Feasibility and clinical implementation of MRI-guided surface brachytherapy.

Purpose: Best practices for high-dose-rate surface applicator brachytherapy treatment (SABT) have long relied on computed tomography (CT)-based imaging to visualize diseased sites for treatment planning. Compared with magnetic resonance (MR)-based imaging, CT provides insufficient soft tissue contrast. This work described the feasibility of clinical implementation of MR-based imaging in SABT planning to provide individualized treatment optimization. Material and methods: A 3D-printed phantom was used to fit Freiberg flap-style (Elekta, The Netherlands) applicator. Images were taken using an optimized pointwise encoding time reduction with radial acquisition (PETRA) MR sequence for catheter visualization, and a helical CT scan to generate parallel treatment plans. This clinical study included three patients undergoing SABT for Dupuytren's contracture/palmar fascial fibromatosis imaged with the same modalities.SABT planning was performed in Oncentra Brachy (Elekta Brachytherapy, The Netherlands) treatment planning software. A geometric analysis was conducted by comparing CT-based digitization with MR-based digitization. CT and MR dwell positions underwent a rigid registration, and average Euclidean distances between dwell positions were calculated. A dosimetric comparison was performed, including point-based dose difference calculations and volumetric segmentations with Dice similarity coefficient (DSC) calculations. Results: Euclidean distances between dwell positions from CT-based and MR-based plans were on average 0.68 ±0.05 mm and 1.35 ±0.17 mm for the phantom and patients, respectively. The point dose difference calculations were on average 0.92% for the phantom and 1.98% for the patients. The D95 and D90 DSC calculations were both 97.9% for the phantom, and on average 93.6% and 94.2%, respectively, for the patients. Conclusions: The sub-millimeter accuracy of dwell positions and high DSC's (> 0.95) of the phantom demonstrated that digitization was clinically acceptable, and accurate treatment plans were produced using MR-only imaging. This novel approach, MRI-guided SABT, will lead to individualized prescriptions for potentially improved patient outcomes.

Radiotherapy-Induced Neurocognitive Impairment Is Driven by Heightened Apoptotic Priming in Early Life and Prevented by Blocking BAX.

Although external beam radiotherapy (xRT) is commonly used to treat central nervous system (CNS) tumors in patients of all ages, young children treated with xRT frequently experience life-altering and dose-limiting neurocognitive impairment (NI) while adults do not. The lack of understanding of mechanisms responsible for these differences has impeded the development of neuroprotective treatments. Using a newly developed mouse model of xRT-induced NI, we found that neurocognitive function is impaired by ionizing radiation in a dose- and age-dependent manner, with the youngest animals being most affected. Histologic analysis revealed xRT-driven neuronal degeneration and cell death in neurogenic brain regions in young animals but not adults. BH3 profiling showed that neural stem and progenitor cells, neurons, and astrocytes in young mice are highly primed for apoptosis, rendering them hypersensitive to genotoxic damage. Analysis of single-cell RNA sequencing data revealed that neural cell vulnerability stems from heightened expression of proapoptotic genes including BAX, which is associated with developmental and mitogenic signaling by MYC. xRT induced apoptosis in primed neural cells by triggering a p53- and PUMA-initiated, proapoptotic feedback loop requiring cleavage of BID and culminating in BAX oligomerization and caspase activation. Notably, loss of BAX protected against apoptosis induced by proapoptotic signaling in vitro and prevented xRT-induced apoptosis in neural cells in vivo as well as neurocognitive sequelae. On the basis of these findings, preventing xRT-induced apoptosis specifically in immature neural cells by blocking BAX, BIM, or BID via direct or upstream mechanisms is expected to ameliorate NI in pediatric patients with CNS tumor. SIGNIFICANCE: Age- and differentiation-dependent apoptotic priming plays a pivotal role in driving radiotherapy-induced neurocognitive impairment and can be targeted for neuroprotection in pediatric patients.

Catheter reconstruction and dosimetric verification of MRI-only treatment planning (MRTP) for interstitial HDR brachytherapy using PETRA sequence.

