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1.
  • Ottosson, Sandra, 1981-, et al. (författare)
  • Weight and body mass index in relation to irradiated volume and to overall survival in patients with oropharyngeal cancer: a retrospective cohort study
  • 2014
  • Ingår i: Radiation Oncology. - 1748-717X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Weight loss is a common problem in patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN) treated with radiotherapy (RT). The aims of the present study were to determine if treated volume (TV), as a measure of the radiation dose burden, can predict weight loss in patients with oropharyngeal cancer and to analyze weight loss and body mass index (BMI) in the same patient group in relation to 5-year overall survival. Methods: The ARTSCAN trial is a prospective, randomized, multicenter trial in patients with SCCHN. Nutritional data from the ARTSCAN trial were analyzed retrospectively using univariate and multivariate statistical methods based on information on percentage weight loss from the start of RT up to five months after the termination of RT (study cohort 1, n = 232) and information on patients' BMI at the start of RT (study cohort 2, n = 203). TV was defined as the volume of the patient receiving at least 95% of the prescribed dose. TV64.6 (Gy) encompasses macroscopic tumor and TV43.7 (Gy) elective lymph nodes of the neck. Results: TV64.6 Gy and TV43.7 Gy were both significantly correlated with higher weight loss up to five months after the termination of RT in study cohort 1 (p < 0.001 for both). BMI at the start of RT was shown to be a prognostic factor for 5-year overall survival in study cohort 2 but weight loss was not. The hazard ratios and 95% confidence intervals were 3.78 (1.46-9.75) and 2.57 (1.43-4.62) in patients with underweight and normal weight, respectively. Conclusions: TV can predict weight loss during RT in patients with oropharyngeal cancer regardless of clinical stage. A high BMI (>25 kg/m(2)) at the start of RT is positively associated with survival in patients with oropharyngeal cancer.
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2.
  • Gaber, Alexander, et al. (författare)
  • Effects of radiation therapy on tissue and serum concentrations of tumour associated trypsin inhibitor and their prognostic significance in rectal cancer patients
  • 2011
  • Ingår i: Radiation Oncology. - 1748-717X. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We have previously demonstrated that elevated concentrations of tumour-associated trypsin inhibitor (TATI) in both tumour tissue (t-TATI) and in serum (s-TATI) are associated with a poor prognosis in colorectal cancer patients. It was also found that s-TATI concentrations were lower in patients with rectal cancer compared to patients with colon cancer. In this study, we investigated the effects of neoadjuvant radiotherapy (RT) on concentrations of t-TATI and s-TATI in patients with rectal cancer. Methods: TATI was analysed in serum, normal mucosa and tumour tissue collected at various time points in 53 rectal cancer patients enrolled in a case-control study where 12 patients received surgery alone, 20 patients 5 x 5 Gy (short-term) preoperative RT and 21 patients 25 x 2 Gy (long-term) preoperative RT. T-TATI was analysed by immunohistochemistry and s-TATI was determined by an immunofluorometric assay. Mann-Whitney U test and Wilcoxon Z (Z) test were used to assess t-TATI and s-TATI concentrations in relation to RT. Spearman's correlation (R) test was used to explore the associations between t-TATI, s-TATI and clinicopathological parameters. Overall survival (OS) according to high and low t-TATI and s-TATI concentrations was estimated by classification and regression tree analysis, Kaplan-Meier analysis and the log rank test. Results: RT did not affect concentrations of t-TATI or s-TATI. In patients receiving short-term but not long-term RT, s-TATI concentrations were significantly higher 4 weeks post surgery than in serum drawn prior to surgery (Z = -3.366, P < 0.001). T-TATI expression correlated with male gender (R = 0.406, P = 0.008). High t-TATI expression in surgical specimens was associated with a significantly shorter OS (P = 0.045). S-TATI concentrations in serum drawn at all time points were associated with an impaired OS (P = 0.035 before RT, P = 0.001 prior to surgery, P = 0.043 post surgery). At all time points, s-TATI correlated with higher age (P < 0.001-0.021) and with increased s-creatinine concentrations assessed prior to surgery (P = 0.041). Conclusions: The results presented here further validate the utility of t-TATI and s-TATI as prognostic biomarkers in patients with rectal cancer, independent of neoadjuvant RT.
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3.
  • Gunnlaugsson, Adalsteinn, et al. (författare)
  • Change in prostate volume during extreme hypo-fractionation analysed with MRI
  • 2014
  • Ingår i: Radiation Oncology. - 1748-717X. ; 9, s. 22-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Hypo-fractionated external beam radiotherapy with narrow CTV-PTV margins is increasingly applied for prostate cancer. This demands a precise target definition and knowledge on target location and extension during treatment. It is unclear how increase in fraction size affects changes in prostate volume during treatment. Our aim was to study prostate volume changes during extreme hypo-fractionation (7 x 6.1 Gy) by using sequential MRIs. Methods: Twenty patients treated with extreme hypo-fractionation were recruited from an on-going prospective randomized phase III trial. An MRI scan was done before start of treatment, at mid treatment and at the end of radiotherapy. The prostate was delineated at each MRI and the volume and maximum extension in left-right, anterior-posterior and cranial-caudal directions were measured. Results: There was a significant increase in mean prostate volume (14%) at mid treatment as compared to baseline. The prostate volume remained enlarged (9%) at the end of radiotherapy. Prostate swelling was most pronounced in the anterior-posterior and cranial-caudal directions. Conclusions: Extreme hypo-fractionation induced a significant prostate swelling during treatment that was still present at the time of last treatment fraction. Our results indicate that prostate swelling is an important factor to take into account when applying treatment margins during short extreme hypo-fractionation, and that tight margins should be applied with caution.
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4.
  • Gunnlaugsson, Adalsteinn, et al. (författare)
  • The effect on the small bowel of 5-FU and oxaliplatin in combination with radiation using a microcolony survival assay
  • 2009
  • Ingår i: Radiation Oncology. - London : BioMed Central. - 1748-717X. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In locally advanced rectal cancer, 5-Fluorouracil (5-FU)-based chemoradiation is the standard treatment. The main acute toxicity of this treatment is enteritis. Due to its potential radiosensitizing properties, oxaliplatin has recently been incorporated in many clinical chemoradiation protocols. The aim of this study was to investigate to what extent 5-FU and oxaliplatin influence the radiation (RT) induced small bowel mucosal damage when given in conjunction with single or split dose RT.Methods: Immune competent balb-c mice were treated with varying doses of 5-FU, oxaliplatin (given intraperitoneally) and total body RT, alone or in different combinations in a series of experiments. The small bowel damage was studied by a microcolony survival assay. The treatment effect was evaluated using the inverse of the slope (D(0)) of the exponential part of the dose-response curve.Results: In two separate experiments the dose-response relations were determined for single doses of RT alone, yielding D(0) values of 2.79 Gy (95% CI: 2.65 - 2.95) and 2.98 Gy (2.66 - 3.39), for doses in the intervals of 5-17 Gy and 5-10 Gy, respectively. Equitoxic low doses (IC5) of the two drugs in combination with RT caused a decrease in jejunal crypt count with significantly lower D(0): 2.30 Gy (2.10 - 2.56) for RT+5-FU and 2.27 Gy (2.08 - 2.49) for RT+oxaliplatin. Adding both drugs to RT did not further decrease D(0):2.28 Gy (1.97 - 2.71) for RT+5-FU+oxaliplatin. A clearly higher crypt survival was noted for split course radiation (3 x 2.5 Gy) compared to a single fraction of 7.5 Gy. The same difference was seen when 5-FU and/or oxaliplatin were added.Conclusion: Combining 5-FU or oxaliplatin with RT lead to an increase in mucosal damage as compared to RT alone in our experimental setting. No additional reduction of jejunal crypt counts was noted when both drugs were combined with single dose RT. The higher crypt survival with split dose radiation indicates a substantial recovery between radiation fractions. This mucosalsparing effect achieved by fractionation was maintained also when chemotherapy was added.
