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Small megavoltage photon fields are increasingly used in modern radiotherapy techniques such as stereotactic radiotherapy. Therefore, it is important to study the reliability of dosimetry in the small-field conditions. The IBA Razor Nano Chamber (Nano chamber) ionization chamber is particularly intended for small-field measurements. In this work, properties of the Nano chamber were studied with both measurements and Monte Carlo (MC) simulations.The measurements and MC simulations were performed with 6 MV, 6 MV FFF and 10 MV FFF photon beams from the Varian TrueBeam linear accelerator. The source-to-surface distance was fixed at 100 cm. The measurements and MC simulations included profiles, percentage depth doses (PDD), and output factors (OF) in square jaw-collimated fields. The MC simulations were performed with the EGSnrc software system in a large water phantom.The measured profiles and PDDs obtained with the Nano chamber were compared against IBA Razor Diode, PTW microDiamond and the PTW Semiflex ionization chamber. These results indicate that the Nano chamber is a high-resolution detector and thus suitable for small field profile measurements down to field sizes 2 × 2 cmThe Nano chamber with its small cavity volume is a potential detector for the small-field dosimetry. In this study, the properties of this detector were characterized with measurements and MC simulations. The determined correction factors

Reduced planning target volume (PTV) margins are commonly used in stereotactic body radiotherapy (SBRT) of the prostate. In addition, MR-only treatment planning is becoming more common in prostate radiotherapy and compared to CT-MRI-based contouring results in notable smaller clinical target volume (CTV). Tight PTV margins coupled with MR-only planning raise a concern whether the margins are adequate enough to cover possible volumetric changes of the prostate. The aim of this study was to evaluate the volumetric change of the prostate and its effect on PTV margin during 5x7.25 Gy SBRT of the prostate. Twenty patients were included in the study. Three MRI scans, first prior to treatment (baseline), second after third fraction (mid-treatment) and third after fifth fraction (end-treatment) were acquired for each patient. Prostate contours were delineated on each MRI scan and used to assess the prostate volume and maximum prostate diameter on left-right (LR), anterior-posterior (AP) and superior-inferior (SI) directions at baseline, mid- and end-treatment. Median (IQR) change in the prostate volume relative to the baseline was 12.0% (3.1, 17.7) and 9.2% (2.0, 18.9) at the mid- and end-treatment, respectively, and the change was statistically significant (p = 0.004 and p = 0.020, respectively). Compared to the baseline, median increase in the maximum LR, SI and AP prostate diameters were 0.8, 2.3 and 1.5 mm at mid-treatment, and 0.5, 2.5 and 2.3 mm at end-treatment, respectively. If prostate contouring is based solely on MRI (e.g., in MR-only protocol), additional margin of 1–2 mm should be considered to account for prostate swelling. The study is part of clinical trial NCT02319239.

BACKGROUND: Optimal radiation therapy (RT) fractionation in early prostate cancer in elderly patients is controversial. We compared acute toxicities of fractionation schedules: 78/2 Gy, 60/3 Gy and 36.25/7.25 Gy, in this single-centre study. We also evaluated the effect of the rectal immobilization system Rectafix on quality of life (QoL). PATIENTS AND METHODS: Seventy-three patients with one or two intermediate prostate cancer risk factors according to National Comprehensive Cancer Network criteria were recruited. Twenty-one patients were treated with 78/2 Gy and 60/3 Gy, and 31 patients with 36.25/7.25 Gy. Their QoL data were assessed with regard to genitourinary, gastrointestinal and sexual wellbeing at the beginning and end of RT and at 3 months after treatment. Rectafix was used in the 78/2 Gy and 60/3 Gy groups. RESULTS: There were no statistically significant QoL differences in between the treatment groups 3 months after RT. The 78/2 Gy group had significantly increased bowel movements between baseline and 3 months after RT (p=0.036). At 3 months after RT, this group also had significantly more erectile dysfunction than the 60/3 Gy group (p=0.025). At the end of RT, the 78/2 Gy group had more symptoms than the 36.25/7.25 Gy group. Rectafix did not reduce acute toxicities in the 78/2 Gy or 60/3 Gy groups. CONCLUSION: Treatment with the 78/2 Gy schedule is no longer to be recommended due to its increased acute toxicity compared to treatments of 60/3 Gy and 36.25/7.25 Gy. The shortest schedule of 36.25 Gy in five fractions seems to be a convenient treatment option with tolerable acute toxicity. publishedVersion

Purpose Surface guided radiotherapy (SGRT) is reported as a feasible setup technique for whole‐breast radiotherapy in deep inspiration breath hold (DIBH), but position errors of bony structures related to deeper parts of the target are not fully known. The aim of this study was to estimate patient setup accuracy and margins obtained with two different SGRT workflows with and without daily kV‐ and/or MV‐based image guidance (IGRT). Methods A total of 50 breast cancer patients were treated in DIBH, using SGRT for the patient setup, and IGRT for isocenter corrections. The patients were treated at two different departments, one using AlignRT® (25 patients) and the other using Catalyst™ (25 patients). Inter‐fractional position errors were analyzed retrospectively in orthogonal and tangential setup images, and analyzed with and without IGRT. Results In the orthogonal kV‐kV images, the systematic residual errors of the bony structures were ≤ 3 mm in both groups with SGRT‐only. When fine‐adjusted by daily IGRT, the errors decreased to ≤ 2 mm; except for the shoulder joint. The residual errors of the ribs in tangential images were between 1 and 2 mm with both workflows. The heart planning margins were between 3 and 7 mm. Conclusions The frequency of IGRT may be considerably reduced with a well‐planned SGRT‐workflow for whole‐breast DIBH with residual errors ≤ 3 mm. This accuracy can be further improved with an IGRT scheme.

Background Cranial radiotherapy may damage the cerebral vasculature. The aim of this study was to understand the prevalence and risk factors of cerebrovascular disease (CVD) and white matter hyperintensities (WMHs) in childhood brain tumors (CBT) survivors treated with radiotherapy. Methods Seventy CBT survivors who received radiotherapy were enrolled in a cross-sectional study at a median 20 years after radiotherapy cessation. The prevalence of and risk factors for CVD were investigated using MRI, MRA, and laboratory testing. Tumors, their treatment, and stroke-related data were retrieved from patients’ files. Results Forty-four individuals (63%) had CVD at a median age of 27 years (range, 16-43 years). The prevalence rates at 20 years for CVD, small-vessel disease, and large-vessel disease were 52%, 38%, and 16%, respectively. Ischemic infarcts were diagnosed in 6 survivors, and cerebral hemorrhage in 2. Lacunar infarcts were present in 7, periventricular or deep WMHs in 34 (49%), and mineralizing microangiopathy in 21 (30%) survivors. Multiple pathologies were detected in 44% of the participants, and most lesions were located in a high-dose radiation area. Higher blood pressure was associated with CVD and a presence of WMHs. Higher cholesterol levels increased the risk of ischemic infarcts and WMHs, and lower levels of high-density lipoprotein and higher waist circumference increased the risk of lacunar infarcts. Conclusions Treating CBTs with radiotherapy increases the risk of early CVD and WMHs in young adult survivors. These results suggest an urgent need for investigating CVD prevention in CBT patients.

