1. |
- Barbeiro, A. R., et al.
(author)
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3D VMAT Verification Based on Monte Carlo Log File Simulation with Experimental Feedback from Film Dosimetry
- 2016
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:11
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Journal article (peer-reviewed)abstract
- A model based on a specific phantom, called QuAArC, has been designed for the evaluation of planning and verification systems of complex radiotherapy treatments, such as volumetric modulated arc therapy (VMAT). This model uses the high accuracy provided by the Monte Carlo (MC) simulation of log files and allows the experimental feedback from the high spatial resolution of films hosted in QuAArC. This cylindrical phantom was specifically designed to host films rolled at different radial distances able to take into account the entrance fluence and the 3D dose distribution. Ionization chamber measurements are also included in the feedback process for absolute dose considerations. In this way, automated MC simulation of treatment log files is implemented to calculate the actual delivery geometries, while the monitor units are experimentally adjusted to reconstruct the dose-volume histogram (DVH) on the patient CT. Prostate and head and neck clinical cases, previously planned with Monaco and Pinnacle treatment planning systems and verified with two different commercial systems (Delta4 and COMPASS), were selected in order to test operational feasibility of the proposed model. The proper operation of the feedback procedure was proved through the achieved high agreement between reconstructed dose distributions and the film measurements (global gamma passing rates > 90% for the 2%/2 mm criteria). The necessary discretization level of the log file for dose calculation and the potential mismatching between calculated control points and detection grid in the verification process were discussed. Besides the effect of dose calculation accuracy of the analytic algorithm implemented in treatment planning systems for a dynamic technique, it was discussed the importance of the detection density level and its location in VMAT specific phantom to obtain a more reliable DVH in the patient CT. The proposed model also showed enough robustness and efficiency to be considered as a pre-treatment VMAT verification system.
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2. |
- Henry, Thomas, et al.
(author)
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Proton Grid Therapy : A Proof-of-Concept Study
- 2017
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In: Technology in Cancer Research & Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 16:6, s. 749-757
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Journal article (peer-reviewed)abstract
- In this work, we studied the possibility of merging proton therapy with grid therapy. We hypothesized that patients with larger targets containing solid tumor growth could benefit from being treated with this method, proton grid therapy. We performed treatment planning for 2 patients with abdominal cancer with the suggested proton grid therapy technique. The proton beam arrays were cross-fired over the target volume. Circular or rectangular beam element shapes (building up the beam grids) were evaluated in the planning. An optimization was performed to calculate the fluence from each beam grid element. The optimization objectives were set to create a homogeneous dose inside the target volume with the constraint of maintaining the grid structure of the dose distribution in the surrounding tissue. The proton beam elements constituting the grid remained narrow and parallel down to large depths in the tissue. The calculation results showed that it is possible to produce target doses ranging between 100% and 130% of the prescribed dose by cross-firing beam grids, incident from 4 directions. A sensitivity test showed that a small rotation or translation of one of the used grids, due to setup errors, had only a limited influence on the dose distribution produced in the target, if 4 beam arrays were used for the irradiation. Proton grid therapy is technically feasible at proton therapy centers equipped with spot scanning systems using existing tools. By cross-firing the proton beam grids, a low tissue dose in between the paths of the elemental beams can be maintained down to the vicinity of a deep-seated target. With proton grid therapy, it is possible to produce a dose distribution inside the target volume of similar uniformity as can be created with current clinical methods.
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3. |
- Jiménez-Ortega, E., et al.
(author)
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Dose painting by means of Monte Carlo treatment planning at the voxel level
- 2017
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In: Physica medica (Testo stampato). - : Elsevier BV. - 1120-1797 .- 1724-191X. ; 42, s. 339-344
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Journal article (peer-reviewed)abstract
- Purpose: To develop a new optimization algorithm to carry out true dose painting by numbers (DPBN) planning based on full Monte Carlo (MC) calculation.Methods: Four configurations with different clustering of the voxel values from PET data were proposed. An optimization method at the voxel level under Lineal Programming (LP) formulation was used for an inverse planning and implemented in CARMEN, an in-house Monte Carlo treatment planning system.Results: Beamlet solutions fulfilled the objectives and did not show significant differences between the different configurations. More differences were observed between the segment solutions. The plan for the dose prescription map without clustering was the better solution.Conclusions: LP optimization at voxel level without dose-volume restrictions can carry out true DPBN planning with the MC accuracy.
