Method to assess the need for re-planning HDR brachytherapy tandem and ring treatments.

High dose rate (HDR) brachytherapy procedures for cervical cancer require multiple applicator insertions for multiple (typically 5) fractions of a single plan, which carries a risk for variability in applicator position between fractions. Due to applicator displacement relative to patient anatomy, the dose to nearby organs-at-risk (OARs) may vary significantly from one fraction to the next. The purpose of this study was to evaluate the effect of changes in HDR tandem and ring (T&R) applicator position on doses to nearby OARs and to present a quick and simple method to estimate doses to OARs inter-fractionally without having to perform a re-plan. Ninety CT image sets for 20 patients, ages 44 to 86, undergoing T&R-based HDR for cervical cancer were used retrospectively for this study. Measures of applicator positional and angular changes relative to the bony anatomy were obtained using image fusion in MIM software, between the planning CT (plan CT) and the CT on the treatment day (CT-TX). Dosimetric data were determined, also using MIM software, using the original (first fraction) dose distribution applied to organs at risk (rectum and bladder), transferred via rigid registration from the plan CT to each CT-TX. Bladder and rectum contours were also transferred from each plan CT to each CT-TX and were tweaked manually to match anatomy on each CT-TX and examined visually for appropriateness. Differences in translation and rotation of the T&R applicator between the planning CT and subsequent individual fractions were recorded and plotted against dose differences between each fraction of treatment and the original (first) fraction. Absolute dose (D2cc) and volume (V50) differences vs positional shifts were calculated and plotted, and the Pearson Product-Moment correlation coefficient between dose parameters and measured positional shifts was determined. Average dosimetric differences between planned dose and subsequent fractional doses obtained through rigid registration were 1.48 ± 1.92 Gy, 14.91 ± 11.92 cm3, 0.56 ± 0.93 Gy, and 1.77 ± 2.18 cm3 for Bladder D2cc, Bladder V50, Rectum D2cc, and Rectum V50, respectively. Correlation between Bladder V50 and sagittal plane rotation gave an r2 of 0.4, showing the most correlation of all parameters studied. Bladder dose and volume increased by a maximum of about 2.7 Gy and 50 cm3 overall for Bladder D2cc and Bladder V50, respectively. Bladder V50 was most sensitive to T&R applicator displacements. We have quantified the effects of applicator positional changes on dose changes for the bladder and rectum. Even large changes in applicator position between fractions did not result in significant changes in dose to these normal tissues, indicating that adaptive re-planning is not necessary.

Considerations for intensity modulated total body or total marrow and lymphoid irradiation.

We compiled a sampling of the treatment techniques of intensity-modulated total body irradiation, total marrow irradiation and total marrow and lymphoid irradiation utilized by several centers across North America and Europe. This manuscript does not serve as a consensus guideline, but rather is meant to serve as a convenient reference for centers that are considering starting an intensity-modulated program.

Excitatory-inhibitory modulation of transcranial focus ultrasound stimulation on human motor cortex.

AIMS: Transcranial focus ultrasound stimulation (tFUS) is a promising non-invasive neuromodulation technology. This study aimed to evaluate the modulatory effects of tFUS on human motor cortex (M1) excitability and explore the mechanism of neurotransmitter-related intracortical circuitry and plasticity. METHODS: Single pulse transcranial magnetic stimulation (TMS)-eliciting motor-evoked potentials (MEPs) were used to assessed M1 excitability in 10 subjects. Paired-pulse TMS was used to measure the effects of tFUS on GABA- and glutamate-related intracortical excitability and 1 H-MRS was used to assess the effects of repetitive tFUS on GABA and Glx (glutamine + glutamate) neurometabolic concentrations in the targeting region in nine subjects. RESULTS: The etFUS significantly increased M1 excitability, decreased short interval intracortical inhibition (SICI) and long interval intracortical inhibition (LICI). The itFUS significantly suppressed M1 excitability, increased SICI, LICI, and decreased intracortical facilitation (ICF). Seven times of etFUS decreased the GABA concentration (6.32%), increased the Glx concentration (12.40%), and decreased the GABA/Glx ratio measured by MRS, while itFUS increased the GABA concentration (18.59%), decreased Glx concentration (0.35%), and significantly increased GABA/Glx ratio. CONCLUSION: The findings support that tFUS with different parameters can exert excitatory and inhibitory neuromodulatory effects on the human motor cortex. We provide novel insights that tFUS change cortical excitability and plasticity by regulating excitatory-inhibition balance related to the GABAergic and glutamatergic receptor function and neurotransmitter metabolic level.