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5.
  • Rasmusson, Elisabeth, et al. (författare)
  • Low rate of lymphedema after extended pelvic lymphadenectomy followed by pelvic irradiation of node-positive prostate cancer
  • 2013
  • Ingår i: Radiation Oncology. - 1748-717X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim of the present study was to evaluate the prevalence and severity of lower limb lymphedema after pelvic lymphadenectomy and radiotherapy to the pelvic lymph nodes in patients with prostate cancer. Methods: Twenty-six patients underwent combined treatment for high-risk node-positive prostate cancer at Skane University Hospital between April 2008 and March 2011. The treatment consisted of extended pelvic lymphadenectomy followed by androgen deprivation therapy and radiotherapy. The pelvic lymphnodes, prostate and seminal vesicles were treated with external beam radiotherapy (EBRT) to an absorbed dose of 50 Gy followed by a brachytherapy (BT) boost of 2x10 Gy to the prostate only. Twenty-two patients accepted an invitation to a clinical examination with focus on lower limb swelling. The median time between the end of radiotherapy and examination was 2.2 years (range 1.2-4.1). Results: Six patients (27%) experienced grade 1 lymphedema and two patients (9%) grade 2 while none had grade 3 or 4 according to the CTC Common Toxicity Criteria scale 4.0. Three patients required treatment with compression stockings. Conclusion: Brachytherapy and pelvic EBRT have a low incidence of lymphedema (at median 2.2 y after treatment) in patients with high-risk node-positive prostate cancer that have undergone pelvic lymph node dissection.
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6.
  • Lindblom, Emely, et al. (författare)
  • Treatment fractionation for stereotactic radiotherapy of lung tumours: a modelling study of the influence of chronic and acute hypoxia on tumour control probability
  • 2014
  • Ingår i: Radiation Oncology. - 1748-717X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer (NSCLC) has led to promising local control and overall survival for fractionation schemes with increasingly high fractional doses. A point has however been reached where the number of fractions used might be too low to allow efficient local inter-fraction reoxygenation of the hypoxic cells residing in the tumour. It was therefore the purpose of this study to investigate the impact of hypoxia and extreme hypofractionation on the tumour control probability (TCP) from SBRT.Methods: A three-dimensional model of tumour oxygenation able to simulate oxygenation changes on the microscale was used. The TCP was determined for clinically relevant SBRT fractionation schedules of 1, 3 and 5 fractions assuming either static tumour oxygenation or that the oxygenation changes locally between fractions due to fast reoxygenation of acute hypoxia without an overall reduction in chronic hypoxia.Results: For the schedules applying three or five fractions the doses required to achieve satisfying levels of TCP were considerably lower when local oxygenation changes were assumed compared to the case of static oxygenation; a decrease in D50 of 17.7 Gy was observed for a five-fractions schedule applied to a 20% hypoxic tumour when fast reoxygenation was modelled. Assuming local oxygenation changes, the total doses required for a tumor control probability of 50% were of similar size for one, three and five fractions.Conclusions: Although attractive from a practical point of view, extreme hypofractionation using just one single fraction may result in impaired local control of hypoxic tumours, as it eliminates the possibility for any kind of reoxygenation.
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9.
  • Ding, Zhen-Yu, et al. (författare)
  • Livin expression is an independent factor in rectal cancer patients with or without preoperative radiotherapy
  • 2013
  • Ingår i: Radiation Oncology. - London, United Kingdom : BioMed Central. - 1748-717X. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This study was aimed to investigate the expression significance of Livin in relation to radiotherapy (RT), clinicopathological and biological factors of rectal cancer patients.Methods: This study included 144 primary rectal cancer patients who participated in a Swedish clinical trial of preoperative radiotherapy. Tissue microarray samples from the excised primary rectal cancers, normal mucosa and lymph node metastases were immunostained with Livin antibody. The proliferation of colon cancer cell lines SW620 and RKO was assayed after Livin knock-down.Results: The expression of Livin was significantly increased from adjacent (P = 0.051) or distant (P = 0.028) normal mucosa to primary tumors. 15.4% (2/13) and 39.7% (52/131) patients with Livin-negative and positive tumors died at 180 months after surgery, and the difference tended to be statistically significant (P = 0.091). In multivariate analyses, the difference achieved statistical significance, independent of TNM stage, local and distant recurrence, grade of differentiation, gender, and age (odds ratio = 5.09, 95% CI: 1.01-25.64, P = 0.048). The in vitro study indicated colon cancer cells with Livin knock-down exhibited decreased proliferation compared with controls after RT.Conclusions: The expression of Livin was was independently related to survival in rectal cancer patients, suggesting Livin as a useful prognostic factor for rectal cancer patients.
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10.
  • Ferreira, Brigida C., et al. (författare)
  • Radiobiological evaluation of forward and inverse IMRT using different fractionations for head and neck tumours
  • 2010
  • Ingår i: Radiation Oncology. - 1748-717X. ; 5, s. 57-
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To quantify the radiobiological advantages obtained by an Improved Forward Planning technique (IFP) and two IMRT techniques using different fractionation schemes for the irradiation of head and neck tumours. The conventional radiation therapy technique (CONVT) was used here as a benchmark. Methods: Seven patients with head and neck tumours were selected for this retrospective planning study. The PTV1 included the primary tumour, PTV2 the high risk lymph nodes and PTV3 the low risk lymph nodes. Except for the conventional technique where a maximum dose of 64.8 Gy was prescribed to the PTV1, 70.2 Gy, 59.4 Gy and 50.4 Gy were prescribed respectively to PTV1, PTV2 and PTV3. Except for IMRT2, all techniques were delivered by three sequential phases. The IFP technique used five to seven directions with a total of 15 to 21 beams. The IMRT techniques used five to nine directions and around 80 segments. The first, IMRT1, was prescribed with the conventional fractionation scheme of 1.8 Gy per fraction delivered in 39 fractions by three treatment phases. The second, IMRT2, simultaneously irradiated the PTV2 and PTV3 with 59.4 Gy and 50.4 Gy in 28 fractions, respectively, while the PTV1 was boosted with six subsequent fractions of 1.8 Gy. Tissue response was calculated using the relative seriality model and the Poisson Linear-Quadratic-Time model to simulate repopulation in the primary tumour. Results: The average probability of total tumour control increased from 38% with CONVT to 80% with IFP, to 85% with IMRT1 and 89% with IMRT2. The shorter treatment time and larger dose per fraction obtained with IMRT2 resulted in an 11% increase in the probability of control in the PTV1 with respect to IFP and 7% relatively to IMRT1 (p < 0.05). The average probability of total patient complications was reduced from 80% with CONVT to 61% with IFP and 31% with IMRT. The corresponding probability of complications in the ipsilateral parotid was 63%, 42% and 20%; in the contralateral parotid it was 50%, 20% and 9%; in the oral cavity it was 2%, 15% and 4% and in the mandible it was 1%, 5% and 3%, respectively. Conclusions: A significant improvement in treatment outcome was obtained with IMRT compared to conventional radiation therapy. The practical and biological advantages of IMRT2, employing a shorter treatment time, may outweigh the small differences obtained in the organs at risk between the two IMRT techniques. This technique is therefore presently being used in the clinic for selected patients with head and neck tumours. A significant improvement in the quality of the dose distribution was obtained with IFP compared to CONVT. Thus, this beam arrangement is used in the clinical routine as an alternative to IMRT.
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12.