Magnetic resonance imaging-only radiotherapy treatment planning (MRI-only RTP) and positron emission tomography (PET)-MRI imaging require generation of synthetic computed tomography (sCT) images from MRI images. In this study, initial dosimetric evaluation was performed for a previously developed MRI-based attenuation correction (MRAC) method for use in MRI-only RTP of the brain. MRAC-based sCT images were retrospectively generated from Dixon MR images of 20 patients who had previously received external beam radiation therapy (EBRT). Bone segmentation performance and Dice similarity coefficient of the sCT conversion method were evaluated for bone volumes on CT images. Dose calculation accuracy was assessed by recalculating the CT-based EBRT plans using the sCT images as the base attenuation data. Dose comparison was done for the sCT- and CT-based EBRT plans in planning target volume (PTV) and organs at risk (OAR). Parametric dose comparison showed mean relative differences of

The aim of this study was to find an optimal optimization skin flash thickness in volumetric modulated arc radiotherapy of the breast in consideration of soft tissue deformations during the treatment course. Ten breast radiotherapy patients with axillary lymph node inclusion were retrospectively planned with volumetric modulated arc radiotherapy technique. The plans were optimized with the planning target volume (PTV) extending outside the skin contour by 0, 5, 7, and 10 mm; and with optimization boluses of 3 or 5 mm on the extended PTV. The final dose was calculated without the bolus. The plans were compared in terms of PTV homogeneity and conformity, and dose minima and maxima. The doses to organs at risk were also evaluated. The doses were recalculated in real patient geometries based on cone beam computed tomography (CBCT) images captured 3 to 6 times during each patient's treatment course. The optimization to the PTV without the PTV extension resulted in the best CTV coverage in the original plans (V95% = 98.0% ± 1.2%). However, when these plans were studied in real CBCT-based patient geometries, the CTV V95% was compromised (94.6% ± 8.3%). In addition, for the surface (4 mm slap inside the PTV 4 mm below the body contour) dose V95% was reduced from the planned 74.7% ± 7.5% to the recalculated 65.5% ± 11.5%. Optimization with an 8-mm bolus to a PTV with 5-mm extension was the most robust choice to ensure the CTV and surface dose coverage (recalculated V95% was 95.2% ± 6.4% and 74.6% ± 8.4%, respectively). In cases with the largest observed deformations, even a 10-mm PTV extension did not suffice to cover the target. Optimization with a 5-mm PTV extension and an 8-mm optimization bolus improved the surface dose and slightly improved the CTV dose when compared to no extension plans. For deformations over 1 cm, no benefit was seen in PTV extensions and replanning is recommended. Frequent tangential and CBCT imaging should be used during treatment course to detect potential large anatomical changes.

Using magnetic resonance imaging (MRI) as the only imaging method for radiotherapy treatment planning (RTP) is becoming more common as MRI-only RTP solutions have evolved. The geometric accuracy of MR images is an essential factor of image quality when determining the suitability of MRI for RTP. The need is therefore clear for clinically feasible quality assurance (QA) methods for the geometric accuracy measurement.This work evaluates long-term stability of geometric accuracy and the validity of a 2D geometric accuracy QA method compared to a prototype 3D method and analysis software in routine QA. The long-term follow-up measurements were conducted on one of the 1.5 T scanners over a period of 19 months using both methods. Inter-scanner variability of geometric distortions was also evaluated in three 1.5 T and three 3 T MRI scanners from a single vendor by using the prototype 3D QA method.The geometric accuracy of the magnetic resonance for radiotherapy (MR-RT) platform remained stable within 2 mm at distances of250 mm from isocenter. All scanners achieved good geometric accuracy with mean geometric distortions of1 mm at150 mm and2 mm at250 mm from the isocenter. Both measurement methods provided relevant information about geometric distortions.Geometric distortions are often considered a limitation of MRI-only RTP. Results indicate that geometric accuracy of modern scanners remain within acceptable limits by default even after many years of clinical use based on the 3D QA evaluation.

In small-field radiotherapy (RT), a significant challenge is to define the amount of radiation dose absorbed in the patient where the quality of the beam has to be measured with high accuracy. The properties of a proposed new beam quality specifier, namely the dose-area-product ratio at 20 and 10 cm depths in water or DAPR20,10, were studied to yield more information on its feasibility over the conventional quality specifier tissue-phantom ratio or TPR20,10. The DAPR20,10 may be measured with a large-area ionization chamber (LAC) instead of small volume chambers or semi-conductors where detector, beam and water phantom positioning and beam perturbations introduce uncertainties. The effects of beam shape, size and energy on the DAPR20,10 were studied and it was shown that the DAPR20,10 increases with increasing beam energy similarly to TPR20,10 but in contrast exhibits a small beam size and shape dependence. The beam profile outside the beam limiting devices has been shown to have a large contribution to the DAPR20,10. There is potential in large area chambers to be used in DAPR measurement and its use in dosimetry of small-beam RT for beam quality measurements.

The purpose of this study is to evaluate the effect of nonrigid and fractionation-corrected dose summation on total doses in radiotherapy and to demonstrate the benefits of such dose summation on clinical decision-making for planning of retreatments. Dose summation of organs at risk (OARs) was investigated for 3 clinical cases with need of retreatment to the same site: head and neck, brain, and mediastinum. Three different summation methods over old and new radiotherapy treatment plans are presented and compared: (1) rigid raw sum with rigid registration of the planning images and direct dose summing; (2) deformable raw sum with deformable image registration and direct dose summing; and (3) deformable biological sum with deformable registration and takes into account the dose per fraction in biological manner in certain critical organs. In 2 cases, a user-defined dose downscaling is applied to take into account the time between the treatments and the healing from the radiation-induced effects. Of the 3 summation methods presented, the deformable biological sum was considered to offer the most biologically plausible account of the treatment. There were remarkable differences between near-maximum doses (D0.1cc) and dose-volume histogram (DVH) curves for OARs between different summation methods. The differences between deformable raw sum and rigid raw sum D0.1cc doses are in the range from −8 Gy to 2 Gy. Similarly, the deviation was from −14 Gy to 5 Gy for the deformable biological sum compared with the rigid raw sum. These differences come from incorrect summation of doses in the rigid raw sum case, and from the dose per fraction effect in biological summation. We conclude that computing the 3-dimensional deformable biological summation could be a valuable tool for treating patients with complex retreatments. It has the potential to assist the oncologist in refining plans for maximally curative doses while respecting appropriate tissue tolerances.

Purpose To investigate different volumetric modulated arc therapy (VMAT) field designs for lymph node positive breast cancer patients when compared to conventional static fields and standard VMAT designs. Methods Nineteen breast cancer patients with lymph node involvement (eleven left and eight right sided) were retrospectively analyzed with different arc designs. Proposed split arc designs with total rotations of 2 × 190° and 2 × 240° were compared to conventional field in field (FinF) and previously published non-split arc techniques with the same amount of total rotations. Results All VMAT plans were superior in dose conformity, when compared to the FinF plans. Split arc design decreased significantly ipsilateral lung dose and heart V5Gy for both left and right sided cases, when compared to non-split VMAT designs. For left sided cases no significant differences were seen in contralateral lung mean dose or V5Gy between different VMAT designs. For right sided cases the contralateral lung dose V5Gy was significantly higher in split VMAT group, when compared to non-split VMAT designs. The contralateral breast dose V5Gy increased significantly for split VMAT plans for both sides, when compared to non-split VMAT designs or FinF plans. Conclusions The proposed split VMAT technique was shown to be superior to previously published non-split VMAT and conventional FinF techniques significantly reducing dose to the ipsilateral lung and heart. However, this came with the expense of an increase in the dose to the contralateral breast and for right-sided cases to the contralateral lung.

