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

PURPOSE: This 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 MATERIALS: A 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. RESULTS: With 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. CONCLUSIONS: 169Yb-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.

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

BACKGROUND: 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). PURPOSE: We propose and evaluate a robust optimization approach to mitigate the effects of rotational uncertainty in the shields with respect to planning criteria. METHODS: 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 HDR BT 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 ±20°, 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 scenario outcomes. RESULTS: We compare dose plans obtained from standard models and their robust counterparts. With dwell times obtained from a linear penalty model (LPM), for 10° errors, the dose to urethra ( D 0.1 c c $D_{0.1cc}$ ) and rectum ( D 0.1 c c $D_{0.1cc}$ and D 1 c c $D_{1cc}$ ) 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 20° and while the deviations increased to a large extent with the standard models, the robust models were capable of handling even such large errors. CONCLUSIONS: We conclude that robust optimization can be used to mitigate the effects from rotational uncertainty and to ensure the treatment plan quality of IMBT.

A novel 169 Yb-based dynamic-shield intensity modulated brachytherapy delivery system for prostate cancer.

PURPOSE: Intensity modulated brachytherapy (IMBT) is a novel high dose rate brachytherapy (HDR BT) technique which incorporates static or dynamic shielding to increase tumor coverage and/or spare healthy tissues. The purpose of this study is to present a novel delivery system (AIM-Brachy) design that can enable dynamic-shield IMBT for prostate cancer. METHODS: The AIM-Brachy system dynamically controls the rotation of platinum shields, placed within interstitial catheters, which partially collimate the radiation emitted from an 169 Yb source. Conventional HDR BT (10 Ci 192 Ir) and IMBT (18 Ci 169 Yb) plans were generated for 12 patients using an in-house column generation-based optimizer, coupled to a Geant4-based dose calculation engine, RapidBrachyMC. Treatment plans were normalized to match the same PTV D90 coverage as the clinical plan. Intershield attenuation effects were taken into account. A sensitivity analysis was performed to evaluate the dosimetric impact of systematic longitudinal source positioning errors ( ± 1 mm, ± 2 mm, and ± 3 mm) and rotational errors ( ± 5 ∘ , ± 10 ∘ , and ± 15 ∘ ) on clinically relevant parameters (PTV D90 and urethra D10 ). RESULTS: The platinum shield reduced the dose rate on the shielded side at 1 cm to 18.1% of the dose rate on the unshielded side. For equal PTV D90 coverage, the urethral D10 was reduced by 13.3%  ±  4.7%, without change to other plan quality indices (PTV V100 , V150, V200 , bladder V75 , rectum V75 , HI, COIN). Delivery times for HDR BT and IMBT were 9.2 ± 1.6 min and 18.6 ± 4.0 min, respectively. In general, the PTV D90 was more sensitive to source positioning errors than rotational errors, while the urethral D10 was more sensitive to rotational errors than source positioning errors. For a typical range of positioning errors ( ± 1 mm, ± 5 ∘ ), the overall tolerance was <2%. CONCLUSIONS: The AIM-Brachy system was proposed to deliver dynamic-shield IMBT for prostate cancer with the potential to create a low dose tunnel within the urethra. The urethra-sparing properties are desirable to minimize the occurrence and severity of urethral strictures or, alternatively, to provide a method for dose escalation.

Can intermediate-energy sources lead to elevated bone doses for prostate and head & neck high-dose-rate brachytherapy?

