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Purpose: The Adaptive Radiation Therapy Individualized Approach-Cervix clinical trial uses predefined clinical directive templates (CDTs) combined with RapidPlan dose-volume histogram estimations (DVHe) to guide plan optimization in the Ethos treatment planning system. The dosimetric scorecard is a scoring tool that quantifies improvements in plan quality after physicians have precisely expressed their complete clinical intent. To our knowledge, this is the first study to use the dosimetric scorecard tool to tune an Ethos CDT to improve resulting plan quality. Methods and Materials: Iterative replanning was used to modify the draft CDT (CDT-1) in Ethos 1.1 to generate a new CDT (CDT-2) that maximized the clinical consensus scorecard's total score compared with CDT-1. CDT-2 was established, and resulting plans were compared with and without a DVHe. Additional fixed field intensity modulated radiation therapy beam geometries were compared between CDT-1 and CDT-2, both with DVHe. After obtaining favorable results when comparing CDT-1 versus CDT-2 for 2 test cases, 10 additional cases were retrospectively identified and tested. Results: CDT-2 reduced organ at risk doses without compromising planning target volume coverage in the initial test cases. When combined with DVHe, CDT-2 marginally outperformed CDT-1. Plan quality further improved with a 19-field geometry. In the expanded analysis, CDT-2 achieved higher scores than CDT-1 in most cases, with the 19-field approach showing superiority. Optimization and calculation time increased by 1.9 minutes, monitor unit (MU)/field decreased by 44.4, whereas beam-on time increased by 2.8 minutes when increasing fields to 19 from 9. Reoptimization with Ethos 1.1 Maintenance Release 1 resulted in decreased MU and minimal score changes. Conclusions: The scorecard is an effective tool to adjust an Ethos CDT to improve the average calculated plan quality. It also allowed for easy evaluation of the dosimetric impact of other planning parameters (beam arrangements and use of DVHe) to identify the best approach. Using a finely tuned CDT is expected to improve planning efficiency and decrease intrainstitutional plan quality variability, benefiting cone beam computed tomography-guided adaptive radiation therapy.
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PURPOSE: The focal radiation therapy (RT) boost technique was shown in a phase III randomized controlled trial (RCT) to improve prostate cancer outcomes without increasing toxicity. This technique relies on the accurate delineation of prostate tumors on MRI. A recent prospective study evaluated radiation oncologists' accuracy when asked to delineate prostate tumors on MRI and demonstrated high variability in tumor contours. We sought to evaluate the impact of contour variability and inaccuracy on predicted clinical outcomes. We hypothesized that radiation oncologists' contour inaccuracies would yield meaningfully worse clinical outcomes. METHODS AND MATERIALS: Forty-five radiation oncologists and 2 expert radiologists contoured prostate tumors on 30 patient cases. Of these cases, those with CT simulation or diagnostic CT available were selected for analysis. A knowledge-based planning model was developed to generate focal RT boost plans for each contour per the RCT protocol. The probability of biochemical failure (BF) was determined using a model from the RCT. The primary metric evaluated was delta BF (DBF = Participant BF - Expert BF). An absolute increase in BF ≥5% was considered clinically meaningful. RESULTS: Eight patient cases and 394 target volumes for focal RT boost planning were included in this analysis. In general, participant plans were associated with worse predicted clinical outcomes compared to the expert plan, with an average absolute increase in BF of 4.3%. Of participant plans, 37% were noted to have an absolute increase in BF of 5% or more. CONCLUSIONS: Radiation oncologists' attempts to contour tumor targets for focal RT boost are frequently inaccurate enough to yield meaningfully inferior clinical outcomes for patients.
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Objective.Online adaptive radiotherapy (OART) is a promising technique for delivering stereotactic accelerated partial breast irradiation (APBI), as lumpectomy cavities vary in location and size between simulation and treatment. However, OART is resource-intensive, increasing planning and treatment times and decreasing machine throughput compared to the standard of care (SOC). Thus, it is pertinent to identify high-yield OART candidates to best allocate resources.Approach.Reference plans (plans based on simulation anatomy), SOC plans (reference plans recalculated onto daily anatomy), and daily adaptive plans were analyzed for 31 sequential APBI targets, resulting in the analysis of 333 treatment plans. Spearman correlations between 22 reference plan metrics and 10 adaptive benefits, defined as the difference between mean SOC and delivered metrics, were analyzed to select a univariate predictor of OART benefit. A multivariate logistic regression model was then trained to stratify high- and low-benefit candidates.Main results.Adaptively delivered plans showed dosimetric benefit as compared to SOC plans for most plan metrics, although the degree of adaptive benefit varied per patient. The univariate model showed high likelihood for dosimetric adaptive benefit when the reference plan ipsilateral breast V15Gy exceeds 23.5%. Recursive feature elimination identified 5 metrics that predict high-dosimetric-benefit adaptive patients. Using leave-one-out cross validation, the univariate and multivariate models classified targets with 74.2% and 83.9% accuracy, resulting in improvement in per-fraction adaptive benefit between targets identified as high- and low-yield for 7/10 and 8/10 plan metrics, respectively.Significance.This retrospective, exploratory study demonstrated that dosimetric benefit can be predicted using only ipsilateral breast V15Gy on the reference treatment plan, allowing for a simple, interpretable model. Using multivariate logistic regression for adaptive benefit prediction led to increased accuracy at the cost of a more complicated model. This work presents a methodology for clinics wishing to triage OART resource allocation.
