A finite element method for modeling diffusion of alpha-emitting particles in tissue.

BACKGROUND: Diffusing alpha-emitters Radiation Therapy ("DaRT") is a promising new modality for the treatment of solid tumors. Interstitial sources containing 224 Ra are inserted into the tumor, producing alpha particles via the decay of 224 Ra and its daughters. The alpha particles are able to produce a "kill region" of several mm due to the diffusion of the alpha-emitting atoms. The Diffusion-Leakage (D-L) model has been proposed to describe the movement of the alpha-emitters used in DaRT in tumor tissue. PURPOSE: To date, estimating the dose delivered under the D-L model has been accomplished with numerical solutions based on finite difference methods, namely DART1D and DART2D, as well as with asymptotic expressions for the long time limit. The aim of this work is to develop a flexible method of finite elements for solving the D-L model and to validate prior solutions of the D-L model. METHODS: We develop a two-dimensional finite element solution to the D-L model implemented using the FEniCS software library. Our approach solves the variational formulation of the D-L equations on an unstructured mesh of triangular Lagrangian elements. We calculate the local dose in the mid- and axial planes of the source and validate our results against the one- and two-dimensional solutions obtained using the previously proposed numerical scheme, DART1D and DART2D. We use our model to estimate the change in dose in the source midplane as a function of the physical parameters used in the D-L model. RESULTS: The local dose at the end of a 30 day treatment period estimated by our numerical method differs from DART1D and DART2D by less than 1% in the source midplane and less than 3% along the source axis over clinically relevant distances, with the largest discrepancies in high gradient areas where the Finite Element Method (FEM) mesh has a higher element density. We find that within current experimentally estimated ranges for D-L model parameters, the dose in the source midplane at a distance of 2 mm can vary by over a factor of 3. CONCLUSIONS: The 2D finite element model reproduces the calculated dose obtained with DART1D and DART2D under the assumptions D-L model. The variation in predicted dose within current experimental ranges for model parameters suggests the necessity of further studies to better determine their statistical distributions. Finally, the FEM model can be used to calculate dose from DaRT in a variety of realistic 2D geometries beyond the D-L model.

Feasibility and Safety of Diffusing Alpha-Emitter Radiation Therapy for Recurrent or Unresectable Skin Cancers.

Importance: Patients with recurrent or unresectable skin cancers have limited treatment options. Diffusing alpha-emitter radiation therapy (DaRT), a novel solid tumor management strategy using alpha-particle interstitial brachytherapy, may address this challenge. Objective: To evaluate the feasibility and safety of using DaRT to manage recurrent or unresectable skin cancers. Design, Setting, and Participants: This prospective cohort study of patients who received a 2-week to 3-week treatment course and were followed up for 24 weeks after treatment during 2021 and 2022 at 2 sites in the US. Patients with malignant skin tumors or soft tissue tumors were recruited if they had limited treatment options for tumors recurrent after prior surgery or external beam radiotherapy or unresectable tumors. Intervention: Patients underwent DaRT to deliver a physical dose of 10 Gy (equivalent weighted dose of 200 CGE) to the tumor. Main Outcomes and Measures: Feasibility of the DaRT procedure was evaluated based on the ability of investigators to successfully deliver radiation to the tumor. Patients were followed up for adverse events (AEs) for 24 weeks and for tumor response by physicians' physical examination and imaging 12 weeks after device removal. Results: This study included 10 participants with recurrent or unresectable skin cancer (median [IQR] age, 72 [68-75] years; 6 males [60%]; 4 females [40%]). Six patients (60%) had recurrent disease, and 4 (40%) had tumors that were deemed unresectable. Tumors were located on the nose, chin, eyelid, scalp, neck, trunk, and extremities. Median (range) tumor volume before treatment was 2.1 cm3 (0.65-12.65 cm3). The mean (SD) prescription dose coverage of the gross tumor volume was 91% (2.8%) with all tumors having coverage of 85% or more. No device-related grade 3 AEs were noted. Common AEs were grade 1 to 2 erythema, edema, and pruritus. At 12 weeks following treatment, there was a 100% complete response rate. Nine of 10 complete responses (90%) were confirmed by CT imaging. Conclusions and Relevance: This cohort study suggests the feasibility and preliminary safety of DaRT in the management of recurrent or unresectable skin cancers. The favorable safety profile and high response rates are promising. A US trial for marketing approval based on this pilot study is under way. Trial Registration: ClinicalTrials.gov Identifier: NCT04377360.

