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1.
Artigo em Inglês | MEDLINE | ID: mdl-33227443

RESUMO

PURPOSE: The value of Cherenkov imaging as an on-patient, real-time, treatment delivery verification system was examined in a 64-patient cohort during routine radiation treatments in a single-center study. METHODS & MATERIALS: Cherenkov cameras were mounted in treatment rooms and used to image patients during their standard radiotherapy regimen for various sites, predominantly for whole breast and total skin electron therapy. For most patients, multiple fractions were imaged, with some involving bolus or scintillators on the skin. Measures of repeatability were calculated with a mean distance to conformity (MDC) for breast irradiation images. RESULTS: In breast treatments, Cherenkov images identified fractions when treatment delivery resulted in dose on the contralateral breast, the arm, or chin, and found non-ideal bolus positioning. In sarcoma treatments, safe positioning of the contralateral leg was monitored. For all 199 imaged breast treatment fields, the inter-fraction MDC was within 7 mm as compared to the first day of treatment (with only 7.5% of treatments exceeding 3 mm), and all but one fell within 7 mm relative to the treatment plan. The value of imaging dose through clear bolus or quantifying surface dose with scintillator dots was examined. Cherenkov imaging also was able to assess field match lines in cerebral-spinal (CSI) and breast irradiation with nodes. Treatment imaging of other anatomical sites confirmed the value of surface dose imaging more broadly. CONCLUSIONS: Daily radiotherapy can be imaged routinely via Cherenkov emissions. Both the real-time images and the post-treatment, cumulative images provide surrogate maps of surface dose delivery that can be used for incident discovery and/or continuous improvement in many delivery techniques. In this initial 64-patient cohort, we discovered six minor incidents using Cherenkov imaging, without which, would have gone undetected. In addition, imaging provides automated, quantitative metrics useful to determining the quality of radiotherapy delivery.

2.
Front Oncol ; 10: 572060, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194670

RESUMO

Introduction: Tumor hypoxia confers both a poor prognosis and increased resistance to oncologic therapies, and therefore, hypoxia modification with reliable oxygen profiling during anticancer treatment is desirable. The OxyChip is an implantable oxygen sensor that can detect tumor oxygen levels using electron paramagnetic resonance (EPR) oximetry. We report initial safety and feasibility outcomes after OxyChip implantation in a first-in-humans clinical trial (NCT02706197, www.clinicaltrials.gov). Materials and Methods: Twenty-four patients were enrolled. Eligible patients had a tumor ≤ 3 cm from the skin surface with planned surgical resection as part of standard-of-care therapy. Most patients had a squamous cell carcinoma of the skin (33%) or a breast malignancy (33%). After an initial cohort of six patients who received surgery alone, eligibility was expanded to patients receiving either chemotherapy or radiotherapy prior to surgical resection. The OxyChip was implanted into the tumor using an 18-G needle; a subset of patients had ultrasound-guided implantation. Electron paramagnetic resonance oximetry was carried out using a custom-built clinical EPR scanner. Patients were evaluated for associated toxicity using the Common Terminology Criteria for Adverse Events (CTCAE); evaluations started immediately after OxyChip placement, occurred during every EPR oximetry measurement, and continued periodically after removal. The OxyChip was removed during standard-of-care surgery, and pathologic analysis of the tissue surrounding the OxyChip was performed. Results: Eighteen patients received surgery alone, while five underwent chemotherapy and one underwent radiotherapy prior to surgery. No unanticipated serious adverse device events occurred. The maximum severity of any adverse event as graded by the CTCAE was 1 (least severe), and all were related to events typically associated with implantation. After surgical resection, 45% of the patients had no histopathologic findings specifically associated with the OxyChip. All tissue pathology was "anticipated" excepting a patient with greater than expected inflammatory findings, which was assessed to be related to the tumor as opposed to the OxyChip. Conclusion: This report of the first-in-humans trial of OxyChip implantation and EPR oximetry demonstrated no significant clinical pathology or unanticipated serious adverse device events. Use of the OxyChip in the clinic was thus safe and feasible.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33002542