Implementing failure mode and effect analysis to improve the safety of volumetric modulated arc therapy for total body irradiation.

PURPOSE: Volumetric-modulated arc therapy for total body irradiation (VMAT-TBI) is a novel radiotherapy technique that has been implemented at our institution. The purpose of this work is to investigate possible failure modes (FMs) in the treatment process and to develop a quality control (QC) program for VMAT-TBI following TG-100 guidelines. METHODS: We formed a multidisciplinary team to map out the complete treatment process of VMAT-TBI following the AAPM TG-100 guidelines. This process map gives a visual representation of the VMAT-TBI workflow from the CT simulation, image processing, contouring, treatment planning, to treatment delivery. From the process map, potential FMs were identified. The occurrence (O), detectability (D), and severity of impact (S) of each FM were assigned according to scoring criteria (1-10) by the multidisciplinary team. A risk priority number (RPN) was calculated from average O, S, and D of each FM (RPN = O x S x D). High risk FMs were identified as 20% of the FMs having the highest RPN scores. After the FMEA analysis, fault-tree analysis (FTA) was performed for each major step of the treatment process to determine the effects of potential failures to the treatment outcome. Effective QC methods were identified to prevent the high risk failures and to improve the safety of the VMAT-TBI program. RESULTS: We identified a total of 55 sub-processes and 128 FMs from the VMAT-TBI workflow. The top five high-risk FMs were: (1) Prescription and/or OAR constraints changed during planning and not communicated to the planner, (2) Patient moves or breathes too heavily during the upper body CT scan (3) Patient moves during the lower body CT scan, (4) Treatment planning system not calculating total body DVH metrics correctly for TBI, (5) Improper optimization criteria used or not sufficient optimization, resulting in suboptimal dose coverage, OAR sparing or excessive hotspots during treatment planning. Two FMs have average severity scores ≥8: Incorrect PTV subdivision/isocenter placement and Prescription and/or OAR constraints changed during planning and not communicated to the planner. Quality assurance and QC interventions including staff training, standard operating procedures, and quality checklists were implemented based on the FMEA and FTA. CONCLUSION: FM and effect analysis was performed to identify high-risk FMs of our VMAT-TBI program. FMEA and FTA were effective in identifying potential FMs and determining the best quality management (QM) measures to implement in the VMAT-TBI program.

Online verification of breath-hold reproducibility using kV-triggered imaging for liver stereotactic body radiation therapy.

PURPOSE: To introduce a new technique for online breath-hold verification for liver stereotactic body radiation therapy (SBRT) based on kilovoltage-triggered imaging and liver dome positions. MATERIAL AND METHODS: Twenty-five liver SBRT patients treated with deep inspiration breath-hold were included in this IRB-approved study. To verify the breath-hold reproducibility during treatment, a KV-triggered image was acquired at the beginning of each breath-hold. The liver dome position was visually compared with the expected upper/lower liver boundaries created by expanding/contracting the liver contour 5 mm in the superior-inferior direction. If the liver dome was within the boundaries, delivery continued; otherwise, beam was held manually, and the patient was instructed to take another breath-hold until the liver dome fell within boundaries. The liver dome was delineated on each triggered image. The mean distance between the delineated liver dome to the projected planning liver contour was defined as liver dome position error edome . The mean and maximum edome of each patient were compared between no breath-hold verification (all triggered images) and with online breath-hold verification (triggered images without beam-hold). RESULTS: Seven hundred thirteen breath-hold triggered images from 92 fractions were analyzed. For each patient, an average of 1.5 breath-holds (range 0-7 for all patients) resulted in beam-hold, accounting for 5% (0-18%) of all breath-holds; online breath-hold verification reduced the mean edome from 3.1 mm (1.3-6.1 mm) to 2.7 mm (1.2-5.2 mm) and the maximum edome from 8.6 mm (3.0-18.0 mm) to 6.7 mm (3.0-9.0 mm). The percentage of breath-holds with edome >5 mm was reduced from 15% (0-42%) without breath-hold verification to 11% (0-35%) with online breath-hold verification. online breath-hold verification eliminated breath-holds with edome >10 mm, which happened in 3% (0-17%) of all breath-holds. CONCLUSION: It is clinically feasible to monitor the reproducibility of each breath-hold during liver SBRT treatment using triggered images and liver dome. Online breath-hold verification improves the treatment accuracy for liver SBRT.

