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OBJECTIVES: Based on a previous phase 1 study, total marrow irradiation (TMI) at 9Gy was added to a myeloablative FluBu4 conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for myeloid malignancies. Here, we report on the long-term toxicity of TMI combined with FluBu4 and compare it to patients who received only FluBu4. METHODS: We retrospectively analyzed 38 consecutive patients conditioned with FluBu4/TMI (n = 15) or FluBu4 (n = 23, control group) who had at least 1 year follow-up post-transplant. The rate of long-term adverse events that have been previously associated with total body irradiation (TBI) was analyzed in the two groups. RESULTS: The baseline characteristics did not differ between the two groups. The control group had a longer median follow-up (71.2 mo) than the TMI group (38.5 mo) (p = .004). The most common adverse events were xerostomia, dental complications, cataracts, or osteopenia and did not differ between the two groups. Cognitive dysfunction or noninfectious pneumonitis, often detected after high dose TBI, were also not different in the two groups (p = .12 and p = .7, respectively). There was no grade 4 adverse event. CONCLUSION: Our results suggest that a conditioning regimen with TMI 9Gy and FluBu4 does not increase long-term adverse events after allogeneic HSCT.
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Bussulfano , Transplante de Células-Tronco Hematopoéticas , Agonistas Mieloablativos , Condicionamento Pré-Transplante , Transplante Homólogo , Vidarabina , Humanos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Vidarabina/análogos & derivados , Vidarabina/administração & dosagem , Vidarabina/efeitos adversos , Bussulfano/efeitos adversos , Bussulfano/administração & dosagem , Estudos Retrospectivos , Agonistas Mieloablativos/efeitos adversos , Agonistas Mieloablativos/uso terapêutico , Agonistas Mieloablativos/administração & dosagem , Irradiação Corporal Total/efeitos adversos , Adulto Jovem , Seguimentos , Medula Óssea/efeitos da radiação , Medula Óssea/efeitos dos fármacos , Idoso , AdolescenteRESUMO
Background and purpose: We proposed an artificial neural network model to predict radiobiological parameters for the head and neck squamous cell carcinoma patients treated with radiation therapy. The model uses the tumor specification, demographics, and radiation dose distribution to predict the tumor control probability and the normal tissue complications probability. These indices are crucial for the assessment and clinical management of cancer patients during treatment planning. Methods: Two publicly available datasets of 31 and 215 head and neck squamous cell carcinoma patients treated with conformal radiation therapy were selected. The demographics, tumor specifications, and radiation therapy treatment parameters were extracted from the datasets used as inputs for the training of perceptron. Radiobiological indices are calculated by open-source software using dosevolume histograms from radiation therapy treatment plans. Those indices were used as output in the training of a single-layer neural network. The distribution of data used for training, validation, and testing purposes was 70, 15, and 15%, respectively. Results: The best performance of the neural network was noted at epoch number 32 with the mean squared error of 0.0465. The accuracy of the prediction of radiobiological indices by the artificial neural network in training, validation, and test phases were determined to be 0.89, 0.87, and 0.82, respectively. We also found that the percentage volume of parotid inside the planning target volume is the significant parameter for the prediction of normal tissue complications probability. Conclusion: We believe that the model has significant potential to predict radiobiological indices and help clinicians in treatment plan evaluation and treatment management of head and neck squamous cell carcinoma patients.
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Accurate segmentation of organs-at-risks (OARs) is a precursor for optimizing radiation therapy planning. Existing deep learning-based multi-scale fusion architectures have demonstrated a tremendous capacity for 2D medical image segmentation. The key to their success is aggregating global context and maintaining high resolution representations. However, when translated into 3D segmentation problems, existing multi-scale fusion architectures might underperform due to their heavy computation overhead and substantial data diet. To address this issue, we propose a new OAR segmentation framework, called OARFocalFuseNet, which fuses multi-scale features and employs focal modulation for capturing global-local context across multiple scales. Each resolution stream is enriched with features from different resolution scales, and multi-scale information is aggregated to model diverse contextual ranges. As a result, feature representations are further boosted. The comprehensive comparisons in our experimental setup with OAR segmentation as well as multi-organ segmentation show that our proposed OARFocalFuseNet outperforms the recent state-of-the-art methods on publicly available OpenKBP datasets and Synapse multi-organ segmentation. Both of the proposed methods (3D-MSF and OARFocalFuseNet) showed promising performance in terms of standard evaluation metrics. Our best performing method (OARFocalFuseNet) obtained a dice coefficient of 0.7995 and hausdorff distance of 5.1435 on OpenKBP datasets and dice coefficient of 0.8137 on Synapse multi-organ segmentation dataset. Our code is available at https://github.com/NoviceMAn-prog/OARFocalFuse.
