Safety and efficacy of GammaTile intracranial brachytherapy implanted during awake craniotomy

INTRODUCTIONGammaTile intracranial brachytherapy (cesium-131 seeds) has demonstrated encouraging safety and local control results, and recently received Food and Drug Administration clearance for newly diagnosed and recurrent brain tumors. The authors present the first reported case of GammaTile intraoperative brachytherapy performed during an awake craniotomy.METHODSA 50-year-old man had a biopsy-proven, 2.8 cm left lateral frontal glioblastoma lesion nearing Broca's area on MRI. Despite several interventions (craniotomy, adjuvant chemoradiation, tumor treating fields) tumor progression occurred near the left parietal resection cavity. Re-resection was planned with awake craniotomy and language mapping. A preoperative planning session involving Radiation Oncology and Neurosurgery identified the area of the expected postoperative bed, and consequently five GammaTiles were ordered, each containing 4 cesium-131 3.5 U seeds.RESULTSDuring surgery, tumor mapping and bipolar stimulation were performed while the patient spoke in complete sentences. Speech arrest occurred upon stimulation at the posterior edge of the gyrus, indicative of language cortex. Microsurgical maximal safe resection subsequently occurred, and areas at risk for residual/recurrence disease were determined in consultation with Radiation Oncology. Subsequently, Neurosurgery placed all five GammaTiles (20 cesium-131 seeds total) after which closure was completed and radioactive surveys of the room remained within state statue. Postoperative dosimetry yielded excellent coverage.CONCLUSIONSThe first reported case of GammaTile intraoperative brachytherapy during awake craniotomy supports the safety and feasibility of this treatment strategy. This case indicates that for patients with tumors adjacent to eloquent cortex, awake craniotomy can allow for custom implantation of intraoperative brachytherapy following maximum safe resection.     

Dosimetric influence of seed spacers and end-weld thickness for permanent prostate brachytherapy

PurposeThe aim of this study was to analyze the dosimetric influence of conventional spacers and a cobalt chloride complex contrast (C4) agent, a novel marker for MRI that can also serve as a seed spacer, adjacent to ¹⁰³Pd, ¹²⁵I, and ¹³¹Cs sources for permanent prostate brachytherapy.Methods and MaterialsMonte Carlo methods for radiation transport were used to estimate the dosimetric influence of brachytherapy end-weld thicknesses and spacers near the three sources. Single-source assessments and volumetric conditions simulating prior patient treatments were computed. Volume–dose distributions were imported to a treatment planning system for dose–volume histogram analyses.ResultsSingle-source assessment revealed that brachytherapy spacers primarily attenuated the dose distribution along the source long axis. The magnitude of the attenuation at 1 cm on the long axis ranged from −10% to −5% for conventional spacers and approximately −2% for C4 spacers, with the largest attenuation for ¹⁰³Pd. Spacer perturbation of dose distributions was less than manufacturing tolerances for brachytherapy sources as gleaned by an analysis of end-weld thicknesses. Volumetric Monte Carlo assessment demonstrated that TG-43 techniques overestimated calculated doses by approximately 2%. Specific dose–volume histogram metrics for prostate implants were not perturbed by inclusion of conventional or C4 spacers in clinical models.ConclusionsDosimetric perturbations of single-seed dose distributions by brachytherapy spacers exceeded 10% along the source long axes adjacent to the spacers. However, no dosimetric impact on volumetric parameters was noted for brachytherapy spacers adjacent to ¹⁰³Pd, ¹²⁵I, or ¹³¹Cs sources in the context of permanent prostate brachytherapy implants.     

