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Despite breast cancer prevalence and widespread adoption of deep inspiration breath-hold (DIBH) radiation techniques, few data exist on the error risks related to using surface-guided (SG) DIBH during breast radiation therapy (RT). Due to the increasingly technical nature of these methods and being a paradigm shift from traditional breast setups/treatments, the associated risk for error is high. Failure modes and effects analysis (FMEA) has been used in identifying risky RT processes yet is time-consuming to perform. A subset of RT staff and a hospital patient-safety representative performed FMEA to study SG-DIBH RT processes. After this group (cohort 1) analyzed these processes, additional scoring data were acquired from RT staff uninvolved in the original FMEA (cohort 2). Cohort 2 received abbreviated FMEA training while using the same process maps that cohort 1 had created, which was done with the goal of validating our results and exploring the feasibility of expedited FMEA training and efficient implementation elsewhere. An extensive review of the SG-DIBH RT process revealed 57 failure modes in 16 distinct steps. Risks deemed to have the highest priority, large risk priority number (RPN), and severity were addressed with policy changes, checklists, and standardization; of these, most were linked with operator error via manual inputs and verification. Reproducibility results showed that 5% of the average RPN between cohorts 1 and 2 was statistically different. Unexpected associations were noted between RPN and RT staff role; 12% of the physicist and therapist average scores were statistically different. Different levels of FMEA training yielded similar scoring within one RT department, suggesting a time-savings can be achieved with abbreviated training. Scores between professions, however, yielded significant differences suggesting the importance of involving staff across disciplines.
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Análise do Modo e do Efeito de Falhas na Assistência à Saúde , Radiocirurgia , Neoplasias Unilaterais da Mama , Suspensão da Respiração , Humanos , Radiocirurgia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Reprodutibilidade dos Testes , Neoplasias Unilaterais da Mama/radioterapiaRESUMO
BACKGROUND AND PURPOSE: Multiple techniques can be used to assist with more accurate patient setup and monitoring during Stereotactic body radiation therapy (SBRT) treatment. This study analyzes the accuracy of 3D surface mapping with Surface-guided radiation therapy (SGRT) in detecting interfraction setup error and intrafraction motion during SBRT treatments of the lung and abdomen. MATERIALS AND METHODS: Seventy-one patients with 85 malignant thoracic or abdominal tumors treated with SBRT were analyzed. For initial patient setup, an alternating scheme of kV/kV imaging or SGRT was followed by cone beam computed tomography (CBCT) for more accurate tumor volumetric localization. The CBCT six degree shifts after initial setup with each method were recorded to assess interfraction setup error. Patients were then monitored continuously with SGRT during treatment. If an intrafractional shift in any direction >2 mm for longer than 2 sec was detected by SGRT, then CBCT was repeated and the recorded deltas were compared to those detected by SGRT. RESULTS: Interfractional shifts after SGRT setup and CBCT were small in all directions with mean values of <5 mm and < 0.5 degrees in all directions. Additionally, 25 patients had detected intrafraction motion by SGRT during a total of 34 fractions. This resulted in 25 (73.5%) additional shifts of at least 2 mm on subsequent CBCT. When comparing the average vector detected shift by SGRT to the resulting vector shift on subsequent CBCT, no significant difference was found between the two. CONCLUSIONS: Surface-guided radiation therapy provides initial setup within 5 mm for patients treated with SBRT and can be used in place of skin marks or planar kV imaging prior to CBCT. In addition, continuous monitoring with SGRT during treatment was valuable in detecting potentially clinically meaningful intrafraction motion and was comparable in magnitude to shifts from additional CBCT scans. PTV margin reduction may be feasible for SBRT in the lung and abdomen when using SGRT for continuous patient monitoring during treatment.
