Intensity-modulated Brachytherapy Research Articles

The dosimetric accuracy of a commercial model-based dose calculation algorithm in modeling a six-groove direction modulated brachytherapy tandem applicator

Objective.With advancements in high-dose rate brachytherapy, the clinical translation of intensity modulated brachytherapy (IMBT) innovations necessitates utilization of model-based dose calculation algorithms (MBDCA) for accurate and rapid dose calculations. This study uniquely benchmarks a commercial MBDCA, BrachyVision ACUROSTM(BVA), against Monte Carlo (MC) simulations, evaluating dose distributions for a novel IMBT applicator, termed as thesix-grooveDirection Modulated Brachytherapy (DMBT) tandem, expanding beyond previous focus on partially shielded vaginal cylinder applicators, through a novel methodology.Approach.The DMBT tandem applicator, made of a tungsten alloy with six evenly spaced grooves, was simulated using the GEANT4 MC code. Subsequently, two main scenarios were created using the BVA and reproduced by the MC simulations: 'Source at the Center of the Water Phantom (SACWP)' and 'Source at the Middle of the Applicator (SAMA)' for three cubical virtual water phantoms (20 cm)3, (30 cm)3, and (40 cm)3. A track length estimator was utilized for dose calculation and 2D/3D scoring were performed. The difference in isodose surfaces/lines (i.e. coverage) at each voxel,ΔDIsodose Levels/Lines, was thus calculated for relevant normalization points (rref).Results.The coverage was comparable, based on 2D scoring, between the BVA and MC isodose surfaces/lines for the region of clinical relevance, (i.e. within 5 cm radius from the source) withΔDIsodose Lines(rref: 1 cm from the source) falling within 2% for the two scenarios for all phantom sizes. For the phantom (20 cm)3,ΔDIsodose Levels(3D scoring) recorded the range [-3.0% +6.5%] ([-7.4% +7.3%]) for 95% of the voxels of the same scoring volume for the SACWP (SAMA) scenario.Significance.The results indicated that the BVA could render comparable coverage as compared to the MC simulations in the region of clinical relevance for different phantom sizes.ΔDIsodose Linesmay offer an advantageous metric for evaluation of MBDCAs in clinical setting.

Monte Carlo dosimetry study of newly designed shielded applicators for intensity modulated brachytherapy of cervical and vaginal cancers

IntroductionThe utilization of metal shields in intensity-modulated brachytherapy (IMBT) enables the modulation of the dose, resulting in improved conformance to the tumor while simultaneously reducing the doses to organs at risk (OARs). Utilizing higher-energy sources like 60Co in IMBT for cervical and vaginal cancers has consistently posed challenges. This study evaluates the dosimetric aspects of modified applicators designed for IMBT using 60Co and 192Ir sources.Materials and MethodsGATE, a Geant4-based simulation code, was utilized to model and simulate four distinct applicators. The clinical applicators were redesigned to place the structure of the source tube and the shield while keeping the general characteristics unchanged. These shields were evaluated by calculating transmission factors (TFs) and the dose homogeneities were also determined.ResultTransmission factors for the IMBT technique in redesigned intrauterine applicators and tungsten shields for iridium and cobalt sources were at least 12.8 and 65.4%, and these values were obtained for the intravaginal applicator at 0.2 and 7.0%, respectively. The dose homogeneities for all combinations of radionuclide-shield were within a 15% range of the non-IMBT applicators.ConclusionThis study has quantitatively evaluated the dosimetric effect of tungsten shields in the IMBT technique for cervical and vaginal cancer using cobalt sources. 192Ir compared to 60Co resulted in higher effectiveness for the designed intrauterine and intravaginal shields. while implementing tungsten shields in the redesigned applicators against the 60Co source may not offer complete protection, it does show promising results in reducing the dose to organs at risk.

169Yb-based high dose rate intensity modulated brachytherapy for focal treatment of prostate cancer

PurposeThis study compares conventional 192Ir-based high dose rate brachytherapy (HDR-BT) with 169Yb-based HDR intensity modulated brachytherapy (IMBT) for focal prostate cancer treatment. Additionally, the study explores the potential to generate less invasive treatment plans with IMBT by reducing the number of catheters needed to achieve acceptable outcomes. Methods and MaterialsA retrospective dosimetric study of ten prostate cancer patients initially treated with conventional 192Ir-based HDR-BT and 5-14 catheters was employed. RapidBrachyMCTPS, a Monte Carlo-based treatment planning system was used to calculate and optimize dose distributions. For 169Yb-based HDR IMBT, a custom 169Yb source combined with 0.8 mm thick platinum shields placed inside 6F catheters was used. Furthermore, dose distributions were investigated when iteratively removing catheters for less invasive treatments. ResultsWith IMBT, the urethra D10 and D0.1cc decreased on average by 15.89 and 15.65 percentage points (pp) and the rectum V75 and D2cc by 1.53 and 11.54 pp, respectively, compared to the conventional clinical plans. Similar trends were observed when the number of catheters decreased. On average, there was an observed increase in PTV V150 from 2.84 pp with IMBT when utilizing all catheters to 8.83 pp when four catheters were removed. PTV V200 increased from 0.42 to 2.96 pp on average. Hotspots in the body were however lower with IMBT compared to conventional clinical plans. Conclusions169Yb-based HDR IMBT for focal treatment of prostate cancer has the potential to successfully deliver clinically acceptable, less invasive treatment with reduced dose to organs at risk.

