3D printing in brachytherapy: A systematic review of gynecological applications.

PURPOSE: To provide a systematic review of the applications of 3D printing in gynecological brachytherapy. METHODS: Peer-reviewed articles relating to additive manufacturing (3D printing) from the 34 million plus biomedical citations in National Center for Biotechnology Information (NCBI/PubMed), and 53 million records in Web of Science (Clarivate) were queried for 3D printing applications. The results were narrowed sequentially to, (1) all literature in 3D printing with final publications prior to July 2022 (in English, and excluding books, proceedings, and reviews), and then to applications in, (2) radiotherapy, (3) brachytherapy, (4) gynecological brachytherapy. Brachytherapy applications were reviewed and grouped by disease site, with gynecological applications additionally grouped by study type, methodology, delivery modality, and device type. RESULTS: From 47,541 3D printing citations, 96 publications met the inclusion criteria for brachytherapy, with gynecological clinical applications compromising the highest percentage (32%), followed by skin and surface (19%), and head and neck (9%). The distribution of delivery modalities was 58% for HDR (Ir-192), 35% for LDR (I-125), and 7% for other modalities. In gynecological brachytherapy, studies included design of patient specific applicators and templates, novel applicator designs, applicator additions, quality assurance and dosimetry devices, anthropomorphic gynecological applicators, and in-human clinical trials. Plots of year-to-year growth demonstrate a rapid nonlinear trend since 2014 due to the improving accessibility of low-cost 3D printers. Based on these publications, considerations for clinical use are provided. CONCLUSIONS: 3D printing has emerged as an important clinical technology enabling customized applicator and template designs, representing a major advancement in the methodology for implantation and delivery in gynecological brachytherapy.

A Single-Institution Retrospective Study of Three-Fraction HDR Accelerated Partial Breast Irradiation.

PURPOSE: Accelerated partial breast irradiation (APBI) delivered with high-dose-rate brachytherapy is a standard of care treatment typically delivered over 10 fractions. The TRIUMPH-T multi-institutional study recently demonstrated promising results using a shorter three fraction regimen, however there are limited additional published series using this regimen. Here, we report our experience and outcomes for patients treated as per the TRIUMPH-T regimen. METHODS AND MATERIALS: This study was a retrospective single-institution analysis of patients who underwent lumpectomy followed by APBI (22.5 Gy in 3 fractions delivered over 2-3 days) using a Strut Adjusted Volume Implant (SAVI) applicator between November 2016 and January 2021. Dose-volume metrics were obtained from the clinically treated plan. Chart review was performed to determine locoregional recurrence and toxicities according to CTCAE v5.0. RESULTS: Between 2016 and 2021, 31 patients were treated per the TRIUMPH-T protocol. Median followup was 31 months from completion of brachytherapy. There were no acute/late Grade 3 or higher toxicities. Cumulative late Grade 1 and 2 toxicities were seen in 58.1% and 9.7% of patients, respectively. Of note, four patients experienced locoregional recurrence: three ipsilateral breast tumor recurrences and one nodal recurrence. All three ipsilateral breast tumor recurrences occurred in patients who would be classified as "cautionary" based on ASTRO consensus guidelines due to age ≤50, lobular histology, or high grade. CONCLUSIONS: Three-fraction HDR brachytherapy APBI was well-tolerated with no grade 3 or higher toxicities and an acceptably small percentage of grade 2 toxicities. Given the small sample size, the number of recurrences suggests that attention to appropriate patient selection is necessary until more long-term followup data is available.

The effect of dose gradients on gamma comparison insensitivity in patient specific QA comparisons.