Objective. The feasibility of MRI-only treatment planning (MRTP) for interstitial high-dose rate (HDR) brachytherapy (BT) was investigated for patients diagnosed with gynecologic cancer.Approach. A clinical MRTP workflow utilizing a 'pointwise encoding time reduction with radial acquisition (PETRA)' sequence was proposed. This is a clinically available MRI sequence optimized to improve interstitial catheter-tissue contrast. Interstitial needles outside the obturator region were reconstructed using MR images only. For catheters penetrating through the obturator, a library-based reconstruction was proposed. In this work, dwell coordinates from the clinical CT-based reconstruction were used as the surrogate for the library-based approach. For MR-only plan, dwell times were activated and assigned as in the clinical plans. The catheter reconstruction was assessed by comparing dwell position coordinates. The dosimetric comparisons between a clinical plan and MR-only plan were assessed for physical and EQD2 dose and volume parameters forD90,D50andD98for clinical target volume (CTV) andD2cc,D0.1ccandD5ccfor OARs.Main results. Catheter reconstruction was possible using the optimized PETRA sequence on MR images. An overall reconstruction difference of 1.7 ± 0.5 mm, attributed to registration-based errors, was found compared to the CT-based reconstruction. The MRTP workflow has the potential to generate a treatment plan with an equivalent dosimetric quality compared to the conventional CT/MRI-based approach. For CTVD90, physical and EQD2 dose and volume parameter differences were 1.5 ± 1.9% and 0.7 ± 1.0 Gy, respectively. ForD2ccOARs, DVH (EQD2) differences were -0.4 ± 1.1% (-0.2 ± 0.5 Gy), 0.5 ± 2.8% (0.2 ± 1.3 Gy) and -0.5 ± 1.4% (-0.2 ± 0.5 Gy) for rectum, bladder, and sigmoid, respectively.Significance. With the proposed MRTP approach, CT imaging may no longer be needed in HDR BT for interstitial gynecologic treatment. A proof-of-concept study was conducted to demonstrated that MRTP using PETRA is feasible, with comparable dosimetric results to the conventional CT/MRI-based approach.

First pointwise encoding time reduction with radial acquisition (PETRA) implementation for catheter detection in interstitial high-dose-rate (HDR) brachytherapy.

PURPOSE: A pointwise encoding time reduction with radial acquisition (PETRA) sequence was optimized to detect empty catheters in interstitial (HDR) brachytherapy with clinically acceptable spatial accuracy for the first time. Image quality and catheter detectability were assessed in phantoms, and the feasibility of PETRA's clinical implementation was assessed on a gynecological cancer patient. METHODS AND RESULTS: Empty catheters embedded in a gelatin phantom displayed positive signal on PETRA and more accurate cross-sections than on clinically employed T2-weighted sequences, differing by 0.4 mm on average from their nominal 2 mm diameter. PETRA presented minimal susceptibility differences and a symmetric metal artifact, contrary to the clinical sequences. The PETRA-CT catheter tip position differences assessed by a treatment planning system (TPS) were < 1 mm. PETRA also detected an interstitial template with empty catheters penetrating a poultry phantom and fused very well with CT. Interstitial catheter positional difference between PETRA and CT images was < 1 mm on average, increasing with distance from isocenter. All interstitial catheters and the employed interstitial template were detected on PETRA images of an endometrial adenocarcinoma patient. Empty needles were traceable using a TPS, with higher spatial resolution and more favorable contrast than on T2-weighted images used for contouring. A treatment plan could be produced by combining information from PETRA for catheter detection and from T2-weighted images for tumor and organs delineation. CONCLUSIONS: PETRA detected successfully and accurately interstitial catheters in phantoms. Its first clinical implementation shows a potential for MR-only treatment planning in interstitial HDR brachytherapy.

Dosimetric Planning Tradeoffs to Reduce Heart Dose Using Machine Learning-Guided Decision Support Software in Patients with Lung Cancer.