The aim of this study was to evaluate the impact of actual rotational setup errors on dose distributions in intracranial stereotactic radiotherapy (SRT) with different alternatives for treatment position selection. A total of 38 SRT fractions from 18 patients were retrospectively evaluated with rotational setup errors obtained from actual treatments. The planning computed tomography (CT) images were rotated according to online cone‐beam CT (CBCT) images and the dose distribution was recalculated to the rotated CT images using three different patient positionings derived from: 1) an automatic 6D match neglecting rotation correction (Auto6D); 2) an automatic 3D match (Auto3D); and 3) a manual 3D match from actual treatment (Treat3D). The mean conformity index (CI) was 0.92 for the original plans and 0.91 for the Auto6D plans. The mean CI decreased significantly (p0.38) was found in the Auto3D and the Treat3D cases between the rotation error and CI, PTVmin or minimum dose of gross tumour volume. In SRT, a treatment plan of comparable quality to 6D rotation correction can be achieved by using 6D registration without a rotational correction in the selection of patient positioning. This was demonstrated for typical rotation errors seen in clinical practice. PACS number(s): 87.55, 87.57

Adjuvant radiotherapy (RT) of left-sided breast cancer (LSBC) with voluntary deep inspiration breath hold (vDIBH) technique reduces the cardiac dose. In this study, the effect of marker block position and the efficacy of breath hold level (BHL) correction based on lateral kV setup images are evaluated to improve the daily reproducibility.A total of 148 consecutive LSBC patients treated with vDIBH RT were included in this study. The real-time position management (RPM) marker block was placed on the abdominal wall in 63 patients (group A) and on the sternum in 85 patients (group S). Acquired 900 (group A) + 1040 (group S) orthogonal image pairs were retrospectively analyzed. The actual BHL was determined from the lateral kV images. The height of the BHL gating window in RPM was corrected if errors of the actual BHL exceeded 4 mm. Setup margins were calculated for the chest wall and for bony surrogates of the lymph node regions.The sternal marker block reduced the random residual errors in the actual BHL (p 0.05). The BHL correction was required for 26/63 patients in group A and for 26/85 patients in group S. Correction of the BHL window significantly reduced both the systematic and the random residual error in both groups. In patients with lymph node irradiation, the effect of both marker placement and BHL window correction was significant in the superior-inferior direction. Correction of the BHL reduced the mean cardiac dose by 0.5 Gy (p 0.01) in group A and 0.6 Gy (p 0.05) in group S.Reproducibility of the BHL can be improved by placing the marker block on the sternum and correcting the height of the BHL window based on lateral kV setup images. Acquisition of lateral kV images in the first 3 fractions and once a week during RT is recommended.

Magnetic resonance imaging (MRI) is the most comprehensive imaging modality for radiation therapy (RT) target delineation of most soft tissue tumors including prostate cancer. We have earlier presented step by step the MRI-only based workflow for RT planning and image guidance for localized prostate cancer. In this study we present early clinical experiences of MRI-only based planning.We have analyzed the technical planning workflow of the first 200 patients having received MRI-only planned radiation therapy for localized prostate cancer in Helsinki University Hospital Cancer center. Early prostate specific antigen (PSA) results were analyzed from n = 125 MRI-only patients (n = 25 RT only, n = 100 hormone treatment + RT) and were compared with the corresponding computed tomography (CT) planned patient group.Technically the MRI-only planning procedure was suitable for 92% of the patients, only 8% of the patients required supplemental CT imaging. Early PSA response in the MRI-only planned group showed similar treatment results compared with the CT planned group and with an equal toxicity level.Based on this retrospective study, MRI-only planning procedure is an effective and safe way to perform RT for localized prostate cancer. It is suitable for the majority of the patients.

Purpose We compared the pre- and post-irradiation viability and cytotoxicity of human peripheral natural killer cell (NK) populations obtained using different isolation methods. Material and methods Three methods were used to enrich total NK cells from buffy coats: (I) a Ficoll-Paque gradient, plastic adherence and a nylon wool column; (II) a discontinuous Percoll gradient; or (III) the Dynal NK cell isolation kit. Subsequently, CD16(+) and CD56(+) NK cell subsets were collected using (IV) flow cytometry or (V) magnetic-activated cell sorting (MACS) NK cell isolation kits. The yield, viability, purity and cytotoxicity of the NK cell populations were measured using trypan blue exclusion, flow cytometry using propidium iodide and (51)Cr release assays after enrichments as well as viability and cytotoxicity after a single radiation dose. Results The purity of the preparations, as measured by the CD16(+) and CD56(+) cell content, was equally good between methods I-III (p = 0.323), but the content of CD16(+) and CD56(+) cells using these methods was significantly lower than that using methods IV and V (p = 0.005). The viability of the cell population enriched via flow cytometry (85.5%) was significantly lower than that enriched via other methods (99.4-98.0%, p = 0.003). The cytotoxicity of NK cells enriched using methods I-III was significantly higher than that of NK cells enriched using methods IV and V (p = 0.000). In vitro the NK cells did not recover cytotoxic activity following irradiation. In addition, we detected considerable inter-individual variation in yield, cytotoxicity and radiation sensitivity between the NK cells collected from different human donors. Conclusions The selection of the appropriate NK cell enrichment method is very important for NK cell irradiation studies. According to our results, the Dynal and MACS NK isolation kits best retained the killing capacity and the viability of irradiated NK cells.

A commercialized implementation of linear Boltzmann transport equation solver, the Acuros XB algorithm (AXB), represents a class of most advanced type ‘c’ photon radiotherapy dose calculation algorithms. The purpose of the study was to quantify the effects of the modifications implemented in the more recent version 11 of the AXB (AXB11) compared to the first commercial implementation, version 10 of the AXB (AXB10), in various anatomical regions in clinical treatment planning. Both versions of the AXB were part of Varian's Eclipse clinical treatment planning system and treatment plans for 10 patients were created using intensity‐modulated radiotherapy (IMRT) and volumetric‐modulated arc radiotherapy (VMAT). The plans were first created with the AXB10 and then recalculated with the AXB11 and full Monte Carlo (MC) simulations. Considering the full MC simulations as reference, a DVH analysis for gross tumor and planning target volumes (GTV and PTV) and organs at risk was performed, and also 3D gamma agreement index (GAI) values within a 15% isodose region and for the PTV were determined. Although differences up to 12% in DVH analysis were seen between the MC simulations and the AXB, based on the results of this study no general conclusion can be drawn that the modifications made in the AXB11 compared to the AXB10 would imply that the dose calculation accuracy of the AXB10 would be inferior to the AXB11 in the clinical patient treatment planning. The only clear improvement with the AXB11 over the AXB10 is the dose calculation accuracy in air cavities. In general, no large deviations are present in the DVH analysis results between the two versions of the algorithm, and the results of 3D gamma analysis do not favor one or the other. Thus it may be concluded that the results of the comprehensive studies assessing the accuracy of the AXB10 may be extended to the AXB11. PACS numbers: 87.55.‐x, 87.55.D‐, 87.55.K‐, 87.55.kd, 87.55.Qr

The objective of this study was to modify volumetric modulated arc therapy (VMAT) design for breast irradiation with axillary lymph node involvement to enhance normal tissue sparing while maintaining good planning target volume (PTV) coverage. Four VMAT plans were generated retrospectively for 10 patients with breast cancer for comparison. First, 2 partial arcs with an avoidance sector (Pavoid) for the lung and the heart were created. Second, a split-arc design with 2 partial arcs was used, changing the collimator angle by splitting the arcs in the middle, resulting in 4 partial arcs (Psplit). Third, the arc angles in the Psplit were modified to emphasize tangential directions, corresponding to the avoidance sector in Pavoid, resulting in 2 lateral and 2 anterior partial arcs. Furthermore, a fifth arc was added to ensure the coverage of axillary lymph nodes (Ptang). Fourth, one of the anterior arcs was removed to limit the number of arcs during treatment (Ptang-1). PTV coverage was the highest in Psplit with a V90%(PTV) of 98.4 ± 0.6%. Also the dose homogeneity and conformity were the best (p

