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To perform a comparison of the different stereotactic body radiotherapy (SBRT) plans between the Varian EDGE and CyberKnife (CK) systems for locally advanced unresectable pancreatic cancer. Fifteen patients with pancreatic cancer were selected in this study. The median planning target volume (PTV) was 28.688 cm3 (5.736–49.246 cm3). The SBRT plans for the EDGE and CK were generated in the Eclipse and Multiplan systems respectively with the same contouring and dose constrains for PTV and organs at risk (OARs). Dose distributions in PTV were evaluated in terms of coverage, conformity index (CI), new conformity index (nCI), homogeneity index (HI), and gradient index (GI). OARs, including spinal cord, bowel, stomach, duodenum and kidneys were statistically evaluated by different dose-volume metrics and equivalent uniform dose (EUD). The volume covered by the different isodose lines (ISDL) ranging from 10 to 100% for normal tissue were also analyzed. All SBRT plans for EDGE and CK met the dose constraints for PTV and OARs. For the PTV, the dosimetric metrics in EDGE plans were lower than that in CK, except that D99 and GI were slightly higher. The EDGE plans with lower CI, nCI and HI were superior to generate more conformal and homogeneous dose distribution for PTV. For the normal tissue, the CK plans were better at OARs sparing. The radiobiological indices EUD of spinal cord, duodenum, stomach, and kidneys were lower for CK plans, except that liver were higher. The volumes of normal tissue covered by medium ISDLs (with range of 20–70%) were lower for CK plans while that covered by high and low ISDLs were lower for EDGE plans. This study indicated that both EDGE and CK generated equivalent plan quality, and both systems can be considered as beneficial techniques for SBRT of pancreatic cancer. EDGE plans offered more conformal and homogeneous dose distribution for PTV, while the CK plans could minimize the exposure of OARs. [ABSTRACT FROM AUTHOR]

Iso-dose maps creation and kerma-area products calculation are important procedures in radiotherapy and medical imaging. In this work, a method is presented to obtain iso-dose maps through digital processing of the images obtained from radiochromic films, which are employed to estimate the dose absorbed by the patient. The kerma-area product in selected regions of interest (ROIs) in the iso-dose map was then evaluated. The images were obtained by scanning the irradiated films using a commercial flatbed scanner. The iso-dose areas were extracted by means of an image segmentation algorithm, while calibration for a particular film to obtain a sensitometric curve relating dose to film darkening, was also made. A software interface allowed introducing the scanned image for the estimation of kerma-area products by defining the ROI interactively. The methods developed in this work allowed to implement a software application to obtain the iso-dose maps and kerma-area product in selected ROIs. [ABSTRACT FROM AUTHOR]

The aim is to study the density, isodose depths, and doses at different points in slab-pinewood-slab (SPS) phantom, solid phantom SP34 (made up of polystyrene), and chest level of actual patient for developing heterogeneous chest phantom mimicking thoracic region of human body. A 6 MV photon beam of field size of 10 cm×10 cm was directed perpendicular to the surface of computed tomography (CT) images of chest level of patient, SPS phantom, and SP34 phantom. Dose was calculated using anisotropic analytical algorithm. Hounsfield units were used to calculate the density of each medium. Isodose depths in all the three sets of CT images were measured. Variations between planned doses on treatment planning system (TPS) and measured on linear accelerator (LA) were calculated for three points, namely, near slab-pinewood interfaces (6 and 18 cm depths) and 10 cm depth in SPS phantom and at the same depths in SP34 phantom. Density of pinewood, SP34 slabs, chest wall, lung, and soft tissue behind lung was measured as 0.329 ± 0.08, 0.999 ± 0.02, 0.898 ± 0.02, 0.291 ± 0.12, and 1.002 ± 0.03 g/cc, respectively. Depths of 100% and 90% isodose curves in all the three sets of CT images were found to be similar. Depths of 80%, 70%, 60%, 50%, and 40% isodose lines in SPS phantom images were found to be equivalent to that in chest images, while it was least in SP34 phantom images. Variations in doses calculated at 6, 10, and 18 cm depths on TPS and measured on LA were found to be 0.36%, 1.65%, and 2.23%, respectively, in case of SPS phantom, while 0.24%, 0.90%, and 0.93%, respectively, in case of SP34 slab phantom. SPS phantom seemed equivalent to the chest level of human body. Dosimetric results of this study indicate that patient-specific quality assurance can be done using chest phantom mimicking thoracic region of human body, which has been fabricated using polystyrene and pinewood.

This is a retrospective study examining the efficacy and safety of Gamma Knife radiosurgery (GKS) in treating patients with cerebral cavernous malformations (CCMs). Between 1993 and 2018, 261 patients with 331 symptomatic CCMs were treated by GKS. The median age was 39.9 years and females were predominant (54%). The median volume of CCMs was 3.1 mL. The median margin dose was 11.9 Gy treat to a median isodose level of 59%. Median clinical and imaging follow-up times were 69 and 61 months, respectively. After the initial hemorrhage that led to CCM diagnosis, 136 hemorrhages occurred in the period prior to GKS (annual incidence = 23.6%). After GKS, 15 symptomatic hemorrhages occurred within the first 2 years of follow-up (annual incidence = 3.22%), and 37 symptomatic hemorrhages occurred after the first 2 years of follow-up (annual incidence = 3.16%). Symptomatic radiation-induced complication was encountered in 8 patients (3.1%). Mortality related to GKS occurred in 1 patient (0.4%). In conclusion, GKS decreased the risk of hemorrhage in CCM patients presenting with symptomatic hemorrhage. GKS is a viable alternative treatment option for patients with surgically-inaccessible CCMs or significant medical comorbidities. [ABSTRACT FROM AUTHOR]

Introduction: Breast conserving surgery (BCS) followed by postoperative whole breast irradiation (WBI) is the current standard of care for early stage breast cancer patients. Boost to the tumor bed is recommended for patients with a higher risk of local recurrence and may be applied with different techniques. Intraoperative electron radiotherapy (IOERT) offers several advantages compared to other techniques, like direct visualization of the tumor bed, better skin sparing, less inter- and intrafractional motion, but also radiobiological effects may be beneficial. Objective of this retrospective analysis of IOERT as boost in breast cancer patients was to assess acute toxicity and early oncological outcomes. Material and Methods: All patients, who have been irradiated between 11/2014 and 01/2018 with IOERT during BCS were analyzed. IOERT was applied using the mobile linear accelerator Mobetron with a total dose of 10 Gy, prescribed to the 90% isodose. After ensured woundhealing, WBI followed with normofractionated or hypofractionated regimens. Patient reports, including diagnostic examinations and toxicity were analyzed after surgery and 6–8 weeks after WBI. Overall survival, distant progression-free survival, in-breast and contralateral breast local progression-free survival were calculated using the Kaplan-Meier method. Furthermore, recurrence patterns were assessed. Results: In total, 157 patients with a median age of 57 years were evaluated. Postoperative adverse events were mild with seroma and hematoma grade 1–2 in 26% and grade 3 in 0.6% of the patients. Wound infections grade 2–3 occurred in 2.2% and wound dehiscence grade 1–2 in 1.9% of the patients. Six to eight weeks after WBI radiotherapy-dependent acute dermatitis grade 1–2 was most common in 90.9% of the patients. Only 4.6% of the patients suffered from dermatitis grade 3. No grade 4 toxicities were documented after surgery or WBI. 2- and 3-year overall survival and distant progression-free survival, were 97.5 and 93.6, and 0.7 and 2.8%, respectively. In-breast recurrence and contralateral breast cancer rates after 3 years were 1.9 and 2.8%, respectively. Conclusion: IOERT boost during BCS is a safe treatment option with low acute toxicity. Short-term recurrence rates are comparable to previously published data and emphasize, that IOERT as boost is an effective treatment. [ABSTRACT FROM AUTHOR]