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4. |
- Jiménez-Ortega, Elisa, et al.
(author)
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Implications of the Harmonization of [18F]FDG-PET/CT Imaging for Response Assessment of Treatment in Radiotherapy Planning
- 2022
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In: Tomography. - : MDPI AG. - 2379-1381 .- 2379-139X. ; 8:2, s. 1097-1112
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Journal article (peer-reviewed)abstract
- The purpose of this work is to present useful recommendations for the use of [18F]FDG-PET/CT imaging in radiotherapy planning and monitoring under different versions of EARL accreditation for harmonization of PET devices. A proof-of-concept experiment designed on an anthropomorphic phantom was carried out to establish the most suitable interpolation methods of the PET images in the different steps of the planning procedure. Based on PET/CT images obtained by using these optimal interpolations for the old EARL accreditation (EARL1) and for the new one (EARL2), the treatment plannings of representative actual clinical cases were calculated, and the clinical implications of the resulting differences were analyzed. As expected, EARL2 provided smaller volumes with higher resolution than EARL1. The increase in the size of the reconstructed volumes with EARL1 accreditation caused high doses in the organs at risk and in the regions adjacent to the target volumes. EARL2 accreditation allowed an improvement in the accuracy of the PET imaging precision, allowing more personalized radiotherapy. This work provides recommendations for those centers that intend to benefit from the new accreditation, EARL2, and can help build confidence of those that must continue working under the EARL1 accreditation.
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5. |
- Kjellsson Lindblom, Emely, et al.
(author)
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Impact of SBRT fractionation in hypoxia dose painting - accounting for heterogeneous and dynamic tumour oxygenation
- 2019
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In: Medical physics (Lancaster). - : Wiley. - 0094-2405 .- 2473-4209. ; 46:5, s. 2512-2521
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Journal article (peer-reviewed)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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6. |
- Lazzeroni, Marta, et al.
(author)
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Evolution of the hypoxic compartment on sequential oxygen partial pressure maps during radiochemotherapy in advanced head and neck cancer
- 2021
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In: Physics and Imaging in Radiation Oncology. - : Elsevier BV. - 2405-6316. ; 17, s. 100-105
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Journal article (peer-reviewed)abstract
- Background and purposeLongitudinal Positron Emission Tomography (PET) with hypoxia-specific radiotracers allows monitoring the time evolution of regions of increased radioresistance and may become fundamental in determining the radiochemotherapy outcome in Head-and-Neck Squamous Cell Carcinoma (HNSCC). The aim of this study was to investigate the evolution of the hypoxic target volume on oxygen partial pressure maps (pO2-HTV) derived from 18FMISO-PET images acquired before and during radiochemotherapy and to uncover correlations between extent and severity of hypoxia and treatment outcome.Material and methods18FMISO-PET/CT images were acquired at three time points (before treatment start, in weeks two and five) for twenty-eight HNSCC patients treated with radiochemotherapy. The images were converted into pO2 maps and corresponding pO2-HTVs (pO2-HTV1, pO2-HTV2, pO2-HTV3) were contoured at 10 mmHg. Different parameters describing the pO2-HTV time evolution were considered, such as the percent and absolute difference between the pO2-HTVs (%HTVi,j and HTVi-HTVj with i,j = 1, 2, 3, respectively) and the slope of the linear regression curve fitting the pO2-HTVs in time. Correlations were sought between the pO2-HTV evolution parameters and loco-regional recurrence (LRR) using the Receiver Operating Characteristic method.ResultsThe Area Under the Curve values for %HTV1,2, HTV1-HTV2, HTV1-HTV3 and the slope of the pO2-HTV linear regression curve were 0.75 (p = 0.04), 0.73 (p = 0.02), 0.73 (p = 0.02) and 0.75 (p = 0.007), respectively. Other parameter combinations were not statistically significant.ConclusionsThe pO2-HTV evolution during radiochemotherapy showed predictive value for LRR. The changes in the tumour hypoxia during the first two treatment weeks may be used for adaptive personalized treatment approaches.
