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1.
  • Brodin, N Patrik, et al. (author)
  • Radiobiological risk estimates of adverse events and secondary cancer for proton and photon radiation therapy of pediatric medulloblastoma.
  • 2011
  • In: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 50:6, s. 806-16
  • Journal article (peer-reviewed)abstract
    • Abstract Introduction. The aim of this model study was to estimate and compare the risk of radiation-induced adverse late effects in pediatric patients with medulloblastoma (MB) treated with either three-dimensional conformal radiotherapy (3D CRT), inversely-optimized arc therapy (RapidArc(®) (RA)) or spot-scanned intensity-modulated proton therapy (IMPT). The aim was also to find dose-volume toxicity parameters relevant to children undergoing RT to be used in the inverse planning of RA and IMPT, and to use in the risk estimations. Material and methods. Treatment plans were created for all three techniques on 10 pediatric patients that have been treated with craniospinal irradiation (CSI) at our institution in 2007-2009. Plans were generated for two prescription CSI doses, 23.4 Gy and 36 Gy. Risk estimates were based on childhood cancer survivor data when available and secondary cancer (SC) risks were estimated as a function of age at exposure and attained age according to the organ-equivalent dose (OED) concept. Results. Estimates of SC risk was higher for the RA plans and differentiable from the estimates for 3D CRT at attained ages above 40 years. The risk of developing heart failure, hearing loss, hypothyroidism and xerostomia was highest for the 3D CRT plans. The risks of all adverse effects were estimated as lowest for the IMPT plans, even when including secondary neutron (SN) irradiation with high values of the neutron radiation weighting factors (WR(neutron)). Conclusions. When comparing RA and 3D CRT treatment for pediatric MB it is a matter of comparing higher SC risk against higher risks of non-cancer adverse events. Considering time until onset of the different complications is necessary to fully assess patient benefit in such a comparison. The IMPT plans, including SN dose contribution, compared favorably to the photon techniques in terms of all radiobiological risk estimates.
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2.
  • Sveistrup, Joen, et al. (author)
  • Prospective assessment of urinary, gastrointestinal and sexual symptoms before, during and after image-guided volumetric modulated arc therapy for prostate cancer
  • 2015
  • In: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 49:1, s. 58-69
  • Journal article (peer-reviewed)abstract
    • Objective: The aim of this study was to prospectively assess the development of 24 urinary, gastrointestinal and sexual symptoms in patients with prostate cancer (PCa) during and after image-guided volumetric modulated arc therapy (IG-VMAT).Material and methods: A total of 87 patients with PCa participated in this study. The patients were asked to complete a modified version of the Prostate Cancer Symptom Scale (PCSS) questionnaire before radiotherapy (RT) (baseline), at the start of RT, at the end of RT and 1 year after RT. Changes in symptoms at the start of RT, at the end of RT and 1 year after RT compared to baseline were analysed by a mixed model analysis of repeated measurements with the following covariates: age, comorbidity, smoking and androgen deprivation therapy (ADT).Results: All urinary problems except for haematuria increased significantly at the end of RT compared to baseline. One year after RT, there was no longer any difference compared to baseline for any of the urinary symptoms. All gastrointestinal symptoms except for nausea increased significantly at the end of RT. One year after RT, patients also reported slightly higher degrees of stool frequency, bowel leakage, planning of toilet visits, flatulence, mucus, gastrointestinal bleeding and impact of gastrointestinal bother on daily activities compared to baseline. All sexual symptoms increased significantly at all times compared to baseline. The use of ADT was associated with worse sexual symptoms.Conclusions: IG-VMAT is a safe treatment for PCa, with few and mild changes in urinary and gastrointestinal symptoms 1 year after RT compared to baseline. Sexual symptoms deteriorated both during and after RT. The use of ADT was associated with worse sexual symptoms.
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3.
  • Wegdén, Marie, et al. (author)
  • Nuclear microprobe analysis of the selective boron uptake obtained with BPA in brain tumour tissue
  • 2004
  • In: Nuclear Instruments & Methods in Physics Research. Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 219-20, s. 67-71
  • Journal article (peer-reviewed)abstract
    • The tumour selective ability of the boron compound boronophenylalanine (BPA), today used in Boron Neutron Capture Therapy in Sweden, has been investigated with the Lund Nuclear Microprobe. The tumour to tissue ratio of the boron concentration, as well as the location of boron within the cells, is critical for the efficiency of the therapy. It is desirable that the boron is accumulated as close as possible to the cell nucleus, since the alpha particles produced in the B-10(n,alpha)Li-7 reaction only have a range of about 10 microns, i.e. a cell diameter. The nuclear reaction B-11(p,alpha)2alpha, which has an especially high cross-section (300 mb) for 660 keV protons, has been used to analyse brain tissue from BPA-injected rats. Previous studies on other boron compounds have shown significant background problems when the alpha particles are detected in the backward direction. By a specially designed set-up, alpha particles in the forward and backward direction are detected simultaneously, and only the coincidences between the two directions are considered to be true boron events. In this way we could achieve excellent background suppression. The analysis shows that BPA indeed is tumour selective. Quantifications show a boron abundance of 150 +/- 20 ng/cm(2) in normal tissue and 567 70 ng/cm(2) in tumour tissue. If the rat is fed with L-dopa before the injection of BPA the uptake increases 3-4 times. The boron is homogeneously distributed in the cellular structure and no specific intracellular accumulation has been shown. (C) 2004 Elsevier B.V. All rights reserved.
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6.
  • af Rosenschöld, Per Munck, et al. (author)
  • The MCNP Monte Carlo Program
  • 2012. - 2nd
  • In: Monte Carlo Calculations in Nuclear Medicine : Applications in Diagnostic Imaging - Applications in Diagnostic Imaging. - : Taylor & Francis. - 9781439841099 - 9781439841105 ; , s. 153-172
  • Book chapter (peer-reviewed)abstract
    • Monte Carlo N-Particle (MCNP) is a Monte Carlo code package allowing coupled neutron, photon, and electron transport calculations. Also, the possibility of performing heavy charged particle transport calculations was recently introduced with the twin MCNPX code package. An arbitrary three-dimensional problem can be formulated through the use of surfaces defining building blocks (“cells” that are assigned density, material, and relevant cross-section tables. The source can be specified as point, surface, or volumes using generic or as a phase/space file.
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7.
  • Agn, Mikael, et al. (author)
  • A modality-adaptive method for segmenting brain tumors and organs-at-risk in radiation therapy planning
  • 2019
  • In: Medical Image Analysis. - : Elsevier BV. - 1361-8415. ; 54, s. 220-237
  • Journal article (peer-reviewed)abstract
    • In this paper we present a method for simultaneously segmenting brain tumors and an extensive set of organs-at-risk for radiation therapy planning of glioblastomas. The method combines a contrast-adaptive generative model for whole-brain segmentation with a new spatial regularization model of tumor shape using convolutional restricted Boltzmann machines. We demonstrate experimentally that the method is able to adapt to image acquisitions that differ substantially from any available training data, ensuring its applicability across treatment sites; that its tumor segmentation accuracy is comparable to that of the current state of the art; and that it captures most organs-at-risk sufficiently well for radiation therapy planning purposes. The proposed method may be a valuable step towards automating the delineation of brain tumors and organs-at-risk in glioblastoma patients undergoing radiation therapy.
