Permanent Breast Seed Implant Research Articles

Seed distribution stability in permanent breast seed implant brachytherapy

PURPOSESIn this study we aim to quantitatively evaluate the stability of implanted seeds in permanent breast seed implant (PBSI) brachytherapy and assess any impact on treatment quality. METHODS AND MATERIALSSixty-seven consecutive patients who received PBSI treatment at BC Cancer Kelowna from 2013 to 2021 with post-implant CT images available were included in this study. For each patient, two sets of post-implant CT scans were retrospectively analyzed: Day0, obtained immediately after implant, and Day30, obtained approximately one month following implant. Seed distributions were quantified using the 90% isodose contour, outlier seed maximum spread, and number of seeds located in the seroma as well as seroma quadrants. These were then compared between Day0 and Day30. Post-implant dosimetry of target volumes as well as critical structures were compared. RESULTSThe 90% isodose volume was found to decrease over time. All seeds remained in the breast region however the maximum spread of seeds increased in all directions from Day0 to Day30. All recorded target volume dosimetric parameters were, on average, lower on Day30 compared to Day0 but mean dosimetry levels still met clinical goals. Dose in critical structures was overall similar. CONCLUSIONSIn this study, we quantitatively described the changes in seed distributions as well as dosimetry from Day0 to Day30 post PBSI procedure. We addressed concerns related to seed stability in breast tissue and provided clinical evidence on dosimetric efficacy of the PBSI technique.

A postimplant dosimetry simulation framework for robustness evaluation in permanent breast seed implant brachytherapy

Permanent breast seed implant (PBSI) brachytherapy is a promising treatment that has the potential to be widely utilized with increased standardization, optimization, and robustness. Excellent early efficacy and very high patient acceptance were reported, however, to further evaluate and improve planning strategies, a framework to quantify plan robustness to implant uncertainties is necessary. In this study, we aim to quantify clinical seed displacement using an automated algorithm and develop and validate a PBSI post-implant dosimetry simulation framework to evaluate PBSI plan robustness to implant uncertainties. Clinical PBSI seed displacements were quantified for 63 consecutive patients. A PBSI simulator was developed in Matlab (2020) by resampling clinical seed displacements and computing a range of possible post-implant dosimetry outcomes under various seed displacement scenarios. Simulations were performed retrospectively on 63 previous clinical plans to evaluate plan robustness to seed displacement. Mean seed displacement for the whole cohort was 10 ± 6 mm. A clinical seed displacement database was established and a user interface was developed for the simulation framework. For all clinical plans, the median (range) value of simulated median ETV V90 in various seed displacement scenarios was 97.8% (87.5-100%). A PBSI postimplant dosimetry simulation framework was developed and validated. Simulation results showed that the current PTV planning margin is sufficient to provide adequate postimplant dose coverage of ETV. This simulator can be used to evaluate plan robustness to seed displacement and will facilitate future research in improving PBSI planning methods.

PO96: Treatment Planning Dosimetry Predictive of Treatment Plan Robustness in Permanent Breast Seed Implant

PO96: Treatment Planning Dosimetry Predictive of Treatment Plan Robustness in Permanent Breast Seed Implant

Feasibility study of defining planning target volume using surgical margins in permanent breast seed implant brachytherapy