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Neoplasias de la Mama , Aprendizaje Automático , Planificación de la Radioterapia Asistida por Computador , Humanos , Neoplasias de la Mama/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Femenino , Radiocirugia/métodosRESUMEN
PURPOSE: Cone beam computed tomography (CBCT)-based online adaptive radiation therapy (ART) is especially beneficial for patients with large interfractional anatomic changes. However, treatment planning and review decisions need to be made at the treatment console in real-time and may be delegated to clinical staff whose conventional scope of practice does not include making such decisions. Therefore, implementation can create new safety risks and inefficiencies. The objective of this work is to systematically analyze the safety and efficiency implications of human decision-making during the treatment session for CBCT-based online ART. METHODS AND MATERIALS: The analysis was performed by applying the Systems-Theoretical Process Analysis technique and its extension for human decision-making. Four centers of different CBCT-based online ART practice models comprised the analysis team. RESULTS: The general radiation therapy control structure was refined to model the interactions between routine treatment delivery staff and in-person or remote support staff. The treatment delivery staff perform 6 key control actions. Eighteen undesirable states of those control actions were identified as affecting safety and/or efficiency. In turn, 97 hazardous clinical scenarios were identified, with the control action "prepare and position patient" having the least number of scenarios and "delineate/edit influencer and target structures" having the most. Five of these are specific to either in-person or remote support during the treatment session, and 12 arise from staff support in general. CONCLUSIONS: An optimally safe and efficient online ART program should require little to no support staff at the treatment console to reduce staff coordination. Uptraining of the staff already at the treatment console is needed to achieve this goal. Beyond the essential knowledge and skills such as contour editing and the selection of an optimal plan, uptraining should also target the specific cognitive biases identified in this work and the cognitive strategies to overcome these biases. Additionally, technological and organizational changes are necessary.
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Tomografía Computarizada de Haz Cónico , Humanos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/métodos , Toma de Decisiones Clínicas , Seguridad del Paciente , Toma de DecisionesRESUMEN
Objective. Adaptive Radiotherapy (ART) is an emerging technique for treating cancer patients which facilitates higher delivery accuracy and has the potential to reduce toxicity. However, ART is also resource-intensive, Requiring extra human and machine time compared to standard treatment methods. In this analysis, we sought to predict the subset of node-negative cervical cancer patients with the greatest benefit from ART, so resources might be properly allocated to the highest-yield patients.Approach. CT images, initial plan data, and on-treatment Cone-Beam CT (CBCT) images for 20 retrospective cervical cancer patients were used to simulate doses from daily non-adaptive and adaptive techniques. We evaluated the coefficient of determination (R2) between dose and volume metrics from initial treatment plans and the dosimetric benefits to theBowelV40Gy,BowelV45Gy,BladderDmean,andRectumDmeanfrom adaptive radiotherapy using reduced 3 mm or 5 mm CTV-to-PTV margins. The LASSO technique was used to identify the most predictive metrics forBowelV40Gy.The three highest performing metrics were used to build multivariate models with leave-one-out validation forBowelV40Gy.Main results. Patients with higher initial bowel doses were correlated with the largest decreases in BowelV40Gyfrom daily adaptation (linear best fit R2= 0.77 for a 3 mm PTV margin and R2= 0.8 for a 5 mm PTV margin). Other metrics had intermediate or no correlation. Selected covariates for the multivariate model were differences in the initialBowelV40GyandBladderDmeanusing standard versus reduced margins and the initial bladder volume. Leave-one-out validation had an R2of 0.66 between predicted and true adaptiveBowelV40Gybenefits for both margins.Significance. The resulting models could be used to prospectively triage cervical cancer patients on or off daily adaptation to optimally manage clinical resources. Additionally, this work presents a critical foundation for predicting benefits from daily adaptation that can be extended to other patient cohorts.