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8.
  • Astradsson, Arnar, et al. (author)
  • Cerebral infarction after fractionated stereotactic radiation therapy of benign anterior skull base tumors
  • 2019
  • In: Clinical and Translational Radiation Oncology. - : Elsevier BV. - 2405-6308. ; 15, s. 93-98
  • Journal article (peer-reviewed)abstract
    • Background: The purpose of this study was to examine the occurrence of cerebral infarction (ischemic stroke), in a large combined cohort of patients with anterior skull base meningiomas, pituitary adenomas and craniopharyngiomas, after fractionated stereotactic radiation therapy (FSRT). Material and Methods: All patients, 18 years and older, with anterior skull base meningiomas, pituitary adenomas and craniopharyngiomas, treated with fractionated stereotactic radiation, in our center, from January 1999 to December 2015 were identified. In total 169 patients were included. The prescription dose to the tumor was 54 Gy for 164 patients (97%) and 46.0–52.2 Gy for 5 patients (3%). Cases of cerebral infarctions subsequent to FSRT were identified from the Danish National Patient Registry and verified with review of case notes. The rate of cerebral infarction after FSRT was compared to the rate in the general population with a one sample t-test after standardization for age and year. We explored if age, sex, disease type, radiation dose and dose per fraction was associated with increased risk of cerebral infarction using univariate Cox models. Results: At a median follow-up of 9.3 years (range 0.1–16.5), 7 of the 169 patients (4.1%) developed a cerebral infarction, at a median 5.7 years (range 1.2–11.5) after FSRT. The mean cerebral infarction rate for the general population was 0.0035 and 0.0048 for the FSRT cohort (p = 0.423). Univariate cox models analysis showed that increasing age correlated significantly with the cerebral infarction risk, with a hazard ratio of 1.090 (p = 0.013). Conclusion: Increased risk of cerebral infarction after FSRT of anterior skull base tumors was associated with age, similar to the general population. Our study revealed that FSRT did not introduce an excess risk of cerebral infarction.
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9.
  • Brodin, N Patrik, et al. (author)
  • Hippocampal sparing radiotherapy for pediatric medulloblastoma: impact of treatment margins and treatment technique.
  • 2014
  • In: Neuro-oncology. - : Oxford University Press (OUP). - 1523-5866 .- 1522-8517. ; 16:4, s. 594-602
  • Journal article (peer-reviewed)abstract
    • BackgroundWe investigated how varying the treatment margin and applying hippocampal sparing and proton therapy impact the risk of neurocognitive impairment in pediatric medulloblastoma patients compared with current standard 3D conformal radiotherapy.MethodsWe included 17 pediatric medulloblastoma patients to represent the variability in tumor location relative to the hippocampal region. Treatment plans were generated using 3D conformal radiotherapy, hippocampal sparing intensity-modulated radiotherapy, and spot-scanned proton therapy, using 3 different treatment margins for the conformal tumor boost. Neurocognitive impairment risk was estimated based on dose-response models from pediatric CNS malignancy survivors and compared among different margins and treatment techniques.ResultsMean hippocampal dose and corresponding risk of cognitive impairment were decreased with decreasing treatment margins (P < .05). The largest risk reduction, however, was seen when applying hippocampal sparing proton therapy-the estimated risk of impaired task efficiency (95% confidence interval) was 92% (66%-98%), 81% (51%-95%), and 50% (30%-70%) for 3D conformal radiotherapy, intensity-modulated radiotherapy, and proton therapy, respectively, for the smallest boost margin and 98% (78%-100%), 90% (60%-98%), and 70% (39%-90%) if boosting the whole posterior fossa. Also, the distance between the closest point of the planning target volume and the center of the hippocampus can be used to predict mean hippocampal dose for a given treatment technique.ConclusionsWe estimate a considerable clinical benefit of hippocampal sparing radiotherapy. In choosing treatment margins, the tradeoff between margin size and risk of neurocognitive impairment quantified here should be considered.
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10.
  • Brodin, N. Patrik, et al. (author)
  • Modeling freedom from progression for standard-risk medulloblastoma : A mathematical tumor control model with multiple modes of failure
  • 2013
  • In: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016. ; 87:2, s. 422-429
  • Journal article (peer-reviewed)abstract
    • Purpose As pediatric medulloblastoma (MB) is a relatively rare disease, it is important to extract the maximum information from trials and cohort studies. Here, a framework was developed for modeling tumor control with multiple modes of failure and time-to-progression for standard-risk MB, using published pattern of failure data. Methods and Materials Outcome data for standard-risk MB published after 1990 with pattern of relapse information were used to fit a tumor control dose-response model addressing failures in both the high-dose boost volume and the elective craniospinal volume. Estimates of 5-year event-free survival from 2 large randomized MB trials were used to model the time-to-progression distribution. Uncertainty in freedom from progression (FFP) was estimated by Monte Carlo sampling over the statistical uncertainty in input data. Results The estimated 5-year FFP (95% confidence intervals [CI]) for craniospinal doses of 15, 18, 24, and 36 Gy while maintaining 54 Gy to the posterior fossa was 77% (95% CI, 70%-81%), 78% (95% CI, 73%-81%), 79% (95% CI, 76%-82%), and 80% (95% CI, 77%-84%) respectively. The uncertainty in FFP was considerably larger for craniospinal doses below 18 Gy, reflecting the lack of data in the lower dose range. Conclusions Estimates of tumor control and time-to-progression for standard-risk MB provides a data-driven setting for hypothesis generation or power calculations for prospective trials, taking the uncertainties into account. The presented methods can also be applied to incorporate further risk-stratification for example based on molecular biomarkers, when the necessary data become available.
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11.
  • Børresen, Betina, et al. (author)
  • Evaluation of single-fraction high dose FLASH radiotherapy in a cohort of canine oral cancer patients
  • 2023
  • In: Frontiers in Oncology. - 2234-943X. ; 13, s. 1-10
  • Journal article (peer-reviewed)abstract
    • Background: FLASH radiotherapy (RT) is a novel method for delivering ionizingradiation, which has been shown in preclinical studies to have a normal tissuesparing effect and to maintain anticancer efficacy as compared to conventionalRT. Treatment of head and neck tumors with conventional RT is commonlyassociated with severe toxicity, hence the normal tissue sparing effect of FLASHRT potentially makes it especially advantageous for treating oral tumors. In thiswork, the objective was to study the adverse effects of dogs with spontaneousoral tumors treated with FLASH RT.Methods: Privately-owned dogs with macroscopic malignant tumors of the oralcavity were treated with a single fraction of ≥30Gy electron FLASH RT andsubsequently followed for 12 months. A modified conventional linear acceleratorwas used to deliver the FLASH RT.Results: Eleven dogs were enrolled in this prospective study. High grade adverseeffects were common, especially if bone was included in the treatment field. Fourout of six dogs, who had bone in their treatment field and lived at least 5 monthsafter RT, developed osteoradionecrosis at 3-12 months post treatment. Thetreatment was overall effective with 8/11 complete clinical responses and 3/11partial responses.Conclusion: This study shows that single-fraction high dose FLASH RT wasgenerally effective in this mixed group of malignant oral tumors, but the risk ofosteoradionecrosis is a serious clinical concern. It is possible that the risk ofosteonecrosis can be mitigated through fractionation and improved doseconformity, which needs to be addressed before moving forward with clinicaltrials in human cancer patients.