PURPOSE: Several radionuclides with high (60Co, 75Se) and intermediate (169Yb, 153Gd) energies have been investigated as alternatives to 192Ir for high-dose-rate brachytherapy. The purpose of this study was to evaluate the impact of tissue heterogeneities for these five high- to intermediate-energy sources in prostate and head & neck brachytherapy. METHODS AND MATERIALS: Treatment plans were generated for a cohort of prostate (n = 10) and oral tongue (n = 10) patients. Dose calculations were performed using RapidBrachyMCTPS, an in-house Geant4-based Monte Carlo treatment planning system. Treatment plans were simulated using 60Co, 192Ir, 75Se, 169Yb, and 153Gd as the active core of the microSelectron v2 source. Two dose calculation scenarios were presented: (1) dose to water in water (Dw,w), and (2) dose to medium in medium (Dm,m). RESULTS: Dw,w overestimates planning target volume coverage compared with Dm,m, regardless of photon energy. The average planning target volume D90 reduction was ∼1% for high-energy sources, whereas larger differences were observed for intermediate-energy sources (1%-2% for prostate and 4%-7% for oral tongue). Dose differences were not clinically relevant (<5%) for soft tissues in general. Going from Dw,w to Dm,m, bone doses were increased two- to three-fold for 169Yb and four- to five-fold for 153Gd, whereas the ratio was close to ∼1 for high-energy sources. CONCLUSIONS: Dw,w underestimates the dose to bones and, to a lesser extent, overestimates the dose to soft tissues for radionuclides with average energies lower than 192Ir. Further studies regarding bone toxicities are needed before intermediate-energy sources can be adopted in cases where bones are in close vicinity to the tumor.

Monte Carlo dosimetric characterization of a new high dose rate 169 Yb brachytherapy source and independent verification using a multipoint plastic scintillator detector.

PURPOSE: A prototype 169 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 169 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). METHODS: 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 3 cm away from the source over a range of 7 cm along the catheter. For the shielded source, measurements were performed with the mPSD placed at 1 cm from the source at four different azimuthal angles ( 0 ∘ , 9 0 ∘ , 18 0 ∘ , and 27 0 ∘ ). RESULTS: 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. CONCLUSIONS: The dose distribution for the bare/shielded 169 Yb source was independently verified using mPSD with good agreement in regions close to the source. The 169 Yb source coupled with the partial-shielding system is an effective technique to deliver IMBT.

Periodicity, time constants of drainage, and the mechanical determinants of peak cardiac output during exercise.

To analyze mechanical adaptations that must occur in the cardiovascular system to reach the high cardiac outputs known to occur at peak aerobic performance, we adapted a computational model of the circulation by adding a second parallel venous compartment as proposed by August Krogh in 1912. One venous compartment has a large compliance and slow time constant of emptying; it is representative of the splanchnic circulation. The other has a low compliance and fast time constant of emptying and is representative of muscle beds. Fractional distribution between the two compartments is an important determinant of cardiac output. Parameters in the model were based on values from animal and human studies normalized to a 70 kg male. The baseline cardiac output was set at 5 L/min, and we aimed for 25 L/min at peak exercise with a fractional flow to the peripheral-muscle region of 90%. Finally, we added the equivalent of a muscle pump. Adjustments in circuit and cardiac parameters alone increased cardiac output to only 15.6 L/min because volume accumulated in the muscle compartment and limited a higher cardiac output. Addition of muscle contractions decompressed the muscle region and allowed cardiac output to increase to 23.4 L/min. The pulsatility of blood flow imposes important constraints on the adaptations of cardiac and circulatory functions because it fixes the times for filling and emptying. Flow is further limited by the limits of cardiac filling on each beat. Muscle contractions play a key role by decompressing volume that would otherwise accumulate in the muscle vasculature and by decreasing the time for stroke return to the right ventricle.NEW & NOTEWORTHY We used a computational model of the circulation and previous human and animal data to model mechanical changes in the heart and circulation that are needed to reach the known high cardiac output at peak aerobic exercise. Key points are that time constants of drainage of circulatory compartments put limits on peak flow in a pulsatile system. Muscle contractions increase the rate of return to the heart and by doing so prevent accumulation of volume in the muscle compartment and greatly increase circulatory capacity.

Dosimetric Considerations for Ytterbium-169, Selenium-75, and Iridium-192 Radioisotopes in High-Dose-Rate Endorectal Brachytherapy.

