. |
- Dasu, Alexandru, et al.
(författare)
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Models for the risk of secondary cancers from radiation therapy
- 2017
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Ingår i: Physica medica (Testo stampato). - London : Elsevier BV. - 1120-1797 .- 1724-191X. ; 42, s. 232-238
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Tidskriftsartikel (refereegranskat)abstract
- The interest in the induction of secondary tumours following radiotherapy has greatly increased as developments in detecting and treating the primary tumours have improved the life expectancy of cancer patients. However, most of the knowledge on the current levels of risk comes from patients treated many decades ago. As developments of irradiation techniques take place at a much faster pace than the progression of the carcinogenesis process, the earlier results could not be easily extrapolated to modern treatments. Indeed, the patterns of irradiation from historically-used orthovoltage radiotherapy and from contemporary techniques like conformal radiotherapy with megavoltage radiation, intensity modulated radiation therapy with photons or with particles are quite different. Furthermore, the increased interest in individualised treatment options raises the question of evaluating and ranking the different treatment plan options from the point of view of the risk for cancer induction, in parallel with the quantification of other long-term effects. It is therefore inevitable that models for risk assessment will have to be used to complement the knowledge from epidemiological studies and to make predictions for newer forms of treatment for which clinical evidence is not yet available. This work reviews the mathematical models that could be used to predict the risk of secondary cancers from radiotherapy-relevant dose levels, as well as the approaches and factors that have to be taken into account when including these models in the clinical evaluation process. These include the effects of heterogeneous irradiation, secondary particles production, imaging techniques, interpatient variability and other confounding factors.
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| 12. |
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| 13. |
- Dasu, Alexandru, et al.
(författare)
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Prostate alpha/beta revisited - an analysis of clinical results from 14168 patients
- 2012
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 51:8, s. 963-974
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Forskningsöversikt (refereegranskat)abstract
- Purpose: To determine the dose response parameters and the fractionation sensitivity of prostate tumours from clinical results of patients treated with external beam radiotherapy.Material and methods: The study was based on 5-year biochemical results from 14168 patients treated with external beam radiotherapy. Treatment data from 11330 patients treated with conventional fractionation have been corrected for overall treatment time and fitted with a logit equation. The results have been used to determine the optimum α/β values that minimise differences in predictions from 2838 patients treated with hypofractionated schedules.Results: Conventional fractionation data yielded logit dose response parameters for all risk groups and for all definitions of biochemical failures. The analysis of hypofractionation data led to very low α/β values (1-1.7 Gy) in all mentioned cases. Neglecting the correction for overall treatment time has little impact on the derivation of α/β values for prostate cancers.Conclusions: These results indicate that the high fractionation sensitivity is an intrinsic property of prostate carcinomas and they support the use of hypofractionation to increase the therapeutic gain for these tumours.
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| 14. |
- Daşu, Alexandru, et al.
(författare)
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Secondary malignancies from prostate cancer radiation treatment : a risk analysis of the influence of target margins and fractionation patterns
- 2011
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 79:3, s. 738-746
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: This study explores the implications for cancer induction of treatment details such as fractionation, planning target volume (PTV) definition, and interpatient variations, which are relevant for the radiation treatment of prostate carcinomas.METHODS AND MATERIALS: Treatment planning data from 100 patients have been analyzed with a risk model based on the United Nations Scientific Committee on the Effects of Atomic Radiation competition model. The risk model can account for dose heterogeneity and fractionation effects characteristic for modern radiotherapy. Biologically relevant parameters from clinical and experimental data have been used with the model.RESULTS: The results suggested that changes in prescribed dose could lead to a modification of the risks for individual organs surrounding the clinical target volume (CTV) but that the total risk appears to be less affected by changes in the target dose. Larger differences are observed for modifications of the margins between the CTV and the PTV because these have direct impact onto the dose level and dose heterogeneity in the healthy tissues surrounding the CTV. Interpatient anatomic variations also have to be taken into consideration for studies of the risk for cancer induction from radiotherapy.CONCLUSIONS: The results have shown the complex interplay between the risk for secondary malignancies, the details of the treatment delivery, and the patient heterogeneity that may influence comparisons between the long-term effects of various treatment techniques. Nevertheless, absolute risk levels seem very small and comparable to mortality risks from surgical interventions, thus supporting the robustness of radiation therapy as a successful treatment modality for prostate carcinomas.
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| 15. |
- Daşu, Alexandru, et al.
(författare)
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Should single or distributed parameters be used to explain the steepness of tumour control probability curves?
- 2003
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 48:3, s. 387-397
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Tidskriftsartikel (refereegranskat)abstract
- Linear quadratic (LQ) modelling allows easy comparison of different fractionation schedules in radiotherapy. However, estimating the radiation effect of a single fractionated treatment introduces many questions with respect to the parameters to be used in the modelling process. Several studies have used tumour control probability (TCP) curves in order to derive the values for the LQ parameters that may be used further for the analysis and ranking of treatment plans. Unfortunately, little attention has been paid to the biological relevance of these derived parameters, either for the initial number of cells or their intrinsic radiosensitivity, or both. This paper investigates the relationship between single values for the TCP parameters and the resulting dose-response curve. The results of this modelling study show how clinical observations for the position and steepness of the TCP curve can be explained only by the choice of extreme values for the parameters, if they are single values. These extreme values are in contradiction with experimental observations. This contradiction suggests that single values for the parameters are not likely to explain reasonably the clinical observations and that some distributions of input parameters should be taken into consideration.
