Comparative evaluation of outcomes amongst different radiosurgery management paradigms for patients with large brain metastasis.

INTRODUCTION: This study compares four management paradigms for large brain metastasis (LMB): fractionated SRS (FSRS), staged SRS (SSRS), resection and postoperative-FSRS (postop-FSRS) or preoperative-SRS (preop-SRS). METHODS: Patients with LBM (≥ 2 cm) between July 2017 and January 2022 at a single tertiary institution were evaluated. Primary endpoints were local failure (LF), radiation necrosis (RN), leptomeningeal disease (LMD), a composite of these variables, and distant intracranial failure (DIF). Gray's test compared cumulative incidence, treating death as a competing risk with a random survival forests (RSF) machine-learning model also used to evaluate the data. RESULTS: 183 patients were treated to 234 LBMs: 31.6% for postop-FSRS, 28.2% for SSRS, 20.1% for FSRS, and 20.1% for preop-SRS. The overall 1-year composite endpoint rates were comparable (21 vs 20%) between nonoperative and operative strategies, but 1-year RN rate was 8 vs 4% (p = 0.012), 1-year overall survival (OS) was 48 vs. 69% (p = 0.001), and 1-year LMD rate was 5 vs 10% (p = 0.052). There were differences in the 1-year RN rates (7% FSRS, 3% postop-FSRS, 5% preop-SRS, 10% SSRS, p = 0.037). With RSF analysis, the out-of-bag error rate for the composite endpoint was 47%, with identified top-risk factors including widespread extracranial disease, > 5 total lesions, and breast cancer histology. CONCLUSION: This is the first study to conduct a head-to-head retrospective comparison of four SRS methods, addressing the lack of randomized data in LBM literature amongst treatment paradigms. Despite patient characteristic trends, no significant differences were found in LF, composite endpoint, and DIF rates between non-operative and operative approaches.

Implementation of superficial radiation therapy (SRT) using SRT-100 Vision™ for non-melanoma skin cancer in a Radiation Oncology clinic.

PURPOSE: This article describes our experience in implementation of superficial radiation therapy (SRT) using SRT-100 Vision™ for non-melanoma skin cancer. METHODS: Following the American Association of Physicists in Medicine Task Group-61 protocol, absolute output (absorbed dose to water at surface (cGy/min)) was measured for three energies (50, 70, and 100 kV) and for six applicators (1.5-5.0 cm in diameter). Percent depth dose (PDD) and profiles were also measured. Timer testing and ultrasound testing were performed. A treatment time calculation worksheet was created. Quality assurance (QA) of SRT-100 Vision was implemented. After treatment workflow for our clinic was developed, end-to-end (E2E) testing was performed using a Rando phantom. Considerations for treatment using SRT-100 Vision were made. RESULTS: Absolute output (cGy/min) decreases as energy increases and applicator size decreases. Due to scatter from the applicator, PDD at depths ≤5 mm does not follow conventional trends but PDD at depths ≥15 mm increases with increasing applicator size. Profiles for the 5 cm applicator do not have strong dependence on depth except profiles at 5 mm for 50 kV. Timer/end errors are negligible for all three energies. Ultrasound images confirm allowed field of view and depth as well as no image artifacts and spatial integrity. Daily, monthly and annual QA of SRT-100 Vision implemented in our clinic is listed in a table format. E2E testing results (<1%) demonstrate the functionality and performance of our treatment workflow. Our considerations for SRT treatment include patient, applicator size and energy selections, patient setup, and shields. CONCLUSIONS: This article is expected to serve as guidance for Radiation Oncology and/or Dermatology clinics aspiring to initiate an SRT program in their clinics.

OptImal Gamma kNife lIghTnIng sOlutioN (IGNITION) score to characterize the solution space of the Gamma Knife FIP optimizer for stereotactic radiosurgery.