PURPOSEThis study investigates the feasibility and potential impacts of utilizing a Groupe Européen de Curiethérapie-European Society for Therapeutic Radiation and Oncology (GEC ESTRO) recommended surgical margin-based planning margin in permanent breast seed implant (PBSI) brachytherapy. METHODS AND MATERIALSSeventy-nine patients were included in this retrospective study. Three margin selections were used for PTV construction: (1) 1.25 or 1.5 cm isotropic margin (PTVPBSI), (2) 2 cm minus surgical margin in each direction as recommended by GEC ESTRO (PTVaniso), and (3) 2 cm minus minimum surgical margin isotropically (PTViso). PTV volume and dose coverage using clinical PBSI plans were compared across three groups. New PBSI plans were constructed on PTVaniso for 20 patients and planning parameters were compared to original plans constructed on PTVPBSI. RESULTSTwenty patients had surgical margins in six directions reported, with a median value of 8 mm anteriorly, and 10 mm in all other directions. PTVaniso (36.3 ± 15.0 cc) was overall smaller than PTVPBSI (55.6 ± 14.3 cc), p value < 0.05. PBSI clinical plans showed satisfactory coverage on PTVaniso, with a median (range) V100 of 97.9% (85.8%–100.0%). Comparing to original treatment plans, new plans constructed on PTVaniso reduced the number of implant seeds and skin dose. CONCLUSIONSClinical PBSI plans provide satisfactory coverage of GEC ESTRO recommended PTVs. In this patient cohort, GEC ESTRO planning margin resulted in smaller target volumes, and therefore, new plans constructed on PTVaniso required fewer implanted seeds and lower skin doses were achieved. However, given PBSI delivery uncertainties, further investigations are required to determine if the GEC ESTRO planning margin will be sufficiently robust.

PO10: Permanent Breast Seed Implant (PBSI) in Re-Irradiation of the Breast

PO10: Permanent Breast Seed Implant (PBSI) in Re-Irradiation of the Breast

Breast PO10: Permanent Breast Seed Implant (PBSI) in Re-Irradiation of the Breast

Breast PO10: Permanent Breast Seed Implant (PBSI) in Re-Irradiation of the Breast

A reliable skin toxicity predictor in permanent breast seed implant brachytherapy

PurposeTo establish skin dose–outcome relationships using a reliable metric in permanent breast seed implant (PBSI). MethodsSixty-seven consecutive patients who underwent PBSI at our institution were included. Skin doses were calculated using two skin dose indices: maximum point dose to the skin surface, Dmax, and D0.2cc for a 2-mm internal skin rind (a surrogate to the dose to 1 cm2 area of skin) from CT-based postoperative treatment plans. Toxicity data were extracted from patients’ charts and photographs. The associations between skin dose and skin toxicity were investigated using the analysis of variance, and the predictive performance of skin dose measures was evaluated using receiver operating characteristic curves. ResultsFor acute reactions, 49.3% of patients had Grade 1, 4.5% Grade 2, and 1.5% Grade 3 toxicity. For telangiectasia at 3 years, very minor and minimally apparent telangiectasia was observed in 25% of patients. Moderate but asymptomatic telangiectasia was observed in 9.1% of cases. Both metrics were significantly associated with the occurrence of acute toxicity and telangiectasia at 3 years (p < 0.01). The predictive values for Dmax and D0.2cc were 0.779 and 0.763, respectively, (p < 0.0001) for acute skin toxicity and 0.786 and 0.810 for telangiectasia (p < 0.0002). Extreme dose outliers (up to 878 Gy) and a high variability were observed for Dmax but not for D0.2cc, illustrating the superior reliability of D0.2cc. ConclusionD0.2cc, as an alternate skin dose measure to Dmax, is a robust metric for measuring skin dose that is simple to calculate, yet is clinically relevant and not prone to inaccuracies inherent to point dose measurement.

75 Permanent Breast Seed Implant for Partial Breast Radiotherapy Following Partial Mastectomy for Favorable Breast Cancer: Results for 67 Patients

75 Permanent Breast Seed Implant for Partial Breast Radiotherapy Following Partial Mastectomy for Favorable Breast Cancer: Results for 67 Patients

Permanent Breast Seed Implant for Partial-Breast Radiotherapy Following Partial Mastectomy for Favorable Breast Cancer: Results for 67 patients