Transperineal ultrasound is a good alternative for intra-fraction motion monitoring for prostate stereotactic body radiotherapy.

PURPOSES: To report our experience in a prospective study of implementing a transperineal ultrasound system to monitor intra-fractional prostate motion for prostate stereotactic body radiotherapy (SBRT). MATERIAL AND METHODS: This IRB-approved prospective study included 23 prostate SBRT patients treated between 04/2016 and 11/2019 at our institution. The prescription doses were 36.25 Gy to the Low-Dose planning target volume (LD-PTV) and 40 Gy to the High-Dose PTV (HD-PTV) in five fractions with 3 mm planning margins. The transperineal ultrasound system was successfully used in 110 of the 115 fractions. For intra-fraction prostate motion, the real-time prostate displacements measured by ultrasound were exported for analysis. The percentage of time prostate movement exceeded a 2 mm threshold was calculated for each fraction of all patients. T-test was used for all statistical comparisons. RESULTS: Ultrasound image quality was adequate for prostate delineation and prostate motion tracking. The setup time for each fraction under ultrasound-guided prostate SBRT was 15.0 ± 4.9 min and the total treatment time per fraction was 31.8 ± 10.5 min. The presence of an ultrasound probe did not compromise the contouring of targets or critical structures. For intra-fraction motion, prostate movement exceeded 2 mm tolerance in 23 of 110 fractions for 11 of 23 patients. For all fractions, the mean percentage of time when the prostate moved more than 2 mm in any direction during each fraction was 7%, ranging from 0% to 62% of a fraction. CONCLUSION: Ultrasound-guided prostate SBRT is a good option for intra-fraction motion monitoring with clinically acceptable efficiency.

Neuroinflammation mechanisms of neuromodulation therapies for anxiety and depression.

Mood disorders are associated with elevated inflammation, and the reduction of symptoms after multiple treatments is often accompanied by pro-inflammation restoration. A variety of neuromodulation techniques that regulate regional brain activities have been used to treat refractory mood disorders. However, their efficacy varies from person to person and lack reliable indicator. This review summarizes clinical and animal studies on inflammation in neural circuits related to anxiety and depression and the evidence that neuromodulation therapies regulate neuroinflammation in the treatment of neurological diseases. Neuromodulation therapies, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES), electroconvulsive therapy (ECT), photobiomodulation (PBM), transcranial ultrasound stimulation (TUS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS), all have been reported to attenuate neuroinflammation and reduce the release of pro-inflammatory factors, which may be one of the reasons for mood improvement. This review provides a better understanding of the effective mechanism of neuromodulation therapies and indicates that inflammatory biomarkers may serve as a reference for the assessment of pathological conditions and treatment options in anxiety and depression.

Contour similarity and its implication on inverse prostate SBRT treatment planning.

PURPOSE: Success of auto-segmentation is measured by the similarity between auto and manual contours that is often quantified by Dice coefficient (DC). The dosimetric impact of contour variability on inverse planning has been rarely reported. The main aim of this study is to investigate whether automatically generated organs-at-risk (OARs) could be used in inverse prostate stereotactic body radiation therapy (SBRT) planning and whether the dosimetric parameters are still clinically acceptable after radiation oncologists modify the OARs. METHODS AND MATERIALS: Planning computed tomography images from 10 patients treated with SBRT for prostate cancer were selected and automatically segmented by commercially available atlas-based software. The automatically generated OAR contours were compared with the manually drawn contours. Two volumetric modulated arc therapy (VMAT) plans, autoRec-VMAT (where only automatically generated rectums were used in optimization) and autoAll-VMAT (where automatically generated OARs were used in inverse optimization) were generated. Dosimetric parameters based on the manually drawn PTV and OARs were compared with the clinically approved plans. RESULTS: The DCs for the rectum contours varied from 0.55 to 0.74 with a mean value of 0.665. Differences of D95 of the PTV between autoRec-VMAT and manu-VMAT plans varied from 0.03% to -2.85% with a mean value of -0.64%. Differences of D0.03cc of manual rectum between the two plans varied from -0.86% to 9.94% with a mean value of 2.71%. D95 of PTV between autoAll-VMAT and manu-VMAT plans varied from 0.28% to -2.9% with a mean value -0.83%. Differences of D0.03cc of manual rectum between the two plans varied from -0.76% to 6.72% with a mean value of 2.62%. CONCLUSION: Our study implies that it is possible to use unedited automatically generated OARs to perform initial inverse prostate SBRT planning. After radiation oncologists modify/approve the OARs, the plan qualities based on the manually drawn OARs are still clinically acceptable, and a re-optimization may not be needed.