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7. |
- Lazzeroni, Marta, et al.
(author)
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Quantification of Tumor Oxygenation Based on FMISO PET : Influence of Location and Oxygen Level of the Well-Oxygenated Reference Region
- 2020
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In: Oxygen Transport to Tissue XLI. - Cham : Springer. - 9783030344597 - 9783030344610 ; 1232, s. 177-182
-
Book chapter (peer-reviewed)abstract
- Tumor hypoxia may play a fundamental role in determining the radiotherapy outcome for several cancer types. Functional imaging with hypoxia specific radiotracers offers a way to visualize and quantify regions of increased radioresistance, which may benefit from dose escalation strategies. Conversion of the uptake in positron emission tomography (PET) images into oxygenation maps offers a way to quantitatively characterize the microenvironment. However, normalization of the uptake with respect to a well-oxygenated reference volume (WOV), which should be properly selected, is necessary when using conversion functions. This study aims at assessing the sensitivity of quantifying tumor oxygenation based on 18F-fluoromisonidazole (FMISO) PET with respect to the choice of the location and the oxygenation level of the WOV in head and neck cancer patients. WOVs varying not only in shape and location but also with respect to the assigned pO2 level were considered. pO2 values other than the standard 60 mmHg were selected according to the specific tissue type included in the volume. For comparison, the volume which would be considered as hypoxic based on a tissue-to-muscle ratio equal to 1.4 was also delineated, as conventionally done in clinical practice. Hypoxia mapping strategies are found highly sensitive to selection of the location of well-oxygenated region, but also on its assigned oxygenation level, which is crucial for hypoxia-guided adaptive dose escalation strategies.
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8. |
- Mondlane, Gracinda, 1987-, et al.
(author)
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Comparative study of the calculated risk of radiation-induced cancer after photon- and proton-beam based radiosurgery of liver metastases
- 2017
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In: Physica medica (Testo stampato). - : Elsevier BV. - 1120-1797 .- 1724-191X. ; 42, s. 263-270
-
Journal article (peer-reviewed)abstract
- IntroductionThe potential of proton therapy to improve the sparing of the healthy tissue has been demonstrated in several studies. However, even small doses delivered to the organs at risk (OAR) may induce long-term detriments after radiotherapy. In this study, we investigated the possibility to reduce the risk of radiation-induced secondary cancers with intensity modulated proton therapy (IMPT), when used for radiosurgery of liver metastases.Material and methodsTen patients, previously treated for liver metastases with photon-beam based stereotactic body radiation therapy (SBRT) were retrospectively planned for radiosurgery with IMPT. A treatment plan comparison was then performed in terms of calculated risk of radiation-induced secondary cancer. The risks were estimated using two distinct models (Dasu et al., 2005; Schneider et al., 2005, 2009). The plans were compared pairwise with a two-sided Wilcoxon signed-rank test with a significance level of 0.05.ResultsReduced risks for induction of fatal and other types of cancers were estimated for the IMPT plans (p < 0.05) with the Dasu et al. model. Using the Schneider et al. model, lower risks for carcinomainduction with IMPT were estimated for the skin, lungs, healthy part of the liver, esophagus and the remaining part of the body (p < 0.05). The risk of observing sarcomas in the bone was also reduced with IMPT (p < 0.05).ConclusionThe findings of this study indicate that the risks of radiation-induced secondary cancers after radiosurgery of liver metastases may be reduced, if IMPT is used instead of photon-beam based SBRT.
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9. |
- Mondlane, Gracinda, 1987-, et al.