  • Han, Yang, et al. (författare)
  • X-radiation inhibits histone deacetylase 1 and 2, upregulates Axin expression and induces apoptosis in non-small cell lung cancer
  • 2012
  • Ingår i: Radiation Oncology. - : BioMed Central. - 1748-717X. ; 7:183
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundHistone deacetylase (HDAC) plays an important role in the deacetylation of histone, which can alter gene expression patterns and affect cell behavior associated with malignant transformation. The aims of this study were to investigate the relationships between HDAC1, HDAC2, clinicopathologic characteristics, patient prognosis and apoptosis, to clarify the mechanism of upregulation of the Axis inhibitor Axin (an important regulator of the Wnt pathway) by X-radiation and to elucidate the effect of siRNA on radiation therapy of non-small cell lung cancer (NSCLC).MethodsHDAC1 and HDAC2 expression levels were measured by immunohistochemistry and reverse transcription PCR. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling and fluorescence activated cell sorting. BE1 cells expressing Axin were exposed to 2 Gy of X-radiation.ResultsExpression of HDAC1 and that of HDAC2 were correlated, and significantly higher in NSCLC tissues than in normal lung tissues (P < 0.05). HDAC1 and HDAC2 expression was correlated with pTNM stage and negatively correlated with differentiation of NSCLC and apoptotic index (P < 0.05). The prognosis of patients with low expression of HDAC1 and HDAC2 was better than that of those with high expression. X-radiation and siRNA inhibited HDAC1 and HDAC2 expression in NSCLC cells and Axin levels were significantly higher in BE1 cells.ConclusionsX-radiation and siRNA inhibit expression of HDAC1 and HDAC2, weaken the inhibitory effect of HDAC on Axin, upregulate Axin expression and induce apoptosis of lung cancer cells. Inhibition of HDAC1 and HDAC2 is a means of enhancing the radiosensitivity of NSCLC.
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14.
  • Jonsson, Joakim H, et al. (författare)
  • Registration accuracy for MR images of the prostate using a subvolume based registration protocol
  • 2011
  • Ingår i: Radiation Oncology. - 1748-717X. ; 6:1, s. 73-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In recent years, there has been a considerable research effort concerning the integration of magnetic resonance imaging (MRI) into the external radiotherapy workflow motivated by the superior soft tissue contrast as compared to computed tomography. Image registration is a necessary step in many applications, e.g. in patient positioning and therapy response assessment with repeated imaging. In this study, we investigate the dependence between the registration accuracy and the size of the registration volume for a subvolume based rigid registration protocol for MR images of the prostate.METHODS: Ten patients were imaged four times each over the course of radiotherapy treatment using a T2 weighted sequence. The images were registered to each other using a mean square distance metric and a step gradient optimizer for registration volumes of different sizes. The precision of the registrations was evaluated using the center of mass distance between the manually defined prostates in the registered images. The optimal size of the registration volume was determined by minimizing the standard deviation of these distances.RESULTS: We found that prostate position was most uncertain in the anterior-posterior (AP) direction using traditional full volume registration. The improvement in standard deviation of the mean center of mass distance between the prostate volumes using a registration volume optimized to the prostate was 3.9 mm (p < 0.001) in the AP direction. The optimum registration volume size was 0 mm margin added to the prostate gland as outlined in the first image series.CONCLUSIONS: Repeated MR imaging of the prostate for therapy set-up or therapy assessment will both require high precision tissue registration. With a subvolume based registration the prostate registration uncertainty can be reduced down to the order of 1 mm (1 SD) compared to several millimeters for registration based on the whole pelvis.
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15.
  • Jonsson, Joakim H, et al. (författare)
  • Treatment planning using MRI data: an analysis of the dose calculation accuracy for different treatment regions
  • 2010
  • Ingår i: Radiation Oncology. - 1748-717X. ; 5, s. 62-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Because of superior soft tissue contrast, the use of magnetic resonance imaging (MRI) as a complement to computed tomography (CT) in the target definition procedure for radiotherapy is increasing. To keep the workflow simple and cost effective and to reduce patient dose, it is natural to strive for a treatment planning procedure based entirely on MRI. In the present study, we investigate the dose calculation accuracy for different treatment regions when using bulk density assignments on MRI data and compare it to treatment planning that uses CT data.METHODS: MR and CT data were collected retrospectively for 40 patients with prostate, lung, head and neck, or brain cancers. Comparisons were made between calculations on CT data with and without inhomogeneity corrections and on MRI or CT data with bulk density assignments. The bulk densities were assigned using manual segmentation of tissue, bone, lung, and air cavities.RESULTS: The deviations between calculations on CT data with inhomogeneity correction and on bulk density assigned MR data were small. The maximum difference in the number of monitor units required to reach the prescribed dose was 1.6%. This result also includes effects of possible geometrical distortions.CONCLUSIONS: The dose calculation accuracy at the investigated treatment sites is not significantly compromised when using MRI data when adequate bulk density assignments are made. With respect to treatment planning, MRI can replace CT in all steps of the treatment workflow, reducing the radiation exposure to the patient, removing any systematic registration errors that may occur when combining MR and CT, and decreasing time and cost for the extra CT investigation.
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18.
  • Lindvall, Peter, et al. (författare)
  • Reproducibility and geometric accuracy of the Fixster system during hypofractionated stereotactic radiotherapy
  • 2008
  • Ingår i: Radiation Oncology. - 1748-717X. ; 3:16
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Hypofractionated radiotherapy has been used for the treatment of AVMs and brain metastases. Hypofractionation necessitates the use of a relocatable stereotactic frame that has to be applied on several occasions. The stereotactic frame needs to have a high degree of reproducibility, and patient positioning is crucial to achieve a high accuracy of the treatment.METHODS:In this study we have, by radiological means, evaluated the reproducibility of the isocenter in consecutive treatment sessions using the Fixster frame. Deviations in the X, Y and Z-axis were measured in 10 patients treated with hypofractionated radiotherapy.RESULTS:The mean deviation in the X-axis was 0.4 mm (range -2.1 - 2.1, median 0.7 mm) and in the Y-axis -0.3 mm (range -1.4 - 0.7, median -0.2 mm). The mean deviation in the Z-axis was -0.6 (range -1.4 - 1.4, median 0.0 mm).CONCLUSION:There is a high degree of reproducibility of the isocenter during successive treatment sessions with HCSRT using the Fixster frame for stereotactic targeting. The high reducibility enables a safe treatment using hypofractionated stereotactic radiotherapy.
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19.
  • Löfdahl, Elisabet, et al. (författare)
  • Compromised quality of life in adult patients who have received a radiation dose towards the basal part of the brain. A case-control study in long-term survivors from cancer in the head and neck region.
  • 2012
  • Ingår i: Radiation oncology (London, England). - 1748-717X. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • ABSTRACT: BACKGROUND: Adult patients with hypothalamic-pituitary disorders have compromised quality of life (QoL). Whether this is due to their endocrine consequences (hypopituitarism), their underlying hypothalamic-pituitary disorder or both is still under debate. The aim of this trial was to measure quality of life (QoL) in long-term cancer survivors who have received a radiation dose to the basal part of the brain and the pituitary. METHODS: Consecutive patients (n=101) treated for oropharyngeal or epipharyngeal cancer with radiotherapy followed free of cancer for a period of 4 to10 years were identified. Fifteen patients (median age 56 years) with no concomitant illness and no hypopituitarism after careful endocrine evaluation were included in a case-control study with matched healthy controls. Doses to the hypothalamic-pituitary region were calculated. QoL was assessed using the Symptom check list (SCL)-90, Nottingham Health Profile (NHP), and Psychological Well Being (PGWB) questionnaires. Level of physical activity was assessed using the Baecke questionnaire. RESULTS: The median accumulated dose was 1.9 Gy (1.5--2.2 Gy) to the hypothalamus and 2.4 Gy (1.8--3.3 Gy) to the pituitary gland in patients with oropharyngeal cancer and 6.0--9.3 Gy and 33.5--46.1 Gy, respectively in patients with epipharyngeal cancer (n=2). The patients showed significantly more anxiety and depressiveness, and lower vitality, than their matched controls. CONCLUSION: In a group of long time survivors of head and neck cancer who hade received a low radiation dose to the hypothalamic-pituitary region and who had no endocrine consequences of disease or its treatment QoL was compromised as compared with well matched healthy controls.
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20.