PURPOSE: Cardiac toxicity is a well-recognized risk after radiation therapy (RT) in patients with non-small cell lung cancer (NSCLC). However, the extent to which treatment planning optimization can reduce mean heart dose (MHD) without untoward increases in lung dose is unknown. METHODS AND MATERIALS: Retrospective analysis of RT plans from 353 consecutive patients with locally advanced NSCLC treated with intensity modulated RT (IMRT) or 3-dimensional conformal RT. Commercially available machine learning-guided clinical decision support software was used to match RT plans. A leave-one-out predictive model was used to examine lung dosimetric tradeoffs necessary to achieve a MHD reduction. RESULTS: Of all 232 patients, 91 patients (39%) had RT plan matches showing potential MHD reductions of >4 to 8 Gy without violating the upper limit of lung dose constraints (lung volume [V] receiving 20 Gy (V20 Gy) <37%, V5 Gy <70%, and mean lung dose [MLD] <20 Gy). When switching to IMRT, 75 of 103 patients (72.8%) had plan matches demonstrating improved MHD (average 2.0 Gy reduction, P < .0001) without violating lung constraints. Examining specific lung dose tradeoffs, a mean ≥3.7 Gy MHD reduction was achieved with corresponding absolute increases in lung V20 Gy, V5 Gy, and MLD of 3.3%, 5.0%, and 1.0 Gy, respectively. CONCLUSIONS: Nearly 40% of RT plans overall, and 73% when switched to IMRT, were predicted to have reductions in MHD >4 Gy with potentially clinically acceptable tradeoffs in lung dose. These observations demonstrate that decision support software for optimizing heart-lung dosimetric tradeoffs is feasible and may identify patients who might benefit most from more advanced RT technologies.

Feasibility of magnetic resonance-only high-dose-rate surface brachytherapy for clinical application.

PURPOSE: In this article, we investigate the feasibility of magnetic resonance (MR)-only imaging for high-dose-rate (HDR) surface brachytherapy (SABT). We examined whether a standard CT-based planning can be replaced with an MR-only planning. For this purpose, the MRI digitization and plan quality check processes were compared against the standard CT-based processes. A prospective clinical implementation of the MR-only planning was evaluated on a clinical data set. METHODS: A pointwise encoding time reduction with radial acquisition (PETRA) sequence was optimized for visualization of Freiburg flap (FF) on MR images. MR and conventional CT images were acquired with a FF applicator (Elekta, Stockholm, Sweden) placed on the following phantoms: (1) flat styrofoam (FST), FF locked-in placed with supporting structure; (2) cast-made facemask, and (3) porcine leg (PL). Catheters were digitized and activated with 10 mm step size on Oncentra Brachy 4.5.3 Treatment Planning System. The CT-only and MR-only treatment plans were generated by optimizing the dose to the target defined as volume at 3 mm skin depth. To compare the plans, the MRI-to-CT alignment was performed via rigid registration. Positional displacements of dwell positions between CT and MR plans were compared on the FST phantom and the relative percent dose difference in 2210 different points from CT or MR-only plans was compared. For all three phantoms, the comparabilities between CT and MR-only plans were assessed by calculating dice similarity coefficient (DSC) for volumes enclosing 150%, 125%, 100%, 95%, 90%, 80%, and 65% isodose lines (V150  -V65 ). The MR images of FF placed on the forearm of a healthy subject were acquired with this optimized PETRA sequence and used for treatment planning. The relative percent dose was calculated on 140 representative points placed at 3 mm skin depth to evaluate the dose to the skin. RESULTS: Using the optimized PETRA sequence, MRTP digitization accuracy was < 1 mm in each dimension and on three-dimensional (3D) displacement for the FST phantom. In each phantom and clinical data set, it was possible to generate MR-only treatment plans with the 3 mm skin depth prescription. In the FST phantom, the mean relative dose at the points was not significantly different (< 0.1% difference) for CT or MR-based plans. The assessment of similarities in dose profiles between CT and MR-only plans' provided DSC values greater than 0.96, 0.92, and 0.73 for all volumes enclosing up to 100%, 125%, and 150% isodose lines, respectively. CONCLUSION: The feasibility of generating a HDR treatment plan with FF using MR-only has been evaluated in phantoms with varying geometry and for a clinical data set. The optimization of a standard MRI sequence-PETRA-implemented in this study showed that FF-based catheters can be digitized and a plan can be generated using only MRI. The resulting MR-only plans were comparable to the conventional CT-based plans, suggesting that MRI alone can generate clinically acceptable plans for FF in phantoms and on a clinical data set. Reliable MR-only treatment planning could improve treatment prescription through more accurate characterization of soft tissue targets.