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Radiocirurgia , Radioterapia Guiada por Imagem , Abdome/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , Humanos , Pulmão , Movimento , Planejamento da Radioterapia Assistida por ComputadorRESUMO
BACKGROUND: There is significant interest in the use of stereotactic ablative radiotherapy (SABR) as a treatment modality for liver metastases. A variety of SABR fractionation schemes are in clinical use. We conducted a phase I dose-escalation study to determine the maximum tolerated dose of single-fraction liver SABR. METHODS: Patients with liver metastases from solid tumors, for whom a critical volume dose constraint could be met, were treated with single-fraction SABR. Seven patients were enrolled to the first group, with a prescription dose of 35 Gy. Dose was then escalated to 40 Gy in a single fraction, and seven more patients were treated at this dose level. Patients were followed for toxicity and underwent serial imaging to assess lesion response and local control. RESULTS: Fourteen patients with 17 liver metastases were treated. There were no dose-limiting toxicities observed at either dose level. Nine of the 13 lesions assessable for treatment response showed a complete radiographic response to treatment; the remainder showed partial response. Local control of irradiated lesions was 100 % at a median imaging follow-up of 2.5 years. Two-year overall survival for all patients was 78 %. CONCLUSIONS: For selected patients with liver metastases, single-fraction SABR at doses of 35 and 40 Gy is tolerable and shows promising signs of efficacy at intermediate follow-up.
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Fracionamento da Dose de Radiação , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de SobrevidaRESUMO
Linacs equipped with flattening filter-free (FFF) megavoltage photon beams are now commercially available. However, the commissioning of FFF beams poses challenges that are not shared with traditional flattened megavoltage X-ray beams. The planning system must model a beam that is peaked in the center and has an energy spectrum that is softer than the flattened beam. Removing the flattening filter also increases the maximum possible dose rates from 600 MU/min up to 2400 MU/min in some cases; this increase in dose rate affects the recombination correction factor, P(ion), used during absolute dose calibration with ionization chambers. We present the first reported experience of commissioning, verification, and clinical use of the collapsed cone convolution superposition (CCCS) dose calculation algorithm for commercially available flattening filter-free beams. Our commissioning data are compared to previously reported measurements and Monte Carlo studies of FFF beams. Commissioning was verified by making point-dose measurement of test plans, irradiating the RPC lung phantom, and performing patient-specific QA. The average point-dose difference between calculations and measurements of all test plans and all patient specific QA measurements is 0.80%, and the RPC phantom absolute dose differences for the two thermoluminescent dosimeters (TLDs) in the phantom planning target volume (PTV) were 1% and 2%, respectively. One hundred percent (100%) of points in the RPC phantom films passed the RPC gamma criteria of 5% and 5 mm. Our results show that the CCCS algorithm can accurately model FFF beams and calculate SBRT dose distributions using those beams.
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Planejamento da Radioterapia Assistida por Computador/métodos , Algoritmos , Antropometria , Humanos , Processamento de Imagem Assistida por Computador , Método de Monte Carlo , Imagens de Fantasmas , Doses de Radiação , Radiografia Torácica , Radioterapia de Intensidade Modulada/métodos , Reprodutibilidade dos Testes , Raios XRESUMO
The purpose of this study is to describe the comprehensive commissioning process and initial clinical performance of the Vero linear accelerator, a new radiotherapy device recently installed at UT Southwestern Medical Center specifically developed for delivery of image-guided stereotactic ablative radiotherapy (SABR). The Vero system utilizes a ring gantry to integrate a beam delivery platform with image guidance systems. The ring is capable of rotating ± 60° about the vertical axis to facilitate noncoplanar beam arrangements ideal for SABR delivery. The beam delivery platform consists of a 6 MV C-band linac with a 60 leaf MLC projecting a maximum field size of 15 × 15 cm² at isocenter. The Vero planning and delivery systems support a range of treatment techniques, including fixed beam conformal, dynamic conformal arcs, fixed gantry IMRT in either SMLC (step-and-shoot) or DMLC (dynamic) delivery, and hybrid arcs, which combines dynamic conformal arcs and fixed beam IMRT delivery. The accelerator and treatment head are mounted on a gimbal mechanism that allows the linac and MLC to pivot in two dimensions for tumor tracking. Two orthogonal kV imaging subsystems built into the ring facilitate both stereoscopic and volumetric (CBCT) image guidance. The system is also equipped with an always-active electronic portal imaging device (EPID). We present our commissioning process and initial clinical experience focusing on SABR applications with the Vero, including: (1) beam data acquisition; (2) dosimetric commissioning of the treatment planning system, including evaluation of a Monte Carlo algorithm in a specially-designed anthropomorphic thorax phantom; (3) validation using the Radiological Physics Center thorax, head and neck (IMRT), and spine credentialing phantoms; (4) end-to-end evaluation of IGRT localization accuracy; (5) ongoing system performance, including isocenter stability; and (6) clinical SABR applications.