OpenKBP-Opt: an international and reproducible evaluation of 76 knowledge-based planning pipelines.

Objective.To establish an open framework for developing plan optimization models for knowledge-based planning (KBP).Approach.Our framework includes radiotherapy treatment data (i.e. reference plans) for 100 patients with head-and-neck cancer who were treated with intensity-modulated radiotherapy. That data also includes high-quality dose predictions from 19 KBP models that were developed by different research groups using out-of-sample data during the OpenKBP Grand Challenge. The dose predictions were input to four fluence-based dose mimicking models to form 76 unique KBP pipelines that generated 7600 plans (76 pipelines × 100 patients). The predictions and KBP-generated plans were compared to the reference plans via: the dose score, which is the average mean absolute voxel-by-voxel difference in dose; the deviation in dose-volume histogram (DVH) points; and the frequency of clinical planning criteria satisfaction. We also performed a theoretical investigation to justify our dose mimicking models.Main results.The range in rank order correlation of the dose score between predictions and their KBP pipelines was 0.50-0.62, which indicates that the quality of the predictions was generally positively correlated with the quality of the plans. Additionally, compared to the input predictions, the KBP-generated plans performed significantly better (P< 0.05; one-sided Wilcoxon test) on 18 of 23 DVH points. Similarly, each optimization model generated plans that satisfied a higher percentage of criteria than the reference plans, which satisfied 3.5% more criteria than the set of all dose predictions. Lastly, our theoretical investigation demonstrated that the dose mimicking models generated plans that are also optimal for an inverse planning model.Significance.This was the largest international effort to date for evaluating the combination of KBP prediction and optimization models. We found that the best performing models significantly outperformed the reference dose and dose predictions. In the interest of reproducibility, our data and code is freely available.

Image-guided volumetric-modulated arc therapy of total body irradiation: An efficient workflow from simulation to delivery.

INTRODUCTION: Using multi-isocenter volumetric-modulated arc therapy (VMAT) for total body irradiation (TBI) may improve dose uniformity and vulnerable tissue protection compared with classical whole-body field technique. Two drawbacks limit its application: (1) VMAT-TBI planning is time consuming; (2) VMAT-TBI plans are sensitive to patient positioning uncertainties due to beam matching. This study presents a robust planning technique with image-guided delivery to improve dose delivery accuracy. In addition, a streamlined sim-to-treat workflow with automatic scripts is proposed to reduce planning time. MATERIALS: Twenty-five patients were included in this study. Patients were scanned in supine head-first and feet-first directions. An automatic workflow was used to (1) create a whole-body CT by registering two CT scans, (2) contour lungs, kidneys, and planning target volume (PTV), (3) divide PTV into multiple sub-targets for planning, and (4) place isocenters. Treatment planning included feathered AP/PA beams for legs/feet and VMAT for the body. VMAT-TBI was evaluated for plan quality, planning/delivery time, and setup accuracy using image guidance. RESULTS: VMAT-TBI planning time can be reduced to a day with automatic scripts. Treatment time took around an hour per fraction. VMAT-TBI improved dose coverage (PTV V100 increased from 76.8 ± 10.5 to 88.5 ± 2.6; p < 0.001) and reduced lung dose (lung mean dose reduced from 10.8 ± 0.7 Gy to 9.4 ± 0.8 Gy, p < 0.001) compared with classic AP/PA technique. CONCLUSION: A VMAT-TBI sim-to-treat workflow with robust planning and image-guided delivery was proposed. VMAT-TBI improved the plan quality compared with classical whole-body field techniques.

Combining automatic plan integrity check (APIC) with standard plan document and checklist method to reduce errors in treatment planning.