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| 16. |
- Daşu, Alexandru, et al.
(författare)
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The effects of hypoxia on the theoretical modelling of tumour control probability
- 2005
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:6, s. 563-571
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Tidskriftsartikel (refereegranskat)abstract
- Theoretical modelling of tumour response is increasingly used for the prediction of treatment result and has even been proposed as ranking criteria in some algorithms for treatment planning. Tumour response to radiation is greatly influenced by the details of tumour microenvironment, especially hypoxia, that unfortunately are not always taken into consideration for these simulations. This paper intends to investigate the effects of various assumptions regarding hypoxia distribution in tumours on the predictions of treatment outcome. A previously developed model for simulating theoretically the oxygenation in biologically relevant tissues, including results from oxygen diffusion, consumption and perfusion limitations in tumours, was used to investigate the effects of the different aspects of hypoxia on the predictions of treatment outcome. Thus, both the continuous distribution of values and the temporal variation of hypoxia patterns were taken into consideration and were compared with a 'black-and-white' simplification with a fully hypoxic compartment and a fully oxic one. It was found that the full distribution of oxygenation in the tissue is needed for accurate results. The 'black-and-white' simplification, while showing the same general trends for the predictions of radiation response, could lead to serious over-estimations of the tumour control probability. It was also found that the presence of some hypoxia for every treatment fraction leads to a decrease in the predicted local control, regardless of the change of the hypoxic pattern throughout the duration of the whole treatment. The results thus suggest that the assumptions regarding tumour hypoxia influence very much the predictions of treatment outcome and therefore they have to be very carefully incorporated into the theoretical modelling.
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| 17. |
- Daşu, Alexandru, et al.
(författare)
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The relationship between vascular oxygen distribution and tissue oxygenation
- 2009
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Ingår i: Advances in Experimental Medicine and Biology. - Boston, MA : Springer US. - 0065-2598 .- 2214-8019. ; 645, s. 255-260
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Tidskriftsartikel (refereegranskat)abstract
- Tumour oxygenation could be investigated through several methods that use various measuring principles and can therefore highlight its different aspects. The results have to be subsequently correlated, but this might not be straightforward due to intrinsic limitations of the measurement methods. This study describes an analysis of the relationship between vascular and tissue oxygenations that may help the interpretation of results. Simulations have been performed with a mathematical model that calculates the tissue oxygenation for complex vascular arrangements by taking into consideration the oxygen diffusion into the tissue and its consumption at the cells. The results showed that while vascular and tissue oxygenations are deterministically related, the relationship between them is not unequivocal and this could lead to uncertainties when attempting to correlate them. However, theoretical simulation could bridge the gap between the results obtained with various methods.
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| 18. |
- Dasu, Alexandru, et al.
(författare)
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The risk for secondary cancers in patients treated for prostate carcinoma – An analysis with the competition dose response model
- 2009
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Ingår i: IFMBE Proceedings. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 1680-0737 .- 1433-9277. ; 25/III, s. 237-240
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Tidskriftsartikel (refereegranskat)abstract
- The risk for radiation-induced cancers has become increasingly important as patient survival following radiotherapy has increased due to the advent of new methods for early detection and advanced treatment. Attempts have been made to quantify the risk of cancer that may be associated with various treatment approaches, but the accuracy of predictions is rather low due to the influence of many confounding factors. It is the aim of this paper to investigate the impact of dose heterogeneity and inter-patient anatomical heterogeneity that may be encountered in a population of patients undergoing radiotherapy and are thought to influence risk predictions. Dose volume histograms from patients treated with radiation for the carcinoma of the prostate have been used to calculate the risk for secondary malignancies using a competition dose-response model previously developed. Biologically-relevant parameters derived from clinical and experimental data have been used for the model. The results suggested that dose heterogeneity plays an important role in predicting the risk for secondary cancer and that it should be taken into account through the use of dose volume histograms. Consequently, dose-response relationships derived for uniform relationships should be used with care to predict the risk for secondary malignancies in heterogeneously irradiated tissues. Inter-patient differences could lead to considerable uncertainties in the shape of the relationship between predicted risk and average tissue dose, as seen in epidemiological studies. They also lead to rather weak correlations between the risk for secondary malignancies and target volumes. The results stress the importance of taking into account the details of the clinical delivery of dose in radiotherapy for treatment plan evaluation or for retrospective analyses of the induction of secondary cancers. Nevertheless, the levels of risks are generally low and they could be regarded as the price of success for the advances in the radiotherapy of the prostate.
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| 19. |
- Dasu, Alexandru, et al.