Clinical Experience and Feasibility of Using 2D-kVimage Online Intervention in the Ultrafractionated Stereotactic Radiation Treatment of Prostate Cancer.

PURPOSE: This study reports clinical experience and feasibility of using a 2-dimensional (2D)-kV image system with online intervention in the ultrafractionated stereotactic body radiation treatment (UF-SBRT) of prostate cancer. METHODS AND MATERIALS: Fifteen patients with prostate cancer who had a low- to intermediate-risk marker implanted received UF-SBRT with online 2D-kV image tracking and a manual beam interruption strategy with a 2-mm motion threshold. A total of 180 kV paired setup images and 1272 intrabeam 2D-kV images were analyzed to evaluate the setup deviation and intratreatment target deviation. Correlation of expected treatment interruptions with a set of parameters (eg, image and treatment time; direction of deviation) was performed (Spearman test). A subset of the data from 22 fractions was re-evaluated to check the differences in analysis results between using the planning position and using the pretreatment setup position as a reference. Margins based on the derived system and random errors were calculated to evaluate the feasibility of the workflow in ensuring prostate coverage during treatment. RESULTS: Mean target motion in 3D propagated from 1.0 mm (setup at 0 minutes) to 2.0 mm (beam on at 7 minutes) to 2.4 mm (end at 13.5 minutes). Out of 75 fractions, 50 were found to require beam interruption. Interruption had a strong correlation with prostate motion along the longitudinal direction and had moderate correlation with prostate motion along the vertical direction and the prostate's treatment starting position along vertical and longitudinal directions. Using the pretreatment position as a reference for intrabeam monitoring, the magnitude of motion deviation from the reference position was reduced by 0.3 mm at a vertical direction and 0.4 mm at lateral and longitudinal directions. The calculated 3D margin to ensure target coverage was 3.7 mm, 4.6 mm, and 5.0 mm in lateral, vertical, and longitudinal directions, respectively. CONCLUSIONS: Prostate motion propagated over time. It is feasible to use a 2D-kV online intrabeam monitoring system with a proper intervention scheme to perform UF-SBRT for prostate cancer.

HDR prostate brachytherapy plan robustness and its effect on in-vivo source tracking error thresholds: A multi-institutional study.

PURPOSE: The purpose of this study was to examine the effect of departmental planning techniques on appropriate in-vivo source tracking error thresholds for high dose rate (HDR) prostate brachytherapy (BT) treatments, and to determine if a single in-vivo source tracking error threshold would be appropriate for the same patient anatomy. METHODS: The prostate, rectum, and urethra were contoured on a single patient transrectal ultrasound (TRUS) dataset. Anonymized DICOM files were disseminated to 16 departments who created an HDR prostate BT treatment plan on the dataset with a prescription dose of 15 Gy in a single fraction. Departments were asked to follow their own local treatment planning guidelines. Source positioning errors were then simulated in the 16 treatment plans and the effect on dose-volume histogram (DVH) indices calculated. Change in DVH indices were used to determine appropriate in-vivo source tracking error thresholds. Plans were considered to require intervention if the following DVH conditions occurred: prostate V100% < 90%, urethra D0.1cc > 118%, and rectumtt Dmax > 80%. RESULTS: There was wide variation in appropriate in-vivo source tracking error thresholds among the 16 participating departments, ranging from 1 to 6 mm. Appropriate in-vivo source tracking error thresholds were also found to depend on the direction of the source positioning error and the endpoint. A robustness parameter was derived, and found to correlate with the sensitivity of plans to source positioning errors. CONCLUSIONS: A single HDR prostate BT in-vivo source tracking error threshold cannot be applied across multiple departments, even for the same patient anatomy. The burden on in-vivo source tracking devices may be eased through improving HDR prostate BT plan robustness during the plan optimisation phase.

Protocol for the measurement of the absorbed dose rate to water for a planar 32P beta emitting brachytherapy source: A multi-institutional validation.