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Radioterapia Guiada por Imagen , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Estudios Retrospectivos , Radioterapia Guiada por Imagen/métodos , Radiometría/métodosRESUMEN
PURPOSE: Evaluate a cone-beam computed tomography (CBCT)-based daily adaptive platform in cervical cancer for multiple endpoints: (1) physics contouring accuracy of daily CTVs, (2) CTV coverage with adapted plans and reduced PTV margins versus non-adapted plans with standard-of-care (SOC) margins, (3) dosimetric improvements to CTV and organs-at-risk (OARs), and (4) on-couch time. METHODS AND MATERIALS: Using a Varian Ethos™ emulator and KV-CBCT scans, we simulated the doses 15 retrospective cervical cancer patients would have received with/without online adaptation for five fractions. We compared contours and doses from SOC plans (5-15 mm CTV-to-PTV margins) to adapted plans (3 mm margins). Auto-segmented CTVs and OARs were reviewed and edited by trained physicists. Physics-edited targets were evaluated by an oncologist. Time spent reviewing and editing auto-segmented structures was recorded. Metrics from the CTV (D99%), bowel (V45Gy, V40Gy), bladder (D50%), and rectum (D50%) were compared. RESULTS: The physician approved the physics-edited CTVs for 55/75 fractions; 16/75 required reductions, and 4/75 required CTV expansions. CTVs were encapsulated by unadapted, SOC PTVs for 56/75 (72%) fractions-representative of current clinical practice. CTVs were completely covered by adapted 3 mm PTVs for 71/75 (94.6%) fractions. CTV D99% values for adapted plans were comparable to non-adapted SOC plans (average difference of -0.9%), while all OAR metrics improved with adaptation. Specifically, bowel V45Gy and V40Gy decreased on average by 87.6 and 109.4 cc, while bladder and rectum D50% decreased by 37.7% and 35.8%, respectively. The time required for contouring and calculating an adaptive plan for 65/75 fractions was less than 20 min (range: 1-29 min). CONCLUSIONS: Improved dose metrics with daily adaption could translate to reduced toxicity while maintaining tumor control. Training physicists to perform contouring edits could minimize the time physicians are required at adaptive sessions improving clinical efficiency. All emulated adaptive sessions were completed within 30 min however extra time will be required for patient setup, image acquisition, and treatment delivery.
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Radioterapia Guiada por Imagen , Radioterapia de Intensidad Modulada , Tomografía Computarizada de Haz Cónico Espiral , Neoplasias del Cuello Uterino , Femenino , Humanos , Planificación de la Radioterapia Asistida por Computador/métodos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/radioterapia , Estudios Retrospectivos , Estudios de Factibilidad , Radioterapia Guiada por Imagen/métodos , Dosificación Radioterapéutica , Tomografía Computarizada de Haz Cónico/métodos , Radioterapia de Intensidad Modulada/métodosRESUMEN
Online adaptive radiotherapy platforms present a unique challenge for commissioning as guidance is lacking and specialized adaptive equipment, such as deformable phantoms, are rare. We designed a novel adaptive commissioning process consisting of end-to-end tests using standard clinical resources. These tests were designed to simulate anatomical changes regularly observed at patient treatments. The test results will inform users of the magnitude of uncertainty from on-treatment changes during the adaptive workflow and the limitations of their systems. We implemented these tests for the cone-beam computed tomography (CT)-based Varian Ethos online adaptive platform. Many adaptive platforms perform online dose calculation on a synthetic CT (synCT). To assess the impact of the synCT generation and online dose calculation on dosimetric accuracy, we conducted end-to-end tests using commonly available equipment: a CIRS IMRT Thorax phantom, PinPoint ionization chamber, Gafchromic film, and bolus. Four clinical scenarios were evaluated: weight gain and weight loss were simulated by adding and removing bolus, internal target shifts were simulated by editing the CTV during the adaptive workflow to displace it, and changes in gas were simulated by removing and reinserting rods in varying phantom locations. The effect of overriding gas pockets during planning was also assessed. All point dose measurements agreed within 2.7% of the calculated dose, with one exception: a scenario simulating gas present in the planning CT, not overridden during planning, and dissipating at treatment. Relative film measurements passed gamma analysis (3%/3 mm criteria) for all scenarios. Our process validated the Ethos dose calculation for online adapted treatment plans. Based on our results, we made several recommendations for our clinical adaptive workflow. This commissioning process used commonly available equipment and, therefore, can be applied in other clinics for their respective online adaptive platforms.