Selection criteria for high-dose-rate surface brachytherapy and electron beam therapy in cutaneous oncology.

PURPOSE: High-dose-rate (HDR) brachytherapy is an alternative treatment to electron external beam radiation therapy (EBRT) of superficial skin lesions. The purpose of this study was to establish the selection criteria for HDR brachytherapy technique (HDR-BT) and EBRT in cutaneous oncology for various clinical scenarios. MATERIAL AND METHODS: The study consists of two parts: a) EBRT and HDR-BT treatment plans comparison analyzing clinical target volumes (CTVs) with different geometries, field sizes, and topologies, and b) development of a prediction model capable of characterization of dose distributions in HDR surface brachytherapy for various geometries of treatment sites. RESULTS: A loss of CTV coverage for the electron plans (D90, D95) was recorded up to 45%, when curvature of the applicator increased over 30°. Values for D2 cm3 for both plans were comparable, and they were in range of ±8% of prescription dose. An increase in higher doses (D0.5 cm3 and D0.1 cm3) was observed in HDR-BT plans, and it was greater for larger lesions. The average increase was 3.8% for D0.5 cm3 and 12.3% for D0.1 cm3. When CTV was approximately flat, electron plans were comparable with HDR-BT plans, having lower average D2 cm3, D0.5 cm3, and D0.1 cm3 of 7.7%. Degradation of quality of electron plans was found to be more dependent on target curvature than on CTV size. CONCLUSIONS: Both EBRT and HDR-BT could be used in treatments of superficial lesions. HDR-BT revealed superior CTV coverage when the surface was very large, complex, curvy, or rounded, and when the topology was complicated. The prediction model can be used for an approximate calculation and quick assessment of radiation dose to organs-at-risk (OARs), at a depth or at a lateral distance from CTV.

Knowledge-based inverse treatment planning for low-dose-rate prostate brachytherapy.

PURPOSE: Permanent low-dose-rate brachytherapy is a widely used treatment modality for managing prostate cancer. In such interventions, treatment planning can be a challenging task and requires experience and skills of the planner. We developed a novel knowledge-based (KB) optimization method based on previous treatment plans. The purpose of this method was to generate clinically acceptable plans that do not require extensive manual adjustments in clinical scenarios. METHODS: Objective functions used in current inverse planning methods are preferably based on spatial invariant dose objectives rather than spatial dose distributions. Therefore, they are prone to return suboptimal plans resulting in time consuming plan adjustments. To overcome this limitation, a KB approach is introduced. The KB model uses the dose distributions of previous clinical plans projected onto a standardized geometry. From those standardized distributions a template plan is generated. The treatment plans were optimized with an in-house developed planning system by solving a constraint inverse optimization problem that mimics the projected template dose plan constraint to DVH metrics. The method is benchmarked under an IRB-approved retrospective study by comparing optimization time, dosimetric performance, and clinical acceptability against current clinical practice. The quality of the KB model is evaluated with a Turing test. RESULTS: The KB model consists of five high-quality treatment plans. Those plans were selected by one of our experts and showed all desired dosimetric features. After generating the model treatment plans were created with one run of the optimizer for the remaining 20 patients. The optimization time including needle optimization ranged from 6 to 29 s. Based on a Wilcoxon signed rank test the new plans are dosimetrically equivalent to current clinical practice. The Turing test showed that the proposed method generates plans that are equivalent to current clinical practice and that the dose prediction drives the optimization to achieve high-quality treatment plans. CONCLUSIONS: This study demonstrated that the proposed KB model was able to capture user-specific features in isodose lines which can be used to generate acceptable treatment plans with a single run of the optimization engine in under a minute. This could potentially reduce the time in the operating room and the time a patient is under anesthesia.

Positional and angular tracking of HDR 192 Ir source for brachytherapy quality assurance using radiochromic film dosimetry.