Introduction: Before the approval of any Intensity Modulated Radiation Therapy or Volumetric Modulated Arc Therapy treatment plan, quality assurance (QA) tests are needed to reveal potential errors such as an inaccurate calculation of the dose distribution, the failure of the record‐and‐verify system, or the delivery system of the linear accelerator. Currently, the method adopted to compare the measured dose distribution with the treatment planning system TPS calculated dose distribution is gamma analysis. However, gamma analysis has been shown to be ineffective for the clinical evaluation of treatment plans. We proposed and tested a new method (the isodose structures method) alternative to gamma analysis. Method: Different errors were introduced in 33 error‐free Head and Neck plans. The modified plans were recalculated using TPS software and the dose distributions obtained were compared to those of the original (error‐free) plans. The comparison was performed using gamma analysis and the new method. The target was to calculate overall and organ‐specific gamma passing rates as well as the overlapping ratio (OR) and volume ratio (VR) factors of the isodose structures method for each error‐included plan. Results: Eight of the 33 plans passed both the gamma analysis and the isodose structures (IS) analysis, ten plans did not pass either of them, while 13 plans which did not pass the IS analysis, passed the gamma analysis. Two plans which did not pass gamma, passed IS analysis. Furthermore, Dose Volume Histogram (DVH) metrics could not detect the low agreement between the dose distributions of two error‐free plans and the respective modified plans. In this case, the IS analysis also allowed us to detect clinically meaningful differences between measured and TPS dose distributions. Conclusions: The IS method analysis clearly showed a high efficiency in detecting clinically relevant differences between TPS and measured dose distributions not seen in gamma analysis and in DVH‐based metrics. Therefore, IS analysis proved to be a valid tool, alternative to gamma analysis for dose comparison in patient‐specific QA test. [ABSTRACT FROM AUTHOR]

Highlights • MR-IGABT in cervix cancer improved target coverage and reduced irradiated volumes. • ISVs correlated with CTV HR volumes showing dose adaptation with tumour size. • From the perspective of normal tissue complications PDR was more sparing than HDR. • Larger EBRT doses of 50 Gy increased the irradiated volumes at doses of 60 Gy. Abstract Purpose To investigate the isodose surface volumes (ISVs) for 85, 75 and 60 Gy EQD2 for locally advanced cervix cancer patients. Materials and methods 1201 patients accrued in the EMBRACE I study were analysed. External beam radiotherapy (EBRT) with concomitant chemotherapy was followed by MR based image-guided adaptive brachytherapy (MR-IGABT). ISVs were calculated using a predictive model based on Total Reference Air Kerma and compared to Point A-standard loading systems. Influence of fractionation schemes and dose rates was evaluated through comparison of ISVs for α / β 10 Gy and 3 Gy. Results Median V85 Gy , V75 Gy and V60 Gy EQD2 10 were 72 cm3, 100 cm3 and 233 cm3, respectively. Median V85 Gy EQD2 10 was 23% smaller than in standard 85 Gy prescription to Point A. For small (<25 cm3), intermediate (25–35 cm3) and large (>35 cm3) CTV HR volumes, the V85 Gy was 57 cm3, 70 cm3 and 89 cm3, respectively. In 38% of EMBRACE patients the V85 Gy was similar to standard plans with 75–85 Gy to Point A. 41% of patients had V85 Gy smaller than standard plans receiving 75 Gy at Point A, while 21% of patients had V85 Gy larger than standard plans receiving 85 Gy at Point A. Conclusions MR-IGABT and individualized dose prescription during EMBRACE I resulted in improved target dose coverage and decreased ISVs compared to standard plans used with classical Point A based brachytherapy. The ISVs depended strongly on CTV HR volume which demonstrates that dose adaptation was performed per individual tumour size and response during EBRT. [ABSTRACT FROM AUTHOR]

Résumé La radiothérapie en conditions stéréotaxiques prend une place de plus en plus importante dans la prise en charge des métastases cérébrales. La principale toxicité est la radionécrose, dont l’incidence augmente avec la taille de la lésion. L’optimisation dosimétrique est donc importante pour le traitement des volumineuses métastases cérébrales afin d’offrir un taux de contrôle local optimal tout en diminuant le risque de radionécrose. Nous présentons ici le cas d’une métastase cérébrale de 30 mm de plus grand axe traitée par irradiation stéréotaxique après irradiation de l’encéphale en totalité, ayant été atteint d’une radionécrose symptomatique. Il a été délivré 24 Gy en trois fractions sur l’isodose 80 % par une technique d’arcthérapie dynamique conformationnelle par Novalis Tx®. Il a alors été réalisé une comparaison de plans dosimétriques : (i) réarrangement de la technique initiale, (ii) arcthérapie volumétrique avec modulation d’intensité avec arcs coplanaires et (iii) arcthérapie volumétrique avec modulation d’intensité avec arcs coplanaires et non coplanaires. Le profil dosimétrique le plus intéressant, en termes de couverture du volume cible prévisionnel (99,2 %) et d’épargne du parenchyme cérébrale sain (V24 Gy = 0,4cm3, V18 Gy = 6,5cm3, V10 Gy = 25,4cm3, V5 = 83,9cm3 [VxGy = volume recevant × Gy]) a été retrouvé avec l’arcthérapie volumétrique avec modulation d’intensité avec arcs coplanaires et non coplanaires. Proposer une arcthérapie volumétrique avec modulation d’intensité stéréotaxique avec arcs coplanaires et non coplanaires pour les métastases cérébrales volumineuses semble être une option intéressante afin de diminuer le risque de développer une radionécrose. Abstract Stereotactic radiotherapy is a major issue in the management of brain metastases. Radionecrosis is a major concern, especially for large lesions. Optimizing dosimetric parameters is essential to allow optimal local control rate while minimizing potential toxicity. We report the case of a 30-mm brain metastases treated with stereotactic radiotherapy after initial whole brain radiotherapy, complicated with symptomatic radionecrosis. A dose of 24 Gy in three fractions on the 80% isodose were delivered using a dynamic conformal arc technique (Novalis TX®). We realized a dosimetric comparison with: (i) optimization of initial conformal arc plan, (ii) volumetric modulated arctherapy with coplanar arcs and (iii) volumetric modulated arctherapy with coplanar and non-coplanar arcs. The optimal dose planning in terms of planning target volume coverage (99.2%) and normal brain sparing (V24 Gy = 0.4 cm3, V18 Gy = 6.5cm3, V10 Gy = 25.4 cm3, V5 = 83.9 cm3) was obtained with volumetric modulated arctherapy with coplanar and non-coplanar arcs. Volumetric modulated arctherapy-based stereotactic irradiation with coplanar and non-coplonar arcs seems an interesting option for the treatment of large brain metastases to optimize dosimetric parameters. [ABSTRACT FROM AUTHOR]

Abstract: This work demonstrates the efficacy of voxel‐based 90Y microsphere dosimetry utilizing post‐therapy SPECT/CT imaging and applies it to the prediction of treatment response for the management of patients with hepatocellular carcinoma (HCC). A 90Y microsphere dosimetry navigator (RapidSphere) within a commercial platform (Velocity, Varian Medical Systems) was demonstrated for three microsphere cases that were imaged using optimized bremsstrahlung SPECT/CT. For each case, the 90Y SPECT/CT was registered to follow‐up diagnostic MR/CT using deformable image registration. The voxel‐based dose distribution was computed using the local deposition method with known injected activity. The system allowed the visualization of the isodose distributions on any of the registered image datasets and the calculation of dose‐volume histograms (DVHs). The dosimetric analysis illustrated high local doses that are characteristic of blood‐flow directed brachytherapy. In the first case, the HCC mass demonstrated a complete response to treatment indicated by a necrotic region in follow‐up MR imaging. This result was dosimetrically predicted since the gross tumor volume (GTV) was well covered by the prescription isodose volume (V150 Gy = 85%). The second case illustrated a partial response to treatment which was characterized by incomplete necrosis of an HCC mass and a remaining area of solid enhancement in follow‐up MR imaging. This result was predicted by dosimetric analysis because the GTV demonstrated incomplete coverage by the prescription isodose volume (V470 Gy = 18%). The third case demonstrated extrahepatic activity. The dosimetry indicated that the prescription (125 Gy) isodose region extended outside of the liver into the duodenum (178 Gy maximum dose). This was predictive of toxicity as the patient later developed a duodenal ulcer. The ability to predict outcomes and complications using deformable image registration, calculated isodose distributions, and DVHs, points to the clinical utility of patient‐specific dose calculations for 90Y radioembolization treatment planning. [ABSTRACT FROM AUTHOR]