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12.
  • Capala, J, et al. (author)
  • Boron neutron capture therapy for glioblastoma multiforme : Clinical studies in Sweden
  • 2003
  • In: Journal of Neuro-Oncology. - 1573-7373. ; 62:1, s. 135-144
  • Journal article (peer-reviewed)abstract
    • A boron neutron capture therapy (BNCT) facility has been constructed at Studsvik, Sweden. It includes two filter/moderator configurations. One of the resulting neutron beams has been optimized for clinical irradiations with a filter/moderator system that allows easy variation of the neutron spectrum from the thermal to the epithermal energy range. The other beam has been designed to produce a large uniform field of thermal neutrons for radio-biological research. Scientific operations of the Studsvik BNCT project are overseen by the Scientific Advisory Board comprised of representatives of major universities in Sweden. Furthermore, special task groups for clinical and preclinical studies have been formed to facilitate collaboration with academia. The clinical Phase II trials for glioblastoma are sponsored by the Swedish National Neuro-Oncology Group and, presently, involve a protocol for BNCT treatment of glioblastoma patients who have not received any therapy other than surgery. In this protocol, p-boronophenylalanine (BPA), administered as a 6-h intravenous infusion, is used as the boron delivery agent. As of January 2002, 17 patients were treated. The 6-h infusion of 900 mg BPA/kg body weight was shown to be safe and resulted in the average blood-boron concentration of 24 μg/g (range: 15-32 μg/g) at the time of irradiation (approximately 2-3 h post-infusion). Peak and average weighted radiation doses to the brain were in the ranges of 8.0-15.5 Gy(W) and 3.3-6.1 Gy(W), respectively. So far, no severe BNCT-related acute toxicities have been observed. Due to the short follow-up time, it is too early to evaluate the efficacy of these studies.
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13.
  • Ceberg, Sofie, et al. (author)
  • Tumor-tracking radiotherapy of moving targets; verification using 3D polymer gel, 2D ion-chamber array and biplanar diode array
  • 2010
  • In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 250:1, s. 235-239
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to carry out a dosimetric verification of a dynamic multileaf collimator (DMLC)-based tumor-tracking delivery during respiratory-like motion. The advantage of tumor-tracking radiation delivery is the ability to allow a tighter margin around the target by continuously following and adapting the dose delivery to its motion. However, there are geometric and dosimetric uncertainties associated with beam delivery system constraints and output variations, and several investigations have to be accomplished before a clinical integration of this tracking technique. Two types of delivery were investigated in this study I) a single beam perpendicular to a target with a one dimensional motion parallel to the MLC moving direction, and II) an intensity modulated arc delivery (RapidArc®) with a target motion diagonal to the MLC moving direction. The feasibility study (I) was made using an 2D ionisation chamber array and a true 3D polymer gel. The arc delivery (II) was verified using polymer gel and a biplanar diode array. Good agreement in absorbed dose was found between delivery to a static target and to a moving target with DMLC tracking using all three detector systems. However, due to the limited spatial resolution of the 2D array a detailed comparison was not possible. The RapidArc® plan delivery was successfully verified using the biplanar diode array and true 3D polymer gel, and both detector systems could verify that the DMLC-based tumor-tracking delivery system has a very good ability to account for respiratory target motion.
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  • Edvardsson, Anneli, et al. (author)
  • Robustness and dosimetric verification of hippocampal-sparing craniospinal pencil beam scanning proton plans for pediatric medulloblastoma
  • 2024
  • In: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 29
  • Journal article (peer-reviewed)abstract
    • Background and PurposeHippocampal-sparing (HS) is a method that can potentially reduce late cognitive complications for pediatric medulloblastoma (MB) patients treated with craniospinal proton therapy (PT). The aim of this study was to investigate robustness and dosimetric plan verification of pencil beam scanning HS PT.Materials and MethodsHS and non-HS PT plans for the whole brain part of craniospinal treatment were created for 15 pediatric MB patients. A robust evaluation of the plans was performed. Plans were recalculated in a water phantom and measured field-by-field using an ion chamber detector at depths corresponding to the central part of hippocampi. All HS and non-HS fields were measured with the standard resolution of the detector and in addition 16 HS fields were measured with high resolution. Measured and planned dose distributions were compared using gamma evaluation.ResultsThe median mean hippocampus dose was reduced from 22.9 Gy (RBE) to 8.9 Gy (RBE), while keeping CTV V95% above 95 % for all nominal HS plans. HS plans were relatively robust regarding hippocampus mean dose, however, less robust regarding target coverage and maximum dose compared to non-HS plans. For standard resolution measurements, median pass rates were 99.7 % for HS and 99.5 % for non-HS plans (p < 0.001). For high-resolution measurements, median pass rates were 100 % in the hippocampus region and 98.2 % in the surrounding region.ConclusionsA substantial reduction of dose in the hippocampus region appeared feasible. Dosimetric accuracy of HS plans was comparable to non-HS plans and agreed well with planned dose distribution in the hippocampus region.
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  • Ek, Hanna, et al. (author)
  • Transitioning from conventional photon therapy to proton therapy for primary brain tumors
  • 2023
  • In: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 62:4, s. 391-399
  • Journal article (peer-reviewed)abstract
    • Introduction: Proton radiation therapy (PT) has become a treatment option alongside photon therapy (XRT) for lower-grade gliomas (LGG). In this single-institution retrospective study, we investigate the patient characteristics and treatment outcomes, including pseudo-progression (PsP), for LGG patients selected for PT. Method: Adult patients with grade 2–3 glioma consecutively treated with radiotherapy (RT) from May 2012 to December 2019 were retrospectively included in this cohort study. Tumor characteristics and treatment data were collected. The groups treated with PT and XRT were compared regarding treatment characteristics, side effects, occurrence of PsP, and survival outcomes. PsP was defined as new or growing lesions followed by either decrease or stabilization during a 12 month-period with no treatment. Results: Out of 143 patients meeting the inclusion criteria, 44 were treated with PT, 98 with XRT and one with mixed PT + XRT. The patients receiving PT were younger, had a lower tumor grade, more oligodendrogliomas and received a lower mean brain and brainstem dose. PsP was observed in 21 out of 126 patients, with no difference between XRT and PT (p =.38). The rate of fatigue in immediate connection to RT (zero to three months after) was higher for XRT than for PT (p =.016). The PT patients had a significantly better PFS and OS than the XRT patients (p =.025 and.035), but in multivariate analysis radiation modality was non-significant. Higher average dose to both brain and brainstem was associated with inferior PFS and OS (p <.001). Median follow-up time were 69 months and 26 months for XRT and PT patients, respectively. Conclusion: Contrary to previous studies, there was no difference in risk of PsP for XRT and PT. PT was associated with lower rates of fatigue <3 months after RT. The superior survival outcomes for PT indicates that the patients with the best prognosis were referred to PT.
