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BACKGROUND: For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. METHODS: The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. DISCUSSION: The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05673148, registered December 21, 2022.
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Neoplasias do Colo , Neoplasias Hepáticas , Radiocirurgia , Neoplasias Retais , Humanos , Estudos Prospectivos , Radiocirurgia/métodos , Neoplasias Hepáticas/terapiaRESUMO
BACKGROUND: Effects of high-dose radiation using protons and photons on bone are relatively unexplored, but high rates of insufficiency fractures are reported, and the causes of this are incompletely understood. Imaging studies with pre- and postradiation scans can help one understand the effect of radiation on bone. QUESTIONS/PURPOSES: The purpose of this study was to assess the effects of high-dose radiation on the trabecular density of bone in the sacrum using CT-derived Hounsfield units (HU). METHODS: Between 2009 and 2015, we treated 57 patients (older then 18 years) with sacral chordoma. Fourteen (25%) of them were treated with radiation only. The general indication for this approach is inoperability resulting from tumor size. Forty-two (74%) patients were treated with transverse sacral resections and high-dose radiotherapy (using either protons or photons or a combination) before surgery and after surgery. During this time period, our indication for this approach generally was symptomatic sacral chordoma in which resection would prevent further growth and reasonable sacrifice of nerve roots was possible. Of those patients, 21 (50%) had CT scans both before and after radiation treatment. We used HU as a surrogate for bone density. CT uses HU to derive information on tissue and bone quantity. A recent study presented reference HU values for normal (mean 133 ± 38 HU), osteoporotic (101 ± 25 HU), and osteopenic bone (79 ± 32 HU). To adjust for scanning protocol-induced changes in HU, we calculated the ratio between bone inside and outside the radiation field rather than using absolute values. To assess the effect of radiation, we tested whether there was a difference in ratio (sacrum/L1) before and after radiation. A control measurement was performed (L2/L1) and also tested for a difference before and after radiation. Statistical analyses were performed using the paired t-test. RESULTS: The effects of radiation appeared confined to the intended field, because the bone density outside the treated field was not observed to decrease. The ratio of HU (a surrogate for bone density) in L2 relative to L1 did not change after radiotherapy (preradiation mean: 0.979 ± 0.009, postradiation mean: 0.980 ± 0.009, mean difference outside the radiation field: -0.001, 95% confidence interval [CI], -0.009 to 0.007, p = 0.799). The ratio of HU within the radiation field relative to L1 decreased after radiotherapy (preradiation mean: 0.895 ± 0.050, postradiation mean: 0.658 ± 0.050, mean difference inside the radiation field: 0.237, 95% CI, 0.187-0.287, p < 0.001), suggesting the bone density stayed the same outside the radiation field but decreased inside the radiation field. CONCLUSIONS: Trabecular bone density decreased after high-dose radiation therapy in a small group of patients with sacral chordoma. High-dose radiation is increasingly gaining acceptance for treating sacral malignancies; further long-term prospective studies using calibrated CT scanners and preferably bone biopsies are needed. LEVEL OF EVIDENCE: Level IV, therapeutic study.
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Cordoma/radioterapia , Doses de Radiação , Sacro/efeitos da radiação , Neoplasias da Coluna Vertebral/radioterapia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Densidade Óssea/efeitos da radiação , Cordoma/diagnóstico por imagem , Cordoma/patologia , Cordoma/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Procedimentos Ortopédicos , Valor Preditivo dos Testes , Radioterapia Adjuvante , Estudos Retrospectivos , Sacro/diagnóstico por imagem , Sacro/patologia , Sacro/cirurgia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/cirurgia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Proton therapy is an effective treatment for ocular melanoma, and other tumors of the eye. The fixed horizontal beamline dedicated to ocular treatments at Massachusetts General Hospital was originally commissioned in 2002, with much of the equipment, safety features, and practices dating back to an earlier implementation at Harvard Cyclotron in the 1970s. PURPOSE: To describe the experience of reevaluation and enhancement of the safety environment for one of the longest continuously operating proton therapy programs. METHODS: Several enhancements in quality control had been introduced throughout the years of operation, as described in this manuscript, to better align the practice with the evolving standards of proton therapy and the demands of a modern hospital. We spotlight the design and results of the failure mode and effect analysis (FMEA), and subsequent actions introduced to mitigate the modes associated with elevated risk. The findings of the FMEA informed the specifications for the new software application, which facilitated the improved management of the treatment workflow and the image-guidance aspects of ocular treatments. RESULTS: Eleven failure modes identified as having the highest risk are described. Six of these were mitigated with the clinical roll-out of a new application for image-guided radiation therapy (IGRT). Others were addressed through task automation, the broader introduction of checklists, and enhancements in pre-treatment staff-led time-out. CONCLUSIONS: Throughout the task of modernizing the safety system of our dedicated ocular beamline, FMEA proved to be an effective instrument in soliciting inputs from the staff about safety and workflow concerns, helping to identify steps associated with elevated failure risks. Risks were reduced with the clinical introduction of a new IGRT application, which integrates quality management tools widely recognized for their role in risk mitigation: automation of the data transfer and workflow steps, and with the introduction of checklists and redundancy cross-checks.