PURPOSE: This is a multi-institutional report on inter-observer and inter-instrument variation in the calibration of the absorbed dose rate for a planar 32P beta emitting brachytherapy source. Measurement accuracy is essential since the dose profile is steep and the source is used for the treatment of tumors that are located in close proximity to healthy nervous system structures. METHODS AND MATERIALS: An RIC-100 32P source was calibrated by three institutions using their own equipment and following their standard procedures. The first institution calibrated the source with an electron diode and EBT3 film. The second institution used an electron diode. The third institution used HD810 film. Additionally, each institution was asked to calibrate the source using an electron diode and procedure that was shared among all institutions and shipped along with the radiation source. The dose rate was reported in units of cGy*min-1 at a water equivalent depth of 1 mm. RESULTS: Close agreement was observed in the measurements from different users and equipment. The variation across all diode detectors and institutions had a standard deviation of 1.8% and maximum difference of 4.6%. The observed variation among two different diode systems used within the same institution had a mean difference of 1.6% and a maximum variation of 1.8%. The variations among film and diode systems used within the same institution had a mean difference of 2.9% and a maximum variation of 4.3% CONCLUSIONS: The absorbed dose rate measurement protocol of the planar beta-emitting 32P source permits consistent dosimetry across three institutions and five different electron diode and radiochromic film systems. The methodologies presented herein should enable measurement consistency among other clinical users, which will help ensure high quality patient treatments and outcomes analysis.

Early outcomes of high-dose-rate brachytherapy combined with ultra-hypofractionated radiation in higher-risk prostate cancer.

PURPOSE: This study evaluated outcomes associated with a high-dose-rate (HDR) brachytherapy boost combined with stereotactic body radiation therapy (SBRT) for patients with higher-risk localized prostate cancer. MATERIALS AND METHODS: We identified 101 patients with National Comprehensive Cancer Network high-risk, unfavorable intermediate-risk, or favorable intermediate-risk with probable extra-prostatic extension treated with HDR brachytherapy (15 Gy x 1 fraction) followed by SBRT (5 Gy x 5 daily fractions to the prostate and/or seminal vesicles and/or pelvic lymph nodes). Androgen deprivation therapy was used in 55.4% of all patients (90% of high-risk, 33% of intermediate-risk). Toxicities according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0 and International Prostate Symptom Scores were prospectively documented at each followup visit. Biochemical relapse was defined as PSA nadir +2ng/mL. RESULTS: The median follow-up time after SBRT was 24.1 months. No grade ≥3 toxicities were observed. The incidence of acute and late grade 2 gastrointestinal toxicities was both 0.99%. Acute and late grade 2 genitourinary (GU) toxicities were observed in 5.9% and 9.9%, respectively. Median time to a grade 2 GU toxicity was 6 months with a 14% 2-year actuarial rate of grade 2 GU toxicity. Median International Prostate Symptom Scores at 24 months was not significantly different than baseline (6 vs. 5; p = 0.24). Inclusion of pelvic lymph nodes and absence of a rectal spacer were significantly associated with more frequent grade ≥1 GU toxicity, but not grade ≥2 GU or gastrointestinal toxicity. The 2-year biochemical relapse free survival was 97%. CONCLUSIONS: HDR brachytherapy combined with SBRT was associated with a favorable early toxicity profile and encouraging cancer control outcomes.

Quantifying clinical severity of physics errors in high-dose rate prostate brachytherapy using simulations.

PURPOSE: To quantitatively evaluate through automated simulations the clinical significance of potential high-dose rate (HDR) prostate brachytherapy (HDRPB) physics errors selected from our internal failure-modes and effect analysis (FMEA). METHODS AND MATERIALS: A list of failure modes was compiled and scored independently by 8 brachytherapy physicists on a one-to-ten scale for severity (S), occurrence (O), and detectability (D), with risk priority number (RPN) = SxOxD. Variability of RPNs across observers (standard deviation/average) was calculated. Six idealized HDRPB plans were generated, and error simulations were performed: single (N = 1722) and systematic (N = 126) catheter shifts (craniocaudal; -1cm:1 cm); single catheter digitization errors (tip and connector needle-tips displaced independently in random directions; 0.1 cm:0.5 cm; N = 44,318); and swaps (two catheters swapped during digitization or connection; N = 528). The deviations due to each error in prostate D90%, urethra D20%, and rectum D1cm3 were analyzed using two thresholds: 5-20% (possible clinical impact) and >20% (potentially reportable events). RESULTS: Twenty-nine relevant failure modes were described. Overall, RPNs ranged from 6 to 108 (average ± 1 standard deviation, 46 ± 23), with responder variability ranging from 19% to 184% (average 75% ± 30%). Potentially reportable events were observed in the simulations for systematic shifts >0.4 cm for prostate and digitization errors >0.3 cm for the urethra and >0.4 cm for rectum. Possible clinical impact was observed for catheter swaps (all organs), systematic shifts >0.2 cm for prostate and >0.4 cm for rectum, and digitization errors >0.2 cm for prostate and >0.1 cm for urethra and rectum. CONCLUSIONS: A high variability in RPN scores was observed. Systematic simulations can provide insight in the severity scoring of multiple failure modes, supplementing typical FMEA approaches.