Purpose: Inverse planning involves iterative optimization of a large number of parameters and is known to be a labor‐intensive procedure. To reduce the scale of computation and improve characterization of isodose plan, this paper presents an isodose feature‐preserving voxelization (IFPV) framework for radiation therapy applications and demonstrates an implementation of inverse planning in the IFPV domain. Methods: A dose distribution in IFPV scheme is characterized by partitioning the voxels into subgroups according to their geometric and dosimetric values. Computationally, the isodose feature‐preserving (IFP) clustering combines the conventional voxels that are spatially and dosimetrically close into physically meaningful clusters. A K‐means algorithm and support vector machine (SVM) runs sequentially to group the voxels into IFP clusters. The former generates initial clusters according to the geometric and dosimetric information of the voxels and SVM is invoked to improve the connectivity of the IFP clusters. To illustrate the utility of the formalism, an inverse planning framework in the IFPV domain is implemented, and the resultant plans of three prostate IMRT and one head‐and‐neck cases are compared quantitatively with that obtained using conventional inverse planning technique. Results: The IFPV generates models with significant dimensionality reduction without compromising the spatial resolution seen in traditional downsampling schemes. The implementation of inverse planning in IFPV domain is demonstrated. In addition to the improved computational efficiency, it is found that, for the cases studied here, the IFPV‐domain inverse planning yields better treatment plans than that of DVH‐based planning, primarily because of more effective use of both geometric and dose information of the system during plan optimization. Conclusions: The proposed IFPV provides a low parametric representation of isodose plan without compromising the essential characteristics of the plan, thus providing a practically valuable framework for various applications in radiation therapy. [ABSTRACT FROM AUTHOR]

Purpose Permanent breast seed implant (PBSI) is a developing brachytherapy technique for the treatment of early-stage breast cancer. In current practice, PBSI uses manual planning strategies to generate clinical treatment plans. In this work, a simulated annealing-based algorithm is developed to demonstrate the first application of inverse optimization for PBSI. Methods and Materials Target, skin, and chest wall muscle contours, exported from a treatment planning system in digital imaging and communications in medicine format, are used as inputs. To optimize, the user defines the dose–volume histogram objectives for the target and specifies a relative weighting for target and skin constraints. A 10-patient cohort of previously treated patients was planned by using the inverse optimization algorithm. Plan quality was compared to the clinically treated manually generated plans using the V 90% , V 100% , V 150% , and V 200% for the planning target volume (PTV), V 90% and D 0.2 cc for skin dose, and PTV conformity indices. Results For each of the 10 patients, patient-wise paired differences between inverse and manual plans were analyzed and presented in box plots. Comparing inverse and manual planning techniques, a statistical difference was not observed ( p > 0.05) in PTV coverage criteria ( V 90% , V 100% ) and dose to skin 2mm . A statistical difference was observed in the inverse plans as a reduction of the V 150% (mean of 6.2%) and increase in conformity index of the 20%, 50%, 90%, and 100% isodose lines. Conclusions This work presents the first application of inverse optimization used to generate PBSI treatment plans. A 10-patient cohort previously treated with PBSI was retrospectively planned for comparison with the clinically treated manually generated plans. [ABSTRACT FROM AUTHOR]

Natural background radiation was measured in the province of Chimborazo (Ecuador) with the following reference coordinates 1°40'00''S 78°39'00''W, where the furthest point to the center of the planet is located. Natural background radiation measurements were performed at 130 randomly selected sites using a Geiger Müller GCA-07W portable detector; these measurements were run at 6 m away from buildings or walls and 1 m above the ground. The global average natural background radiation established by UNSCEAR is 2.4 mSv y −1 . In the study area measurements ranged from 0.57 mSv y −1 to 3.09 mSv y −1 with a mean value of 1.57 mSv y −1 , the maximum value was recorded in the north of the study area at 5073 metres above sea level (m.a.s.l.), and the minimum value was recorded in the southwestern area at 297 m.a.s.l. An isodose map was plotted to represent the equivalent dose rate due to natural background radiation. An analysis of variance (ANOVA) between the data of the high and low regions of the study area showed a significant difference (p < α), in addition a linear correlation coefficient of 0.92 was obtained, supporting the hypothesis that in high altitude zones extraterrestrial radiation contributes significantly to natural background radiation. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. Methods: The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Results: Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. Conclusions: The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice. [ABSTRACT FROM AUTHOR]

Background: Herein, the authors evaluated how the time to testosterone rebound (TTR) after radiotherapy (RT) and 6 months of androgen deprivation therapy (ADT) impacted the risk of prostate cancer-specific mortality (PCSM) and cardiovascular-specific mortality (CVM) among men with varying comorbidity extent.Methods: Between 1995 and 2001, a total of 206 men who were randomized to receive RT either alone or with 6 months of ADT for unfavorable-risk PC and who had a comorbidity score assigned using the Adult Comorbidity Evaluation 27 metric comprised the study cohort. Multivariable competing risk regression was used to evaluate the impact of and possible interaction between comorbidity and TTR on PCSM and CVM.Results: After a median follow-up of 18.19 years, 30 men (18.6%), 39 men (24.2%), and 92 men (57.1%), respectively, had died of PC, CV disease, or other causes. As TTR increased, PCSM significantly decreased in men with no or minimal (adjusted hazard ratio [AHR], 0.53, 95% confidence interval [95% CI], 0.34-0.84 [P =.007]) and moderate to severe (AHR, 0.37; 95% CI, 0.14-0.99 [P = .048]) comorbidity. However, increasing TTR significantly increased the risk of CVM among men with moderate to severe comorbidity (AHR, 1.87; 95% CI, 1.40-2.49 [P <.001]), but not those with no or minimal comorbidity (AHR, 0.86; 95% CI, 0.57-1.29 [P =.46]), leading to a significant interaction between TTR and comorbidity (P = .001).Conclusions: The results of the current study indicate that considering an intermittent course of ADT such that the TTR approaches 18 months, instead of continuous long-term administration of ADT, in men with moderate to severe comorbidity and high-risk PC may reduce the increased risk of CVM without increasing the risk of PCSM. Cancer 2018;124:1391-9. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Introduction: The determination of accurate dose distribution is an issue of fundamental importance in radiotherapy, especially with regard to the fact that the human body is a heterogeneous medium. Therefore, the present study aimed to analyze the density and isodose depth profiles of 6 MV beam in a SP34 slab-wooden dust (pine)-SP34 slab (SWS) heterogeneous phantom. Materials and Methods: The density of SP34 slab, wooden dust of pine, and thoracic region of 10 patients were calculated using computed tomography (CT) images. The depths of isodose lines were measured for 6 MV beam on the CT images of the chest, SP34 slab phantom, and SWS phantom. Dose calculation was performed at the depths of 2, 13, and 21 cm in both phantoms. Furthermore, patientspecific quality assurance (QA) was implemented using both phantoms. Results: The mean densities of the lung, SP34 slabs, and wooden dust were 0.29, 0.99, and 0.27 gm/cc respectively. The mean depths of different isodose lines in the SWS phantom were found to be equivalent to those in actual patients. Furthermore, the percentage variation between the planned and measured doses was higher in the SWS phantom as compared to that in the SP34 phantom. Furthermore, the percentage variation between the planned and measured doses in patient-specific QA was higher in the SWS phantom as compared to that in the SP34 phantom. Conclusion: As the findings indicated, the density and isodose depth profiles of the SWS phantom were equivalent to those of the actual thoracic region of human. [ABSTRACT FROM AUTHOR]

Osteoradionecrosis is defined as bone death secondary to radiotherapy. There is a relationship between the radiation dose received and the occurrence of osteoradionecrosis of the jaws, with the risk increasing above a dose of 60 Gy. In cases of class III mandibular osteoradionecrosis, a segmental resection can be indicated. Current practice is to completely remove the affected bone up to the point where the bone looks healthy and is bleeding. Exact resection planning and the use of guided surgery based on imaging of the bone changes have not been reported so far. This article describes a method whereby the radiotherapy dose information is incorporated into the imaging of the affected bone in order to plan a three-dimensional (3D) virtual guided resection and reconstruction of the mandible in osteoradionecrosis. The method enables 3D visualization of each desired dose field in relation to the 3D model of the affected bone. Two types of application – for resection and reconstruction – are described. [ABSTRACT FROM AUTHOR]