(author)
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Comparison of gastric-cancer radiotherapy performed with volumetric modulated arc therapy or single-field uniform-dose proton therapy
- 2017
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 56:6, s. 832-838
-
Journal article (peer-reviewed)abstract
- Background: Proton-beam therapy of large abdominal cancers has been questioned due to the large variations in tissue density in the abdomen. The aim of this study was to evaluate the importance of these variations for the dose distributions produced in adjuvant radiotherapy of gastric cancer (GC), implemented with photon-based volumetric modulated arc therapy (VMAT) or with proton-beam single-field uniform-dose (SFUD) method. Material and methods: Eight GC patients were included in this study. For each patient, a VMAT- and an SFUD-plan were created. The prescription dose was 45 Gy (IsoE) given in 25 fractions. The plans were prepared on the original CT studies and the doses were thereafter recalculated on two modified CT studies (one with extra water filling and the other with expanded abdominal air-cavity volumes). Results: Compared to the original VMAT plans, the SFUD plans resulted in reduced median values for the V18 of the left kidney (26%), the liver mean dose (14.8 Gy (IsoE)) and the maximum dose given to the spinal cord (26.6 Gy (IsoE)). However, the PTV coverage decreased when the SFUD plans were recalculated on CT sets with extra air- (86%) and water-filling (87%). The added water filling only led to minor dosimetric changes for the OARs, but the extra air caused significant increases of the median values of V18 for the right and left kidneys (10% and 12%, respectively) and of V10 for the liver (12%). The density changes influenced the dose distributions in the VMAT plans to a minor extent. Conclusions: SFUD was found to be superior to VMAT for the plans prepared on the original CT sets. However, SFUD was inferior to VMAT for the modified CT sets.
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10. |
- Mondlane, Gracinda, 1987-, et al.
(author)
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Dosimetric Comparison of Plans for Photon- or Proton-Beam Based Radiosurgery of Liver Metastases
- 2016
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In: International Journal of Particle Therapy. - 2331-5180. ; 3:2, s. 277-284
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Journal article (peer-reviewed)abstract
- Purpose: Radiosurgery treatment of liver metastases with photon beams has been an established method for more than a decade. One method commonly used is the stereotactic body radiation therapy (SBRT) technique. The aim of this study was to investigate the potential sparing of the organs at risk (OARs) that the use of intensity-modulated proton therapy (IMPT), instead of SBRT, could enable.Patients and Methods: A comparative treatment-planning study of photon-beam and proton-beam based liver-cancer radiosurgery was performed. Ten patients diagnosed with liver metastasis and previously treated with SBRT at the Karolinska University Hospital were included in the study. New IMPT plans were prepared for all patients, while the original plans were set as reference plans. The IMPT planning was performed with the objective of achieving the same target dose coverage as with the SBRT plans. Pairwise dosimetric comparisons of the treatment plans were then performed for the OARs. A 2-sided Wilcoxon signed-rank test with significance level of 5% was carried out.Results: Improved sparing of the OARs was made possible with the IMPT plans. There was a significant decrease of the mean doses delivered to the following risk organs: the nontargeted part of the liver (P = .002), the esophagus (P = .002), the right kidney (P = .008), the spinal cord (P = .004), and the lungs (P = .002). The volume of the liver receiving less than 15 Gy was significantly increased with the IMPT plans (P = .004).Conclusion: The IMPT-based radiosurgery plans provided similar target coverage and significant dose reductions for the OARs compared with the photon-beam based SBRT plans. Further studies including detailed information about varying tissue heterogeneities in the beam path, due to organ motion, are required to evaluate more accurately whether IMPT is preferable for the radiosurgical treatment of liver metastases.
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11. |
- Mondlane, Gracinda, 1987-, et al.