Background and Purpose. Although several methods have been developed to predict the outcome of patients with prostate cancer, early diagnosis of individual patient remains challenging. The aim of the present study was to correlate tumor perfusion parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and clinical prognostic factors and further to explore the diagnostic value of DCE-MRI parameters in early stage prostate cancer. Patients and Methods. Sixty-two newly diagnosed patients with histologically proven prostate adenocarcinoma were enrolled in our prospective study. Transrectal ultrasound-guided biopsy (12 cores, 6 on each lobe) was performed in each patient. Pathology was reviewed and graded according to the Gleason system. DCE-MRI was performed and analyzed using a two-compartmental model; quantitative parameters including volume transfer constant (Ktrans), reflux constant (Kep), and initial area under curve (iAUC) were calculated from the tumors and correlated with prostate-specific antigen (PSA), Gleason score, and clinical stage. Results. Ktrans (0.11 ± 0.02 min−1 versus 0.16 ± 0.06 min−1; p<0.05), Kep (0.38 ± 0.08 min−1 versus 0.60 ± 0.23 min−1; p<0.01), and iAUC (14.33 ± 2.66 mmoL/L/min versus 17.40 ± 5.97 mmoL/L/min; p<0.05) were all lower in the clinical stage T1c tumors (tumor number, n=11) than that of tumors in clinical stage T2 (n=58). Serum PSA correlated with both tumor Ktrans (r=0.304, p<0.05) and iAUC (r=0.258, p<0.05). Conclusions. Our study has confirmed that DCE-MRI is a promising biomarker that reflects the microcirculation of prostate cancer. DCE-MRI in combination with clinical prognostic factors may provide an effective new tool for the basis of early diagnosis and treatment decisions.

BACKGROUND Diffusion-weighted imaging (DWI) with measurement of apparent diffusion coefficient (ADC) allows for assessment of tumor aggressiveness. The objective of this study was to evaluate the changes of ADC value in prostate cancer after volumetric-modulated arc radiotherapy (VMAT) and to identify magnetic resonance imaging (MRI) biomarkers for monitoring tissue changes after radiotherapy. PATIENTS AND METHODS Thirty-seven patients with biopsy-proven prostate cancer treated with VMAT underwent serial MRI examinations including DWI before radiotherapy, and at 3 and 12 months after radiotherapy. ADC values of the tumor and healthy prostate tissue were measured and compared at these three time points. RESULTS The tumor ADC value increased significantly 3 months after radiotherapy (p

Purpose: To determine whether bones could be localized accurately by using MR images only in radiotherapytreatment planning. Furthermore, to measure absorbed dose in a material behind different parts of the bone, and to evaluate dose calculation error in a pseudo‐CT image by assuming a single electron density for the bones. Methods: A dedicated phantom was constructed using fresh deer bones and gelatine. The accuracy of the bone edge location and the bone diameter in MR images were evaluated by comparing those in the images with the actual measures. The absorbed dose behind the bones was measured by a matrix detector at 6 and 15 MV. Thedose calculation error in the bulk density pseudo‐CT image was quantified by comparing the calculation results with those obtained in a standard CTimage by superposition and Monte Carlo algorithms (TPSs: Xio 4.60 and Monaco 3.00, Elekta CMS Software). Results: The examination of bone position revealed that the bones can be localized within a 1‐mm‐pixel‐size in the MR images. The measured dose behind less than 2.5‐cm‐thick femur indicated that the absorbed dose behind the middle part of the bone is approximately one percentage unit (6 MV: 1.3%, 15 MV: 0.9%) smallerthan that of the physically narrower bone edge. The calculations illustrated that the bulk density pseudo‐CT image used causes errors up to nearly 2% to the dose behind the middle part, but also, the edge of the femur. Conclusions: This research ascertains that the bone localization is not a restrictive issue for radiotherapytreatment planning by using MR imageonly. The work indicates also that the decrease in absorbed dose is not necessarily dependent on the diameter of the bone. Future research shouldinvestigate the generation of more complex pseudo‐CT images and the dosecalculations by using these. Supported by Elekta.

In this study, the clinical benefit of the improved accuracy of the Acuros XB (AXB) algorithm, implemented in a commercial radiotherapy treatment planning system (TPS), Varian Eclipse, was demonstrated with beams traversing a high‐Z material. This is also the first study assessing the accuracy of the AXB algorithm applying volumetric modulated arc therapy (VMAT) technique compared to full Monte Carlo (MC) simulations. In the first phase the AXB algorithm was benchmarked against point dosimetry, film dosimetry, and full MC calculation in a water‐filled anthropometric phantom with a unilateral hip implant. Also the validity of the full MC calculation used as reference method was demonstrated. The dose calculations were performed both in original computed tomography (CT) dataset, which included artifacts, and in corrected CT dataset, where constant Hounsfield unit (HU) value assignment for all the materials was made. In the second phase, a clinical treatment plan was prepared for a prostate cancer patient with a unilateral hip implant. The plan applied a hybrid VMAT technique that included partial arcs that avoided passing through the implant and static beams traversing the implant. Ultimately, the AXB‐calculated dose distribution was compared to the recalculation by the full MC simulation to assess the accuracy of the AXB algorithm in clinical setting. A recalculation with the anisotropic analytical algorithm (AAA) was also performed to quantify the benefit of the improved dose calculation accuracy of type ‘c’ algorithm (AXB) over type ‘b’ algorithm (AAA). The agreement between the AXB algorithm and the full MC model was very good inside and in the vicinity of the implant and elsewhere, which verifies the accuracy of the AXB algorithm for patient plans with beams traversing through high‐Z material, whereas the AAA produced larger discrepancies. PACS numbers: 87.55.‐x, 87.55.D‐, 87.55.K‐, 87.55.kd, 87.55.Qr

We evaluated adequate setup margins for the radiotherapy (RT) of pelvic tumors based on overall position errors of bony landmarks. We also estimated the difference in setup accuracy between the male and female patients. Finally, we compared the patient rotation for 2 immobilization devices. The study cohort included consecutive 64 male and 64 female patients. Altogether, 1794 orthogonal setup images were analyzed. Observer-related deviation in image matching and the effect of patient rotation were explicitly determined. Overall systematic and random errors were calculated in 3 orthogonal directions. Anisotropic setup margins were evaluated based on residual errors after weekly image guidance. The van Herk formula was used to calculate the margins. Overall, 100 patients were immobilized with a house-made device. The patient rotation was compared against 28 patients immobilized with CIVCO's Kneefix and Feetfix. We found that the usually applied isotropic setup margin of 8mm covered all the uncertainties related to patient setup for most RT treatments of the pelvis. However, margins of even 10.3mm were needed for the female patients with very large pelvic target volumes centered either in the symphysis or in the sacrum containing both of these structures. This was because the effect of rotation (p ≤ 0.02) and the observer variation in image matching (p ≤ 0.04) were significantly larger for the female patients than for the male patients. Even with daily image guidance, the required margins remained larger for the women. Patient rotations were largest about the lateral axes. The difference between the required margins was only 1mm for the 2 immobilization devices. The largest component of overall systematic position error came from patient rotation. This emphasizes the need for rotation correction. Overall, larger position errors and setup margins were observed for the female patients with pelvic cancer than for the male patients.