OBJECTIVES: The objective of this study is to evaluate the user-defined optimization settings in the Fast Inverse Planning (FIP) optimizer in Leksell GammaPlan® and determine the parameters that result in the best stereotactic radiosurgery (SRS) plan quality for brain metastases, benign tumors, and arteriovenous malformations (AVMs). METHODS: Thirty patients with metastases and 30 with benign lesions-vestibular schwannoma, AVMs, pituitary adenoma, and meningioma-treated with SRS were evaluated. Each target was planned by varying the low dose (LD) and beam-on-time (BOT) penalties in increments of 0.1, from 0 to 1. The following plan quality metrics were recorded for each plan: Paddick conformity index (PCI), gradient index (GI), BOT, and maximum organ-at-risk (OAR) doses. A novel objective score matrix was calculated for each target using a linearly weighted combination of the aforementioned metrics. A histogram of optimal solutions containing the five best scores was extracted. RESULTS: A total of 7260 plans were analyzed with 121 plans per patient for the range of LD/BOT penalties. The ranges of PCI, GI, and BOT across all metastatic lesions were 0.58-0.97, 2.1-3.8, and 8.8-238 min, respectively, and were 0.13-0.97, 2.1-3.8, and 8.8-238 min, respectively, for benign lesions. The objective score matrix showed unique optimal solutions for metastatic lesions and benign lesions. Additionally, the plan metrics of the optimal solutions were significantly improved compared to the clinical plans for metastatic lesions with equivalent metrics for all other cases. CONCLUSION: In this study, FIP optimizer was evaluated to determine the optimal solution space to maximize PCI and minimize GI, BOT and OAR doses simultaneously for single metastatic/benign/non-neoplastic targets. The optimal solution chart was determined using a novel objective score which provides novice and expert planners a roadmap to generate the most optimal plans efficiently using FIP.

A study on inter-planner plan quality variability using a manual planning- or Lightning dose optimizer-approach for single brain lesions treated with the Gamma Knife® Icon™.

PURPOSE: The purpose of this study is to investigate inter-planner plan quality variability using a manual forward planning (MFP)- or fast inverse planning (FIP, Lightning)-approach for single brain lesions treated with the Gamma Knife® (GK) Icon™. METHODS: Thirty patients who were previously treated with GK stereotactic radiosurgery or radiotherapy were selected and divided into three groups (post-operative resection cavity, intact brain metastasis, and vestibular schwannoma [10 patients per group]). Clinical plans for the 30 patients were generated by multiple planners using FIP only (1), a combination of FIP and MFP (12), and MFP only (17). Three planners (Senior, Junior, and Novice) with varying experience levels re-planned the 30 patients using MFP and FIP (two plans per patient) with planning time limit of 60 min. Statistical analysis was performed to compare plan quality metrics (Paddick conformity index, gradient index, number of shots, prescription isodose line, target coverage, beam-on-time (BOT), and organs-at-risk doses) of MFP or FIP plans among three planners and to compare plan quality metrics between each planner's MFP/FIP plans and clinical plans. Variability in FIP parameter settings (BOT, low dose, and target max dose) and in planning time among the planners was also evaluated. RESULTS: Variations in plan quality metrics of FIP plans among three planners were smaller than those of MFP plans for all three groups. Junior's MFP plans were the most comparable to the clinical plans, whereas Senior's and Novice's MFP plans were superior and inferior, respectively. All three planners' FIP plans were comparable or superior to the clinical plans. Differences in FIP parameter settings among the planners were observed. Planning time was shorter and variations in planning time among the planners were smaller for FIP plans in all three groups. CONCLUSIONS: The FIP approach is less planner dependent and more time-honored than the MFP approach.

Optic disc dose reduction in ocular brachytherapy using 125 I notched COMS plaques: A simulation study based on current clinical practice.

PURPOSE: Although notched Collaborative Ocular Melanoma Study (COMS) plaques have been widely used, optic disc dose reduction by notched COMS plaques has not been discussed in the literature. Therefore, this study investigated optic disc dose reduction in ocular brachytherapy using 125 I notched COMS plaques in comparison with optic disc dose for 125 I standard COMS plaques. METHODS: For this simulation study, an in-house brachytherapy dose calculation program was developed using MATLAB software by incorporating the American Association of Physicists in Medicine Task Group-43 Update (AAPM TG-43U1) dosimetry formalism with a line source approximation in a homogeneous water medium and COMS seed coordinates in the AAPM TG 129. Using this program, optic disc doses for standard COMS plaques (from 12 to 22 mm in diameter in 2 mm increments) and notched COMS plaques with one seed removed (Case #1, from 12 to 22 mm) and with two seeds removed (Case #2, from 14 to 22 mm) were calculated as a function of tumor margin-to-optic disc distance (DT) for various tumor basal dimensions (BDs) for prescription depths from 1 to 10 mm in 1 mm intervals. A dose of 85 Gy for an irradiation time of 168 h was prescribed to each prescription depth. Then absolute and relative optic disc dose reduction by notched COMS plaques (Cases #1 and #2) was calculated for all prescription depths. RESULTS: Optic disc dose reduction by notched COMS plaques (Cases #1 and #2) had five unique trends related to maximum optic disc dose reduction and corresponding optimal DT for each BD in each plaque. It increased with increasing prescription depth. CONCLUSIONS: The results presented in this study would enable the clinician to choose an adequate plaque type among standard and notched 125 I COMS plaques and a prescription depth to minimize optic disc dose.