Feasibility of a Tungsten-181 HDR brachytherapy source: Analysis of isotope production and source dosimetry

BackgroundInterest in Intensity Modulated Brachytherapy (IMBT) for High Dose Rate Brachytherapy (HDR) treatments has steadily increased in recent years. However, intensity modulation is not best optimized for currently used HDR sources since they emit high energy photons. To that end, the focus on IMBT has moved to middle energy sources, such as Ytterbium-169; yet even Yb-169 emits some high energy photons at a low yield. We present an alternative isotope, Tungsten-181 (T1/2 = 121 days) that is interesting due to its complete lack of high energy photon emissions. (Eavg = 58.9 keV, Emed = 57.5 keV) making it potentially favorable as high dose rate brachytherapy source from both a medical physics and health physics perspective. PurposeThe purpose of this study was to determine the feasibility of using W-181 as an HDR brachytherapy source; in this study we focused on W-181's production, dosimetric properties, and intensity modulation capabilities. MethodsWe determined the isotope production kinetics, its Dose Rate Constant, Radial Dose Function, photon self-absorption, and the shielding intensity modulation capabilities for a W-181 pellet source geometry using the MCNP6.2 Computer Simulations Code. All simulations were performed using a personal computer running an AMD Ryzen 5 3600 6-Core Processor 3.59 GHz. The number of histories run for each study were selected to produce relative simulation convergence errors in the MCNP tally output of less than 2%.Dosimetric calculations were made using the MCNP6.2 computer simulations code and activation analyses were determined mathematically using a Catenary kinetics analysis (also known as a Bateman Analysis) of W-181 and Tantlum-182 production from the neutron activation of a pure Tungsten-180 stable target. Since W-181 emits middle energy photons and has a high density, we also assessed the effects of photon self-absorption within a tungsten pellet. ResultsFrom our analysis, we determined that a 3.5 mm long and 0.6 mm in diameter is feasible for clinical applications. Our activation analyses found that these pellets can achieve W-181 activities up to 7.9Ci and 13Ci using neutron fluence rates of 4E14 cm−2 s−1 and 1E15 cm−2 s−1 respectively, which then would provide a dose rate of 1.84 ± 0.01 cG y/Ci/min at a depth of 1 cm from the source. Using our resulting Monte Carlo simulated Dose Rate Constant of 1.24 ± 0.02 cGy h−1∙U−1, a W-181 source in this geometry would require a source activity upwards of 10Ci for use in HDR treatments. In the intensity modulation analysis, only 0.1 mm of gold shielding was found to reduce a pellet's absorbed dose by over 50% while 0.3 mm of gold shielding, which is thin enough to theoretically fit between an HDR pellet and the inner catheter wall, was found to reduce the pellet's absorbed dose by over 85%. ConclusionsWhile W-181 has a lower specific activity than Ir-192 and Yb-169, it shows great promise as an isotope for use in Intensity Modulated Brachytherapy due to its easily shielded photons. We therefore expect that W-181 may lend itself best for use as a multi-pellet configuration in IMBT.

Intensity-modulated vaginal brachytherapy applicator and single- and multi-channel applicators in vaginal cuff brachytherapy.

To compare the dosimetric performance of vaginal intensity-modulated brachytherapy (IM-BRT) applicator and single- (SC-BRT) and multi-channel brachytherapy (MC-BRT) applicators for vaginal cuff brachytherapy (VC-BRT). Fifteen patients with uterine-confined endometrium cancer who received adjuvant VC-BRT were included in this study. IM-BRT, SC-BRT, and MC-BRT treatment plans were created for two different clinical target volume (CTV) definitions: 1. Standard CTV, called CTVs; and 2. Virtually defined CTV, called CTVv, with asymmetrical tumor extension > 5 mm in thickness. Plan comparison was performed using dose-volume histogram (DVH) and treatment planning parameters. According to DVH analysis, D98 for CTVv and D2 for both CTVs and CTVv showed statistically significant differences between IM-BRT and SC-BRT plans, but there was no significant difference between IM-BRT and MC-BRT plans in terms of D98 and D2 for both CTVs and CTVv. Additionally, for CTVv plans, IM-BRT was found to be significantly superior to SC-BRT for the rectum (D2cc, V5Gy, and V7Gy), bladder (D2cc and V7Gy), and small bowel (D2cc, V5Gy, and V7Gy). On the other hand, DVH parameters of the sigmoid showed large difference between IM-BRT and SC-BRT plans, but it was not statistically significant. Similarly, the use of IM-BRT applicator demonstrated a noticeable dose reduction in all defined OARs when compared with MC-BRT applicator, but statistically significant for the rectum V7Gy (p = 0.03) only. While the IM-BRT applicator is still in pre-clinical phase, our investigation demonstrated the proof-of-concept in real patient treatment plans with promising dosimetric results compared with SC-BRT and MC-BRT plans in selected patient group.