PURPOSE: To quantify and verify the dosimetric impact of high-dose rate (HDR) source positional uncertainty in brachytherapy, and to introduce a model for three-dimensional (3D) position tracking of the HDR source based on a two-dimensional (2D) measurement. This model has been utilized for the development of a comprehensive source quality assurance (QA) method using radiochromic film (RCF) dosimetry including assessment of different digitization uncertainties. METHODS: An algorithm was developed and verified to generate 2D dose maps of the mHDR-V2 192 Ir source (Elekta, Veenendaal, Netherlands) based on the AAPM TG-43 formalism. The limits of the dosimetric error associated with source (0.9 mm diameter) positional uncertainty were evaluated and experimentally verified with EBT3 film measurements for 6F (2.0 mm diameter) and 4F (1.3 mm diameter) size catheters at the surface (4F, 6F) and 10 mm further (4F only). To quantify this uncertainty, a source tracking model was developed to incorporate the unique geometric features of all isodose lines (IDLs) within any given 2D dose map away from the source. The tracking model normalized the dose map to its maximum, then quantified the IDLs using blob analysis based on features such as area, perimeter, weighted centroid, elliptic orientation, and circularity. The Pearson correlation coefficients (PCCs) between these features and source coordinates (x, y, z, θy , θz ) were calculated. To experimentally verify the accuracy of the tracking model, EBT3 film pieces were positioned within a Solid Water® (SW) phantom above and below the source and they were exposed simultaneously. RESULTS: The maximum measured dosimetric variations on the 6F and 4F catheter surfaces were 39.8% and 36.1%, respectively. At 10 mm further, the variation reduced to 2.6% for the 4F catheter which is in agreement with the calculations. The source center (x, y) was strongly correlated with the low IDL-weighted centroid (PCC = 0.99), while the distance to source (z) was correlated with the IDL areas (PCC = 0.96) and perimeters (PCC = 0.99). The source orientation θy was correlated with the difference between high and low IDL-weighted centroids (PCC = 0.98), while θz was correlated with the elliptic orientation of the 60-90% IDLs (PCC = 0.97) for a maximum distance of z = 5 mm. Beyond 5 mm, IDL circularity was significant, therefore limiting the determination of θz (PCC ≤ 0.48). The measured positional errors from the film sets above and below the source indicated a source position at the bottom of the catheter (-0.24 ± 0.07 mm). CONCLUSIONS: Isodose line features of a 2D dose map away from the HDR source can reveal its spatial coordinates. RCF was shown to be a suitable dosimeter for source tracking and dosimetry. This technique offers a novel source QA method and has the potential to be used for QA of commercial and customized applicators.

Development and clinical implementation of semi-automated treatment planning including 3D printable applicator holders in complex skin brachytherapy.

PURPOSE: High-dose-rate brachytherapy (HDR-BT) is a treatment option for malignant skin diseases compared to external beam radiation therapy, HDR-BT provides improved target coverage, better organ sparing, and has comparable treatment times. This is especially true for large clinical targets with complex topologies. To standardize and improve the quality and efficacy of the treatments, a novel streamlined treatment approach in complex skin HDR-BT was developed and implemented. This approach consists of auto generated treatment plans and a 3D printable applicator holder (3D-AH). MATERIALS AND METHODS: The in-house developed planning system automatically segments computed tomography simulation images (a), optimizes a treatment plan (b), and generates a model of the 3D-AH (c). The 3D-AH is used as an immobilization device for the flexible Freiburg flap applicator used to deliver treatment. The developed, automated planning is compared against the standard clinical plan generation process for a flat 10 × 10 cm2 field, curved fields with radii of 4, 6, and 8 cm, and a representative clinical case. The quality of the 3D print is verified via an additional CT of the flap applicator latched into the holder, followed by an automated rigid registration with the original planning CT. Finally, the methodology is implemented and tested clinically under an IRB approval. RESULTS: All automatically generated plans were reviewed and accepted for clinical use. For the clinical workflow, the coverage achieved at a prescription depth for the flat 4, 6, and 8 cm applicator was (100.0 ± 4.9)%, (100.0 ± 4.9)%, (96.0 ± 0.3)%, and (98.4 ± 0.3)%, respectively. For auto planning, the coverage was (99.9 ± 0.3)%, (100.0 ± 0.2)%, (100.0 ± 0.3)%, and (100.1 ± 0.2)%. For the clinical test case, the D90 for the clinical workflow and auto planning was found to be 93.5% and 100.29% of the prescribed dose, respectively. Processing of the patient's CT to generate trajectories and positions as well as the 3D model of the applicator took <5 min. CONCLUSION: This workflow automates time intensive catheter digitizing and treatment planning. Compared to printing full applicators, the use of 3D-AH reduces the complexity of the 3D prints, the amount of the material to be used, the time of 3D printing, and amount of quality assurance required. The proposed methodology improves the overall treatment plan quality in complex HDR-BT and impact patient treatment outcomes potentially.