Low-Dose-Rate Brachytherapy Combined With Ultrahypofractionated Radiation Therapy for Clinically Localized, Intermediate-Risk Prostate Cancer: Results From a Prospective Trial.

PURPOSE: To report early toxicity and tumor control outcomes of Pd-103 brachytherapy with ultrahypofractionated stereotactic radiation therapy (RT) for intermediate-risk prostate cancer. METHODS AND MATERIALS: This prospective trial included 40 patients with intermediate-risk prostate cancer who underwent low-dose-rate (Pd-103) brachytherapy (prescription dose, 100 Gy), followed 1 month later with ultrahypofractionated stereotactic RT (25 Gy in 5 fractions) to the prostate and seminal vesicles. The primary endpoint was the rate of grade 2+ genitourinary toxicity at 12 months using Common Terminology Criteria for Adverse Events v 4.0. Secondary endpoints included patient-reported quality-of-life metrics (International Prostate Scoring System [IPSS], International Index of Erectile Function, and Expanded Prostate Cancer Index Composite-bowel). Biochemical failure was defined as prostate-specific antigen nadir +2 ng/mL. Posttreatment biopsies were performed at between 24 and 36 months; median follow-up was 36 months. RESULTS: The rate of grade 2 urinary toxicity at 12 months was 25% with no grade 3 urinary toxicity noted. Mean IPSS at baseline and 12 and 24 months was 5, 10, and 6.2, respectively. Mean change in IPSS from baseline at 12 months was +5.5 (interquartile range, 1-9.75) and +1.05 (interquartile range, -3 to 3.25) at 24 months. Grade 2 bowel toxicity was 5% at 12 months with no grade 3 bowel toxicity noted. Mean Expanded Prostate Cancer Index Composite-bowel domain scores at baseline and 12 months were 92.8 and 90.3, respectively. Of patients who were potent (International Index of Erectile Function ≥21) at baseline, 75% remained potent at 12 months. Of 40 patients, 28 underwent posttreatment prostate biopsy (PPB), which was negative (n = 20) or demonstrated severe treatment effect (n = 8). No patient had a positive PPB or developed biochemical failure during the follow-up period. One patient without a PPB developed osseous metastases at 18 months posttreatment in the absence of biochemical failure. CONCLUSION: Low-dose-rate brachytherapy in combination with ultrahypofractionated stereotactic RT was safe and effective for intermediate-risk prostate cancer in early results of this trial.

Three-dimensional printing in radiation oncology: A systematic review of the literature.

PURPOSE/OBJECTIVES: Three-dimensional (3D) printing is recognized as an effective clinical and educational tool in procedurally intensive specialties. However, it has a nascent role in radiation oncology. The goal of this investigation is to clarify the extent to which 3D printing applications are currently being used in radiation oncology through a systematic review of the literature. MATERIALS/METHODS: A search protocol was defined according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Included articles were evaluated using parameters of interest including: year and country of publication, experimental design, sample size for clinical studies, radiation oncology topic, reported outcomes, and implementation barriers or safety concerns. RESULTS: One hundred and three publications from 2012 to 2019 met inclusion criteria. The most commonly described 3D printing applications included quality assurance phantoms (26%), brachytherapy applicators (20%), bolus (17%), preclinical animal irradiation (10%), compensators (7%), and immobilization devices (5%). Most studies were preclinical feasibility studies (63%), with few clinical investigations such as case reports or series (13%) or cohort studies (11%). The most common applications evaluated within clinical settings included brachytherapy applicators (44%) and bolus (28%). Sample sizes for clinical investigations were small (median 10, range 1-42). A minority of articles described basic or translational research (11%) and workflow or cost evaluation studies (3%). The number of articles increased over time (P < 0.0001). While outcomes were heterogeneous, most studies reported successful implementation of accurate and cost-effective 3D printing methods. CONCLUSIONS: Three-dimensional printing is rapidly growing in radiation oncology and has been implemented effectively in a diverse array of applications. Although the number of 3D printing publications has steadily risen, the majority of current reports are preclinical in nature and the few clinical studies that do exist report on small sample sizes. Further dissemination of ongoing investigations describing the clinical application of developed 3D printing technologies in larger cohorts is warranted.