(author)
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Estimation of Risk of Normal-tissue Toxicity Following Gastric Cancer Radiotherapy with Photon- or Scanned Proton-beams
- 2018
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In: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:5, s. 2619-2625
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Journal article (peer-reviewed)abstract
- Background/Aim: Gastric cancer (GC) radiotherapy involves irradiation of large tumour volumes located in the proximities of critical structures. The advantageous dose distributions produced by scanned-proton beams could reduce the irradiated volumes of the organs at risk (OARs). However, treatment-induced side-effects may still appear. The aim of this study was to estimate the normal tissue complication probability (NTCP) following proton therapy of GC, compared to photon radiotherapy. Patients and Methods: Eight GC patients, previously treated with volumetric-modulated arc therapy (VMAT), were retrospectively planned with scanned proton beams carried out with the single-field uniform-dose (SFUD) method. A beam-specific planning target volume was used for spot positioning and a clinical target volume (CTV) based robust optimisation was performed considering setup- and range-uncertainties. The dosimetric and NTCP values obtained with the VMAT and SFUD plans were compared. Results: With SFUD, lower or similar dose-volume values were obtained for OARs, compared to VMAT. NTCP values of 0% were determined with the VMAT and SFUD plans for all OARs (p>0.05), except for the left kidney (p<0.05), for which lower toxicity was estimated with SFUD. Conclusion: The NTCP reduction, determined for the left kidney with SFUD, can be of clinical relevance for preserving renal function after radiotherapy of GC.
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12. |
- Mondlane, Gracinda, 1987-, et al.
(author)
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Estimation of the risk for radiation-induced liver disease following photon- or proton-beam radiosurgery of liver metastases
- 2018
-
In: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 13
-
Journal article (peer-reviewed)abstract
- Background: Radiotherapy of liver metastases is commonly being performed with photon-beam based stereotactic body radiation therapy (SBRT). The high risk for radiation-induced liver disease (RILD) is a limiting factor in these treatments. The use of proton-beam based SBRT could potentially improve the sparing of the healthy part of the liver. The aim of this study was to use estimations of normal tissue complication probability (NTCP) to identify liver-metastases patients that could benefit from being treated with intensity-modulated proton therapy (IMPT), based on the reduction of the risk for RILD.Methods: Ten liver metastases patients, previously treated with photon-beam based SBRT, were retrospectively planned with IMPT. A CTV-based robust optimisation (accounting for setup and range uncertainties), combined with a PTV-based conventional optimisation, was performed. A robustness criterion was defined for the CTV (V95% > 98% for at least 10 of the 12 simulated scenarios). The NTCP was estimated for different endpoints using the Lyman-Kutcher-Burman model. The ΔNTCP (NTCPIMPT − NTCPSBRT) for RILD was registered for each patient. The patients for which the NTCP (RILD) < 5% were also identified. A generic relative biological effectiveness of 1.1 was assumed for the proton beams.Results: For all patients, the objectives set for the PTV and the robustness criterion set for the CTV were fulfilled with the IMPT plans. An improved sparing of the healthy part of the liver, right kidney, lungs, spinal cord and the skin was achieved with the IMPT plans, compared to the SBRT plans. Mean liver doses larger than the threshold value of 32 Gy led to NTCP values for RILD exceeding 5% (7 patients with SBRT and 3 patients with the IMPT plans). ΔNTCP values (RILD) ranging between − 98% and − 17% (7 patients) and between 0 and 2% (3 patients), were calculated.Conclusions: In this study, liver metastases patients that could benefit from being treated with IMPT, based on the NTCP reductions, were identified. The clinical implementation of such a model-based approach to select liver metastases patients to proton therapy needs to be made with caution while considering the uncertainties involved in the NTCP estimations.
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13. |
- Mondlane, Gracinda, et al.
