| 1. |
- Mondlane, Gracinda, 1987-
(författare)
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Comparative study of Radiation Therapy of Targets in the Upper Abdomen with Photon- or Scanned Proton-beams
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Recently, there has been an increase in the number of proton beam therapy (PBT) centers operating worldwide. For certain cases, proton beams have been shown to provide dosimetric and radiobiological advantages when used for cancer treatment, compared to the regular photon-beam based treatments. Under ideal circumstances, the dose given to the tissues surrounding a target can be reduced with PBT. The risk for side effects following treatment is then expected to decrease. Until present, mainly stationary targets, e.g. targets in the brain, have been treated with PBT. There is currently a growing interest to treat also target volumes in other parts of the body with PBT. However, there are sources of uncertainties, which must be more carefully considered when PBT is used, especially for PBT carried out with scanned proton beams. PBT is more sensitive to anatomical changes, e.g. organ motion or a variable gas content in the intestines, which requires that special precautions are taken prior to treating new tumour sites. In photon beam radiotherapy (RT) of moving targets, the main consequence of organ motion is the loss of sharpness of the dose gradients (dose smearing). When scanned proton beams are used, dose deformation caused by the fluctuations in the proton beam range, due to varying tissue heterogeneities (e.g., the ribs moving in and out of the beam path) and the so-called interplay effect, can be expected to impact the dose distributions in addition to the dose smearing. The dosimetric uncertainties, if not accounted for, may cause the planned and accurately calculated dose distribution to be distorted, compromising the main goal of RT of achieving the maximal local disease control while accepting certain risks for normal tissue complications.Currently there is a lack of clinical follow-up data regarding the outcome of PBT for different tumour sites, in particular for extra-cranial tumour sites in moving organs. On the other hand, the use of photon beams for this kind of cancer treatment is well-stablished. A treatment planning comparison between RT carried out with photons and with protons may provide guidelines for when PBT could be more suitable. New clinical applications of particle beams in cancer therapy can also be transferred from photon-beam treatments, for which there is a vast clinical experience. The evaluation of the different uncertainties influencing RT of different tumour sites carried out with photon- and with proton-beams, will hopefully create an understanding for the feasibility of treating cancers with scanned proton beams instead of photon beams. The comparison of two distinct RT modalities is normally performed by studying the dosimetric values obtained from the dose volume histograms (DVH). However, in dosimetric evaluations, the outcome of the treatments in terms of local disease control and healthy tissue toxicity are not estimated. In this regard, radiobiological models can be an indispensable tool for the prediction of the outcome of cancer treatments performed with different types of ionising radiation. In this thesis, different factors that should be taken into consideration in PBT, for treatments influenced by organ motion and density heterogeneities, were studied and their importance quantified.This thesis consists of three published articles (Articles I, II and III). In these reports, the dosimetric and biological evaluations of photon-beam and scanned proton-beam RT were performed and the results obtained were compared. The studies were made for two tumour sites influenced by organ motion and density changes, gastric cancer (GC) and liver metastases. For the GC cases, the impact of changes in tissue density, resulting from variable gas content (which can be observed inter-fractionally), was also studied. In this thesis, both conventional fractionations (implemented in the planning for GC treatments) and hypofractionated regimens (implemented in the planning for the liver metastases cases) were considered. In this work, it was found that proton therapy provided the possibility to reduce the irradiations of the normal tissue located near the target volumes, compared to photon beam RT. However, the effects of density changes were found to be more pronounced in the plans for PBT. Furthermore, with proton beams, the reduction of the integral dose given to the OARs resulted in reduced risks of treatment-induced secondary malignancies.
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| 2. |
- Mondlane, Gracinda, 1987-, et al.
(författare)
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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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Ingår i: Physica medica (Testo stampato). - : Elsevier BV. - 1120-1797 .- 1724-191X. ; 42, s. 263-270
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Mondlane, Gracinda, 1987-, et al.
(författare)
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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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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 56:6, s. 832-838
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Mondlane, Gracinda, 1987-, et al.
(författare)
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Dosimetric Comparison of Plans for Photon- or Proton-Beam Based Radiosurgery of Liver Metastases
- 2016
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Ingår i: International Journal of Particle Therapy. - 2331-5180. ; 3:2, s. 277-284
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Mondlane, Gracinda, 1987-, et al.
(författare)
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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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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:5, s. 2619-2625
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Mondlane, Gracinda, 1987-, et al.
(författare)
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Estimation of the risk for radiation-induced liver disease following photon- or proton-beam radiosurgery of liver metastases
- 2018
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Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X .- 1748-717X. ; 13
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Mondlane, Gracinda, 1987-
(författare)
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Radiation therapy of upper gastrointestinal cancers with scanned proton beams : A treatment planning study
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Proton beam therapy (PBT), using scanned beams, is an emerging modality used for the treatment of cancer. The clinical advantages of PBT, compared to commonly used photon beam therapy, have been demonstrated in different studies. However, the techniques used for planning and delivering treatments with photon beams have gradually been improved over the years. With the introduction of PBT in the clinic, guidelines to select patients to photon- or proton-beam therapy are indispensable.A simple approach used for selecting patients for PBT is based on the patient age. The paediatric patient group is considered to be the most radiosensitive and, therefore, in larger need of RT techniques that provide improved sparing of the organs at risk (OARs). With the increasing number of cancer clinics with access to PBT, combined with the constant clinical need of reducing the frequency of acute and late toxicities, there has been an increased use of PBT also for adult patients. At present, there is only limited clinical follow-up data available regarding the outcome of PBT for different tumour sites, in particular for extra-cranial tumours. The use of photon beams for such cancer treatments is, on the other hand, well-established. Therefore, the expected benefit of using proton beams in cancer therapy can be translated from the results obtained in the clinical experience attained from photon-beam treatments. The evaluation of the different uncertainties influencing the radiotherapy (RT) of different tumour sites carried out with photon- or proton-beams, will also create an improved understanding of the feasibility of treating cancer with scanned proton beams instead of with photon beams. The comparison of two distinct RT modalities is normally performed by studying the calculated dose distributions superimposed on the patient CT images and by evaluating the dosimetric values obtained from the dose volume histograms (DVHs). The dosimetric evaluation can be complemented with treatment outcome predictions in terms of local disease control and normal tissue toxicity. In this regard, radiobiological models can be an indispensable tool for the prediction of the outcome of cancer treatments performed with different types of ionising radiation. These estimates can in turn be used in the decision process for selecting patients for treatments with a specific RT modality.This thesis consists of five articles. In these studies, treatment plans for RT with scanned proton-beams have been prepared and compared with clinical plans used for photon-beam based RT. For this purpose, dosimetric and biological-model based evaluations of these plans were performed. These studies were carried out for two distinct upper gastrointestinal (GI) cancers, namely, gastric cancer (GC) and liver metastases. RT treatments with both conventional fractionation schemes (implemented in the planning for the GC treatments) and hypofractionated regimens (implemented in the planning for the liver metastases cases) were considered. For the GC cases, the impact of changes in tissue density, resulting from a variable gas content (which can be observed inter-fractionally), was investigated. Proton therapy was found to provide the possibility to reduce the doses given to normal tissues surrounding the target volumes, compared to photon RT. This dose reduction with PBT resulted in reduced risks for both treatment-induced normal tissue toxicities and secondary malignancies. The impact of the introduced density changes on the dose distributions were found to be more pronounced for the PBT plans, if plan robustness approaches were disregarded. The findings presented in this thesis can be of clinical importance in the selection process between different RT modalities.
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