A Novel Brachytherapy Needle Design to Reduce Urethra Dose in HDR Prostate Brachytherapy.

Ultrasound-guided high-dose-rate (HDR) prostate brachytherapy is a safe and effective treatment option for prostate cancer patients; however, some patients still experience acute and late genitourinary (GU) toxicity. It has been reported that urethra dose is associated with the incidence and severity of GU toxicity. Therefore, a technique that can further spare the urethra while ensuring adequate target coverage is highly desirable. Intensity modulated brachytherapy (IMBT) designs, such as rotating shield brachytherapy (RSBT), offer ideal dosimetry on-paper but are challenging to implement clinically due to the need for high precision in moving mechanisms and the use of non-conventional HDR sources, such as 153Gd, electronic, and 169Yb. In this study, we propose a novel clinically implementable solution based on the direction modulated brachytherapy (DMBT) design concept, which has no moving parts and works effectively with the commercially available 192Ir sources. The widely used GammaMedPlus (GMP) 192Ir sources, with outer diameters of 0.9 mm, was simulated using the GEANT4 Monte Carlo (MC) simulation code. The novel DMBT needle concept consists of a 14-gauge nitinol needle with an outer diameter of 2.1 mm and a crust thickness of 0.1 mm, which housed a platinum shield inside. A single groove, consistent with the outer diameter of each source, was incorporated inside the platinum shield to accommodate the HDR source. The maximum thickness of the shield was 0.8 mm. To evaluate the effectiveness of the DMBT needle concept in reducing urethra dose, two proof-of-concept in silico DMBT plans were created from the standard clinical plan by replacing two needles close to the urethra with the DMBT needles. The dosimetrical comparisons between the two DMBT plans, and the clinical BT plan were done by assessing the target coverage, and urethral, bladder and rectum dose. The MC results showed that the use of the novel DMBT needle could reduce the radiation dose by approximately 35% at 1 cm distance from the needle behind the platinum shield, as compared to the unshielded side. Additionally, when using the same dose volume histogram (DVH) planning criteria as the original plan, the DMBT plan reduced the maximum urethral dose at the pre-apical region by 16% and 28% for 0 mm and 2 mm planning organ at risk (PRV) margins, respectively, while maintaining equivalent V100 and D90 target coverage. The novel DMBT needle design offers a promising solution for reducing the dose to the pre-apical region of the urethra without compromising target coverage, increasing the dose to other organs-at-risk, or increasing the treatment time.

The population percentile allowance method for determining systematic spatial error tolerances for temporary intensity modulated brachytherapy.

Multiple approaches are under development for delivering temporary intensity modulated brachytherapy (IMBT) using partially shielded applicators wherein the delivered dose distributions are sensitive to spatial uncertainties in both the applicator position and shield orientation, rather than only applicator position as with conventional high-dose-rate brachytherapy (HDR-BT). Sensitivity analyses to spatial uncertainties have been reported as components of publications on these emerging technologies, however, a generalized framework for the rigorous determination of the spatial uncertainty tolerances of dose-volume parameters is needed. To derive and present the population percentile allowance (PPA) method, a generalized mathematical and statistical framework to evaluate the tolerance of temporary IMBT approaches to spatial uncertainties in applicator position and shield orientation. A mathematical formalism describing geometric applicator position and shield orientation shifts was derived that supports straight and curved applicators and applies to serial and helical rotating shield brachytherapy (RSBT) and direction modulated brachytherapy (DMBT). The PPA method entails defining the percentage of a patient population receiving a given therapy that is, allowed to receive dose-volume errors in the target volume and specified organs at risk of a defined percentage or less, then determining what combinations of applicator position and shield orientation systematic errors would be expected to produce that outcome in the population. The PPA method was applied to the use case of multi-shield helical 169 Yb-based RSBT for cervical cancer, with 45° and 180° shield emission angles. A total of 37 cervical cancer patients were considered in the population, with average (±1standarddeviation) HR-CTV volumes of 79 cm3 ±37 cm3 and optimized baseline treatment plans (no spatial uncertainties applied) created for each patient to meet dose-volume requirements of 85 GyEQD2 (equivalent uniform dose in 2Gy fraction), with D2cc tolerance doses of 90GyEQD2 , 75GyEQD2 , and 75GyEQD2 for bladder, rectum, and sigmoid colon, respectively. For the PPA requirement that 90% of cervical cancer patients receiving multi-shield helical RSBT could have a maximum dose-volume uncertainty of 10% for high-risk clinical target volume (HR-CTV) D90 (minimum dose to hottest 90%) and bladder, rectum, and sigmoid colon D2cc (minimum dose to hottest 2 cm3 ), the tolerance systematic applicator position and shield orientation uncertainties were approximately±1.0mm and±4.25°, respectively. For±1.5mm and±5° systematic applicator position and shield orientation tolerances, 90% of the patients considered would have a maximum dose-volume uncertainty of 12.8% or less. The PPA method was formalized to determine the temporary IMBT spatial uncertainty tolerances that would be expected to result in an allowed percentage of a population of patients receiving relative dose-volume errors above a defined percentage. Multi-shield, helical 169 Yb-based RSBT for cervical cancer was evaluated and tolerances determined, which, if applied on each treatment fraction, would represent an extreme situation. The PPA method is applicable to a variety of temporary IMBT approaches and can be used to rigorously determine the design parameters for the delivery systems such as mechanical driver motor accuracy, shield angle backlash, applicator rotation, and applicator fixation stability.