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Neoplasias Oculares , Terapia com Prótons , Humanos , Prótons , Síncrotrons , Neoplasias Oculares/radioterapia , CiclotronsRESUMO
PURPOSE: The Pediatric Normal Tissue Effects in the Clinic (PENTEC) hearing loss (HL) task force reviewed investigations on cochlear radiation dose-response relationships and risk factors for developing HL. Evidence-based dose-response data are quantified to guide treatment planning. METHODS AND MATERIALS: A systematic review of the literature was performed to correlate HL with cochlear dosimetry. HL was considered present if a threshold exceeded 20 dB at any frequency. Radiation dose, ototoxic chemotherapy exposure, hearing profile including frequency spectra, interval to HL, and age at radiation therapy (RT) were analyzed. RESULTS: Literature was systematically reviewed from 1970 to 2021. This resulted in 739 abstracts; 19 met inclusion for meta-analysis, and 4 included data amenable to statistical modeling. These 4 studies included 457 cochleas at risk in patients treated with RT without chemotherapy, and 398 cochlea treated with chemotherapy. The incidence and severity of cochlear HL from RT exposure alone is related to dose and age. Risk of HL was <5% in cochlea receiving a mean dose ≤35 Gy but increased to 30% at 50 Gy. HL risk ranged from 25% to 40% in children under the age of 5 years at diagnosis, declining to 10% in older children for any radiation dose. Probability of similar severe HL occurred at doses 18.3 Gy higher for children <3 versus >3 years of age. High-frequency HL was most common, with average onset occurring 3.6 years (range, 0.4-13.2 years) after RT. Exposure to platinum-based chemotherapies added to the rates of HL at a given cochlear dose level, with 300 mg/m2 shifting the dose response by 7 Gy. CONCLUSIONS: In children treated with RT alone, risk of HL was low for cochlear dose <35 Gy and rose when dose exceeded 35 Gy without clear RT dose dependence. High-frequency HL was most prevalent, but all frequencies were affected. Children younger than 5 years were at highest risk of developing HL, although independent effects of dose and age were not fully elucidated. Future reports with more granular data are needed to better delineate time to onset of HL and the effects of chemoradiotherapy.
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Background: For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. Methods: The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. Discussion: The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC.
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Treatment planning tools that use biologically related models for plan optimization and/or evaluation are being introduced for clinical use. A variety of dose-response models and quantities along with a series of organ-specific model parameters are included in these tools. However, due to various limitations, such as the limitations of models and available model parameters, the incomplete understanding of dose responses, and the inadequate clinical data, the use of biologically based treatment planning system (BBTPS) represents a paradigm shift and can be potentially dangerous. There will be a steep learning curve for most planners. The purpose of this task group is to address some of these relevant issues before the use of BBTPS becomes widely spread. In this report, the authors (1) discuss strategies, limitations, conditions, and cautions for using biologically based models and parameters in clinical treatment planning; (2) demonstrate the practical use of the three most commonly used commercially available BBTPS and potential dosimetric differences between biologically model based and dose-volume based treatment plan optimization and evaluation; (3) identify the desirable features and future directions in developing BBTPS; and (4) provide general guidelines and methodology for the acceptance testing, commissioning, and routine quality assurance (QA) of BBTPS.