Background: To identify optimization of dose distributions of target volumes and decrease of radiation doses to normal tissues during stereotactic body radiation therapy (SBRT) for pancreatic cancer with dose-limiting auto-shells.Methods: With the same prescription dose, dose constraints of normal organs and calculation algorithm, treatment plans of each eligible patient were re-generated with 3 shells, 5 shells and 7 shells, respectively. The prescription isodose line and beam number of each patient in 3-shell, 5-shell and 7-shell plan remained the same. Hence, a triplet data set of dosimetric parameters was generated and analyzed.Results: As the increase of shell number, the conformal index, volumes encompassed by 100% prescription isodose line and 30% prescription isodose line significantly decreased. The new conformal index was higher in 3-shell group than that in 5-shell and 7-shell group. A sharper dose fall-off was found in 5-shell and 7-shell group compared to 3-shell group. And the tumor coverage in 7-shell was better than that of 3-shell and 5-shell. Lower D5cc of the intestine, D10cc of the stomach, Dmax of the spinal cord and smaller V10 of the spleen was confirmed in 7-shell group compared to 3-shell group.Conclusions: More conformal dose distributions of target volumes and lower radiation doses to normal organs could be performed with the increase of dose-limiting auto-shells, which may be more beneficial to potential critical organs without established dose constraints. [ABSTRACT FROM AUTHOR]

Purpose/Objective(s): In stereotactic radiosurgery (SRS), the multiple isocenters for multiple targets dynamic conformal arc (MIMT DCA) technique is traditionally used to treat multiple brain metastases, with one isocenter for each target. The single isocenter for multiple targets (SIMT) technique has recently been adopted to reduce the treatment time at the cost of plan quality. The objective of this study was to develop a restricted single isocenter for multiple targets DCA (RSIMT DCA) technique that can significantly reduce the treatment time but still maintain similar plan quality as the MIMT DCA technique. Materials and Methods: Treating multiple brain metastases with a single isocenter poses a challenge to SRS planning using DCA beams that are intrinsically 3D and do not modulate the beam intensity to spare the normal tissue between targets. To address this obstacle, we have developed a RSIMT DCA technique and used it to treat SRS patients with multiple brain metastases since February 2015. This planning approach is similar to the SIMT technique except that the number of targets for each isocenter is restricted and the distance between the isocenter and target is limited. In this technique, the targets are first split into small batches so that all targets in a batch are within a chosen distance (e.g., 7 cm) of each other. All targets in a batch are combined into one target and the geometric center of the combined target is the isocenter for the group of DCA beams associated with that batch. Each DCA group typically consists of 3-4 DCA beams to irradiate 1-3 targets. For each DCA beam, the collimator angle is adjusted to minimize the exposure of normal tissue between targets. The dose of each treatment group is normalized so that the maximal point dose to the combined target is 125% of the prescription dose, which is equivalent to normalize the prescription dose to 80% isodose line. If the maximal point dose of a target is <123%, an additional beam is used to boost the maximal point dose of that target to 125%. To evaluate the plan quality, we randomly selected 10 cases planned with the RSIMT DCA technique, and re-planned them using the MIMT DCA technique. There were in total 38 PTVs, and 22 isocenters were used to treat all of these targets. The prescription for each target was 20 Gy with a maximal point dose of 25 Gy. Plan quality indexes were calculated and compared. Paired sample t-test was performed to determine if the mean normalized difference, (RSIMT-MIMT)/MIMT of each plan index was statistically significantly (p-value < 5%) larger than 0. Results: Satisfactory PTV coverage (V20Gy>95% and V19Gy=100%) was achieved for all plans using either technique. Most PTVs have a maximal point dose between 24.9 and 25.1 Gy, with 2 PTVs between 24.5 and 24.9 Gy. Overall, the plan quality was slightly better for the MIMT DCA technique and the normalized difference was statistically significantly larger than 0 for all investigated dose quality indexes. The normalized difference of body mean dose and conformity index (CI) between the RSIMT and MIMT techniques was respectively 4.2% (p=0.002) and 9.4% (p=0.001), indicating similar plan quality globally and in the high dose area. The difference was more pronounced for the mid-to-low dose spillage with the ratios of V12Gy and V10Gy/VPTV being 13.9% (p=3.8×10-6) and 14.9% (p=1.3×10-5), respectively. The treatment time was reduced by 30%-50% with the RSIMT DCA technique. Conclusion: The RSIMT DCA technique can produce satisfactory SRS plans for treating multiple targets and can significantly reduce the treatment time. [ABSTRACT FROM AUTHOR]

Purpose: Anatomical motion, both cyclical and aperiodic, can impact the dose delivered during external beam radiation. In this work, we evaluate the use of a research version of the clinical TomoTherapy® dose calculator to calculate dose with intrafraction rigid motion. We also evaluate the feasibility of a method of motion compensation for helical tomotherapy using the jaws and MLC. Methods: Treatment plans were created using the TomoTherapy treatment planning system. Dose was recalculated for several simple rigid motion traces including a 4 mm step motion applied either longitudinally or transversely, and a sinusoidal motion. The calculated dose volumes were compared to dose measurements that were performed by translating the phantom with the same motion traces used in the calculations. Measurements were made using film and ion chambers. Finally, the delivery plans were modified to compensate for the motion by sweeping the jaws for longitudinal motion and shifting the MLC leaves for transverse motion, and the calculations and measurements were repeated. Results: A transverse step motion shifted the dose that was delivered after the step occurred, but otherwise did not impact the dose distribution. Film measurements agreed with dose calculations to within 2%/2 mm for 99% of dose points within the 50% isodose line. A shift in the MLC leaf delivery pattern successfully compensated for the step motion to within the 3 mm accuracy allowed by the finite leaf widths. A longitudinal step motion impacted the dose in the interior of the target volume to a degree that was dependent on the planning field width and step size. Film measurements agreed with dose calculations to within 2%/2 mm for 98% of dose points within the 50% isodose line. Shifts in the jaw position successfully compensated for the longitudinal step motion. Sinusoidal (breathing‐like) motion was also studied, with similar results. Conclusions: A research version of the clinical TomoTherapy dose calculator has been shown to accurately calculate the dose from treatment plans delivered in the presence of arbitrary rigid motion. Modifications to the delivery plan using jaw and MLC leaf shifts that follow the motion can successfully compensate for the target motion. [ABSTRACT FROM AUTHOR]

Radiobiological experiments such as small animal whole or partial body irradiation, cell culture irradiation, tissue culture irradiation, require accurate and reproducible irradiation dosimetry to allow the work to be interpreted and repeated and for valid comparisons to be made by other laboratories. Limited standardized protocols are available for small animal dosimetry when using 137 Cs irradiators. Methods for mapping dose distributions and to determine the regions of isodose such as Gafchromic film, ionization chambers or arrays of Thermoluminescent Dosimeters (TLDs) may result in low-resolution mappings, is very laborious, time-consuming and allows for dosimeter placement inaccuracies in regions of high-dose gradients. Our new approach takes advantage of Fricke solution properties and has been adapted so that it can be performed in 96-well plates. Fricke dosimetry depends on the oxidation of ferrous ions (Fe2+) to ferric ions (Fe3+) by ionizing radiation. The increased concentration of ferric ions is measured spectrophotometrically at 304 nm. The Fricke dosimeter is 96% water by weight; therefore, it lends itself well to a determination of absorbed dose to water. This dosimeter is used in a dose range of 5–400 Gy and for dose rates of up to 10 6 Gy/s. This new methodology approach allow us to have an absolute dosimetry system, with proven performance, having 96 independent dosimeters on plates of small dimensions. A 3D array of hundreds of independent dosimeters analyzed with a mathematical software to create 3D-surface plots lead that absorbed dose can be estimated in virtually any area of the chamber. Our method could be used for standardization of dosimetry within and between laboratories and for intercomparison programs, which is becoming clear that is needed to be implemented for the radiobiology research procedures. [ABSTRACT FROM AUTHOR]