A practical method of estimating medium-heterogeneity corrected dose without a Monte Carlo calculation in ocular brachytherapy using 125I COMS plaques.

PURPOSE: To provide a practical method of estimating medium-heterogeneity corrected dose without a Monte Carlo (MC) calculation in ocular brachytherapy using 125I Collaborative Ocular Melanoma Study (COMS) plaques. METHODS AND MATERIALS: Using egs_brachy, MC simulations (1) under task group-43 assumptions with fully loaded seed configurations in water (HOMO) and (2) with effects of plaque backing, insert and inter-seed interactions (HETERO) were performed for seven 125I COMS plaques (10 mm-22 mm in diameter), and homogeneous dose (DHOMO) and heterogeneous dose (DHETERO) for central-axis and off-axis points were determined. For DHOMO, 85 Gy was normalized to a depth of 5 mm. Central-axis heterogeneity correction factors (HCFs) from a depth of 0 mm (inner sclera) to 22 mm (opposite retina) were derived from a ratio of DHETERO to DHOMO. Off-axis HCFs for optic disc/macula and lens as a function of distance from optic disc/macula (DT/MT) for various basal dimensions of tumor (BD/BM) were derived from DHETERO/DHOMO. RESULTS: Central-axis HCF varied with a dose reduction of 10.3-19.8% by heterogeneity. Off-axis HCF for optic disc/macula varied significantly depending on DT/MT and BD/BM with a dose reduction of 11.3-38.3%. Off-axis HCF for lens had a dependence on MT and BM with its variation of 11.0-19.0%. A clinical example of using HCFs to estimate DHETERO was presented. CONCLUSIONS: The practical method of using depth-dependent central-axis HCF and DT/MT- and BD/BM-dependent off-axis HCF provided in this study will facilitate a heterogeneous dose estimate for 125I COMS plaques without MC calculations.

Clinical application of an institutional fractionated stereotactic radiosurgery (FSRS) program for brain metastases delivered with MRIdianⓇ BrainTx™.

Single-fraction stereotactic radiosurgery (SRS) or fractionated SRS (FSRS) are well established strategies for patients with limited brain metastases. A broad spectrum of modern dedicated platforms are currently available for delivering intracranial SRS/FSRS; however, SRS/FSRS delivered using traditional CT-based platforms relies on the need for diagnostic MR images to be coregistered to planning CT scans for target volume delineation. Additionally, the on-board image guidance on traditional platforms yields limited inter-fraction and intra-fraction real-time visualization of the tumor at the time of treatment delivery. MR Linacs are capable of obtaining treatment planning MR and on-table MR sequences to enable visualization of the targets and organs-at-risk and may subsequently help identify anatomical changes prior to treatment that may invoke the need for on table treatment adaptation. Recently, an MR-guided intracranial package (MRIdian A3i BrainTxTM) was released for intracranial treatment with the ability to perform high-resolution MR sequences using a dedicated brain coil and cranial immobilization system. The objective of this report is to provide, through the experience of our first patient treated, a comprehensive overview of the clinical application of our institutional program for FSRS adaptive delivery using MRIdian's A3i BrainTx system-highlights include reviewing the imaging sequence selection, workflow demonstration, and details in its delivery feasibility in clinical practice, and dosimetric outcomes.

Dosimetric Impact of Lesion Number, Size, and Volume on Mean Brain Dose with Stereotactic Radiosurgery for Multiple Brain Metastases.