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  • Enger, Shirin A., et al. (author)
  • Dosimetry for gadolinium neutron capture therapy (GdNCT)
  • 2013
  • In: Radiation Measurements. - : Elsevier BV. - 1879-0925 .- 1350-4487. ; 59, s. 233-240
  • Journal article (peer-reviewed)abstract
    • Background Gadolinium (Gd) neutron capture therapy (GdNCT) is based on a neutron capture reaction (NCR) that involves emission of both short and long range products. The aim of this study was to investigate both the microscopic and macroscopic contributions of the absorbed dose involved in GdNCT. Methods Cylindrical containers with diameters 1-30 mm filled with a solution of Gd were irradiated with epithermal neutrons. The background neutron dose as well as the prompt gamma dose has been calculated and measured by means of film dosimetry for the largest cylinder. Monte Carlo codes MCNP5(b) and GEANT4 have been utilized for calculation the absorbed dose. Results and discussion Results from the film dosimetry are in agreement with the calculations for high doses while for low doses the measured values are higher than the calculated results. For the largest cylinder, the prompt gamma dose from GdNCR neutron is at least five times higher than the background dose. For a cell cluster model, in the first 0.1 mm the major contribution to the absorbed dose is from IC electrons. If Gd atoms were homogeneously distributed in the nuclei of all tumour cells, capture events between neutron and Gd atoms close to DNA could kill the tumour cells and give cross-fire dose from IC electrons to the cells located in the 0.1 mm range. Conclusions For a correct GdNCT dosimetry both microscopic part of the dose delivered by short-range low energy electrons and macroscopic part delivered by the prompt gamma should be considered.
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  • Enger, Shirin A., et al. (author)
  • Gadolinium neutron capture brachytherapy (GdNCB), a new treatment method for intravascular brachytherapy
  • 2006
  • In: Medical physics (Lancaster). - : Wiley. - 0094-2405. ; 33:1, s. 46-51
  • Journal article (peer-reviewed)abstract
    • Restenosis is a major problem after balloon angioplasty and stent implantation. The aim of this study is to introduce gadolinium neutron capture brachytherapy (GdNCB) as a suitable modality for treatment of stenosis. The utility of GdNCB in intravascular brachytherapy (IVBT) of stent stenosis is investigated by using the GEANT4 and MCNP4B Monte Carlo radiation transport codes. To study capture rate, Kerma, absorbed dose and absorbed dose rate around a Gd-containing stent activated with neutrons, a 30 mm long, 5 mm diameter gadolinium foil is chosen. The input data is a neutron spectrum used for clinical neutron capture therapy in Studsvik, Sweden. Thermal neutron capture in gadolinium yields a spectrum of high-energy gamma photons, which due to the build-up effect gives an almost flat dose delivery pattern to the first 4 mm around the stent. The absorbed dose rate is 1.33 Gy/min, 0.25 mm from the stent surface while the dose to normal tissue is in order of 0.22 Gy/min, i.e., a factor of 6 lower. To spare normal tissue further fractionation of the dose is also possible. The capture rate is relatively high at both ends of the foil. The dose distribution from gamma and charge particle radiation at the edges and inside the stent contributes to a nonuniform dose distribution. This will lead to higher doses to the surrounding tissue and may prevent stent edge and in-stent restenosis. The position of the stent can be verified and corrected by the treatment plan prior to activation. Activation of the stent by an external neutron field can be performed days after catherization when the target cells start to proliferate and can be expected to be more radiation sensitive. Another advantage of the nonradioactive gadolinium stent is the possibility to avoid radiation hazard to personnel.
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19.
  • Enger, Shirin A., et al. (author)
  • Monte Carlo calculations of thermal neutron capture in gadolinium : a comparison of GEANT4 and MCNP with measurements
  • 2006
  • In: Medical physics (Lancaster). - : Wiley. - 0094-2405. ; 33:2, s. 337-341
  • Journal article (peer-reviewed)abstract
    • GEANT4 is a Monte Carlo code originally implemented for high-energy physics applications and is well known for particle transport at high energies. The capacity of GEANT4 to simulate neutron transport in the thermal energy region is not equally well known. The aim of this article is to compare MCNP, a code commonly used in low energy neutron transport calculations and GEANT4 with experimental results and select the suitable code for gadolinium neutron capture applications. To account for the thermal neutron scattering from chemically bound atoms [S(alpha,beta)] in biological materials a comparison of thermal neutron fluence in tissue-like poly(methylmethacrylate) phantom is made with MCNP4B, GEANT4 6.0 patch1, and measurements from the neutron capture therapy (NCT) facility at the Studsvik, Sweden. The fluence measurements agreed with MCNP calculated results considering S(alpha,beta). The location of the thermal neutron peak calculated with MCNP without S(alpha,beta) and GEANT4 is shifted by about 0.5 cm towards a shallower depth and is 25%-30% lower in amplitude. Dose distribution from the gadolinium neutron capture reaction is then simulated by MCNP and compared with measured data. The simulations made by MCNP agree well with experimental results. As long as thermal neutron scattering from chemically bound atoms are not included in GEANT4 it is not suitable for NCT applications.
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20.
  • Gram, D., et al. (author)
  • Residual positioning errors and uncertainties for pediatric craniospinal irradiation and the impact of image guidance
  • 2020
  • In: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 15:1
  • Journal article (peer-reviewed)abstract
    • Background Optimal alignment is of utmost importance when treating pediatric patients with craniospinal irradiation (CSI), especially with regards to field junctions and multiple isocenters and techniques applying high dose gradients. Here, we investigated the setup errors and uncertainties for pediatric CSI using different setup verification protocols. Methods A total of 38 pediatric patients treated with CSI were identified for whom treatment records and setup images were available. The setup images were registered retrospectively to the reference image using an automated tool and matching on bony anatomy, subsequently, the impact of different correction protocols was simulated. Results For an action-level (AL)-protocol and a non-action level (NAL)-protocol, the translational residual setup error can be as large as 24 mm for an individual patient during a single fraction, and the rotational error as large as 6.1 degrees. With daily IGRT, the maximum setup errors were reduced to 1 mm translational and 5.4 degrees rotational versus 1 mm translational and 2.4 degrees rotational for 3- and 6- degrees of freedom (DoF) couch shifts, respectively. With a daily 6-DoF IGRT protocol for a wide field junction irradiation technique, the residual positioning uncertainty was below 1 mm and 1 degrees for translational and rotational directions, respectively. The largest rotational uncertainty was found for the patients' roll even though this was the least common type of rotational error, while the largest translational uncertainty was found in the patients' anterior-posterior-axis. Conclusions These results allow for informed margin calculation and robust optimization of treatments. Daily IGRT is the superior choice for setup of pediatric patients treated with CSI, although centers that do not have this option could use the results presented here to improve their margins and uncertainty estimates for a more accurate treatment alignment.