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Órgãos em Risco , Tomografia Computadorizada por Raios X , Tomografia Computadorizada por Raios X/métodos , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
[This corrects the article DOI: 10.3389/fmed.2023.1269689.].
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Background: Clinical attempts to find benefit from specifically targeting and boosting resistant hypoxic tumor subvolumes have been promising but inconclusive. While a first preclinical murine tumor type showed significant improved control with hypoxic tumor boosts, a more thorough investigation of efficacy from boosting hypoxic subvolumes defined by electron paramagnetic resonance oxygen imaging (EPROI) is necessary. The present study confirms improved hypoxic tumor control results in three different tumor types using a clonogenic assay and explores potential confounding experimental conditions. Materials and methods: Three murine tumor models were used for multi-modal imaging and radiotherapy: MCa-4 mammary adenocarcinomas, SCC7 squamous cell carcinomas, and FSa fibrosarcomas. Registered T2-weighted MRI tumor boundaries, hypoxia defined by EPROI as pO2 ≤ 10 mmHg, and X-RAD 225Cx CT boost boundaries were obtained for all animals. 13 Gy boosts were directed to hypoxic or equal-integral-volume oxygenated tumor regions and monitored for regrowth. Kaplan-Meier survival analysis was used to assess local tumor control probability (LTCP). The Cox proportional hazards model was used to assess the hazard ratio of tumor progression of Hypoxic Boost vs. Oxygenated Boost for each tumor type controlling for experimental confounding variables such as EPROI radiofrequency, tumor volume, hypoxic fraction, and delay between imaging and radiation treatment. Results: An overall significant increase in LTCP from Hypoxia Boost vs. Oxygenated Boost treatments was observed in the full group of three tumor types (p < 0.0001). The effects of tumor volume and hypoxic fraction on LTCP were dependent on tumor type. The delay between imaging and boost treatments did not have a significant effect on LTCP for all tumor types. Conclusion: This study confirms that EPROI locates resistant tumor hypoxic regions for radiation boost, increasing clonogenic LTCP, with potential enhanced therapeutic index in three tumor types. Preclinical absolute EPROI may provide correction for clinical hypoxia images using additional clinical physiologic MRI.
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Although radiotherapy is one of the most important curative treatments for cancer, its clinical application is associated with undesired therapeutic effects on normal or healthy tissues. The use of targeted agents that can simultaneously achieve therapeutic and imaging functions could constitute a potential solution. Herein, we developed 2-deoxy-d-glucose (2DG)-labeled poly(ethylene glycol) (PEG) gold nanodots (2DG-PEG-AuD) as a tumor-targeted computed tomography (CT) contrast agent and radiosensitizer. The key advantages of the design are its biocompatibility and targeted AuD with excellent sensitivity in tumor detection via avid glucose metabolism. As a consequence, CT imaging with enhanced sensitivity and remarkable radiotherapeutic efficacy could be attained. Our synthesized AuD displayed linear enhancement of CT contrast as a function of its concentration. In addition, 2DG-PEG-AuD successfully demonstrated significant augmentation of CT contrast in both in vitro cell studies and in vivo tumor-bearing mouse models. In tumor-bearing mice, 2DG-PEG-AuD showed excellent radiosensitizing functions after intravenous injection. Results from this work indicate that 2DG-PEG-AuD could greatly potentiate theranostic capabilities by providing high-resolution anatomical and functional images in a single CT scan and therapeutic capability.