  • Nyholm, Tufve, et al. (författare)
  • Systematisation of spatial uncertainties for comparison between a MR and a CT-based radiotherapy workflow for prostate treatments
  • 2009
  • Ingår i: Radiation Oncology. - 1748-717X. ; 4:54
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In the present work we compared the spatial uncertainties associated with a MR-based workflow for external radiotherapy of prostate cancer to a standard CT-based workflow. The MR-based workflow relies on target definition and patient positioning based on MR imaging. A solution for patient transport between the MR scanner and the treatment units has been developed. For the CT-based workflow, the target is defined on a MR series but then transferred to a CT study through image registration before treatment planning, and a patient positioning using portal imaging and fiducial markers. Methods: An "open bore" 1.5T MRI scanner, Siemens Espree, has been installed in the radiotherapy department in near proximity to a treatment unit to enable patient transport between the two installations, and hence use the MRI for patient positioning. The spatial uncertainty caused by the transport was added to the uncertainty originating from the target definition process, estimated through a review of the scientific literature. The uncertainty in the CT-based workflow was estimated through a literature review.Results: The systematic uncertainties, affecting all treatment fractions, are reduced from 3-4 mm (ISd) with a CT based workflow to 2-3 mm with a MR based workflow. The main contributing factor to this improvement is the exclusion of registration between MR and CT in the planning phase of the treatment.
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21.
  • Nyholm, Tufve, et al. (författare)
  • Variability in prostate and seminal vesicle delineations defined on magnetic resonance images, a multi-observer, -center and -sequence study
  • 2013
  • Ingår i: Radiation Oncology. - : BioMed Central. - 1748-717X. ; 8, s. 126-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The use of magnetic resonance (MR) imaging as a part of preparation for radiotherapy is increasing. For delineation of the prostate several publications have shown decreased delineation variability using MR compared to computed tomography (CT). The purpose of the present work was to investigate the intra- and inter-physician delineation variability for prostate and seminal vesicles, and to investigate the influence of different MR sequence settings used clinically at the five centers participating in the study.Methods: MR series from five centers, each providing five patients, were used. Two physicians from each center delineated the prostate and the seminal vesicles on each of the 25 image sets. The variability between the delineations was analyzed with respect to overall, intra-and inter-physician variability, and dependence between variability and origin of the MR images, i.e. the MR sequence used to acquire the data.Results: The intra-physician variability in different directions was between 1.3 - 1.9 mm and 3 - 4 mm for the prostate and seminal vesicles respectively (1 std). The inter-physician variability for different directions were between 0.7 - 1.7 mm and approximately equal for the prostate and seminal vesicles. Large differences in variability were observed for individual patients, and also for individual imaging sequences used at the different centers. There was however no indication of decreased variability with higher field strength.Conclusion: The overall delineation variability is larger for the seminal vesicles compared to the prostate, due to a larger intra-physician variability. The imaging sequence appears to have a large influence on the variability, even for different variants of the T2-weighted spin-echo based sequences, which were used by all centers in the study.
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22.
  • Olsson, Erik, 1960, et al. (författare)
  • Hippocampal volumes in patients exposed to low-dose radiation to the basal brain. A case--control study in long-term survivors from cancer in the head and neck region.
  • 2012
  • Ingår i: Radiation oncology (London, England). - 1748-717X. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • ABSTRACT: BACKGROUND: An earlier study from our group of long time survivors of head and neck cancer who had received a low radiation dose to the hypothalamic-pituitary region, with no signs of recurrence or pituitary dysfunction, had their quality of life (QoL) compromised as compared with matched healthy controls. Hippocampal changes have been shown to accompany several psychiatric conditions and the aim of the present study was to test whether the patients' lowered QoL was coupled to a reduction in hippocampal volume. METHODS: Patients (11 men and 4 women, age 31--65) treated for head and neck cancer 4--10 years earlier and with no sign of recurrence or pituitary dysfunction, and 15 matched controls were included. The estimated radiation doses to the basal brain including the hippocampus (1.5 -- 9.3 Gy) had been calculated in the earlier study. The hippocampal volumetry was done on coronal sections from a 1.5 T MRI scanner. Measurements were done by two independent raters, blinded to patients and controls, using a custom method for computer assisted manual segmentation. The volumes were normalized for intracranial volume which was also measured manually. The paired t test and Wilcoxon's signed rank test were used for the main statistical analysis. RESULTS: There was no significant difference with respect to left, right or total hippocampal volume between patients and controls. All mean differences were close to zero, and the two-tailed 95% confidence interval for the difference in total, normalized volume does not include a larger than 8% deficit in the patients. CONCLUSION: The study gives solid evidence against the hypothesis that the patients' lowered quality of life was due to a major reduction of hippocampal volume.
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23.
  • Sjöberg, Carl, et al. (författare)
  • Clinical evaluation of multi-atlas based segmentation of lymph node regions in head and neck and prostate cancer patients
  • 2013
  • Ingår i: Radiation Oncology. - : BioMed Central. - 1748-717X. ; 8, s. Article number: 229-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Semi-automated segmentation using deformable registration of selected atlas cases consisting of expert segmented patient images has been proposed to facilitate the delineation of lymph node regions for three-dimensional conformal and intensity-modulated radiotherapy planning of head and neck and prostate tumours. Our aim is to investigate if fusion of multiple atlases will lead to clinical workload reductions and more accurate segmentation proposals compared to the use of a single atlas segmentation, due to a more complete representation of the anatomical variations. Methods: Atlases for lymph node regions were constructed using 11 head and neck patients and 15 prostate patients based on published recommendations for segmentations. A commercial registration software (Velocity AI) was used to create individual segmentations through deformable registration. Ten head and neck patients, and ten prostate patients, all different from the atlas patients, were randomly chosen for the study from retrospective data. Each patient was first delineated three times, (a) manually by a radiation oncologist, (b) automatically using a single atlas segmentation proposal from a chosen atlas and (c) automatically by fusing the atlas proposals from all cases in the database using the probabilistic weighting fusion algorithm. In a subsequent step a radiation oncologist corrected the segmentation proposals achieved from step (b) and (c) without using the result from method (a) as reference. The time spent for editing the segmentations was recorded separately for each method and for each individual structure. Finally, the Dice Similarity Coefficient and the volume of the structures were used to evaluate the similarity between the structures delineated with the different methods. Results: For the single atlas method, the time reduction compared to manual segmentation was 29% and 23% for head and neck and pelvis lymph nodes, respectively, while editing the fused atlas proposal resulted in time reductions of 49% and 34%. The average volume of the fused atlas proposals was only 74% of the manual segmentation for the head and neck cases and 82% for the prostate cases due to a blurring effect from the fusion process. After editing of the proposals the resulting volume differences were no longer statistically significant, although a slight influence by the proposals could be noticed since the average edited volume was still slightly smaller than the manual segmentation, 9% and 5%, respectively. Conclusions: Segmentation based on fusion of multiple atlases reduces the time needed for delineation of lymph node regions compared to the use of a single atlas segmentation. Even though the time saving is large, the quality of the segmentation is maintained compared to manual segmentation.
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24.
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25.
  • Taheri-Kadkhoda, Zahra, 1969, et al. (författare)
  • Intensity-modulated radiotherapy of nasopharyngeal carcinoma: a comparative treatment planning study of photons and protons.
