A re-activation model for 169Yb intensity modulated brachytherapy sources accounting for spatiotemporal isotopic composition.

BACKGROUND: Intensity modulated brachytherapy based on partially shielded intracavitary and interstitial applicators is possible with a cost-effective 169Yb production method. 169Yb is a traditionally expensive isotope suitable for this purpose, with an average γ-ray energy of 93 keV. Re-activating a single 169Yb source multiple times in a nuclear reactor between clinical uses was shown to theoretically reduce cost by approximately 75% relative to conventional single-activation sources. With re-activation, substantial spatiotemporal variation in isotopic source composition is expected between activations via 168Yb burnup and 169Yb decay, resulting in time dependent neutron transmission, precursor usage, and reactor time needed per re-activation. PURPOSE: To introduce a generalized model of radioactive source production that accounts for spatiotemporal variation in isotopic source composition to improve the efficiency estimate of the 169Yb production process, with and without re-activation. METHODS AND MATERIALS: A time-dependent thermal neutron transport, isotope transmutation, and decay model was developed. Thermal neutron flux within partitioned sub-volumes of a cylindrical active source was calculated by raytracing through the spatiotemporal dependent isotopic composition throughout the source, accounting for thermal neutron attenuation along each ray. The model was benchmarked, generalized, and applied to a variety of active source dimensions with radii ranging from 0.4 to 1.0 mm, lengths from 2.5 to 10.5 mm, and volumes from 0.31 to 7.85 mm3, at thermal neutron fluxes from 1 × 1014 to 1 × 1015 n cm-2 s-1. The 168Yb-Yb2O3 density was 8.5 g cm-3 with 82% 168Yb-enrichment. As an example, a reference re-activatable 169Yb active source (RRS) constructed of 82%-enriched 168Yb-Yb2O3 precursor was modeled, with 0.6 mm diameter, 10.5 mm length, 3 mm3 volume, 8.5 g cm-3 density, and a thermal neutron activation flux of 4 × 1014 neutrons cm-2 s-1. RESULTS: The average clinical 169Yb activity for a 0.99 versus 0.31 mm3 source dropped from 20.1 to 7.5 Ci for a 4 × 1014 n cm-2 s-1 activation flux and from 20.9 to 8.7 Ci for a 1 × 1015 n cm-2 s-1 activation flux. For thermal neutron fluxes ≥2 × 1014 n cm-2 s-1, total precursor and reactor time per clinic-year were maximized at a source volume of 0.99 mm3 and reached a near minimum at 3 mm3. When the spatiotemporal isotopic composition effect was accounted for, average thermal neutron transmission increased over RRS lifetime from 23.6% to 55.9%. A 28% reduction (42.5 days to 30.6 days) in the reactor time needed per clinic-year for the RRS is predicted relative to a model that does not account for spatiotemporal isotopic composition effects. CONCLUSIONS: Accounting for spatiotemporal isotopic composition effects within the RRS results in a 28% reduction in the reactor time per clinic-year relative to the case in which such changes are not accounted for. Smaller volume sources had a disadvantage in that average clinical 169Yb activity decreased substantially below 20 Ci for source volumes under 1 mm3. Increasing source volume above 3 mm3 adds little value in precursor and reactor time savings and has a geometric disadvantage.

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

BACKGROUND: 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. PURPOSE: 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. METHODS: 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 (± 1 standard deviation) 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 2 Gy fraction), with D2cc tolerance doses of 90 GyEQD2 , 75 GyEQD2 , and 75 GyEQD2 for bladder, rectum, and sigmoid colon, respectively. RESULTS: 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 ± 1.0 mm and ± 4.25°, respectively. For ± 1.5 mm 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. CONCLUSION: 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.

Measurements of fetal dose with Mevion S250i proton therapy system with HYPERSCAN.