(författare)
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The risk of secondary cancers in patients treated for prostate carcinoma : an analysis with competition dose response model
- 2009
-
Ingår i: IFMBE Proceedings. - Berlin : Springer. - 9783642039010 ; , s. 237-240
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Konferensbidrag (refereegranskat)abstract
- The risk for radiation-induced cancers has become increasingly important as patient survival following radiotherapy has increased due to the advent of new methods for early detection and advanced treatment. Attempts have been made to quantify the risk of cancer that may be associated with various treatment approaches, but the accuracy of predictions is rather low due to the influence of many confouding factors. It is the aim of this paper to investigate the impact of dose heterogeneity and inter-patient anatomical heterogeneity that may be encountered in a population of patients undergoing radiotheray and are thought to influence risk predictions. Dose volume histograms from patients treated with radiation for the carcinoma of the prostate have been used to calculate the risk for secondary malignancies using a competition dose-response model previously developed. Biologically-relevant parameters derived from clinical and experimental data have been used for the model. The results suggested that dose heterogeneity plays an important role in predicting the risk for secondary cancer and that it should be taken into account throught the use of dose volume histograms. Consequently, dose-response relationships derived for uniform relationships should be used with care to predict the risk for secondary malignancies in heterogeneously irradiated tissues. Inter-patient differences could lead to considerable uncertainties in the shape of the relationship between predicted risk and average tissue dose, as seen in epidemiological studies. They also lead to rather weak correlations between the risk for secondary malignancies and target volumes. The results stress the importance of taking into account the details of the clinical delivery of dose in radiotherapy plan evaluation or for retrospective analyses of the induction of secondary cancers. Nevertheless, the levels of risks are generally low and they could be regarded as teh price of success for the advances in the radiotherapy of the prostate.
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| 20. |
- Daşu, Alexandru, et al.
(författare)
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The use of risk estimation models for the induction of secondary cancers following radiotherapy
- 2005
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:4, s. 339-347
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Tidskriftsartikel (refereegranskat)abstract
- Theoretical predictions of cancer risk from radiotherapy may be used as a complementary criterion for the selection of successful treatment plans together with the classical approach of estimating the possible deterministic effects. However, any such attempts must take into consideration the specific features of radiation treatment. This paper explores several possible methods for estimating the risk of cancer following radiotherapy in order to investigate the influences of the fractionation and the non-uniformity of the dose to the irradiated organ. The results indicate that dose inhomogeneity plays an important role in predicting the risk for secondary cancer and therefore for predictive purposes it must be taken into account through the use of the dose volume histograms. They also suggest that the competition between cell killing and the induction of carcinogenic mutations has to be taken into consideration for more realistic risk estimations. Furthermore, more realistic parameters could be obtained if this competition is also included in analyses of epidemiological data from radiotherapy applications.
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| 21. |
- Daşu, Alexandru, et al.
(författare)
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Theoretical simulation of tumour oxygenation and results from acute and chronic hypoxia
- 2003
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 48:17, s. 2829-2842
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Tidskriftsartikel (refereegranskat)abstract
- The tumour microenvironment is considered to be responsible for the outcome of cancer treatment and therefore it is extremely important to characterize and quantify it. Unfortunately, most of the experimental techniques available now are invasive and generally it is not known how this influences the results. Non-invasive methods on the other hand have a geometrical resolution that is not always suited for the modelling of the tumour response. Theoretical simulation of the microenvironment may be an alternative method that can provide quantitative data for accurately describing tumour tissues. This paper presents a computerized model that allows the simulation of the tumour oxygenation. The model simulates numerically the fundamental physical processes of oxygen diffusion and consumption in a two-dimensional geometry in order to study the influence of the different parameters describing the tissue geometry. The paper also presents a novel method to simulate the effects of diffusion-limited (chronic) hypoxia and perfusion-limited (acute) hypoxia. The results show that all the parameters describing tissue vasculature are important for describing tissue oxygenation. Assuming that vascular structure is described by a distribution of inter-vessel distances, both the average and the width of the distribution are needed in order to fully characterize the tissue oxygenation. Incomplete data, such as distributions measured in a non-representative region of the tissue, may not give relevant tissue oxygenation. Theoretical modelling of tumour oxygenation also allows the separation between acutely and chronically hypoxic cells, a distinction that cannot always be seen with other methods. It was observed that the fraction of acutely hypoxic cells depends not only on the fraction of collapsed blood vessels at any particular moment, but also on the distribution of vessels in space as well. All these suggest that theoretical modelling of tissue oxygenation starting from the basic principles is a robust method that can be used to quantify the tissue oxygenation and to provide input parameters for other simulations.
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| 22. |
- Daşu, Alexandru, et al.
(författare)
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Theoretical simulation of tumour oxygenation--practical applications
- 2006
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Ingår i: Advances in Experimental Medicine and Biology. - : Springer US. - 0065-2598 .- 2214-8019. ; 578, s. 357-362
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Tidskriftsartikel (refereegranskat)abstract
- Theoretical simulation of tissue oxygenation is a robust method that can be used to quantify the tissue oxygenation for a variety of applications. However, it is necessary that the relevant input parameters are used for the model describing the tumour microenvironment. The results of the simulations presented in this article suggest that the accuracy of the simulations depends very much on the method of calculation of the effects of the temporal change of the hypoxic pattern due to the opening and the closure of blood vessels. Thus, the use of average oxygenations might lead to dangerous overestimations of the treatment response. This indicates that care should be taken when incorporating hypoxia information into the biological modelling of tumour response.
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| 23. |
- Dasu, Alexandru, et al.
(författare)
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Treatment modelling : the influence of micro-environmental conditions.