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Física Médica , Modelos Biológicos , Planejamento da Radioterapia Assistida por Computador/normas , Relatório de Pesquisa , Sociedades Científicas , Benchmarking , Humanos , Método de Monte Carlo , Controle de QualidadeRESUMO
INTRODUCTION: Unscheduled machine downtime can cause treatment interruptions and adversely impact patient treatment outcomes. Conventional Quality Assurance (QA) programs of a proton Pencil Beam Scanning (PBS) system ensure its operational performance by keeping the beam parameters within clinical tolerances but often do not reveal the underlying issues of the device prior to a machine malfunction event. In this study, we propose a Predictive Maintenance (PdM) approach that leverages an advanced analytical tool built on a deep neural network to detect treatment delivery machine issues early. METHODS: Beam delivery log file data from daily QA performed at the Burr Proton Center of Massachusetts General Hospital were collected. A novel PdM framework consisting of long short-term memory-based autoencoder (LSTM-AE) modeling of the proton PBS delivery system and a Mahalanobis distance-based error metric evaluation was constructed to detect rare anomalous machine events. These included QA beam pauses, clinical operational issues, and treatment interruptions. The model was trained in an unsupervised fashion on the QA data of normal sessions so that the model learned characteristics of normal machine operation. The anomaly is quantified as the multivariate deviation between the model predicted data and the measured data of the day using Mahalanobis distance (M-Score). Two-layer and three-layer Long short-term memory-based stacked autoencoder (LSTM-SAE) models were optimized for exploring model performance improvement. Model validation was performed with two clinical datasets and was analyzed using the area under the precision-recall curve (AUPRC) and the area under the receiver operating characteristic (AUROC). RESULTS: LSTM-SAE models showed strong performance in predicting QA beam pauses for both clinical validation datasets. Despite severe skew in the dataset, the model achieved AUPRC of 0.60 and 0.82 and AUROC of 0.75 and 0.92 in the respective 2018 and 2020 datasets. Moreover, these amount to 2.8-fold and 10.7-fold enhancement compared to the respective baseline event rates. In addition, in terms of treatment interruption events, model prediction enabled 3.88-fold and 51.2-fold detection improvement, while the detection improvement for clinical operational issues was 1.04-fold and 1.37-fold, respectively, in the 2018 and 2020 datasets. CONCLUSION: Our novel deep LSTM-SAE-based framework allows for highly discriminative prediction of anomalous machine events and demonstrates great promise for enabling PdM for proton PBS beam delivery.
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Terapia com Prótons , Prótons , Humanos , Redes Neurais de ComputaçãoRESUMO
Dose uncertainty induced by respiratory motion remains a major concern for treating thoracic and abdominal lesions using particle beams. This Task Group report reviews the impact of tumor motion and dosimetric considerations in particle radiotherapy, current motion-management techniques, and limitations for different particle-beam delivery modes (i.e., passive scattering, uniform scanning, and pencil-beam scanning). Furthermore, the report provides guidance and risk analysis for quality assurance of the motion-management procedures to ensure consistency and accuracy, and discusses future development and emerging motion-management strategies. This report supplements previously published AAPM report TG76, and considers aspects of motion management that are crucial to the accurate and safe delivery of particle-beam therapy. To that end, this report produces general recommendations for commissioning and facility-specific dosimetric characterization, motion assessment, treatment planning, active and passive motion-management techniques, image guidance and related decision-making, monitoring throughout therapy, and recommendations for vendors. Key among these recommendations are that: (1) facilities should perform thorough planning studies (using retrospective data) and develop standard operating procedures that address all aspects of therapy for any treatment site involving respiratory motion; (2) a risk-based methodology should be adopted for quality management and ongoing process improvement.