Background and purpose: Recent studies have shown that it is possible to conduct entire radiotherapy treatment planning (RTP) workflow using only MR images. This study aims to develop a generalized intensity-based method to generate synthetic CT (sCT) images from standard T2-weighted (T2(W)) MR images of the pelvis.Materials and methods: This study developed a generalized dual model HU conversion method to convert standard T2(W) MR image intensity values to synthetic HU values, separately inside and outside of atlas-segmented bone volume contour. The method was developed and evaluated with 20 and 35 prostate cancer patients, respectively. MR images with scanning sequences in clinical use were acquired with four different MR scanners of three vendors.Results: For the generated synthetic CT (sCT) images of the 35 prostate patients, the mean (and maximal) HU differences in soft and bony tissue volumes were 16 +/- 6 HUs (34 HUs) and -46 +/- 56 HUs (181 HUs), respectively, against the true CT images. The average of the PTV mean dose difference in sCTs compared to those in true CTs was -0.6 +/- 0.4% (-1.3%).Conclusions: The study provides a generalized method for sCT creation from standard T2(W) images of the pelvis. The method produced clinically acceptable dose calculation results for all the included scanners and MR sequences. (c) 2017 Elsevier B.V. All rights reserved.

Small treatment fields are increasingly used with modern radiotherapy (RT) techniques, such as in stereotactic radiotherapy (SRT) [1]. The use of small fields enables more precise treatment, but wi...

The purpose of this study was to investigate the effects of breath hold reproducibility on positional and dosimetric errors in radiotherapy of patients with left-sided breast cancer (LSBC) treated with voluntary deep inspiration breath hold (vDIBH) technique. Clinical data from 2 groups of patients with LSBC were retrospectively investigated: (1) those irradiated for the whole breast only (WB group, n = 20) using typically from 3 to 5 breath holds per treatment session and (2) those irradiated simultaneously also for supraclavicular lymph nodes (WB + SLN group, n = 27) using from 7 to 9 breath holds per fraction. Setup and field images (n = 1365) from tangential breast fields, and anterior and posterior lymph node fields were analyzed to obtain total, inter-, and intrafractional residual positional errors of the chest wall and clavicle. The dosimetric effect of intrafractional positional errors was investigated at the abutment level of breast and lymph node fields. The total systematic setup error in the longitudinal (superior-inferior [SI]) direction was 1.4 and 1.9 mm (1 standard deviation, p = 0.049) for the WB and WB + SLN groups, respectively, whereas in the anterior/lateral direction, the error was 1.2 mm for both groups. In the SI direction, the systematic intrafractional error was also larger in the WB + SLN group (1.9 vs 1.1 mm, p = 0.003). The latter positional errors correlated moderately (ρ = 0.51) with the number of breath holds. Mean intrafractional errors of at least 2 mm were observed for 38% of the patients in the WB + SLN group. These errors resulted in a dosimetric error from 8.3% to 10.1% (1 cc). The total localization errors and needed setup margins were wider for the WB + SLN group, due to increased amount of breath holds in treatment session. Mean intrafraction movements ≥ 2 mm were shown to occur with this patient group in the SI direction, requiring intrafractional positional monitoring and corrective actions in daily practice.

In radiotherapy, target tissues are defined best on MR images due to their superior soft tissue contrast. Computed tomography imaging is geometrically accurate and it is needed for dose calculation and generation of reference images for treatment localization. Co-registration errors between MR and computed tomography images can be eliminated using magnetic resonance imaging-only based treatment planning. Use of ionizing radiation can be avoided which is especially important in adaptive treatments requiring several re-scans. We commissioned magnetic resonance imaging-only based procedure for external radiotherapy, treatment planning of the prostate cancer. Geometrical issues relevant in radiotherapy, were investigated including quality assurance testing of the scanner, evaluation of the displacement of skin contour and radiosensitive rectum wall, and detection of intraprostatic fiducial gold seed markers used for treatment localization. Quantitative analysis was carried out for 30 randomly chosen patients. Systematic geometrical errors were within 2.2 mm. The gold seed markers were correctly identified for 29 out of the 30 patients. Positions of the seed midpoints were consistent within 1.3 mm in magnetic resonance imaging and computed tomography. Positional error of rectal anterior wall due to susceptibility effect was minimal. Geometrical accuracy of the investigated equipment and procedure was sufficient for magnetic resonance imaging-only based radiotherapy, treatment planning of the prostate cancer including treatment virtual simulation.

In radiotherapy (RT), target soft tissues are best defined on MR images. In several cases, CT imaging is needed only for dose calculation and generation of digitally reconstructed radiographs (DRRs). Image co-registration errors between MRI and CT can be avoided by using MRI-only based treatment planning, especially in the pelvis. Since electron density information can not be directly derived from the MRI, a method is needed to convert MRI data into CT like data. We investigated whether there is a relationship between MRI intensity and Hounsfield unit (HU) values for the pelvic bones. The aim was to generate a method to convert bone MRI intensity into HU data surrogate for RT treatment planning.The HU conversion model was generated for 10 randomly chosen prostate cancer patients and independent validation was performed in another 10 patients. Data consisted of 800 image voxels chosen within the pelvic bones in both T1/T2*-weighted gradient echo and CT images. Relation between MRI intensity and electron density was derived from calibrated HU-values. The proposed method was tested by constructing five "pseudo"-CT series.We found that the MRI intensity is related to the HU value within a HU range from 0 to 1400 within the pelvic bones. The mean prediction error of the conversion model was 135 HU. Dose calculation based on the pseudo-CT images was accurate and the generated DRRs were of good quality.The proposed method enables generation of clinically relevant pseudo-CT data for the pelvic bones from one MRI series. It is simpler than previously reported approaches which require either acquisition of several MRI series or T2* maps with special imaging sequences. The method can be applied with commercial clinical image processing software. The application requires segmentation of the bones in the MR images.

We estimated cost/benefit ratios for different quality control programs of radiation output measurements of medical linear accelerators. The cost/benefit ratios of quality control (QC) programs (a combination of output measurement time interval and measurement action levels) were defined as workload divided by achievable dose accuracy. Dose accuracy was assumed to be inversely proportional to the 99% confidence limit of shifts of total treatment doses and workload as inversely proportional to the output measurement time interval. Our previously reported method was used to estimate the distribution of shifts of total treatment doses due to changes in accelerator radiation output (Gy/MU). The confidence limits of dose shifts were estimated for different QC programs and for different levels of output measurement reproducibility. Output shifts used in the estimations had previously been observed for four linear accelerators over 5 years. We observed that the cost/benefit ratio increases remarkably when the output measurement time interval is less than 1 month. The ratio depends strongly on the action levels and reproducibility of the QC measurements. Improvement of these factors optimizes the cost/benefit ratio by a factor of several times. The most cost-effective output measurement time interval to achieve 99% confidence limits of ±2, ±2.5 or ±3% for dose shifts ranged from 0.25 month to as much as 6 months depending on the factors given above and the intended accuracy level. It is several times more cost effective to increase dose accuracy by lowering the action levels of the QC measurements and by attempting to improve their reproducibility than by simply shortening the time interval of the output measurements. Methods improving utilization and interpretation of the results of the QC measurements play a key role in further optimization of cost/benefit ratios in dosimetric QC.