Background: This work explores how the choice of prescription isodose line (IDL) affects the dose gradient, target coverage, and treatment time for Gamma Knife radiosurgery when a smaller shot is encompassed within a larger shot at the same stereotactic coordinates (shot within shot technique).Methods: Beam profiles for the 4, 8, and 16 mm collimator settings were extracted from the treatment planning system and characterized using Gaussian fits. The characterized data were used to create over 10,000 shot within shot configurations by systematically changing collimator weighting and choice of prescription IDL. Each configuration was quantified in terms of the dose gradient, target coverage, and beam-on time. By analyzing these configurations, it was found that there are regions of overlap in target size where a higher prescription IDL provides equivalent dose fall-off to a plan prescribed at the 50% IDL. Furthermore, the data indicate that treatment times within these regions can be reduced by up to 40%. An optimization strategy was devised to realize these gains. The strategy was tested for seven patients treated for 1-4 brain metastases (20 lesions total).Results: For a single collimator setting, the gradient in the axial plane was steepest when prescribed to the 56-63% (4 mm), 62-70% (8 mm), and 77-84% (16 mm) IDL, respectively. Through utilization of the optimization technique, beam-on time was reduced by more than 15% in 16/20 lesions. The volume of normal brain receiving 12 Gy or above also decreased in many cases, and in only one instance increased by more than 0.5 cm3.Conclusions: This work demonstrates that IDL optimization using the shot within shot technique can reduce treatment times without degrading treatment plan quality. [ABSTRACT FROM AUTHOR]

Background: Spontaneous cervical artery dissection (sCAD) is an important etiology of juvenile stroke. The gold standard for the diagnosis of sCAD is convential angiography. However, magnetic resonance imaging (MRI)/MR angiography (MRA) and computed tomography (CT)/CT angiography (CTA) are frequently used alternatives. New developments such as multislice CT/CTA have enabled routine acquisition of thinner sections with rapid imaging times. The goal of this study was to compare the capability of recent developed 128-slice CT/CTA to MRI/MRA to detect radiologic features of sCAD.Methods: Retrospective review of patients with suspected sCAD (n = 188) in a database of our Stroke center (2008-2014), who underwent CT/CTA and MRI/MRA on initial clinical work-up. A control group of 26 patients was added. All Images were evaluated concerning specific and sensitive radiological features for dissection by two experienced neuroradiologists. Imaging features were compared between the two modalities.Results: Forty patients with 43 dissected arteries received both modalities (29 internal carotid arteries [ICAs] and 14 vertebral arteries [VAs]). All CADs were identified in CT/CTA and MRI/MRA. The features intimal flap, stenosis, and lumen irregularity appeared in both modalities. One high-grade stenosis was identified by CT/CTA that was expected occluded on MRI/MRA. Two MRI/MRA-confirmed pseudoaneurysms were missed by CT/CTA. None of the controls evidenced specific imaging signs for dissection.Conclusions: CT/CTA is a reliable and better available alternative to MRI/MRA for diagnosis of sCAD. CT/CTA should be used to complement MRI/MRA in cases where MRI/MRA suggests occlusion. [ABSTRACT FROM AUTHOR]

Purpose To demonstrate that V 60 Gy, V 75 Gy, and V 85 Gy isodose surface volumes can be accurately estimated from total reference air kerma (TRAK) in cervix cancer MRI-guided brachytherapy (BT). Methods and Materials 60 Gy, 75 Gy, and 85 Gy isodose surface volumes levels were obtained from treatment planning systems (V TPS ) for 239 EMBRACE study patients from five institutions treated with various dose rates, fractionation schedules and applicators. An equation for estimating V TPS from TRAK was derived. Furthermore, a surrogate Point A dose (Point A*) was proposed and tested for correlation with V 75 Gy. Results Predicted volumes V pred = 4965 (TRAK/dref) 3/2 + 170 (TRAK/dref) − 1.5 gave the best fit to V TPS . The difference between V TPS and predicted volumes was 0.0% ± 2.3%. All volumes were predicted within 10%. The prediction was valid for ( 1 ) high-dose rate and pulsed dose rate, ( 2 ) intracavitary vs. intracavitary/interstitial applicators, and ( 3 ) tandem-ring, tandem-ovoid, and mold. Point A* = 14 TRAK was converted to total EQD 2 and showed high correlation with V 75 Gy. Conclusions TRAK derived Isodose surface volumes may become a tool for assessment of treatment intensity. Furthermore, surrogate Point A ∗ doses can be applied for both intracavitary and intracavitary/interstitial BT and can be used to compare treatments across fractionation schedules. [ABSTRACT FROM AUTHOR]

Background: By the use of PSMA positron emission tomography (PET) detection of prostate cancer lesions with a high sensitivity and specificity combined with a favorable lesion to background contrast is feasible. Therefore, PSMA-PET is increasingly used for planning of radiotherapy treatment; however, any data on intermediate-term outcome is missing so far.Methods: Patients with high-risk or very high risk prostate cancer, referred for salvage radiotherapy (SRT, n = 22) between 2013 and 2015, underwent PSMA-PET prior to therapy. Irradiation was planned on PET data with boost to macroscopic tumors/metastases. Treatment related toxicity was measured using Common Terminology Criteria for Adverse Events (CTCAE, v4.0).Result: Findings in PSMA-PET led to treatment modifications in 77% of SRT patients compared to available CT information. One patient did not receive irradiation due to disseminated disease, the other patients received increased boost doses to macroscopic disease and/or inclusion of additional target volumes. Toxicity was low as only 2 patients reported toxicities > grade 1. With a Median follow-up time of 29 in patients that were not lost to follow-up, prolonged PSA responses below baseline were observed in the majority of patients (14 of 20). In hormone-naïve SRT patients (n = 11), radiotherapy led to prolonged PSA decrease in 8/11 patients, however with 3 of these 8 patients receiving repeated PSMA based irradiation of novel lesions during follow-up.Conclusion: PSMA-PET guided planning of radiotherapy led to change of treatment in the majority of patients. Treatment related toxicity was well tolerated and promising results regarding intermediate-term PSA decrease were observed.Trial Registration: No trial registration was performed due to retrospective evaluation. [ABSTRACT FROM AUTHOR]

Purpose This study aims to extend the observation that the 12 Gy-radiosurgical-volume (V12Gy) correlates with the incidence of radiation necrosis in patients with intracranial tumors treated with radiosurgery by using target volume to predict V12Gy. V12Gy based on the target volume was used to predict the radiation necrosis probability ( P) directly. Also investigated was the reduction in radiation necrosis rates ( ΔP) as a result of optimizing the prescription isodose lines for linac-based SRS. Methods Twenty concentric spherical targets and 22 patients with brain tumors were retrospectively studied. For each case, a standard clinical plan and an optimized plan with prescription isodose lines based on gradient index were created. V12Gy were extracted from both plans to analyze the correlation between V12Gy and target volume. The necrosis probability P as a function of V12Gy was evaluated. To account for variation in prescription, the relation between V12Gy and prescription was also investigated. Results A prediction model for radiation-induced necrosis was presented based on the retrospective study. The model directly relates the typical prescribed dose and the target volume to the radionecrosis probability; V12Gy increased linearly with the target volume (R2 > 0.99). The linear correlation was then integrated into a logistic model to predict P directly from the target volume. The change in V12Gy as a function of prescription was modeled using a single parameter, s (=−1.15). Relatively large ΔP was observed for target volumes between 7 and 28 cm3 with the maximum reduction (8-9%) occurring at approximately 18 cm3. Conclusions Based on the model results, optimizing the prescription isodose line for target volumes between 7 and 28 cm3 results in a significant reduction in necrosis probability. V12Gy based on the target volume could provide clinicians a predictor of radiation necrosis at the contouring stage thus facilitating treatment decisions. [ABSTRACT FROM AUTHOR]

Background: Emerging techniques such as brain hypo-fractionated radiotherapy (HF-RT) involve complex cases with limited guidelines for plan quality and normal tissue tolerances. The purpose of the present study was to statistically parameterize irradiated volume independently of dose prescription, or margin to determine what spread in achievable irradiated volume one may expect for a given case.Methods: We defined EXT as the total tissue within the external contour of the patient (including the target) and we defined BMP as the contour of the brain minus PTV. Irradiated volumes of EXT and BMP at specific doses (i.e. 50, 60%, etc., of the prescribed dose) were extracted from 135 single-target HF-RT clinical cases, each planned with a single-arc, homogeneous (SAHO) approach in which target maximum dose (Dmax) was constrained to <130% of the prescribed dose. Irradiated volumes were subsequently measured for cases involving 2 targets (N = 29), 3 targets (N = 7) and >3 targets (N = 10) to investigate the effect of target number. We also examined the effect of shape complexity. A series of best fit curves with confidence and prediction intervals were generated for irradiated volume versus total target volume and the resulting model was subsequently validated on a subsequent set of 23 consecutive prospective cases not originally used in curve-fitting. A subset of 30 HF-RT cases were re-planned with a well-published four-arc, heterogeneous (FAHE) radiosurgery planning approach (Dmax could exceed 130%) to demonstrate how technique affects irradiated volume.Results: For SAHO, strong correlation (R2 > 0.98) was found for predicting irradiated volumes. For a given total target volume, irradiated-volume increased by a range of 1.4-2.9× for >3 versus single-targets depending on isodose level. Shape complexity had minor impact on irradiated volume. There was no statistical difference in irradiated volumes between validation and input data (p > 0.2). The FAHE-generated irradiated volumes yielded curves and prediction and confidence bands that agreed well with published data indicating that the proposed approach is feasible for cross-institutional comparisons.Conclusions: A description of irradiated volume for linac-based HF-RT is proposed based on population data. We have demonstrated that the proposed approach is feasible for inter and intra-institutional comparisons. [ABSTRACT FROM AUTHOR]