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Aceleradores de Partículas/instrumentação , Radiocirurgia/instrumentação , Radioterapia Guiada por Imagem/métodos , Algoritmos , Antropometria , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Neoplasias Pulmonares/radioterapia , Método de Monte Carlo , Imagens de Fantasmas , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Software , Neoplasias da Coluna Vertebral/radioterapia , Raios XRESUMO
Purpose: Stereotactic radiosurgery (SRS) immobilization with an open face mask is more comfortable and less invasive than frame based, but concerns about intrafraction motion must be addressed. Surface-guided radiation therapy (SGRT) is an attractive option for intrafraction patient monitoring because it is continuous, has submillimeter accuracy, and uses no ionizing radiation. The purpose of this study was to investigate the dosimetric consequences of uncorrected intrafraction patient motion detected during frameless linac-based SRS. Methods and Materials: Fifty-five SRS patients were monitored during treatment using SGRT between January 1, 2017, and September 30, 2020. If SGRT detected motion >1 mm, imaging was repeated and the necessary shifts were made before continuing treatment. For the 25 patients with intrafraction 3-dimensional vector shifts of ≥1 mm, we moved the isocenter in the planning system using the translational shifts from the repeat imaging and recalculated the plans to determine the dosimetric effect of the shifts. Planning target volume (PTV) coverage, minimum gross tumor volume (GTV) dose (relative and absolute), and normal brain V12 were evaluated. Wilcoxon signed rank tests were used to compare planned and simulated dosimetric parameters and median 2 sample tests were used to investigate these differences between cone and multileaf collimator (MLC) plans. Results: For simulated plans, V12 increased by a median of 0.01 cc (P = .006) and relative GTV minimum dose and PTV coverage decreased by a median of 15.8% (P < .001) and 10.2 % (P < .001), respectively. Absolute minimum GTV dose was found to be significantly lower in the simulated plans (P < .001). PTV coverage decreased more for simulated cone plans than for simulated MLC plans (11.6% vs 4.7%, P = .011) but median V12 differences were found to be significantly larger for MLC plans (-0.34 cc vs -0.01 cc, P = .011). Differences in GTV minimum dose between cone and MLC plans were not statistically significant. Conclusions: SGRT detected clinically meaningful intrafraction motion during frameless SRS, which could lead to large underdoses and increased normal brain dose if uncorrected.
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The aim of this study is to compare two methodologies of prostate localization in a large cohort of patients. Daily prostate localization using B-mode ultrasound has been performed at the Nebraska Medical Center since 2000. More recently, a technology using electromagnetic transponders implanted within the prostate was introduced into our clinic (Calypso(R)). With each technology, patients were localized initially using skin marks. Localization error distributions were determined from offsets between the initial setup positions and those determined by ultrasound or Calypso. Ultrasound localization data was summarized from 16619 imaging sessions spanning 7 years; Calypso localization data consists of 1524 fractions in 41 prostate patients treated in the course of a clinical trial at five institutions and 640 localizations from the first 16 patients treated with our clinical system. Ultrasound and Calypso patients treated between March and September 2007 at the Nebraska Medical Center were analyzed and compared, allowing a single institutional comparison of the two technologies. In this group of patients, the isocenter determined by ultrasound-based localization is on average 5.3 mm posterior to that determined by Calypso, while the systematic and random errors and PTV margins calculated from the ultrasound localizations were 3 - 4 times smaller than those calculated from the Calypso localizations. Our study finds that there are systematic differences between Calypso and ultrasound for prostate localization.