We evaluated the effect of lesion number and volume for brain metastasis treated with SRS using GammaKnife® ICON™ (GK) and CyberKnife® M6™ (CK). Four sets of lesion sizes (<5 mm, 5-10 mm, >10-15 mm, and >15 mm) were contoured and prescribed a dose of 20 Gy/1 fraction. The number of lesions was increased until a threshold mean brain dose of 8 Gy was reached; then individually optimized to achieve maximum conformity. Across GK plans, mean brain dose was linearly proportional to the number of lesions and total GTV for all sizes. The numbers of lesions needed to reach this threshold for GK were 177, 57, 29, and 10 for each size group, respectively; corresponding total GTVs were 3.62 cc, 20.37 cc, 30.25 cc, and 57.96 cc, respectively. For CK, the threshold numbers of lesions were 135, 35, 18, and 8, with corresponding total GTVs of 2.32 cc, 12.09 cc, 18.24 cc, and 41.52 cc respectively. Mean brain dose increased linearly with number of lesions and total GTV while V8 Gy, V10 Gy, and V12 Gy showed quadratic correlations to the number of lesions and total GTV. Modern dedicated intracranial SRS systems allow for treatment of numerous brain metastases especially for ≤10 mm; clinical evidence to support this practice is critical to expansion in the clinic.

Field output correction factors of stereotactic cones for a diode detector: Dependence on cone size, measurement setup, reference field size and photon energy.

This study investigated if field output correction factors (FOCFs) of Varian stereotactic cones for Edge detectorTM had dependence on cone size, measurement setup, reference field size and/or photon energy. Field output factors (FOFs) of stereotactic cones were measured at three depths (1.5 cm, 5 cm and 10 cm) in two different setups (source-to-surface distance (SSD) and source-to-axis distance (SAD)) with two photon energies (6 MV and 6 MV flattening filter free) using the Edge detector and Exradin® W2 scintillator. Two reference fields (10 × 10 cm2 and 4 × 4 cm2) were chosen. FOCFs for the Edge detector were determined by calculating FOFW2/FOFEdge and compared among cones and between depths, setups, reference fields and energies. It is concluded that FOCFs for the Edge detector have dependence on cone size, SSD/SAD setup and energy for small cones, but do not have dependence on depth and reference field size.

Zero Setup Margin Mask versus Frame Immobilization during Gamma Knife® Icon™ Stereotactic Radiosurgery for Brain Metastases.

We compared the clinical outcomes of BM treated with mask immobilization with zero-SM (i.e., zero-PTV) to standard zero-SM frame immobilization SRS. Consecutive patients with BM, 0.5−2.0 cm in maximal diameter, treated with single-fraction SRS (22−24 Gy) during March 2019−February 2021 were included. Univariable and multivariable analysis were performed using the Kaplan−Meier method and Cox proportional hazards regression. A total of 150 patients with 453 BM met inclusion criteria. A total of 129 (28.5%) lesions were treated with a zero-SM mask immobilization and 324 (71.5%) with zero-SM frame immobilization. Frame immobilization treatments were associated with a higher proportion of gastrointestinal and fewer breast-cancer metastases (p = 0.024), and a higher number of treated lesions per SRS course (median 7 vs. 3; p < 0.001). With a median follow up of 15 months, there was no difference in FFLF between the mask and frame immobilization groups on univariable (p = 0.29) or multivariable analysis (p = 0.518). Actuarial FFLF at 1 year was 90.5% for mask and 92% for frame immobilization (p = 0.272). Radiation necrosis rates at 1 year were 12.5% for mask and 4.1% for frame immobilization (p = 0.502). For BM 0.5−2.0 cm in maximal diameter treated with single-fraction SRS using 22−24 Gy, mask immobilization with zero SM produces comparable clinical outcomes to frame immobilization. The initial findings support omitting a SM when using mask immobilization with this treatment approach on a Gamma Knife® Icon™.

A patient-specific QA comparison between 2D and 3D diode arrays for single-lesion SRS and SBRT treatments.