RESUMO

PURPOSE: The extreme microscopic heterogeneity of tumors makes it difficult to characterize tumor hypoxia. We evaluated how changes in the spatial resolution of oxygen imaging could alter measures of tumor hypoxia and their correlation to radiation therapy response. METHODS AND MATERIALS: Cherenkov-Excited Luminescence Imaging (CELI) in combination with an oxygen probe, Oxyphor PtG4 was used to directly image tumor pO2 distributions with 0.2 mm spatial resolution at the time of radiation delivery. These pO2 images were analyzed with variations of reduced spatial resolution from 0.2 mm to 5 mm, to investigate the influence of how reduced imaging spatial resolution would affect the observed tumor hypoxia. As an in vivo validation test, mice bearing tumor xenografts were imaged for hypoxic fraction and median pO2 to examine the predictive link with tumor response to radiation therapy, while accounting for spatial resolution. RESULTS: In transitioning from voxel sizes of 200 µm to 3mm, the median pO2 values increased by a few mmHg, while the hypoxic fraction decreased by more than 50%. When looking at radiation-responsive tumors, the median pO2 values changed just a few mmHg as a result of treatment, while the hypoxic fractions changed by as much as 50%. This latter change, however, could only be seen when sampling was performed with high spatial resolution. Median pO2 or similar quantities obtained from low resolution measurements are commonly used in clinical practice, however these parameters are much less sensitive to changes in the tumor microenvironment than the tumor hypoxic fraction obtained from high-resolution oxygen images. CONCLUSIONS: This study supports the hypothesis that for adequate measurements of the tumor response to radiation therapy, oxygen imaging with high spatial resolution is required in order to accurately characterize the hypoxic fraction.

4.
J Appl Clin Med Phys ; 21(6): 158-162, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32306551

RESUMO

PURPOSE: The novel scintillator-based system described in this study is capable of accurately and remotely measuring surface dose during Total Skin Electron Therapy (TSET); this dosimeter does not require post-exposure processing or annealing and has been shown to be re-usable, resistant to radiation damage, have minimal impact on surface dose, and reduce chances of operator error compared to existing technologies e.g. optically stimulated luminescence detector (OSLD). The purpose of this study was to quantitatively analyze the workflow required to measure surface dose using this new scintillator dosimeter and compare it to that of standard OSLDs. METHODS: Disc-shaped scintillators were attached to a flat-faced phantom and a patient undergoing TSET. Light emission from these plastic discs was captured using a time-gated, intensified, camera during irradiation and converted to dose using an external calibration factor. Time required to complete each step (daily QA, dosimeter preparation, attachment, removal, registration, and readout) of the scintillator and OSLD surface dosimetry workflows was tracked. RESULTS: In phantoms, scintillators and OSLDs surface doses agreed within 3% for all data points. During patient imaging it was found that surface dose measured by OSLD and scintillator agreed within 5% and 3% for 35/35 and 32/35 dosimetry sites, respectively. The end-to-end time required to measure surface dose during phantom experiments for a single dosimeter was 78 and 202 sec for scintillator and OSL dosimeters, respectively. During patient treatment, surface dose was assessed at 7 different body locations by scintillator and OSL dosimeters in 386 and 754 sec, respectively. CONCLUSION: Scintillators have been shown to report dose nearly twice as fast as OSLDs with substantially less manual work and reduced chances of human error. Scintillator dose measurements are automatically saved to an electronic patient file and images contain a permanent record of the dose delivered during treatment.

5.
Phys Med Biol ; 65(9): 095004, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32135522

RESUMO

This study demonstrates remote imaging for in vivo detection of radiation-induced tumor microstructural changes by tracking the diffusive spread of injected intratumor UV excited tattoo ink using Cherenkov-excited luminescence imaging (CELI). Micro-liter quantities of luminescent tattoo ink with UV absorption and visible emission were injected at a depth of 2 mm into mouse tumors prior to receiving a high dose treatment of radiation. X-rays from a clinical linear accelerator were used to excite phosphorescent compounds within the tattoo ink through Cherenkov emission. The in vivo phosphorescence was detected using a time-gated intensified CMOS camera immediately after injection, and then again at varying time points after the ink had broken down with the apoptotic tumor cells. Ex vivo tumors were imaged post-mortem using hyperspectral cryo-fluorescence imaging to quantify necrosis and compared to Cherenkov-excited light imaging of diffusive ink spread measured in vivo. Imaging of untreated control mice showed that ink distributions remained constant after four days with less than 3% diffusive spread measured using full width at 20% max. For all mice, in vivo CELI measurements matched within 12% of the values estimated by the high-resolution ex vivo sliced luminescence imaging of the tumors. The tattoo ink spread in treated mice was found to correlate well with the nonperfusion necrotic core volume (R2 = 0.92) but not well with total tumor volume changes (R2 = 0.34). In vivo and ex vivo findings indicate that the diffusive spread of the injected tattoo ink can be related to radiation-induced necrosis, independent of total tumor volume change. Tracking the diffusive spread of the ink allows for distinguishing between an increase in tumor size due to new cellular growth and an increase in tumor size due to edema. Furthermore, the imaging resolution of CELI allows for in vivo tracking of subtle microenvironmental changes which occur earlier than tumor shrinkage and this offers the potential for novel, minimally invasive radiotherapy response assay without interrupting a singular clinical workflow.


Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Processamento de Imagem Assistida por Computador/métodos , Tinta , Luminescência , Imagens de Fantasmas , Animais , Proliferação de Células , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Camundongos , Camundongos Nus , Células Tumorais Cultivadas , Raios X , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Nat Commun ; 11(1): 573, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996677

RESUMO

Hypoxia in solid tumors is thought to be an important factor in resistance to therapy, but the extreme microscopic heterogeneity of the partial pressures of oxygen (pO2) between the capillaries makes it difficult to characterize the scope of this phenomenon without invasive sampling of oxygen distributions throughout the tissue. Here we develop a non-invasive method to track spatial oxygen distributions in tumors during fractionated radiotherapy, using oxygen-dependent quenching of phosphorescence, oxygen probe Oxyphor PtG4 and the radiotherapy-induced Cherenkov light to excite and image the phosphorescence lifetimes within the tissue. Mice bearing MDA-MB-231 breast cancer and FaDu head neck cancer xenografts show different pO2 responses during each of the 5 fractions (5 Gy per fraction), delivered from a clinical linear accelerator. This study demonstrates subsurface in vivo mapping of tumor pO2 distributions with submillimeter spatial resolution, thus providing a methodology to track response of tumors to fractionated radiotherapy.


Assuntos
Fracionamento da Dose de Radiação , Processamento de Imagem Assistida por Computador/métodos , Oxigênio/química , Radioterapia/métodos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Engenharia Biomédica/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/radioterapia , Linhagem Celular Tumoral , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Xenoenxertos , Humanos , Hipóxia , Metaloporfirinas , Camundongos , Pressão Parcial , Aceleradores de Partículas
7.
Int J Radiat Oncol Biol Phys ; 106(2): 422-429, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669563

RESUMO

PURPOSE: Patients have reported sensations of seeing light flashes during radiation therapy, even with their eyes closed. These observations have been attributed to either direct excitation of retinal pigments or generation of Cherenkov light inside the eye. Both in vivo human and ex vivo animal eye imaging was used to confirm light intensity and spectra to determine its origin and overall observability. METHODS AND MATERIALS: A time-gated and intensified camera was used to capture light exiting the eye of a patient undergoing stereotactic radiosurgery in real time, thereby verifying the detectability of light through the pupil. These data were compared with follow-up mechanistic imaging of ex vivo animal eyes with thin radiation beams to evaluate emission spectra and signal intensity variation with anatomic depth. Angular dependency of light emission from the eye was also measured. RESULTS: Patient imaging showed that light generation in the eye during radiation therapy can be captured with a signal-to-noise ratio of 68. Irradiation of ex vivo eye samples confirmed that the spectrum matched that of Cherenkov emission and that signal intensity was largely homogeneous throughout the entire eye, from the cornea to the retina, with a slight maximum near 10 mm depth. Observation of the signal external to the eye was possible through the pupil from 0° to 90°, with a detected emission near 2500 photons per millisecond (during peak emission of the ON cycle of the pulsed delivery), which is over 2 orders of magnitude higher than the visible detection threshold. CONCLUSIONS: By quantifying the spectra and magnitude of the signal, we now have direct experimental observations that Cherenkov light is generated in the eye during radiation therapy and can contribute to perceived light flashes. Furthermore, this technique can be used to further study and measure phosphenes in the radiation therapy clinic.


Assuntos
Luz , Fenômenos Fisiológicos Oculares/efeitos da radiação , Radiocirurgia , Razão Sinal-Ruído , Animais , Humanos , Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Pupila/fisiologia , Suínos
8.
Med Phys ; 46(11): 5227-5237, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31472093