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Relapse after allogeneic stem cell transplantation (allo-SCT) remains the primary cause of treatment failure. A second SCT can result in long-term survival in a subset of patients, but the relapse rate remains high. We conducted a single-center, phase 1, modified 3 + 3 dose-escalation study of the feasibility of combining intensity-modulated total marrow irradiation (IM-TMI) with fludarabine and melphalan for conditioning. Between December 2015 and May 2020, 21 patients with relapsed hematologic disease undergoing second or greater allo-SCT were treated with IM-TMI doses of 6 Gy, 9 Gy, or 12 Gy. Dose-limiting toxicity was defined as a grade 3 or higher treatment-related adverse event; mucositis was the primary dose-limiting toxicity. The median times to neutrophil and platelet engraftment were 10 and 18 days, respectively. The 1-year cumulative incidence of graft-versus-host disease was 65% (95% confidence interval CI, 38-83). The nonrelapse mortality at 2 years was 17% (95% CI, 4-39). Cumulative incidence of relapse at 2 years was 35% (95% CI, 13-58). Two-year progression-free survival and overall survival were 48% and 50%. We conclude that combining IM-TMI with fludarabine-melphalan is feasible. We recommend 12 Gy of IM-TMI with fludarabine-melphalan for second SCT, although 9 Gy may be used for older or underweight patients.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Melfalan/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
We evaluated the impact of respiratory motion on the lung dose during linac-based intensity-modulated total marrow irradiation (IMTMI) using two different approaches: (1) measurement of doses within the lungs of an anthropomorphic phantom using thermoluminescent detectors (TLDs) and (2) treatment delivery measurements using ArcCHECK where gamma passing rates (GPRs) and the mean lung doses were calculated and compared with and without motion. In the first approach, respiratory motions were simulated using a programmable motion platform by using typical published peak-to-peak motion amplitudes of 5, 8, and 12 mm in the craniocaudal (CC) direction, denoted here as M1, M2, and M3, respectively, with 2 mm in both anteroposterior (AP) and lateral (LAT) directions. TLDs were placed in five selected locations in the lungs of a RANDO phantom. Average TLD measurements obtained with motion were normalized to those obtained with static phantom delivery. The mean dose ratios were 1.01 (0.98-1.03), 1.04 (1.01-1.09), and 1.08 (1.04-1.12) for respiratory motions M1, M2, and M3, respectively. To determine the impact of directional respiratory motion, we repeated the experiment with 5-, 8-, and 12-mm motion in the CC direction only. The differences in average TLD doses were less than 1% when compared with the M1, M2, and M3 motions indicating a minimal impact from CC motion on lung dose during IMTMI. In the second experimental approach, we evaluated extreme respiratory motion 15 mm excursion in only the CC direction. We placed an ArcCHECK device on a commercial motion platform and delivered the clinical IMTMI plans of five patients. We compared, with and without motion, the dose volume histograms (DVHs) and mean lung dose calculated with the ArcCHECK-3DVH tool as well as GPR with 3%, 5%, and 10% dose agreements and a 3-mm constant distance to agreement (DTA). GPR differed by 11.1 ± 2.1%, 3.8 ± 1.5%, and 0.1 ± 0.2% with dose agreement criteria of 3%, 5%, and 10%, respectively. This indicates that respiratory motion impacts dose distribution in small and isolated parts of the lungs. More importantly, the impact of respiratory motion on the mean lung dose, a critical indicator for toxicity in IMTMI, was not statistically significant (p > 0.05) based on the Student's t-test. We conclude that most patients treated with IMTMI will have negligible dose uncertainty due to respiratory motion. This is particularly reassuring as lung toxicity is the main concern for future IMTMI dose escalation studies.