Adjuvant partial breast radiotherapy (PBRT) is standard of care for early stage favorable breast cancer according to GEC-ESTRO, ASTRO, and ABS Guidelines. Modalities include both external bream and brachytherapy. We hypothesize that PBRT delivered by Low Dose Rate brachytherapy permanent breast seed implants (PBSI) as a single 2-hour procedure would be well received and well tolerated. From 07/12-10/18, 67 postmenopausal women with unifocal T1N0 invasive ductal breast cancer or DCIS, ER positive, negative margins, grade 1 or 2, and no LVI received PBRT using permanent implantation of stranded Pd-103 seeds on an REB approved Phase 2 trial. Following breast conserving surgery, PBSI delivered 90 Gy to the seroma + margin (1.25 to 1.5cm: max PTV 125 cc). Implants were planned with CT simulation and performed as an outpatient procedure under light anesthesia, guided by live ultrasound (US). Visualization of the seroma on both CT and US is essential. Post implant CT dosimetry used fusion with the original planning scan for seroma delineation. Evaluations were at 1, 2, 6, and 12 months and then annually. More than 95% of women suitable by oncologic criteria would consent to PBSI. Only about 40% are technically suitable due to seroma volume, location, or lack of visibility on CT or US. For 67 patients, median seroma volume was 6.6 cc (1.7-20.4), PTV 61 cc (31-117), # of needles 18 (10-30) and seeds 75 (42-134). In Day 0 dosimetry, median seroma D90 was 132 Gy (V100:97%), seroma+ 5mm 106 Gy (V100:93%) and seroma+10mm 80 Gy (V100:85%). Seroma location was 58% lateral, 31% anterior, 9% inframammary fold and one lower inner quadrant. The local reaction peaks at 6 weeks and is limited to the skin overlying the implant: 51% had grade 1 erythema, 12% superficial desquamation. Needle puncture marks are not visible at 4 weeks. Late reactions (> 2 years) are generally minimal: 35% no sequelae, 43% localized palpable asymptomatic fibrosis, 20% minimally apparent telangiectasia (6% more significant but asymptomatic), 22% slight lateral contour change or skin dimpling. All cases with more pronounced breast contour change (n=6) followed deforming surgery (nipple excision, marked post-operative nipple deviation, etc.). With a minimum of 6 months follow-up, 94% of respondents were “very satisfied” or “totally satisfied.” At a median follow up of 3.3 years (6-75 months), there has been one in-breast recurrence (different quadrant) detected at 12 months and treated with mastectomy at the patient’s request. Three patients have had biopsies of palpable fibrosis, all negative for malignancy. Two patients have had contralateral breast cancers, one of whom had partial mastectomy followed by a second PBSI, while the other opted for bilateral mastectomy for reasons of cancer anxiety despite satisfaction with the first procedure. Our experience with PBSI for PBRT is favorable with a high patient acceptance and satisfaction, excellent early efficacy and very satisfactory cosmesis.

Postmortem evidence of neuroinflammation in bipolar disorder: a systematic review

Permanent breast seed implant (PBSI) is a developing brachytherapy technique for the treatment of early-stage breast cancer. In current practice, PBSI uses manual planning strategies to generate clinical treatment plans. In this work, a simulated annealing-based algorithm is developed to demonstrate the first application of inverse optimization for PBSI.Target, skin, and chest wall muscle contours, exported from a treatment planning system in digital imaging and communications in medicine format, are used as inputs. To optimize, the user defines the dose–volume histogram objectives for the target and specifies a relative weighting for target and skin constraints. A 10-patient cohort of previously treated patients was planned by using the inverse optimization algorithm. Plan quality was compared to the clinically treated manually generated plans using the V90%, V100%, V150%, and V200% for the planning target volume (PTV), V90% and D0.2 cc for skin dose, and PTV conformity indices.For each of the 10 patients, patient-wise paired differences between inverse and manual plans were analyzed and presented in box plots. Comparing inverse and manual planning techniques, a statistical difference was not observed (p > 0.05) in PTV coverage criteria (V90%, V100%) and dose to skin2mm. A statistical difference was observed in the inverse plans as a reduction of the V150% (mean of 6.2%) and increase in conformity index of the 20%, 50%, 90%, and 100% isodose lines.This work presents the first application of inverse optimization used to generate PBSI treatment plans. A 10-patient cohort previously treated with PBSI was retrospectively planned for comparison with the clinically treated manually generated plans.