- 2008
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Ingår i: Acta Oncol. - : Informa Healthcare. - 1651-226X .- 0284-186X. ; 47:5, s. 896-905
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The interest in theoretical modelling of radiation response has grown steadily from a fast method to estimate the gain of new treatment strategies to an individualisation tool that may be used as part of the treatment planning algorithms. While the advantages of biological optimisation of plans are obvious, accurate theoretical models and realistic information about the micro-environmental conditions in tissues are needed. This paper aimed to investigate the clinical implications of taking into consideration the details of the tumour microenvironmental conditions. The focus was on the availability of oxygen and other nutrients to tumour cells and the relationship between cellular energy reserves and DNA repair ability as this is thought to influence the response of the various hypoxic cells. The choice of the theoretical models for predicting the response (the linear quadratic model or the inducible repair model) was also addressed. The modelling performed in this project has shown that the postulated radiobiological differences between acute and chronic hypoxia have some important clinical implications which may help to understand the mechanism behind the current success rates of radiotherapy. The results also suggested that it is important to distinguish between the two types of hypoxia in predictive assays and other treatment simulations.
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| 24. |
- Dasu, Alexandru, et al.
(författare)
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What is the Clinically Relevant Relative Biologic Effectiveness? A Warning for Fractionated Treatments With High Linear Energy Transfer Radiation
- 2008
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier. - 0360-3016 .- 1879-355X. ; 70:3, s. 867-874
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study the clinically relevant relative biologic effectiveness (RBE) of fractionated treatments with high linear energy transfer (LET) radiation and to identify the important factors that might influence the transfer of tolerance and curative levels from low LET radiation. These are important questions in the light of the growing interest for the therapeutic use of radiation with higher LET than electrons or photons.METHODS AND MATERIALS: The RBE of various fractionated schedules was analyzed with theoretical models for radiation effect, and the resulting predictions were compared with the published clinical and experimental data regarding fractionated irradiation with high LET radiation.RESULTS: The clinically relevant RBE increased for greater doses per fraction, in contrast to the predictions from single-dose experiments. Furthermore, the RBE for late-reacting tissues appeared to modify more quickly than that for early-reacting tissues. These aspects have quite important clinical implications, because the increased biologic effectiveness reported for this type of radiation would otherwise support the use of hypofractionation. Thus, the differential between acute and late-reacting tissues could put the late-reacting normal tissues at more risk from high LET irradiation; however, at the same time, it could increase the therapeutic window for slow-growing tumors.CONCLUSIONS: The modification of the RBE with the dose per fraction must be carefully taken into consideration when devising fractionated treatments with high LET radiation. Neglecting to do so might result in an avalanche of complications that could obscure the potential advantages of the therapeutic use of this type of radiation.
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| 25. |
- Dasu, Alexandru, et al.
(författare)
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Will intrafraction repair have negative consequences on extreme hypofractionation in prostate radiation therapy?
- 2015
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Ingår i: British Journal of Radiology. - : British Institute of Radiology. - 0007-1285 .- 1748-880X. ; 88:1056, s. Article ID 20150588-
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the present study was to investigate the impact of increasing fraction delivery time on the outcome of hypofractionated radiation therapy for prostate cancer.Methods: Monoexponential and biexponential repair models have been used for patients with prostate cancer to study the loss of biochemical control at 5 years for several clinically relevant irradiation times. The theoretical predictions were compared with newly reported clinical results from 4607 patients undergoing conventionally fractionated and hypofractionated prostate radiation therapy.Results: Time-demanding irradiation techniques appear to lead to biochemical control rates that sometimes are about 10–20 percentage points below predictions that neglect intrafraction repair. This difference appears to be of the same order of magnitude as that predicted by moderately slow to slow repair taking place during the irradiation time. The impact is largest for the patient risk groups receiving doses corresponding to the steepest part of the dose–response curve. By contrast, for treatment techniques requiring irradiation times shorter than about 20 min, the impact of intrafraction repair appears to be much smaller and probably difficult to be observed in the light of other sources of uncertainty in clinical data.Conclusion: Neglecting intrafraction repair might overestimate the effectiveness of some treatment schedules and could also influence any subsequent estimations of fractionation sensitivity for prostate tumours.Advances in knowledge: The effect of intrafraction repair for prostate cancer should be taken into account for long irradiation sessions as might be expected from scanned beams and/or from multiple intrafraction imaging sessions to check the positioning of the patient.
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| 26. |
- Flejmer, Anna M., 1971-, et al.