New treatment approaches are needed for hormone refractory prostate cancer. Oncolytic adenoviruses are promising anti-cancer agents, and their efficacy can be improved by combining with conventional therapies such as ionizing radiation. The aim of this study was to determine the timing of oncolytic adenovirus treatment with regard to radiation and study the mechanisms of synergy in combination treatment. Prostate cancer cells were infected with oncolytic adenoviruses, irradiated and synergy mechanisms were assessed. In vivo models of combination treatment were tested. Radiation and oncolytic viruses were synergistic when viral infection was scheduled 24 hr after irradiation. Combination of oncolytic adenovirus with radiotherapy significantly increased antitumor efficacy in vivo compared to either agent alone. Microarray analysis showed dysregulated pathways including cell cycle, mTOR and antigen processing pathways. Functional analysis showed that adenoviral infection was accompanied with degradation of proteins involved in DNA break repair. Mre11 was degraded for subsequent inactivation of Chk2-Thr68 in combination treated cells, while cH2AX-Ser139 was elevated implicating the persistence of DNA double strand breaks. Increased autophagocytosis was seen in combination treated cells. Combination treatment did not increase apoptosis or virus replication. The results provide evidence of the antitumor efficacy of combining oncolytic adenoviruses with irradiation as a therapeutic strategy for the treatment of prostate cancer. Further, these findings propose a molecular mechanism that may be important in radiation induced cell death, autophagy and viral cytopathic effect. ' 2009 UICC

Residual position errors of the lymph node (LN) surrogates and humeral head (HH) were determined for 2 different arm fixation devices in radiotherapy (RT) of breast cancer: a standard wrist-hold (WH) and a house-made rod-hold (RH). The effect of arm position correction (APC) based on setup images was also investigated. A total of 113 consecutive patients with early-stage breast cancer with LN irradiation were retrospectively analyzed (53 and 60 using the WH and RH, respectively). Residual position errors of the LN surrogates (Th1-2 and clavicle) and the HH were investigated to compare the 2 fixation devices. The position errors and setup margins were determined before and after the APC to investigate the efficacy of the APC in the treatment situation. A threshold of 5mm was used for the residual errors of the clavicle and Th1-2 to perform the APC, and a threshold of 7mm was used for the HH. The setup margins were calculated with the van Herk formula. Irradiated volumes of the HH were determined from RT treatment plans. With the WH and the RH, setup margins up to 8.1 and 6.7mm should be used for the LN surrogates, and margins up to 4.6 and 3.6mm should be used to spare the HH, respectively, without the APC. After the APC, the margins of the LN surrogates were equal to or less than 7.5/6.0mm with the WH/RH, but margins up to 4.2/2.9mm were required for the HH. The APC was needed at least once with both the devices for approximately 60% of the patients. With the RH, irradiated volume of the HH was approximately 2 times more than with the WH, without any dose constraints. Use of the RH together with the APC resulted in minimal residual position errors and setup margins for all the investigated bony landmarks. Based on the obtained results, we prefer the house-made RH. However, more attention should be given to minimize the irradiation of the HH with the RH than with the WH.

To investigate the conversion of prostate cancer radiotherapy (RT) target definition from CT-based planning into an MRI-only-based planning procedure.Using the CT- and MRI-only-based RT planning protocols, 30 prostate cancer patients were imaged in the RT fixation position. Two physicians delineated the prostate in both CT and T2-weighted MRI images. The CT and MRI images were coregistered based on gold seeds and anatomic borders of the prostate. The uncertainty of the coregistration, as well as differences in target volumes and uncertainty of contour delineation were investigated. Conversion of margins and dose constraints from CT- to MRI-only-based treatment planning was assessed.On average, the uncertainty of image coregistration was 0.4 ± 0.5 mm (one standard deviation, SD), 0.9 ± 0.8 mm and 0.9 ± 0.9 mm in the lateral, anterior-posterior and base-apex direction, respectively. The average ratio of the prostate volume between CT and MRI was 1.20 ± 0.15 (one SD). Compared to the CT-based contours, the MRI-based contours were on average 2-7 mm smaller in the apex, 0-1 mm smaller in the rectal direction and 1-4 mm smaller elsewhere.When converting from a CT-based planning procedure to an MRI-based one, the overall planning target volumes (PTV) are prominently reduced only in the apex. The prostate margins and dose constraints can be retained by this conversion.

A method was developed to estimate the spread of treatment doses due to a given output measurement, time interval and action level in external photon beam radiotherapy. The method exploits empirical or simulated data of both output stability and the reproducibility of the absolute output measurements and relative constancy checks. The spread of an output and the probability that an output is outside the predefined tolerance limits were estimated for different quality control procedures of the output. The use of internationally recommended output measurement intervals of 3, 1 and 0.25 months together with an action level of +/-2% results in the out-of-tolerance probability up to 49%, 26% and 3%, respectively, while the output is kept within up to +/-5.5%, +/-4.0% and +/-2.0%, respectively. It was also found that the action level has more prominent relative influence than the measurement interval. The results suggest that similar treatment quality can be achieved by doubling the output measurement time interval and lowering the action level from +/-2% to +/-1.5% and the constancy check action level from +/-3% to +/-2%.

Rationale and Objectives The goal was to improve informativeness in the determination of liver perfusion with a clinically available iodinated computed tomography (CT) contrast agent by developing open multicompartmental modeling. Materials and Methods Contrast-enhanced functional CT (fCT) examinations were conducted with temporal resolutions of 200–500 msec to 6 New Zealand White rabbits. First, we applied conventional open two-compartment model for the determination of arterial and portal blood flows (F A and F P ), blood and interstitial volume fractions (f b and f i ), and capillary permeability–surface area product (PS) of liver parenchyma. Then, we improved the modeling of vascular physiology by developing three- and open four-compartment models. For comparison, conventional single-compartment model was applied. We determined F A and F P also by using the peak-gradient method. Results Conventional two-compartment model yielded identical fittings with single-compartment model and does not provide unique solutions for f b and f i . The presented open four-compartment model provided F A and F P values of 0.40 ± 0.19 and 1.99 ± 0.57 mL/min/mL (tissue), f b and f i values of 0.30 ± 0.05 and 0.19 ± 0.04 mL/mL (tissue), and PS values of 4.0 ± 1.7 mL/min/mL (tissue). F A and F P are in a good agreement with those derived by using the peak-gradient method. Conclusions With the use of clinical extracellular iodinated CT contrast agent, the presented open four-compartment model provided physiological arterial and portal blood flow values and is also a potential tool in the assessment of blood and interstitial volume fractions and capillary permeability–surface area product. Moreover, the model requires neither measurements from hepatic vein or from other organs nor visual determination of arterial or portal phase.

Rationale and Objectives. To evaluate liver and liver tumor perfusions by using two different modelling methods: gamma-variate fitting and a single-compartment model. Materials and Methods. 5 New Zealand White rabbits with VX2 tumor implanted into the liver via portal injections were studied. Contrast-enhanced functional CT (fCT) examinations with temporal resolution of 200–500 milliseconds were conducted before tumor inoculation. Thereafter, two or three follow-up studies were conducted. A gamma-variate fitting method was used to determine fractional blood volumes (BV), and a single-compartment model method was used to determine fractional blood volumes (BV), blood flows (BF), and mean transit times (MTT) for normal and tumorous liver regions. Results. For tumorous regions in liver, the gamma-variate fitting and the single-compartment model methods showed statistically significant increases in arterial perfusions (P < 0.01) and decreases in portal perfusions (P < 0.01 with single-compartment model, and P < 0.05 with gamma-variate fitting) when compared with normal liver regions. The single-compartment model showed statistically significant increases (P < 0.01) in MTTs in tumorous regions. In normal liver regions, portal BFs decreased and MTTs increased after tumor inoculation, but the changes were statistically not significant. Conclusion. The gamma-variate fitting and the single-compartment model methods showed definite differences in perfusions between normal and tumorous regions in liver. The single-compartment model showed slightly more distinction and was faster. More importantly, both methods can easily be applied in the clinical environment in the assessment of liver perfusion.