A novel direction modulated brachytherapy technique for urethra sparing in high-dose-rate brachytherapy of prostate cancer

PurposeImage-guided high-dose-rate (HDR) prostate brachytherapy is a safe and effective treatment option for prostate cancer patients; however, some patients still experience acute and late genitourinary (GU) toxicity. Studies have shown that urethral dose is associated with the incidence and severity of GU toxicity. Therefore, a technique that can further spare the urethra while ensuring adequate target coverage is highly desirable. Intensity modulated brachytherapy (IMBT) designs, such as rotating shield brachytherapy (RSBT), offer ideal dosimetry theoretically but are challenging to implement clinically due to the need for high precision in moving the treatment delivery mechanisms synchronized with the source loading. In this study, we propose a novel relatively easy-to-implement solution based on the direction modulated brachytherapy (DMBT) design concept, which does not involve moving parts and works effectively with the ubiquitous 192Ir source. Materials and MethodsThe popular Varian VS2000 (VS) and GammaMedPlus (GMP) 192Ir sources, with outer diameters of 0.6 mm and 0.9 mm, respectively, were simulated using the GEANT4 Monte Carlo (MC) simulation code. The novel DMBT needle concept consists of a 14-gauge nitinol needle, which houses a platinum shield inside. A single groove, consistent with the outer diameter of each source, was incorporated inside the platinum shield to accommodate the HDR source. The maximum thickness of the shield was 1.1 mm (0.8 mm) for the VS (GMP) source. To evaluate the effectiveness of the DMBT needle concept in reducing urethral dose, 6 patient cases were studied and DMBT plans were created by replacing two needles close to the urethra with the DMBT needles. The dosimetric comparisons between the DMBT and reference clinical plans were done by assessing the dose-volume histogram (DVH) planning criteria for the target coverage and organs-at-risk. ResultsThe MC results showed that the use of the novel DMBT needle design with the VS source (GMP source) could reduce the dose by 49.6% (39.2%) at 1 cm from the needle behind the platinum shield, as compared to the unshielded side. Additionally, when using the same DVH planning criteria as the original plan, the DMBT plan with the VS (GMP) source reduced the maximum urethral dose by 10.3% ± 5.6% (8.1% ± 5.0%) and 17.7% ± 14.2% (16.6% ± 13.3%) for 0 mm and 2 mm margins, respectively, while maintaining equivalent V90% and D100 target coverage. ConclusionThe novel DMBT technique offers a promising clinically implementable solution for sparing urethra, particularly in pre-apical region, without compromising the target coverage or increasing treatment time.

Dosimetric impact of a robust optimization approach to mitigate effects from rotational uncertainty in prostate intensity modulated brachytherapy.

Intensity modulated brachytherapy (IMBT) is an emerging technology for cancer treatment, in which radiation sources are shielded to shape the dose distribution. The rotatable shields provide an additional degree of freedom, but also introduce an additional, directional, type of uncertainty, compared to conventional high dose-rate brachytherapy (HDR BT). We propose and evaluate a robust optimization approach to mitigate the effects of rotational uncertainty in the shields with respect to planningcriteria. A previously suggested prototype for platinum-shielded prostate 169 Yb-based dynamic IMBT is considered. We study a retrospective patient data set (anatomical contours and catheter placement) from two clinics, consisting of six patients that had previously undergone conventional 192 Ir high dose-rate brachytherapy treatment. The Monte Carlo based treatment planning software RapidBrachyMCTPS is used for dose calculations. In our computational experiments, we investigate systematic rotational shield errors of ±10 and ±20degrees, and the same systematic error is applied to all dwell positions in each scenario. This gives us three scenarios, one nominal and two with errors. The robust optimization approach finds a compromise between the average and worst-case scenariooutcomes. We compare dose plans obtained from standard models and their robust counterparts. With dwell times obtained from a linear penalty model, for 10degrees errors, the dose to urethra (D0.1cc ) and rectum (D0.1cc and D1cc ) increase with up to 5% and 7%, respectively, in the worst-case scenario, while with the robust counterpart, the corresponding increases were 3% and 3%. For all patients and all evaluated criteria, the worst-case scenario outcome with the robust approach had lower deviation compared to the standard model, without compromising target coverage. We also evaluated shield errors up to 20degrees and while the deviations increased to a large extent with the standard models, the robust models were capable of handling even such largeerrors. We conclude that robust optimization can be used to mitigate the effects from rotational uncertainty and to ensure the treatment plan quality ofIMBT. This article is protected by copyright. All rights reserved.