BACKGROUND: While many have speculated on the reasons for gamma comparison insensitivity for patient-specific quality assurance analysis, the true reasons for insensitivity have not yet been elucidated. Failing to understand the reasons for this technique's insensitivity limits our ability to either improve the gamma metric to increase sensitivity of the comparison or the capacity to develop new comparison techniques that circumvent the limitations of the gamma comparison. PURPOSE: To understand the underlying cause(s) for gamma comparison insensitivity and determine if simple plan characteristics can quantitatively predict for gamma comparison sensitivity. METHODS: Known MLC and MU errors of varying magnitudes were induced on simple test fields to preliminarily investigate where gamma failures first begin to appear as error magnitude is increased. Gamma value maps between error-induced plan calculations and error-free plan calculations were created for 20 IMRT and 20 VMAT cases, each on three different detector geometries-ArcCHECK, MapCHECK, and Delta4. Gamma value maps were qualitatively compared to dose-gradient maps, and quantitative comparisons were performed between various plan descriptors and the computed gamma sensitivity for five different classes of induced errors were utilized to determine if any plan descriptor could predict the gamma sensitivity on a case-by-case basis. All comparisons were performed in a calculation-only scenario to remove uncertainties introduced by comparisons made with real patient specific QA measurements. RESULTS: Gamma value maps with increasing induced error magnitude illustrated that gamma comparisons fail first in high-dose, low-gradient regions of the field. Conversely, in areas of high gradient, gamma values typically remain low, even in the presence of large errors, regardless of detector geometry and gamma normalization setting. Thus, the complex, and often overlapping, high dose gradients in plans appear to be a limiting factor in gamma comparison sensitivity as the number of points along these gradients may often outnumber the points available for failing the comparison in lower gradient regions of the field. None of the simple plan descriptors studied were able to quantitively predict gamma comparison sensitivity, suggesting that quantitatively predicting the sensitivity of gamma comparisons on a case-by-case basis may require a combination of multiple factors or metrics not studied here. CONCLUSIONS: Simple plan descriptors and the number of points in high-dose, low-gradient regions of the field did not quantitively predict for gamma comparison sensitivity. However, it is clear from gradient and gamma value maps that gamma comparisons fail first in high-dose, low-gradient regions of the field in the presence of known induced errors, which we have shown to be independent of detector geometry and gamma comparison normalization setting. Gamma comparison sensitivity is thus limited by the ever-increasing complexity of plans and is particularly important to consider as treatment volumes become smaller and the complexity of overlapping plan gradients increases. This suggests that new methods for patient-specific QA comparisons are required to circumvent this limitation.

Ovarian Transposition Before Pelvic Radiation Therapy: Spatial Distribution and Dose Volume Analysis.

PURPOSE: There is a paucity of data analyzing the anatomic locations and dose volume metrics achieved for surgically transposed ovaries in patients desiring fertility or hormonal preservation receiving pelvic radiation therapy (RT), which were examined herein. METHODS AND MATERIALS: This is a retrospective study including women who underwent ovarian transposition before pelvic RT between 2010 to 2020. The craniocaudal (CC) distance of the ovary centroid to the (1) plane of the sacral promontory, (2) iliac crest, and (3) the nearest distance between the ovary edge and RT planning target volume (PTV) were measured (cm). The area under the receiver operating characteristic curve and cut-point analysis estimating ovary location outside the PTV was performed. RESULTS: Thirty-one ovaries were analyzed from 18 patients. Thirteen (72.2%) were treated with intensity modulated RT, and 5 (27.8%) were treated with 3-dimensional conformal radiation therapy. Most ovaries were located above the sacral promontory (64.5%, n = 20), below the iliac crest (96.8%, n = 30), and outside the PTV (64.5%, n = 20). The median distance from the ovaries to the sacral promontory, iliac crest, and PTV was 0.8 cm (interquartile range [IQR], -0.83 to 1.59 cm), -3.22 cm (IQR, -5.12 to -1.84 cm), and 0.9 cm (IQR, -1.0 to 1.9 cm), respectively. The area under the receiver operating characteristic curve and cut-point analysis demonstrated that distance from the iliac crest predicted an ovary to be outside the PTV with an optimal cut-point of -3.0 cm (C-index = 0.82). The median mean and maximum (Dmax) ovary doses were 15.5 Gy (IQR, 9.6-20.2 Gy) and 32.2 Gy (IQR 24.8-46.5 Gy), respectively. CONCLUSIONS: Despite most transposed ovaries being located outside the PTV, nearly all remained below the iliac crest and received RT doses associated with a high risk of ovarian failure. These findings deepen our understanding of the spatial relationship between transposed ovaries and dose to inform surgical and pre-RT planning and suggest that more aggressive ovary-sparing strategies are warranted.