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  • Gram, Daniel, et al. (author)
  • The risk of radiation-induced neurocognitive impairment and the impact of sparing the hippocampus during pediatric proton cranial irradiation
  • 2023
  • In: Acta Oncologica. - 0284-186X. ; 62:2, s. 134-140
  • Journal article (peer-reviewed)abstract
    • Background and purpose: Hippocampus is a central component for neurocognitive function and memory. We investigated the predicted risk of neurocognitive impairment of craniospinal irradiation (CSI) and the deliverability and effects of hippocampal sparing. The risk estimates were derived from published NTCP models. Specifically, we leveraged the estimated benefit of reduced neurocognitive impairment with the risk of reduced tumor control. Material and methods: For this dose planning study, a total of 504 hippocampal sparing intensity modulated proton therapy (HS-IMPT) plans were generated for 24 pediatric patients whom had previously received CSI. Plans were evaluated with respect to target coverage and homogeneity index to target volumes, maximum and mean dose to OARs. Paired t-tests were used to compare hippocampal mean doses and normal tissue complication probability estimates. Results: The median mean dose to the hippocampus could be reduced from 31.3 GyRBE to 7.3 GyRBE (p <.001), though 20% of these plans were not considered clinically acceptable as they failed one or more acceptance criterion. Reducing the median mean hippocampus dose to 10.6 GyRBE was possible with all plans considered as clinically acceptable treatment plans. By sparing the hippocampus to the lowest dose level, the risk estimation of neurocognitive impairment could be reduced from 89.6%, 62.1% and 51.1% to 41.0% (p <.001), 20.1% (p <.001) and 29.9% (p <.001) for task efficiency, organization and memory, respectively. Estimated tumor control probability was not adversely affected by HS-IMPT, ranging from 78.5 to 80.5% for all plans. Conclusions: We present estimates of potential clinical benefit in terms of neurocognitive impairment and demonstrate the possibility of considerably reducing neurocognitive adverse effects, minimally compromising target coverage locally using HS-IMPT.
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22.
  • Knöös, Tommy, et al. (author)
  • Modelling of an Orthovoltage X-ray Therapy Unit with the EGSnrc Monte Carlo Package
  • 2007
  • In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6596 .- 1742-6588. ; 74, s. 86-95
  • Conference paper (peer-reviewed)abstract
    • Simulations with the EGSnrc code package of an orthovoltage x-ray machine have been performed. The BEAMnrc code was used to transport electrons, produce x-ray photons in the target and transport of these through the treatment machine down to the exit level of the applicator. Further transport in water or CT based phantoms was facilitated by the DOSXYZnrc code. Phase space files were scored with BEAMnrc and analysed regarding the energy spectra at the end of the applicator. Tuning of simulation parameters was based on the half-value layer quantity for the beams in either Al or Cu. Calculated depth dose and profile curves have been compared against measurements and show good agreement except at shallow depths. The MC model tested in this study can be used for various dosimetric studies as well as generating a library of typical treatment cases that can serve as both educational material and guidance in the clinical practice
  •  
23.
  • Konradsson, Elise, et al. (author)
  • Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients
  • 2021
  • In: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 11
  • Journal article (peer-reviewed)abstract
    • FLASH radiotherapy has emerged as a treatment technique with great potential to increase the differential effect between normal tissue toxicity and tumor response compared to conventional radiotherapy. To evaluate the feasibility of FLASH radiotherapy in a relevant clinical setting, we have commenced a feasibility and safety study of FLASH radiotherapy in canine cancer patients with spontaneous superficial solid tumors or microscopic residual disease, using the electron beam of our modified clinical linear accelerator. The setup for FLASH radiotherapy was established using a short electron applicator with a nominal source-to-surface distance of 70 cm and custom-made Cerrobend blocks for collimation. The beam was characterized by measuring dose profiles and depth dose curves for various field sizes. Ten canine cancer patients were included in this initial study; seven patients with nine solid superficial tumors and three patients with microscopic disease. The administered dose ranged from 15 to 35 Gy. To ensure correct delivery of the prescribed dose, film measurements were performed prior to and during treatment, and a Farmer-type ion-chamber was used for monitoring. Treatments were found to be feasible, with partial response, complete response or stable disease recorded in 11/13 irradiated tumors. Adverse events observed at follow-up ranging from 3-6 months were mild and consisted of local alopecia, leukotricia, dry desquamation, mild erythema or swelling. One patient receiving a 35 Gy dose to the nasal planum, had a grade 3 skin adverse event. Dosimetric procedures, safety and an efficient clincal workflow for FLASH radiotherapy was established. The experience from this initial study will be used as a basis for a veterinary phase I/II clinical trial with more specific patient inclusion selection, and subsequently for human trials.
  •  
24.
  • Lempart, Michael, et al. (author)
  • A deeply supervised convolutional neural network ensemble for multilabel segmentation of pelvic OARs
  • 2021
  • In: Radiotherapy and Oncology. - 1879-0887. ; 161:Suppl 1, s. 1417-1418
  • Conference paper (other academic/artistic)abstract
    • Accurate delineation of organs at risk (OAR) is a crucial step in radiation therapy (RT) treatment planning but is a manual and time-consuming process. Deep learning-based methods have shown promising results for medical image segmentation and can be used to accelerate this task. Nevertheless, it is rarely applied to complex structures found in the pelvis region, where manual segmentation can be difficult, costly and is not always feasible. The aim of this study was to train and validate a model, based on a modified U-Net architecture, for automated and improved multilabel segmentation of 10 pelvic OAR structures (total bone marrow, lower pelvis bone marrow, iliac bone marrow, lumosacral bone marrow, bowel cavity, bowel, small bowel, large bowel, rectum, and bladder).
  •  
25.