PP04 Presentation Time: 9:30 AM: 169Yb-Based High Dose Rate Intensity Modulated Brachytherapy for Focal Treatment of Prostate Cancer

<h3>Purpose</h3> Intensity-modulated brachytherapy (IMBT) is a developing application of brachytherapy where high-density metallic shields located inside the catheters are used to modulate radiations allowing the production of anisotropic dose distributions at each source dwell position. By rotating the shields during the treatment, the radiation is directed towards the tumour, resulting in better tumour conformity, while sparing the surrounding radiation-sensitive healthy tissues. This study compares conventional ¹⁹²Ir-based high dose rate (HDR) brachytherapy to ¹⁶⁹Yb-based HDR IMBT for focal treatment of prostate cancer and evaluates less invasive IMBT plans that use fewer catheters. <h3>Materials and Methods</h3> RapidBrachyMCTPS, an in-house treatment planning system (TPS) that takes into consideration the different organs' tissue composition and mass densities, was used to conduct a retrospective dosimetric study for two patients previously treated with conventional ¹⁹²Ir-based focal HDR brachytherapy and 5 catheters. The initial HDR ¹⁹²Ir-based treatment plan was first simulated and optimized in RapidBrachyMCTPS, which utilizes Fast Mixed Integer Optimization (FMIO), followed by IMBT treatment plans using the AIM-Brachy's shielded ¹⁶⁹Yb source. Furthermore, dose distributions were investigated when decreasing the number of catheters down from 5 to 2 ensuring the same coverage of dose to the target volume to produce less invasive treatment plans. <h3>Results</h3> The resulting dosimetric indices calculated with RapidBrachyMCTPS and the clinical TPS were compared. For the same planning treatment volume (PTV) D₉₀ coverage, IMBT results show a reduction in the urethra D₁₀ for the first and second patients of 11.75% and 25.44% for 5 catheters, of 13.37% and 22.77% for 4 catheters, of 9.98% and 21.71% for 3 catheters and 8.68% and 25.13% for 2 catheters. A decrease in the rectum D_2cc by up to 27.44% and 0.77% for the first and second patients respectively were recorded. The decrease of the dose to the urethra resulted in an increase of the PTV V₁₅₀ between 2.05-4.41% for patient 1 and 11.53-17.00% for patient 2. Similarly, the PTV V₂₀₀ increased between 0.92-4.54% for patient 1 and 9.28-25.69% for the second patient. All dosimetric indices of interest are presented in Table 1. <h3>Conclusions</h3> IMBT has the potential to successfully deliver less invasive focal prostate brachytherapy treatments with reduced dose spillage in healthy tissues leading to fewer side effects improving patients' quality of life.

Intensity-modulated brachytherapy for vaginal cancer.

This study aimed to evaluate the dose modulation potential of static and dynamic steel-shielded applicators using the Geant4 Application for Emission Tomography (GATE) Monte Carlo code for the treatment of vaginal cancer. The GATE TOOLKIT (version 9.0) was used to simulate vaginal cancer intensity-modulated brachytherapy (IMBT) in a pelvic water-equivalent phantom. IMBT performance of a multichannel static and single-channel dynamic steel-shielded applicator was compared to that of a conventional multichannel Plexiglas applicator. DoseActors were defined to calculate the absorbed dose and attached to the voxelized target and organs at risk (OARs). 60Co and 192Ir high-dose-rate seeds were used as irradiation sources. Dynamic IMBT decreased the D2cc of the rectum and bladder by 28.67 and 28.11% using the 60Co source and by 40.00 and 36.34% using the 192Ir source, respectively. Static IMBT decreased the D2cc for the rectum and bladder by 11.69 and 9.29% using the 60Co source and by 22.21 and 17.71% using the 192Ir source, respectively. In contrast, absorbed dose parameters (D5, D90, and D100) for the target in the three techniques showed a mean relative variation of 0.96% (0.00-7.49%) for both sources. Static and dynamic IMBT using steel-shielded applicators provided relatively better OAR protection while maintaining similar target coverage in the treatment of vaginal cancer.

BEBIG 60Co HDR brachytherapy source dosimetric parameters validation using GATE Geant4-based simulation code

PurposeThis study aims to validate the dosimetric characteristics of High Dose Rate (HDR) 60Co source (Co0.A86 model) using GATE Geant4-based Monte Carlo code. According to the recommendation of the American Association of Physicists in Medicine (AAPM) task group report number 43, the dosimetric parameters of a new brachytherapy source should be verified either experimentally or by Monte Carlo calculation before clinical applications. The validated 60Co source in this study will be used for the simulation of intensity-modulated brachytherapy (IMBT) of vaginal cancer using the same GATE Geant4-based Monte Carlo code in the future. Materials and methodsGATE (version 9.0) simulation code was used to model and calculate the required TG-43U1 dosimetric data of the 60Co HDR source. DoseActors were defined for calculation of dose rate constant, radial dose function, and anisotropy function in a water phantom with an 80 cm radius. ResultsThe dose rate constant was obtained as 1.070±0.008cGy.h−1.U−1 which shows a relative difference of 2.01% compared to the consensus value, 1.092 ​cGy.h−1.U−1. The calculated results of anisotropy and radial dose functions starting from 0.1 cm to 10 cm around the source showed excellent agreement with the results of published studies. The mean variation of the radial dose and anisotropy functions values from the consensus data were 1% and 0.9% respectively. ConclusionFindings from this investigation revealed that the validation of the HDR 60Co source is feasible by the GATE Geant4-based Monte Carlo code. As a result, the GATE Monte Carlo code can be used for the verification of the brachytherapy treatment planning system.