IMRT QA and gamma comparisons: The impact of detector geometry, spatial sampling, and delivery technique on gamma comparison sensitivity.

PURPOSE: To separately quantify sensitivity differences in patient-specific quality assurance comparisons analyzed with the gamma comparison for different measurement geometries, spatial samplings, and delivery techniques [intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT)]. METHODS: Error-free calculations for 20 IMRT and 20 VMAT cases were compared to calculations with known induced errors of varying magnitudes, using gamma comparisons. Five error types (MU scaling, three different MLC errors, and collimator errors) were induced in plan calculations on three different detector geometries - ArcCHECK, MapCHECK, and Delta 4. To study detector geometry sensitivity effects alone, gamma comparisons were made with 1 mm error-free calculations compared to 1 mm error-induced calculations for each device. Effects of spatial sampling were studied by making the same gamma comparisons, but down-sampling the error-induced calculations to the real spatial sampling of each device. Additionally, 1 mm vs 1 mm comparisons between the IMRT and VMAT cases were compared to investigate sensitivity differences between IMRT and VMAT using IMRT and VMAT cohorts with similar ranges of plan complexity and average aperture size. For each case, induced error type, and device, five different gamma criteria were studied to ensure sensitivity differences between devices, spatial sampling scenarios, and delivery technique were not gamma criterion specific, resulting in over 36,000 gamma comparisons. RESULTS: For IMRT cases, Delta4 and MapCHECK devices had similar error sensitivities for lagging leaf, bank shift, and MU errors, while the ArcCHECK had considerably lower sensitivity than the planar-type devices. For collimator errors and perturbational leaf errors the ArcCHECK had higher error sensitivity than planar-type devices. This behavior was independent of gamma parameters (percent dose difference, distance-to-agreement, and low dose threshold), though use of local normalization resulted in error sensitivites that were markedly similar between all three devices. Differences between detector geometries were less pronounced for VMAT deliveries. Error sensitivity for a given gamma criterion when comparing IMRT and VMAT deliveries on the same devices showed that VMAT plans were more sensitive to some specific error types and less sensitive to others, when compared to IMRT plans. For the ArcCHECK device, the sensitivity of IMRT and VMAT cases was quite similar, whereas this was not the case for the planar-type devices. When comparing error sensitivity between 1 mm vs 1 mm calculations and 1 mm vs the real spatial sampling for each device, results showed that increased spatial sampling did not systematically increase error sensitivity. CONCLUSIONS: Noticeable differences in error sensitivity were observed for different detector geometries, but differences were dependent on induced error type, and a particular device geometry did not offer universal improvements in error sensitivity across studied error types. This study demonstrates that the sensitivity of the gamma comparison does not largely hinge on detector spatial sampling. VMAT deliveries were generally less sensitive to errors when compared to IMRT plans for the planar-type devices, while similar sensitivities were observed between delivery techniques for the ArcCHECK device. Results of this work suggest that a universal gamma criterion is inappropriate for IMRT QA and that the percent pixels passing is an insufficient metric for evaluating quality assurance checks in the clinic.

Using in vivo EPID images to detect and quantify patient anatomy changes with gradient dose segmented analysis.

