Clinical feasibility of a commercially available MRI-only method for radiotherapy treatment planning of the brain.

BACKGROUND: Advancements in deep-learning based synthetic computed tomography (sCT) image conversion methods have enabled the development of magnetic resonance imaging (MRI)-only based radiotherapy treatment planning (RTP) of the brain. PURPOSE: This study evaluates the clinical feasibility of a commercial, deep-learning based MRI-only RTP method with respect to dose calculation and patient positioning verification performance in RTP of the brain. METHODS: Clinical validation of dose calculation accuracy was performed by a retrospective evaluation for 25 glioma and 25 brain metastasis patients. Dosimetric and image quality of the studied MRI-only RTP method was evaluated by a direct comparison of the sCT-based and computed tomography (CT)-based external beam radiation therapy (EBRT) images and treatment plans. Patient positioning verification accuracy of sCT images was evaluated retrospectively for 10 glioma and 10 brain metastasis patients based on clinical cone-beam computed tomography (CBCT) imaging. RESULTS: An average mean dose difference of Dmean = 0.1% for planning target volume (PTV) and 0.6% for normal tissue (NT) structures were obtained for glioma patients. Respective results for brain metastasis patients were Dmean = 0.5% for PTVs and Dmean =1.0% for NTs. Global three-dimensional (3D) gamma pass rates using 2%/2 mm dose difference and distance-to-agreement (DTA) criterion were 98.0% for the glioma subgroup, and 95.2% for the brain metastasis subgroup using 1%/1 mm criterion. Mean distance differences of <1.0 mm were observed in all Cartesian directions between CT-based and sCT-based CBCT patient positioning in both subgroups. CONCLUSIONS: In terms of dose calculation and patient positioning accuracy, the studied MRI-only method demonstrated its clinical feasibility for RTP of the brain. The results encourage the use of the studied method as part of a routine clinical workflow.

Radiation-induced prostate swelling during SBRT of the prostate.

BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Acute Side-effects of Different Radiotherapy Treatment Schedules in Early Prostate Cancer.

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.

Properties of IBA Razor Nano Chamber in small-field radiation therapy using 6 MV FF, 6 MV FFF, and 10 MV FFF photon beams.

BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS: 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 cm2 and appropriate for the PDD measurements. The field output correction factors kQclin, Qmsrfclin, fmsr and field OFs ΩQclin, Qmsrfclin, fmsr were determined according to TRS-483 protocol In the 6 MV FF and FFF beams, the determined correction factors kQclin, Qmsrfclin, fmsr were within 1.2% for the field sizes of 1 × 1 cm2-3 × 3 cm2 and the experimental and MC defined field output factors ΩQclin,Qmsrfclin,fmsr showed good agreement. CONCLUSION: The 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 kQclin, Qmsrfclin, fmsr are novel results for the NC in the TrueBeam fields.

Dose-area product ratio in external small-beam radiotherapy: beam shape, size and energy dependencies in clinical photon beams.

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 DAPR20,10may 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 DAPR20,10were studied and it was shown that the DAPR20,10increases with increasing beam energy similarly to TPR20,10but 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.

Radiation-induced accelerated aging of the brain vasculature in young adult survivors of childhood brain tumors.

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.

Assessment of MRI-Based Attenuation Correction for MRI-Only Radiotherapy Treatment Planning of the Brain.

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 <0.4% for PTV and <1.0% for OARs. Mean gamma index pass rates of 95.7% with the 2%/2 mm agreement criterion and 96.5% with the 1%/1 mm agreement criterion were determined for glioma and metastasis patients, respectively. Based on the results, MRI-only RTP using sCT images generated from MRAC images can be a feasible alternative for radiotherapy of the brain.

Quality assurance measurements of geometric accuracy for magnetic resonance imaging-based radiotherapy treatment planning.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: The geometric accuracy of the magnetic resonance for radiotherapy (MR-RT) platform remained stable within 2 mm at distances of <250 mm from isocenter. All scanners achieved good geometric accuracy with mean geometric distortions of <1 mm at <150 mm and <2 mm at <250 mm from the isocenter. Both measurement methods provided relevant information about geometric distortions. CONCLUSIONS: 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.

AlignRT® and Catalyst™ in whole-breast radiotherapy with DIBH: Is IGRT still needed?

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.

Contralateral tissue sparing in lymph node-positive breast cancer radiotherapy with VMAT technique.