RESUMO

PURPOSE: We demonstrate the feasibility of optical imaging as a quality assurance tool for static small beamlets, and pretreatment verification tool for radiosurgery and volumetric-modulated arc therapy (VMAT) plans. METHODS: Small static beams and clinical VMAT plans were simulated in a treatment planning system (TPS) and delivered to a cylindrical tank filled with water-based liquid scintillator. Emission was imaged using a blue-sensitive, intensified CMOS camera time-gated to the linac pulses. For static beams, percentage depth and cross beam profiles of projected intensity distribution were compared to TPS data. Two-dimensional (2D) gamma analysis was performed on all clinical plans, and the technique was tested for sensitivity against common errors (multileaf collimator position, gantry angle) by inducing deliberate errors in the VMAT plans control points. The technique's detection limits for spatial resolution and the smallest number of control points that could be imaged reliably were also tested. The sensitivity to common delivery errors was also compared against a commercial 2.5D diode array dosimeter. RESULTS: A spatial resolution of 1 mm was achieved with our imaging setup. The optical projected percentage depth intensity profiles agreed to within 2% relative to the TPS data for small static square beams (5, 10, and 50 mm2 ). For projected cross beam profiles, a gamma pass rate >99% was achieved for a 3%/1 mm criteria. All clinical plans passed the 3%/3 mm criteria with >95% passing rate. A static 5 mm beam with 20 Monitor Units could be measured with an average percent difference of 5.5 ± 3% relative to the TPS. The technique was sensitive to multileaf collimator errors down to 1 mm and gantry angle errors of 1°. CONCLUSIONS: Optical imaging provides ample spatial resolution for imaging small beams. The ability to faithfully image down to 20 MU of 5 mm, 6 MV beamlets prove the ability to perform quality assurance for each control point within dynamic plans. The technique is sensitive to small offset errors in gantry angles and multileaf collimator (MLC) leaf positions, and at certain scenario, it exhibits higher sensitivity than a commercial 2.5D diode array.


Assuntos
Imagem Óptica , Radiocirurgia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada , Dosimetria Fotográfica , Humanos , Razão Sinal-Ruído , Fatores de Tempo
9.
J Biomed Opt ; 24(7): 1-6, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31313537

RESUMO

Previous work has shown that capturing optical emission from plastic discs attached directly to the skin can be a viable means to accurately measure surface dose during total skin electron therapy. This method can provide accurate dosimetric information rapidly and remotely without the need for postprocessing. The objective of this study was to: (1) improve the robustness and usability of the scintillators and (2) enhance sensitivity of the optical imaging system to improve scintillator emission detection as related to tissue surface dose. Baseline measurements of scintillator optical output were obtained by attaching the plastic discs to a flat tissue phantom and simultaneously irradiating and imaging them. Impact on underlying surface dose was evaluated by placing the discs on-top of the active element of an ionization chamber. A protective coating and adhesive backing were added to allow easier logistical use, and they were also subjected to disinfection procedures, while verifying that these changes did not affect the linearity of response with dose. The camera was modified such that the peak of detector quantum efficiency better overlapped with the emission spectra of the scintillating discs. Patient imaging was carried out and surface dose measurements were captured by the updated camera and compared to those produced by optically stimulated luminescence detectors (OSLD). The updated camera was able to measure surface dose with < 3 % difference compared to OSLD­Cherenkov emission from the patient was suppressed and scintillation detection was enhanced by 25 × and 7 × , respectively. Improved scintillators increase underlying surface dose on average by 5.2 ± 0.1 % and light output decreased by 2.6 ± 0.3 % . Disinfection had < 0.02 % change on scintillator light output. The enhanced sensitivity of the imaging system to scintillator optical emission spectrum can now enable a reduction in physical dimensions of the dosimeters without loss in ability to detect light output.


Assuntos
Câmaras gama , Imagem Óptica , Contagem de Cintilação , Desenho de Equipamento , Humanos , Processamento de Imagem Assistida por Computador , Imagem Óptica/instrumentação , Imagem Óptica/métodos , Imagens de Fantasmas , Contagem de Cintilação/instrumentação , Contagem de Cintilação/métodos , Imagem Corporal Total
10.
Phys Med Biol ; 64(14): 145021, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31146269

RESUMO

The goal of this study was to test the utility of time-gated optical imaging of head and neck (HN) radiotherapy treatments to measure surface dosimetry in real-time and inform possible interfraction replanning decisions. The benefit of both Cherenkov and scintillator imaging in HN treatments is direct daily feedback on dose, with no change to the clinical workflow. Emission from treatment materials was characterized by measuring radioluminescence spectra during irradiation and comparing emission intensities relative to Cherenkov emission produced in phantoms and scintillation from small plastic targets. HN treatment plans were delivered to a phantom with bolus and mask present to measure impact on signal quality. Interfraction superficial tumor reduction was simulated on a HN phantom, and cumulative Cherenkov images were analyzed in the region of interest (ROI). HN human patient treatment was imaged through the mask and compared with the dose distribution calculated by the treatment planning system. The relative intensity of radioluminescence from the mask was found to be within 30% of the Cherenkov emission intensity from tissue-colored clay. A strong linear relationship between normalized cumulative Cherenkov intensity and tumor size was established ([Formula: see text]). The presence of a mask above a scintillator ROI was found to decrease mean pixel intensity by >40% and increase distribution spread. Cherenkov imaging through mask material is shown to have potential for surface field verification and tracking of superficial anatomy changes between treatment fractions. Imaging of scintillating targets provides a direct imaging of surface dose on the patient and through transparent bolus material. The first imaging of a patient receiving HN radiotherapy was achieved with a signal map which qualitatively matches the surface dose plan.