PURPOSE: To characterize potential dose to the fetus for all modes of delivery (dynamic adaptive aperture, static adaptive aperture, and no adaptive aperture) for the Mevion S250i Proton Therapy System with HYPERSCAN and compare the findings with those of other available proton systems. MATERIALS AND METHODS: Fetal dose measurements were performed for all three modes of dose delivery on the Mevion S250i Proton therapy system with HYPERSCAN (static aperture, dynamic aperture and uncollimated). Standard treatment plans were created in RayStation for a left-sided brain lesion treated with a vertex field, a left lateral field, and a posterior field. Measurements were performed using WENDI and the RANDO with the detector placed at representative locations to mimic the growth and movement of the fetus at different gestational stages. RESULTS: The fetal dose measurements varied with fetus position and the largest measured dose was 64.7 µSv per 2 Gy (RBE) fraction using the dynamic aperture. The smallest estimated fetal dose was 45.0 µSv per 2 Gy (RBE) at the base of the RANDO abdomen (47 cm from isocenter to the outer width of WENDI and 58.5 cm from the center of the WENDI detector) for the static aperture delivery. The vertex fields at all depths had larger contributions to the total dose than the other two and the dynamic aperture plans resulted in the highest dose measured for all depths. CONCLUSION: The reported doses are lower than reported doses using a double-scattering system. This work suggests that avoiding vertex fields and using the static aperture will help minimize dose to the fetus.

169 Yb-based rotating shield brachytherapy for prostate cancer.

PURPOSE: To present a system for the treatment of prostate cancer in a single-fraction regimen using 169 Yb-based rotating shield brachytherapy (RSBT) with a single-catheter robotic delivery system. The proposed system is innovative because it can deliver RSBT through multiple implanted needles independently, in serial, using flexible catheters, with no inter-needle shielding effects and without the need to rotate multiple shielded catheters inside the needles simultaneously, resulting in a simple, mechanically robust, delivery approach. RSBT was compared to conventional 192 Ir-based high-dose-rate brachytherapy (HDR-BT) in a treatment planning study with dose escalation and urethral sparing goals, representing single-fraction brachytherapy monotherapy and brachytherapy as a boost to external beam radiotherapy, respectively. A prototype mechanical delivery system was constructed and quantitatively evaluated as a proof of concept. METHODS: Treatment plans for twenty-six patients with single fraction prescriptions of 20.5 and 15 Gy, were created for dose escalation and urethral sparing, respectively. The RSBT and HDR-BT delivery systems were modeled with one partially shielded 999 GBq (27 Ci) 169 Yb source and one 370 GBq (10 Ci) 192 Ir source, respectively. A prototype angular drive system for helical source delivery was constructed. Mechanical accuracy measurements of source translational position and angular orientation in a simulated treatment delivery setup were obtained using the prototype system. RESULTS: For dose escalation, with equivalent urethra D10% , PTV D90% for RSBT vs HDR-BT increased from 22.6 ± 0.0 Gy (average ± standard deviation) to 29.3 ± 0.9 Gy, or 29.9 % ± 3.0%, with treatment times of 51.4 ± 6.1 min for RSBT and 15.8 ± 2.3 min for 10 Ci 192 Ir-based HDR-BT. For urethra sparing, with equivalent PTV D90 % , urethra D10% for RSBT vs HDR-BT decreased for RSBT vs HDR-BT from 15.6 ± 0.4 Gy to 12.0 ± 0.4 Gy, or 23.1% ± 3.5%, with treatment times of 30.0 ± 3.7 min for RSBT and 12.3 ± 1.8 min for HDR-BT. Differences between measured vs predicted rotating catheter positions (corresponding to source position) were within 0.18 mm ± 0.12 mm longitudinally and 0.07° ± 0.78°. CONCLUSION: 169 Yb-based RSBT can increase PTV D90% or decrease urethral D10% relative to HDR-BT with treatment times of less than 1 h using a single-source robotic delivery system with treatment delivered in a single fraction. The prototype helical delivery system was able to demonstrate adequate mechanical accuracy.

Needle-free cervical cancer treatment using helical multishield intracavitary rotating shield brachytherapy with the 169 Yb Isotope.