PURPOSE: To investigate differences between prescribed and postimplant calculated dose in 192Ir high-dose-rate endorectal brachytherapy (HDR-EBT) by evaluating dose to clinical target volume (CTV) and organs at risk (OARs) calculated with a Monte Carlo-based dose calculation software, RapidBrachyMC. In addition, dose coverage, conformity, and homogeneity were compared among the radionuclides 192Ir, 75Se, and 169Yb for use in HDR-EBT. METHODS AND MATERIALS: Postimplant dosimetry was evaluated using 23 computed tomography (CT) images from patients treated with HDR-EBT using the 192Ir microSelectron v2 (Elekta AB, Stockholm, Sweden) source and the Intracavitary Mold Applicator Set (Elekta AB, Stockholm, Sweden), which is a flexible applicator capable of fitting a tungsten rod for OAR shielding. Four tissue segmentation schemes were evaluated: (1) TG-43 formalism, (2) materials and nominal densities assigned to contours of foreign objects, (3) materials and nominal densities assigned to contoured organs in addition to foreign objects, and (4) materials specified as in (3) but with voxel mass densities derived from CT Hounsfield units. Clinical plans optimized for 192Ir were used, with the results for 75Se and 169Yb normalized to the D90 of the 192Ir clinical plan. RESULTS: In comparison to segmentation scheme 4, TG-43-based dosimetry overestimates CTV D90 by 6% (P = .00003), rectum D50 by 24% (P = .00003), and pelvic bone D50 by 5% (P = .00003) for 192Ir. For 169Yb, CTV D90 is overestimated by 17% (P = .00003) and rectum D50 by 39% (P = .00003), and pelvic bone D50 is significantly underestimated by 27% (P = .007). Postimplant dosimetry calculations also showed that a 169Yb source would give 20% (P = .00003) lower rectum V60 and 17% (P = .00008) lower rectum D50. CONCLUSIONS: Ignoring high-Z materials in dose calculation contributes to inaccuracies that may lead to suboptimal dose optimization and disagreement between prescribed and calculated dose. This is especially important for low-energy radionuclides. Our results also show that with future magnetic resonance imaging-based treatment planning, loss of CT density data will only affect calculated dose in nonbone OARs by 2% or less and bone OARs by 13% or less across all sources if material composition and nominal mass densities are correctly assigned.

Microdosimetric Evaluation of Current and Alternative Brachytherapy Sources-A Geant4-DNA Simulation Study.

PURPOSE: Radioisotopes such as 75Se, 169Yb, and 153Gd have photon energy spectra and half-lives that make them excellent candidates as alternatives to 192Ir for high-dose-rate brachytherapy. The aim of the present study was to evaluate the relative biological effectiveness (RBE) of current (192Ir, 125I, 103Pd) and alternative (75Se, 169Yb, 153Gd) brachytherapy radionuclides using Monte Carlo simulations of lineal energy distributions. METHODS AND MATERIALS: Brachytherapy sources (microSelectron v2 [192Ir, 75Se, 169Yb, 153Gd], SelectSeed [125I], and TheraSeed [103Pd]) were placed in the center of a spherical water phantom with a radius of 40 cm using the Geant4 Monte Carlo simulation toolkit. The kinetic energy of all primary, scattered, and fluorescence photons interacting in a scoring volume were tallied at various depths from the source. Electron tracks were generated by sampling the photon interaction spectrum and tracking all the interactions down to 10 eV using the event-by-event capabilities of the Geant4-DNA models. The dose mean lineal energy (y¯D) values were obtained through random sampling of transfer points and overlaying spherical scoring volumes within the associated volume of the tracks. The scoring volume diameter was determined by fitting the y¯D ratio for 125I to its observed RBE. RESULTS: y¯D increased with the increasing distance from the source for 192Ir, 75Se, and 169Yb, remained constant for 153Gd and 125I, and decreased for 103Pd. The diameter at which the y¯D ratio coincided with the RBE of 1.15 to 1.20 for 125I was ∼25 to 40 nm. The RBE (reference 1 MeV photons) at high doses and dose rates for 192Ir, 75Se, 169Yb, 153Gd, 125I, and 103Pd was 1.028 to 1.034, 1.05 to 1.07, 1.12 to 1.15, 1.16 to 1.21, 1.15 to 1.20, and 1.17 to 1.22, respectively. CONCLUSIONS: The radiation quality of the radionuclides under investigation was greater than that of high-energy photons. The present study has provided a set of values to modify the prescription doses for brachytherapy to account for the variation in radiation quality among radionuclides.

RapidBrachyMCTPS: a Monte Carlo-based treatment planning system for brachytherapy applications.