Development and Clinical Validation of a 3D Ultrasound System for Permanent Breast Seed Implant Brachytherapy

Permanent Breast Seed Implant (PBSI) is a novel form of breast brachytherapy completed in a single 1-2h procedure. PBSI planning uses CT simulation and treatment involves implanting Pd-103 seeds in and around the breast seroma via needles inserted through a template and guided by free-hand 2D ultrasound. The seroma shape and size vary from CT images to ultrasound and currently neither 3D images nor real-time guidance are available for PBSI. A 3D ultrasound (3DUS) system has been developed to fulfill these needs. This study extends this work to validate the 3DUS clinical implementation in PBSI planning and delivery procedure.

A Simulation-Based Education Program for Permanent Breast Seed Implant Brachytherapy

Medical simulation platforms have been utilized to educate a broad spectrum of healthcare professionals and have been correlated with positive effects on learner proficiency and patient outcomes. In radiation therapy, brachytherapy is a procedural technique that requires considerable manual skill to perform proficiently and may benefit from the application of technology-enhanced medical simulation education programs. The University of Calgary will offer a brachytherapy training program with mandatory simulation component in an Area of Focused Competence (AFC); a diploma program accredited by the Royal College of Physicians and Surgeons of Canada. The Purpose of this study is to demonstrate validity evidence to support the use of a simulation-based education program in teaching permanent breast seed implant (PBSI) brachytherapy to radiation oncology learners.

Post-implant analysis in permanent breast seed implant: automated plan reconstruction using simulated annealing.

PurposePost-implant analysis in permanent breast seed implant (PBSI) brachytherapy is an important component of the quality assurance process that indicates dosimetric quality relevant to patient outcome, indicating salvage therapy if inadequate, as well as providing feedback to the brachytherapy team to improve future treatments. To measure geometric indices on implant quality, plan reconstruction must be performed to correlate each planned and post-implant seed location. In this work, a simulated-annealing-based algorithm is developed to perform this plan reconstruction automatically.Material and methodsThe plan reconstruction algorithm was developed in MATLAB, taking the patient pre-treatment and post-implant (Day 0) plan and associated contours as inputs. For 19 treated patients, a reconstruction was obtained that defined the correspondence between each planned and post-implant seed. The simulated-annealing algorithm was used to reconstruct each patient 10 times to assess the variability in convergence. Manual reconstructions performed by at least two independent observers to obtain consensus were defined as the ground truth; these were compared to the automatic reconstructions obtained by the algorithm. Metrics on seed placement accuracy and needle strand angulation were calculated for the patients.ResultsThe algorithm performed reconstructions on 19 patients (1235 seeds) with ground-truth reconstructions, obtaining 97 ± 8% correct matches. This strong performance indicates the ability to incorporate this algorithm into the clinical quality assurance workflow.ConclusionsThe plan reconstruction algorithm developed herein performed very well in a 19-patient cohort. This algorithm can be incorporated into the clinical process to assist in the assessment of center-specific seed placement accuracy and can be used to gather implant metrics in an automated, standardized fashion for future PBSI trials.

A randomized controlled trial testing a hyaluronic acid spacer injection for skin toxicity reduction of brachytherapy accelerated partial breast irradiation (APBI): a study protocol

BackgroundAccelerated partial breast irradiation (APBI) is a treatment option for selected early stage breast cancer patients. Some APBI techniques lead to skin toxicity with the skin dose as main risk factor. We hypothesize that a spacer injected between the skin and target volume reduces the skin dose and subsequent toxicity in permanent breast seed implant (PBSI) patients.MethodsIn this parallel-group, single-center, randomized controlled trial, the effect of a subcutaneous spacer injection on skin toxicity among patients treated with PBSI is tested. Eligibility for participation is derived from international guidelines for suitable patients for partial breast radiotherapy, e.g. women aged ≥ 50 years with a histologically proven non-lobular breast carcinoma and/or ductal carcinoma in situ (DCIS), tumor size ≤ 3 cm, node-negative, and PBSI technically feasible. Among exclusion criteria are neoadjuvant chemotherapy, lymphovascular invasion, and allergy for hyaluronic acid. For the patients allocated to receive spacer, after the PBSI procedure, 4–10 cc of biodegradable hyaluronic acid (Barrigel™, Palette Life Sciences, Santa Barbara, CA, USA or Restylane SubQ®, Galderma Benelux, Breda, the Netherlands) is injected directly under the skin using ultrasound guidance to create an extra 0.5–1 cm space between the treatment volume and the skin. The primary outcome is the rate of telangiectasia at two years, blindly assessed using Bentzen’s 4-point scale. Secondary outcomes include: local recurrence; disease-free and overall survival rates; adverse events (pain, redness, skin/subcutaneous induration, radiation dermatitis, pigmentation, surgical site infection); skin dose; cosmetic and functional results; and health-related quality of life.A Fisher’s exact test will be used to test differences between groups on the primary outcome.Previous studies found 22.4% telangiectasia at two years. We expect the use of a spacer could reduce the occurrence of telangiectasia to 7.7%. A sample size of 230 patients will allow for a 10% lost to follow-up rate.DiscussionIn this study, the effect of a subcutaneous spacer injection on the skin dose, late skin toxicity, and cosmetic outcome is tested in patients treated with PBSI in the setting of breast-conserving therapy. Our results will be relevant for most forms of breast brachytherapy as well as robotic radiosurgery, as skin spacers could protect the skin with these other techniques.Trial registrationNetherlands Trial Register, NTR6549. Registered on 27 June 2017.