A dose verification tool for high-dose-rate interstitial brachytherapy treatment planning in accelerated partial breast irradiation

PurposeTo develop a dose verification tool for high-dose-rate interstitial brachytherapy treatment planning in accelerated partial breast irradiation.Methods and MaterialsWe have developed a software tool for interstitial brachytherapy treatment planning assessment. The software contains a database of seven ¹⁹²Ir source models and is able to estimate the dose distribution using the Task Group 43 and the Sievert integral algorithms. Dose–volume histogram analysis and dose quality assurance (QA) criteria including conformity (COnformal INdex [COIN] and conformation number [CN]), homogeneity (homogeneity index [HI]) parameters were implemented in the software to evaluate and to compare between the doses estimated by the two algorithms and a dose extracted from an external treatment planning system (TPS).ResultsThe tool was evaluated and validated on four clinical cases treated by high-dose-rate interstitial brachytherapy. The doses provided by the Task Group 43 and the Sievert integral algorithms were evaluated by establishing the dose–volume histogram analysis and then by calculating the QA criteria. The algorithms were validated by comparing the dose at different anatomic points with their corresponding dose points provided from TPS. The differences were considered in good agreement (within 5%).ConclusionsPretreatment dose verification is an important step in the QA of brachytherapy accelerated partial breast irradiation. A simple, fast, and accurate method of dose verification is therefore needed. The software proposed in this study could fulfill these requirements. In addition, it is freely available for using by anyone wishing to do a QA on any TPS.     

The American Brachytherapy Society prostate brachytherapy LDR/HDR simulation workshops: Hands-on,step-by-step training in the process of quality assurance

PurposeEducation and training on prostate brachytherapy for radiation oncology and medical physics residents in the United States is inadequate, resulting in fewer competent radiation oncology personnel to perform implants, and is a factor in the subsequent decline of an important, potentially curative cancer treatment modality for patients with cancer. The American Brachytherapy Society (ABS) leadership has recognized the need to establish a sustainable medical simulation low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy workshop program that includes physician–physicist teams to rapidly translate knowledge to establish high-quality brachytherapy programs.MethodsThe ABS, in partnership with industry and academia, has held three radiation oncology team–based LDR/HDR workshops composed of physician–physicist teams in Chicago in 2017, in Houston in 2018, and in Denver in 2019. The predefined key metric of success is the number of attendees who returned to their respective institutions and were actively performing brachytherapy within 6 months of the prostate brachytherapy workshop.ResultsOf the 111 physician/physicist teams participating in the Chicago, Houston, and Denver prostate brachytherapy workshops, 87 (78%) were actively performing prostate brachytherapy (51 [59%] HDR and 65 [75%] LDR).ConclusionsThe ABS prostate brachytherapy LDR/HDR simulation workshop has provided a successful education and training structure for medical simulation of the critical procedural steps in quality assurance to shorten the learning curve for delivering consistently high-quality brachytherapy implants for patients with prostate cancer. An ABS initiative, intended to bend the negative slope of the brachytherapy curve, is currently underway to train 300 new competent brachytherapy teams over the next 10 years.     

Prostate-specific antigen spikes with 131Cs brachytherapy. Is there a difference with other radioisotopes?

PurposeThere is a suggestion that a dose-rate effect exists for the prostate-specific antigen (PSA) spike after brachytherapy. ¹³¹Cs is a newer radioisotope with a half-life of 9.7 days that is being used for prostate brachytherapy. There is no published data on the PSA spike with this radioisotope and the goal of this study was to quantify PSA spikes with ¹³¹Cs and compare it with published data for other isotopes.Methods and MaterialsWe have been maintaining a prospective database for all patients treated with ¹³¹Cs prostate brachytherapy at our institution. We selected patients for whom followup PSA was available for at least 24 months. The PSA spike was defined as an increase of 0.2 ng/mL, followed by a decline to prespike level.ResultsOne hundred twenty-three patients had monotherapy, whereas 32 had external beam radiation therapy followed by a brachytherapy boost. Median followup was 36 months and mean numbers of PSAs obtained were 7. Forty-six (29.7%) patients had a PSA spike. The mean time and duration for the PSA spike were 12.5 and 8.8 months, respectively. The mean magnitude of increase and mean PSA value at increase were 0.63 and 1.56 ng/mL, respectively.ConclusionsThe incidence of a PSA spike in our series is consistent with reported numbers for other radioisotopes. The occurrence of the spike at 12.5 months appears to be at the early end of the spectrum reported for ¹²⁵I, but the duration and magnitude are similar to other radioisotopes.     