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Radioterapia de Intensidad Modulada , Humanos , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodos , Tomografía Computarizada de Haz Cónico/métodos , Tomografía Computarizada por Rayos X , Radiometría , Planificación de la Radioterapia Asistida por Computador/métodos , Fantasmas de ImagenRESUMEN
BACKGROUND: Precision medicine incorporating genetic profiling is becoming a standard of care in medical oncology. However, in the field of radiation oncology there is limited use of genetic profiling and the impact of germline genetic biomarkers on radiosensitivity, radioresistance, or patient outcomes after radiation therapy is poorly understood. In HNSCC, the toxicity associated with treatment can cause delays or early cessation which has been associated with worse outcomes. Identifying potential biomarkers which can help predict toxicity, as well as response to treatment, is of significant interest. METHODS: Patients with HNSCC who received RT and underwent next generation sequencing of somatic tumor samples, transcriptome RNA-seq with matched normal tissue samples were included. Patients were then grouped by propensity towards increased late vs. early toxicity (Group A) and those without (Group B), assessed by CTCAE v5.0. The groups were then analyzed for association of specific germline variants with toxicity and clinical outcomes. RESULTS: In this study we analyzed 37 patients for correlation between germline variants and toxicity. We observed that TSC2, HLA-A, TET2, GEN1, NCOR2 and other germline variants were significantly associated with long term toxicities. 34 HNSCC patients treated with curative intent were evaluated for clinical outcomes. Group A had significantly improved overall survival as well as improved rates of locoregional recurrence and metastatic disease. Specific variants associated with improved clinical outcomes included TSC2, FANCD2, and PPP1R15A, while the HLA-A and GEN1 variants were not correlated with survival or recurrence. A group of five HLA-DMA/HLA-DMB variants was only found in Group B and was associated with a higher risk of locoregional recurrence. CONCLUSIONS: This study indicates that germline genetic biomarkers may have utility in predicting toxicity and outcomes after radiation therapy and deserve further investigation in precision radiation medicine approaches.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/patología , Células Germinativas , Antígenos HLA-A , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Recurrencia Local de Neoplasia/genética , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
PURPOSE: Motion management of tumors within the lung and abdomen is challenging because it requires balancing tissue sparing with accuracy of hitting the target, while considering treatment delivery efficiency. Physicists can play an important role in analyzing four-dimensional computed tomography (4DCT) data to recommend the optimal respiratory gating parameters for a patient. The goal of this work was to develop a standardized procedure for making recommendations regarding gating parameters and planning margins for lung and gastrointestinal stereotactic body radiotherapy (SBRT) treatments. In doing so, we hoped to simplify decision-making and analysis, and provide a tool for troubleshooting complex cases. METHODS: Factors that impact gating decisions and planning target volume (PTV) margins were identified. The gating options included gating on exhale with approximately a 50% duty cycle (Gate3070), exhale gating with a reduced duty cycle (Gate4060), and treating for most of respiration, excluding only extreme inhales and exhales (Gate100). A standard operating procedure was developed, as well as a physics consult document to communicate motion management recommendations to other members of the treatment team. This procedure was implemented clinically for 1 year and results are reported below. RESULTS: Identified factors that impact motion management included the magnitude of motion observed on 4DCT, the regularity of breathing and quality of 4DCT data, and ability to observe the target on fluoroscopy. These were collated into two decision tables-one specific to lung tumors and another for gastrointestinal tumors-such that a physicist could answer a series of questions to determine the optimal gating and PTV margin. The procedure was used clinically for 252 sites from 213 patients treated with respiratory-gated SBRT and standardized practice across our 12-member physics team. CONCLUSION: Implementation of a standardized procedure for respiratory gating had a positive impact in our clinic, improving efficiency and ease of 4DCT analysis and standardizing gating decision-making amongst physicists.
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Neoplasias Pulmonares , Radiocirugia , Tomografía Computarizada Cuatridimensional/métodos , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirugía , Movimiento (Física) , Movimiento , Radiocirugia/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Respiración , Flujo de TrabajoRESUMEN
BACKGROUND: The quality of radiotherapy delivery has been shown to significantly impact clinical outcomes including patient survival. To identify errors, institutions perform Patient Specific Quality Assurance (PSQA) assessing each individual radiotherapy plan prior to starting patient treatments. Externally administered Dosimetry Audits have found problems despite institutions passing their own PSQA. Hence a new audit concept which assesses the institution's ability to detect errors with their routine PSQA is needed. METHODS: Purposefully introduced edits which simulated treatment delivery errors were embedded into radiation treatment plans of participating institutions. These were designed to produce clinically significant changes yet were mostly within treatment delivery specifications. Actual impact was centrally assessed for each plan. Institutions performed PSQA on each plan, without knowing which contained errors. RESULTS: Seventeen institutions using six radiation treatment planning systems and two delivery systems performed PSQA on twelve plans each. Seventeen erroneous plans (across seven institutions) passed PSQA despite causing >5% increase in spinal cord dose relative to the original plans. Six plans (from four institutions) passed despite a >10% increase. CONCLUSIONS: This novel audit concept evolves beyond testing an institution's ability to deliver a single test case, to increasing the number of errors caught by institutions themselves, thus increasing quality of radiation therapy and impacting every patient treated. Administered remotely this audit also provides advantages in cost, environmental impact, and logistics.
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Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada , Ensayos Clínicos como Asunto , Humanos , Garantía de la Calidad de Atención de Salud , Radiometría , Dosificación RadioterapéuticaRESUMEN
BACKGROUND: Radiation therapy plays an important role for symptom palliation for intrathoracic malignancies ineligible for curative-intent therapy. Limited data exists regarding the role of stereotactic body radiation therapy (SBRT) versus conformal radiation in intrathoracic tumors for palliation. We report the efficacy of hypofractionated RT (or palliative SBRT) in the symptom management and durable control of lung and non-lung intrathoracic tumors. METHODS: We performed a retrospective review of ninety-two thoracic lesions across 76 patients who completed palliative SBRT with doses ranging 25-50 Gy in 5-10 fractions between 2009 and 2019. Symptoms (cough, chest pain, hemoptysis, shortness of breath) were assessed at consult and 1-6 months follow-up. Local control was evaluated using follow-up CT imaging via RECIST criteria. Descriptive statistics were used to evaluate symptom palliation and Kaplan-Meier method to analyze local control. RESULTS: Of primary lung (Cohort P) lesions, 40% showed stable symptoms, 30% never developed symptoms, and 19% showed symptom relief. CT imaging 1-6 months post-SBRT showed 91% with partial response (PR) or stable disease (SD) in Cohort P and 87% with PR or SD in metastatic (Cohort M) lesions. In patients with initial PR/SD, local control until death was achieved in 71% of Cohort P and 84% of Cohort M. Of our symptomatic patients (Cohort S), 98% showed no symptom progression post-radiotherapy. All patients with hemoptysis at presentation achieved hemostasis post-radiotherapy. CONCLUSIONS: Palliative SBRT has the advantage of higher biologic dose without protracted course for patients with limited prognosis. Patients showed significant symptom palliation and long-term local control. Palliative SBRT represents a reasonable treatment modality for incurable thoracic malignancies.