Assuntos
Algoritmos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imagem Óptica/métodos , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/métodos , Contagem de Cintilação/instrumentação , Elétrons , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Radiometria/métodos , Dosagem Radioterapêutica , Contagem de Cintilação/métodos
11.
Med Phys ; 46(7): 3067-3077, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30980725

RESUMO

PURPOSE: The purpose of this study was to demonstrate high resolution optical luminescence sensing, referred to as Cherenkov excited luminescence scanning imaging (CELSI), could be achieved during a standard dynamic treatment plan for a whole breast radiotherapy geometry. METHODS: The treatment plan beams induce Cherenkov light within tissue, and this excitation projects through the beam trajectory across the medium, inducing luminescence where there can be molecular reporter. Broad beams generally produce higher signal but low spatial resolution, yet for dynamic plans the scanning of the multileaf collimator allows for a beam-narrowing strategy by recursively temporal differencing each of the Cherenkov images and associated luminescence images. Then reconstruction from each of these size-reduced beamlets defined by the differenced Cherenkov images provides a well-conditioned matrix inversion, where the spatial frequencies are limited by the higher signal-to-noise ratio beamlets. A built-in stepwise convergence relies on stepwise beam size reduction, which is associated with a widening of the bandwidth of Cherenkov spatial frequency and resultant increase in spatial resolution. For the phantom experiments, europium nanoparticles were used as luminescent probes and embedded at depths ranging from 3 to 8 mm. An intensity modulated radiotherapy (IMRT) plan was used to test this. RESULTS: The Cherenkov images spatially guided where the luminescence was measured from, providing high lateral resolution, and iterative reconstruction convergence showed that optimization of the initial and stopping beamlet widths could be achieved with 15 and 4.5 mm, respectively, using a luminescence imaging frame rate of 5/s. With the IMRT breast plan, the original lateral resolution was improved 2X, that is, 0.08-0.24 mm for target depths of 3-8 mm. In comparison, a dynamic wedge (DW) plan showed an inferior image fidelity, with relative contrast recovery decreasing from 0.86 to 0.79. The methodology was applied to a three-dimensional dataset to reconstruct Cherenkov excited luminescence intensity distributions showing volumetric recovery of a 0.5 mm diameter object composed of 0.5 µM luminescent microbeads. CONCLUSIONS: High resolution CELSI was achieved with a clinical breast external beam radiotherapy (EBRT) plan. It is anticipated that this method can allow visualization and localization for luminescence/fluorescence tagged vasculature, lymph nodes, or superficial tagged regions with most dynamic treatment plans.


Assuntos
Mama/efeitos da radiação , Luminescência , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/instrumentação , Humanos , Radioterapia de Intensidade Modulada
12.
Phys Med Biol ; 64(12): 125025, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31035267

RESUMO

Surface dosimetry is required for ensuring effective administration of total skin electron therapy (TSET); however, its use is often reduced due to the time consuming and complex nature of acquisition. A new surface dose imaging technique was characterized in this study and found to provide accurate, rapid and remote measurement of surface doses without the need for post-exposure processing. Disc-shaped plastic scintillators (1 mm thick × 15 mm [Formula: see text]) were chosen as optimal-sized samples and designed to attach to a flat-faced phantom for irradiation using electron beams. Scintillator dosimeter response to radiation damage, dose rate, and temperature were studied. The effect of varying scintillator diameter and thickness on light output was evaluated. Furthermore, the scintillator emission spectra and impact of dosimeter thickness on surface dose were also quantified. Since the scintillators were custom-machined, dosimeter-to-dosimeter variation was tested. Scintillator surface dose measurements were compared to those obtained by optically stimulated luminescence dosimeters (OSLD). Light output from scintillator dosimeters evaluated in this study was insensitive to radiation damage, temperature, and dose rate. Maximum wavelength of emission was found to be 422 nm. Dose reported by scintillators was linearly related to that from OSLDs. Build-up from placement of scintillators and OSLDs had a similar effect on surface dose (4.9% increase). Variation among scintillator dosimeters was found to be 0.3 ± 0.2%. Scintillator light output increased linearly with dosimeter thickness (~1.9 × /mm). All dosimeter diameters tested were able to accurately measure surface dose. Scintillator dosimeters can potentially improve surface dosimetry-associated workflow for TSET in the radiation oncology clinic. Since scintillator data output can be automatically recorded to a patient medical record, the chances of human error in reading out and recording surface dose are minimized.