The purpose of this study is to compare patient-specific quality assurance (PSQA) results between two dimensional (2D) diode (SRS MapCHECK®) and 3D diode (ArcCHECK®) arrays. Twenty-eight intracranial stereotactic radiosurgery (SRS) and 26 lung stereotactic body radiation therapy (SBRT) clinical plans with a single lesion were selected and categorized into 4 groups: 20 SRS dynamic conformal arc therapy (DCAT) plans (Group A), 8 SRS volumetric modulated arc therapy (VMAT) plans (Group B), 6 SBRT DCAT plans (Group C) and 20 SBRT VMAT plans (Group D). An individual field of each plan was delivered on SRS MapCHECK and ArcCHECK and QA analysis was performed using 4 gamma criteria of dose difference/distance-to-agreement of 3%/3 mm, 3%/2 mm, 2%/2 mm and 2%/1 mm. Statistical analysis was performed to compare PSQA results between the 2 QA devices. For all 4 groups and all 4 gamma criteria, average gamma passing rates were higher with SRS MapCHECK.

Optic Disc Dose Comparison Between 125I and 103Pd Collaborative Ocular Melanoma Study (COMS) Plaques Based on Current Clinical Practice.

Purpose The purpose of this study is to compare optic disc dose (ODD) between 125I and 103Pd Collaborative Ocular Melanoma Study (COMS) plaques in ocular brachytherapy. Methods A previously validated in-house brachytherapy dose calculation program was used for ODD calculations. ODD was calculated as a function of tumor margin-to-optic disc distance (DT) up to 5 mm for various tumor basal dimensions (BDs), for a prescription depth of 5 mm, and for standard and notched COMS plaques loaded with 125I (model: IAI-125A) and 103Pd (model: IAPd-103A) seeds. ODD calculations were repeated for prescription depths from 2 mm to 10 mm in 1 mm intervals. A prescribed dose of 85 Gy (irradiation time: 120 hours) was normalized to each prescription depth. Dose conversion factors (DCFs) for each prescription depth were calculated by taking a ratio of [total reference air kerma (TRAK) per seed]prescription depth to [TRAK per seed]5 mm. ODD reduction by notched COMS plaques was calculated for each prescription depth by subtracting ODD for notched COMS plaques from ODD for standard COMS plaques. Results Trends of ODD as a function of DT for various BDs are similar between the two seed types in both standard and notched COMS plaques. However, due to the energy difference, there exists a transition distance (dt) for each BD in each plaque at which ODD for 125I COMS plaques equals that for 103Pd COMS plaques. For small BDs, at DT dt, the opposite is observed. For the largest 1-3 BD(s), contrarily, dt occurs within the tumor, and thus, ODD for 125I COMS plaquesis always higher. Trends of ODD reduction by notched COMS plaques as a function of DT for various BDs are the same for the two seed types except that maximum ODD reduction by 103Pd COMS notched plaques is larger. DCF increases with increasing prescription depth for both seed types. Conclusions There exist ODD differences between 125I and 103Pd COMS plaques and the differences depend on DT, BD, plaque size, and prescription depth.

Dose Summation Strategies for External Beam Radiation Therapy and Brachytherapy in Gynecologic Malignancy: A Review from the NRG Oncology and NCTN Medical Physics Subcommittees.

Definitive, nonsurgical management of gynecologic malignancies involves external beam radiation therapy (EBRT) and/or brachytherapy (BT). Summation of the cumulative dose is critical to assess the total biologic effective dose to targets and organs at risk. Cumulative dose calculation from EBRT and BT can be performed with or without image registration (IR) and biologic dose summation. Among these dose summation strategies, linear addition of dose-volume histogram (DVH) parameters without IR is the global standard for composite dose reporting. This approach stems from an era without image guidance and simple external beam and brachytherapy treatment approaches. With technological advances, EBRT and high-dose-rate BT have evolved to allow for volume-based treatment planning and delivery. Modern conformal therapeutic radiation involves volumetric or intensity modulated EBRT, capable of simultaneously treating multiple targets at different specified dose levels. Therefore, given the complexity of modern radiation treatment, the linear addition of DVH parameters from EBRT and high-dose-rate BT is challenging to represent the combined dose distribution. Deformable image registration (DIR) between EBRT and image guided brachytherapy (IGBT) data sets may provide a more nuanced calculation of multimodal dose accumulation. However, DIR is still nascent in this regard, and needs further development for accuracy and efficiency for clinical use. Biologic dose summation can combine physical dose maps from EBRT and each IGBT fraction, thereby generating a composite DVH from the biologic effective dose. However, accurate radiobiologic parameters are tissue-dependent and not well characterized. A combination of voxel-based DIR and biologic weighted dose maps may be the best approximation of dose accumulation but remains invalidated. The purpose of this report is to review dose summation strategies for EBRT and BT, including conventional equivalent dose in 2-Gy fractions dose summation without image registration, physical dose summation using 3-dimensional rigid IR and DIR, and biologic dose summation. We also provide general clinical workflows for IGBT with a focus on cervical cancer.