  • Lempart, Michael, et al. (author)
  • Pelvic U-Net : multi-label semantic segmentation of pelvic organs at risk for radiation therapy anal cancer patients using a deeply supervised shuffle attention convolutional neural network
  • 2022
  • In: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 17:1
  • Journal article (peer-reviewed)abstract
    • Background: Delineation of organs at risk (OAR) for anal cancer radiation therapy treatment planning is a manual and time-consuming process. Deep learning-based methods can accelerate and partially automate this task. The aim of this study was to develop and evaluate a deep learning model for automated and improved segmentations of OAR in the pelvic region. Methods: A 3D, deeply supervised U-Net architecture with shuffle attention, referred to as Pelvic U-Net, was trained on 143 computed tomography (CT) volumes, to segment OAR in the pelvic region, such as total bone marrow, rectum, bladder, and bowel structures. Model predictions were evaluated on an independent test dataset (n = 15) using the Dice similarity coefficient (DSC), the 95th percentile of the Hausdorff distance (HD95), and the mean surface distance (MSD). In addition, three experienced radiation oncologists rated model predictions on a scale between 1–4 (excellent, good, acceptable, not acceptable). Model performance was also evaluated with respect to segmentation time, by comparing complete manual delineation time against model prediction time without and with manual correction of the predictions. Furthermore, dosimetric implications to treatment plans were evaluated using different dose-volume histogram (DVH) indices. Results: Without any manual corrections, mean DSC values of 97%, 87% and 94% were found for total bone marrow, rectum, and bladder. Mean DSC values for bowel cavity, all bowel, small bowel, and large bowel were 95%, 91%, 87% and 81%, respectively. Total bone marrow, bladder, and bowel cavity segmentations derived from our model were rated excellent (89%, 93%, 42%), good (9%, 5%, 42%), or acceptable (2%, 2%, 16%) on average. For almost all the evaluated DVH indices, no significant difference between model predictions and manual delineations was found. Delineation time per patient could be reduced from 40 to 12 min, including manual corrections of model predictions, and to 4 min without corrections. Conclusions: Our Pelvic U-Net led to credible and clinically applicable OAR segmentations and showed improved performance compared to previous studies. Even though manual adjustments were needed for some predicted structures, segmentation time could be reduced by 70% on average. This allows for an accelerated radiation therapy treatment planning workflow for anal cancer patients.
  •  
26.
  • Lempart, Michael, et al. (author)
  • Volumetric modulated arc therapy dose prediction and deliverable treatment plan generation for prostate cancer patients using a densely connected deep learning model
  • 2021
  • In: Physics and imaging in radiation oncology. - : Elsevier BV. - 2405-6316. ; 19, s. 112-119
  • Journal article (peer-reviewed)abstract
    • Background and purpose: Radiation therapy treatment planning is a manual, time-consuming task that might be accelerated using machine learning algorithms. In this study, we aimed to evaluate if a triplet-based deep learning model can predict volumetric modulated arc therapy (VMAT) dose distributions for prostate cancer patients. Materials and methods: A modified U-Net was trained on triplets, a combination of three consecutive image slices and corresponding segmentations, from 160 patients, and compared to a baseline U-Net. Dose predictions from 17 test patients were transformed into deliverable treatment plans using a novel planning workflow. Results: The model achieved a mean absolute dose error of 1.3%, 1.9%, 1.0% and ≤ 2.6% for clinical target volume (CTV) CTV_D100%, planning target volume (PTV) PTV_D98%, PTV_D95% and organs at risk (OAR) respectively, when compared to the clinical ground truth (GT) dose distributions. All predicted distributions were successfully transformed into deliverable treatment plans and tested on a phantom, resulting in a passing rate of 100% (global gamma, 3%, 2 mm, 15% cutoff). The dose difference between deliverable treatment plans and GT dose distributions was within 4.4%. The difference between the baseline model and our improved model was statistically significant (p < 0.05) for CVT_D100%, PTV_D98% and PTV_D95%. Conclusion: Triplet-based training improved VMAT dose distribution predictions when compared to 2D. Dose predictions were successfully transformed into deliverable treatment plans using our proposed treatment planning procedure. Our method may automate parts of the workflow for external beam prostate radiation therapy and improve the overall treatment speed and plan quality.
  •  
27.
  • Lundemann, Michael, et al. (author)
  • Feasibility of multi-parametric PET and MRI for prediction of tumour recurrence in patients with glioblastoma
  • 2019
  • In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 46:3, s. 603-613
  • Journal article (peer-reviewed)abstract
    • Background: Recurrence in glioblastoma patients often occur close to the original tumour and indicates that the current treatment is inadequate for local tumour control. In this study, we explored the feasibility of using multi-modality imaging at the time of radiotherapy planning. Specifically, we aimed to identify parameters from pre-treatment PET and MRI with potential to predict tumour recurrence. Materials and methods: Sixteen patients were prospectively recruited and treated according to established guidelines. Multi-parametric imaging with 18 F-FET PET/CT and 18 F-FDG PET/MR including diffusion and dynamic contrast enhanced perfusion MRI were performed before radiotherapy. Correlations between imaging parameters were calculated. Imaging was related to the voxel-wise outcome at the time of tumour recurrence. Within the radiotherapy target, median differences of imaging parameters in recurring and non-recurring voxels were calculated for contrast-enhancing lesion (CEL), non-enhancing lesion (NEL), and normal appearing grey and white matter. Logistic regression models were created to predict the patient-specific probability of recurrence. The most important parameters were identified using standardized model coefficients. Results: Significant median differences between recurring and non-recurring voxels were observed for FDG, FET, fractional anisotropy, mean diffusivity, mean transit time, extra-vascular, extra-cellular blood volume and permeability derived from scans prior to chemo-radiotherapy. Tissue-specific patterns of voxel-wise correlations were observed. The most pronounced correlations were observed for 18 F-FDG- and 18 F-FET-uptake in CEL and NEL. Voxel-wise modelling of recurrence probability resulted in area under the receiver operating characteristic curve of 0.77 from scans prior to therapy. Overall, FET proved to be the most important parameter for recurrence prediction. Conclusion: Multi-parametric imaging before radiotherapy is feasible and significant differences in imaging parameters between recurring and non-recurring voxels were observed. Combining parameters in a logistic regression model enabled patient-specific maps of recurrence probability, where 18 F-FET proved to be most important. This strategy could enable risk-adapted radiotherapy planning.
  •  
28.
  • Munck af Rosenschöld, Per, et al. (author)
  • Current status of dosimetry at the boron neutron capture therapy facility at Studsvik, Sweden
  • 2002
  • In: Research and Development in Neutron Capture Therapy. - 9788832329094 ; , s. 437-441
  • Conference paper (peer-reviewed)abstract
    • The beam was successfully characterized in air and in phantom using various radiation dosimeter:,. The determination of the thermal neutron and photon components of the mixed beam in phantom can be determined with acceptable uncertainties, while the uncertainty of the high-energy neutron component is considerable but of limited clinical significance. The beam intensity is sufficiently high for reasonably short treatment times. A novel approach to in-vivo dosimetry and quality assurance of treatment time in terms of monitor units was introduced in order to comply with national regulations regarding radiation therapy.
  •  
29.
  • Munck af Rosenschöld, Per, et al. (author)
  • Impact of [18F]-fluoro-ethyl-tyrosine PET imaging on target definition for radiation therapy of high-grade glioma.