PURPOSE: To investigate the utility of gradient dose segmented analysis (GDSA) in combination with in vivo electronic portal imaging device (EPID) images to predict changes in the PTV mean dose for patient cases. Also, we use the GDSA to retrospectively analyze patients treated in our clinic to assess deviations for different treatment sites and use time-series data to observe any day-to-day changes. METHODS: In vivo EPID transit images acquired on the Varian Halcyon were analyzed for simulated errors in a phantom, including gas bubbles, weight loss, patient shifts, and an arm erroneously in the field. GDSA threshold parameters were tuned to maximize the coefficient of determination (R2 ) between GDSA metrics and the change in the PTV mean dose (Dmean ) as estimated in a treatment planning system (TPS). Similarly for a gamma analysis, the gamma criteria were adjusted to maximize R2 between gamma pass rate and the change in the PTV Dmean from the TPS. The predictive accuracy of these models was tested on patient data measuring the mean and standard deviation of the difference in the predicted change in PTV Dmean and the change in PTV Dmean measured in the TPS. This analysis was extended retrospectively for every patient treated over a 23-month period (n = 852 patients) to assess the range of expected deviations that occurred during routine clinical operation, as well as to assess any differences between treatment sites. Grouping patients treated on the same day, a time-series analysis was performed to determine if GDSA metrics could add value in tracking machine behavior over time. RESULTS: For the phantom data, analyzing the errors, except for shifts, and comparing the change in PTV Dmean and GDSA mean, a maximal R2  = 0.90 was found for a dose threshold of 5% and gradient threshold of 3 mm. For the gamma approach a linear fit between the gamma pass rate for change in the PTV Dmean was assessed for different criteria, using the same image data. A maximal, R2  = 0.84 was found for a gamma criteria of 3%/3 mm, 45% lower dose threshold. For patient data, the predictive accuracy of the change in the PTV Dmean using the GDSA approach and the gamma approach was 0.09 ± 0.98 % and - 0.65 ± 2.21%, respectively. Comparing the two approaches the accuracy did not significantly differ (P = 0.38), whereas the precision of the GDSA prediction is significantly less (P < 0.001). The dosimetric impact of shifts was not detectable with either the GDSA or gamma approach. Analysis of all patients treated over 23 months showed that over 95% of fractions treated deviated from the first fraction by 2% or less. Deviations> 2% occurred most frequently for the later fractions of head-and-neck and lung treatments. Additionally, averaging the GDSA mean metric over all patients on a given treatment day showed that changes in the machine output on the order of 1% could be identified. CONCLUSIONS: GDSA of in vivo EPID images is a useful technique for monitoring patient changes during the course of treatment, particularly weight loss and tumor shrinkage. The GDSA mean provides a quantitative estimate of the change in the PTV Dmean , giving a simple, quantitative metric by which to flag patients with clinically meaningful deviations in treatment. Averaging the GDSA metric over all patients treated on a given day and tracking daily variations can also provide a flag for any systematic deviations in treatment due to machine performance.

A review of patient questions from physicist-patient consults.

PURPOSE: To provide insight into the types of questions asked to medical physicists by patients during one-on-one physicist-patient consults at one institution. MATERIALS AND METHODS: Medical physicists trained in patient communication techniques met with patients to provide an overview of the treatment planning and delivery processes, discuss the patient's treatment plan, and answer any technical questions. From August 2016 to December 2019, 152 physicist-patient consults were conducted. In the initial months of the study (August 2016-December 2017), following each physicist-patient consult, all patient questions were documented by the physicists. For the remaining time period (January 2018-December 2019), any newly encountered questions were periodically added to the list. The questions were compiled into a comprehensive list and organized into categories. RESULTS: There were a total of 88 unique patient questions. These questions fit into four topical categories. Fifty-four questions (61.4%) were in the "Treatment Planning and Delivery Questions" category, 15 questions (17.1%) were in the "General Radiation Questions or Concerns" category, 13 questions (14.8%) were in the "Safety and Quality Assurance Questions" category, and 6 questions (6.8%) were in the "Medical Questions" category. Overall, patients were primarily concerned about how radiation works, the treatment planning and delivery processes, and what is being done to keep them safe throughout their treatment. CONCLUSION: Physicist-patient consults provided an opportunity to address the technical aspects of radiation therapy with patients in greater detail. The fact that patient questions could be conveniently grouped into only four topical categories indicates that it may be straightforward for other medical physicists to prepare for effectively addressing technical questions during physicist-patient consults.

IMRT QA: Selecting gamma criteria based on error detection sensitivity.