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Purpose: Total marrow irradiation (TMI) involves optimization of extremely large target volumes and requires extensive clinical experience and time for both treatment planning and delivery. Although volumetric modulated arc therapy (VMAT) achieves substantial reduction in treatment delivery time, planning process still presents a challenge due to use of multiple isocenters and multiple overlapping arcs. We developed and evaluated a knowledge-based planning (KBP) model for VMAT-TMI to address these clinical challenges. Methods: Fifty-one patients previously treated in our clinic were selected for the model training, while 22 patients from another clinic were used as a test set. All plans used a 3-isocenter to cover sub-target volumes of head and neck (HN), chest, and pelvis. Chest plan was performed first and then used as the base dose for both the HN and pelvis plans to reduce hot spots around the field junctions. This resulted in a wide range of dose-volume histograms (DVH). To address this, plans without the base-dose plan were optimized and added to the library to train the model. Results: KBP achieved our clinical goals (95% of PTV receives 100% of Rx) in a single day, which used to take 4-6 days of effort without KBP. Statistically significant reductions with KBP were observed in the mean dose values to brain, lungs, oral cavity and lenses. KBP substantially improved 105% dose spillage (14.1% ± 2.4% vs 31.8% ± 3.8%), conformity index (1.51 ± 0.06 vs 1.81 ± 0.12) and homogeneity index (1.25 ± 0.02 vs 1.33 ± 0.03). Conclusions: KBP improved dosimetric performance with uniform quality. It reduced dependence on planner experience and achieved a factor of 5 reduction in planning time to produce quality plans to allow its wide-spread clinical implementation.
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PURPOSE: Preclinical radiation replicating clinical intensity modulated radiation therapy (IMRT) techniques can provide data translatable to clinical practice. For this work, treatment plans were created for oxygen-guided dose-painting in small animals using inverse-planned IMRT. Spatially varying beam intensities were achieved using 3-dimensional (3D)-printed compensators. METHODS AND MATERIALS: Optimized beam fluence from arbitrary gantry angles was determined using a verified model of the XRAD225Cx treatment beam. Compensators were 3D-printed with varied thickness to provide desired attenuation using copper/polylactic-acid. Spatial resolution capabilities were investigated using printed test-patterns. Following American Association of Physicists in Medicine TG119, a 5-beam IMRT plan was created for a miniaturized (â¼1/8th scale) C-shape target. Electron paramagnetic resonance imaging of murine tumor oxygenation guided simultaneous integrated boost (SIB) plans conformally treating tumor to a base dose (Rx1) with boost (Rx2) based on tumor oxygenation. The 3D-printed compensator intensity modulation accuracy and precision was evaluated by individually delivering each field to a phantom containing radiochromic film and subsequent per-field gamma analysis. The methodology was validated end-to-end with composite delivery (incorporating 3D-printed tungsten/polylactic-acid beam trimmers to reduce out-of-field leakage) of the oxygen-guided SIB plan to a phantom containing film and subsequent gamma analysis. RESULTS: Resolution test-patterns demonstrate practical printer resolution of â¼0.7 mm, corresponding to 1.0 mm bixels at the isocenter. The miniaturized C-shape plan provides planning target volume coverage (V95% = 95%) with organ sparing (organs at risk Dmax < 50%). The SIB plan to hypoxic tumor demonstrates the utility of this approach (hypoxic tumor V95%,Rx2 = 91.6%, normoxic tumor V95%,Rx1 = 95.7%, normal tissue V100%,Rx1 = 7.1%). The more challenging SIB plan to boost the normoxic tumor rim achieved normoxic tumor V95%,Rx2 = 90.9%, hypoxic tumor V95%,Rx1 = 62.7%, and normal tissue V100%,Rx2 = 5.3%. Average per-field gamma passing rates using 3%/1.0 mm, 3%/0.7 mm, and 3%/0.5 mm criteria were 98.8% ± 2.8%, 96.6% ± 4.1%, and 90.6% ± 5.9%, respectively. Composite delivery of the hypoxia boost plan and gamma analysis (3%/1 mm) gave passing results of 95.3% and 98.1% for the 2 measured orthogonal dose planes. CONCLUSIONS: This simple and cost-effective approach using 3D-printed compensators for small-animal IMRT provides a methodology enabling preclinical studies that can be readily translated into the clinic. The presented oxygen-guided dose-painting demonstrates that this methodology will facilitate studies driving much needed biologic personalization of radiation therapy for improvements in patient outcomes.