  • 2008
  • Ingår i: Radiation oncology (London, England). - 1748-717X. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The aim of this treatment planning study was to investigate the potential advantages of intensity-modulated (IM) proton therapy (IMPT) compared with IM photon therapy (IMRT) in nasopharyngeal carcinoma (NPC). METHODS: Eight NPC patients were chosen. The dose prescriptions in cobalt Gray equivalent (GyE) for gross tumor volumes of the primary tumor (GTV-T), planning target volumes of GTV-T and metastatic (PTV-TN) and elective (PTV-N) lymph node stations were 72.6 GyE, 66 GyE, and 52.8 GyE, respectively. For each patient, nine coplanar fields IMRT with step-and-shoot technique and 3D spot-scanned three coplanar fields IMPT plans were prepared. Both modalities were planned in 33 fractions to be delivered with a simultaneous integrated boost technique. All plans were prepared and optimized by using the research version of the inverse treatment planning system KonRad (DKFZ, Heidelberg). RESULTS: Both treatment techniques were equal in terms of averaged mean dose to target volumes. IMPT plans significantly improved the tumor coverage and conformation (P < 0.05) and they reduced the averaged mean dose to several organs at risk (OARs) by a factor of 2-3. The low-to-medium dose volumes (0.33-13.2 GyE) were more than doubled by IMRT plans. CONCLUSION: In radiotherapy of NPC patients, three-field IMPT has greater potential than nine-field IMRT with respect to tumor coverage and reduction of the integral dose to OARs and non-specific normal tissues. The practicality of IMPT in NPC deserves further exploration when this technique becomes available on wider clinical scale.
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26.
  • Adrian, Gabriel, et al. (författare)
  • Primary tumor volume and prognosis for patients with p16-positive and p16-negative oropharyngeal squamous cell carcinoma treated with radiation therapy
  • 2022
  • Ingår i: Radiation Oncology. - : Springer Nature. - 1748-717X. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prescribed radiation dose to patients with oropharyngeal squamous cell carcinoma (OPSCC) is standardized, even if the prognosis for individual patients may differ. Easy-at-hand pre-treatment risk stratification methods are valuable to individualize therapy. In the current study we assessed the prognostic impact of primary tumor volume for p16-positive and p16-negative tumors and in relationship to other prognostic factors for outcome in patients with OPSCC treated with primary radiation therapy (RT). Methods: Five hundred twenty-three OPSCC patients with p16-status treated with primary RT (68.0 Gy to 73.1 Gy in 7 weeks, or 68.0 Gy in 4.5 weeks), with or without concurrent chemotherapy, within three prospective trials were included in the study. Local failure (LF), progression free survival (PFS) and overall survival (OS) in relationship to the size of the primary gross tumor volume (GTV-T) and other prognostic factors were investigated. Efficiency of intensified RT (RT with total dose 73.1 Gy or given within 4.5 weeks) was analyzed in relationship to tumor volume. Results: The volume of GTV-T and p16-status were found to be the strongest prognostic markers for LF, PFS and OS. For p16-positive tumors, an increase in tumor volume had a significantly higher negative prognostic impact compared with p16-negative tumors. Within a T-classification, patients with a smaller tumor, compared with a larger tumor, had a better prognosis. The importance of tumor volume remained after adjusting for nodal status, age, performance status, smoking status, sex, and hemoglobin-level. The adjusted hazard ratio for OS per cm3 increase in tumor volume was 2.3% (95% CI 0–4.9) for p16-positive and 1.3% (95% 0.3–2.2) for p16-negative. Exploratory analyses suggested that intensified RT could mitigate the negative impact of a large tumor volume. Conclusions: Outcome for patients with OPSCC treated with RT is largely determined by tumor volume, even when adjusting for other established prognostic factors. Tumor volume is significantly more influential for patients with p16-positive tumors. Patients with large tumor volumes might benefit by intensified RT to improve survival.
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27.
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28.
  • Björeland, Ulrika, et al. (författare)
  • Hyaluronic acid spacer in prostate cancer radiotherapy : dosimetric effects, spacer stability and long-term toxicity and PRO in a phase II study
  • 2023
  • Ingår i: Radiation Oncology. - : BioMed Central (BMC). - 1748-717X. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Perirectal spacers may be beneficial to reduce rectal side effects from radiotherapy (RT). Here, we present the impact of a hyaluronic acid (HA) perirectal spacer on rectal dose as well as spacer stability, long-term gastrointestinal (GI) and genitourinary (GU) toxicity and patient-reported outcome (PRO).METHODS: In this phase II study 81 patients with low- and intermediate-risk prostate cancer received transrectal injections with HA before external beam RT (78 Gy in 39 fractions). The HA spacer was evaluated with MRI four times; before (MR0) and after HA-injection (MR1), at the middle (MR2) and at the end (MR3) of RT. GI and GU toxicity was assessed by physician for up to five years according to the RTOG scale. PROs were collected using the Swedish National Prostate Cancer Registry and Prostate cancer symptom scale questionnaires.RESULTS: There was a significant reduction in rectal V70% (54.6 Gy) and V90% (70.2 Gy) between MR0 and MR1, as well as between MR0 to MR2 and MR3. From MR1 to MR2/MR3, HA thickness decreased with 28%/32% and CTV-rectum space with 19%/17% in the middle level. The cumulative late grade ≥ 2 GI toxicity at 5 years was 5% and the proportion of PRO moderate or severe overall bowel problems at 5 years follow-up was 12%. Cumulative late grade ≥ 2 GU toxicity at 5 years was 12% and moderate or severe overall urinary problems at 5 years were 10%.CONCLUSION: We show that the HA spacer reduced rectal dose and long-term toxicity.
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29.
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30.
  • Edmund, Jens M., et al. (författare)
  • A review of substitute CT generation for MRI-only radiation therapy
  • 2017
  • Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 12
  • Forskningsöversikt (refereegranskat)abstract
    • Radiotherapy based on magnetic resonance imaging as the sole modality (MRI-only RT) is an area of growing scientific interest due to the increasing use of MRI for both target and normal tissue delineation and the development of MR based delivery systems. One major issue in MRI-only RT is the assignment of electron densities (ED) to MRI scans for dose calculation and a similar need for attenuation correction can be found for hybrid PET/MR systems. The ED assigned MRI scan is here named a substitute CT (sCT). In this review, we report on a collection of typical performance values for a number of main approaches encountered in the literature for sCT generation as compared to CT. A literature search in the Scopus database resulted in 254 papers which were included in this investigation. A final number of 50 contributions which fulfilled all inclusion criteria were categorized according to applied method, MRI sequence/contrast involved, number of subjects included and anatomical site investigated. The latter included brain, torso, prostate and phantoms. The contributions geometric and/or dosimetric performance metrics were also noted. The majority of studies are carried out on the brain for 5-10 patients with PET/MR applications in mind using a voxel based method. T1 weighted images are most commonly applied. The overall dosimetric agreement is in the order of 0.3-2.5%. A strict gamma criterion of 1% and 1mm has a range of passing rates from 68 to 94% while less strict criteria show pass rates > 98%. The mean absolute error (MAE) is between 80 and 200 HU for the brain and around 40 HU for the prostate. The Dice score for bone is between 0.5 and 0.95. The specificity and sensitivity is reported in the upper 80s% for both quantities and correctly classified voxels average around 84%. The review shows that a variety of promising approaches exist that seem clinical acceptable even with standard clinical MRI sequences. A consistent reference frame for method benchmarking is probably necessary to move the field further towards a widespread clinical implementation.
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31.
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32.
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33.
  • Engvall, Gunn, 1955-, et al. (författare)
  • Children's experiences and responses towards an intervention for psychological preparation for radiotherapy.
  • 2018
  • Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Children can experience distress when undergoing radiotherapy as a reaction to being scared of and unfamiliar with the procedure. The aim was to evaluate children's experiences and responses towards an intervention for psychological preparation for radiotherapy.METHODS: A case control design with qualitative content analysis of semi-structured interviews and statistical analysis of anxiety ratings were used for evaluating a strategy for psychological preparation and distraction. Fifty-seven children aged 2 to 18 years and their parents participated - 30 children in the baseline group and 27 in the intervention group. Child interviews were performed and the child and their parents rated the child's anxiety.RESULTS: The intervention was most appropriate for the younger children, who enjoyed the digital story, the stuffed animal and training with their parents. There were some technical problems and the digital story was not detailed enough to fit exactly with various cancer diagnoses. Children described suggestions for improvement of the intervention. The ratings of the child's anxiety during radiation treatment showed no differences between the baseline group and the intervention group.CONCLUSIONS: The children of all the age groups experienced their interventions as positive. The strength of the intervention was that it encouraged interaction within the family and provided an opportunity for siblings and peers to take part in what the child was going through. Future research on children's experiences to interventions should be encouraged. The intervention and the technical solutions could improve by further development.