QA procedures for multimodality preclinical tumor drug response testing.

PURPOSE: There are growing expectations that imaging biomarkers for tumor therapeutic drug response assessment will speed up preclinical testing of anticancer drugs in rodent models. The only imaging biomarker presently approved by the U.S. Food and Drug Administration is tumor size measurement based on either World Health Organization (WHO) criteria or Response Evaluation Criteria in Solid Tumors (RECIST). Frequently, preclinical data are accumulated from multiple research centers on multiple continents using scanners from different manufacturers and sometimes even using different imaging modalities. Very expensive cancer drug response studies can be compromised by inadequate controls to assure precision and accuracy of tumor size measurements. This project was undertaken to develop standardized quality assurance (QA) procedures using a multimodality preclinical tumor response phantom to validate the accuracy of tumor size measurements based on WHO criteria, RECIST, or global tumor volume criteria for evaluation of cytostatic drugs. METHODS: A tumor response phantom containing five low contrast test objects designed to simulate animal tumor models was made of tissue-mimicking materials. Imaging of the phantom was performed using three modalities in two institutions to evaluate size measurement of tumor-simulating test objects. RESULTS: Evaluation of tumor measurements from the three commonly used imaging devices in two different institutions for monitoring tumor size changes showed that a single phantom for multiple modalities was feasible. The tumor response phantom validated precision and accuracy of tumor response data input from ultrasound, computed tomography, and/or magnetic resonance imaging devices. CONCLUSIONS: Measurement results show that the standardized QA procedures using the tumor response phantom can provide a rationale check of data that excludes input from poorly maintained instruments, inadequate measurement protocols, or random operator error that frequently introduce unacceptable variability or systematic error in multiple institutions trials.

Circular collimator arc versus dynamic conformal arc treatment planning for linac-based stereotactic radiosurgery of an intracranial small single lesion: a perspective of lesion asymmetry.

BACKGROUND: Although circular collimator arcs (CCA) and dynamic conformal arcs (DCA) are commonly used linear accelerator-based treatment planning techniques for intracranial stereotactic radiosurgery (SRS) of a small single lesion, these two techniques have not been rigorously compared in terms of tumor shape. Therefore, this study compared clinical CCA plans with re-planned DCA plans using conformity index (CI) and V12Gy (volume of normal brain tissue receiving 12 Gy or higher) from a perspective of asymmetry (Asym) of planning target volume (PTV). METHODS: Ninety-five clinical CCA plans delivered for a small single lesion with PTV size < 1.4 cm3 were selected and re-planned using DCA. PTV Asym (%) was defined and calculated from three dimensions of PTV. A pair of the 95 plans was first considered as one group without grouping and then categorized into two groups with respective to either PTV size or PTV Asym, and four groups with respect to PTV size and PTV Asym. For grouping, median values of PTV size and PTV Asym were used. A non-parametric paired test was performed for CI and V12Gy to compare CCA and DCA plans in each group. RESULTS: Median values of PTV size and PTV Asym were 0.415 cm3 (range: 0.076 cm3-1.369 cm3) and 6.12% (range: 0.52-25.74%), respectively. DCA plans had a lower average CI value than CCA plans for all groups. CCA plans had a smaller average V12Gy value than DCA plans for lesions with PTV Asym ≤6.12%, while CCA and DCA plans had similar average V12Gy values for lesions with PTV Asym > 6.12%. CONCLUSIONS: The DCA technique is recommended when a lesion has PTV Asym > 6.12% regardless of PTV size. For lesions with PTV Asym ≤6.12%, a technique choice would depend on the preference of CI or V12Gy.

A practical approach to estimating optic disc dose and macula dose without treatment planning in ocular brachytherapy using 125I COMS plaques.