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Terapia com Prótons , Planejamento da Radioterapia Assistida por Computador , Movimento (Física) , Radiometria/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos RetrospectivosRESUMO
BACKGROUND AND PURPOSE: Few studies on radiotherapy of cardiac targets exist, and none using a gating method according to cardiac movement. This study aimed to evaluate the dose-volume advantage of using cardiac-respiratory double gating (CRDG) in terms of target location with additional ECG signals in comparison to respiratory single gating (RSG) for proton radiotherapy of targets in the heart. MATERIALS AND METHODS: Cardiac motion was modeled using a cardiac-gated four-dimensional computed tomography scan obtained at the end-expiration. Plans with the prescription dose of 50 Gy (RSG and CRDG plans at diastole and systole phases) were compared in terms of clinically relevant dose-volume criteria for various target sizes and seven cardiac subsites. Potential dose sparing by utilizing CRDG over RSG was quantified in terms of surrounding organ at risk (OAR) doses while the dose coverage to the targets was fully ensured. RESULTS: The average mean dose reductions were 28 ± 10% when gated at diastole and 21 ± 12% at systole in heart and 30 ± 17% at diastole and 8 ± 9% at systole in left ventricle compared to respiratory single gating. The diastole phase was optimal for gated treatments for all target locations except right ventricle and interventricular septum. The right ventricle target was best treated at the systole phase. However, an optimal gating phase for the interventricular septum target could not be determined. CONCLUSIONS: We have studied the dose-volume benefits of CRDG for each cardiac subsite, and demonstrated that CRDG may spare organs at risk better than RSG.
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To promote accurate image-guided radiotherapy (IGRT) for a proton pencil beam scanning (PBS) system, a new quality assurance (QA) procedure employing a cone-shaped scintillator detector has been developed for multiple QA tasks in a semi-automatic manner. The cone-shaped scintillator detector (XRV-124, Logos Systems, CA) is sensitive to both x-ray and proton beams. It records scintillation on the cone surface as a 2D image, from which the geometry of the radiation field that enters and exits the cone can be extracted. Utilizing this feature, QA parameters that are essential to PBS IGRT treatment were measured and analyzed. The first applications provided coincidence checks of laser, imaging and radiation isocenters, and dependencies on gantry angle and beam energies. The analysis of the Winston-Lutz test was made available by combining the centricity measurements of the x-ray beam and the pencil beam. The accuracy of the gantry angle was validated against console readings provided by the digital encoder and an agreement of less than 0.2° was found. The accuracy of the position measurement was assessed with a robotic patient positioning system (PPS) and an agreement of less than 0.5 mm was obtained. The centricity of the two onboard x-ray imaging systems agreed well with that from the routinely used Digital Imaging Positioning System (DIPS), up to a consistent small shift of (-0.5 mm, 0.0 mm, -0.3 mm). The pencil beam spot size, in terms of σ of Gaussian fitting, agreed within 0.2 mm for most energies when compared to the conventional measurements by a 2D ion-chamber array (MatriXX-PT, IBA Dosimetry, Belgium). The cone-shaped scintillator system showed advantages in making multi-purpose measurements with a single setup. The in-house algorithms were successfully implemented to measure and analyze key QA parameters in a semi-automatic manner. This study presents an alternative and more efficient approach for IGRT QA for PBS and potentially for linear accelerators.
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Radioterapia Guiada por Imagem/métodos , Algoritmos , Humanos , Terapia com Prótons/métodos , Radioterapia Guiada por Imagem/instrumentação , Contagem de Cintilação/instrumentação , Contagem de Cintilação/métodosRESUMO
In proton therapy, range uncertainties induced by the conversion from x-ray CT (xCT) Hounsfield units (HU) to relative stopping power (RSP) compromise the precision of dose delivery. To reduce range uncertainties induced by HU-converted RSPs, this study investigates optimizing the RSP of individual voxels in xCT iteratively based on multi-projection proton radiography (pRG) acquired using a single amorphous silicon flat panel imager. Time-resolved dose rate functions (DRF) were measured by the imager placed downstream of a test phantom consisting of tissue substitute materials. Water equivalent path lengths (WEPL) in the pRG were derived. By rotating the phantom, multiple pRG projections were acquired at angles from 0 to 358° with an increment of 2°. X-ray CT of the phantom was acquired and co-registered with the pRG acquisition coordinates. RSPs of individual xCT voxels were optimized iteratively by minimizing the difference between the measured WEPLs and the calculated WEPLs by ray tracing with HU-converted RSPs. Pixels in pRGs that exhibited severe proton range mixing were rejected for the optimization. Tikhonov regularization was applied under the assumption that HU-converted RSPs are inaccurate, but the inaccuracy is within a few percent. While ~50% of WEPL pixels were rejected due to severe range mixing in pRG, RSPs of >90% CT voxels could still be optimized if multiple pRG projections, e.g. ⩾12, around the phantom are utilized. For tissue substitute materials in a cylindrical phantom, percentage errors of RSPs were reduced from a range of -8% to +4% to be within ±2%. Further optimization, achieved by implementing a material-specific regularization parameter, reduced percent errors to be within ±0.5%. This study demonstrates the concept of optimizing RSPs of individual CT voxels with multi-projection pRGs acquired by a single flat panel imager, which could be further explored and implemented in proton therapy to reduce range uncertainties.