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 < 0.02) in Psplit, and a smaller high-dose volume was distributed to the ipsilateral lung, heart, and humeral head, than in the other designs. In Ptang and Ptang-1, the PTV coverage was acceptable with V90%(PTV) of 97.9 ± 0.8% and 98.0 ± 0.8%, respectively, and low-dose volumes in normal tissue were smaller compared with Psplit. The removal of 1 partial arc from Ptang (Ptang-1) did not have a significant effect on dose parameters. In Pavoid, the contralateral breast and lung volumes of low-dose level were the smallest. However, the PTV coverage was reduced (V90% = 97.0 ± 1.6%), and the heart, ipsilateral lung, and humeral head received significantly higher doses than in other designs. The modified split-arc methods Ptang and Ptang-1, emphasizing tangential directions, were close to the original split-arc method in PTV coverage while reducing the dose to the healthy tissues distant from the PTV. Ptang-1 is seen as a favorable treatment option over Ptang with less treatment time.

Optimal selection of optimization bolus thickness in planning of VMAT breast radiotherapy treatments.

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.

Monte Carlo investigation on the effect of air gap under bolus in post-mastectomy radiotherapy.

OBJECTIVES: To investigate the dosimetric effect of air gaps under bolus on skin dose for left-sided post-mastectomy radiotherapy with loco regional involvement. METHODS: Eight patients were planned retrospectively with volume modulated arc therapy (VMAT) and conventional static Field-in-Field (FinF) methods. Three different setups were applied for the 5-mm bolus over the chest wall having 0, 5 or 10 mm air gap under the bolus. The dose calculation was performed using Monte Carlo (MC) simulation. In addition, Analytic Anisotropic Algorithm (AAA) was used to demonstrate the differences observed in clinical setting. RESULTS: The investigated air gaps under the bolus had minimal effect on surface dose for FinF plans (relative difference ≤ 2.6%), whereas for VMAT plans the surface dose decreased 13.6% when compared to the case with no air gap. In both FinF and VMAT, the largest differences between AAA and MC were seen at the surface where AAA underestimated the dose by 1.5 Gy (p < 0.05) on average; while the dose in the target volume excluding the surface was relatively similar being on average 0.3 Gy (p > 0.05) larger with AAA than with MC calculations. CONCLUSIONS: The surface dose was significantly lower with VMAT technique than with FinF technique. Possible air gaps under the bolus reduced the surface dose significantly further for VMAT but not for FinF treatments, which may have clinical impact on recurrence rate. AAA was shown to underestimate the surface dose when compared to MC calculation.

Dynamic Contrast-Enhanced Imaging as a Prognostic Tool in Early Diagnosis of Prostate Cancer: Correlation with PSA and Clinical Stage.

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 (K trans), reflux constant (K ep), and initial area under curve (iAUC) were calculated from the tumors and correlated with prostate-specific antigen (PSA), Gleason score, and clinical stage. Results: K trans (0.11 ± 0.02 min-1 versus 0.16 ± 0.06 min-1; p < 0.05), K ep (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 K trans (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.

Dosimetric effects of anatomical deformations and positioning errors in VMAT breast radiotherapy.

AIM: Traditional radiotherapy treatment techniques of the breast are insensitive for deformations and swelling of the soft tissue. The purpose of this study was to evaluate the dose changes seen with tissue deformations using different image matching methods when VMAT technique was used, and compare these with tangential technique. METHODS: The study included 24 patients with breast or chest wall irradiations, nine of whom were bilateral. In addition to planar kV setup imaging, patients underwent weekly cone-beam computed tomography (CBCT) imaging to evaluate soft tissue deformations. The effect of the deformations was evaluated on VMAT plans optimized with 5-mm virtual bolus to create skin flash, and compared to standard tangential plans with 2.5 cm skin flash. Isocenter positioning using 2D imaging and CBCT were compared. RESULTS: With postural changes and soft tissue deformations, the target coverage decreased more in the VMAT plans than in the tangential plans. The planned V90% coverage was 98.3% and 99.0% in the tangential and VMAT plans, respectively. When tattoo-based setup and online 2D match were used, the coverage decreased to 97.9% in tangential and 96.5% in VMAT plans (P < 0.001). With automatic CBCT-based image match the respective coverages were 98.3% and 98.8%. In the cases of large soft tissue deformations, the replanning was needed for the VMAT plan, whereas the tangential plan still covered the whole target volume. CONCLUSIONS: The skin flash created using an optimization bolus for VMAT plans was in most cases enough to take into account the soft tissue deformations seen in breast VMAT treatments. However, in some cases larger skin flash or replanning were needed. The use of 2D match decreased the target coverage for VMAT plans but not for FinF plans when compared to 3D match. The use of CBCT match is recommended when treating breast/chest wall patients with VMAT technique.

MRI-only based radiation therapy of prostate cancer: workflow and early clinical experience.

BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Natural Killer Cell Viability After Hyperthermia Alone or Combined with Radiotherapy with or without Cytokines.