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Neoplasias Pulmonares , Radiocirugia , Humanos , Neoplasias Pulmonares/radioterapia , Cuidados Paliativos , Hipofraccionamiento de la Dosis de Radiación , Estudios RetrospectivosRESUMEN
PURPOSE: The purpose of this study was to evaluate if HPV status serves as an independent predictor of early and late dysphagia outcomes when considered alongside standard patient characteristics and dose metrics for head and neck cancer patients treated with radiotherapy. METHODS AND MATERIALS: The age, sex, smoking history, cancer type (oropharyngeal vs non-oropharyngeal), HPV status, and early and late dysphagia outcomes were obtained for 99 retrospective head and neck cancer patients treated at our clinic with radiotherapy. Additionally for each patient, the mean radiation dose to the pharynx, superior/middle/inferior pharyngeal constrictor muscles, and cricopharyngeus was calculated. The predictive power of these clinical characteristics and radiation metrics was evaluated using chi-square tests for categorical variables and t-tests for continuous variables. Then multi-variate logistic models were built for each outcome using a single dose metric at a time, and either HPV status, cancer type, or both. Multi-variate models were built using both top-down and bottom-up technique to establish the most predictive independent covariates. RESULTS: In the univariate analysis for early dysphagia, cancer type (p = 0.04) and four dose metrics (p ≤ 0.02) were significantly associated with outcome, while for late dysphagia, only cancer type (p = 0.04) was associated with outcome. In the multivariate analysis for early dysphagia, cancer type, smoking history, and mean dose to the five structures were consistently selected as covariates. For late dysphagia, either HPV status or cancer type was selected in each model and the mean dose to the cricopharyngeus was selected in one model. CONCLUSION: While HPV is a known contributing factor for tumor prognosis in oropharyngeal cancers, its role in normal tissue toxicities for head and neck cancers has not previously been evaluated. Our results indicate having an oropharyngeal cancer may increase a patient's risk of high-grade early and late dysphagia while HPV status was seldom selected.
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Trastornos de Deglución , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Trastornos de Deglución/etiología , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Músculos Faríngeos , Estudios RetrospectivosRESUMEN
PURPOSE: Implementing new online adaptive radiation therapy technologies is challenging because extra clinical resources are required particularly expert contour review. Here, we provide the first assessment of Varian's Ethos™ adaptive platform for prostate cancer using no manual edits after auto-segmentation to minimize this impact on clinical efficiency. METHODS: Twenty-five prostate patients previously treated at our clinic were re-planned using an Ethos™ emulator. Clinical target volumes (CTV) included intact prostate and proximal seminal vesicles. The following clinical margins were used: 3 mm posterior, 5 mm left/right/anterior, and 7 mm superior/inferior. Adapted plans were calculated for 10 fractions per patient using Ethos's auto-segmentation and auto-planning workflow without manual contouring edits. Doses and auto-segmented structures were exported to our clinical treatment planning system where contours were modified as needed for all 250 CTVs and organs-at-risk. Dose metrics from adapted plans were compared to unadapted plans to evaluate CTV and OAR dose changes. RESULTS: Overall 96% of fractions required auto-segmentation edits, although corrections were generally minor (<10% of the volume for 70% of CTVs, 88% of bladders, and 90% of rectums). However, for one patient the auto-segmented CTV failed to include the superior portion of prostate that extended into the bladder at all 10 fractions resulting in under-contouring of the CTV by 31.3% ± 6.7%. For the 24 patients with minor auto-segmentation corrections, adaptation improved CTV D98% by 2.9% ± 5.3%. For non-adapted fractions where bladder or rectum V90% exceeded clinical thresholds, adaptation reduced them by 13.1% ± 1.0% and 6.5% ± 7.3%, respectively. CONCLUSION: For most patients, Ethos's online adaptive radiation therapy workflow improved CTV D98% and reduced normal tissue dose when structures would otherwise exceed clinical thresholds, even without time-consuming manual edits. However, for one in 25 patients, large contour edits were required and thus scrutiny of the daily auto-segmentation is necessary and not all patients will be good candidates for adaptation.