Objectives. Based on single-arm trial data (BOLT), sonidegib was approved in the US and EU to treat locally advanced basal cell carcinomas (BCCs) ineligible for curative surgery or radiotherapy. Vismodegib, the other approved targeted therapy, also was assessed in a single-arm trial (ERIVANCE). We examined the comparative effectiveness of the two drugs using a matching-adjusted indirect comparison (MAIC) versus an unadjusted indirect comparison. Methods. After comparing trials and identifying potential prognostic factors, an MAIC was conducted to adjust for differences in key patient baseline characteristics. Due to BOLT’s small sample size, the number of matching variables was restricted to two. Efficacy results for sonidegib were generated so that selected baseline characteristics matched those from ERIVANCE and were compared with published ERIVANCE results. Results. Matching variables were baseline percentages of patients receiving prior radiotherapy and surgery. After weighting, sonidegib objective response rate (ORR) and median progression-free survival (PFS) were effectively unchanged (prematched versus postmatched ORR and PFS, 56.1% versus 56.7% and 22.1 versus 22.1 months, resp.). Vismodegib’s ORR and PFS were 47.6% and 9.5 months. Conclusions. Comparative effectiveness of sonidegib versus vismodegib remains unchanged after adjusting BOLT patient-level data to match published ERIVANCE baseline percentages of patients receiving prior surgery and radiotherapy. [ABSTRACT FROM AUTHOR]

Aim To evaluate the impact of radiochromic film positioning relative to the central beam axis ( CAX) in proton beam therapy. Secondarily, to compare the dosimetric measurements obtained by RTQA and EBT film and to compare these to the doses calculated by the treatment planning system ( TPS). Methods The EBT and RTQA dosimetric radiochromic films were immersed in a water phantom and irradiated with a proton beam. The films were placed parallel to the CAX and at a 5° angle on the horizontal plane to assess the effect of film inclination on Bragg peak profiles. Calibration was performed by irradiating small pieces of film at doses ranging from 0.0 Gy to 3.5 Gy in increments of 0.5 Gy. The TPS was used to create treatment plans for two different geometrical targets (cylindrical and cuboidal). After irradiation, all film pieces were scanned on a flatbed scanner and red channel data were extracted from the 48-bit RGB images using ImageJ, Photoshop, Origin8, and Excel software. The dose distributions from the irradiated films were compared to the dose obtained from the TPS. Bragg peak profiles were abstracted from the irradiated films and compared. Results The dosimetric measurements obtained by both EBT and RTQA positioned at a 5° to the CAX closely matched the dose calculated by the TPS for the cylindrical target. In contrast, dose distributions measured in the cuboidal targets were less precise. Gamma index ( GI) values (3%/3 mm acceptance criteria for isodose >90% of dose) were 99.8% and 93% for EBT film placed at a 5° angle versus 47.1% and 80.8% for EBT film parallel to the beam. The dosimetric measurements in RTQA film positioned parallel to the CAX showed GI values with <27% agreement with the TPS-calculated dose. Conclusion Our finding show that RTQA film can be used to accurately measure doses in the proton beam at the region of Bragg peak; however, to obtain the most accurate readings, the film should be positioned at a small angle to the CAX. [ABSTRACT FROM AUTHOR]

Purpose: To report findings from an in vivo dosimetry program implemented for all stereotactic body radiation therapy patients over a 31-month period and discuss the value and challenges of utilizing in vivo electronic portal imaging device (EPID) dosimetry clinically.Methods and Materials: From December 2013 to July 2016, 117 stereotactic body radiation therapy-volumetric modulated arc therapy patients (100 lung, 15 spine, and 2 liver) underwent 602 EPID-based in vivo dose verification events. A developed model-based dose reconstruction algorithm calculates the 3-dimensional dose distribution to the patient by back-projecting the primary fluence measured by the EPID during treatment. The EPID frame-averaging was optimized in June 2015. For each treatment, a 3%/3-mm γ comparison between our EPID-derived dose and the Eclipse AcurosXB-predicted dose to the planning target volume (PTV) and the ≥20% isodose volume were performed. Alert levels were defined as γ pass rates <85% (lung and liver) and <80% (spine). Investigations were carried out for all fractions exceeding the alert level and were classified as follows: EPID-related, algorithmic, patient setup, anatomic change, or unknown/unidentified errors.Results: The percentages of fractions exceeding the alert levels were 22.6% for lung before frame-average optimization and 8.0% for lung, 20.0% for spine, and 10.0% for liver after frame-average optimization. Overall, mean (± standard deviation) planning target volume γ pass rates were 90.7% ± 9.2%, 87.0% ± 9.3%, and 91.2% ± 3.4% for the lung, spine, and liver patients, respectively.Conclusions: Results from the clinical implementation of our model-based in vivo dose verification method using on-treatment EPID images is reported. The method is demonstrated to be valuable for routine clinical use for verifying delivered dose as well as for detecting errors. [ABSTRACT FROM AUTHOR]

The aim is to study the density, isodose depths, and doses at different points in slab-pinewood-slab (SPS) phantom, solid phantom SP34 (made up of polystyrene), and chest level of actual patient for developing heterogeneous chest phantom mimicking thoracic region of human body. A 6 MV photon beam of field size of 10 cm × 10 cm was directed perpendicular to the surface of computed tomography (CT) images of chest level of patient, SPS phantom, and SP34 phantom. Dose was calculated using anisotropic analytical algorithm. Hounsfield units were used to calculate the density of each medium. Isodose depths in all the three sets of CT images were measured. Variations between planned doses on treatment planning system (TPS) and measured on linear accelerator (LA) were calculated for three points, namely, near slab-pinewood interfaces (6 and 18 cm depths) and 10 cm depth in SPS phantom and at the same depths in SP34 phantom. Density of pinewood, SP34 slabs, chest wall, lung, and soft tissue behind lung was measured as 0.329 ± 0.08, 0.999 ± 0.02, 0.898 ± 0.02, 0.291 ± 0.12, and 1.002 ± 0.03 g/cc, respectively. Depths of 100% and 90% isodose curves in all the three sets of CT images were found to be similar. Depths of 80%, 70%, 60%, 50%, and 40% isodose lines in SPS phantom images were found to be equivalent to that in chest images, while it was least in SP34 phantom images. Variations in doses calculated at 6, 10, and 18 cm depths on TPS and measured on LA were found to be 0.36%, 1.65%, and 2.23%, respectively, in case of SPS phantom, while 0.24%, 0.90%, and 0.93%, respectively, in case of SP34 slab phantom. SPS phantom seemed equivalent to the chest level of human body. Dosimetric results of this study indicate that patient-specific quality assurance can be done using chest phantom mimicking thoracic region of human body, which has been fabricated using polystyrene and pinewood. [ABSTRACT FROM AUTHOR]