(author)
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Evaluation of the risk for radiation-induced liver disease following photon- or proton-beam radiosurgery of liver metastases
-
Other publication (other academic/artistic)abstract
- Background: Radiotherapy of liver metastases is being performed with photon-beam stereotactic body radiation therapy (SBRT). However, the high risk for radiation-induced liver disease (RILD) is the treatment limiting factor. The use of proton beams in these treatments could improve the sparing of the healthy part of the liver. The aim of this study was to evaluate the use of estimations of normal tissue complication probability (NTCP) to identify liver-metastases patients that could benefit from being treated with intensity-modulated proton therapy (IMPT), based on the reduction of the risk for RILD. Methods: Ten liver metastases patients, previously treated with photon-beam radiosurgery, were retrospectively planned with IMPT. A CTV-based robust optimisation (accounting for setup and range uncertainties) combined with PTV-based conventional optimisation, was performed. A robustness criterion was defined for the CTV (V95%>98% for at least 10 of the 12 simulated scenarios). The NTCP was estimated for different endpoints using the Lyman-Kutcher-Burman model. The ΔNTCP (NTCPIMPT - NTCPSBRT) for RILD was registered for each patient. The patients for which the NTCP (RILD) < 5 % were also identified. A generic relative biological effectiveness of 1.1 was assumed for the proton beams. Results: For all patients, the objectives set for the PTV and the robustness criterion set for the CTV were fulfilled with the IMPT plans. An improved sparing of the healthy part of the liver, right kidney, lungs, spinal cord and the skin, was achieved with the IMPT plans. Mean liver doses larger than the threshold value of 32 Gy led to values of NTCP for RILD exceeding 5 % (7 patients for SBRT and 3 patients for IMPT). ΔNTCP values (RILD) ranging between -98% and -17 % (7 patients) and between 0 % and 2 % (3 patients) were estimated. Conclusions: In this study, liver metastases patients that could benefit from being treated with IMPT, based on the NTCP reductions, could be identified. The clinical implementation of such model-based approach to select liver metastases patients to proton therapy needs to be made with caution and considering the uncertainties involved in the NTCP estimations.
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14. |
- Thomas, Henry, et al.
(author)
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Development of an interlaced-crossfiring geometry for proton grid therapy
- 2017
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 56:11, s. 1437-1443
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Journal article (peer-reviewed)abstract
- Background: Grid therapy has in the past normally been performed with single field photon-beamgrids. In this work, we evaluated a method to deliver grid therapy based on interlacing and crossfiringgrids of mm-wide proton beamlets over a target volume, by Monte Carlo simulations.Material and methods: Dose profiles for single mm-wide proton beamlets (1, 2 and 3 mm FWHM) inwater were simulated with the Monte Carlo code TOPAS. Thereafter, grids of proton beamlets weredirected toward a cubic target volume, located at the center of a water tank. The aim was to deliver anearly homogeneous dose to the target, while creating high dose heterogeneity in the normal tissue,i.e., high gradients between valley and peak doses in the grids, down to the close vicinity of thetarget.Results: The relative increase of the beam width with depth was largest for the smallest beams(þ6.9mm for 1 mm wide and 150MeV proton beamlets). Satisfying dose coverage of the cubic targetvolume (r< ±5%) was obtained with the interlaced-crossfiring setup, while keeping the grid pattern ofthe dose distribution down to the target (valley-to-peak dose ratio<0.5 less than 1 cm before the tar-get). Center-to-center distances around 7–8 mm between the beams were found to give the best com-promise between target dose homogeneity and low peak doses outside of the target.Conclusions: A nearly homogeneous dose distribution can be obtained in a target volume by crossfir-ing grids of mm-wide proton-beamlets, while maintaining the grid pattern of the dose distribution atlarge depths in the normal tissue, close to the target volume. We expect that the use of this methodwill increase the tumor control probability and improve the normal tissue sparing in grid therapy.
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15. |
- Tsubouchi, Toshiro, et al.