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Algoritmos , Imagens de Fantasmas , Terapia com Prótons , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/normas , HumanosRESUMO
Taking advantage of Bragg peak and small spot size, pencil beam scanning proton therapy can deliver a highly conformal dose distribution to target while sparing normal tissues. However, such dose distributions can be highly sensitive to the proton range uncertainty which can reach 5% or higher in lung tissue. One proposed method for reducing range uncertainty is to measure the water equivalent path length (WEPL) by proton radiography. In this study, we followed a newly proposed proton beam radiography technique based on energy resolved dose functions (ERDF) to construct a Monte Carlo model for a single detector energy-resolved proton radiography system (SDPRS). This SDPRS model was constructed in the Monte Carlo software package TOPAS (TOol for PArticle Simulation) and it includes the Mevion HYPERSCAN™ pencil beam scanning treatment head and a 2D dose detector positioned downstream as the imager. A calibration phantom containing a number of tissue equivalent materials was simulated to evaluate the accuracy in WEPL measurement by SDPRS. The mean deviation of the obtained relative stopping power (RSP) from the reference values was 0.31%. Proton radiographs of an anthropomorphic head phantom were also generated to demonstrate the clinical relevance of the technique. Effects of different energy layer spacing and measurement noise were also studied.
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Cabeça/diagnóstico por imagem , Método de Monte Carlo , Imagens de Fantasmas , Prótons , Radiografia/métodos , Calibragem , HumanosRESUMO
PURPOSE: Long-term survivors of Ewing sarcoma (ES) and osteosarcoma may be at risk for therapy-related acute leukemia or myelodysplastic syndrome (t-AL/MDS). METHODS AND MATERIALS: We retrospectively reviewed the clinicopathologic characteristics of 1071 patients with osteosarcoma (n = 757) and ES (n = 314) who were treated between 1985 and 2014. Multivariable competing risk analysis was used to analyze predictors of t-AL/MDS, including a radiation dose (≥55.8 Gy vs <55.8 Gy) × disease site (pelvis/spine vs other) interaction term. A supplemental nested case-control study was conducted to assess the association between cumulative chemotherapy dose and t-AL/MDS. RESULTS: The median follow-up for surviving patients was 97 months (range, 0.03-380). Twenty patients developed t-AL/MDS, all of whom received chemotherapy and 15 of whom were treated with radiation therapy. Radiation therapy to ≥55.8 Gy was associated with development of t-AL/MDS (adjusted hazard ratio, 2.89; 95% confidence interval [CI], 1.23-6.80; P = .015), and there was a significant radiation dose × disease site interaction term (adjusted hazard ratio, 6.70; 95% CI, 2.71-16.53; Pinteraction < .001). The 5-year cumulative incidence of t-AL/MDS in patients receiving ≥55.8 Gy radiation therapy to the pelvis or spine was 5.0% (95% CI, 0.9-14.9) for osteosarcoma and 10.7% for ES (95% CI, 3.3-23.2). In our nested case-control study, cumulative doses of ifosfamide and etoposide were associated with development of t-AL/MDS. CONCLUSIONS: Patients with osteosarcoma and ES receiving ≥55.8 Gy of radiation therapy to the pelvis or spine appear to be at increased risk for t-AL/MDS. Treatment with high cumulative doses of chemotherapy may further augment this risk.