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Fibrossarcoma/radioterapia , Impressão Tridimensional , Radioterapia de Intensidade Modulada/instrumentação , Animais , Cobre , Espectroscopia de Ressonância de Spin Eletrônica , Fibrossarcoma/diagnóstico por imagem , Fibrossarcoma/metabolismo , Camundongos , Tratamentos com Preservação do Órgão/métodos , Oxigênio/metabolismo , Imagens de Fantasmas , Poliésteres , Estudo de Prova de Conceito , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Hipóxia Tumoral , Filme para Raios XRESUMO
Total marrow radiation is an emerging treatment modality used in patients undergoing stem cell transplantation. We present a rare case of a patient undergoing total marrow irradiation with concurrent ablative stem cell transplantation with local failures in two out-of-field areas that were not included in the clinical target volume A 31-year-old female patient initially presented with abdominal pain secondary to chronic myelogenous leukemia. She underwent dasatinib treatment for years, but subsequently developed recurrence and underwent consolidation systemic chemotherapy followed by allogeneic stem cell transplantation with adjuvant total marrow irradiation. Several months later, she noticed increased left jaw swelling and dysphagia with associated right ankle swelling. Biopsy of the right ankle and left mandible were consistent with recurrent myeloid sarcoma. This case report suggests that inclusion of the mandible and lower extremities may be necessary when performing total marrow radiation.
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PURPOSE: MRI is the gold-standard imaging modality for brain tumor diagnosis and delineation. The purpose of this work was to investigate the feasibility of performing brain stereotactic radiosurgery (SRS) with a 0.35 T MRI-guided linear accelerator (MRL) equipped with a double-focused multileaf collimator (MLC). Dosimetric comparisons were made vs a conventional C-arm-mounted linac with a high-definition MLC. METHODS: The quality of MRL single-isocenter brain SRS treatment plans was evaluated as a function of target size for a series of spherical targets with diameters from 0.6 cm to 2.5 cm in an anthropomorphic head phantom and six brain metastases (max linear dimension = 0.7-1.9 cm) previously treated at our clinic on a conventional linac. Each target was prescribed 20 Gy to 99% of the target volume. Step-and-shoot IMRT plans were generated for the MRL using 11 static coplanar beams equally spaced over 360° about an isocenter placed at the center of the target. Couch and collimator angles are fixed for the MRL. Two MRL planning strategies (VR1 and VR2) were investigated. VR1 minimized the 12 Gy isodose volume while constraining the maximum point dose to be within ±1 Gy of 25 Gy which corresponded to normalization to an 80% isodose volume. VR2 minimized the 12 Gy isodose volume without the maximum dose constraint. For the conventional linac, the TB1 method followed the same strategy as VR1 while TB2 used five noncoplanar dynamic conformal arcs. Plan quality was evaluated in terms of conformity index (CI), conformity/gradient index (CGI), homogeneity index (HI), and volume of normal brain receiving ≥12 Gy (V12Gy ). Quality assurance measurements were performed with Gafchromic EBT-XD film following an absolute dose calibration protocol. RESULTS: For the phantom study, the CI of MRL plans was not significantly different compared to a conventional linac (P > 0.05). The use of dynamic conformal arcs and noncoplanar beams with a conventional linac spared significantly more normal brain (P = 0.027) and maximized the CGI, as expected. The mean CGI was 95.9 ± 4.5 for TB2 vs 86.6 ± 3.7 (VR1), 88.2 ± 4.8 (VR2), and 88.5 ± 5.9 (TB1). Each method satisfied a normal brain V12Gy ≤ 10.0 cm3 planning goal for targets with diameter ≤2.25 cm. The mean V12Gy was 3.1 cm3 for TB2 vs 5.5 cm3 , 5.0 cm3 and 4.3 cm3 , for VR1, VR2, and TB1, respectively. For a 2.5-cm diameter target, only TB2 met the V12Gy planning objective. The MRL clinical brain plans were deemed acceptable for patient treatment. The normal brain V12Gy was ≤6.0 cm3 for all clinical targets (maximum target volume = 3.51 cm3 ). CI and CGI ranged from 1.12-1.65 and 81.2-88.3, respectively. Gamma analysis pass rates (3%/1mm criteria) exceeded 97.6% for six clinical targets planned and delivered on the MRL. The mean measured vs computed absolute dose difference was -0.1%. CONCLUSIONS: The MRL system can produce clinically acceptable brain SRS plans for spherical lesions with diameter ≤2.25 cm. Large lesions (>2.25 cm) should be treated with a linac capable of delivering noncoplanar beams.
