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.

Comparison of outcomes for MR-guided versus CT-guided high-dose-rate interstitial brachytherapy in women with locally advanced carcinoma of the cervix.

OBJECTIVE: The purpose was to compare local control (LC), overall survival (OS) and dose to the organs at risk (OAR) in women with locally advanced cervical cancer treated with MR-guided versus CT-guided interstitial brachytherapy (BT). METHODS: 56 patients (29 MR, 27 CT) were treated with high-dose-rate (HDR) interstitial BT between 2005-2015. The MR patients had been prospectively enrolled on a Phase II clinical trial. Data were analyzed using Kaplan-Meier (K-M) and Cox proportional hazards statistical modeling in JMP® & R®. RESULTS: Median follow-up time was 19.7months (MR group) and 18.4months (CT group). There were no statistically significant differences in patient age at diagnosis, histology, percent with tumor size >4cm, grade, FIGO stage or lymph node involvement between the groups. Patients in the MR group had more lymphovascular involvement compared to patients in the CT group (p<0.01). When evaluating plans generated, there were no statistically significant differences in median cumulative dose to the high-risk clinical target volume or the OAR. 2-year K-M LC rates for MR-based and CT-based treatments were 96% and 87%, respectively (log-rank p=0.65). At 2years, OS was significantly better in the MR-guided cohort (84% vs. 56%, p=0.036). On multivariate analysis, squamous histology was associated with longer OS (HR 0.23, 95% CI 0.07-0.72) in a model with MR BT (HR 0.35, 95% CI 0.08-1.18). There was no difference in toxicities between CT and MR BT. CONCLUSION: In this population of locally advanced cervical-cancer patients, MR-guided HDR BT resulted in estimated 96% 2-year local control and excellent survival and toxicity rates.

Outcomes with volume-based dose specification in CT-planned high-dose-rate brachytherapy for stage I-II cervical carcinoma: A 10-year institutional experience.

OBJECTIVE: To determine prognostic factors for progression-free survival (PFS) and overall survival (OS) for stage I-II cervical-cancer patients treated using computed-tomography (CT)-planned high-dose-rate (HDR) intracavitary brachytherapy (BT). METHODS: A total of 150 patients were treated for Stage I-II cervical cancer using CT-planned BT between 4/2004 and 10/2014. Of these, 128 were eligible for inclusion. Kaplan-Meier local control (LC), pelvic control (PC), overall survival (OS), and PFS estimates were calculated. RESULTS: After a median follow-up of 30months, the 2-year LC rate was 96%, PFS was 88%, and OS was 88%. Overall, 18 patients (14%) experienced any recurrence (AR), 8 had distant recurrence only and 10 had a combination of local, pelvic, regional, and distant recurrence. No patients had LR only. A prognostic factor for AR was tumor size >4cm (p=0.01). Patients with tumors >4cm were 3.3 times more likely to have AR than those with tumors ≤4cm (hazard ratio [HR]=3.3; 95% confidence interval [CI] 1.28-9.47). Point A was 85% of prescription for tumors < 4 cm and decreased approximately 3% over 5 fractions compared to 90% of prescription for tumors > 4 cm that decreased approximately 4% over 5 fractions. Two patients (2%) experienced grade≥2 late toxicity. There were no acute or late grade≥3 toxicities. CONCLUSION: CT-planned BT resulted in excellent local control and survival. Large tumor size was associated with an increased risk of recurrence outside the radiation field and worse PFS and OS. A volume-optimized plan treated a smaller area than a point A standard plan for patients with Stage I-II cervical cancer that have received chemoradiation. Given the outstanding LC achieved with modern therapy including chemoradiation, HDR, and image-based BT, further efforts to combat spread outside the radiation field with novel therapies are warranted.

Real-time active MR-tracking of metallic stylets in MR-guided radiation therapy.