(author)
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Quantitative evaluation of potential irradiation geometries for carbon-ion beam grid therapy
- 2018
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In: Medical physics (Lancaster). - : Wiley. - 0094-2405 .- 2473-4209. ; 45:3, s. 1210-1221
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Journal article (peer-reviewed)abstract
- Purpose: Radiotherapy using grids containing cm-wide beam elements has been carried out sporadically for more than a century. During the past two decades, preclinical research on radiotherapy with grids containing small beam elements, 25 m-0.7 mm wide, has been performed. Grid therapy with larger beam elements is technically easier to implement, but the normal tissue tolerance to the treatment is decreasing. In this work, a new approach in grid therapy, based on irradiations with grids containing narrow carbon-ion beam elements was evaluated dosimetrically. The aim formulated for the suggested treatment was to obtain a uniform target dose combined with well-defined grids in the irradiated normal tissue. The gain, obtained by crossfiring the carbon-ion beam grids over a simulated target volume, was quantitatively evaluated.Methods: The dose distributions produced by narrow rectangular carbon-ion beams in a water phantom were simulated with the PHITS Monte Carlo code. The beam-element height was set to 2.0 cm in the simulations, while the widths varied from 0.5 to 10.0 mm. A spread-out Bragg peak (SOBP) was then created for each beam element in the grid, to cover the target volume with dose in the depth direction. The dose distributions produced by the beam-grid irradiations were thereafter constructed by adding the dose profiles simulated for single beam elements. The variation of the valley-to-peak dose ratio (VPDR) with depth in water was thereafter evaluated. The separation of the beam elements inside the grids were determined for different irradiation geometries with a selection criterion.Results: The simulated carbon-ion beams remained narrow down to the depths of the Bragg peaks. With the formulated selection criterion, a beam-element separation which was close to the beam-element width was found optimal for grids containing 3.0-mm-wide beam elements, while a separation which was considerably larger than the beam-element width was found advantageous for grids containing 0.5-mm-wide beam elements. With the single-grid irradiation setup, the VPDRs were close to 1.0 already at a distance of several cm from the target. The valley doses given to the normal tissue at 0.5 cm distance from the target volume could be limited to less than 10% of the mean target dose if a crossfiring setup with four interlaced grids was used.Conclusions: The dose distributions produced by grids containing 0.5- and 3.0-mm wide beam elements had characteristics which could be useful for grid therapy. Grids containing mm-wide carbon-ion beam elements could be advantageous due to the technical ease with which these beams can be produced and delivered, despite the reduced threshold doses observed for early and late responding normal tissue for beams of millimeter width, compared to submillimetric beams. The treatment simulations showed that nearly homogeneous dose distributions could be created inside the target volumes, combined with low valley doses in the normal tissue located close to the target volume, if the carbon-ion beam grids were crossfired in an interlaced manner with optimally selected beam-element separations. The formulated selection criterion was found useful for the quantitative evaluation of the dose distributions produced by the different irradiation setups.
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16. |
- Ureba, Ana, et al.
(author)
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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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In: Oxygen Transport to Tissue XLII. - Cham : Springer. - 9783030482367 - 9783030482381 ; 1269, s. 185-190
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Book chapter (peer-reviewed)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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17. |
- Ureba, Ana, et al.
(author)
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Biologically guided automated treatment planning and evaluation : potential for treatment adaptation in head and neck cancer
- 2023
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 62:11, s. 1389-1393
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Journal article (peer-reviewed)abstract
- Radiation therapy is among the main treatment options offered as a non-surgical solution in the treatment of cancer. This technology-driven treatment modality has evolved significantly over the past few decades, aiming to improve the therapeutic ratio and local tumour control. Modern external beam radiotherapy such as intensity modulated radiotherapy (IMRT), intensity modulated arc therapy (IMAT) or volumetric arc therapy (VMAT), and intensity modulated proton therapy (IMPT) approaches modulate intensity to deliver precisely the radiation doses required to specific areas within the tumour, and to spare nearby organs [Citation1,Citation2]. The use of these techniques in combination with image-guided techniques and multimodality imaging has provided more accurate radiotherapy allowing for a reduction of long-term adverse effects [Citation3]. Nowadays, most treatment planning systems (TPS) integrate imaging information for the diagnosis, planning, and delivery process, offering tools for image registration and fusion, dose calculation, and optimisation, among others.
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18. |
- Ureba, Ana, et al.