Purpose: To test the hypothesis that intensity modulated radiation therapy (IMRT) reduces acute hematologic and gastrointestinal (GI) toxicity for patients with locoregionally advanced cervical cancer.Methods and Materials: We enrolled patients with stage IB-IVA cervical carcinoma in a single-arm phase II trial involving 8 centers internationally. All patients received weekly cisplatin concurrently with once-daily IMRT, followed by intracavitary brachytherapy, as indicated. The primary endpoint was the occurrence of either acute grade ≥3 neutropenia or clinically significant GI toxicity within 30 days of completing chemoradiation therapy. A preplanned subgroup analysis tested the hypothesis that positron emission tomography-based image-guided IMRT (IG-IMRT) would lower the risk of acute neutropenia. We also longitudinally assessed patients' changes in quality of life.Results: From October 2011 to April 2015, 83 patients met the eligibility criteria and initiated protocol therapy. The median follow-up was 26.0 months. The incidence of any primary event was 26.5% (95% confidence interval [CI] 18.2%-36.9%), significantly lower than the 40% incidence hypothesized a priori from historical data (P=.012). The incidence of grade ≥3 neutropenia and clinically significant GI toxicity was 19.3% (95% CI 12.2%-29.0%) and 12.0% (95% CI 6.7%-20.8%), respectively. Compared with patients treated without IG-IMRT (n=48), those treated with IG-IMRT (n=35) had a significantly lower incidence of grade ≥3 neutropenia (8.6% vs 27.1%; 2-sided χ2P=.035) and nonsignificantly lower incidence of grade ≥3 leukopenia (25.7% vs 41.7%; P=.13) and any grade ≥3 hematologic toxicity (31.4% vs 43.8%; P=.25).Conclusions: IMRT reduces acute hematologic and GI toxicity compared with standard treatment, with promising therapeutic outcomes. Positron emission tomography IG-IMRT reduces the incidence of acute neutropenia. [ABSTRACT FROM AUTHOR]

Introduction: 90 Sr/ 90 Y source has been used for the intravascular brachytherapy to prevent coronary restenosis in the patients who have undergone angioplasty. The aim of this research is to determine the dose distribution of 90 Sr/ 90 Y source in a water phantom. Materials and Methods: In the present work, MCNP code has been applied to calculate the dose distribution around a 3 cm length of 90 Sr/ 90 Y source in a 30×30×30 cm 3 water phantom. Also, the exact geometry of the source has been used in this simulation. Tally *F8:e which is suitable for beta ray dosimetry has been evaluated with less than %5 relative error in a sphere having 0.2 mm radius. Results: The isodose curve for 10, 20, 40, and 90% depth dose (PDD) were derived based on the calculated dose curves along the parallel and perpendicular axis to the source. Discussion and Conclusion: The results obtained in this work are in a good agreement with the experimental result published by Buckley et al. and the International Atomic Energy Agency (IAEA) report in a water phantom. Therefore, the result of this research can be used in the intravascular brachytherapy.

Objective To investigate gamma knife radiosurgery (GKS) for benign tumor-associated secondary trigeminal neuralgia (TN). Methods Between 2006 and 2015, 21 patients with secondary TN due to meningioma were treated using GKS. Their mean age was 56.5 ± 12.2 years. The 50% isodose was 12.5 ± 1.1 Gy for the first GKS for the meningioma. Retrogasserian targeting of the trigeminal nerve at 90 Gy with a 4-mm collimator was used for the second GKS. Results The pain duration until GKS was 1.9 ± 1.9 years. The meningiomas were located in the cisternal space in 13 patients (56.5%) and involved the skull base in 8 patients (43.5%). The mean duration of follow-up was 3.7 ± 2.7 years. The pain control outcome was a Marseilles Pain Scale (MPS) score of I to IV in 15 patients (71%) and a score of V in 6 patients (29%). For these latter patients, we performed a second GKS targeting the trigeminal nerve and resulting in MPS scores of I to IV. The tumor size did not increase in any patient and decreased by >10% in 12 (80%) of the 15 patients who were followed for at least 1 year. Trigeminal nerve visibility may improve after tumor shrinkage. Retrogasserian trigeminal nerve targets may be used even with invisible trigeminal nerves using Meckel's cave as an anatomic marker. Conclusions Here we show the reproducible feasibility of a 2-session GKS procedure using higher radiation doses, the first dose to treat the tumor and the second to treat the trigeminal nerves using retrogasserian targeting. [ABSTRACT FROM AUTHOR]

Purpose: Magnetic resonance imaging (MRI)-guided Co-60 provides daily and intrafractional MRI soft tissue imaging for improved target and critical organ tracking. To increase delivery efficiency, the system uses three Co-60 sources at 120? apart, allowing up to 600 cGy combined dose rate at isocenter. Despite the potential tripling in output, creating a delivery plan that uses all three sources is considerably unintuitive. Here, the authors computerize the triplet orientation optimization using column generation, an approach that was demonstrated effective in integrated beam orientation and fluence optimization for noncoplanar therapies. To achieve a better plan quality without increasing the treatment time, the authors then solve a fluence map optimization (FMO) problem while regularizing the fluence maps to reduce the number of deliverable MLC segments. Methods: Three patients--one prostate, one lung, and one head and neck boost plan (H&NBoost)-- were evaluated in this study. For each patient, the beamlet doses were calculated using Monte Carlo, under a 0.35 T magnetic field, for 180 equally spaced coplanar beams grouped into 60 triplets. The beamlet size is 1.05×0.5 cm determined by the MLC leaf thickness and step size. The triplets were selected using the column generation algorithm. The FMO problem was formulated using an L2-norm dose fidelity term and an L1-norm anisotropic total variation regularization term, which allows controlling the number of MLC segments, and hence the treatment time, with minimal degradation to the dose. The authors' Fluence Regularization and Optimized Selection of Triplets (FROST) plans were compared against the clinical treatment plans (CLNs) produced by an experienced dosimetrist. PTV homogeneity, max dose, mean dose, D95, D98, and D99 were evaluated. OAR max and mean doses, as well as R50, defined as the ratio of the 50% isodose volume over the planning target volume were investigated. Results: The mean PTV D95, D98, and D99 differ by +0.04%, +0.07%, and +0.25% of the prescription dose between planning methods. The mean PTV homogeneity was virtually same with values at 0.8788 (FROST) and 0.8812 (CLN). R50 decreased by 0.67 comparing FROST to CLN. On average, FROST reduced Dmax and Dmean of OARs by 7.30% and 6.08% of the prescription dose, respectively. The manual CLN planning processes required numerous trial and error runs. The FROST plans on the other hand required minimal human intervention. Conclusions: Efficient delivery of MRI-guided Co-60 therapy needs the output of multiple sources yet suffers from unintuitive and laborious manual beam selection processes. Computerized triplet orientation optimization improves both planning efficiency and plan dosimetry. The novel fluence map regularization provides additional controls over the number of MLC segments and treatment time. [ABSTRACT FROM AUTHOR]

Carbon ions are an up-and-coming ion species, currently being used in charged particle radiotherapy. As it is well established that there are considerable interindividual differences in radiosensitivity in the general population that can significantly influence clinical outcomes of radiotherapy, we evaluate the degree of these differences in the context of carbon ion therapy compared with conventional radiotherapy. In this study, we evaluate individual radiosensitivity following exposure to carbon-13 ions or γ-rays in peripheral blood lymphocytes of healthy individuals based on the frequency of ionizing radiation (IR)-induced DNA double strand breaks (DSBs) that was either misrepaired or left unrepaired to form chromosomal aberrations (CAs) (simply referred to here as DSBs for brevity). Levels of DSBs were estimated from the scoring of CAs visualized with telomere/centromere-fluorescence in situ hybridization (TC-FISH). We examine radiosensitivity at the dose of 2 Gy, a routinely administered dose during fractionated radiotherapy, and we determined that a wide range of DSBs were induced by the given dose among healthy individuals, with highly radiosensitive individuals harboring more IR-induced breaks in the genome than radioresistant individuals following exposure to the same dose. Furthermore, we determined the relative effectiveness of carbon irradiation in comparison to γ-irradiation in the induction of DSBs at each studied dose (isodose effect), a quality we term "relative dose effect" (RDE). This ratio is advantageous, as it allows for simple comparison of dose-response curves. At 2 Gy, carbon irradiation was three times more effective in inducing DSBs compared with γ-irradiation (RDE of 3); these results were confirmed using a second cytogenetic technique, multicolor-FISH. We also analyze radiosensitivity at other doses (0.2-15 Gy), to represent hypo- and hyperfractionation doses and determined that RDE is dose dependent: high ratios at low doses, and approaching 1 at high doses. These results could have clinical implications as IR-induced DNA damage and the ensuing CAs and genomic instability can have significant cellular consequences that could potentially have profound implications for long-term human health after IR exposure, such as the emergence of secondary cancers and other pathobiological conditions after radiotherapy. [ABSTRACT FROM AUTHOR]