Feasibility of improving patient’s safety with in vivo dose tracking in intracavitary and interstitial HDR brachytherapy

PurposeThe in vivo dosimetric monitoring in HDR brachytherapy is important for improving patient safety. However, there are very limited options available for clinical application. In this study, we present a new in vivo dose measurement system with a plastic scintillating detector (PSD) for GYN HDR brachytherapy.MethodsAn FDA approved PSD system, called OARtrac (AngioDynamics, Latham, NY), was used with various applicators for in vivo dose measurements for GYN patients. An institutional workflow was established for the clinical implementation of the dosimetric system. Action levels were proposed based on the measurement and system uncertainty for measurement deviations. From October 2018 to September 2019, a total of 75 measurements (48 fractions) were acquired from 14 patients who underwent HDR brachytherapy using either a multichannel cylinder, Venezia applicator, or Syed-Neblett template. The PSDs were placed in predetermined catheters/channels. A planning CT was acquired for treatment planning in Oncentra (Elekta, Version-4.5.2) TPS. The PSDs were contoured on the CT images, and the PSD D_90% values were used as the expected doses for comparison with the measured doses.ResultsThe mean difference from patient measurements was ?0.22% ± 5.98%, with 26% being the largest deviation from the expected value (Syed case). Large deviations were observed when detectors were placed in the area where dose rates were less than 1 cGy/s.ConclusionsThe establishment of clinical workflow for the in vivo dosimetry for both the intracavitary and interstitial GYN HDR brachytherapy will potentially improve the safety of the patient treatment.     

Dosimetric differences between intraoperative and postoperative plans using Cs-131 in transrectal ultrasound–guided brachytherapy for prostatic carcinoma

The aim of the study was to investigate the differences between intraoperative and postoperative dosimetry for transrectal ultrasound–guided transperineal prostate implants using cesium-131 (¹³¹Cs). Between 2006 and 2010, 166 patients implanted with ¹³¹Cs had both intraoperative and postoperative dosimetry studies. All cases were monotherapy and doses of 115 were prescribed to the prostate. The dosimetric properties (D₉₀, V₁₅₀, and V₁₀₀ for the prostate) of the studies were compared. Two conformity indices were also calculated and compared. Finally, the prostate was automatically sectioned into 6 sectors (anterior and posterior sectors at the base, midgland, and apex) and the intraoperative and postoperative dosimetry was compared in each individual sector. Postoperative dosimetry showed statistically significant changes (p < 0.01) in every dosimetric value except V₁₅₀. In each significant case, the postoperative plans showed lower dose coverage. The conformity indexes also showed a bimodal frequency distribution with the index indicating poorer dose conformity in the postoperative plans. Sector analysis revealed less dose coverage postoperatively in the base and apex sectors with an increase in dose to the posterior midgland sector. Postoperative dosimetry overall and in specific sectors of the prostate differs significantly from intraoperative planning. Care must be taken during the intraoperative planning stage to ensure complete dose coverage of the prostate with the understanding that the final postoperative dosimetry will show less dose coverage.     

Lung-conserving treatment of a pulmonary oligometastasis with a wedge resection and 131Cs brachytherapy

PurposeSoft-tissue sarcomas most frequently metastasize to the lung. Surgical resection of pulmonary metastases is the primary treatment modality. Although lobectomy is widely acknowledged as the standard procedure to treat primary pulmonary tumors, the standard for pulmonary metastases is not well defined; furthermore, compromised lung function may tip the scales in favor of a less invasive approach. Here, we report the results of a patient treated with wedge resection and intraoperative cesium-131 (¹³¹Cs).Methods and MaterialsA 58-year-old African American female was diagnosed with the American Joint Committee on Cancer Stage IIA mixed uterine leiomyosarcoma and underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by adjuvant external beam radiotherapy to a total dose of 45 Gy and vaginal brachytherapy to a total dose of 20 Gy. At 2 years, a routine CT scan of the chest revealed metastasis to right upper lobe of the lung. The patient's poor pulmonary function, related to a 45 pack-year smoking history and chronic emphysema, precluded a lobectomy.ResultsAfter the patient underwent a lung-sparing wedge resection of the pulmonary right upper lobe metastasis and intraoperative brachytherapy with ¹³¹Cs seeds to a total dose of 80 Gy, she remained disease free in the implanted area. At a 2-year followup, imaging continued to reveal 100% local control of the area treated with wedge resection and intraoperative ¹³¹Cs brachytherapy. The patient had no complications from this treatment.ConclusionsSuch treatment approach may become an attractive option in patients with oligometastatic disease and compromised pulmonary function.     