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Neoplasias Ósseas/radioterapia , Sobreviventes de Câncer , Síndromes Mielodisplásicas/etiologia , Segunda Neoplasia Primária/etiologia , Osteossarcoma/radioterapia , Sarcoma de Ewing/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Adulto JovemRESUMO
Inverse-planned intensity modulated radiation therapy (IMRT) is often able to achieve complex treatment planning goals that are unattainable with forward three-dimensional (3D) conformal planning. However, the common use of IMRT has introduced several new challenges. The potentially high degree of modulation in IMRT beams risks the loss of some advantages of 3D planning, such as excellent target coverage and high delivery efficiency. Previous attempts to reduce beam complexity by smoothing often result in plan degradation because the smoothing algorithm cannot distinguish between areas of desirable and undesirable modulation. The purpose of this work is to introduce and evaluate adaptive diffusion smoothing (ADS), a novel procedure designed to preferentially reduce IMRT beam complexity. In this method, a discrete diffusion equation is used to smooth IMRT beams using diffusion coefficients, automatically defined for each beamlet, that dictate the degree of smoothing allowed for each beamlet. This yields a method that can distinguish between areas of desirable and undesirable modulation. The ADS method has been incorporated into our optimization system as a weighted cost function penalty, with two diffusion coefficient definitions designed to promote: (1) uniform smoothing everywhere or (2) smoothing based on cost function gradients with respect to the plan beamlet intensities. The ADS method (with both coefficient types) has been tested in a phantom and in two clinical examples (prostate and head/neck). Both types of diffusion coefficients produce plans with reduced modulation and minimal dosimetric impact, but the cost function gradient-based coefficients show more potential for reducing beam modulation without affecting dosimetric plan quality. In summary, adaptive diffusion smoothing is a promising tool for ensuring that only the necessary amount of beam modulation is used, promoting more efficient and accurate IMRT planning, QA, and delivery.
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Algoritmos , Análise Numérica Assistida por Computador , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Difusão , Dosagem RadioterapêuticaRESUMO
PURPOSE: To develop a spectral-spatial (SPSP) excitation RF pulse for simultaneous water and lipid suppression in proton (1H) magnetic resonance spectroscopic imaging (MRSI) of body extremities. METHODS: An SPSP excitation pulse is designed to excite Creatine (Cr) and Choline (Cho) metabolite signals while suppressing the overwhelming water and lipid signals. The SPSP pulse is designed using a recently proposed multidimensional Shinnar-Le Roux (SLR) RF pulse design method. A minimum-phase spectral selectivity profile is used to minimize signal loss from T2â decay. RESULTS: The performance of the SPSP pulse is evaluated via Bloch equation simulations and phantom experiments. The feasibility of the proposed method is demonstrated using three-dimensional, short repetition-time, free induction decay-based 1H-MRSI in the thigh muscle at 3T. CONCLUSION: The proposed SPSP excitation pulse is useful for simultaneous water and lipid suppression. The proposed method enables new applications of high-resolution 1H-MRSI in body extremities.