PURPOSE/OBJECTIVES: To report our experience of combining three approaches of an automatic plan integrity check (APIC), a standard plan documentation, and checklist methods to minimize errors in the treatment planning process. MATERIALS/METHODS: We developed APIC program and standardized plan documentation via scripting in the treatment planning system, with an enforce function of APIC usage. We used a checklist method to check for communication errors in patient charts (referred to as chart errors). Any errors in the plans and charts (referred to as the planning errors) discovered during the initial chart check by the therapists were reported to our institutional Workflow Enhancement (WE) system. Clinical Implementation of these three methods is a progressive process while the APIC was the major progress among the three methods. Thus, we chose to compared the total number of planning errors before (including data from 2013 to 2014) and after (including data from 2015 to 2018) APIC implementation. We assigned the severity of these errors into five categories: serious (S), near miss with safety net (NM), clinical interruption (CLI), minor impediment (MI), and bookkeeping (BK). The Mann-Whitney U test was used for statistical analysis. RESULTS: A total of 253 planning error forms, containing 272 errors, were submitted during the study period, representing an error rate of 3.8%, 3.1%, 2.1%, 0.8%, 1.9% and 1.3% of total number of plans in these years respectively. A marked reduction of planning error rate in the S and NM categories was statistically significant (P < 0.01): from 0.6% before APIC to 0.1% after APIC. The error rate for all categories was also significantly reduced (P < 0.01), from 3.4% before APIC and 1.5% per plan after APIC. CONCLUSION: With three combined methods, we reduced both the number and the severity of errors significantly in the process of treatment planning.

Automated planning of whole breast irradiation using hybrid IMRT improves efficiency and quality.

PURPOSE: To develop an automated workflow for whole breast irradiation treatment planning using hybrid intensity modulated radiation therapy (IMRT) approach and to demonstrate that this workflow can improve planning quality and efficiency when compared to manual planning. METHODS: The auto planning framework was built based on scripting with MIM and Pinnacle systems. MIM workflows were developed to automatically segment normal structures and targets, identify landmarks for beam placement, select beam energies, and set beam configurations. Pinnacle scripts were generated from the MIM workflow to create hybrid IMRT plans automatically. Each hybrid IMRT plan included two prescriptions: a three-dimensional (3D) prescription consisted of two open tangent beams, and an IMRT prescription consisted of two step-and-shoot IMRT beams. The 3D prescription delivered a full prescription dose to the maximum dose point, and the IMRT prescription was optimized to deliver a uniform dose to the entire breast while sparing dose to the normal structures. For 30 patients, the auto plans were compared with clinically accepted manual plans using the paired sample t-test. RESULTS: The auto planning process took approximately 8 min to complete. The mean dice coefficients between auto-segmentation and manual contours were 0.98, 0.94 and 0.88 for the lungs, heart, and PTVeval_Breast, respectively. The MUs of the auto plans was on average 13% higher than that of the manual plans. Auto planning improved plan quality significantly: percentage volume receiving 95% of the prescription dose (V95%) of the PTVeval_Breast increased from 91.5% to 93.2% (P = 0.001), V105% of the PTVeval_Breast decreased from 7.2% to 1.2% (P = 0.013), V20Gy of the ipsilateral lung decreased from 13.1% to 10.4% (P = 0.001) and mean heart dose for left-sided breast patients decreased from 1.2 Gy to 0.9 Gy (P < 0.001). CONCLUSION: An automated treatment planning process can make the planning process efficient with improved plan quality.

Assessment of Setup Accuracy Using Anatomical Landmarks for Breast and Chest Wall Irradiation With Surface Guided Radiation Therapy.

PURPOSE: This study aimed to determine setup accuracy using anatomic landmarks for breast irradiation with and without surface guided radiation therapy (SGRT) and assess setup time with SGRT. METHODS AND MATERIALS: This study included 115 patients with 1945 treatment fractions. Patients were treated with 4 techniques: tangents, tangents using deep-inspiration breath hold, and tangents with regional nodal irradiation with and without deep-inspiration breath hold. A total of 915 portal verification images were analyzed to determine setup errors for the skin, chest wall (CW), and heart. Setup error at each landmark was defined as the mean and maximum distances between the projected planning structure and the delineated structure on the portal image. Setup time for each fraction was determined using 2 recorded time outs: one upon the patient entering the treatment room and another before radiation beam on. RESULTS: Setup errors for the skin were significantly reduced with SGRT for all 4 treatment techniques (P < .001). On average, the mean and maximum errors for the skin decreased from 3.5 mm to 2.3 mm (P < .001) and from 7.6 mm to 5.6 mm (P < .001), respectively. Setup errors for the CW were not significantly different for tangent treatments, but significantly different for locoregional treatments. For all patients, the average mean and maximum errors for the CW were reduced from 3.1 mm to 3.0 mm (P = .21) and from 6.1 mm to 5.5 mm (P = .001), respectively. No significant change in setup errors for the heart was observed. Setup times with SGRT were slightly longer (P < .01), and the average setup time increased from 5.4 to 6.3 minutes. CONCLUSIONS: Using anatomic landmarks, we confirm that SGRT improved patient setup accuracy with a slight, but clinically nonsignificant increase in setup time.