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Neoplasias de la Próstata , Tomografía Computarizada de Haz Cónico Espiral , Tomografía Computarizada de Haz Cónico , Humanos , Masculino , Órganos en Riesgo , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
PURPOSE: The use of interstitial needles, combined with intracavitary applicators, enables customized dose distributions and is beneficial for complex cases, but increases procedure time. Overall, applicator selection is not standardized and depends on physician expertise and preference. The purpose of this study is to determine whether dose prediction models can guide needle supplementation decision-making for cervical cancer. MATERIALS AND METHODS: Intracavitary knowledge-based models for organ-at-risk (OAR) dose estimation were trained and validated for tandem-and-ring/ovoids (T&R/T&O) implants. Models were applied to hybrid cases with 1-3 implanted needles to predict OAR dose without needles. As a reference, 70/67 hybrid T&R/T&O cases were replanned without needles, following a standardized procedure guided by dose predictions. If a replanned dose exceeded the dose objective, the case was categorized as requiring needles. Receiver operating characteristic (ROC) curves of needle classification accuracy were generated. Optimal classification thresholds were determined from the Youden Index. RESULTS: Needle supplementation reduced dose to OARs. However, 67%/39% of replans for T&R/T&O met all dose constraints without needles. The ROC for T&R/T&O models had an area-under-curve of 0.89/0.86, proving high classification accuracy. The optimal threshold of 99%/101% of the dose limit for T&R/T&O resulted in classification sensitivity and specificity of 78%/86% and 85%/78%. CONCLUSIONS: Needle supplementation reduced OAR dose for most cases but was not always required to meet standard dose objectives, particularly for T&R cases. Our knowledge-based dose prediction model accurately identified cases that could have met constraints without needle supplementation, suggesting that such models may be beneficial for applicator selection.
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Braquiterapia , Neoplasias del Cuello Uterino , Braquiterapia/métodos , Suplementos Dietéticos , Femenino , Humanos , Agujas , Dosificación Radioterapéutica , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
INTRODUCTION: Quality assurance (QA) of treatment plans in clinical trials improves protocol compliance and patient outcomes. Retrospective use of knowledge-based-planning (KBP) in clinical trials has demonstrated improved treatment plan quality and consistency. We report the results of prospective use of KBP for real-time QA of treatment plan quality in the TROG 15.03 FASTRACK II trial, which evaluates efficacy of stereotactic ablative body radiotherapy (SABR) for kidney cancer. METHODS: A KBP model was generated based on single institution data. For each patient in the KBP phase (open to the last 31 patients in the trial), the treating centre submitted treatment plans 7 days prior to treatment. A treatment plan was created by using the KBP model, which was compared with the submitted plan for each organ-at-risk (OAR) dose constraint. A report comparing each plan for each OAR constraint was provided to the submitting centre within 24 h of receiving the plan. The centre could then modify the plan based on the KBP report, or continue with the existing plan. RESULTS: Real-time feedback using KBP was provided in 24/31 cases. Consistent plan quality was in general achieved between KBP and the submitted plan. KBP review resulted in replan and improvement of OAR dosimetry in two patients. All centres indicated that the feedback was a useful QA check of their treatment plan. CONCLUSION: KBP for real-time treatment plan review was feasible for 24/31 cases, and demonstrated ability to improve treatment plan quality in two cases. Challenges include integration of KBP feedback into clinical timelines, interpretation of KBP results with respect to clinical trade-offs, and determination of appropriate plan quality improvement criteria.
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Neoplasias Renales/cirugía , Órganos en Riesgo/efectos de la radiación , Radiocirugia/métodos , Planificación de la Radioterapia Asistida por Computador/normas , Estudios de Seguimiento , Humanos , Neoplasias Renales/patología , Bases del Conocimiento , Pronóstico , Estudios Prospectivos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodosRESUMEN
PURPOSE: Our purpose was to investigate the effect of automated knowledge-based planning (KBP) on real-world clinical workflow efficiency, assess whether manual refinement of KBP plans improves plan quality across multiple disease sites, and develop a data-driven method to periodically improve KBP automated planning routines. METHODS AND MATERIALS: Using clinical knowledge-based automated planning routines for prostate, prostatic fossa, head and neck, and hypofractionated lung disease sites in a commercial KBP solution, workflow efficiency was compared in terms of planning time in a pre-KBP (n = 145 plans) and post-KBP (n = 503) patient cohort. Post-KBP, planning was initialized with KBP (KBP-only) and subsequently manually refined (KBP +human). Differences in planning time were tested for significance using a 2-tailed Mann-Whitney U test (P < .05, null hypothesis: planning time unchanged). Post-refinement plan quality was assessed using site-specific dosimetric parameters of the original KBP-only plan versus KBP +human; 2-tailed paired t test quantified statistical significance (Bonferroni-corrected P < .05, null hypothesis: no dosimetric difference after refinement). If KBP +human significantly improved plans across the cohort, optimization objectives were changed to create an updated KBP routine (KBP'). Patients were replanned with KBP' and plan quality was compared with KBP +human as described previously. RESULTS: KBP significantly reduced planning time in all disease sites: prostate (median: 7.6 hrs â 2.1 hrs; P < .001), prostatic fossa (11.1 hrs â 3.7 hrs; P = .001), lung (9.9 hrs â 2.0 hrs; P < .001), and head and neck (12.9 hrs â 3.5 hrs; P <.001). In prostate, prostatic fossa, and lung disease sites, organ-at-risk dose changes in KBP +human versus KBP-only were minimal (<1% prescription dose). In head and neck, KBP +human did achieve clinically relevant dose reductions in some parameters. The head and neck routine was updated (KBP'HN) to incorporate dose improvements from manual refinement. The only significant dosimetric differences to KBP +human after replanning with KBP'HN were in favor of the new routine. CONCLUSIONS: KBP increased clinical efficiency by significantly reducing planning time. On average, human refinement offered minimal dose improvements over KBP-only plans. In the single disease site where KBP +human was superior to KBP-only, differences were eliminated by adjusting optimization parameters in a revised KBP routine.