Conventional vs machine learning–based treatment planning in prostate brachytherapy: Results of a Phase I randomized controlled trial

PurposeThe purpose of this study was to evaluate the noninferiority of Day 30 dosimetry between a machine learning–based treatment planning system for prostate low-dose-rate (LDR) brachytherapy and the conventional, manual planning technique. As a secondary objective, the impact of planning technique on clinical workflow efficiency was also evaluated.Materials and Methods41 consecutive patients who underwent I-125 LDR monotherapy for low- and intermediate-risk prostate cancer were accrued into this single-institution study between 2017 and 2018. Patients were 1:1 randomized to receive treatment planning using a machine learning–based prostate implant planning algorithm (PIPA system) or conventional, manual technique. Treatment plan modifications by the radiation oncologist were evaluated by computing the Dice coefficient of the prostate V_150% isodose volume between either the PIPA—or conventional—and final approved plans. Additional evaluations between groups evaluated the total planning time and dosimetric outcomes at preimplant and Day 30.Results21 and 20 patients were treated using the PIPA and conventional techniques, respectively. No significant differences were observed in preimplant or Day 30 prostate D_90%, V_100%, rectum V₁₀₀, or rectum D_1cc between PIPA and conventional techniques. Although the PIPA group had a larger proportion of patients with plans requiring no modifications (Dice = 1.00), there was no significant difference between the magnitude of modifications between each arm. There was a large significant advantage in mean planning time for the PIPA arm (2.38 ± 0.96 min) compared with the conventional (43.13 ± 58.70 min) technique (p >> 0.05).ConclusionsA machine learning–based planning workflow for prostate LDR brachytherapy has the potential to offer significant time savings and operational efficiencies, while producing noninferior postoperative dosimetry to that of expert, conventional treatment planners.     

Virtual reality-based simulation improves gynecologic brachytherapy proficiency,engagement, and trainee self-confidence

PURPOSEIntracavitary brachytherapy is critical in treatment of cervical cancer with the highest rates of local control and survival. Only about 50% of graduating residents express confidence to develop a brachytherapy practice with caseload as the greatest barrier. We hypothesize that virtual reality (VR)-based intracavitary brachytherapy simulation will improve resident confidence, engagement, and proficiency.METHODSWe created a VR training video of an intracavitary brachytherapy case performed by a board-certified gynecologic radiation oncologist and medical physicist. Residents performed a timed intracavitary procedure on a pelvic simulator before and after viewing the VR simulation module on a commercially available VR headset while five objective measures of implant quality were recorded. The residents completed a pre- and postsimulation questionnaire assessing self-confidence, procedural knowledge, and perceived usefulness of the session.RESULTSThere were 14 residents, including five postgraduate year (PGY)-2, three PGY-3, four PGY-4, and two PGY-5, who participated in the VR curriculum. There were improvements in resident confidence (1.43–3.36), and subjective technical skill in assembly (1.57–3.50) and insertion (1.64–3.21) after the simulation. Average time of implant decreased from 5:51 to 3:34 (p = 0.0016). Median technical proficiencies increased from 4/5 to 5/5. Overall, the residents found VR to be a useful learning tool and indicated increased willingness to perform the procedure again.CONCLUSIONSVR intracavitary brachytherapy simulation improves residents’ self-confidence, subjective and objective technical skills, and willingness to perform brachytherapy. Furthermore, VR is an immersive, engaging, time-efficient, inexpensive, and enjoyable tool that promotes residents interest in brachytherapy.     