Intensity Modulated High Dose Rate (HDR) Brachytherapy Using Patient Specific 3D Metal Printed Applicators: Proof of Concept.

PurposeIn high-dose-rate (HDR) brachytherapy, an anisotropic dose distribution may be desirable for achieving a higher therapeutic index, particularly when the anatomy imposes challenges. Several methods to deliver intensity-modulated brachytherapy (IMBT) have been proposed in the literature, however practical implementation is lacking due to issues of increased delivery times and complicated delivery mechanisms. This study presents the novel approach of designing a patient-specific inner shape of an applicator with 3D metal printing for IMBT using an inverse plan optimization model.MethodsThe 3D printed patient-specific HDR applicator has an external shape that resembles the conventional brachytherapy applicator. However, at each dwell position of the HDR source, the shielding walls in the interior are divided into six equiangular sections with varying thicknesses. We developed a mathematical model to simultaneously optimize the shielding thicknesses and dwell times according to the patient’s anatomical information to achieve the best possible target coverage. The model, which is a bi-convex optimization problem, is solved using alternating minimization. Finally, the applicator design parameters were input into 3D modeling software and saved in a 3D printable file. The applicator has been tested with both a digital phantom and a simulated clinical cervical cancer patient.ResultsThe proposed approach showed substantial improvements in the target coverage over the conventional method. For the phantom case, 99.18% of the target was covered by the prescribed dose using the proposed method, compared to only 58.32% coverage achieved by the conventional method. For the clinical case, the proposed method increased the coverage of the target from 56.21% to 99.92%. In each case, both methods satisfied the treatment constraints for neighboring OARs.ConclusionThe study simulates the concept of the IMBT with inverse planning using the 3D printed applicator design. The non-isotropic dose map can be produced with optimized shielding patterns and tailored to individual patient’s anatomy, to plan a more conformal plan.

Integration of rotatable tandem applicator to conventional ovoid applicator toward complete framework of intensity modulated brachytherapy (IMBT) for cervical cancer

A new tandem applicator with tungsten shield for Ir-192 radiation source used in intra-cavitary brachytherapy (ICBT) enabled intensity modulated brachytherapy (IMBT) in cervical cancer treatment through fluence-modulation by rotating shield. Our previous work employed group-wise and element-wise sparsity constraints for plan optimization of tandem applicator to minimizes the number of activated angles and source dwell points for delivery efficiency. It, however, did not incorporate the ovoid applicators into the optimizing process, which is generally used to prevent cancer recurrence. To integrate ovoid applicators to the new tandem applicator, this work proposed a comprehensive framework that modifies 1) dose deposition matrix for inverse planning, and 2) plan optimizing algorithm. The dose deposition matrix was newly formulated by the Monte-Carlo simulated dose distribution for 10 positions of ovoid applicators, followed by combining those with tandem-associated dose deposition matrix. The plan optimizing algorithm decomposed entire elements into tandem and ovoid applicators, which were governed by different constraints adaptive to specified plan objectives. The integrated framework was compared against conventional ICBT, and IMBT with tandem only for three patients with asymmetric dose distributions. Integrated IMBT framework resulted in the most optimal plans. Including fluence-modulation by rotating-shield outperformed conventional ICBT in dose sparing to critical organs. Adopting ovoid applicators to the optimization yielded more conformal dose distribution around inferior, laterally expanded region of target volume. The resulting plans reduced D5cc and D2cc by 30.9% and 27.8% for critical organs over conventional ICBT, and by 20.6% and 21.5% for target volume over IMBT with tandem only.

On the impact of absorbed dose specification, tissue heterogeneities, and applicator heterogeneities on Monte Carlo-based dosimetry of Ir-192, Se-75, and Yb-169 in conventional and intensity-modulated brachytherapy for the treatment of cervical cancer.