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Enfermedades Pulmonares , Radioterapia de Intensidad Modulada , Automatización , Humanos , Bases del Conocimiento , Masculino , Órganos en Riesgo , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Recursos HumanosRESUMEN
BACKGROUND: Optimizing the therapeutic ratio for radiation therapy (RT) in head and neck squamous cell carcinoma (HNSCC) is uniquely challenging owing to high rates of early and late toxicity involving nearby organs at risk. These toxicities have a profound impact on treatment compliance and quality of life. Emerging evidence suggests that RT dose alone cannot fully account for the variable severity of RT-related adverse events (rtAEs) observed in HNSCC patients. Next-generation sequencing has become an increasingly valuable tool with widespread use in the oncology field and is being robustly explored for predicting rtAEs beyond dosimetric data. METHODS: Patients who had Foundation Medicine sequencing data and received RT for primary or locally recurrent HNSCC were selected for this study. Early and late toxicity data were collected and reported based on Common Terminology Criteria for Adverse Events version 5.0. Dosimetric parameters were collected for pertinent structures. RESULTS: A total of HNSCC 37 patients were analyzed in this study. Genetic alterations in BRCA2, ERBB3, NOTCH1 and CCND1 were all associated with higher mean grade of toxicity with BRCA2 alteration implicated in all toxicity parameters evaluated including mucositis, early dysphagia, xerostomia and to a lesser extent, late dysphagia. Interestingly, patients who exhibited alterations in both BRCA2 and ERBB3 experienced a twofold or greater increase in early dysphagia, early xerostomia and late dysphagia compared to ERBB3 alteration alone. Furthermore, several gene alterations were associated with improved toxicity outcomes. Within an RT supersensitive patient subset, alterations were found in TNFAIP3, HNF1A, SPTA1 and CASP8. All of these alterations were not found in the RT insensitive patient subset. We found 17 gene alterations in the RT insensitive patient subset that were not found in the RT supersensitive patient subset. CONCLUSION: Despite consistent RT dosimetric parameters, patients with HNSCC experience heterogeneous patterns of rtAEs. Identifying factors associated with toxicity outcomes offers a new avenue for personalized precision RT therapy and prophylactic management. Here, next-generation sequencing in a population of HNSCC patients correlates several genetic alterations with severity of rtAEs. Further analysis is urgently needed to identify genetic patterns associated with rtAEs in order to reduce harmful outcomes in this challenging population.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Recurrencia Local de Neoplasia , Calidad de Vida , Carcinoma de Células Escamosas de Cabeza y Cuello/genéticaRESUMEN
PURPOSE: Establish and compare two metrics for monitoring beam energy changes in the Halcyon platform and evaluate the accuracy of these metrics across multiple Halcyon linacs. METHOD: The first energy metric is derived from the diagonal normalized flatness (FDN ), which is defined as the ratio of the average measurements at a fixed off-axis equal distance along the open profiles in two diagonals to the measurement at the central axis with an ionization chamber array (ICA). The second energy metric comes from the area ratio (AR) of the quad wedge (QW) profiles measured with the QW on the top of the ICA. Beam energy is changed by adjusting the magnetron current in a non-clinical Halcyon. With D10cm measured in water at each beam energy, the relationships between FDN or AR energy metrics to D10cm in water is established with linear regression across six energy settings. The coefficients from these regressions allow D10cm (FDN ) calculation from FDN using open profiles and D10cm (QW) calculation from AR using QW profiles. RESULTS: Five Halcyon linacs from five institutions were used to evaluate the accuracy of the D10cm (FDN ) and the D10cm (QW) energy metrics by comparing to the D10cm values computed from the treatment planning system (TPS) and D10cm measured in water. For the five linacs, the D10cm (FDN ) reported by the ICA based on FDN from open profiles agreed with that calculated by TPS within -0.29 ± 0.23% and 0.61% maximum discrepancy; the D10cm (QW) reported by the QW profiles agreed with that calculated by TPS within -0.82 ± 1.27% and -2.43% maximum discrepancy. CONCLUSION: The FDN -based energy metric D10cm (FDN ) can be used for acceptance testing of beam energy, and also for the verification of energy in periodic quality assurance (QA) processes.