(författare)
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Impact of physiological breathing motion for breast cancer radiotherapy with proton beam scanning - An in silico study
- 2017
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Ingår i: Physica medica (Testo stampato). - : Elsevier BV. - 1120-1797 .- 1724-191X. ; 39, s. 88-94
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates the impact of breathing motion on proton breast treatment plans. Twelve patients with CT datasets acquired during breath-hold-at-inhalation (BHI), breath-hold-at-exhalation (BHE) and in free-breathing (FB) were included in the study. Proton plans were designed for the left breast for BHI and subsequently recalculated for BHE or designed for FB and recalculated for the extreme breath-hold phases. The plans were compared from the point of view of their target coverage and doses to organs-at-risk. The median amplitude of breathing motion determined from the positions of the sternum was 4.7 mm (range 0.5-14.6 mm). Breathing motion led to a degradation of the dose coverage of the target (heterogeneity index increased from 4-7% to 8-11%), but the degraded values of the dosimetric parameters of interest fulfilled the clinical criteria for plan acceptance. Exhalation decreased the lung burden [average dose 3.1-4.5 Gy (RBE)], while inhalation increased it [average dose 5.8-6.8 Gy (RBE)]. The individual values depended on the field arrangement. Smaller differences were seen for the heart [average dose 0.1-0.2 Gy (RBE)] and the LAD [1.9-4.6 Gy (RBE)]. Weak correlations were generally found between changes in dosimetric parameters and respiratory motion. The differences between dosimetric parameters for various breathing phases were small and their expected clinical impact is consequently quite small. The results indicated that the dosimetric parameters of the plans corresponding to the extreme breathing phases are little affected by breathing motion, thus suggesting that this motion might have little impact for the chosen beam orientations with scanned proton beams.
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| 27. |
- Fowler, Jack F., et al.
(författare)
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Is the α/β ratio for prostate tumours really low and does it vary with the level of risk at diagnosis?
- 2013
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research (IIAR). - 0250-7005 .- 1791-7530. ; 33:3, s. 1009-1011
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To answer the questions: Is the α/β ratio (radiosensitivity to size of dose-per-fraction) really low enough to justify using a few large dose fractions instead of the traditional many small doses? Does this parameter vary with prognostic risk factors? Methods and Materials: Three large statistical overviews are critiqued, with results for 5,000, 6,000 and 14,000 patients with prostate carcinoma, respectively. Results: These major analyses agree in finding the average α/β ratio to be less than 2 Gy: 1.55, (95% confidence interval=0.46-4.52), 1.4 (0.9-2.2), and the third analysis 1.7 (1.4-2.2) by ASTRO and 1.6 (1.2-2.2) by Phoenix criteria. All agree that α/β values do not vary significantly with the low, intermediate, high and “all included” risk factors. Conclusion: The high sensitivity to dose-per-fraction is an intrinsic property of prostate carcinomas and this supports the use of hypofractionation to increase the therapeutic gain for these tumours with dose-volume modelling to reduce the risk of late complications in rectum and bladder.
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| 28. |
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| 29. |
- Fowler, Jack, et al.
(författare)
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Optimum overall treatment time in radiation oncology
- 2015
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Bok (refereegranskat)abstract
- John "Jack" Fowler has been a busy radiation biology researcher and teacher. He has written 581 papers over the last 65 plus years. He has also received nearly every honor the medical physics field can bestow. But Jack is not done. He says it is time he wrote a book. Jack's new book, Optimum overall treatment time in radiation oncology, sums up the key concepts relating to optimum fractionation in radiation therapy that have interested him all these years.
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| 30. |
- Gudowska, Irena, et al.
(författare)
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Radiation burden from secondary doses to patients undergoing radiation therapy with photons and light ions and radiation doses from imaging modalities
- 2014
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Ingår i: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 161:1-4, s. 357-362
-
Tidskriftsartikel (refereegranskat)abstract
- Ionising radiation is increasingly used for the treatment of cancer, being the source of a considerable fraction of the medical irradiation to patients. With the increasing success rate of cancer treatments and longer life expectancy of the treated patients, the issue of secondary cancer incidence is of growing concern, especially for paediatric patients who may live long after the treatment and be more susceptible to carcinogenesis. Also, additional imaging procedures like CT, kV and MV imaging and PET, alone or in conjunction with radiation therapy, may add to the radiation burden associated with the risk of occurrence of secondary cancers. This work has been based on literature studies and is focussed on the assessment of secondary doses to healthy tissues that are delivered by the use of modern radiation therapy and diagnostic imaging modalities in the clinical environment.
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| 31. |
- Kjellsson Lindblom, Emely, et al.
(författare)
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Hypoxia Induced by Vascular Damage at High Doses Could Compromise the Outcome of Radiotherapy
- 2019
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:5, s. 2337-2340
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: This study investigated the impact of temporary vascular collapse on tumour control probability (TCP) in stereotactic body radiotherapy (SBRT), taking into account different radiosensitivities of chronically and acutely hypoxic cells. Materials and Methods: Three-dimensional tumours with heterogeneous oxygenation were simulated assuming different fractions of collapsed vessels at every treatment fraction. The modelled tumours contained a chronically hypoxic subvolume of 30-60% of the tumour diameter, and a hypoxic fraction ≤5 mm Hg of 30-50%. The rest of the tumours were well-oxygenated at the start of the simulated treatment. Results: For all simulated cases, the largest reduction in TCP from 97% to 2% was found in a tumour with a small chronically hypoxic core treated with 60 Gy in eight fractions and assuming a treatment-induced vascular collapse of 35% in the well-oxygenated region. Conclusion: The timing of SBRT fractions should be considered together with the tumour oxygenation to avoid loss of TCP in SBRT.
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| 32. |
- 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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| 33. |
- Kjellsson Lindblom, Emely, et al.