  • 2015
  • In: Neuro-Oncology. - : Oxford University Press (OUP). - 1523-5866 .- 1522-8517. ; 17:5, s. 757-763
  • Journal article (peer-reviewed)abstract
    • We sought to assess the impact of amino-acid (18)F-fluoro-ethyl-tyrosine (FET) positron emission tomography (PET) on the volumetric target definition for radiation therapy of high-grade glioma versus the current standard using MRI alone. Specifically, we investigated the influence of tumor grade, MR-defined tumor volume, and the extent of surgical resection on PET positivity.
  •  
30.
  • Munck af Rosenschöld, Per (author)
  • Mixed Beam Dosimetry - From Reactor Core to BNCT Patient
  • 2003
  • Doctoral thesis (other academic/artistic)abstract
    • Accurate radiation dosimetry is of paramount importance in order to ensure safe delivery of radiotherapy, and for the possibility of meaningful evaluation of clinical trials, as the radiation absorbed dose is correlated to tissue response. The aim of the studies described in this thesis was to investigate and devise novel approaches to mixed beam dosimetry in boron neutron capture therapy (BNCT). The computer model of the epithermal neutron beam at the Studsvik BNCT facility was described and experimentally verified. Good agreement was generally obtained in phantom (<5%) for the photon and fast neutron absorbed dose, and thermal neutron fluence, which can be seen as verification of the computer model. However, the calculated in-air photon kerma (photon contamination) of the beam was about 39% lower than the measured value. The effective energy of this photon contamination was investigated using photon kerma transmission through bismuth. The calculated photon spectrum consisted mainly of 478 keV gamma-rays from boron neutron capture in the collimator, while the measurements indicated a higher effective energy; an actual photon spectrum comprising of 53% and 47% relative 478 keV and 2.22 MeV fluence free in air, respectively, reproduced the measured transmission within 3%. The validated computer model of the mixed beam was subsequently used to calculate beam-dependent correction factors for the detectors used for dosimetry under reference conditions. Efforts were made to adhere to the (kQ) formalism and practice used in conventional radiotherapy, rather than that previously used in neutron radiotherapy. The calculations showed that commonly used ionization chambers could be employed in the epithermal neutron beam at Studsvik with kQ factors ranging between 1.02 and 1.10. The methodology employed ensured measurements with uncertainties of the thermal neutron fluence (1.4%, 1 SD), and the photon absorbed dose (2.5%, 1 SD) comparable to conventional radiotherapy standards. The measurement of the fast neutron absorbed dose, however, was associated with substantial uncertainties (24%, 1 SD). Clinical trials ensued, and the treatment procedure, as well as aspects of the clinical dosimetry, at the Studsvik facility is discussed in this thesis. Novel methods for verification of the clinical dosimetry in BNCT, which are presented in this thesis, ensure therapeutic safety. The methods presented include verification of the clinical dosimetry both prior to and following therapy. The verification employed prior to therapy was shown to have an uncertainty of 6.0% (1 SD), while the in vivo dosimetry method utilized in a post-therapy analysis benefits from improvements, as the uncertainty of 11.2% (1 SD) was estimated. This thesis presents a comprehensive discourse on the mixed beam dosimetry of epithermal neutron beams designed for BNCT.
  •  
31.
  • Munck af Rosenschöld, Per, et al. (author)
  • Prompt gamma tomography during BNCT – a feasibility study
  • 2006
  • In: Journal of Instrumentation. - 1748-0221. ; 1
  • Journal article (peer-reviewed)abstract
    • The success of clinical boron neutron capture therapy (BNCT) lies in the ability to manage the radiobiological effect on the tumour and healthy tissue, and thus, accurate dosimetry measurements is pertinent for each individual patient. In the present work we investigate the possibility of performing online prompt gamma tomography (PGT) during BNCT. A prototype detector system was constructed, which is in principle a pin-hole collimator with a HPGe crystal to be mounted on a C-bow device, with shielding of lithium-plastic and lead. The detector system was used to measure on a phantom placed in an epithermal neutron beam and on a 137Cs-source. The possibility of tomographic reconstruction using the detector system was tested on a phantom filled with a 131I-solution with a smaller sphere inserted containing a higher specific activity (ratio 10:1). The detector system was possible to operate up to about 6 × 108 cm-2 s-1 thermal neutron fluence at the peak in the phantom, at which time it was saturated. A 478 keV boron-peak was visible in the measured spectra but the signal-to-noise-ratio was rather low. No post-irradiation damage or neutron activation was detectable. A tomographic reconstruction of the phantom filled with 131I-solutions was performed using an algorithm developed in house and based on the MLEM method. The image quality is fairly good and the results provide a clear indication that the detector system can be used to obtain data that enables tomographic reconstruction. A spatial resolution of the detector system of about 2 cm was obtained from both the measurement on the 137Cs-source and the 131I-phantom. In conclusion, the presented feasibility study on a prototype PGT system is encouraging further studies specifically directed at improving the signal-to-noise-ratio in measurements in epithermal neutron beams.
  •  
32.
  • Munck af Rosenschöld, Per, et al. (author)
  • Quality assurance of patient dosimetry in boron neutron capture therapy
  • 2004
  • In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 43:4, s. 404-411
  • Journal article (peer-reviewed)abstract
    • The verification of the correctness of planned and executed treatments is imperative for safety in radiotherapy. The purpose of the present work is to describe and evaluate the quality assurance (QA) procedures for patient dosimetry implemented at the boron neutron capture therapy (BNCT) facility at Studsvik, Sweden. The dosimetric complexity of the mixed neutron-photon field during BNCT suggests a careful verification of routine procedures, specifically the treatment planning calculations. In the present study, two methods for QA of patient dosimetry are presented. The first is executed prior to radiotherapy and involves an independent check of the planned absorbed dose to be delivered to a point in the patient for each treatment field. The second QA procedure involves in vivo dosimetry measurements using posttreatment activation analysis. Absorbed dose conversion factors taking the difference in material composition and geometry of the patient and the PMMA phantom used for reference dosimetry were determined using the Monte Carlo method. The agreement of the QA procedure prior to radiotherapy reveals an acceptably small deviation for 60 treatment fields of ±4.2% (1 SD), while the in vivo dosimetry method presented may benefit from improvements, as the deviations observed were quite substantial (±12%, 1 SD), and were unlikely to be due to actual errors in the clinical dosimetry.
  •  
33.