Electronic intracavitary brachytherapy quality management based on risk analysis: The report of AAPM TG 182.

PURPOSE: The purpose of this study was to provide guidance on quality management for electronic brachytherapy. MATERIALS AND METHODS: The task group used the risk-assessment approach of Task Group 100 of the American Association of Physicists in Medicine. Because the quality management program for a device is intimately tied to the procedure in which it is used, the task group first designed quality interventions for intracavitary brachytherapy for both commercial electronic brachytherapy units in the setting of accelerated partial-breast irradiation. To demonstrate the methodology to extend an existing risk analysis for a different application, the task group modified the analysis for the case of post-hysterectomy, vaginal cuff irradiation for one of the devices. RESULTS: The analysis illustrated how the TG-100 methodology can lead to interventions to reduce risks and improve quality for each unit and procedure addressed. CONCLUSION: This report provides a model to guide facilities establishing a quality management program for electronic brachytherapy.

Dose-response linearization in radiochromic film dosimetry based on multichannel normalized pixel value with an integrated spectral correction for scanner response variations.

PURPOSE: To introduce a model that reproducibly linearizes the response from radiochromic film (RCF) dosimetry systems at extended dose range. To introduce a correction method, generated from the same scanned images, which corrects for scanner temporal response variation and scanner bed inhomogeneity. METHODS: Six calibration curves were established for different lot numbers of EBT3 GAFCHROMIC™ film model based on four EPSON scanners [10000XL (2 units), 11000XL, 12000XL] at three different centers. These films were calibrated in terms of absorbed dose to water based on TG51 protocol or TRS398 with dose ranges up to 40 Gy. The film response was defined in terms of a proposed normalized pixel value ( n P V RGB ) as a summation of first-order equations based on information from red, green, and blue channels. The fitting parameters of these equations are chosen in a way that makes the film response equal to dose at the time of calibration. An integrated set of correction factors (one per color channel) was also introduced. These factors account for the spatial and temporal changes in scanning states during calibration and measurements. The combination of n P V RGB and this "fingerprint" correction formed the basis of this new protocol and it was tested against net optical density ( n e t O D X = R , G , B ) single-channel dosimetry in terms of accuracy, precision, scanner response variability, scanner bed inhomogeneity, noise, and long-term stability. RESULTS: Incorporating multichannel features (RGB) into the normalized pixel value produced linear response to absorbed dose (slope of 1) in all six RCF dosimetry systems considered in this study. The "fingerprint" correction factors of each of these six systems displayed unique patterns at the time of calibration. The application of n P V RGB to all of these six systems could achieve a level of accuracy of ± 2.0% in the dose range of interest within modeled uncertainty level of 2.0%-3.0% depending on the dose level. Consistent positioning of control and measurement film pieces and integrating the multichannel correction into the response function formalism mitigated possible scanner response variations of as much as ± 10% at lower doses and scanner bed inhomogeneity of ± 8% to the established level of uncertainty at the time of calibration. The system was also able to maintain the same level of accuracy after 3 and 6 months post calibration. CONCLUSIONS: Combining response linearity with the integrated correction for scanner response variation lead to a sustainable and practical RCF dosimetry system that mitigated systematic response shifts and it has the potential to reduce errors in reporting relative information from the film response.

Evaluating the influence of prostate-specific antigen kinetics on metastasis in men with PSA recurrence after partial gland therapy.