BACKGROUND: The effects of hyperthermia and irradiation, alone and in combination, on natural killer (NK) cell viability were investigated in vitro. The roles of interleukin-2 (IL-2) and interferon (IFN) α, ß and γ in rescuing NK cells from hyperthermia and irradiation were studied. MATERIALS AND METHODS: Non-selected NK cells were used as effector cells and K-562 cells as target cells. NK and K-562 cells were treated at 37 to 45°C for 0 to 180 min. The cells were irradiated at room temperature using single doses from 0 to 60 Gy. Recombinant IL-2 at 100 to 450 U/ml and recombinant IFNα, ß and γ at 1,000 U/ml were used for different periods of time. NK cell viability was measured by intracellular adenosine tri-, and diphosphate (ATP, ADP) levels via luminometer, trypan blue exclusion and propidium iodide (PI) staining. Binding capacity of NK effector cells to target K-562 cells was also microscopically assessed. RESULTS: Thermal treatments between 37 and 41°C did not significantly affect the ATP levels of NK cells. Between 41°C and 42°C, ATP levels significantly decreased, whilst there was an insignificant reduction up to 45°C. At 42°C or higher, no recovery was detectable. At 42°C, the ATP level of NK cells rescued by IL-2 were significantly higher than those of controls at 37°C. IFNα, ß and γ had no significant effects. A combination of heating at 42°C and irradiation at 20 Gy significantly reduced the ATP levels (p<0.001) more than heating and irradiation alone. At 42°C, IL-2 abolished the reduction of ATP levels by heating and irradiation. This effect was dependent on heating time and irradiation dose. The ATP/ADP ratio did not significantly change when NK cells were heated for different times at 42°C. Thermal treatment of target K-562 cells at temperatures from 37 to 45°C reduced the number of NK cells binding K-652 cells. CONCLUSION: In vitro, NK cell viability was strongly reduced between 41°C and 42°C. At 42°C, the combination of irradiation and thermal treatment reduced the ATP levels in NK cells. However, IL-2 restored cell viability depending on thermal and radiation doses.

The robustness of dual isocenter VMAT radiation therapy for bilateral lymph node positive breast cancer.

PURPOSE: To investigate the use of dual isocenters for VMAT planning in patients with lymph node positive synchronous bilateral breast cancer (BBC) compared to a single isocenter option. METHODS: Treatment plans of 11 patients with lymph node positive BBC were retrospectively analyzed using two different VMAT planning techniques: dual-isocenter split-arc VMAT plans (Iso2) were compared with mono-isocenter VMAT plans (Iso1). For Iso2 plans, PTV dose was investigated after introducing ±2 and ±5 mm couch shift errors between the two isocenters in the lateral, longitudinal and vertical direction. RESULTS: For both techniques the planning aims for PTV coverage and OARs were met. The mean dose for the bilateral lungs and heart was reduced from 11.3 Gy and 3.8 Gy to 10.9 Gy (p < .05) and 3.6 Gy (p < .05), respectively, for Iso2 plans when compared to Iso1 plans. Positive statistically significant correlation (rho = 0.76, p = .006) was found between PTV volume and D2ccPTV for Iso1 plans. No clinically significant change was seen in the D98CTV or D2ccPTV after the 2 and 5 mm errors were introduced between isocenters for Iso2 plans. CONCLUSIONS: The split arc method was shown to be a feasible treatment technique in the case of synchronous BBC for both mono and dual isocenter techniques. The dose parameters were slightly favoring dual-isocenter option instead of mono-isocenter. The dual-isocenter method was shown to be a robust treatment option in the presence of ≤5 mm errors in the shifts between the two isocenters.

Intensity-based dual model method for generation of synthetic CT images from standard T2-weighted MR images - Generalized technique for four different MR scanners.

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 (T2w) MR images of the pelvis. MATERIALS AND METHODS: This study developed a generalized dual model HU conversion method to convert standard T2w 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 ±â€¯6 HUs (34 HUs) and -46 ±â€¯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 ±â€¯0.4% (-1.3%). CONCLUSIONS: The study provides a generalized method for sCT creation from standard T2w images of the pelvis. The method produced clinically acceptable dose calculation results for all the included scanners and MR sequences.

Diffusion-weighted MRI Provides a Useful Biomarker for Evaluation of Radiotherapy Efficacy in Patients with Prostate Cancer.

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<0.0001). There was a further increase of tumor ADC from 3 to 12 months after radiotherapy (p<0.01). The ADC of healthy prostate tissue did not show any significant changes. CONCLUSION: The ADC value is a useful biomarker for evaluating the efficacy of radiotherapy in prostate cancer.