BACKGROUND: It has been reported that proximity of the tumor to the optic disc and macula, and radiation dose to the critical structures are substantial risk factors for vision loss following plaque brachytherapy. However, there is little dosimetry data published on this. In this study, therefore, the relationship between distance from tumor margin and radiation dose to the optic disc and macula in ocular brachytherapy using 125I Collaborative Ocular Melanoma Study (COMS) plaques was comprehensively investigated. From the information, this study aimed to allow for estimation of optic disc dose and macula dose without treatment planning. METHODS: An in-house brachytherapy dose calculation program utilizing the American Association of Physicists in Medicine Task Group-43 U1 formalism with a line source approximation in a homogenous water phantom was developed and validated against three commercial treatment planning systems (TPS). Then optic disc dose and macula dose were calculated as a function of distance from tumor margin for various tumor basal dimensions for seven COMS plaques (from 10 mm to 22 mm in 2 mm increments) loaded with commercially available 125I seeds models (IAI-125A, 2301 and I25.S16). A prescribed dose of 85 Gy for an irradiation time of 168 h was normalized to a central-axis depth of 5 mm. Dose conversion factors for each seed model were obtained by taking ratios of total reference air kerma per seed at various prescription depths (from 1 mm to 10 mm in 1 mm intervals) to that at 5 mm. RESULTS: The in-house program demonstrated relatively similar accuracy to commercial TPS. Optic disc dose and macula dose decreased as distance from tumor margin and tumor basal dimension increased. Dose conversion factors increased with increasing prescription depth. There existed dose variations (<8%) among three 125I seed models. Optic disc dose and macula dose for each COMS plaque and for each seed model are presented in a figure format. Dose conversion factors for each seed model are presented in a tabular format. CONCLUSIONS: The data provided in this study would enable clinicians in any clinic using 125I COMS plaques to estimate optic disc dose and macula dose without dose calculations.

Failure modes and effects analysis for ocular brachytherapy.

PURPOSE: The aim of the study was to identify potential failure modes (FMs) having a high risk and to improve our current quality management (QM) program in Collaborative Ocular Melanoma Study (COMS) ocular brachytherapy by undertaking a failure modes and effects analysis (FMEA) and a fault tree analysis (FTA). METHODS AND MATERIALS: Process mapping and FMEA were performed for COMS ocular brachytherapy. For all FMs identified in FMEA, risk priority numbers (RPNs) were determined by assigning and multiplying occurrence, severity, and lack of detectability values, each ranging from 1 to 10. FTA was performed for the major process that had the highest ranked FM. RESULTS: Twelve major processes, 121 sub-process steps, 188 potential FMs, and 209 possible causes were identified. For 188 FMs, RPN scores ranged from 1.0 to 236.1. The plaque assembly process had the highest ranked FM. The majority of FMs were attributable to human failure (85.6%), and medical physicist-related failures were the most numerous (58.9% of all causes). After FMEA, additional QM methods were included for the top 10 FMs and 6 FMs with severity values > 9.0. As a result, for these 16 FMs and the 5 major processes involved, quality control steps were increased from 8 (50%) to 15 (93.8%), and major processes having quality assurance steps were increased from 2 to 4. CONCLUSIONS: To reduce high risk in current clinical practice, we proposed QM methods. They mainly include a check or verification of procedures/steps and the use of checklists for both ophthalmology and radiation oncology staff, and intraoperative ultrasound-guided plaque positioning for ophthalmology staff.

Construction of a preclinical multimodality phantom using tissue-mimicking materials for quality assurance in tumor size measurement.

World Health Organization (WHO) and the Response Evaluation Criteria in Solid Tumors (RECIST) working groups advocated standardized criteria for radiologic assessment of solid tumors in response to anti-tumor drug therapy in the 1980s and 1990s, respectively. WHO criteria measure solid tumors in two-dimensions, whereas RECIST measurements use only one-dimension which is considered to be more reproducible (1, 2, 3,4,5). These criteria have been widely used as the only imaging biomarker approved by the United States Food and Drug Administration (FDA) (6). In order to measure tumor response to anti-tumor drugs on images with accuracy, therefore, a robust quality assurance (QA) procedures and corresponding QA phantom are needed. To address this need, the authors constructed a preclinical multimodality (for ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI)) phantom using tissue-mimicking (TM) materials based on the limited number of target lesions required by RECIST by revising a Gammex US commercial phantom (7). The Appendix in Lee et al. demonstrates the procedures of phantom fabrication (7). In this article, all protocols are introduced in a step-by-step fashion beginning with procedures for preparing the silicone molds for casting tumor-simulating test objects in the phantom, followed by preparation of TM materials for multimodality imaging, and finally construction of the preclinical multimodality QA phantom. The primary purpose of this paper is to provide the protocols to allow anyone interested in independently constructing a phantom for their own projects. QA procedures for tumor size measurement, and RECIST, WHO and volume measurement results of test objects made at multiple institutions using this QA phantom are shown in detail in Lee et al. (8).