PURPOSE: To develop an active MR-tracking system to guide placement of metallic devices for radiation therapy. METHODS: An actively tracked metallic stylet for brachytherapy was constructed by adding printed-circuit micro-coils to a commercial stylet. The coil design was optimized by electromagnetic simulation, and has a radio-frequency lobe pattern extending ∼5 mm beyond the strong B0 inhomogeneity region near the metal surface. An MR-tracking sequence with phase-field dithering was used to overcome residual effects of B0 and B1 inhomogeneities caused by the metal, as well as from inductive coupling to surrounding metallic stylets. The tracking system was integrated with a graphical workstation for real-time visualization. The 3 Tesla MRI catheter-insertion procedures were tested in phantoms and ex vivo animal tissue, and then performed in three patients during interstitial brachytherapy. RESULTS: The tracking system provided high-resolution (0.6 × 0.6 × 0.6 mm(3) ) and rapid (16 to 40 frames per second, with three to one phase-field dithering directions) catheter localization in phantoms, animals, and three gynecologic cancer patients. CONCLUSION: This is the first demonstration of active tracking of the shaft of metallic stylet in MR-guided brachytherapy. It holds the promise of assisting physicians to achieve better targeting and improving outcomes in interstitial brachytherapy.

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.

In vitro radiosensitization by gold nanoparticles during continuous low-dose-rate gamma irradiation with I-125 brachytherapy seeds.

This communication reports the first experimental evidence of gold nanoparticle (AuNP) radiosensitization during continuous low-dose-rate (LDR) gamma irradiation with low-energy brachytherapy sources. HeLa cell cultures incubated with and without AuNP were irradiated with an I-125 seed plaque designed to produce a relatively homogeneous dose distribution in the plane of the cell culture slide. Four sets of irradiation experiments were conducted at low-dose rates ranging from 2.1 to 4.5cGy/h. Residual γH2AX was measured 24h after irradiation and used to compare radiation damage to the cells with and without AuNP. The data demonstrate that the biological effect when irradiating in the presence of 0.2mg/ml concentration of AuNP is about 70%-130% greater than without AuNP. Meanwhile, without radiation, the AuNP showed minimal effect on the cancer cells. These findings provide in vitro evidence that AuNP may be employed as radiosensitizers during continuous LDR brachytherapy. FROM THE CLINICAL EDITOR: In this basic science paper, the application of gold nanoparticles as radiosensitizing agents for low dose rate gamma radiation therapy is discussed, demonstrating efficacy in cell culture models.

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.

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.

Updated results of magnetic resonance imaging guided partial prostate brachytherapy for favorable risk prostate cancer: implications for focal therapy.

PURPOSE: We report updated results of magnetic resonance imaging guided partial prostate brachytherapy and propose a definition of biochemical failure following focal therapy. MATERIALS AND METHODS: From 1997 to 2007, 318 men with cT1c, prostate specific antigen less than 15 ng/ml, Gleason 3 + 4 or less prostate cancer received magnetic resonance imaging guided brachytherapy in which only the peripheral zone was targeted. To exclude benign prostate specific antigen increases due to prostatic hyperplasia, we investigated the usefulness of defining prostate specific antigen failure as nadir +2 with prostate specific antigen velocity greater than 0.75 ng/ml per year. Cox regression was used to determine the factors associated with prostate specific antigen failure. RESULTS: Median followup was 5.1 years (maximum 12.1). While 36 patients met the nadir +2 criteria, 16 of 17 biopsy proven local recurrences were among the 26 men who also had a prostate specific antigen velocity greater than 0.75 ng/ml per year (16 of 26 vs 1 of 10, p = 0.008). Using the nadir +2 definition, prostate specific antigen failure-free survival for low risk cases at 5 and 8 years was 95.1% (91.0-97.3) and 80.4% (70.7-87.1), respectively. This rate improved to 95.6% (91.6-97.7) and 90.0% (82.6-94.3) using nadir +2 with prostate specific antigen velocity greater than 0.75 ng/ml per year. For intermediate risk cases survival was 73.0% (55.0-84.8) at 5 years and 66.4% (44.8-81.1) at 8 years (the same values as using nadir +2 with prostate specific antigen velocity greater than 0.75 ng/ml per year). CONCLUSIONS: Requiring a prostate specific antigen velocity greater than 0.75 ng/ml per year in addition to nadir +2 appears to better predict clinical failure after therapies that target less than the whole gland. Further followup will determine whether magnetic resonance imaging guided brachytherapy targeting the peripheral zone produces comparable cancer control to whole gland treatment in men with low risk disease. However, at this time it does not appear adequate for men with even favorable intermediate risk disease.

A Bayesian nonrigid registration method to enhance intraoperative target definition in image-guided prostate procedures through uncertainty characterization.