Assuntos
Elétrons/uso terapêutico , Dosimetria por Luminescência Estimulada Opticamente/instrumentação , Dosimetria por Luminescência Estimulada Opticamente/métodos , Imagens de Fantasmas , Contagem de Cintilação/instrumentação , Neoplasias Cutâneas/radioterapia , Algoritmos , Humanos , Dosagem Radioterapêutica , Neoplasias Cutâneas/patologia
13.
J Hematol ; 8(3): 132-136, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32300458

RESUMO

Primary cutaneous anaplastic large cell lymphoma (pcALCL) is a rare form of non-Hodgkins lymphoma. Current frontline treatments for pcALCL include surgical resection, anthracycline-based chemotherapy, and/or radiation therapy (RT) depending on disease severity. While brentuximab vedotin (BV) has been used for refractory/relapsed cases, it recently received Food and Drug Administration (FDA) approval for use in combination with chemotherapy for peripheral T-cell lymphomas. In this case report, we utilized a combined modality therapy of RT and BV for a limited stage aggressive pcALCL presentation for which routine management is contraindicated. A 59-year-old man with a history of peripheral vascular disease (PVD) presented with an aggressive pcALCL involving the left inferior eyelid and small ipsilateral level II hypermetabolic lymph nodes at stage IIE. Due to the patient's history of PVD, the tumor's rapid growth, possible lymph node involvement, and eye proximity, BV was chosen as the initial chemotherapy treatment followed by RT. Complete metabolic resolution of the primary cutaneous lesion and lymphadenopathy was reached after BV treatment alone; complete clinical response of the primary tumor was reached following radiation therapy. Relapse occurred within 7 months. Salvage cyclophosphamide, vincristine, etoposide, and prednisone were not effective. Retreatment with BV + RT is currently being used to treat the new lesions. Our case illustrates that a combination of BV and RT can be a safe and effective initial treatment in patients with limited stage pcALCL who cannot tolerate anthracycline-based chemotherapy. Our patient had a complete response but ultimately relapsed; thus larger clinical trials are needed to better understand early-stage disease.

14.
Med Phys ; 45(6): 2639-2646, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29663425

RESUMO

PURPOSE: The purpose of this study was to identify the optimal treatment geometry for total skin electron therapy (TSET) using a new optimization metric from Cherenkov image analysis, and to investigate the sensitivity of the Cherenkov imaging method to floor scatter effects in this unique treatment setup. METHODS: Cherenkov imaging using an intensified charge coupled device (ICCD) was employed to measure the relative surface dose distribution as a 2D image in the total skin electron treatment plane. A 1.2 m × 2.2 m × 1 cm white polyethylene sheet was placed vertically at a source to surface distance (SSD) of 300 cm, and irradiated with 6 MeV high dose rate TSET beams. The linear accelerator coordinate system used stipulates 0° is the bottom of the gantry arc, and progresses counterclockwise so that gantry angle 270° produces a horizontal beam orthogonal to the treatment plane. First, all unique pairs of treatment beams were analyzed to determine the performance of the currently recommended symmetric treatment angles (±20° from the horizontal), compared to treatment geometries unconstrained to upholding gantry angle symmetry. This was performed on two medical linear accelerators (linacs). Second, the extent of the floor scatter contributions to measured surface dose at the extended SSD required for TSET were imaged using three gantry angles of incidence: 270° (horizontal), 253° (-17°), and 240° (-30°). Images of the surface dose profile at each angle were compared to the standard concrete floor when steel plates, polyvinyl chloride (PVC), and solid water were placed on the ground at the base of the treatment plane. Postprocessing of these images allowed for comparison of floor material-based scatter profiles with previously published simulation results. RESULTS: Analysis of the symmetric treatment geometry (270 ± 20°) and the identified optimal treatment geometry (270 + 23° and 270 - 17°) showed a 16% increase in the 90% isodose area for the latter field pair on the first linac. The optimal asymmetric pair for the second linac (270 + 25° and 270 - 17°) provided a 52% increase in the 90% isodose area when compared to the symmetric geometry. Difference images between Cherenkov images captured with test materials (steel, PVC, and solid water) and the control (concrete floor) demonstrated relative changes in the two-dimensional (2D) dose profile over a 1 × 1.9 m region of interest (ROI) that were consistent with published simulation data. Qualitative observation of the residual images demonstrates localized increases and decreases with respect to the change in floor material and gantry angle. The most significant changes occurred when the beam was most directly impinging the floor (gantry angle 240°, horizontal -30°), where the PVC floor material decreased scatter dose by 1-3% in 7.2% of the total ROI area, and the steel plate increased scatter dose by 1-3% in 7.0% of the total ROI area. CONCLUSIONS: An updated Cherenkov imaging method identified asymmetric, machine-dependent TSET field angle pairs that provided much larger 90% isodose areas than the commonly adopted symmetric geometry suggested by Task Group 30 Report 23. A novel demonstration of scatter dose Cherenkov imaging in the TSET field was established.