PURPOSE: The gamma comparison is widely used to evaluate the agreement between measurements and treatment planning system calculations in patient-specific intensity modulated radiation therapy (IMRT) quality assurance (QA). However, recent publications have raised concerns about the lack of sensitivity when employing commonly used gamma criteria. Understanding the actual sensitivity of a wide range of different gamma criteria may allow the definition of more meaningful gamma criteria and tolerance limits in IMRT QA. We present a method that allows the quantitative determination of gamma criteria sensitivity to induced errors which can be applied to any unique combination of device, delivery technique, and software utilized in a specific clinic. METHODS: A total of 21 DMLC IMRT QA measurements (ArcCHECK®, Sun Nuclear) were compared to QA plan calculations with induced errors. Three scenarios were studied: MU errors, multi-leaf collimator (MLC) errors, and the sensitivity of the gamma comparison to changes in penumbra width. Gamma comparisons were performed between measurements and error-induced calculations using a wide range of gamma criteria, resulting in a total of over 20 000 gamma comparisons. Gamma passing rates for each error class and case were graphed against error magnitude to create error curves in order to represent the range of missed errors in routine IMRT QA using 36 different gamma criteria. RESULTS: This study demonstrates that systematic errors and case-specific errors can be detected by the error curve analysis. Depending on the location of the error curve peak (e.g., not centered about zero), 3%/3 mm threshold = 10% at 90% pixels passing may miss errors as large as 15% MU errors and ±1 cm random MLC errors for some cases. As the dose threshold parameter was increased for a given %Diff/distance-to-agreement (DTA) setting, error sensitivity was increased by up to a factor of two for select cases. This increased sensitivity with increasing dose threshold was consistent across all studied combinations of %Diff/DTA. Criteria such as 2%/3 mm and 3%/2 mm with a 50% threshold at 90% pixels passing are shown to be more appropriately sensitive without being overly strict. However, a broadening of the penumbra by as much as 5 mm in the beam configuration was difficult to detect with commonly used criteria, as well as with the previously mentioned criteria utilizing a threshold of 50%. CONCLUSIONS: We have introduced the error curve method, an analysis technique which allows the quantitative determination of gamma criteria sensitivity to induced errors. The application of the error curve method using DMLC IMRT plans measured on the ArcCHECK® device demonstrated that large errors can potentially be missed in IMRT QA with commonly used gamma criteria (e.g., 3%/3 mm, threshold = 10%, 90% pixels passing). Additionally, increasing the dose threshold value can offer dramatic increases in error sensitivity. This approach may allow the selection of more meaningful gamma criteria for IMRT QA and is straightforward to apply to other combinations of devices and treatment techniques.

FusionArc optimization: a hybrid volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) planning strategy.

PURPOSE: To introduce a hybrid volumetric modulated arc therapy/intensity modulated radiation therapy (VMAT/IMRT) optimization strategy called FusionArc that combines the delivery efficiency of single-arc VMAT with the potentially desirable intensity modulation possible with IMRT. METHODS: A beamlet-based inverse planning system was enhanced to combine the advantages of VMAT and IMRT into one comprehensive technique. In the hybrid strategy, baseline single-arc VMAT plans are optimized and then the current cost function gradients with respect to the beamlets are used to define a metric for predicting which beam angles would benefit from further intensity modulation. Beams with the highest metric values (called the gradient factor) are converted from VMAT apertures to IMRT fluence, and the optimization proceeds with the mixed variable set until convergence or until additional beams are selected for conversion. One phantom and two clinical cases were used to validate the gradient factor and characterize the FusionArc strategy. Comparisons were made between standard IMRT, single-arc VMAT, and FusionArc plans with one to five IMRT∕hybrid beams. RESULTS: The gradient factor was found to be highly predictive of the VMAT angles that would benefit plan quality the most from beam modulation. Over the three cases studied, a FusionArc plan with three converted beams achieved superior dosimetric quality with reductions in final cost ranging from 26.4% to 48.1% compared to single-arc VMAT. Additionally, the three beam FusionArc plans required 22.4%-43.7% fewer MU∕Gy than a seven beam IMRT plan. While the FusionArc plans with five converted beams offer larger reductions in final cost--32.9%-55.2% compared to single-arc VMAT--the decrease in MU∕Gy compared to IMRT was noticeably smaller at 12.2%-18.5%, when compared to IMRT. CONCLUSIONS: A hybrid VMAT∕IMRT strategy was implemented to find a high quality compromise between gantry-angle and intensity-based degrees of freedom. This optimization method will allow patients to be simultaneously planned for dosimetric quality and delivery efficiency without switching between delivery techniques. Example phantom and clinical cases suggest that the conversion of only three VMAT segments to modulated beams may result in a good combination of quality and efficiency.