The purpose of this study was to evaluate the impact of dose reporting schemes and tissue/applicator heterogeneities for 192 Ir-, 75 Se-, and 169 Yb-based MRI-guided conventional and intensity-modulated brachytherapy. Treatment plans using a variety of dose reporting and tissue/applicator segmentation schemes were generated for a cohort (n=10) of cervical cancer patients treated with 192 Ir-based Venezia brachytherapy. Dose calculations were performed using RapidBrachyMCTPS, a Geant4-based research Monte Carlo treatment planning system. Ultimately, five dose calculation scenarios were evaluated: (a) dose to water in water (Dw,w ); (b) Dw,w taking the applicator material into consideration (Dw,wApp ); (c) dose to water in medium (Dw,m ); (d and e) dose to medium in medium with mass densities assigned either nominally per structure (Dm,m (Nom) ) or voxel-by-voxel (Dm,m ). Ignoring the plastic Venezia applicator (Dw,wApp ) overestimates Dm,m by up to 1% (average) with high energy source (192 Ir and 75 Se) and up to 2% with 169 Yb. Scoring dose to water (Dw,wApp or Dw,m ) generally overestimates dose and this effect increases with decreasing photon energy. Reporting dose other than Dm,m (or Dm,m Nom ) for 169 Yb-based conventional and intensity-modulated brachytherapy leads to a simultaneous overestimation (up to 4%) of CTVHR D90 and underestimation (up to 2%) of bladder D2cc due to a significant dip in the mass-energy absorption ratios at the depths of nearby targets and OARs. Using a nominal mass-density assignment per structure, rather than a CT-derived voxel-by-voxel assignment for MRI-guided brachytherapy, amounts to a dose error up to 1% for all radionuclides considered. The effects of the considered dose reporting schemes trend correspondingly between conventional and intensity-modulated brachytherapy. In the absence of CT-derived mass densities, MRI-only-based dosimetry can adequately approximate Dm,m by assigning nominal mass densities to structures. Tissue and applicator heterogeneities do not significantly impact dosimetry for 192 Ir and 75 Se, but do for 169 Yb; dose reporting must be explicitly defined since Dw,m and Dw,w may overstate the dosimetric benefits.

Evolution of Brachytherapy Applicators for the Treatment of Cervical Cancer.

Brachytherapy applicators have come a long way since Danlos developed early intracavitary applicators to treat cervical cancer patients. Therefore, this review will help in the neoteric designs of intracavitary applicators. A detailed literature survey of the gynecological brachytherapy applicators from the era of preloading to conceptual intensity-modulated brachytherapy applicators has been carried out. Depending on the extent of the disease and patient anatomy, the selection of brachytherapy applicators plays a pivotal role in the treatment of cervical cancer. Furthermore, the selection of the applicators is also based on the imaging modalities to be used for applicator reconstruction and treatment planning. Dose acceleration in the target and reduction in nearby organs at risk can be optimized using an applicator having the capabilities of intensity-modulated brachytherapy. Now, three-dimensional printed applicators are used for patient-specific tailor-made treatment and they are fast replacing the old conventional applicators. Newer advancements in technology have greatly influenced the neoteric designs of intracavitary brachytherapy applicators.

A novel minimally invasive dynamic-shield, intensity-modulated brachytherapy system for the treatment of cervical cancer.

To present a novel, MRI-compatible dynamicshield intensity modulated brachytherapy (IMBT) applicator and delivery system using 192 Ir, 75 Se, and 169 Yb radioisotopes for the treatment of locally advanced cervical cancer. Needle-free IMBT is a promising technique for improving target coverage and organs at risk (OAR) sparing. The IMBT delivery system dynamically controls the rotation of a novel tungsten shield placed inside an MRI-compatible, 6-mm wide intrauterine tandem. Using 36 cervical cancer cases, conventional intracavitary brachytherapy (IC-BT) and intracavitary/interstitial brachytherapy (IC/IS-BT) (10Ci 192 Ir) plans were compared to IMBT (10Ci 192 Ir; 11.5Ci 75 Se; 44Ci 169 Yb). All plans were generated using the Geant4-based Monte Carlo dose calculation engine, RapidBrachyMC. Treatment plans were optimized then normalized to the same high-risk clinical target volume (HR-CTV) D90 and the D2cc for bladder, rectum, and sigmoid in the research brachytherapy planning system, RapidBrachyMCTPS. Plans were renormalized until either of the three OAR reached dose limits to calculate the maximum achievable HR-CTV D90 and D98 . Compared to IC-BT, IMBT with either of the three radionuclides significantly improves the HR-CTV D90 and D98 by up to 5.2%±0.3% (P<0.001) and 6.7%±0.5% (P<0.001), respectively, with the largest dosimetric enhancement when using 169 Yb followed by 75 Se and then 192 Ir. Similarly, D2cc for all OAR improved with IMBT by up to 7.7%±0.6% (P<0.001). For IC/IS-BT cases, needle-free IMBT achieved clinically acceptable plans with 169 Yb-based IMBT further improving HR-CTV D98 by 1.5%±0.2% (P=0.034) and decreasing sigmoid D2cc by 1.9%±0.4% (P=0.048). Delivery times for IMBT are increased by a factor of 1.7, 3.3, and 2.3 for 192 Ir, 75 Se, and 169 Yb, respectively, relative to conventional 192 Ir BT. Dynamic shield IMBT provides a promising alternative to conventional IC- and IC/IS-BT techniques with significant dosimetric enhancements and even greater improvements with intermediate energy radionuclides. The ability to deliver a highly conformal, OAR-sparing dose without IS needles provides a simplified method for improving the therapeutic ratio less invasively and in a less resource intensive manner.

Plan optimization with L0-norm and group sparsity constraints for a new rotational, intensity-modulated brachytherapy for cervical cancer.