PURPOSE: Although current Delphi Consensus guidelines do not recommend a specific definition of biochemical recurrence after partial gland therapy, these guidelines acknowledge that serial prostate-specific antigen (PSA) tests remain the best marker for monitoring disease after treatment. The purpose of this study was to determine whether PSA velocity at failure per the Phoenix (nadir + 2 ng/mL) definition is associated with metastasis and prostate cancer-specific mortality (PCSM) in a cohort of patients who experienced PSA failure after partial gland therapy. METHODS: Between 1997 and 2007, 285 patients with favorable risk prostate cancer underwent partial prostate brachytherapy to the peripheral zone. PSA velocity was calculated for 94 patients who experienced PSA failure per the Phoenix (nadir + 2) definition. Fine and Gray competing risks regression was performed to determine whether PSA velocity and other clinical factors were associated with metastasis and PCSM. RESULTS: The median time to PSA failure was 4.2 years (interquartile range: 2.2, 7.9), and the median followup time after PSA failure was 6.5 years (3.5-9.7). Seventeen patients developed metastases, and five experienced PCSM. On multivariate analysis, PSA velocity ≥3.0 ng/mL/year (adjusted hazard ratio 5.97; [2.57, 13.90]; p < 0.001) and PSA nadir (adjusted hazard ratio 0.39; [0.24, 0.64]; p < 0.001) were significantly associated with metastasis. PSA velocity ≥3.0 ng/mL/year was also associated with PCSM (HR 15.3; [1.8, 128.0]; p = 0.012) on univariate analysis. CONCLUSIONS: Rapid PSA velocity at PSA failure after partial gland treatment may be prognostic for long-term outcomes.

Long-term outcomes of partial prostate treatment with magnetic resonance imaging-guided brachytherapy for patients with favorable-risk prostate cancer.

BACKGROUND: Partial prostate treatment has emerged as a potential method for treating patients with favorable-risk prostate cancer while minimizing toxicity. The authors previously demonstrated poor rates of biochemical disease control for patients with National Comprehensive Cancer Network (NCCN) intermediate-risk disease using partial gland treatment with brachytherapy. The objective of the current study was to estimate the rates of distant metastasis and prostate cancer-specific mortality (PCSM) for this cohort. METHODS: Between 1997 and 2007, a total of 354 men with clinical T1c disease, a prostate-specific antigen (PSA) level < 15 ng/mL, and Gleason grade ≤3 + 4 prostate cancer underwent partial prostate treatment with brachytherapy to the peripheral zone under 0.5-Tesla magnetic resonance guidance. The cumulative incidences of metastasis and PCSM for the NCCN very low-risk, low-risk, and intermediate-risk groups were estimated. Fine and Gray competing risk regression was used to evaluate clinical factors associated with time to metastasis. RESULTS: A total of 22 patients developed metastases at a median of 11.0 years (interquartile range, 6.9-13.9 years). The 12-year metastasis rates for patients with very low-risk, low-risk, and intermediate-risk disease were 0.8% (95% confidence interval [95% CI], 0.1%-4.4%), 8.7% (95% CI, 3.4%-17.2%), and 15.7% (95% CI, 5.7%-30.2%), respectively, and the 12-year PCSM estimates were 1.6% (95% CI, 0.1%-7.6%), 1.4% (95% CI, 0.1%-6.8%), and 8.2% (95% CI, 1.9%-20.7%), respectively. On multivariate analysis, NCCN risk category (low risk: hazard ratio, 6.34 [95% CI, 1.18-34.06; P = .03] and intermediate risk: hazard ratio, 6.98 [95% CI, 1.23-39.73; P = .03]) was found to be significantly associated with the time to metastasis. CONCLUSIONS: Partial prostate treatment with brachytherapy may be associated with higher rates of distant metastasis and PCSM for patients with intermediate-risk disease after long-term follow-up. Treatment of less than the full gland may not be appropriate for this cohort.

A novel approach to an automated needle insertion in brachytherapy procedures.