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Fenômenos Eletromagnéticos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Ultrassonografia , Abdome , Humanos , Funções Verossimilhança , Masculino , Movimento , Nebraska , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Próteses e Implantes , Radiografia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Pele , Fatores de TempoRESUMO
PURPOSE: The spinal nerves have been observed to have a similar single-session dose tolerance to that of the spinal cord in pigs. Small-animal studies have shown that spinal cord dose tolerance depends on the length irradiated. This work aims to determine whether a dose-length effect exists for spinal nerves. METHODS AND MATERIALS: Twenty-seven Yucatan minipigs underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiation therapy. A 0.5 cm length of the left-sided C6, C7, and C8 spinal nerves was targeted. The pigs were distributed into 6 groups with prescription doses of 16 Gy (n = 5), 18 Gy (n = 5), 20 Gy (n = 5), 22 Gy (n = 5), 24 Gy (n = 5), or 36 Gy (n = 2) and corresponding maximum doses of 16.7, 19.1, 21.3, 23.1, 25.5, and 38.6 Gy, respectively. Neurologic status was assessed with a serial electrodiagnostic examination and daily observation of gait for approximately 52 weeks. A histopathologic examination of paraffin-embedded sections with Luxol fast blue/periodic acid-Schiff's staining was also performed. RESULTS: Marked gait change was observed in 8 of 27 irradiated pigs. The latency for responding pigs was 11 to 16 weeks after irradiation. The affected animals presented with a limp in the left front limb, and 62.5% of these pigs had electrodiagnostic evidence of denervation in the C6 and C7 innervated muscles. A probit analysis showed the dose associated with a 50% incidence of gait change is 23.9 Gy (95% confidence interval, 22.5-25.8 Gy), which is 20% higher than that reported in a companion study where a 1.5 cm length was irradiated. All symptomatic pigs had demyelination and fibrosis in the irradiated nerves, but the contralateral nerves and spinal cord were normal. CONCLUSIONS: A dose-length effect was observed for single-session irradiation of the spinal nerves in a Yucatan minipig model.
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Radiocirurgia , Nervos Espinhais/efeitos da radiação , Animais , Relação Dose-Resposta à Radiação , Feminino , Atividade Motora/fisiologia , Atividade Motora/efeitos da radiação , Nervos Espinhais/fisiologia , SuínosRESUMO
PURPOSE: This study was performed to determine the dose-related incidence of neuropathy from single-session irradiation of the C6-C8 spinal nerves using a pig model and to test the hypothesis that the spinal nerves and spinal cord have the same tolerance to full cross-sectional irradiation. METHODS AND MATERIALS: Twenty-five Yucatan minipigs received study treatment. Each animal underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiation therapy. A 1.5-cm length of the left-sided C6, C7, and C8 spinal nerves was targeted. Pigs were distributed into 5 groups with prescription doses of 16 (n = 7), 18 (5), 20 (5), 22 (5), or 24 (3) Gy with corresponding maximum nerve doses of 17.3, 19.5, 21.6, 24.1, and 26.2 Gy. The neurologic status of all animals was followed for approximately 52 weeks by serial electrodiagnostic examination and daily observation of gait. Histopathologic examination of paraffin-embedded sections with Luxol fast blue/periodic acid-Schiff staining was performed on bilateral spinal nerves and the spinal cord. RESULTS: Marked gait change was observed in 15 of the 25 irradiated pigs. Affected animals presented with a limp in their left front limb, and electromyography demonstrated evidence of denervation in C6 and C7 innervated muscles. Probit analysis showed the ED50 for gait change after irradiation of the spinal nerves to be 19.7 Gy (95% confidence interval, 18.5-21.1). The latency for all responding pigs was 9 to 15 weeks after irradiation. All symptomatic pigs had demyelination and fibrosis in their irradiated nerves, whereas contralateral nerves and spinal cord were normal. CONCLUSIONS: The ED50 for symptomatic neuropathy after full cross-sectional irradiation of the spinal nerves was found to be 19.7 Gy. The dose response of the C6-C8 spinal nerves is not significantly different from that of full cross-sectional irradiation of the spinal cord as observed in companion studies.