The dosimetric impact of single, dual, and triple tandem applicators in the treatment of intact uterine cancer.

PURPOSE: To identify an optimal afterloading technique for high-dose-rate brachytherapy treatments in patients with medically inoperable uterine cancer. METHODS AND MATERIALS: Eighteen treatment plans were generated using point and volume-based techniques for three patients using a single, dual, and triple tandem. Dosimetric parameters of the target and critical structures were evaluated. RESULTS: Similar target coverage was achieved for each patient using volume-based planning; however, differences were evident when comparing point-based plans for the three applicators. In Patient 1, with a cylindrical uterus (8 cm by 4.5 cm), similar results were achieved with all three applicators (V95 [Single]=90.6%, V95 [Dual]=90.6%, and V95 [Triple]=91.5%). In Patient 2, who had a more spherical uterus (5 cm by 5.4 cm), the dual tandem was inferior to the others (V95=65.9% vs. 83.7% with triple and 85.8% with single tandem). Analysis of isodose distributions showed that the dual tandem failed to achieve adequate coverage of the central portion of the fundus. In Patient 3, who had a uterus (6 cm by 5.5 cm) in close proximity to the bladder (0.5 cm) and bowel, both the triple and dual tandem point-based plans achieved better coverage than the single tandem, given dose constraints on the bladder and bowel, with uterus V95 of 83.4% (Triple), 84.9% (Dual), and 73.7% (Single), respectively. CONCLUSIONS: For inoperable uterine cancer, optimal high-dose-rate applicator selection depends on the anatomy and location of the uterus and critical organs. The triple tandem applicator provides greater latitude in dose and anatomic uterus coverage as compared with either single or dual tandem applicators.

Real time 4D IMRT treatment planning based on a dynamic virtual patient model: proof of concept.

PURPOSE: To develop a novel four-dimensional (4D) intensity modulated radiation therapy (IMRT) treatment planning methodology based on dynamic virtual patient models. METHODS: The 4D model-based planning (4DMP) is a predictive tracking method which consists of two main steps: (1) predicting the 3D deformable motion of the target and critical structures as a function of time during treatment delivery; (2) adjusting the delivery beam apertures formed by the dynamic multi-leaf collimators (DMLC) to account for the motion. The key feature of 4DMP is the application of a dynamic virtual patient model in motion prediction, treatment beam adjustment, and dose calculation. A lung case was chosen to demonstrate the feasibility of the 4DMP. For the lung case, a dynamic virtual patient model (4D model) was first developed based on the patient's 4DCT images. The 4D model was capable of simulating respiratory motion of different patterns. A model-based registration method was then applied to convert the 4D model into a set of deformation maps and 4DCT images for dosimetric purposes. Based on the 4D model, 4DMP treatment plans with different respiratory motion scenarios were developed. The quality of 4DMP plans was then compared with two other commonly used 4D planning methods: maximum intensity projection (MIP) and planning on individual phases (IP). RESULTS: Under regular periodic motion, 4DMP offered similar target coverage as MIP with much better normal tissue sparing. At breathing amplitude of 2 cm, the lung V20 was 23.9% for a MIP plan and 16.7% for a 4DMP plan. The plan quality was comparable between 4DMP and IP: PTV V97 was 93.8% for the IP plan and 93.6% for the 4DMP plan. Lung V20 of the 4DMP plan was 2.1% lower than that of the IP plan and Dmax to cord was 2.2 Gy higher. Under a real time irregular breathing pattern, 4DMP had the best plan quality. PTV V97 was 90.4% for a MIP plan, 88.6% for an IP plan and 94.1% for a 4DMP plan. Lung V20 was 20.1% for the MIP plan, 17.8% for the IP plan and 17.5% for the 4DMP plan. The deliverability of the real time 4DMP plan was proved by calculating the maximum leaf speed of the DMLC. CONCLUSIONS: The 4D model-based planning, which applies dynamic virtual patient models in IMRT treatment planning, can account for the real time deformable motion of the tumor under different breathing conditions. Under regular motion, the quality of 4DMP plans was comparable with IP and superior to MIP. Under realistic motion in which breathing amplitude and period change, 4DMP gave the best plan quality of the three 4D treatment planning techniques.