PURPOSE: To assess the capability of an intracavitary 169 Yb-based helical multishield rotating shield brachytherapy (RSBT) delivery system to treat cervical cancer. The proposed RSBT delivery system contains a pair of 1.25 mm thick platinum partial shields with 45° and 180° emission angles, which travel in a helical pattern within the applicator. METHODS: A helically threaded tandem applicator with a 45° tandem curvature containing a helically threaded catheter was designed. A 0.6 mm diameter 169 Yb source with a length of 10.5 mm was simulated. A 37-patient treatment planning study, based on Monte Carlo dose calculations using MCNP5, was conducted with high-risk clinical target volumes (HR-CTVs) of 41.2-192.8 cm3 (average ± standard deviation of 79.9 ± 35.8 cm3 ). All patients were assumed to receive 25 fractions of 1.8 Gy of external beam radiation therapy (EBRT) before receiving 5 fractions of high-dose-rate brachytherapy (HDR-BT). For each patient, 192 Ir-based intracavitary (IC) HDR-BT, 192 Ir-based intracavitary/interstitial (IC/IS) HDR-BT using a hybrid applicator with eight IS needles, and 169 Yb-based RSBT plans were generated. RESULTS: For the IC, IC/IS, and RSBT treatment plans, 38%, 84%, and 86% of the plans, respectively, met the planning goal of an HR-CTV D90 (minimum dose to hottest 90%) of 85 GyEQD2 (α/ß = 10 Gy). Median (25th percentile, 75th percentile) treatment times for IC, IC/IS, and RSBT were 11.71 (6.62, 15.40) min, 68.00 (45.02, 80.02) min, and 25.30 (13.87, 35.39) min, respectively. 192 Ir activities ranging from 159.1-370 GBq (4.3-10 Ci) and 169 Yb activities ranging from 429.2-999 GBq (11.6-27 Ci) were used, which correspond to the same clinical ranges of dose rates at 1 cm off-source-axis in water. Extra needle insertion and planning time beyond that needed for intracavitary-only approaches was accounted for in the IC/IS treatment time calculations. CONCLUSION: 169 Yb-based RSBT for cervical cancer met the HR-CTV D90 goal of 85 Gy in a greater percentage of the patients considered than IC/IS (86% vs 84%, respectively) and can reduce overall treatment time relative to IC/IS. 169 Yb-based RSBT could be used to replace IC/IS in instances where IC/IS treatment is not available, especially in instances when HR-CTV volumes are ≥30 cm3 .

Efficient 169 Yb high-dose-rate brachytherapy source production using reactivation.

PURPOSE: To present and quantify the effectiveness of a method for the efficient production of 169 Yb high-dose-rate brachytherapy sources with 27 Ci activity upon clinical delivery, which have about the same dose rate in water at 1 cm from the source center as 10 Ci 192 Ir sources. MATERIALS: A theoretical framework for 169 Yb source activation and reactivation using thermal neutrons in a research reactor and 168 Yb-Yb2 O3 precursor is derived and benchmarked against published data. The model is dependent primarily on precursor 168 Yb enrichment percentage, active source volume of the active element, and average thermal neutron flux within the active source. RESULTS: Efficiency gains in 169 Yb source production are achievable through reactivation, and the gains increase with active source volume. For an average thermal neutron flux within the active source of 1 × 1014  n cm-2  s-1 , increasing the active source volume from 1 to 3 mm3 decreased reactor-days needed to generate one clinic-year of 169 Yb from 256 days yr-1 to 59 days yr-1 , and 82%-enriched precursor dropped from 80 mg yr-1 to 21 mg yr-1 . A resource reduction of 74%-77% is predicted for an active source volume increase from 1 to 3 mm3 . CONCLUSIONS: Dramatic cost savings are achievable in 169 Yb source production costs through reactivation if active sources larger than 1 mm3 are used.

Effectiveness of Rotating Shield Brachytherapy for Prostate Cancer Dose Escalation and Urethral Sparing.