(författare)
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Radiation-induced vascular damage and the impact on the treatment outcome of stereotactic body radiotherapy
- 2019
-
Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:6, s. 2721-2727
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: The aim of this study was to investigate radiation-induced tumour vascular damage and its impact thereof on the outcome of stereotactic body radiotherapy (SBRT). Materials and Methods: Vessel densities in animal tumours before and after a single dose of 20 Gy were quantified and used as input for simulations of three-dimensional tumours with heterogeneous oxygenation. SBRT treatments of the modelled tumours in 1-8 fractions were simulated. The impact of vessel collapse on the outcome of SBRT was investigated by calculating tumour control probability (TCP) and the dose required to obtain a TCP of 50% (D50). Results: A radiation-induced increase of acute hypoxia in tumours during SBRT treatment could be simulated based on the experimental data. The D50 values for these tumours were higher than for the simulated tumours without vessel collapse. Conclusion: The vascular changes after high doses of radiation could compromise the outcome of SBRT by increasing tumour hypoxia.
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| 34. |
- Lazzeroni, Marta, et al.
(författare)
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Evaluation of third treatment week as temporal window for assessing responsiveness on repeated FDG-PET scans in Non-Small Cell Lung Cancer patients
- 2018
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Ingår i: Physica medica (Testo stampato). - : Elsevier BV. - 1120-1797 .- 1724-191X. ; 46, s. 45-51
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Early assessment of tumour response to treatment with repeated FDG-PET-CT imaging has potential for treatment adaptation but it is unclear what the optimal time window for this evaluation is. Previous studies indicate that changes in SUVmean and the effective radiosensitivity (alpha(eff), accounting for uptake variations and accumulated dose until the second FDG-PET-CT scan) are predictive of 2-year overall survival (OS) when imaging is performed before radiotherapy and during the second week. This study aims to investigate if multiple FDG-PET-derived quantities determined during the third treatment week have stronger predictive power.Methods: Twenty-eight lung cancer patients were imaged with FDG-PET-CT before radiotherapy (PET1) and during the third week (PET2). SUVmean, SUVmax, SUVpeak, MTV41%-50% (Metabolic Tumour Volume), TLG41%-50% (Total Lesion Glycolysis) in PET1 and PET2 and their change (), as well as average alpha(eff) (<(alpha)over bar >(eff)) and the negative fraction of alpha(eff) values (f(alpha eff) (< 0)) were determined. Correlations were sought between FDG-PET-derived quantities and OS with ROC analysis.Results: Neither SUVmean, SUVmax, SUVpeak in PET1 and PET2 (AUC = 0.5-0.6), nor their changes (AUC = 0.5-0.6) were significant for outcome prediction purposes. Lack of correlation with OS was also found for (alpha) over bar (eff) (AUC = 0.5) and f(alpha eff) (<) 0 (AUC = 0.5). Threshold-based quantities (MTV41%-50%, TLG41%-50%) and their changes had AUC= 0.5-0.7. P-values were in all cases >> 0.05.Conclusions: The poor OS predictive power of the quantities determined from repeated FDG-PET-CT images indicates that the third week of treatment might not be suitable for treatment response assessment. Comparatively, the second week during the treatment appears to be a better time window.
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| 35. |
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| 36. |
- Lindblom, Emely, et al.
(författare)
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Accounting for Two Forms of Hypoxia for Predicting Tumour Control Probability in Radiotherapy : An In Silico Study
- 2018
-
Ingår i: Advances in Experimental Medicine and Biology. - Cham : Springer International Publishing. - 0065-2598 .- 2214-8019. ; 1042, s. 183-187, s. 183-187
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Tidskriftsartikel (refereegranskat)abstract
- The progress in functional imaging and dose delivery has opened the possibility of targeting tumour hypoxia with radiotherapy. Advanced approaches apply quantitative information on tumour oxygenation retrieved from imaging in dose prescription. These do not, however, take into account the potential difference in radiosensitivity of chronically and acutely hypoxic cells. It was the aim of this study to evaluate the implications of assuming the same or different sensitivities for the hypoxic cells. An in silico 3D-model of a hypoxic tumour with heterogeneous oxygenation was used to model the probabilities of tumour control with different radiotherapy regimens. The results show that by taking into account the potential lower radioresistance of chronically hypoxic cells deprived of oxygen and nutrients, the total dose required to achieve a certain level of control is substantially reduced for a given fractionation scheme in comparison to the case when chronically and acutely hypoxic cells are assumed to have similar features. The results also suggest that the presence of chronic hypoxia could explain the success of radiotherapy for some hypoxic tumours. Given the implications for clinical dose escalation trials, further exploration of the influence of the different forms of hypoxia on treatment outcome is therefore warranted.
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| 37. |
- Lindblom, Emely, et al.