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34.
  • Freislederer, P., et al. (författare)
  • Recent advanced in Surface Guided Radiation Therapy
  • 2020
  • Ingår i: Radiation oncology (London, England). - : Springer Science and Business Media LLC. - 1748-717X. ; 15:1
  • Forskningsöversikt (refereegranskat)abstract
    • The growing acceptance and recognition of Surface Guided Radiation Therapy (SGRT) as a promising imaging technique has supported its recent spread in a large number of radiation oncology facilities. Although this technology is not new, many aspects of it have only recently been exploited. This review focuses on the latest SGRT developments, both in the field of general clinical applications and special techniques.SGRT has a wide range of applications, including patient positioning with real-time feedback, patient monitoring throughout the treatment fraction, and motion management (as beam-gating in free-breathing or deep-inspiration breath-hold). Special radiotherapy modalities such as accelerated partial breast irradiation, particle radiotherapy, and pediatrics are the most recent SGRT developments.The fact that SGRT is nowadays used at various body sites has resulted in the need to adapt SGRT workflows to each body site. Current SGRT applications range from traditional breast irradiation, to thoracic, abdominal, or pelvic tumor sites, and include intracranial localizations.Following the latest SGRT applications and their specifications/requirements, a stricter quality assurance program needs to be ensured. Recent publications highlight the need to adapt quality assurance to the radiotherapy equipment type, SGRT technology, anatomic treatment sites, and clinical workflows, which results in a complex and extensive set of tests.Moreover, this review gives an outlook on the leading research trends. In particular, the potential to use deformable surfaces as motion surrogates, to use SGRT to detect anatomical variations along the treatment course, and to help in the establishment of personalized patient treatment (optimized margins and motion management strategies) are increasingly important research topics. SGRT is also emerging in the field of patient safety and integrates measures to reduce common radiotherapeutic risk events (e.g. facial and treatment accessories recognition).This review covers the latest clinical practices of SGRT and provides an outlook on potential applications of this imaging technique. It is intended to provide guidance for new users during the implementation, while triggering experienced users to further explore SGRT applications.
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35.
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36.
  • Gram, D., et al. (författare)
  • Residual positioning errors and uncertainties for pediatric craniospinal irradiation and the impact of image guidance
  • 2020
  • Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 15:1
  • Tidskriftsartikel (refereegranskat)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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37.
  • Jonsson, Joakim H., et al. (författare)
  • Accuracy of inverse treatment planning on substitute CT images derived from MR data for brain lesions
  • 2015
  • Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In this pilot study we evaluated the performance of a substitute CT (s-CT) image derived from MR data of the brain, as a basis for optimization of intensity modulated rotational therapy, final dose calculation and derivation of reference images for patient positioning. Methods: S-CT images were created using a Gaussian mixture regression model on five patients previously treated with radiotherapy. Optimizations were compared using D-max, D-min, D-median and D-mean measures for the target volume and relevant risk structures. Final dose calculations were compared using gamma index with 1%/1 mm and 3%/3 mm acceptance criteria. 3D geometric evaluation was conducted using the DICE similarity coefficient for bony structures. 2D geometric comparison of digitally reconstructed radiographs (DRRs) was performed by manual delineation of relevant structures on the s-CT DRR that were transferred to the CT DRR and compared by visual inspection. Results: Differences for the target volumes in optimization comparisons were small in general, e.g. a mean difference in both D-min and D-max within similar to 0.3%. For the final dose calculation gamma evaluations, 100% of the voxels passed the 1%/1 mm criterion within the PTV. Within the entire external volume between 99.4% and 100% of the voxels passed the 3%/3 mm criterion. In the 3D geometric comparison, the DICE index varied between approximately 0.8-0.9, depending on the position in the skull. In the 2D DRR comparisons, no appreciable visual differences were found. Conclusions: Even though the present work involves a limited number of patients, the results provide a strong indication that optimization and dose calculation based on s-CT data is accurate regarding both geometry and dosimetry.
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38.
  • Lempart, Michael, et al. (författare)
  • 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
  • Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 17:1
  • Tidskriftsartikel (refereegranskat)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.
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39.
  • Lerner, Minna, et al. (författare)
  • Clinical validation of a commercially available deep learning software for synthetic CT generation for brain
  • 2021
  • Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Most studies on synthetic computed tomography (sCT) generation for brain rely on in-house developed methods. They often focus on performance rather than clinical feasibility. Therefore, the aim of this work was to validate sCT images generated using a commercially available software, based on a convolutional neural network (CNN) algorithm, to enable MRI-only treatment planning for the brain in a clinical setting. Methods: This prospective study included 20 patients with brain malignancies of which 14 had areas of resected skull bone due to surgery. A Dixon magnetic resonance (MR) acquisition sequence for sCT generation was added to the clinical brain MR-protocol. The corresponding sCT images were provided by the software MRI Planner (Spectronic Medical AB, Sweden). sCT images were rigidly registered and resampled to CT for each patient. Treatment plans were optimized on CT and recalculated on sCT images for evaluation of dosimetric and geometric endpoints. Further analysis was also performed for the post-surgical cases. Clinical robustness in patient setup verification was assessed by rigidly registering cone beam CT (CBCT) to sCT and CT images, respectively. Results: All sCT images were successfully generated. Areas of bone resection due to surgery were accurately depicted. Mean absolute error of the sCT images within the body contour for all patients was 62.2 ± 4.1 HU. Average absorbed dose differences were below 0.2% for parameters evaluated for both targets and organs at risk. Mean pass rate of global gamma (1%/1 mm) for all patients was 100.0 ± 0.0% within PTV and 99.1 ± 0.6% for the full dose distribution. No clinically relevant deviations were found in the CBCT-sCT vs CBCT-CT image registrations. In addition, mean values of voxel-wise patient specific geometric distortion in the Dixon images for sCT generation were below 0.1 mm for soft tissue, and below 0.2 mm for air and bone. Conclusions: This work successfully validated a commercially available CNN-based software for sCT generation. Results were comparable for sCT and CT images in both dosimetric and geometric evaluation, for both patients with and without anatomical anomalies. Thus, MRI Planner is feasible to use for radiotherapy treatment planning of brain tumours.
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40.
  • Lund, Mikael, et al. (författare)
  • Effects on heart function of neoadjuvant chemotherapy and chemoradiotherapy in patients with cancer in the esophagus or gastroesophageal junction : a prospective cohort pilot study within a randomized clinical trial
  • 2015
  • Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neoadjuvant therapy for cancer of the esophagus or gastroesophageal (GE)-junction is well established. The pros and cons of chemoradiotherapy and chemotherapy are debated. Chemoradiotherapy might impair cardiac function eliciting postoperative morbidity. The aim of this pilot study was to describe acute changes in left ventricular function following chemoradiotherapy or chemotherapy. Methods: Patients with esophageal and (GE)-junction cancer enrolled at our center into a multicenter trial comparing neoadjuvant chemoradiotherapy and chemotherapy were eligible. Patients were randomized to receive cisplatin and 5-fluorouracil with or without the addition of 40 Gy radiotherapy prior to surgery. Left ventricular function was evaluated using echocardiography and plasma N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) before and after neoadjuvant treatment. The primary outcome measure was left ventricular global strain (GS). Clinical effects were assessed using repeated exercise tests. Linear mixed models were used to analyze the effects of treatment group, and the interaction between groups. Results: 40 patients participated (chemoradiotherapy, n = 17; chemotherapy, n = 23). In the chemoradiotherapy group there was no change in left ventricular global strain but mitral annular plane systolic excursion (MAPSE) of the ventricular septum, early diastolic filling velocity (E-velocity), and the ratio of early to late ventricular filling velocities (E/A ratio) decreased significantly (p = 0.02, p = 0.01, and p = 0.03, respectively). No changes were observed in the chemotherapy group. There was a trend towards an interaction effect for MAPSE sept and E (p = 0.09 and p = 0.09). NT-proBNP increased following chemoradiotherapy (p = 0.05) but not after chemotherapy (p > 0.99), and there was a trend towards an interaction effect (p = 0.07). Working capacity decreased following neoadjuvant treatment (chemoradiotherapy p = 0.001, chemotherapy p = 0.03) and was more pronounced after chemoradiotherapy with a trend towards an interaction effect (p = 0.10). Conclusions: Neoadjuvant chemoradiotherapy but not chemotherapy before surgery for cancer of the esophagus or GE-junction seems to induce an acute negative effect on both systolic and diastolic left ventricular function. Future studies on neoadjuvant treatment for esophageal cancer are suggested to add measurements of cardiac function.