Assuntos
Elétrons/uso terapêutico , Radioterapia/métodos , Diagnóstico por Imagem/instrumentação , Diagnóstico por Imagem/métodos , Arquitetura de Instituições de Saúde , Humanos , Micose Fungoide/radioterapia , Cuidados Paliativos , Aceleradores de Partículas , Radioterapia/instrumentação , Dosagem Radioterapêutica , Espalhamento de Radiação , Pele/diagnóstico por imagem , Pele/efeitos da radiação , Neoplasias Cutâneas/radioterapia
15.
J Cutan Pathol ; 45(6): 458-462, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29512830

RESUMO

Mycosis fungoides in palmoplantar localization (MFPP) is a rare variant of MF that is confined to the hands and feet. Patients commonly receive treatment over many years for suspected palmoplantar dermatitis before the diagnosis is made. Most MFPP patients remain at patch or plaque stage, and often respond to treatment with radiotherapy. Herein, we describe a 77-year-old man who suffered 6 years of hand and foot dermatitis that failed multiple treatments, most notably TNF-α inhibitors and mycophenolate mofetil. He eventually developed a tumor on the hand, which was biopsied to reveal a dense dermal infiltrate of large lymphocytes (CD3+/CD4-/CD8-/TCR-BetaF1+/partial CD30+). A subsequent biopsy of an eczematous patch from his hand revealed an epidermotropic and syringotropic infiltrate comprised of smaller lymphocytes with a concordant immunophenotype and matching clonal peak with TCR gene rearrangement. He was diagnosed with MFPP and started on radiotherapy with a modest response; therefore, a decision was made to start brentuximab vedotin, which resulted in a complete response. MFPP is an exceedingly rare variant of MF that can show large-cell transformation and progress in stage. We highlight a possible association between disease progression and immunosuppressants and the potential role for treatment with brentuximab.


Assuntos
Imunoconjugados/uso terapêutico , Micose Fungoide/tratamento farmacológico , Micose Fungoide/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Idoso , Biomarcadores Tumorais/análise , Brentuximab Vedotin , Ligante CD30/análise , Ligante CD30/biossíntese , Transformação Celular Neoplásica/patologia , , Mãos , Humanos , Masculino
16.
Phys Med Biol ; 63(9): 095009, 2018 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-29588437

RESUMO

The purpose of this study was to measure surface dose by remote time-gated imaging of plastic scintillators. A novel technique for time-gated, intensified camera imaging of scintillator emission was demonstrated, and key parameters influencing the signal were analyzed, including distance, angle and thickness. A set of scintillator samples was calibrated by using thermo-luminescence detector response as reference. Examples of use in total skin electron therapy are described. The data showed excellent room light rejection (signal-to-noise ratio of scintillation SNR ≈ 470), ideal scintillation dose response linearity, and 2% dose rate error. Individual sample scintillation response varied by 7% due to sample preparation. Inverse square distance dependence correction and lens throughput error (8% per meter) correction were needed. At scintillator-to-source angle and observation angle <50°, the radiant energy fluence error was smaller than 1%. The achieved standard error of the scintillator cumulative dose measurement compared to the TLD dose was 5%. The results from this proof-of-concept study documented the first use of small scintillator targets for remote surface dosimetry in ambient room lighting. The measured dose accuracy renders our method to be comparable to thermo-luminescent detector dosimetry, with the ultimate realization of accuracy likely to be better than shown here. Once optimized, this approach to remote dosimetry may substantially reduce the time and effort required for surface dosimetry.