Developing a MLC modifier program to improve fiducial detection for MV/kV imaging during hypofractionated prostate volumetric modulated arc therapy.

PURPOSE: To develop an Eclipse plug-in (MLC_MODIFIER) that automatically modifies control points to expose fiducials obscured by MLC during VMAT, thereby facilitating tracking using periodic MV/kV imaging. METHOD: Three-dimensional fiducial tracking was performed during VMAT by pairing short-arc (3°) MV digital tomosynthesis (DTS) images to triggered kV images. To evaluate MLC_MODIFIER efficacy, two cohorts of patients were considered. For first 12 patients, plans were manually edited to expose one fiducial marker. Next for 15 patients, plans were modified using MLC_MODIFIER script. MLC_MODIFIER evaluated MLC apertures at appropriate angles for marker visibility. Angles subtended by control points were compressed and low-dose "imaging" control points were inserted and exposed one marker with 1 cm margin. Patient's images were retrospectively reviewed to determine rate of MV registration failures. Failure categories were poor DTS image quality, MLC blockage of fiducials, or unknown reasons. Dosimetric differences in rectum, bladder, and urethra D1 cc, PTV maximum dose, and PTV dose homogeneity (PTV HI) were evaluated. Statistical significance was evaluated using Fisher's exact and Student's t test. RESULT: Overall MV registration failures, failures due to poor image quality, MLC blockage, and unknown reasons were 33% versus 8.9% (P < 0.0001), 8% versus 6.4% (P < 0.05), 13.6% versus 0.1% (P < 0.0001), and 7.6% versus 2.4% (P < 0.0001) for manually edited and MLC_MODIFIER plans, respectively. PTV maximum and HI increased on average from unmodified plans by 2.1% and 0.3% (P < 0.004) and 22.0% and 3.3% (P < 0.004) for manually edited and MLC_MODIFIED plans, respectively. Changes in bladder, rectum, and urethra D1CC were similar for each method and less than 0.7%. CONCLUSION: Increasing fiducial visibility via an automated process comprised of angular compression of control points and insertion of additional "imaging" control points is feasible. Degradation of plan quality is minimal. Fiducial detection and registration success rates are significantly improved compared to manually edited apertures.

Novel intraoperative radiotherapy utilizing prefabricated custom three-dimensionally printed high-dose-rate applicators.

BACKGROUND: Intraoperative radiotherapy (IORT) is an effective strategy for the delivery of high doses of radiotherapy to a residual tumor or resection cavity with relative sparing of nearby healthy tissues. This strategy is an important component of the multimodality management of pediatric soft tissue sarcomas, particularly in cases where patients have received prior courses of external beam radiotherapy. PURPOSE: Tumor beds with significant topographic irregularity remain a therapeutic challenge because existing IORT technologies are typically most reliable with flat surfaces. To address this limitation, we have developed a novel strategy to create custom, prefabricated high-dose-rate (HDR)-IORT applicators designed to match the shape of an anticipated surgical cavity. METHODS AND MATERIALS: Silastic applicators are constructed using three-dimensional (3D) printing and are derived from volumetric segmentation of preoperative imaging. RESULTS: HDR preplanning with the applicators improves dosimetric accuracy and minimizes incremental operative time. In this report, we describe the fabrication process for the 3D-printed applicators and detail our experience utilizing this strategy in two pediatric patients who underwent HDR-IORT as part of complex base of skull sarcoma resections. CONCLUSIONS: Early experience suggests that usage of the custom applicators is feasible, versatile for a variety of clinical situations, and enables the uniform delivery of high superficial doses of radiotherapy to irregularly shaped surgical cavities.

Placement of an absorbable rectal hydrogel spacer in patients undergoing low-dose-rate brachytherapy with palladium-103.