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41.
  • Mannerberg, Annika, et al. (författare)
  • Dosimetric effects of adaptive prostate cancer radiotherapy in an MR-linac workflow
  • 2020
  • Ingår i: Radiation oncology (London, England). - : Springer Science and Business Media LLC. - 1748-717X. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The purpose was to evaluate the dosimetric effects in prostate cancer treatment caused by anatomical changes occurring during the time frame of adaptive replanning in a magnetic resonance linear accelerator (MR-linac) workflow. METHODS: Two MR images (MR1 and MR2) were acquired with 30 min apart for each of the 35 patients enrolled in this study. The clinical target volume (CTV) and organs at risk (OARs) were delineated based on MR1. Using a synthetic CT (sCT), ultra-hypofractionated VMAT treatment plans were created for MR1, with three different planning target volume (PTV) margins of 7 mm, 5 mm and 3 mm. The three treatment plans of MR1, were recalculated onto MR2 using its corresponding sCT. The dose distribution of MR2 represented delivered dose to the patient after 30 min of adaptive replanning, omitting motion correction before beam on. MR2 was registered to MR1, using deformable registration. Using the inverse deformation, the structures of MR1 was deformed to fit MR2 and anatomical changes were quantified. For dose distribution comparison the dose distribution of MR2 was warped to the geometry MR1. RESULTS: The mean center of mass vector offset for the CTV was 1.92 mm [0.13 - 9.79 mm]. Bladder volume increase ranged from 12.4 to 133.0% and rectum volume difference varied between -10.9 and 38.8%. Using the conventional 7 mm planning target volume (PTV) margin the dose reduction to the CTV was 1.1%. Corresponding values for 5 mm and 3 mm PTV margin were 2.0% and 4.2% respectively. The dose to the PTV and OARs also decreased from D1 to D2, for all PTV margins evaluated. Statistically significant difference was found for CTV Dmin between D1 and D2 for the 3 mm PTV margin (p < 0.01). CONCLUSIONS: A target underdosage caused by anatomical changes occurring during the reported time frame for adaptive replanning MR-linac workflows was found. Volume changes in both bladder and rectum caused large prostate displacements. This indicates the importance of thorough position verification before treatment delivery and that the workflow needs to speed up before introducing margin reduction.
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42.
  • Mondlane, Gracinda, 1987-, et al. (författare)
  • Estimation of the risk for radiation-induced liver disease following photon- or proton-beam radiosurgery of liver metastases
  • 2018
  • Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 13
  • 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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43.
  • Mörén, Lina, et al. (författare)
  • Characterization of the serum metabolome following radiation treatment in patients with high-grade gliomas
  • 2016
  • Ingår i: Radiation Oncology. - : BioMed Central. - 1748-717X. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Glioblastomas progress rapidly making response evaluation using MRI insufficient since treatment effects are not detectable until months after initiation of treatment. Thus, there is a strong need for supplementary biomarkers that could provide reliable and early assessment of treatment efficacy. Analysis of alterations in the metabolome may be a source for identification of new biomarker patterns harboring predictive information. Ideally, the biomarkers should be found within an easily accessible compartment such as the blood. Method: Using gas-chromatographic-time-of-flight-mass spectroscopy we have analyzed serum samples from 11 patients with glioblastoma during the initial phase of radiotherapy. Fasting serum samples were collected at admittance, on the same day as, but before first treatment and in the morning after the second and fifth dose of radiation. The acquired data was analyzed and evaluated by chemometrics based bioinformatics methods. Our findings were compared and discussed in relation to previous data from microdialysis in tumor tissue, i.e. the extracellular compartment, from the same patients. Results: We found a significant change in metabolite pattern in serum comparing samples taken before radiotherapy to samples taken during early radiotherapy. In all, 68 metabolites were lowered in concentration following treatment while 16 metabolites were elevated in concentration. All detected and identified amino acids and fatty acids together with myo-inositol, creatinine, and urea were among the metabolites that decreased in concentration during treatment, while citric acid was among the metabolites that increased in concentration. Furthermore, when comparing results from the serum analysis with findings in tumor extracellular fluid we found a common change in metabolite patterns in both compartments on an individual patient level. On an individual metabolite level similar changes in ornithine, tyrosine and urea were detected. However, in serum, glutamine and glutamate were lowered after treatment while being elevated in the tumor extracellular fluid. Conclusion: Cross-validated multivariate statistical models verified that the serum metabolome was significantly changed in relation to radiation in a similar pattern to earlier findings in tumor tissue. However, all individual changes in tissue did not translate into changes in serum. Our study indicates that serum metabolomics could be of value to investigate as a potential marker for assessing early response to radiotherapy in malignant glioma.
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44.
  • Nilsson, Martin P., et al. (författare)
  • Patterns of recurrence in anal cancer : A detailed analysis
  • 2020
  • Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Anal cancer is a rare disease, which might be the reason for the "one size fits all" approach still used for radiotherapy target contouring. To refine and individualize future guidelines, detailed and contemporary pattern of recurrence studies are needed. Methods: Consecutive anal cancer patients, all treated with curative intent intensity-modulated radiotherapy (IMRT), were retrospectively studied (n = 170). Data was extracted from medical records and radiological images. Radiotherapy planning CT's and treatment plans were reviewed, and recurrences were mapped and categorized according to radiation dose. Results: The mean dose to the primary tumor was 59.0 Gy. With a median follow-up of 50 months (range 14-117 months), 5-year anal cancer specific survival was 86.1%. Only 1 of 20 local recurrences was located outside the high dose (CTVT) volume. More patients experienced a distant recurrence (n = 34; 20.0%) than a locoregional recurrence (n = 24; 14.1%). Seven patients (4.2%) had a common iliac and/or para-aortic (CI/PA) recurrence. External iliac lymph node involvement (P = 0.04), and metastases in ≥3 inguinal or pelvic lymph node regions (P = 0.02) were associated with a 15-18% risk of CI/PA recurrence. Following chemoradiotherapy, 6 patients with recurrent or primary metastatic CI/PA lymph nodes were free of recurrence at last follow-up. The overall rate of ano-inguinal lymphatic drainage (AILD) recurrence was 2 of 170 (1.2%), and among patients with inguinal metastases at initial diagnosis it was 2 of 65 (3.1%). Conclusions: We conclude that other measures than increased margins around the primary tumor are needed to improve local control. Furthermore, metastatic CI/PA lymph nodes, either at initial diagnosis or in the recurrent setting, should be considered potentially curable. Patients with certain patterns of metastatic pelvic lymph nodes might be at an increased risk of harboring tumor cells also in the CI/PA lymph nodes.
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45.