(författare)
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Defining the hypoxic target volume based on positron emission tomography for image guided radiotherapy – the influence of the choice of the reference region and conversion function
- 2017
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Ingår i: Acta Oncologica. - Oxfordshire : Taylor & Francis. - 0284-186X .- 1651-226X. ; 56:6, s. 819-825
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypoxia imaged by positron emission tomography (PET) is a potential target for optimization in radiotherapy. However, the implementation of this approach with respect to the conversion of intensities in the images into oxygenation and radiosensitivity maps is not straightforward. This study investigated the feasibility of applying two conversion approaches previously derived for 18F-labeled fluoromisonidazole (18F-FMISO)-PET images for the hypoxia tracer 18F-flortanidazole (18F-HX4).Material and methods: Ten non-small-cell lung cancer patients imaged with 18F-HX4 before the start of radiotherapy were considered in this study. PET image uptake was normalized to a well-oxygenated reference region and subsequently linear and non-linear conversions were used to determine tissue oxygenations maps. These were subsequently used to delineate hypoxic volumes based partial oxygen pressure (pO2) thresholds. The results were compared to hypoxic volumes segmented using a tissue-to-background ratio of 1.4 for 18F-HX4 uptake.Results: While the linear conversion function was not found to result in realistic oxygenation maps, the non-linear function resulted in reasonably sized sub-volumes in good agreement with uptake-based segmented volumes for a limited range of pO2 thresholds. However, the pO2 values corresponding to this range were significantly higher than what is normally considered as hypoxia. The similarity in size, shape, and relative location between uptake-based sub-volumes and volumes based on the conversion to pO2 suggests that the relationship between uptake and pO2 is similar for 18F-FMISO and 18F-HX4, but that the model parameters need to be adjusted for the latter.Conclusions: A non-linear conversion function between uptake and oxygen partial pressure for 18F-FMISO-PET could be applied to 18F-HX4 images to delineate hypoxic sub-volumes of similar size, shape, and relative location as based directly on the uptake. In order to apply the model for e.g., dose-painting, new parameters need to be derived for the accurate calculation of dose-modifying factors for this tracer.
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| 38. |
- Lindblom, Emely, et al.
(författare)
-
High brachytherapy doses can counteract hypoxia in cervical cancer – a modelling study
- 2017
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 62:2, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- Tumour hypoxia is a well-known adverse factor for the outcome of radiotherapy. For cervical tumours in particular, several studies indicate large variability in tumour oxygenation. However, clinical evidence shows that the management of cervical cancer including brachytherapy leads to high rate of success. It was the purpose of this study to investigate whether the success of brachytherapy for cervical cancer, seemingly regardless of oxygenation status, could be explained by the characteristics of the brachytherapy dose distributions.To this end, a previously used in silico model of tumour oxygenation and radiation response was further developed to simulate the treatment of cervical cancer employing a combination of external beam radiotherapy and intracavitary brachytherapy. Using a clinically-derived brachytherapy dose distribution and assuming a homogeneous dose delivered by external radiotherapy, cell survival was assessed on voxel level by taking into account the variation of sensitivity with oxygenation as well as the effects of repair, repopulation and reoxygenation during treatment. Various scenarios were considered for the conformity of the brachytherapy dose distribution to the hypoxic region in the target.By using the clinically-prescribed brachytherapy dose distribution and varying the total dose delivered with external beam radiotherapy in 25 fractions, the resulting values of the dose for 50% tumour control, D 50, were in agreement with clinically-observed values for high cure rates if fast reoxygenation was assumed. The D 50 was furthermore similar for the different degrees of conformity of the brachytherapy dose distribution to the tumour, regardless of whether the hypoxic fraction was 10%, 25%, or 40%. To achieve 50% control with external RT only, a total dose of more than 70 Gy in 25 fractions would be required for all cases considered.It can thus be concluded that the high doses delivered in brachytherapy can counteract the increased radioresistance caused by hypoxia if fast reoxygenation is assumed.
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| 39. |
- Lindblom, Emely, et al.
(författare)
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Optimal fractionation in radiotherapy for non-small cell lung cancer - a modelling approach
- 2015
-
Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 54:9, s. 1592-1598
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Tidskriftsartikel (refereegranskat)abstract
- Background. Conventionally fractionated radiotherapy (CFRT) has proven ineffective in treating non-small cell lung cancer while more promising results have been obtained with stereotactic body radiotherapy (SBRT). Hypoxic tumours, however, might present a challenge to extremely hypofractionated schedules due to the decreased possibility for inter-fraction fast reoxygenation. A potentially successful compromise might be found in schedules employing several fractions of varying fractional doses. In this modelling study, a wide range of fractionation schedules from single-fraction treatments to heterogeneous, multifraction schedules taking into account repair, repopulation, reoxygenation and radiosensitivity of the tumour cells, has been explored with respect to the probability of controlling lung tumours.Material and methods. The response to radiation of tumours with heterogeneous spatial and temporal oxygenation was simulated including the effects of accelerated repopulation and intra-fraction repair. Various treatments with respect to time, dose and fractionation were considered and the outcome was estimated as Poisson-based tumour control probability for local control.Results. For well oxygenated tumours, heterogeneous fractionation could increase local control while hypoxic tumours are not efficiently targeted by such treatments despite reoxygenation. For hypofractionated treatments employing large doses per fraction, a synergistic effect was observed between intra-fraction repair and inter-fraction fast reoxygenation of the hypoxic cells as demonstrated by a reduction in D50 from 53.3 Gy for 2 fractions to 52.7 Gy for 5 fractions.Conclusions. For well oxygenated tumours, heterogeneous fractionation schedules could increase local control rates substantially compared to CFRT. For hypoxic tumours, SBRT-like hypofractionated schedules might be optimal despite the increased risk of intra-fraction repair due to a synergistic effect with inter-fraction reoxygenation.
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| 40. |
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| 41. |
- Lindblom, Emely, et al.