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Tolerância a Radiação , Radiocirurgia/métodos , Medula Espinal/efeitos da radiação , Nervos Espinhais/efeitos da radiação , Animais , Relação Dose-Resposta à Radiação , Feminino , Doenças do Sistema Nervoso Periférico/etiologia , Doses de Radiação , Medula Espinal/patologia , Nervos Espinhais/patologia , Suínos , Porco MiniaturaRESUMO
PURPOSE: To analyze characteristics of intrafraction prostate motion, monitored using the Calypso system, and investigate dosimetric consequences of the motion for different clinical target volume (CTV) to planning target volume (PTV) margins. METHODS AND MATERIALS: Motion characteristics were analyzed for 1,267 tracking sessions and 35 patients. Using prostate-PTV margins of 0, 1, 2, 3, and 5 mm, dose metrics for the prostate gland, bladder, and rectum were evaluated for scenarios including patient population, individual patients showing the greatest motion during the course of treatment, and the individual session with the largest overall movement. Composite dose distributions incorporating motion blurring were calculated by convolving static intensity-modulated radiotherapy plans with corresponding motion probability functions. RESULTS: For prostate-PTV margins of 2 mm or greater, intrafraction motion did not compromise prostate dose coverage for either the patient population or individual patients. For the patient showing the largest overall movement, the prostate equivalent uniform dose was reduced by only 17.4 cGy (0.23%), and the minimum prostate dose remained greater than 95% of the nominal dose. For margins less than 2 mm, the prostate dose-volume histogram in the same patient was slightly compromised, and the equivalent uniform dose was reduced by 38.5 cGy (0.51%). Sparing of the bladder and rectum was improved substantially by reducing margins. CONCLUSIONS: Although significant motion can be observed during individual fractions, the dosimetric consequences are insignificant during a typical course of radiotherapy (30-40 fractions) with CTV-PTV margins of 2 mm or greater provided that the Calypso system is applied for pretreatment localization. Further reduction of the margin is possible if intrafraction realignment is performed.
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Movimento , Neoplasias da Próstata/radioterapia , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Eficiência Biológica Relativa , Humanos , Masculino , Especificidade de Órgãos , Dosagem RadioterapêuticaRESUMO
BACKGROUND AND PURPOSE: This study was performed to test the hypothesis that spinal cord radiosensitivity is significantly modified by uniform versus laterally non-uniform dose distributions. MATERIALS AND METHODS: A uniform dose distribution was delivered to a 4.5-7.0 cm length of cervical spinal cord in 22 mature Yucatan minipigs for comparison with a companion study in which a laterally non-uniform dose was given [1]. Pigs were allocated into four dose groups with mean maximum spinal cord doses of 17.5 ± 0.1 Gy (n=7), 19.5 ± 0.2 Gy (n=6), 22.0 ± 0.1 Gy (n=5), and 24.1 ± 0.2 Gy (n=4). The study endpoint was motor neurologic deficit determined by a change in gait within one year. Spinal cord sections were stained with a Luxol fast blue/periodic acid Schiff combination. RESULTS: Dose-response curves for uniform versus non-uniform spinal cord irradiation were nearly identical with ED(50)'s (95% confidence interval) of 20.2 Gy (19.1-25.8) and 20.0 Gy (18.3-21.7), respectively. No neurologic change was observed for either dose distribution when the maximum spinal cord dose was ≤ 17.8 Gy while all animals experienced deficits at doses ≥ 21.8 Gy. CONCLUSION: No dose-volume effect was observed in pigs for the dose distributions studied and the endpoint of motor neurologic deficit; however, partial spinal cord irradiation resulted in less debilitating neurologic morbidity and histopathology.