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Neoplasias Encefálicas , Radiocirurgia , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Estudos de Viabilidade , Humanos , Imageamento por Ressonância Magnética , Aceleradores de Partículas , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
While it is well-established that hypoxia is a major factor that affects clinical outcomes in cervical cancer, widespread usage of clinically available methods to detect and evaluate hypoxia during the course of treatment have not been established. This review compares these methods, summarizes their strengths and weaknesses, and assesses the pathways for their useful employment to alter clinical practice. We conducted a search on PubMed for literature pertaining to imaging hypoxic cervical cancer, and implemented keywords related to oxygen measurement tools to improve the relevance of the search results.Oxygenation level-dependent applications of MRI have demonstrated hypoxia-induced radioresistance, and changes in cervix tumor oxygenation from hyperoxic therapy.The hypoxic areas within tumors can be indirectly identified in dynamic contrast-enhanced images, where they generally display low signal enhancement, and diffusion-weighted images, which demonstrates areas of restricted diffusion (which correlates with hypoxia). Positron emmision tomography, used independently and with other imaging modalities, has demonstrated utility in imaging hypoxia through tracers specific for low oxygen levels, like Cu-ATSM tracers and nitroimidazoles. Detecting hypoxia in the tumors of patients diagnosed with cervical cancer via medical imaging and non-imaging tools like electron paramagnetic resonance oximetry can be utilized clinically, such as for guiding radiation and post-treatment surveillance, for a more personalized approach to treatment. The merits of these methods warrant further investigation via comparative effectiveness research and large clinical trials into their clinical applications.
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Hipóxia Celular/fisiologia , Neoplasias do Colo do Útero/diagnóstico , Meios de Contraste , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Imagem Multimodal/métodos , Oximetria/métodos , Oxigênio/metabolismo , Tomografia por Emissão de Pósitrons , Neoplasias do Colo do Útero/metabolismoRESUMO
BACKGROUND: Fiducial markers are frequently used before treatment for image-guided patient setup in radiation therapy (RT), but can also be used during treatment for image-guided intrafraction motion detection. This report describes our implementation of automatic marker detection with periodic kV imaging (TrueBeam v2.5) to monitor and correct intrafraction motion during prostate RT. METHODS: We evaluated the reproducibility and accuracy of software fiducial detection using a phantom with 3 implanted fiducial markers. Clinical implementation for patients with intraprostatic fiducials receiving volumetric modulated arc therapy (VMAT) utilized periodic on-board kV imaging with 10 s intervals during treatment delivery. For each image, the software automatically identified fiducial locations and determined whether their distance relative to planned locations were within a 3 mm tolerance. Motion was corrected if either ≥2 fiducials in a single image or ≥1 fiducial in sequential images were out of tolerance. RESULTS: Phantom studies demonstrated poorer performance of linear fiducials compared to collapsible fiducials, and wide variability to accurately detect fiducials across eight software settings. For any given setting, results were relatively reproducible and precise to ~0.5 mm. Across 17 patients treated with a median of 20 fractions, the software recommended a shift in 44% of fractions, and a shift was actually implemented after visual confirmation of movement greater than the 3 mm threshold in 20% of fractions. Adjustment of our approach led to improved accuracy for the latter (n = 7) patient subset. On average, table repositioning added 3.0 ± 0.3 min to patient time on table. Periodic kV imaging increased skin dose by an estimated 1 cGy per treatment arc. CONCLUSIONS: Periodic kV imaging with automatic detection of motion during VMAT prostate treatments is commercially available, and can be successfully implemented to mitigate effects of intrafraction motion with careful attention to software settings.