(author)
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Non-linear conversion of HX4 uptake for automatic segmentation of hypoxic volumes and dose prescription
- 2018
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In: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:4, s. 485-490
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Journal article (other academic/artistic)abstract
- Background: Tumour hypoxia is associated with increased radioresistance and poor response to radiotherapy. Pre-treatment assessment of tumour oxygenation could therefore give the possibility to tailor the treatment by calculating the required boost dose needed to overcome the increased radioresistance in hypoxic tumours. This study concerned the derivation of a non-linear conversion function between the uptake of the hypoxia-PET tracer 18F-HX4 and oxygen partial pressure (pO2).Material and methods: Building on previous experience with FMISO including experimental data on tracer uptake and pO2, tracer-specific model parameters were derived for converting the normalised HX4-uptake at the optimal imaging time point to pO2. The conversion function was implemented in a Python-based computational platform utilising the scripting and the registration modules of the treatment planning system RayStation. Subsequently, the conversion function was applied to determine the pO2 in eight non-small-cell lung cancer (NSCLC) patients imaged with HX4-PET before the start of radiotherapy. Automatic segmentation of hypoxic target volumes (HTVs) was then performed using thresholds around 10 mmHg. The HTVs were compared to sub-volumes segmented based on a tumour-to-blood ratio (TBR) of 1.4 using the aortic arch as the reference oxygenated region. The boost dose required to achieve 95% local control was then calculated based on the calibrated levels of hypoxia, assuming inter-fraction reoxygenation due to changes in acute hypoxia but no overall improvement of the oxygenation status.Results: Using the developed conversion tool, HTVs could be obtained using pO2 a threshold of 10 mmHg which were in agreement with the TBR segmentation. The dose levels required to the HTVs to achieve local control were feasible, being around 70–80 Gy in 24 fractions.Conclusions: Non-linear conversion of tracer uptake to pO2 in NSCLC imaged with HX4-PET allows a quantitative determination of the dose-boost needed to achieve a high probability of local control.
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19. |
- Ureba, Ana, et al.
(author)
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Photon and Proton Dose Painting Based on Oxygen Distribution – Feasibility Study and Tumour Control Probability Assessment
- 2022
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In: Oxygen Transport to Tissue XLIII. - Cham : Springer. - 9783031141898 - 9783031141904 ; 1395, s. 223-228
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Conference paper (peer-reviewed)abstract
- Solid tumours may present hypoxic sub-regions of increased radioresistance. Hypoxia quantification requires of clinically implementable, non-invasive and reproducible techniques as positron emission tomography (PET). PET-based dose painting strategies aiming at targeting those sub-regions may be limited by the resolution gap between the PET imaging resolution and the smaller scale at which hypoxia occurs. The ultimate benefit of the usage of dose painting may be reached if the planned dose distribution can be performed and delivered consistently. This study aimed at assessing the feasibility of two PET-based dose painting strategies using two beam qualities (photon or proton beams) in terms of tumour control probability (TCP), accounting for underlying oxygen distribution at sub-millimetre scale.A tumour oxygenation model at submillimetre scale was created consisting of three regions with different oxygen partial pressure distributions, being hypoxia decreasing from core to periphery. A published relationship between uptake and oxygen partial pressure was used and a PET image of the tumour was simulated. The fundamental effects that limit the PET camera resolution were considered by processing the uptake distribution with a Gaussian 3D filter and re-binning to a PET image voxel size of 2 mm. Prescription doses to overcome tumour hypoxia were calculated based on the processed images, and planned using robust optimisation.Normal tissue complication probabilities and TCPs after the delivery of the planned doses were calculated for the nominal plan and the lowest bounds of the dose volume histograms resulting from the robust scenarios planned, taking into account the underlying oxygenation at submillimetre scale. Results were presented for the two beam qualities and the two dose painting strategies: by contours (DPBC) and by using a voxel grouping-based approach (DPBOX).In the studied case, DPBOX outperforms DPBC with respect to TCP regardless the beam quality, although both dose painting strategy plans demonstrated robust target coverage.
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