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Processamento de Imagem Assistida por Computador/métodos , Perna (Membro)/fisiologia , Espectroscopia de Ressonância Magnética/métodos , Músculo Esquelético/fisiologia , Algoritmos , Humanos , Perna (Membro)/diagnóstico por imagem , Lipídeos , Músculo Esquelético/diagnóstico por imagem , Imagens de Fantasmas , Prótons , ÁguaRESUMO
PURPOSE: The purpose of this work is to evaluate the performance of dual-energy CT (DECT) for determining proton stopping power ratios (SPRs) in an experimental environment and to demonstrate its potential advantages over conventional single-energy CT (SECT) in clinical conditions. METHODS: Water equivalent range (WER) measurements of 12 tissue-equivalent plastic materials and 12 fresh animal tissue samples are performed in a 195 MeV broad proton beam using the dose extinction method. SECT and DECT scans of the samples are performed with a dual-source CT scanner (Siemens SOMATOM Definition Flash). The methods of Schneider et al. (1996), Bourque et al. (2014), and Lalonde et al. (2017) are used to predict proton SPR on SECT and DECT images. From predicted SPR values, the WER of the proton beam through the sample is predicted for SECT and DECT using Monte Carlo simulations and compared to the measured WER. RESULTS: For homogeneous tissue-equivalent plastic materials, results with DECT are consistent with experimental measurements and show a systematic reduction of SPR uncertainty compared to SECT, with root-mean-square errors of 1.59% versus 0.61% for SECT and DECT, respectively. Measurements with heterogeneous animal samples show a clear reduction of the bias on range predictions in the presence of bones, with -0.88% for SECT versus -0.58% and -0.14% for both DECT methods. An uncertainty budget allows isolating the effect of CT number conversion to SPR and predicts improvements by DECT over SECT consistently with theoretical predictions, with 0.34% and 0.31% for soft tissues and bones in the experimental setup compared to 0.34% and 1.14% with the theoretical method. CONCLUSIONS: The present work uses experimental measurements in a realistic clinical environment to show potential benefits of DECT for proton therapy treatment planning. Our results show clear improvements over SECT in tissue-equivalent plastic materials and animal tissues. Further work towards using Monte Carlo simulations for treatment planning with DECT data and a more detailed investigation of the uncertainties on I-value and limitations on the Bragg additivity rule could potentially further enhance the benefits of this imaging technology for proton therapy.
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Terapia com Prótons , Radioterapia Guiada por Imagem , Tomografia Computadorizada por Raios X/métodos , Método de Monte Carlo , Radiometria , Dosagem RadioterapêuticaRESUMO
Radiotherapy for pancreatic cancer is limited by the tolerance of local organs at risk (OARs) and frequent overlap of the planning target volume (PTV) and OAR volumes. Using lexicographic ordering (LO), a hierarchical optimization technique, with generalized equivalent uniform dose (gEUD) cost functions, we studied the potential of intensity modulated radiation therapy (IMRT) to increase the dose to pancreatic tumors and to areas of vascular involvement that preclude surgical resection [surgical boost volume (SBV)]. We compared 15 forward planned three-dimensional conformal (3DCRT) and IMRT treatment plans for locally advanced unresectable pancreatic cancer. We created IMRT plans optimized using LO with gEUD-based cost functions that account for the contribution of each part of the resulting inhomogeneous dose distribution. LO-IMRT plans allowed substantial PTV dose escalation compared with 3DCRT; median increase from 52 Gy to 66 Gy (a=-5,p<0.005) and median increase from 50 Gy to 59 Gy (a=-15,p<0.005). LO-IMRT also allowed increases to 85 Gy in the SBV, regardless of a value, along with significant dose reductions in OARs. We conclude that LO-IMRT with gEUD cost functions could allow dose escalation in pancreas tumors with concomitant reduction in doses to organs at risk as compared with traditional 3DCRT.
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Algoritmos , Neoplasias Pancreáticas/radioterapia , Lesões por Radiação/etiologia , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Medição de Risco/métodos , Simulação por Computador , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Humanos , Modelos Biológicos , Lesões por Radiação/prevenção & controle , Proteção Radiológica , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Fatores de RiscoRESUMO
Optimization problems in IMRT inverse planning are inherently multicriterial since they involve multiple planning goals for targets and their neighbouring critical tissue structures. Clinical decisions are generally required, based on tradeoffs among these goals. Since the tradeoffs cannot be quantitatively determined prior to optimization, the decision-making process is usually indirect and iterative, requiring many repetitive optimizations. This situation becomes even more challenging for cases with a large number of planning goals. To address this challenge, a multicriteria optimization strategy called lexicographic ordering (LO) has been implemented and evaluated for IMRT planning. The LO approach is a hierarchical method in which the planning goals are categorized into different priority levels and a sequence of sub-optimization problems is solved in order of priority. This prioritization concept is demonstrated using two clinical cases (a simple prostate case and a relatively complex head and neck case). In addition, a unique feature of LO in a decision support role is discussed. We demonstrate that a comprehensive list of planning goals (e.g., approximately 23 for the head and neck case) can be optimized using only a few priority levels. Tradeoffs between different levels have been successfully prohibited using the LO method, making the large size problem representations simpler and more manageable. Optimization time needed for each level was practical, ranging from approximately 26 s to approximately 217 s. Using prioritization, the LO approach mimics the mental process often used by physicians as they make decisions handling the various conflicting planning goals. This method produces encouraging results for difficult IMRT planning cases in a highly intuitive manner.
Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Radioterapia de Intensidade Modulada/instrumentação , Radioterapia de Intensidade Modulada/métodos , Algoritmos , Interpretação Estatística de Dados , Técnicas de Apoio para a Decisão , Relação Dose-Resposta à Radiação , Humanos , Modelos Estatísticos , Modelos Teóricos , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Assistida por Computador , Fatores de TempoRESUMO
For proton therapy, an accurate conversion of CT HU to relative stopping power (RSP) is essential. Validation of the conversion based on real tissue samples is more direct than the current practice solely based on tissue substitutes and can potentially address variations over the population. Based on a novel dose extinction method, we measured water equivalent path lengths (WEPL) on animal tissue samples to evaluate the accuracy of CT HU to RSP conversion and potential variations over a population. A broad proton beam delivered a spread out Bragg peak to the samples sandwiched between a water tank and a 2D ion-chamber detector. WEPLs of the samples were determined from the transmission dose profiles measured as a function of the water level in the tank. Tissue substitute inserts and Lucite blocks with known WEPLs were used to validate the accuracy. A large number of real tissue samples were measured. Variations of WEPL over different batches of tissue samples were also investigated. The measured WEPLs were compared with those computed from CT scans with the Stoichiometric calibration method. WEPLs were determined within ±0.5% percentage deviation (% std/mean) and ±0.5% error for most of the tissue surrogate inserts and the calibration blocks. For biological tissue samples, percentage deviations were within ±0.3%. No considerable difference (<1%) in WEPL was observed for the same type of tissue from different sources. The differences between measured WEPLs and those calculated from CT were within 1%, except for some bony tissues. Depending on the sample size, each dose extinction measurement took around 5 min to produce ~1000 WEPL values to be compared with calculations. This dose extinction system measures WEPL efficiently and accurately, which allows the validation of CT HU to RSP conversions based on the WEPL measured for a large number of samples and real tissues.
Assuntos
Terapia com Prótons/métodos , Doses de Radiação , Água , Calibragem , Radiometria , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios XRESUMO
While proton beam models in treatment planning systems are generally assumed invariant with respect to the beam deliveries at different gantry angles. Physical properties of scanning pencil beams can change. The gantry angle dependent properties include the delivered charge to the monitor unit chamber, the spot position and the spot shape. The aim of this study is to investigate the extent of the changes and their dosimetric impacts using historical pencil beam scanning (PBS) treatment data. Online beam delivery records at the time of the patient-specific qualify assurance were retrospectively collected for a total of 34 PBS fields from 28 patients treated at our institution. For each field, proton beam properties at two different gantry angles (the planned and zero gantry angles) were extracted by a newly-developed machine log analysis method and used to reconstruct the delivered dose distributions in the cubic water phantom geometry. The reconstructed doses at the two different angles and a planar dose measurement by a 2D ion-chamber array were compared and the dosimetric impacts of the gantry angle dependency were accessed by a 3D γ-index analysis. In addition, the pencil beam spot size was independently characterized as a function of the gantry angle and the beam energy. The dosimetric effects of the perturbed beam shape were also investigated. Comparisons of spot-by-spot beam positions between both gantry angles show a mean deviation of 0.4 and 0.7 mm and a standard deviation of 0.3 and 0.6 mm for x and y directions, respectively. The delivered giga-protons per spot show a percent mean difference and a standard deviation of 0.01% and 0.3%, respectively, from each planned spot weight. These small deviations lead to an excellent agreement in dose comparisons with an average γ passing rate of 99.1%. When each calculation for both planned and zero gantry angles was compared to the measurement, a high correlation in γ values was also observed, also indicating the dosimetric differences are small when a field is delivered at different gantry angles. Utilizing the online beam delivery records, the gantry angle dependencies of the PBS beam delivery were assessed and quantified. The study confirms the variations of the physical properties to be sufficiently small within the clinical tolerances without taking into account the gantry angle variation.