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Benchmarking , Planificación de la Radioterapia Asistida por Computador , Humanos , Modelos Lineales , Aceleradores de Partículas , Fotones , Dosificación RadioterapéuticaRESUMEN
PURPOSE: To establish a framework for the evaluation of knowledge-based planning routines that empowers new adopters to select systems that best match their clinical priorities. We demonstrate the power of this framework using 4 publicly available prostate routines. METHODS AND MATERIALS: Four publicly available prostate routines (CCMB, Miami, UCSD, WUSTL) were automatically applied across a 25-patient cohort using Eclipse scripting and a PTV prescription of V81 Gy = 95%. The institutions' routines differed in contouring guidelines for planning target volume (PTV) and organs at risk, beam arrangements, and optimization parameters. Model-estimated dose-volume histograms (DVHs) and deliverable postoptimization DVHs were extracted from plans to calculate average DVHs for each routine. Each routine's average calculated DVH was subtracted from the average DVH for all plans and from the model's average predicted DVH for comparison. DVH metrics for PTV (DMAX, D1%, D99%, DMIN), Rectum (DMAX, V70, V60, V40), Bladder (V75, V40), Femur (DMAX), and PenileBulb (DMEAN) were compared with the average using 2-sided paired t tests (Bonferroni-corrected P < .05). To control for contouring effects, the full analysis was conducted for 2 PTV margin schemas: 5 mm uniform and 3 mm or 7 mm posterior/else. RESULTS: Calculated plans generally aligned with their routine's DVH estimations, except CCMB organ-at-risk Dmaxes. Dosimetric parameter differences were not significant, with the exception of PTV DMAX (Miami = 111.1% [P < .001]), PTV D99% (Miami = 97.4% [P = .05]; UCSD = 97.4% [P = .03]; CCMB = 98.5% [P = .001]), Rectum V40 (Miami = 19.1% [P < .001]; UCSD = 22.7% [P = .003]; CCMB = 53.5% [P < .001]), and Femur DMAX (WUSTL = 48.6% [P = .001.]; CCMB = 37.9% [P < .001]). Overall, UCSD and Miami had lower rectum doses, and CCMB and WUSTL had higher PTV homogeneity. Conclusions were unchanged with different PTV margin schemas. CONCLUSIONS: Using publicly available knowledge-based planning routines spares clinicians substantial effort in developing new models. Our results allow clinicians to select the prostate routine that matches their clinical priorities, and our methodology sets the precedent for comparing routines for different treatment sites.
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Neoplasias de la Próstata/epidemiología , Estudios de Cohortes , Humanos , Bases del Conocimiento , MasculinoRESUMEN
PURPOSE: To evaluate whether automated knowledge-based planning (KBP) (a) is noninferior to human-driven planning across multiple disease sites and (b) systematically affects dosimetric plan quality and variability. METHODS AND MATERIALS: Clinical KBP automated planning routines were developed for prostate, prostatic fossa, hypofractionated lung, and head and neck. Clinical implementation consisted of independent generation of human-generated and KBP plans (145 cases across all sites), followed by blinded plan selection. Reviewing physicians were prompted to select a single plan; when plan equivalence was volunteered, this scored as KBP selection. Plan selection analysis used a noninferiority framework testing the hypothesis that KBP is not worse than human-driven planning (threshold: lower 95% confidence interval [CI] > 0.45 = noninferiority; > 0.5 = superiority). Target and organ-at-risk metrics were compared by dose differencing: ΔDx = Dx, human-Dx, KBP (2-tailed paired t test, Bonferroni-corrected P < .05 significance threshold). To evaluate the aggregated effect of KBP on planning performance, we examined post-KBP dosimetric parameters against 183 plans generated just before KBP implementation (2-tailed unpaired t test, Bonferroni-corrected P < .05). RESULTS: Across all disease sites, the KBP success rate (physician preferred + equivalent) was noninferior compared with human-driven planning (83 of 145 = 57.2%; range, 49.2%-65.3%) but did not cross the threshold for superiority. The KBP success rate in respective disease sites was superior with head and neck ([22 + 2]/36 = 66.7%; 95% CI, 51%-82%) and noninferior for lung stereotactic body radiation therapy ([21 + 2]/36 = 63.9%; 95% CI, 48%-80%) but did not meet noninferiority criteria with prostate ([16 + 3]/41 = 46.3%; 95% CI, 31%-62%) or prostatic fossa ([17 + 0]/32 = 53.1%; 95% CI, 36%-70%). Prostate, prostatic fossa, and head and neck showed significant differences in KBP-selected plans versus human-selected plans, with KBP generally exhibiting greater organ-at-risk sparing and human plans exhibiting better target homogeneity. Analysis of plan quality pre- and post-KBP showed some reductions in organ doses and quality metric variability in prostate and head and neck. CONCLUSIONS: Fully automated KBP was noninferior to human-driven plan optimization across multiple disease sites. Dosimetric analysis of treatment plans before and after KBP implementation showed a systematic shift to higher plan quality and lower variability with the introduction of KBP.