Dosimetry for 131Cs and 125I seeds in solid water phantom using radiochromic EBT film

PurposeTo measure the 2D dose distributions with submillimeter resolution for ¹³¹Cs (model CS-1 Rev2) and ¹²⁵I (model 6711) seeds in a Solid Water phantom using radiochromic EBT film for radial distances from 0.06 cm to 5 cm. To determine the TG-43 dosimetry parameters in water by applying Solid Water to liquid water correction factors generated from Monte Carlo simulations.MethodsEach film piece was positioned horizontally above and in close contact with a ¹³¹Cs or ¹²⁵I seed oriented horizontally in a machined groove at the center of a Solid Water phantom, one film at a time. A total of 74 and 50 films were exposed to the ¹³¹Cs and ¹²⁵I seeds, respectively. Different film sizes were utilized to gather data in different distance ranges. The exposure time varied according to the seed air-kerma strength and film size in order to deliver doses in the range covered by the film calibration curve. Small films were exposed for shorter times to assess the near field, while larger films were exposed for longer times in order to assess the far field. For calibration, films were exposed to either 40 kV (M40) or 50 kV (M50) x-rays in air at 100.0 cm SSD with doses ranging from 0.2 Gy to 40 Gy. All experimental, calibration and background films were scanned at a 0.02 cm pixel resolution using a CCD camera-based microdensitometer with a green light source. Data acquisition and scanner uniformity correction were achieved with Microd3 software. Data analysis was performed using ImageJ, FV, IDL and Excel software packages. 2D dose distributions were based on the calibration curve established for 50 kV x-rays. The Solid Water to liquid water medium correction was calculated using the MCNP5 Monte Carlo code. Subsequently, the TG-43 dosimetry parameters in liquid water medium were determined.ResultsValues for the dose-rate constants using EBT film were 1.069±0.036 and 0.923±0.031 cGy U⁻¹ h⁻¹ for ¹³¹Cs and ¹²⁵I seed, respectively. The corresponding values determined using the Monte Carlo method were 1.053±0.014 and 0.924±0.016 cGy U⁻¹ h⁻¹ for ¹³¹Cs and ¹²⁵I seed, respectively. The radial dose functions obtained with EBT film measurements and Monte Carlo simulations were plotted for radial distances up to 5 cm, and agreed within the uncertainty of the two methods. The 2D anisotropy functions obtained with both methods also agreed within their uncertainties.ConclusionEBT film dosimetry in a Solid Water phantom is a viable method for measuring ¹³¹Cs (model CS-1 Rev2) and ¹²⁵I (model 6711) brachytherapy seed dose distributions with submillimeter resolution. With the Solid Water to liquid water correction factors generated from Monte Carlo simulations, the measured TG-43 dosimetry parameters in liquid water for these two seed models were found to be in good agreement with those in the literature.     

Real-time dose-rate monitoring with gynecologic brachytherapy: Results of an initial clinical trial

PurposeA nanoscintillator-based fiber-optic dosimeter (nanoFOD) was developed to measure real-time dose rate during high-dose-rate (HDR) brachytherapy. A trial was designed to prospectively test clinical feasibility in gynecologic implants.Methods and MaterialsA clinical trial enrolled women undergoing vaginal cylinder HDR brachytherapy. The nanoFOD was fixed to the cylinder alongside two thermoluminescent dosimeters (TLDs). Treatment was delivered and real-time dose rates captured by the nanoFOD. The nanoFOD and TLD positions were identified in CT images and used to extract the treatment planning system (TPS) calculated dose. The nanoFOD and TLD cumulative doses were compared with the TPS.ResultsNine women were enrolled for 30 fractions, and real-time data were available in 27 treatments. The median ratio of nanoFOD/TPS dose was 1.00 (IQR 0.94–1.02), with a TLD/TPS ratio of 1.01 (IQR 0.98–1.04). Of the nanoFOD dose measurements, 63% were within 5% of the TPS, 26% between 5 and 10% of the TPS, and the remaining 11% between 10 and 20% of the TPS dose. Of the TLD measurements, 70% were within 5% of the TPS, 22% between 5 and 10% of the TPS, and 7% between 10 and 20% of the TPS dose.ConclusionsReal-time dose-rate measurements during HDR brachytherapy were feasible using the nanoFOD and cumulative dose per fraction showed reasonable agreement to TLD and TPS doses. Additional studies to determine dose thresholds that would yield a low false alarm rate and ongoing device development efforts to improve localization of the scintillator in CT images are needed before this detector should be used to inform clinical decisions.     