Background and purpose: The human body is composed of various inhomogenous tissues with a variety of physical and radiological properties. These inhomogeneities could change isodose distributions, increase the probability of geometric errors, and eventually lead to missing of the target irradiation or incorrect isodose coverage in conformal radiation therapy (CRT) due to the uncertainties resulted from the effect of such inhomogeneties on isodose curves. In this study, the effect of inhomogeneities on dosimetric accuracy of the CRT of prostate was investigated using Monte Carlo simulation method. Materials and methods: An anthropomorphic pelvis phantom was used in two modes representing a homogeneous and heterogeneous phantom. Three dimensional (3D) CRT planning composed of five fields were performed on the CT images of the phantoms using the CorPLAN treatment planning system (TPS) of a 2100C/D Varian linac. Delivery of 3DCRT was also simulated by EGSnrc Monte Carlo code for the same conditions used in the CorPLAN TPS. The dose distributions resulted from the MC simulations were compared with those of the CorPLAN TPS for both of the phantoms based on the "dose difference (DD) percentages" and "distance to agreement (DTA)" parameters. Results: Findings indicated that the heterogeneity leads to an overdose estimation at the target location up to 2.8% and 4.4% for the 6 and 18 MV energies, respectively by the CorPLAN TPS compared with the MC simulation data. The average DD and DTA for the homogeneous phantom were 2.7%-3.4mm and 1.6%-2.3 mm while for the inhomogeneous phantom they were 5.5%-3.7 mm and 6.0%-2.5 mm at the 6 and 18 MV energies, respectively. Conclusion: Our results indicates that the accuracy of the dosimetry parameters estimated by the CorPLAN TPS at 18 MV is more than that of 6 MV energy. But, the heterogeneity deteriorates more the accuracy level of such dosimetry parameters estimated by this commercial TPS at 18 MV energy. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is based on the premise of accurate dose delivery to target volumes within a patient, while minimizing dose to surrounding tissues. Recent developments in the treatment of breast cancer have focused on “gating” the delivery of the treatment beams to minimize the effect of patient motion during treatment, and increasing separation between the target volume and organs at risk (OAR), such as lung, heart and left anterior descending coronary artery. The basic principle involves rapidly switching the treatment beam on or off depending on the patient breathing cycle. It is therefore important to know the characteristics of gated treatments such as latency. Methods: In this work an electrical PIN diode circuit (EPDC) was designed for quality assurance (QA) purposes to examine beam latency timing properties. Evaluation of the EPDC was performed on a TrueBeam™ (Varian, Palo Alto) linear accelerator and its internal gating system. The EPDC was coupled to a moving stage to simulate a binary pattern with fast beam triggering within predefined limits, the so called “gating window”. Pulses of radiation were measured with the PIN diode and the results were compared to measurements of current produced across the linac target. Processing of the beam pulses and calculation of the latency timings was performed by an Atmega328P microcontroller. Results: For beam-on latencies, 2.11 ms (6 MV) and 2.12 ms (10 MV) were measured using the PIN diode, compared to 2.13 ms (6 MV) and 2.15 ms (10 MV) using the target current signal. For beam-off latencies, 57.69 ms (6 MV) and 57.73 ms (10 MV) were measured using the PIN diode, compared to 57.33 ms (6 MV) and 56.01 ms (10 MV) using the target current. Conclusions: PIN diodes can be used for accurate determination of the beam-on and beam-off latency characteristics, which could potentially lead to improvements in gated radiotherapy treatments, for example optimizing the gating windows and in estimating dosimetric errors associated with treatment beam latencies. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this work is to examine the trade-off between prescription isodose and dose gradients in orthovoltage stereotactic radiosurgery. Methods: Point energy deposition kernels (EDKs) describing photon and electron transport were calculated using Monte Carlo methods. EDKs were generated from 10 to 250 keV, in 10 keV increments. The EDKs were converted to pencil beam kernels and used to calculate dose profiles through isocenter from a 4π isotropic delivery from all angles of circularly collimated beams. Monoenergetic beams and an orthovoltage polyenergetic spectrum were analyzed. The dose gradient index (DGI) is the ratio of the 50% prescription isodose volume to the 100% prescription isodose volume and represents a metric by which dose gradients in stereotactic radiosurgery (SRS) may be evaluated. Results: Using the 4π dose profiles calculated using pencil beam kernels, the relationship between DGI and prescription isodose was examined for circular cones ranging from 4 to 18 mm in diameter and monoenergetic photon beams with energies ranging from 20 to 250 keV. Values were found to exist for prescription isodose that optimize DGI. Conclusions: The relationship between DGI and prescription isodose was found to be dependent on both field size and energy. Examining this trade-off is an important consideration for designing optimal SRS systems. [ABSTRACT FROM AUTHOR]

Stereotactic Radiation Therapy is a type of external beam radiation therapy that delivers high dose to a relatively small target volume in one or few fractions, a technique that requires extremely conformal dose distributions, so the highest dose being delivered centrally in the tumor volume with a rapid fall off of dose to spare the adjacent healthy tissue. The dose is prescribed to the tumor periphery, usually to the 80% isodose (60-90%), the aim being that 95% of the target volume (PTV) is conformally covered by the prescription isodose surface and 99% of the target volume (PTV) receives a minimum of 90% of the prescription. Stereotactic radiotherapy can be used as a primary therapy for early stage primitive cancer or metastatic tumors (cranial or extra-cranial tumors), for patients in a good health conditions, with minimum 6 months life expectancy, and relatively small tumors. [ABSTRACT FROM AUTHOR]

Purpose: To provide a comprehensive characterization of a novel respiratory surrogate that uses optical surface imaging (OSI) for accurate tidal volume (TV) measurement, dynamic airflow (TV') calculation, and quantitative breathing pattern (BP) estimation during free breathing (FB), belly breathing (BB), chest breathing (CB), and breath hold (BH). Methods: Optical surface imaging, which captures all respiration-induced torso surface motion, was applied to measure respiratory TV, TV', and BP in three common breathing patterns. Eleven healthy volunteers participated in breathing experiments with concurrent OSI-based and conventional spirometric measurements under an institutional review board approved protocol. This OSI-based technique measures dynamic TV from torso volume change (▵ Vtorso = TV) in reference to full exhalation and airflow (TV'= dTV/dt). Volume conservation, excluding exchanging air, was applied for OSI-based measurements under negligible pleural pressure variation in FB, BB, and CB. To demonstrate volume conservation, a constant TV was measured during BH while the chest and belly are moving ("pretended" respiration). To assess the accuracy of OSI-based spirometry, a conventional spirometer was used as the standard for both TV and TV'. Using OSI, BP was measured as BPOSI = ▵ Vchest /▵ Vtorso and BP can be visualized using BPSHI = SHIchest/(SHIchest+SHIbelly), where surface height index (SHI) is defined as the mean vertical distance within a region of interest on the torso surface. A software tool was developed for OSI image processing, volume calculation, and BP visualization, and another tool was implemented for data acquisition using a Bernoulli-type spirometer. Results: The accuracy of the OSI-based spirometry is -21±33 cm3 or -3.5%±6.3%averaged from 11 volunteers with 76±28 breathing cycles on average in FB. Breathing variations between two separate acquisitions with approximate 30-min intervals are substantial: -1%±34% (ranging from -64% to 40%) in TV, 4%±20% (ranging from -50% to 26%) in breathing period (T), and -1%±34% (ranging from-49%to44%)inBP. The airflowaccuracy and variation (between two exercises) are-1±54cm3/s and -5%±30%, respectively. The slope of linear regression between OSI-TV and spirometric TV is 0.93 (R2 = 0.95) for FB, 0.96 (R2 = 0.98) for BB, and 0.95 (R2 = 0.95) for CB. The correlation between the two spirometric measurements is 0.98±0.01. BP increases from BB, FB to CB, while TV increases from FB, BB, to CB. Under BH, 4% volume variation (range) on average was observed. Conclusions: The OSI-based technique provides an accurate measurement of tidal volume, airflow rate, and breathing pattern; all affect internal organ motion. This technique can be applied to various breathing patterns, including FB, BB, and CB. Substantial breathing irregularities and irreproducibility were observed and quantified with the OSI-based technique. These breathing parameters are useful to quantify breathing conditions, which could be used for effective tumor motion predictions. [ABSTRACT FROM AUTHOR]