Three dimensional intensity modulated brachytherapy (IMBT): dosimetry algorithm and inverse treatment planning.

PURPOSE: The feasibility of intensity modulated brachytherapy (IMBT) to improve dose conformity for irregularly shaped targets has been previously investigated by researchers by means of using partially shielded sources. However, partial shielding does not fully explore the potential of IMBT. The goal of this study is to introduce the concept of three dimensional (3D) intensity modulated brachytherapy and solve two fundamental issues regarding the application of 3D IMBT treatment planning: The dose calculation algorithm and the inverse treatment planning method. METHODS: A 3D IMBT treatment planning system prototype was developed using the MATLAB platform. This system consists of three major components: (1) A comprehensive IMBT source calibration method with dosimetric inputs from Monte Carlo (EGSnrc) simulations; (2) a "modified TG-43" (mTG-43) dose calculation formalism for IMBT dosimetry; and (3) a physical constraint based inverse IMBT treatment planning platform utilizing a simulated annealing optimization algorithm. The model S700 Axxent electronic brachytherapy source developed by Xoft, Inc. (Fremont, CA), was simulated in this application. Ten intracavitary accelerated partial breast irradiation (APBI) cases were studied. For each case, an "isotropic plan" with only optimized source dwell time and a fully optimized IMBT plan were generated and compared to the original plan in various dosimetric aspects, such as the plan quality, planning, and delivery time. The issue of the mechanical complexity of the IMBT applicator is not addressed in this study. RESULTS: IMBT approaches showed superior plan quality compared to the original plans and tht isotropic plans to different extents in all studied cases. An extremely difficult case with a small breast and a small distance to the ribs and skin, the IMBT plan minimized the high dose volume V200 by 16.1% and 4.8%, respectively, compared to the original and the isotropic plans. The conformity index for the target was increased by 0.13 and 0.04, respectively. The maximum dose to the skin was reduced by 56 and 28 cGy, respectively, per fraction. Also, the maximum dose to the ribs was reduced by 104 and 96 cGy, respectively, per fraction. The mean dose to the ipsilateral and contralateral breasts and lungs were also slightly reduced by the IMBT plan. The limitations of IMBT are the longer planning and delivery time. The IMBT plan took around 2 h to optimize, while the isotropic plan optimization could reach the global minimum within 5 min. The delivery time for the IMBT plan is typically four to six times longer than the corresponding isotropic plan. CONCLUSIONS: In this study, a dosimetry method for IMBT sources was proposed and an inverse treatment planning system prototype for IMBT was developed. The improvement of plan quality by 3D IMBT was demonstrated using ten APBI case studies. Faster computers and higher output of the source can further reduce plan optimization and delivery time, respectively.

Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source.

A low-energy electronic brachytherapy source (EBS), the model S700 Axxent x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V(100) reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95.2% in water phantoms without RBE enhancement (planned BED). About 10% increase in the source output is required to raise BED PTV V(100) to 95%. As a conclusion, the composite effect of dose reduction in the target due to heterogeneities and RBE enhancement results in a net effect of 5.3% target BED coverage loss for electronic brachytherapy. Therefore, it is suggested that about 10% increase in the source output may be necessary to achieve sufficient target coverage higher than 95%.

Specific absorbed fractions for internal electron emitters derived for a set of anatomically realistic reference pregnant female models.

The specific absorbed fraction (Phi), defined by the Medical Internal Radiation Dose Committee, is generally applied to evaluate the average absorbed dose in a target organ as a result of radioactive materials deposited in a source organ. This paper reports a new set of Phi values for internal electron emitters ranging from 10 keV to 4 MeV from various internal organs of the mother to the fetus based on three newly developed pregnant female tomographic models, called RPI-P3, RPI-P6 and RPI-P9. The results show a linear log relationship between Phi values and electron energy. The linear log coefficients have been derived and reported. The relationship between Phi values and mean distances between source organs and the fetus were also determined to allow for individual dosimetry. Since the RPI-P models have finer details of human anatomy and more realistic organ volumes and geometries, which follow the latest ICRP reference values, the newly derived Phi values could be used as reference values in determination of the dose to the fetus from internal electron emitters.