PURPOSE: Rates of rectal toxicity after low-dose-rate (LDR) brachytherapy for prostate cancer are dependent on rectal dose, which is associated with rectal distance from prostate and implanted seeds. Placement of a hydrogel spacer between the prostate and rectum has proven to reduce the volume of the rectum exposed to higher radiation dose levels in the setting of external beam radiotherapy. We present our findings with placing a rectal hydrogel spacer in patients following LDR brachytherapy, and we further assess the impact of this placement on dosimetry and acute rectal toxicity. METHODS AND MATERIALS: Between January 2016 and April 2017, 74 patients had placement of a hydrogel spacer, immediately following a Pd-103 seed-implant procedure. Brachytherapy was delivered as follows: as a monotherapy to 26 (35%) patients; as part of planned combination therapy with external beam radiotherapy to 40 (54%) patients; or as a salvage monotherapy to eight (11%) patients. Postoperative MRI was used to assess separation achieved with rectal spacer. Acute toxicity was assessed retrospectively using Radiation Oncology Therapy Group radiation toxicity grading system. Rectal dosimetry was compared with a consecutive cohort of 136 patients treated with seed implantation at our institution without a spacer, using a 2-tailed paired Student's t test (p < 0.05 for statistical significance). RESULTS: On average, 11.2-mm (SD 3.3) separation was achieved between the prostate and the rectum. The resultant mean rectal volume receiving 100% of prescribed dose (V100%), dose to 1 cc of rectum (D1cc), and dose to 2 cc of rectum (D2cc) were 0 (SD 0.05 cc), 25.3% (SD 12.7), and 20.5% (SD 9.9), respectively. All rectal dosimetric parameters improved significantly for the cohort with spacer placement as compared with the nonspacer cohort. Mean prostate volume, prostate V100 and dose to 90% of gland (D90) were 29.3 cc (SD 12.4), 94.0% (SD 3.81), and 112.4% (SD 12.0), respectively. Urethral D20, D5cc, and D1cc were 122.0% (SD 17.27), 133.8% (SD 22.8), and 144.0% (SD 25.4), respectively. After completing all treatments, at the time of first the followup, 7 patients reported acute rectal toxicity-6 experiencing Grade 1 rectal discomfort and 1 (with preexisting hemorrhoids) experiencing Grade 1 bleeding. CONCLUSIONS: Injection of rectal spacer is feasible in the post-LDR brachytherapy setting and reduces dose to the rectum with minimal toxicity. Prostate and urethral dosimetries do not appear to be affected by the placement of a spacer. Further studies with long-term followup are warranted to assess the impact on reduction of late rectal toxicity.

A fast inverse treatment planning strategy facilitating optimized catheter selection in image-guided high-dose-rate interstitial gynecologic brachytherapy.

PURPOSE: Interstitial high-dose rate (HDR) brachytherapy is an important therapeutic strategy for the treatment of locally advanced gynecologic (GYN) cancers. The outcome of this therapy is determined by the quality of dose distribution achieved. This paper focuses on a novel yet simple heuristic for catheter selection for GYN HDR brachytherapy and their comparison against state of the art optimization strategies. The proposed technique is intended to act as a decision-supporting tool to select a favorable needle configuration. MATERIALS: The presented heuristic for catheter optimization is based on a shrinkage-type algorithm (SACO). It is compared against state of the art planning in a retrospective study of 20 patients who previously received image-guided interstitial HDR brachytherapy using a Syed Neblett template. From those plans, template orientation and position are estimated via a rigid registration of the template with the actual catheter trajectories. All potential straight trajectories intersecting the contoured clinical target volume (CTV) are considered for catheter optimization. Retrospectively generated plans and clinical plans are compared with respect to dosimetric performance and optimization time. RESULTS: All plans were generated with one single run of the optimizer lasting 0.6-97.4 s. Compared to manual optimization, SACO yields a statistically significant (P ≤ 0.05) improved target coverage while at the same time fulfilling all dosimetric constraints for organs at risk (OARs). Comparing inverse planning strategies, dosimetric evaluation for SACO and "hybrid inverse planning and optimization" (HIPO), as gold standard, shows no statistically significant difference (P > 0.05). However, SACO provides the potential to reduce the number of used catheters without compromising plan quality. CONCLUSION: The proposed heuristic for needle selection provides fast catheter selection with optimization times suited for intraoperative treatment planning. Compared to manual optimization, the proposed methodology results in fewer catheters without a clinically significant loss in plan quality. The proposed approach can be used as a decision support tool that guides the user to find the ideal number and configuration of catheters.