The aim of this work is to build a framework that comprehends inverse planning procedure and plan optimization algorithm tailored to a novel directional beam intensity-modulated brachytherapy (IMBT) of cervical cancer using a rotatable, single-channel radiation shield. Inverse planning is required for finding optimal beam emitting direction, source dwell position and dwell time, which begin with creating a kernel matrix for each structure based on Monte-Carlo simulated dose distribution in the rotatable shield. For efficient beam delivery and less transit dose, the number of source dwell positions and angles needs to be minimized. It can be solved by L0-norm regularization for fewest possible dwell points, and by group sparsity constraint in L2,p-norm (0≤p<1) besides L0-norm for fewest active applicator rotating angles. The dose distributions from our proposed algorithms were compared to those of conventional tandem-based intracavitary brachytherapy (ICR) plans for six cervical cancer patients. The algorithmic performance was evaluated in delivery efficiency and plan quality relative to the unconstrained algorithm. The proposed framework yielded substantially enhanced plan quality over the conventional ICR plans. The L0-norm and (group sparsity+L0-norm) constrained algorithms reduced the number of source dwell points by 60 and 70% and saved 5 and 8 rotational angles on average (7 and 11 angles for highly modulated cases), relative to the unconstrained algorithm, respectively. Though both algorithms reduced the optimal source dwell positions and angles, the group sparsity constrained optimization with L0-norm was more effective than the L0-norm constraint only, mainly because of considering physical constraints of the new IMBT applicator. With much fewer dwell points compared to the unconstrained, the proposed algorithms led to statistically similar plan quality in dose volume histograms and iso-dose lines. It also demonstrated that the plan optimized by rotating the applicator resulted in much better plan quality than that of conventional applicator-based plans.

Monte Carlo dosimetric characterization of a new high dose rate Yb brachytherapy source and independent verification using a multipoint plastic scintillator detector.

A prototype Yb source was developed in combination with a dynamic rotating platinum shield system (AIM-Brachy) to deliver intensity modulated brachytherapy (IMBT). The purpose of this study was to evaluate the dosimetric characteristics of the bare/shielded Yb source using Monte Carlo (MC) simulations and perform an independent dose verification using a dosimetry platform based on a multipoint plastic scintillator detector (mPSD). The TG-43U1 dosimetric parameters were calculated for the source model using RapidBrachyMCTPS. Real-time dose rate measurements were performed in a water tank for both the bare/shielded source using a custom remote afterloader. For each dwell position, the dose rate was independently measured by the three scintillators (BCF-10, BCF-12, and BCF-60). For the bare source, dose rate was measured at distances up to 3cm away from the source over a range of 7cm along the catheter. For the shielded source, measurements were performed with the mPSD placed at 1cm from the source at four different azimuthal angles ( , 9 , 18 , and 27 ). The dosimetric parameters were tabulated for the source model. For the bare source, differences between measured and calculated along-away dose rates were generally below 5-10%. Along the transverse axis, deviations were, on average (range), 3.3% (0.6-6.2%) for BCF-10, 1.7% (0.9-2.9%) for BCF-12, and 2.2% (0.3-4.4%) for BCF-60. The maximum dose rate reduction due to shielding at a radial distance of 1 cm was 88.8±1.2%, compared to 83.5±0.5% as calculated by MC. The dose distribution for the bare/shielded Yb source was independently verified using mPSD with good agreement in regions close to the source. The Yb source coupled with the partial-shielding system is an effective technique to deliver IMBT.

The clinical impact of MicroRNA-21 in low rectal cancers treated with curative radiotherapy in the organ preserving setting.

e16120 Background: Neoadjuvant chemoradiotherapy (CRT) in curatively intended doses may result in clinical complete response (cCR) in selected patients, allowing for non-surgical management (NSM) of patients with low rectal cancers. MicroRNA-21-5p (miR-21), ubiquitous upregulated in cancer, has been associated with treatment response in rectal cancers treated with standard preoperative CRT. The aim of the present study was to investigate this association in low rectal cancers treated in the NSM setting. Methods: Forty eight patients from our single-arm phase II trial (NCT00952926) were available for analyses. All patients had resectable, T2 or T3, N0–N1, low adenocarcinomas and received 65Gy (intensity-modulated radiotherapy plus brachytherapy boost) and oral tegafur-uracil. Patients with cCR 6 weeks after treatment (clinical examination, magnetic-resonance imaging and biopsy) were referred to observation and followed closely. The miR expression, in the diagnostic biopsies, was measured by qPCR in 20 µl reactions using TaqMan MicroRNA Assays. The protocol using custom RT and preamplification pools was followed. The miR-193a-5p, -27a and –let7g were used for normalization based on previous recommendations from our group. The relationship between miR-21 expression and cCR was assessed using the Wilcoxon rank-sum tests. Results: Thirty-eight patients achieved cCR after treatment and were followed in observation while 10 patients proceeded to surgery due to a non-cCR. MicroRNA-21 was successfully analyzed in all samples. The median tumor expression of miR-21 in patients proceeding to surgery was significantly higher compared to patients achieving cCR, 24.3 (95% confidence interval (CI) 17.1-36.8) and 16.6 (95% CI 13.9-21.1), p = 0.02, respectively. Conclusions: The present results support a clinical impact of miR-21 in rectal cancer treated with CRT, comparable with results seen in patients treated in the standard preoperative setting, and may assist in the selection of patients for an organ preserving approach.