(författare)
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Survival and tumour control probability in tumours with heterogeneous oxygenation : A comparison between the linear-quadratic and the universal survival curve models for high doses
- 2014
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 53:8, s. 1035-1040
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Tidskriftsartikel (refereegranskat)abstract
- Background: The validity of the linear-quadratic (LQ) model at high doses has been questioned due to a decreasing agreement between predicted survival and experimental cell survival data. A frequently proposed alternative is the universal survival curve (USC) model, thought to provide a better fit in the high-dose region. The comparison between the predictions of the models has mostly been performed for uniform populations of cells with respect to sensitivity to radiation. This study aimed to compare the two models in terms of cell survival and tumour control probability (TCP) for cell populations with mixed sensitivities related to their oxygenation.Methods: The study was performed in two parts. For the first part, cell survival curves were calculated with both models assuming various homogeneous populations of cells irradiated with uniform doses. For the second part, a realistic 3D-model of complex tumour oxygenation was used to study the impact of the differences in cell survival on the modelled tumour control probability. Cellular response was assessed with the LQ and USC models at voxel level and a Poisson TCP model at tumour level.Results: For hypoxic tumours, the disputed continuous bend of the LQ survival curve was counteracted by the increased radio-resistance of the hypoxic cells and the survival curves started to diverge only at much higher doses than for oxic tumours. This was also reflected by the TCP curves for hypoxic tumours for which the difference in D50 values for the LQ and USC models was reduced from 5.4 to 0.2 Gy for 1 and 3 fractions respectively in a tumour with only 1.1% hypoxia and from 9.5 to 0.4 Gy in a tumour with 11.1% hypoxia.Conclusions: For a large range of fractional doses including hypofractionated schemes, the difference in predicted survival and tumour control probability between the LQ and USC models for tumours with heterogeneous oxygenation was found to be negligible.
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| 42. |
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| 43. |
- Lindblom, Emely, et al.
(författare)
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Treatment fractionation for stereotactic radiotherapy of lung tumours: a modelling study of the influence of chronic and acute hypoxia on tumour control probability
- 2014
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Ingår i: Radiation Oncology. - 1748-717X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer (NSCLC) has led to promising local control and overall survival for fractionation schemes with increasingly high fractional doses. A point has however been reached where the number of fractions used might be too low to allow efficient local inter-fraction reoxygenation of the hypoxic cells residing in the tumour. It was therefore the purpose of this study to investigate the impact of hypoxia and extreme hypofractionation on the tumour control probability (TCP) from SBRT.Methods: A three-dimensional model of tumour oxygenation able to simulate oxygenation changes on the microscale was used. The TCP was determined for clinically relevant SBRT fractionation schedules of 1, 3 and 5 fractions assuming either static tumour oxygenation or that the oxygenation changes locally between fractions due to fast reoxygenation of acute hypoxia without an overall reduction in chronic hypoxia.Results: For the schedules applying three or five fractions the doses required to achieve satisfying levels of TCP were considerably lower when local oxygenation changes were assumed compared to the case of static oxygenation; a decrease in D50 of 17.7 Gy was observed for a five-fractions schedule applied to a 20% hypoxic tumour when fast reoxygenation was modelled. Assuming local oxygenation changes, the total doses required for a tumor control probability of 50% were of similar size for one, three and five fractions.Conclusions: Although attractive from a practical point of view, extreme hypofractionation using just one single fraction may result in impaired local control of hypoxic tumours, as it eliminates the possibility for any kind of reoxygenation.
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| 44. |
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| 45. |
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| 46. |
- Marcu, Loredana G., et al.
(författare)
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Radiotherapy and clinical radiobiology of head and neck cancer
- 2018
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Bok (refereegranskat)abstract
- Common factors that lead to treatment failure in head and neck cancer are the lack of tumour oxygenation, the accelerated division of cancer cells during treatment, and radioresistance. These tumour-related challenges and possible ways to overcome them are covered in this book, authored by three medical physicists and a clinical oncologist who explain how different radiobiological findings have led to the development of various treatment techniques for head and neck cancer. Novel treatment techniques as supported by current scientific evidence are comprehensively explored, as well as the major challenges that arise in the retreatment of patients who have already undergone a form of radiotherapy for primary head and neck cancer.
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| 47. |
- Marcu, Loredana G., et al.
(författare)
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The six Rs of head and neck cancer radiotherapy
- 2015
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Ingår i: Contemporary Issues in Head and Neck Cancer Management. - Rijeka : InTech. - 9789535121350 ; , s. 35-58
-
Bokkapitel (refereegranskat)abstract
- While the management of head and neck cancer has evolved over the last few decades, there are still several challenges and unanswered questions that need solutions. This book is a small compilation of some topical aspects regarding head and neck cancer treatment, including the etiology of HPV-positive oropharyngeal cancers and risk factors in the young population, the challenge of surgical margin definition and the perennial problem of systemic treatment due to distant metastases. Radiobiological aspects are also covered through the Rs of radiotherapy, with a couple of chapters being dedicated to radioresistance and tumour microenvironment. Contemporary Issues in Head and Neck Cancer Management comes as an addition to the existing literature that aims to tackle this radiobiologically challenging tumour.
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| 48. |
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| 49. |
- 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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- 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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