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Marcadores Fiduciais , Movimento , Imagens de Fantasmas , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Software , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Órgãos em Risco/efeitos da radiação , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
Single-isocenter volumetric modulated arc therapy (VMAT) technique can provide stereotactic radiosurgery (SRS) treatment with improved delivery efficiency for treating multiple metastases. Nevertheless, planning is time consuming and verification of frame-based SRS setup, especially at noncoplanar angles, can be challenging. We report on a single-isocenter VMAT technique with a special focus on improving treatment workflow and delivery verification to exploit the minimized patient motion of the frame-based SRS. We developed protocols for preplanning and verification for VMAT and evaluated them for ten patient cases. Preplans based on MRI were used to generate comparable treatment plans using CT taken on the day of treatment after frame placement. Target positioning accuracy was evaluated by stereoscopic in-room kV imaging. Dosimetric accuracy of the noncoplanar plan delivery was validated using measurement-guided 3D dose reconstruction as well as film-based end-to-end test with a Rando phantom. Average absolute differences of homogeneity indices, conformity indices, and V12Gy between MR preplans and CT-based plans were within 5%. In-room imaging positioning accuracy of 0.4 mm was verified to be independent of the distance to the isocenter. For treatment verification, average local and global passing rates of the 3D gamma (1 mm, 3%) were 86% and 99%, respectively. D99 values were matched within 5% for individual target structures (>0.5 cc). Additional film analysis confirmed dosimetric accuracy for small targets that had large verification errors in the 3D dose reconstruction. Our results suggest that the advantages of frame-based SRS and noncoplanar single-isocenter VMAT technique can be combined for efficient and accurate treatment of patients with multiple metastases.
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Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Imageamento por Ressonância Magnética/métodos , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Tomografia Computadorizada por Raios X/métodos , Algoritmos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Órgãos em Risco/efeitos da radiação , Prognóstico , Dosagem RadioterapêuticaRESUMO
PURPOSE: It has been known for over 100 years that tumor hypoxia, a near-universal characteristic of solid tumors, decreases the curative effectiveness of radiation therapy. However, to date, there are no reports that demonstrate an improvement in radiation effectiveness in a mammalian tumor on the basis of tumor hypoxia localization and local hypoxia treatment. METHODS AND MATERIALS: For radiation targeting of hypoxic subregions in mouse fibrosarcoma, we used oxygen images obtained using pulse electron paramagnetic resonance pO2 imaging combined with 3D-printed radiation blocks. This achieved conformal radiation delivery to all hypoxic areas in FSa fibrosarcomas in mice. RESULTS: We demonstrate that treatment delivering a radiation boost to hypoxic volumes has a significant (P = .04) doubling of tumor control relative to boosts to well-oxygenated volumes. Additional dose to well-oxygenated tumor regions minimally increases tumor control beyond the 15% control dose to the entire tumor. If we can identify portions of the tumor that are more resistant to radiation, it might be possible to reduce the dose to more sensitive tumor volumes without significant compromise in tumor control. CONCLUSIONS: This work demonstrates in a single, intact mammalian tumor type that tumor hypoxia is a local tumor phenomenon whose treatment can be enhanced by local radiation. Despite enormous clinical effort to overcome hypoxic radiation resistance, to our knowledge this is the first such demonstration, even in preclinical models, of targeting additional radiation to hypoxic tumor to improve the therapeutic ratio.