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Medula Espinal/efeitos da radiação , Animais , Relação Dose-Resposta à Radiação , Feminino , Doses de Radiação , Tolerância a Radiação , Suínos , Porco MiniaturaRESUMO
BACKGROUND AND PURPOSE: Paralysis observed during a study of vertebral bone tolerance to single-session irradiation led to further study of the dose-related incidence of motor peripheral neuropathy. MATERIALS AND METHODS: During a bone tolerance study, cervical spinal nerves of 15 minipigs received bilateral irradiation to levels C5-C8 distributed into three dose groups with mean maximum spinal nerve doses of 16.9 ± 0.3 Gy (n=5), 18.7 ± 0.5 Gy (n=5), and 24.3 ± 0.8 Gy (n=5). Changes developing in the gait of the group of pigs receiving a mean maximum dose of 24.3 Gy after 10-15 weeks led to the irradiation of two additional animals. They received mean maximum dose of 24.9 ± 0.2 Gy (n=2), targeted to the left spinal nerves of C5-C8. The followup period was one year. Histologic sections from spinal cords and available spinal nerves were evaluated. MR imaging was performed on pigs in the 24.9 Gy group. RESULTS: No pig that received a maximum spinal nerve point dose ≤19.0 Gy experienced a change in gait while all pigs that received ≥24.1 Gy experienced paralysis. Extensive degeneration and fibrosis were observed in irradiated spinal nerves of the 24.9 Gy animals. All spinal cord sections were normal. Irradiated spinal nerve regions showed increased thickness and hypointensity on MR imaging. CONCLUSION: The single-session tolerance dose of the cervical spinal nerves lies between 19.0 and 24.1 Gy for this model.
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Paralisia/etiologia , Radiocirurgia/efeitos adversos , Nervos Espinhais/efeitos da radiação , Animais , Imageamento por Ressonância Magnética , Doses de Radiação , SuínosRESUMO
BACKGROUND: The aim of this study is to compare three methodologies of prostate localization and to determine if there are significant differences in the techniques. METHODS: Daily prostate localization using cone beam CT or orthogonal kV imaging has been performed at UT Southwestern Medical Center since 2006. Prostate patients are implanted with gold seeds, which are matched with the planning CT or DRR before treatment. More recently, a technology using electromagnetic transponders implanted within the prostate was introduced into our clinic (Calypso®). With each technology, patients are localized initially using skin marks and the room lasers. In this study, patients were localized with Calypso and either CBCT or kV orthogonal images in the same treatment session, allowing a direct comparison of the technologies. Localization difference distributions were determined from the difference in the offsets determined by CBCT/kV imaging and Calypso. CBCT-Calypso and kV imaging-Calypso localization data were summarized from over 900 and 250 fractions each, respectively. The Wilcoxon signed rank test is used to determine if the localization differences are statistically significant. We also calculated Pearson's product-moment correlation coefficient (R2) to determine if there is a linear relationship between the shifts determined by Calypso and the radiographic techniques. RESULTS: The differences between CBCT-Calypso and kV imaging-Calypso localizations are -0.18 ± 2.90 mm, -0.79 ± 2.18 mm, -0.01 ± 1.20 mm and -0.09 ± 1.40 mm, 0.48 ± 1.50 mm, 0.08 ± 1.04 mm, respectively, in the AP, SI, and RL directions. The Pearson product-moment correlation coefficients for the CBCT-Calypso shifts were 0.71, 0.92 and 0.88 and for the OBI-Calypso comparison were 0.95, 0.89 and 0.85. The percentage of localization differences that were less than 3 mm were 86.1%, 84.5% and 96.0% for the CBCT-Calypso comparison and 95.8%, 94.3% and 97% for the kV OBI-Calypso comparison. No trends were observed in the Bland-Altman analysis. CONCLUSIONS: Localization of the prostate using electromagnetic transponders agrees well with radiographic techniques and each technology is suitable for high precision radiotherapy. This study finds that there is more uncertainty in CBCT localization of the prostate than in 2D orthogonal imaging, but the difference is not clinically significant.