PURPOSE: This study introduces a probabilistic nonrigid registration method for use in image-guided prostate brachytherapy. Intraoperative imaging for prostate procedures, usually transrectal ultrasound (TRUS), is typically inferior to diagnostic-quality imaging of the pelvis such as endorectal magnetic resonance imaging (MRI). MR images contain superior detail of the prostate boundaries and provide substructure features not otherwise visible. Previous efforts to register diagnostic prostate images with the intraoperative coordinate system have been deterministic and did not offer a measure of the registration uncertainty. The authors developed a Bayesian registration method to estimate the posterior distribution on deformations and provide a case-specific measure of the associated registration uncertainty. METHODS: The authors adapted a biomechanical-based probabilistic nonrigid method to register diagnostic to intraoperative images by aligning a physician's segmentations of the prostate in the two images. The posterior distribution was characterized with a Markov Chain Monte Carlo method; the maximum a posteriori deformation and the associated uncertainty were estimated from the collection of deformation samples drawn from the posterior distribution. The authors validated the registration method using a dataset created from ten patients with MRI-guided prostate biopsies who had both diagnostic and intraprocedural 3 Tesla MRI scans. The accuracy and precision of the estimated posterior distribution on deformations were evaluated from two predictive distance distributions: between the deformed central zone-peripheral zone (CZ-PZ) interface and the physician-labeled interface, and based on physician-defined landmarks. Geometric margins on the registration of the prostate's peripheral zone were determined from the posterior predictive distance to the CZ-PZ interface separately for the base, mid-gland, and apical regions of the prostate. RESULTS: The authors observed variation in the shape and volume of the segmented prostate in diagnostic and intraprocedural images. The probabilistic method allowed us to convey registration results in terms of posterior distributions, with the dispersion providing a patient-specific estimate of the registration uncertainty. The median of the predictive distance distribution between the deformed prostate boundary and the segmented boundary was ≤3 mm (95th percentiles within ±4 mm) for all ten patients. The accuracy and precision of the internal deformation was evaluated by comparing the posterior predictive distance distribution for the CZ-PZ interface for each patient, with the median distance ranging from -0.6 to 2.4 mm. Posterior predictive distances between naturally occurring landmarks showed registration errors of ≤5 mm in any direction. The uncertainty was not a global measure, but instead was local and varied throughout the registration region. Registration uncertainties were largest in the apical region of the prostate. CONCLUSIONS: Using a Bayesian nonrigid registration method, the authors determined the posterior distribution on deformations between diagnostic and intraprocedural MR images and quantified the uncertainty in the registration results. The feasibility of this approach was tested and results were positive. The probabilistic framework allows us to evaluate both patient-specific and location-specific estimates of the uncertainty in the registration result. Although the framework was tested on MR-guided procedures, the preliminary results suggest that it may be applied to TRUS-guided procedures as well, where the addition of diagnostic MR information may have a larger impact on target definition and clinical guidance.

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.

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.

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.

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.

Patient-reported quality of life after salvage brachytherapy for radio-recurrent prostate cancer: A prospective Phase II study.

BACKGROUND: Patient-reported quality of life (QOL) after salvage brachytherapy for radiorecurrent prostate cancer has not been well-characterized prospectively. METHODS: We examined 25 men who recurred after primary radiotherapy for prostate cancer and received MRI-guided salvage brachytherapy as part of a prospective Phase II study. These patients received prospectively a validated patient-reported QOL questionnaire to fill out at baseline, as well as 3, 15, and 27 months after re-irradiation to determine the degree of sexual, bowel, and urinary dysfunction (maximum dysfunction score=100). RESULTS: On average, sexual function continued to decline with time, and patients had significantly worse sexual function scores at 27 months than baseline (p=0.01). Although bowel and urinary symptoms worsened acutely at 3 or 15 months, they showed on average some improvement by 27 months, and there were no significant differences between baseline and 27-month urinary or bowel scores. An interval to re-irradiation less than 4.5 years and prior brachytherapy were each associated significantly with the largest decrements in bowel function (p=0.035). CONCLUSION: Similar to the patterns seen in the de novo setting, patients who receive salvage brachytherapy report a worsening of bowel and urinary symptoms followed by some improvement by 27 months, while sexual function steadily declines over time. Interval to re-irradiation and type of prior radiation received may be used to counsel and optimize selection of men for salvage brachytherapy with regard to QOL endpoints.