One of the most challenging phases in interstitial brachytherapy is the placement of the needles. In these medical procedures, the needles are inserted inside the tissue to guide the positioning of the radioactive sources. The low-dose-rate radioactive sources are placed inside the tissue permanently, whereas a radioactive source in the high-dose-rate brachytherapy is temporarily placed in the desired positions so that the delivery of the prescription dose to the clinical targets can be achieved. Consequently, the precise needle placement directly influences the radiation dose delivery and the treatment outcomes of patients. Any deviation from the desired position of the radioactive sources can cause a suboptimal dose distribution and inadequate tumor coverage. Therefore, it is of significant importance to develop a robust and sophisticated tool that can perform the automatic needle placement with a high level of accuracy for different medical procedures and conditions. In this study, we propose a novel concept for the automatic needle insertion using a new miniature automated robotic system. The mathematical model of this system was presented in detail, allowing the implementation of the model predictive control that can be used to govern the mechanism. The purpose of this approach was to minimize the lateral components of the generalized reactive force which is responsible for the tissue displacement and, consequently, for the needle deflection. The proposed approach was designed to predict and to compensate for the unmeasured disturbances, such as needle deflection or tissue resistance and reactive force, and it was capable of correcting them without waiting until the effect appears at the output of the system causing the needle deviation from the desired positions. The extensive simulation of the system was presented to evaluate the feasibility of the method and the parameters of interest including displacements, system errors and system responses to the change in the environmental conditions.

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.

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.

Custom-made micro applicators for high-dose-rate brachytherapy treatment of chronic psoriasis.

PURPOSE: In this study, we present the treatment of the psoriatic nail beds of patients refractory to standard therapies using high-dose-rate (HDR) brachytherapy. The custom-made micro applicators (CMMA) were designed and constructed for radiation dose delivery to small curvy targets with complicated topology. The role of the HDR brachytherapy treatment was to stimulate the T cells for an increased immune response. MATERIAL AND METHODS: The patient diagnosed with psoriatic nail beds refractory to standard therapies received monthly subunguinal injections that caused significant pain and discomfort in both hands. The clinical target was defined as the length from the fingertip to the distal interphalangeal joint. For the accurate and reproducible setup in the multi-fractional treatment delivery, the CMMAs were designed. Five needles were embedded into the dense plastic mesh and covered with 5 mm bolus material for each micro applicator. Five CMMAs were designed, resulting in the usage of 25 catheters in total. RESULTS: The prescription dose was planned to the depth of the anterior surface of the distal phalanx, allowing for the sparing of the surrounding tissue. The total number of the active dwell positions was 145 with step size of 5 mm. The total treatment time was 115 seconds with a 7.36 Ci activity of the 192Ir source. The treatment resulted in good pain control. The patient did not require further injections to the nail bed. After this initial treatment, additional two patients with similar symptoms received HDR brachytherapy. The treatment outcome was favorable in all cases. CONCLUSIONS: The first HDR brachytherapy treatment of psoriasis of the nail bed is presented. The initial experience revealed that brachytherapy treatment was well-tolerated and resulted in adequate control of the disease. A larger cohort of patients will be required for additional conclusions related to the long-term clinical benefits.

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.

Computerized System for Safety Verification of External Beam Radiation Therapy Planning.

PURPOSE: To report an assessment of in-house software, Verifier, developed to improve efficacy and efficiency of the radiation therapy (RT) treatment planning process and quality control review (QCR). METHODS AND MATERIALS: Radiation therapy plan parameters retrieved from our treatment planning database are used by automated tests to give 75 types of warnings, such as prescription and plan discrepancies. The software is continuously updated on the basis of new issues, ideas, and planning policies. Verifier was retrospectively assessed (2007-2015) by examining impact on treatment plan revisions, frequency of quality improvement incident reports of avoidable RT plan-related safety events, unaddressed issues, and staff efficiency. RESULTS: Plan revisions for specific issues declined dramatically in response to implementation of corresponding Verifier tests. Between 2012 and 2015 our institution's total rate of plan revisions dropped from 18.0% to 11.2%. Between 2008 and 2015 specific tests were added to Verifier while the rate of corresponding avoidable safety events was reduced from 0.34% to 0.00% over the same period. Simulations suggest Verifier saves approximately 2 to 5 minutes per QCR. CONCLUSIONS: The decrease in quantifiable metrics of plan revisions and incident reports suggests automatic RT plan-checking software enhances patient safety and clinical efficiency. Although only modest time savings may be gained using Verifier for the QCR itself, the greater impact on efficiency is through avoiding late-stage plan modifications and improving documentation via automation. We encourage other institutions to consider working toward adding similar technologies to enhance their RT quality assurance programs.