MR- versus CT-based high-dose-rate interstitial brachytherapy for vaginal recurrence of endometrial cancer.

PURPOSE: To compare clinical outcomes of MR-based versus CT-based high-dose-rate interstitial brachytherapy (ISBT) for vaginal recurrence of endometrioid endometrial cancer (EC). METHODS AND MATERIALS: We reviewed 66 patients with vaginal recurrent EC; 18 had MR-based ISBT on a prospective clinical trial and 48 had CT-based treatment. Kaplan-Meier survival modeling was used to generate estimates for local control (LC), disease-free interval (DFI), and overall survival (OS), and multivariate Cox modeling was used to assess prognostic factors. Toxicities were evaluated and compared. RESULTS: Median followup was 33 months (CT 30 months, MR 35 months). Median cumulative equivalent dose in 2-Gy fractions was 75.5 Gy for MR-ISBT and 73.8 Gy for CT-ISBT (p = 0.58). MR patients were older (p = 0.03) and had larger tumor size (>4 cm vs. ≤ 4 cm) compared to CT patients (p = 0.04). For MR-based versus CT-based ISBT, 3-year KM rate for local control was 100% versus 78% (p = 0.04), DFI was 69% versus 55% (p = 0.1), and OS was 63% versus 75% (p = 0.81), respectively. On multivariate analysis, tumor Grade 3 was associated with worse OS (HR 3.57, 95% CI 1.25, 11.36) in a model with MR-ISBT (HR 0.56, 95% CI 0.16, 1.89). Toxicities were not significantly different between the two modalities. CONCLUSION: Despite worse patient prognostic features, MR-ISBT was associated with a significantly better (100%) 3-year local control, comparable survival, and improved DFI rates compared to CT. Toxicities did not differ compared to CT-ISBT patients. Tumor grade contributed as the most significant predictor for survival. Larger prospective studies are needed to assess the impact of MR-ISBT on survival outcomes.

Intraoperative implantation of a mesh of directional palladium sources (CivaSheet): Dosimetry verification, clinical commissioning, dose specification, and preliminary experience.

PURPOSE: To present the clinical commissioning of a novel 103Pd directional brachytherapy device (CivaSheet) for intraoperative radiation therapy. METHODS AND MATERIALS: Clinical commissioning for the CivaSheet consisted of establishing: (1) source strength calibration capabilities, (2) experimental verification of TG-43 dosimetry parameters, (3) treatment planning system validation, and (4) departmental practice for dose specification and source ordering. Experimental verification was performed in water with radiochromic film calibrated with a 37 kVp X-ray beam. Percentage difference ([measurements - calculation]/calculation) and distance to agreement (difference between film-to-source distance and distance that minimized the percentage difference) were calculated. Nomogram values (in U/100 Gy) for all configurations (up to 20 × 20 sources) were calculated for source ordering. Clinical commissioning was used on patients enrolled in an ongoing Institutional Review Board-approved protocol. RESULTS: A source calibration procedure was established, and the treatment planning system was commissioned within standard clinical uncertainties. Percentage dose differences (distances to agreement) between measured and calculated doses were 8.6% (-0.12 mm), 0.6% (-0.01 mm), -6.4% (0.22 mm), and -10.0% (0.44 mm) at depths of 2.3, 5.1, 8.0, and 11.1 mm, respectively. All differences were within the experimental uncertainties. Nomogram values depended on sheet size and spatial extent. A value of 2.4U/100 Gy per CivaDot was found to satisfy most cases, ranging from 2.3 to 3.3U/100 Gy. Nomogram results depended on elongation of the treatment area with a higher variation observed for smaller treatment areas. Postimplantation dose evaluation was feasible. CONCLUSIONS: Commissioning and clinical deployment of CivaSheet was feasible using BrachyVision for postoperative dose evaluation. Experimental verification confirmed that the available TG-43 dosimetry parameters are accurate for clinical use.

Prospective Clinical Implementation of a Novel Magnetic Resonance Tracking Device for Real-Time Brachytherapy Catheter Positioning.