The equivalent dose contribution from high-dose-rate brachytherapy to positive pelvic lymph nodes in locally advanced cervical cancer.

PURPOSE: Definitive radiation therapy for locally advanced cervical cancer involves external beam radiation therapy (EBRT) and high-dose-rate (HDR) brachytherapy. There remains controversy and practice pattern variation regarding the optimal radiation dose to metastatic pelvic lymph nodes (LNs). This study investigates the contribution of the pelvic LN dose from HDR brachytherapy. METHODS AND MATERIALS: For 17 patients with 36 positive pelvic LNs, each LN was contoured on a computed tomography (CT) plan for EBRT and on brachytherapy planning CTs using positron emission tomographic images obtained before chemoradiation. The mean delivered dose from each plan was recorded, and an equivalent dose in 2-Gy fractions (EQD2) was calculated. A Student's t test was performed to determine if the mean delivered dose is significantly different from the mean prescribed dose and EQD2. RESULTS: The average prescribed dose from the total EBRT was 54.09 Gy. The average prescribed HDR dose to International Commission on Radiation Units point A was 26.81 Gy. The average doses delivered to the involved LNs from EBRT and brachytherapy were 54.25 and 4.31 Gy, respectively, with the corresponding EQD2 of 53.45 and 4.00 Gy. There was no statistically significant difference (p < 0.05) between the mean delivered and the prescribed doses for EBRT and between the delivered dose and the EQD2 for EBRT and brachytherapy. CONCLUSIONS: Our study shows that the HDR contribution is 7% (4.00 Gy) of the total EQD2 (57.45 Gy). The HDR contribution should be accounted for when prescribing the EBRT boost dose to pelvic LNs for the optimal therapeutic dose.

Clinical response of pelvic and para-aortic lymphadenopathy to a radiation boost in the definitive management of locally advanced cervical cancer.

PURPOSE: Optimal treatment with radiation for metastatic lymphadenopathy in locally advanced cervical cancer remains controversial. We investigated the clinical dose response threshold for pelvic and para-aortic lymph node boost using radiographic imaging and clinical outcomes. METHODS AND MATERIALS: Between 2007 and 2011, 68 patients were treated for locally advanced cervical cancer; 40 patients had clinically involved pelvic and/or para-aortic lymph nodes. Computed tomography (CT) or 18F-labeled fluorodeoxyglucose-positron emission tomography scans obtained pre- and postchemoradiation for 18 patients were reviewed to assess therapeutic radiographic response of individual lymph nodes. External beam boost doses to involved nodes were compared to treatment response, assessed by change in size of lymph nodes by short axis and change in standard uptake value (SUV). Patterns of failure, time to recurrence, overall survival (OS), and disease-free survival (DFS) were determined. RESULTS: Sixty-four lymph nodes suspicious for metastatic involvement were identified. Radiation boost doses ranged from 0 to 15 Gy, with a mean total dose of 52.3 Gy. Pelvic lymph nodes were treated with a slightly higher dose than para-aortic lymph nodes: mean 55.3 Gy versus 51.7 Gy, respectively. There was no correlation between dose delivered and change in size of lymph nodes along the short axis. All lymph nodes underwent a decrease in SUV with a complete resolution of abnormal uptake observed in 68%. Decrease in SUV was significantly greater for lymph nodes treated with ≥54 Gy compared to those treated with <54 Gy (P=.006). Median follow-up was 18.7 months. At 2 years, OS and DFS for the entire cohort were 78% and 50%, respectively. Locoregional control at 2 years was 84%. CONCLUSIONS: A biologic response, as measured by the change in SUV for metastatic lymph nodes, was observed at a dose threshold of 54 Gy. We recommend that involved lymph nodes be treated to this minimum dose.