  • Nilsson, Martin P., et al. (författare)
  • Sarcopenia and dosimetric parameters in relation to treatment-related leukopenia and survival in anal cancer
  • 2021
  • Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Treatment-related white blood cell (WBC) toxicity has been associated with an inferior prognosis in different malignancies, including anal cancer. The aim of the present study was to investigate predictors of WBC grade ≥ 3 (G3+) toxicity during chemoradiotherapy (CRT) of anal cancer. Methods: Consecutive patients with locally advanced (T2 ≥ 4 cm—T4 or N+) anal cancer scheduled for two cycles of concomitant 5-fluorouracil and mitomycin C chemotherapy were selected from an institutional database (n = 106). All received intensity modulated radiotherapy (IMRT; mean dose primary tumor 59.5 Gy; mean dose elective lymph nodes 45.1 Gy). Clinical data were extracted from medical records. The highest-grade WBC toxicity was recorded according to CTCAE version 5.0. Pelvic bone marrow (PBM) was retrospectively contoured and dose-volume histograms were generated. The planning CT was used to measure sarcopenia. Dosimetric, anthropometric, and clinical variables were tested for associations with WBC G3+ toxicity using the Mann–Whitney test and logistic regression. Cox proportional hazard regression was used to assess predictors for overall survival (OS) and anal cancer specific survival (ACSS). Results: WBC G3+ was seen in 50.9% of the patients, and 38.7% were sarcopenic. None of the dosimetric parameters showed an association with WBC G3+ toxicity. The most significant predictor of WBC G3+ toxicity was sarcopenia (adjusted OR 4.0; P = 0.002). Sarcopenia was also associated with an inferior OS (adjusted HR 3.9; P = 0.01), but not ACSS (P = 0.07). Sensitivity analysis did not suggest that the inferior prognosis for sarcopenic patients was a consequence of reduced doses of chemotherapy or a prolonged radiation treatment time. Patients who experienced WBC G3+ toxicity had an inferior OS and ACSS, even after adjustment for sarcopenia. Conclusions: Sarcopenia was associated with increased risks of both WBC G3+ toxicity and death following CRT for locally advanced anal cancer. In this study, radiation dose to PBM was not associated with WBC G3+ toxicity. However, PBM was not used as an organ at risk for radiotherapy planning purposes and doses to PBM were high, which may have obscured any dose–response relationships.
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46.
  • Olafsdottir, HS, et al. (författare)
  • Short-course compared to long-course palliative radiotherapy for oesophageal cancer: a single centre observational cohort study
  • 2021
  • Ingår i: Radiation oncology (London, England). - : Springer Science and Business Media LLC. - 1748-717X. ; 16:1, s. 153-
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundCommon symptoms of oesophageal cancer are dysphagia, pain, and bleeding. These symptoms can be relieved with palliative radiotherapy. The aim of this study was to analyse the outcome of two different palliative radiotherapy schedules.MethodsWe conducted a retrospective cohort study on palliative radiotherapy for oesophageal cancer given at Karolinska University Hospital. Patients included were treated with either short-course (20 Gy in 4 Gy fractions daily, 5 consecutive workdays) or long-course (30–39 Gy in 3 Gy fractions, 10–13 consecutive workdays) palliative external beam radiotherapy between January 2009 and December 2013. The primary endpoint was dysphagia relief and secondary endpoints were adverse events, re-interventions, and overall survival. Cox regression analyses were used to estimate the effect of treatment schedule on survival.ResultsA total of 128 patients received external beam radiotherapy under the study period, of these 75 (58.6%) received short-course radiotherapy and 53 (41.4%) long-course radiotherapy. Sixteen (30.8%) patients experienced dysphagia relief after short-course radiotherapy and 9 (22.0%) patients after long-course radiotherapy (p = 0.341). Acute toxicity was less frequent after short-course radiotherapy than after long-course radiotherapy, particularly oesophagitis (35.4% vs. 56.0%,p = 0.027) and nausea/emesis (18.5% vs. 36.0%p = 0.034). Re-interventions tended to be more common after short-course radiotherapy (32.0%) than after long-course radiotherapy (18.9%) (p = 0.098). There was no difference in overall survival between the two groups.ConclusionsShort- and long-course palliative radiotherapy for oesophageal cancer were equally effective to relieve dysphagia and no difference was seen in overall survival. Acute toxicity was, however, more frequent and more severe after long-course radiotherapy. Our results suggest that short-course radiotherapy is better tolerated with equal palliative effects as long-course radiotherapy.
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47.
  • Persson, Emilia, et al. (författare)
  • Investigation of the clinical inter-observer bias in prostate fiducial marker image registration between CT and MR images
  • 2021
  • Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: Inter-modality image registration between computed tomography (CT) and magnetic resonance (MR) images is associated with systematic uncertainties and the magnitude of these uncertainties is not well documented. The purpose of this study was to investigate the potential uncertainty of gold fiducial marker (GFM) registration for localized prostate cancer and to estimate the inter-observer bias in a clinical setting. Methods: Four experienced observers registered CT and MR images for 42 prostate cancer patients. Manual GFM identification was followed by a landmark-based registration. The absolute difference between observers in GFM identification and the displacement of the clinical target volume (CTV) was investigated. The CTV center of mass (CoM) vector displacements, DICE-index and Hausdorff distances for the observer registrations were compared against a clinical baseline registration. The time allocated for the manual registrations was compared. Results: Absolute difference in GFM identification between observers ranged from 0.0 to 3.0 mm. The maximum CTV CoM displacement from the clinical baseline was 3.1 mm. Displacements larger than or equal to 1 mm, 2 mm and 3 mm were 46%, 18% and 4%, respectively. No statistically significant difference was detected between observers in terms of CTV displacement. Median DICE-index and Hausdorff distance for the CTV, with their respective ranges were 0.94 [0.70–1.00] and 2.5 mm [0.7–8.7]. Conclusions: Registration of CT and MR images using GFMs for localized prostate cancer patients was subject to inter-observer bias on an individual patient level. A CTV displacement as large as 3 mm occurred for individual patients. These results show that GFM registration in a clinical setting is associated with uncertainties, which motivates the removal of inter-modality registrations in the radiotherapy workflow and a transition to an MRI-only workflow for localized prostate cancer.
  •  
48.
  • Persson, Emilia, et al. (författare)
  • MR-PROTECT : Clinical feasibility of a prostate MRI-only radiotherapy treatment workflow and investigation of acceptance criteria
  • 2020
  • Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Retrospective studies on MRI-only radiotherapy have been presented. Widespread clinical implementations of MRI-only workflows are however limited by the absence of guidelines. The MR-PROTECT trial presents an MRI-only radiotherapy workflow for prostate cancer using a new single sequence strategy. The workflow incorporated the commercial synthetic CT (sCT) generation software MriPlanner™ (Spectronic Medical, Helsingborg, Sweden). Feasibility of the workflow and limits for acceptance criteria were investigated for the suggested workflow with the aim to facilitate future clinical implementations. Methods: An MRI-only workflow including imaging, post imaging tasks, treatment plan creation, quality assurance and treatment delivery was created with questionnaires. All tasks were performed in a single MR-sequence geometry, eliminating image registrations. Prospective CT-quality assurance (QA) was performed prior treatment comparing the PTV mean dose between sCT and CT dose-distributions. Retrospective analysis of the MRI-only gold fiducial marker (GFM) identification, DVH- analysis, gamma evaluation and patient set-up verification using GFMs and cone beam CT were performed. Results: An MRI-only treatment was delivered to 39 out of 40 patients. The excluded patient was too large for the predefined imaging field-of-view. All tasks could successfully be performed for the treated patients. There was a maximum deviation of 1.2% in PTV mean dose was seen in the prospective CT-QA. Retrospective analysis showed a maximum deviation below 2% in the DVH-analysis after correction for rectal gas and gamma pass-rates above 98%. MRI-only patient set-up deviation was below 2 mm for all but one investigated case and a maximum of 2.2 mm deviation in the GFM-identification compared to CT. Conclusions: The MR-PROTECT trial shows the feasibility of an MRI-only prostate radiotherapy workflow. A major advantage with the presented workflow is the incorporation of a sCT-generation method with multi-vendor capability. The presented single sequence approach are easily adapted by other clinics and the general implementation procedure can be replicated. The dose deviation and the gamma pass-rate acceptance criteria earlier suggested was achievable, and these limits can thereby be confirmed. GFM-identification acceptance criteria are depending on the choice of identification method and slice thickness. Patient positioning strategies needs further investigations to establish acceptance criteria.
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