Development of a 3D ultrasound guidance system for permanent breast seed implantation.

Permanent breast seed implantation (PBSI) is a promising radiotherapy technique for early-stage breast cancer, completed in a single visit by permanently implanting 103 Pd seeds using needles inserted through a template and guided by two-dimensional (2D) ultrasound (US). However, operator dependence has been highlighted as a limitation of this procedure. Consequently, we propose and have developed an intraoperative guidance system using three-dimensional (3D) US and an instrumented mechanical arm to provide intraoperative 3D imaging and needle template tracking. A mechatronic 3D US scanner reconstructs a 3D image from 150 2D images. A tracked mechanical arm mounted to the scanner locates four fiducial points on the template, registering the template to the 3D image. 3D reconstruction was validated for linear and volumetric measurement accuracy using phantoms of known geometry. In vivo breast US image quality was evaluated in a healthy volunteer. The encoded arm was calibrated and validated using a jig with divots at known locations relative to the scanner and the scanner registered to the 3D US image using intersecting strings in a fluid-filled test jig. Template registration accuracy was assessed using a machined test jig. Tracking accuracy was assessed in a liquid medium by comparing tracked and imaged needle tip positions. Finally, the system was used to guide a mock procedure in a patient-specific phantom and micro-CT imaging used to evaluate its accuracy. Geometric validation showed median distances within ±1.1% of expected values and volumetric validation showed differences of ≤4.1%. Tracking arm point measurements showed an average error of 0.43mm and 3D US volume registration showed target registration error ≤0.9mm. Mean template registration accuracy in each axis of translation/rotation was ≤1.3mm/1.0°. Mean needle-targeting error was 2.5mm and 1.6° for needle tips and trajectories, respectively. Mean needle tip and angular errors of the phantom procedure were 2.1mm and 2.6°. Modeled seed displacement of the phantom procedure showed mean error of 2.6mm and a maximum of 3.8mm. A 3D US guidance system for PBSI has been developed. Benchtop performance and image quality in volunteer scans are satisfactory. A phantom PBSI procedure was successfully delivered using the system with maximum seed error within dosimetric benchmarks (<5mm). Translation of the device into the clinic is forthcoming.

Inter-Centre Validation of Plan Reconstruction in Permanent Breast Seed Implant

Inter-Centre Validation of Plan Reconstruction in Permanent Breast Seed Implant

Appropriate timing for postimplant imaging in permanent breast seed implant: Results from a serial CT study