  • Niyazi, Maximilian, et al. (author)
  • ESTRO-EANO guideline on target delineation and radiotherapy details for glioblastoma
  • 2023
  • In: Radiotherapy and Oncology. - 0167-8140. ; 184
  • Journal article (peer-reviewed)abstract
    • Background and Purpose: Target delineation in glioblastoma is still a matter of extensive research and debate. This guideline aims to update the existing joint European consensus on delineation of the clinical target volume (CTV) in adult glioblastoma patients. Material and Methods: The ESTRO Guidelines Committee identified 14 European experts in close interaction with the ESTRO clinical committee and EANO who discussed and analysed the body of evidence concerning contemporary glioblastoma target delineation, then took part in a two-step modified Delphi process to address open questions. Results: Several key issues were identified and are discussed including i) pre-treatment steps and immobilisation, ii) target delineation and the use of standard and novel imaging techniques, and iii) technical aspects of treatment including planning techniques and fractionation. Based on the EORTC recommendation focusing on the resection cavity and residual enhancing regions on T1-sequences with the addition of a reduced 15 mm margin, special situations are presented with corresponding potential adaptations depending on the specific clinical situation. Conclusions: The EORTC consensus recommends a single clinical target volume definition based on postoperative contrast-enhanced T1 abnormalities, using isotropic margins without the need to cone down. A PTV margin based on the individual mask system and IGRT procedures available is advised; this should usually be no greater than 3 mm when using IGRT.
  •  
34.
  • Persson, Bertil R, et al. (author)
  • “Abscopal” Effect of Radiation Therapy Combined with Immune-Therapy Using IFN-γ Gene Transfected Syngeneic Tumor Cells, in Rats with Bilateral Implanted N29 Tumors
  • 2011
  • In: ISRN Immunology. - : Hindawi Limited. - 2090-5645 .- 2090-5653. ; 2011
  • Journal article (peer-reviewed)abstract
    • The tumor growth rate response was studied on N29 rat glioma tumor cells subcutaneously implanted on both hind legs of Fischer-344 rats. At around 30 days after inoculation, RT was given with 60Co gamma radiation with 4 daily fractions of 5 Gy only to the right-lateral tumors. At days 26, 42, and 54 after inoculation, immunization was performed with irradiated syngeneic IFNγ-gene transfected cells. Tumor growth rate (TGR % per day) of the right-lateral irradiated tumor was significantly decreased (P<0.01) after RT alone and with the combination of RT and immunization. But immunization alone gave no significant decrease of the TGR but significantly increased time of survival. The TGR of the unirradiated left-lateral tumors was significantly decreased (P<0.02) only in the group of rats treated with RT alone. It is apparent that tumor cells killed by the radiation mediate suppression of tumor cells outside the target area. This effect is called the abscopal effect.
  •  
35.
  • Persson, Bertil R, et al. (author)
  • Radiation immunomodulatory gene tumor therapy of rats with intracerebral glioma tumors.
  • 2010
  • In: Radiation Research. - 0033-7587. ; 173:4, s. 433-440
  • Journal article (peer-reviewed)abstract
    • Single-fraction radiation therapy with 5 or 15 Gy (60)Co gamma radiation was combined with intraperitoneal injections of syngeneic interferon gamma (IFN-gamma)-transfected cells in rats with intracerebral N29 or N32 glioma tumors at days 7, 21 and 35 after inoculation. For intracerebral N29 tumors, single-fraction radiation therapy with 5 or 15 Gy had no significant effect on the survival time. Immunization with IFN-gamma-transfected N29 cells significantly increased the survival time by 61%. Single-fraction radiation therapy with 5 Gy combined with immunization increased the survival time significantly by 87% and complete remissions by 75% while with 15 Gy the survival time increased 45% with 38% complete remissions. For intracerebral N32 tumors, single-fraction radiation therapy with 15 Gy increased the survival time significantly by 20%. Immunization by itself had no significant effect with IFN-gamma-transfected N32 cells, but combined with 15 Gy single-fraction radiation therapy it increased survival time significantly by 40%, although there were no complete remissions. Based on these findings, we suggest a new therapeutic regimen for malignant glioma using single-fraction radiation therapy with a target absorbed dose of the order of 5-10 Gy combined with clinically verified immunotherapy.
  •  
36.
  • Persson, Bertil R, et al. (author)
  • Survival of rats with N29 brain tumours after irradiation with 5 or 15 Gy and immunization with IFN-gamma secreting tumour cells
  • 2008
  • In: BioMedical Engineering and Informatics : New Development and the Future - Proceedings of the 1st International Conference on BioMedical Engineering and Informatics, BMEI 2008 - New Development and the Future - Proceedings of the 1st International Conference on BioMedical Engineering and Informatics, BMEI 2008. - 9780769531182 ; 2, s. 243-247
  • Conference paper (peer-reviewed)abstract
    • Intra cerebral tumours were inoculated into the brain of Fischer-344 syngeneic rats. After one week they were treated with either 5 or 15 Gy of Co-60-gamma radiation. The first immunization was given 1 hour before the radiation treatment and then two more times with 14-day intervals. Immunization was performed with 3 x 10(6) radiation sterilized IFN-gamma secreting tumour cells (N29) injected intraperitoneally. Neither radiation therapy with 5 or 15 Gy nor immunization with N29 cells alone had any significant effect on the length of survival of N29 tumour bearing rats. But radiation therapy with 5 Gy combined with immunization with IFN-gamma secreting syngeneic N29 cells resulted in 63 % complete remissions and significantly (p < 0.05) increased survival for the tumour bearing rats. Corresponding combination with 15 Gy RT resulted in 50% complete remissions. There is a possibility of a synergistic effect by optimal combination of radiation therapy and immunization.
  •  
37.
  • Tonning Olsson, Ingrid, et al. (author)
  • Neurocognitive development after pediatric brain tumor - a longitudinal, retrospective cohort study
  • 2024
  • In: Child Neuropsychology. - : Informa UK Limited. - 0929-7049 .- 1744-4136. ; 30:1, s. 22-44
  • Journal article (peer-reviewed)abstract
    • Survivors of Pediatric Brain Tumors (PBTs) treated with cranial radiation therapy (CRT) often experience a decline in neurocognitive test scores. Less is known about the neurocognitive development of non-irradiated survivors of PBTs. The aim of this study was to statistically model neurocognitive development after PBT in both irradiated and non-irradiated survivors and to find clinical variables associated with the rate of decline in neurocognitive scores. A total of 151 survivors were included in the study. Inclusion criteria: Diagnosis of PBT between 2001 and 2013 or earlier diagnosis of PBT and turning 18 years of age between 2006 and 2013. Exclusion criteria: Death within a year from diagnosis, neurocutaneous syndromes, severe intellectual disability. Clinical neurocognitive data were collected retrospectively from medical records. Multilevel linear modeling was used to evaluate the rate of decline in neurocognitive measures and factors associated with the same. A decline was found in most measures for both irradiated and non-irradiated survivors. Ventriculo-peritoneal (VP) shunting and treatment with whole-brain radiation therapy (WBRT) were associated with a faster decline in neurocognitive scores. Male sex and supratentorial lateral tumor were associated with lower scores. Verbal learning measures were either stable or improving. Survivors of PBTs show a pattern of decline in neurocognitive scores irrespective of treatment received, which suggests the need for routine screening for neurocognitive rehabilitation. However, survivors treated with WBRT and/or a VP shunt declined at a faster rate and appear to be at the highest risk of negative neurocognitive outcomes and to have the greatest need for neurocognitive rehabilitation.
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