PURPOSE: We designed and built dedicated active magnetic resonance (MR)-tracked (MRTR) stylets. We explored the role of MRTR in a prospective clinical trial. METHODS AND MATERIALS: Eleven gynecologic cancer patients underwent MRTR to rapidly optimize interstitial catheter placement. MRTR catheter tip location and orientation were computed and overlaid on images displayed on in-room monitors at rates of 6 to 16 frames per second. Three modes of actively tracked navigation were analyzed: coarse navigation to the approximate region around the tumor; fine-tuning, bringing the stylets to the desired location; and pullback, with MRTR stylets rapidly withdrawn from within the catheters, providing catheter trajectories for radiation treatment planning (RTP). Catheters with conventional stylets were inserted, forming baseline locations. MRTR stylets were substituted, and catheter navigation was performed by a clinician working inside the MRI bore, using monitor feedback. RESULTS: Coarse navigation allowed repositioning of the MRTR catheters tips by 16 mm (mean), relative to baseline, in 14 ± 5 s/catheter (mean ± standard deviation [SD]). The fine-tuning mode repositioned the catheter tips by a further 12 mm, in 24 ± 17 s/catheter. Pullback mode provided catheter trajectories with RTP point resolution of ∼1.5 mm, in 1 to 9 s/catheter. CONCLUSIONS: MRTR-based navigation resulted in rapid and optimal placement of interstitial brachytherapy catheters. Catheters were repositioned compared with the initial insertion without tracking. In pullback mode, catheter trajectories matched computed tomographic precision, enabling their use for RTP.

Rectum and bladder spacing in cervical cancer brachytherapy using a novel injectable hydrogel compound.

PURPOSE: The aim of this study was to evaluate injection of a novel hydrogel (TraceIT; Augmenix, Waltham, MA) between the cervix, rectum, and bladder in female cadavers compared with, and in addition to, the current standard of gauze packing, for organ-at-risk sparing in cervical cancer brachytherapy planning. METHODS AND MATERIALS: This brachytherapy cadaver study used T2-weighted MRI and CT imaging to compare three scenarios: (1) gauze packing alone, (2) hydrogel injection placed in the cervical fornices and rectovaginal septum, and (3) gauze packing in conjunction with hydrogel injection. Hydrogel distribution was evaluated. Doses to 2 cm3 volumes (D2cc) for the rectum, bladder, and sigmoid were collected. Statistical significance (p < 0.05) was evaluated using a two-tailed paired t test. RESULTS: Hydrogel was successfully injected to space the bladder and rectum from the cervix in all five cadavers. The spacer was easily identifiable on both CT and MRI. The use of hydrogel in addition to packing resulted in a 22% decrease in rectum D2cc dose (p = 0.02), a 10% decrease in bladder D2cc (p = 0.27), and no change in sigmoid D2cc dose. No difference was observed between hydrogel only vs. gauze packing only. CONCLUSIONS: Our results revealed a significant clinically meaningful decrease in rectal D2cc associated with the use of hydrogel in addition to gauze packing-TraceIT hydrogel holds promise as a spacer in cervical cancer therapy.

A fast multitarget inverse treatment planning strategy optimizing dosimetric measures for high-dose-rate (HDR) brachytherapy.

PURPOSE: In this study, we introduce a novel, fast, inverse treatment planning strategy for interstitial high-dose-rate (HDR) brachytherapy with multiple regions of interest solely based on dose-volume-histogram-related dosimetric measures (DMs). METHODS: We present a new problem formulation of the objective function that approximates the indicator variables of the standard DM optimization problem with a smooth logistic function. This problem is optimized by standard gradient-based methods. The proposed approach is then compared against state-of-the-art optimization strategies. RESULTS: All generated plans fulfilled prescribed DMs for all organs at risk. Compared to clinical practice, a statistically significant improvement (p=0.01) in coverage of target structures was achieved. Simultaneously, DMs representing high-dose regions were significantly reduced (p=0.01). The novel optimization strategies run-time was (0.8 ± 0.3) s and thus outperformed the best competing strategies of the state of the art. In addition, the novel DM-based approach was associated with a statistically significant (p=0.01) increase in the number of active dwell positions and a decrease in the maximum dwell time. CONCLUSIONS: The generated plans showed a clinically significant increase in target coverage with fewer hot spots, with an optimization time approximately three orders of magnitude shorter than manual optimization currently used in clinical practice. As optimization is solely based on DMs, intuitive, interactive, real-time treatment planning, which motivated the adoption of manual optimization in our clinic, is possible.