PurposePostimplant analysis in permanent breast seed implant (PBSI) is performed at inconsistent times subsequent to seed implantation across cancer centers, creating challenges in the interpretation of dosimetric data and ultimately the correlation with clinical outcomes. The purpose of this study is to determine the most appropriate time postimplant to perform this analysis. Methods and MaterialsNine patients treated at our institution with PBSI were included in this analysis. Each underwent 4 postimplant CT scans: 0, 15, 30, and 60 days postimplant. A model of the accumulated dose was created by deformably registering the Day 15, 30, and 60 postimplant CT scans and dose matrices to the Day 0 scan, scaling for seed decay. The results from this model were compared to each individual postplan by integral comparison of dose–volume histogram curves for a dose evaluation volume. ResultsThe Day 30 postplan showed the best agreement with the accumulated dose model and the smallest interpatient variability across the patient cohort. The mean (±SD) for the dose evaluation volume V90, V100, V150, and V200 for the accumulated dose model was 90 ± 7%, 86 ± 8%, 66 ± 14%, and 41 ± 16%, respectively. ConclusionsBased on the results of this patient cohort, we recommend that postimplant dosimetric analysis for PBSI be performed approximately 30 days following the implant.

Who Should Bear the Cost of Convenience? A Cost-effectiveness Analysis Comparing External Beam and Brachytherapy Radiotherapy Techniques for Early Stage Breast Cancer

AimsStandard treatment for early breast cancer includes whole breast irradiation (WBI) after breast-conserving surgery. Recently, accelerated partial breast irradiation (APBI) has been proposed for well-selected patients. A cost and cost-effectiveness analysis was carried out comparing WBI with two APBI techniques. Materials and methodsAn activity-based costing method was used to determine the treatment cost from a societal perspective of WBI, high dose rate brachytherapy (HDR) and permanent breast seed implants (PBSI). A Markov model comparing the three techniques was developed with downstream costs, utilities and probabilities adapted from the literature. Sensitivity analyses were carried out for a wide range of variables, including treatment costs, patient costs, utilities and probability of developing recurrences. ResultsOverall, HDR was the most expensive ($14 400), followed by PBSI ($8700), with WBI proving the least expensive ($6200). The least costly method to the health care system was WBI, whereas PBSI and HDR were less costly for the patient. Under cost-effectiveness analyses, downstream costs added about $10 000 to the total societal cost of the treatment. As the outcomes are very similar between techniques, WBI dominated under cost-effectiveness analyses. ConclusionsWBI was found to be the most cost-effective radiotherapy technique for early breast cancer. However, both APBI techniques were less costly to the patient. Although innovation may increase costs for the health care system it can provide cost savings for the patient in addition to convenience.

115: Proposal for a Permanent Breast Seed Implant (PBSI) Training Program

115: Proposal for a Permanent Breast Seed Implant (PBSI) Training Program

Sci‐Thur PM – Brachytherapy 03: Identifying the impact of seroma visualization on permanent breast seed implant brachytherapy

Purpose:Uncertainties in target identification can reduce treatment accuracy in permanent breast seed implant (PBSI) brachytherapy. This study evaluates the relationship between seroma visualization and seed placement accuracy.Methods:Spatially co‐registered CT and 3D ultrasound (US) images were acquired for 10 patients receiving PBSI. Seromas were retrospectively contoured independently by 3 radiation oncologists on both CT and US and respective consensus volumes were defined, CTVCT and CTVUS. The seroma clarity and inter‐user conformity index (CI), as well as inter‐modality CI, volume, and positional differences were evaluated. Correlations with seed placement accuracy were then assessed. CTVs were expanded by 1.25cm to create PTVCT and PTVUS and evaluate the conformity with PTVClinical (CTVClinical+1.25cm) used in treatment planning. The change in PTV coincidence by expanding PTVClinical by 0.25cm was determined.Results:CTVUS were a mean 68 ± 12% smaller than CTVCT and generally had improved clarity and inter‐user conformity. No correlations between seed displacement and CTVUS‐CTVCT positional difference or CI were observed. Greater seed displacements were associated with larger CTVUS‐CTVCT volume differences (r=−0.65) and inter‐user CT CI (r=−0.74). A median (range) 88% (71–99%) of PTVCT and 83% (69–100%) of PTVUS were contained within PTVClinical. Expanding treatment margins to 1.5cm increased coincidence to 98% (86–100%) and 94% (82–100%), respectively.Conclusions:Differences in seroma visualization impacts seed displacement in PBSI. Reducing dependence on CT by incorporating 3DUS into target identification, or expanding CT‐based treatment margins to 1.5cm may reduce or mitigate uncertainties related to seroma visualization.