Background Adjuvant radiotherapy (RT) of left-sided breast cancer is increasingly performed in voluntary deep inspiration breath-hold (vDIBH). The aim of this study was to estimate the reproducibility of breath-hold level (BHL) and to find optimal bony landmarks for matching of orthogonal setup images to minimise setup margins. Methods 1067 sets of images with an orthogonal setup and tangential field from 67 patients were retrospectively analysed. Residual position errors were determined in the tangential treatment field images for different matches of the setup images. Variation of patient posture and BHL were analysed for position errors of the vertebrae, clavicula, ribs and sternum in the setup and tangential field images. The BHL was controlled with a Varian RPM® system. Setup margins were calculated using the van Herk’s formula. Patients who underwent lymph node irradiation were also investigated. Results For the breast alone, the midway compromise of the ribs and sternum was the best general choice for matching of the setup images. The required margins were 6.5 mm and 5.3 mm in superior-inferior (SI) and lateral/anterior-posterior (LAT/AP) directions, respectively. With the individually optimised image matching position also including the vertebrae, slightly smaller margins of 6.0 mm and 4.8 mm were achieved, respectively. With the individually optimised match, margins of 7.5 mm and 10.8 mm should be used in LAT and SI directions, respectively, for the lymph node regions. These margins were considered too large. The reproducibility of the BHL was within 5 mm in the AP direction for 75% of patients. Conclusions The smallest setup margins were obtained when the matching position of the setup images was individually optimised for each patient. Optimal match for the breast alone is not optimal for the lymph node region, and, therefore, a threshold of 5 mm was introduced for residual position errors of the sternum, upper vertebrae, clavicula and chest wall to retain minimal setup margins of 5 mm. Because random interfraction variation in patient posture was large, we recommend daily online image guidance. The BHL should be verified with image guidance. BioMed Central open access

Background. Reduction of saliva secretion is a common side effect following radiotherapy (RT) for cancer of the head and neck region. The aim of this study is to predict the post-RT salivary function for individual patients prior to treatment and to recognise possible differences in individual radiosensitivity.Material and methods. A predictive model for post-RT salivary function was validated for 64 head and neck cancer patients. The input parameters for the model were salivary excretion fraction (sEF) measured by 99mTc-pertechnetate scintigraphy, total stimulated salivary flow and mean absorbed dose for the major salivary glands. SEF values after RT relative to the baseline before RT (rEF) were compared among the patients using the distance ΔrEF between single gland rEF and the corresponding expected value at the dose response curve.Results. A significant correlation (R = 0.86, p = 0.018) was found between the modelled and the measured values of stimulated salivary flow six months after RT. The average prediction error for the saliva flow rate was 6 ml/15 min. A linear relationship between ΔrEF for the left and the right parotid glands was observed both six (R = 0.53) and 12 (R = 0.79) months after RT. The average of absolute values of ΔrEF was 0.20 for parotid glands and 0.22 for submandibular glands.Conclusions. The salivary flow model was validated for 64 patients. The results imply, that one explanation for the discrepancies between the predicted and the measured salivary flow rate values and the common variations found in ΔrEF for the parotid glands may be differences in patients’ individual response to radiation. However, quantitative extraction of individual radiosensitivity would require further studies in order to take it into account in predictive models.

For long it has been recognized that tumor necrosis factor alpha (TNFa) has anticancer characteristics, and its use as a cancer therapeutic was proposed already in the 1980s. However, its systemic toxicity has limited its usability. Oncolytic viruses, selectively cancer-killing viruses, have shown great potency, and one of their most useful aspects is their ability to produce high amounts of transgene products locally, resulting in high local versus systemic concentrations. Therefore, the overall magnitude of tumor cell killing results from the combination of oncolysis, transgene-mediated direct effect such as TNFa-mediated apoptosis, and, perhaps most significantly, from activation of the host immune system against the tumor. We generated a novel chimeric oncolytic adenovirus expressing human TNFa, Ad5/3-D24-hTNFa, whose efficacy and immunogenicity were tested in vitro and in vivo. The hTNFa-expressing adenovirus showed increased cancer-eradicating potency, which was shown to be because of elevated apoptosis and necrosis rates and induction of various immune responses. Interestingly, we saw increase in immunogenic cell death markers in Ad5/3-d24-hTNFa-treated cells. Moreover, tumors treated with Ad5/3-D24-hTNFa displayed enhanced presence of OVA-specific cytotoxic T cells. We thus can conclude that tumor eradication and antitumor immune responses mediated by Ad5/3-d24-hTNFa offer a new potential drug candidate for cancer therapy.

Purpose. This study introduces methods to conduct image-guided radiotherapy (IGRT) of the pelvis with either cone-beam computed tomography (CBCT) or planar localization images by relying solely on magnetic resonance imaging (MRI)-based reference images.Material and methods. Feasibility of MRI-based reference images for IGRT was evaluated against kV CBCT (50 scans, 5 prostate cancer patients) and kV & MV planar (5 & 5 image pairs and patients) localization images by comparing the achieved patient position corrections to those obtained by standard CT-based reference images. T1/T2*-weighted in-phase MRI, Hounsfield unit conversion-based heterogeneous pseudo-CT, and bulk pseudo-CT images were applied for reference against localization CBCTs, and patient position corrections were obtained by automatic image registration. IGRT with planar localization images was performed manually by 10 observers using reference digitally reconstructed radiographs (DRRs) reconstructed from the pseudo-CTs and standard CTs. Quality of pseudo-DRRs against CT-DRRs was evaluated with image similarity metrics.Results. The SDs of differences between CBCT-to-MRI and CBCT-to-CT automatic gray-value registrations were ≤ 1.0 mm & ≤ 0.8° and ≤ 2.5 mm & ≤ 3.6° with 10 cm diameter cubic VOI and prostate-shaped VOI, respectively. The corresponding values for reference heterogeneous pseudo-CT were ≤ 1.0 mm & ≤ 0.7° and ≤ 2.2 mm & ≤ 3.3°, respectively. Heterogeneous pseudo-CT was the only type of MRI-based reference image working reliably with automatic bone registration (SDs were ≤ 0.9 mm & ≤ 0.7°). The differences include possible residual errors from planning CT to MRI registration. The image similarity metrics were significantly (p ≤ 0.01) better in agreement between heterogeneous pseudo-DRRs and CT-DRRs than between bulk pseudo-DRRs and CT-DRRs. The SDs of differences in manual registrations (3D) with planar kV and MV localization images were ≤ 1.0 mm and ≤ 1.7 mm, respectively, between heterogeneous pseudo-DRRs and CT-DRRs, and ≤ 1.4 mm and ≤ 2.1 mm between bulk pseudo-DRRs and CT-DRRs.Conclusion. This study demonstrated that it is feasible to conduct IGRT of the pelvis with MRI-based reference images.