Inverse-optimized 3D conformal planning: minimizing complexity while achieving equivalence with beamlet IMRT in multiple clinical sites.

PURPOSE: Inverse planned intensity modulated radiation therapy (IMRT) has helped many centers implement highly conformal treatment planning with beamlet-based techniques. The many comparisons between IMRT and 3D conformal (3DCRT) plans, however, have been limited because most 3DCRT plans are forward-planned while IMRT plans utilize inverse planning, meaning both optimization and delivery techniques are different. This work avoids that problem by comparing 3D plans generated with a unique inverse planning method for 3DCRT called inverse-optimized 3D (IO-3D) conformal planning. Since IO-3D and the beamlet IMRT to which it is compared use the same optimization techniques, cost functions, and plan evaluation tools, direct comparisons between IMRT and simple, optimized IO-3D plans are possible. Though IO-3D has some similarity to direct aperture optimization (DAO), since it directly optimizes the apertures used, IO-3D is specifically designed for 3DCRT fields (i.e., 1-2 apertures per beam) rather than starting with IMRT-like modulation and then optimizing aperture shapes. The two algorithms are very different in design, implementation, and use. The goals of this work include using IO-3D to evaluate how close simple but optimized IO-3D plans come to nonconstrained beamlet IMRT, showing that optimization, rather than modulation, may be the most important aspect of IMRT (for some sites). METHODS: The IO-3D dose calculation and optimization functionality is integrated in the in-house 3D planning/optimization system. New features include random point dose calculation distributions, costlet and cost function capabilities, fast dose volume histogram (DVH) and plan evaluation tools, optimization search strategies designed for IO-3D, and an improved, reimplemented edge/octree calculation algorithm. The IO-3D optimization, in distinction to DAO, is designed to optimize 3D conformal plans (one to two segments per beam) and optimizes MLC segment shapes and weights with various user-controllable search strategies which optimize plans without beamlet or pencil beam approximations. IO-3D allows comparisons of beamlet, multisegment, and conformal plans optimized using the same cost functions, dose points, and plan evaluation metrics, so quantitative comparisons are straightforward. Here, comparisons of IO-3D and beamlet IMRT techniques are presented for breast, brain, liver, and lung plans. RESULTS: IO-3D achieves high quality results comparable to beamlet IMRT, for many situations. Though the IO-3D plans have many fewer degrees of freedom for the optimization, this work finds that IO-3D plans with only one to two segments per beam are dosimetrically equivalent (or nearly so) to the beamlet IMRT plans, for several sites. IO-3D also reduces plan complexity significantly. Here, monitor units per fraction (MU/Fx) for IO-3D plans were 22%-68% less than that for the 1 cm × 1 cm beamlet IMRT plans and 72%-84% than the 0.5 cm × 0.5 cm beamlet IMRT plans. CONCLUSIONS: The unique IO-3D algorithm illustrates that inverse planning can achieve high quality 3D conformal plans equivalent (or nearly so) to unconstrained beamlet IMRT plans, for many sites. IO-3D thus provides the potential to optimize flat or few-segment 3DCRT plans, creating less complex optimized plans which are efficient and simple to deliver. The less complex IO-3D plans have operational advantages for scenarios including adaptive replanning, cases with interfraction and intrafraction motion, and pediatric patients.