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Diagnóstico por Imagem/métodos , Neoplasias da Próstata/radioterapia , Radioterapia (Especialidade)/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Fenômenos Eletromagnéticos , Humanos , Masculino , Radiografia/métodosRESUMO
PURPOSE: This study was performed to determine swine spinal cord tolerance to single-fraction, partial-volume irradiation 1 year after receiving uniform irradiation to 30 Gy in 10 fractions. METHODS AND MATERIALS: A 10-cm length of spinal cord (C3-T1) was uniformly irradiated to 30 Gy in 10 consecutive fractions and reirradiated 1 year later with a single radiosurgery dose centered within the previously irradiated segment. Radiosurgery was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter, which was positioned laterally to the cervical spinal cord, resulting in a dose distribution with the 90%, 50%, and 10% isodose lines traversing the ipsilateral, central, and contralateral spinal cord, respectively. Twenty-three pigs were stratified into six dose groups with mean maximum spinal cord doses of 14.9 ± 0.1 Gy (n = 2), 17.1 ± 0.3 Gy (n = 3), 19.0 ± 0.1 Gy (n = 5), 21.2 ± 0.1 Gy (n = 5), 23.4 ± 0.2 Gy (n = 5), and 25.4 ± 0.4 Gy (n = 3). The mean percentage of spinal cord volumes receiving ≥10 Gy for the same groups were 34% ± 1%, 40% ± 1%, 46% ± 3%, 52% ± 1%, 56 ± 3%, and 57% ± 1%. The study endpoint was motor neurologic deficit as determined by a change in gait during a 1- year follow-up period. RESULTS: A steep dose-response curve was observed with a 50% incidence of paralysis (ED(50)) for the maximum point dose of 19.7 Gy (95% confidence interval, 17.4-21.4). With two exceptions, histology was unremarkable in animals with normal neurologic status, while all animals with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side, with relative sparing of gray matter. Histologic comparison with a companion study of de novo irradiated animals revealed that retreatment responders had more extensive tissue damage, including infarction of gray matter, only at prescription doses >20 Gy. CONCLUSION: Pigs receiving spinal radiosurgery 1 year after receiving 30 Gy in 10 fractions were not at significantly higher risk of developing motor deficits than pigs that received radiosurgery alone.
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Lesões Experimentais por Radiação/complicações , Tolerância a Radiação , Radiocirurgia/efeitos adversos , Medula Espinal/efeitos da radiação , Animais , Vértebras Cervicais , Relação Dose-Resposta à Radiação , Feminino , Transtornos Neurológicos da Marcha/etiologia , Bainha de Mielina/patologia , Bainha de Mielina/efeitos da radiação , Doses de Radiação , Lesões Experimentais por Radiação/patologia , Radiocirurgia/métodos , Retratamento , Medula Espinal/patologia , Suínos , Porco Miniatura , Fatores de TempoRESUMO
PURPOSE: To determine the spinal cord tolerance to single-fraction, partial-volume irradiation in swine. METHODS AND MATERIALS: A 5-cm-long cervical segment was irradiated in 38-47-week-old Yucatan minipigs using a dedicated, image-guided radiosurgery linear accelerator. The radiation was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter that was positioned lateral to the cervical spinal cord, resulting in a dose distribution with the 90%, 50%, and 10% isodose lines traversing the ipsilateral, central, and contralateral spinal cord, respectively. The dose was prescribed to the 90% isodose line. A total of 26 pigs were stratified into eight dose groups of 12-47 Gy. The mean maximum spinal cord dose was 16.9 ± 0.1, 18.9 ± 0.1, 21.0 ± 0.1, 23.0 ± 0.2, and 25.3 ± 0.3 Gy in the 16-, 18-, 20-, 22-, and 24-Gy dose groups, respectively. The mean percentage of spinal cord volumes receiving ≥ 10 Gy for the same groups were 43% ± 3%, 48% ± 4%, 51% ± 2%, 57% ± 2%, and 59% ± 4%. The study endpoint was motor neurologic deficit determined by a change in gait during a 1-year follow-up period. RESULTS: A steep dose-response curve was observed with a median effective dose for the maximum dose point of 20.0 Gy (95% confidence interval, 18.3-21.7). Excellent agreement was observed between the occurrence of neurologic change and the presence of histologic change. All the minipigs with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side, with relative sparing of the gray matter. The histologic findings were unremarkable in the minipigs with normal neurologic status. CONCLUSIONS: Our results have indicated that for a dose distribution with a steep lateral gradient, the pigs had a lower median effective dose for paralysis than has been observed in rats and more closely resembles that for rats, mice, and guinea pigs receiving uniform spinal cord irradiation.