This work evaluates influences of susceptibility-induced bone outline shift and perturbations, and bone segmentation errors on external radiotherapy dose calculation accuracy in magnetic resonance imaging (MRI)-based pseudo-computed tomography (CT) images of the male pelvis.T₁/T₂*-weighted fast gradient echo, T₁-weighted spin echo and T₂-weighted fast spin echo images were used in bone detection investigation. Bone edge location and bone diameter in MRI were evaluated by comparing those in the images with actual physical measurements of fresh deer bones positioned in a gelatine phantom. Dose calculation accuracy in pseudo-CT images was investigated for 15 prostate cancer patients. Bone outlines in T₁/T₂*-weighted images were contoured and additional segmentation errors were simulated by expanding and contracting the bone contours with 1 mm spacing. Heterogeneous pseudo-CT images were constructed by adopting a technique transforming the MRI intensity values into Hounsfield units with separate conversion models within and outside of bone segment.Bone edges and diameter in the phantom were illustrated correctly within a 1 mm-pixel size in MRI. Each 1 mm-sized systematic error in bone segment resulted in roughly 0.4% change to the prostate dose level in the pseudo-CT images. The prostate average (range) dose levels in pseudo-CT images with additional systematic bone segmentation errors of -2 mm, 0 mm and 2 mm were 0.5% (-0.5-1.4%), -0.2% (-1.0-0.7%), and -0.9% (-1.8-0.0%) compared to those in CT images, respectively, in volumetric modulated arc therapy treatment plans calculated by Monte Carlo algorithm.Susceptibility-induced bone outline shift and perturbations do not result in substantial uncertainty for MRI-based dose calculation. Dose consistency of 2% can be achieved reliably for the prostate if heterogeneous pseudo-CT images are constructed with ≤± 2 mm systematic error in bone segment.

Aim Patient setup errors were aimed to be reduced in radiotherapy (RT) of head-and-neck (H&N) cancer. Some remedies in patient setup procedure were proposed for this purpose. Background RT of H&N cancer has challenges due to patient rotation and flexible anatomy. Residual position errors occurring in treatment situation and required setup margins were estimated for relevant bony landmarks after the remedies made in setup process and compared with previous results. Materials and methods The formation process for thermoplastic masks was improved. Also image matching was harmonized to the vertebrae in the middle of the target and a 5 mm threshold was introduced for immediate correction of systematic errors of the landmarks. After the remedies, residual position errors of bony landmarks were retrospectively determined from 748 orthogonal X-ray images of 40 H&N cancer patients. The landmarks were the vertebrae C1–2, C5–7, the occiput bone and the mandible. The errors include contributions from patient rotation, flexible anatomy and inter-observer variation in image matching. Setup margins (3D) were calculated with the Van Herk formula. Results Systematic residual errors of the landmarks were reduced maximally by 49.8% ( p ≤ 0.05) and the margins by 3.1 mm after the remedies. With daily image guidance the setup margins of the landmarks were within 4.4 mm, but larger margins of 6.4 mm were required for the mandible. Conclusions Remarkable decrease in the residual errors of the bony landmarks and setup margins were achieved through the remedies made in the setup process. The importance of quality assurance of the setup process was demonstrated.

The lack of electron density information in magnetic resonance images (MRI) poses a major challenge for MRI-based radiotherapy treatment planning (RTP). In this study the authors convert MRI intensity values into Hounsfield units (HUs) in the male pelvis and thus enable accurate MRI-based RTP for prostate cancer patients with varying tissue anatomy and body fat contents.T1/T2*-weighted MRI intensity values and standard computed tomography (CT) image HUs in the male pelvis were analyzed using image data of 10 prostate cancer patients. The collected data were utilized to generate a dual model HU conversion technique from MRI intensity values of the single image set separately within and outside of contoured pelvic bones. Within the bone segment local MRI intensity values were converted to HUs by applying a second-order polynomial model. This model was tuned for each patient by two patient-specific adjustments: MR signal normalization to correct shifts in absolute intensity level and application of a cutoff value to accurately represent low density bony tissue HUs. For soft tissues, such as fat and muscle, located outside of the bone contours, a threshold-based segmentation method without requirements for any patient-specific adjustments was introduced to convert MRI intensity values into HUs. The dual model HU conversion technique was implemented by constructing pseudo-CT images for 10 other prostate cancer patients. The feasibility of these images for RTP was evaluated by comparing HUs in the generated pseudo-CT images with those in standard CT images, and by determining deviations in MRI-based dose distributions compared to those in CT images with 7-field intensity modulated radiation therapy (IMRT) with the anisotropic analytical algorithm and 360° volumetric-modulated arc therapy (VMAT) with the Voxel Monte Carlo algorithm.The average HU differences between the constructed pseudo-CT images and standard CT images of each test patient ranged from -2 to 5 HUs and from 22 to 78 HUs in soft and bony tissues, respectively. The average local absolute value differences were 11 HUs in soft tissues and 99 HUs in bones. The planning target volume doses (volumes 95%, 50%, 5%) in the pseudo-CT images were within 0.8% compared to those in CT images in all of the 20 treatment plans. The average deviation was 0.3%. With all the test patients over 94% (IMRT) and 92% (VMAT) of dose points within body (lower than 10% of maximum dose suppressed) passed the 1 mm and 1% 2D gamma index criterion. The statistical tests (t- and F-tests) showed significantly improved (p ≤ 0.05) HU and dose calculation accuracies with the soft tissue conversion method instead of homogeneous representation of these tissues in MRI-based RTP images.This study indicates that it is possible to construct high quality pseudo-CT images by converting the intensity values of a single MRI series into HUs in the male pelvis, and to use these images for accurate MRI-based prostate RTP dose calculations.

Magnetic resonance (MR) images are used increasingly in external radiotherapy target delineation because of their superior soft tissue contrast compared to computed tomography (CT) images. Nevertheless, radiotherapy treatment planning has traditionally been based on the use of CT images, due to the restrictive features of MR images such as lack of electron density information. This research aimed to measure absorbed radiation doses in material behind different bone parts, and to evaluate dose calculation errors in two pseudo-CT images; first, by assuming a single electron density value for the bones, and second, by converting the electron density values inside bones from T(1)∕T(2)∗-weighted MR image intensity values.A dedicated phantom was constructed using fresh deer bones and gelatine. The effect of different bone parts to the absorbed dose behind them was investigated with a single open field at 6 and 15 MV, and measuring clinically detectable dose deviations by an ionization chamber matrix. Dose calculation deviations in a conversion-based pseudo-CT image and in a bulk density pseudo-CT image, where the relative electron density to water for the bones was set as 1.3, were quantified by comparing the calculation results with those obtained in a standard CT image by superposition and Monte Carlo algorithms.The calculations revealed that the applied bulk density pseudo-CT image causes deviations up to 2.7% (6 MV) and 2.0% (15 MV) to the dose behind the examined bones. The corresponding values in the conversion-based pseudo-CT image were 1.3% (6 MV) and 1.0% (15 MV). The examinations illustrated that the representation of the heterogeneous femoral bone (cortex denser compared to core) by using a bulk density for the whole bone causes dose deviations up to 2% both behind the bone edge and the middle part of the bone (diameter2.5 cm), but in the opposite directions. The measured doses and the calculated ones in the standard CT image were within 0.4% (through gelatine only) and 0.9% (behind bones).This study indicates that the decrease in absorbed dose is not dependent on the bone diameter with all types of bones. Thus, performing dose calculation in a pseudo-CT image by assuming a single electron density value for the bones can lead to a substantial misrepresentation of the dose distribution profile. This work showed that dose calculation accuracy can be improved by using a pseudo-CT image in which the electron density values have been converted from the MR image intensity values inside bones.