Current state of the art brachytherapy treatment planning dosimetry algorithms

Following literature contributions delineating the deficiencies introduced by the approximations of conventional brachytherapy dosimetry, different model-based dosimetry algorithms have been incorporated into commercial systems for ¹⁹²Ir brachytherapy treatment planning. The calculation settings of these algorithms are pre-configured according to criteria established by their developers for optimizing computation speed vs accuracy. Their clinical use is hence straightforward. A basic understanding of these algorithms and their limitations is essential, however, for commissioning; detecting differences from conventional algorithms; explaining their origin; assessing their impact; and maintaining global uniformity of clinical practice.Conventional, Task Group (TG)43-based¹ dosimetry marked an improvement over prior dose calculation formalisms for brachytherapy treatment planning by advocating the use of a source strength quantity traceable to international standards, the introduction of two-dimensional (2D) source anisotropy, and global uniformity in source characterization as well as clinical dosimetry practice. In the past decade, brachytherapy has progressed from the traditional surgical paradigm to modern three-dimensional (3D) image-based treatment planning systems (TPSs) and dose delivery. The information available through patient imaging, however, had not been fully exploited since TG43-based dosimetry relies on source-specific data pre-calculated in a standard homogeneous water geometry.^1–3 Hence, it disregards patient-specific radiation scatter conditions and the radiological differences of tissue or applicator materials from water.In response to literature on the effect of these shortcomings, which has been reviewed in several recent publications,^4–7 TPSs have become commercially available that include improved dosimetry algorithms, collectively referred to as model-based dosimetry algorithms (MBDCAs). At the time of writing, these include a deterministic solver of the linear Boltzmann transport equation (LBTE)^8–10 and a collapsed cone superposition (CCS) algorithm^11–17 for ¹⁹²Ir high-dose-rate (HDR) applications.This work reviews the basic features of these algorithms and their clinical implementation and presents illustrative results of their performance. Monte Carlo (MC) simulation is also briefly discussed since, besides being a candidate MBDCA for clinical implementation, it is used for obtaining input data for MBDCAs, as well as for their testing.     

Cesium-131 prostate brachytherapy: A single institutional long-term experience

AimsTo report on the PSA outcomes in men undergoing prostate seed implant (PSI) with Cesium-131 at a single institution.Materials and MethodsAll patients who underwent prostate brachytherapy with Cesium-131 (¹³¹Cs) at our institution and had the potential for at least 24 months of follow up were included in this study. Results are reported for the by NCCN risk group (low, low/high-intermediate, and high), as well as by treatment received (monotherapy, combination external beam radiation + PSI, or trimodal therapy with androgen deprivation). The Phoenix definition (absolute nadir plus 2 ng/mL) was used to define biochemical freedom from disease (BFD).ResultsEight hundred and six men have undergone prostate brachytherapy with Cesium-131 at our institution, and 669 men were included in analysis. Median follow up was 60.0 months (range: 0–144 months). According to NCCN risk categories, 29.9% were low-, 55.6% intermediate-, and 14.5% high-risk. Using the Phoenix criteria, 5/10-year BFD was 97.1/95.3% for patients in the low-risk category, 94.0/90.1% for patients in the intermediate-risk category, and 86.2/56.6% for patients in the high-risk category. PSA ≤0.2 ng/dL at 4 years was predictive of 10 year biochemical control: 96.3% vs 70.4%, p < 0.001.ConclusionsThe present study demonstrates that prostate brachytherapy with ¹³¹Cs achieves excellent long-term biochemical control.