Despite being considered the gold standard for brachytherapy dosimetry, Monte Carlo (MC) has yet to be implemented into a software for brachytherapy treatment planning. The purpose of this work is to present RapidBrachyMCTPS, a novel treatment planning system (TPS) for brachytherapy applications equipped with a graphical user interface (GUI), optimization tools and a Geant4-based MC dose calculation engine, RapidBrachyMC. Brachytherapy sources and applicators were implemented in RapidBrachyMC and made available to the user via a source and applicator library in the GUI. To benchmark RapidBrachyMC, TG-43 parameters were calculated for the microSelectron v2 (192Ir) and SelectSeed (125I) source models and were compared against previously validated MC brachytherapy codes. The performance of RapidBrachyMC was evaluated for a prostate high dose rate case. To assess the accuracy of RapidBrachyMC in a heterogeneous setup, dose distributions with a cylindrical shielded/unshielded applicator were validated against film measurements in a Solid WaterTM phantom. TG-43 parameters calculated using RapidBrachyMC generally agreed within 1%-2% of the results obtained in previously published work. For the prostate case, clinical dosimetric indices showed general agreement with Oncentra TPS within 1%. Simulation times were on the order of minutes on a single core to achieve uncertainties below 2% in voxels within the prostate. The calculation time was decreased further using the multithreading features of Geant4. In the comparison between MC-calculated and film-measured dose distributions, at least 95% of points passed the 3%/3 mm gamma index criteria in all but one case. RapidBrachyMCTPS can be used as a post-implant dosimetry toolkit, as well as for MC-based brachytherapy treatment planning. This software is especially well suited for the development of new source and applicator models.

Microdosimetry calculations for monoenergetic electrons using Geant4-DNA combined with a weighted track sampling algorithm.

The aim of this study was to calculate microdosimetric distributions for low energy electrons simulated using the Monte Carlo track structure code Geant4-DNA. Tracks for monoenergetic electrons with kinetic energies ranging from 100 eV to 1 MeV were simulated in an infinite spherical water phantom using the Geant4-DNA extension included in Geant4 toolkit version 10.2 (patch 02). The microdosimetric distributions were obtained through random sampling of transfer points and overlaying scoring volumes within the associated volume of the tracks. Relative frequency distributions of energy deposition f(>E)/f(>0) and dose mean lineal energy ([Formula: see text]) values were calculated in nanometer-sized spherical and cylindrical targets. The effects of scoring volume and scoring techniques were examined. The results were compared with published data generated using MOCA8B and KURBUC. Geant4-DNA produces a lower frequency of higher energy deposits than MOCA8B. The [Formula: see text] values calculated with Geant4-DNA are smaller than those calculated using MOCA8B and KURBUC. The differences are mainly due to the lower ionization and excitation cross sections of Geant4-DNA for low energy electrons. To a lesser extent, discrepancies can also be attributed to the implementation in this study of a new and fast scoring technique that differs from that used in previous studies. For the same mean chord length ([Formula: see text]), the [Formula: see text] calculated in cylindrical volumes are larger than those calculated in spherical volumes. The discrepancies due to cross sections and scoring geometries increase with decreasing scoring site dimensions. A new set of [Formula: see text] values has been presented for monoenergetic electrons using a fast track sampling algorithm and the most recent physics models implemented in Geant4-DNA. This dataset can be combined with primary electron spectra to predict the radiation quality of photon and electron beams.

Practical aspects of 153Gd as a radioactive source for use in brachytherapy.

The goal of this study was to investigate the production, purification and immobilization techniques for a 153Gd brachytherapy source. We have investigated the maximum attainable specific activity of 153Gd through the irradiation of Gd2O3 enriched to 30.6% 152Gd at McMaster Nuclear Reactor. The advantage of producing 153Gd through this production pathway is the possibility to irradiate pre-sealed pellets of 152Gd enriched Gd2O3, thereby removing the need to perform chemical separation with large quantities of radio-impurities. However, small amounts of long-lived impurities are produced from the irradiation of enriched 152Gd targets due to traces of Eu in the sample. If the amount of impurities produced is deemed unacceptable, 153Gd can be isolated as an aqueous solution, chemically separated from impurities and loaded onto a sorbent with a high affinity for Gd before encapsulation.