Assuntos
Elétrons/uso terapêutico , Contagem de Cintilação/instrumentação , Neoplasias Cutâneas/radioterapia , Humanos , Neoplasias Cutâneas/patologia , Fatores de Tempo
17.
J Biomed Opt ; 23(3): 1-4, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29560623

RESUMO

Radiation therapy produces Cherenkov optical emission in tissue, and this light can be utilized to activate molecular probes. The feasibility of sensing luminescence from a tissue molecular oxygen sensor from within a human body phantom was examined using the geometry of the axillary lymph node region. Detection of regions down to 30-mm deep was feasible with submillimeter spatial resolution with the total quantity of the phosphorescent sensor PtG4 near 1 nanomole. Radiation sheet scanning in an epi-illumination geometry provided optimal coverage, and maximum intensity projection images provided illustration of the concept. This work provides the preliminary information needed to attempt this type of imaging in vivo.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imagem Óptica/métodos , Radioterapia , Humanos , Imagem Óptica/instrumentação , Imagens de Fantasmas , Razão Sinal-Ruído
18.
J Med Imaging (Bellingham) ; 5(1): 015001, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29322071

RESUMO

Imaging of Cherenkov light emission from patient tissue during fractionated radiotherapy has been shown to be a possible way to visualize beam delivery in real time. If this tool is advanced as a delivery verification methodology, then a sequence of image processing steps must be established to maximize accurate recovery of beam edges. This was analyzed and developed here, focusing on the noise characteristics and representative images from both phantoms and patients undergoing whole breast radiotherapy. The processing included temporally integrating video data into a single, composite summary image at each control point. Each image stack was also median filtered for denoising and ultimately thresholded into a binary image, and morphologic small hole removal was used. These processed images were used for day-to-day comparison computation, and either the Dice coefficient or the mean distance to conformity values can be used to analyze them. Systematic position shifts of the phantom up to 5 mm approached the observed variation values of the patient data. This processing algorithm can be used to analyze the variations seen in patients being treated concurrently with daily Cherenkov imaging to quantify the day-to-day disparities in delivery as a quality audit system for position/beam verification.

19.
Radiat Res ; 189(2): 197-204, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29251551

RESUMO

In this work, Cherenkov-excited molecular sensing was used to assess the potential for simultaneous quantitative sensing of two NIR fluorophores within tissue-simulating phantoms through spectral separation of signals. Cherenkov emissions induced by external beam gamma photon radiation treatment to tissues/tissue-simulating phantoms were detectable over the 500-900-nm wavelength range. The presence of blood was demonstrated to reduce the integrated intensity of detected Cherenkov emissions by nearly 50%, predominantly at wavelengths below 620 nm. The molecular dyes, IRDye 680RD and IRDye 800CW, have excitation and emission spectra at longer wavelengths than the strongest blood absorption peaks, and also where the intensity of Cherenkov light is at its lowest, so that the emission signal relative to background signal is maximized. Tissue phantoms composed of 1% intralipid and 1% blood were used to simulate human breast tissue, and vials containing fluorophore were embedded in the media, and irradiated with gamma photons for Cherenkov excitation. We observed that fluorescence emissions excited by the Cherenkov signal produced within the phantom could be detected at 5-mm depth into the media within a 0.1-25 µ M fluorophore concentration range. The detected fluorescence signals from these dyes showed linear relationships with radiation doses down to the cGy level. In vivo tests were successful only within the range near a µ M, suggesting that these could be used for metabolic probes in vivo where the local concentrations are near this range.


Assuntos
Imagens de Fantasmas , Radioterapia/instrumentação , Animais , Raios Infravermelhos , Camundongos
20.
Biomed Opt Express ; 9(9): 4217-4234, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30615721

RESUMO

Cherenkov-excited luminescence scanned imaging (CELSI) is achieved with external beam radiotherapy to map out molecular luminescence intensity or lifetime in tissue. Just as in fluorescence microscopy, the choice of excitation geometry can affect the imaging time, spatial resolution and contrast recovered. In this study, the use of spatially patterned illumination was systematically studied comparing scan shapes, starting with line scan and block patterns and increasing from single beams to multiple parallel beams and then to clinically used treatment plans for radiation therapy. The image recovery was improved by a spatial-temporal modulation-demodulation method, which used the ability to capture simultaneous images of the excitation Cherenkov beam shape to deconvolve the CELSI images. Experimental studies used the multi-leaf collimator on a clinical linear accelerator (LINAC) to create the scanning patterns, and image resolution and contrast recovery were tested at different depths of tissue phantom material. As hypothesized, the smallest illumination squares achieved optimal resolution, but at the cost of lower signal and slower imaging time. Having larger excitation blocks provided superior signal but at the cost of increased radiation dose and lower resolution. Increasing the scan beams to multiple block patterns improved the performance in terms of image fidelity, lower radiation dose and faster acquisition. The spatial resolution was mostly dependent upon pixel area with an optimized side length near 38mm and a beam scan pitch of P = 0.33, and the achievable imaging depth was increased from 14mm to 18mm with sufficient resolving power for 1mm sized test objects. As a proof-of-concept, in-vivo tumor mouse imaging was performed to show 3D rendering and quantification of tissue pO2 with values of 5.6mmHg in a tumor and 77mmHg in normal tissue.

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