PURPOSE: To compare single-fraction 153Gd-based rotating shield brachytherapy (RSBT) for prostate cancer with conventional 192Ir-based high-dose-rate brachytherapy (HDR-BT) in a planning study that radiobiologically accounts for dose rate and relative biological effectiveness. RSBT was used for planning target volume (PTV) dose escalation without increasing urethral dose for monotherapy, or for urethral sparing without decreasing PTV dose as a boost to external beam radiation therapy. METHODS AND MATERIALS: Twenty-six patients were studied. PTV doses were expressed as equivalent dose delivered in 2 Gy fractions (EQD2), accounting for relative biological effectiveness (1.00 for 192Ir and 1.15 for 153Gd), dose protraction (114-minute repair half-time), and tumor dose response (α/ß of 3.41 Gy). HDR-BT dose was prescribed such that 90% of the PTV received 110% of the prescription dose of 19 Gy for dose escalation and 15 Gy for urethral sparing, corresponding to EQD290% values (minimum EQD2 to the hottest 90% of the PTV) of 93.9 GyEQD2 and 60.7 GyEQD2, respectively. Twenty 90.95 GBq 153Gd RSBT sources and one 370 GBq 192Ir HDR-BT source were modeled. RESULTS: For dose escalation with fresh sources, RSBT increased PTV EQD290% by 42.5% ± 8.4% (average ± standard deviation) without increasing urethral D10%, with treatment times of 216.8 ± 28.9 minutes versus 15.1 ± 2.1 minutes. After 1 half-life (240.4 days for 153Gd and 73.8 days for 192Ir), EQD290% increased 20.5% ± 9.1%. For urethral sparing with fresh sources, RSBT decreased urethral D10% by 26.0% ± 3.4% without decreasing PTV EQD290%, with treatment times of 133.6 ± 16.5 minutes versus 12.0 ± 1.7 minutes. After 1 half-life, urethral D10% decreased 20.2% ± 4.8%. CONCLUSIONS: RSBT can increase PTV EQD90% or decrease urethral D10% relative to HDR-BT at the cost of increased treatment time. Source aging reduces RSBT benefit, but RSBT remains theoretically superior to HDR-BT by >20% after 1 half-life has elapsed.

Multisource Rotating Shield Brachytherapy Apparatus for Prostate Cancer.

PURPOSE: Our purpose is to present a novel multisource rotating shield brachytherapy (RSBT) apparatus for the simultaneous precise angular and linear positioning of partially shielded 153Gd brachytherapy sources in interstitial needles for the treatment of locally advanced prostate cancer. It is designed to lower the dose to nearby healthy tissues, the urethra in particular, relative to conventional high-dose-rate brachytherapy techniques. METHODS AND MATERIALS: Following needle implantation through the patient template, an angular drive mechanism is docked to the patient template. Each needle is coupled to a multisource afterloader catheter by a connector passing through a shaft. The shafts are rotated about their axes by translating a moving template between 2 stationary templates. The shafts' surfaces and moving template holes are helically threaded with the same pattern such that translation of the moving template causes simultaneous rotation of the shafts. The rotation of each shaft is mechanically transmitted to the catheter-source-shield combination, inside the needles, via several key-keyway pairs. The catheter angles are simultaneously incremented throughout treatment, and only a single 360° rotation of all catheters is needed for a full treatment. For each rotation angle, source depth in each needle is controlled by a multisource afterloader, which is proposed as an array of belt-driven linear actuators, each of which drives a wire that controls catheter depth in a needle. RESULTS: Treatment plans demonstrated that RSBT with the proposed apparatus reduced urethral D0.1cm3 (the minimum dose delivered to the hottest 0.1cm3 of the urethra) below that of conventional high-dose-rate brachytherapy by 31% for urethral dose gradient volume within 3 mm of the urethra surface. Treatment time to deliver 20 Gy with the proposed multisource RSBT apparatus by use of nineteen 62.4-GBq 153Gd sources was 122 minutes. CONCLUSIONS: The proposed RSBT delivery apparatus enables a mechanically feasible urethra-sparing treatment technique for prostate cancer in a clinically reasonable time frame.