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Oxigênio/metabolismo , Radioterapia Guiada por Imagem/métodos , Animais , Linhagem Celular Tumoral , Espectroscopia de Ressonância de Spin Eletrônica , Estimativa de Kaplan-Meier , Camundongos , Hipóxia Tumoral/efeitos da radiaçãoRESUMO
INTRODUCTION: Spine stereotactic body radiation therapy (SBRT) achieves favorable outcomes compared to conventional radiotherapy doses/fractionation. The spinal cord is the principal dose-limiting organ-at-risk (OAR), and safe treatment requires precise immobilization/localization. Therefore, image guidance is paramount to successful spine SBRT. Conventional X-ray imaging and alignment to surrogate bony anatomy may be inadequate, whereas magnetic resonance imaging (MRI) directly visualizes the dose-limiting cord. This work assessed the dosimetric capability of the ViewRay (ViewRay Inc. Oakwood Village, OH) magnetic resonance (MR) guided linac (MR-Linac) for spine SBRT. METHODS: Eight spine SBRT patients without orthopedic hardware who were previously treated on a TrueBeam using volumetric modulated arc therapy (VMAT) were re-planned using MR-Linac fixed-field intensity-modulated radiation therapy (IMRT). Phantom measurements using film, ionization chamber, and a commercial diode-array assessed feasibility. Plans included a variety of prescriptions (30-50 Gy in 3-10 fractions). RESULTS: MR-Linac plans satisfied all clinical goals. Compared to VMAT plans, both entrance dose and heterogeneity increased (Dmax: 134±3% vs. 120±2%, p=0.0270), while conformality decreased (conformity index: 1.28±0.06 vs. 1.06±0.06, p=0.0005), and heterogeneity increased. However, while not statistically significant, MR-linac cord sparing improved (cord Dmax: 16.1±2.7Gy vs. 19.5±1.6Gy, p=0.2066; cord planning organ at risk volume (cord PRV) Dmax: 20.0±2.6Gy vs. 24.5±2.0Gy, p=0.0996). Delivery time increased but was acceptable (14.39±1.26min vs. 9.57±1.19min). Ionization chamber measurements agreed with planned dose to within 2.5%. Film and diode measurements demonstrated accurate/precise delivery of dose gradients between the target and the cord. CONCLUSION: Spine SBRT with the MR-Linac is feasible as verified via re-planning eight clinical cases followed by delivery verification in phantoms using film, diodes, and an ionization chamber. Real-time visualization of the dose-limiting cord during spine SBRT may enable cord-based gating, reduced margins, alternate dose schemas, and/or adaptive therapy.
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In this phase 1 study, we tested increasing doses of total marrow irradiation (TMI) in addition to standard intravenous melphalan at 200 mg/m2 (Mel200) in the conditioning regimen prior to autologous stem cell transplant (ASCT) for multiple myeloma (NCT02043847). Twelve patients aged 18-75 with relapsed myeloma were enrolled in the study and received Mel200 and TMI 3 Gy (n = 3), 6 Gy (n = 3), or 9 Gy (n = 6) prior to transplant. There were no grade 4 extra-hematologic toxicities and a maximum tolerated dose was not reached. Median time to neutrophil and platelet engraftment was 11 and 13 d, respectively. At day 90, 73% of patients were in CR or VGPR. Median progression free survival (PFS) was 449 d and median overall survival (OS) was 966 d. We conclude that TMI at a dose of 9 Gy can be safely combined with Mel200 in therapeutic regimens for autologous transplant. Initial clinical results will prompt a phase 2 study.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante , Adulto , Idoso , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Dose Máxima Tolerável , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Recidiva , Retratamento , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Resultado do Tratamento , Irradiação Corporal Total/efeitos adversos , Irradiação Corporal Total/métodosRESUMO
Frame-based stereotactic radiosurgery (SRS) requires fixation of an invasive head ring to ensure accurate targeting. Minimizing waiting time with a fixed head ring is important for patient comfort and satisfaction. We report a practical preplanning solution for the Brainlab iPlan treatment planning system that reduces waiting time by expediting the planning process on treatment day. A water-filled anthropomorphic head phantom was used to acquire a surrogate CT image set for preplanning and fused with patient's MRI, which was obtained before the day of treatment. Once an acceptable preplan was obtained, it was saved as a plan template and the phantom image set was removed from the Brainlab database to prevent any confusion and mix-up of image sets. On the treatment day, the patient's CT and MRI were fused, and the customized beam settings of the preplan template were then applied and optimized. Up to 10-fold of reduction in treatment plan time was demonstrated by bench testing with multiple planners and a variety of cases. Loading the plan template and fine-tuning the preconfigured beam settings took only a small fraction of the preplan time to restore the conformity and dose falloff comparable to those of the preplan. For instance, preplan time was 2 hr for a two-isocenter case, whereas, it took less than 20 min for a less experienced planner to plan it on the day of treat-ment using the preplan method. The SRS preplanning technique implemented in this study for the Brainlab iPlan treatment planning system offers an opportunity to explore possible beam configurations thoroughly, optimize planning parameters, resolve gantry angle clearance issues, and communicate and address challenges with physicians before the treatment day. Preplanning has been proven to improve plan quality and to improve efficiency in our clinic, especially for multiple-isocenter and dosimetrically challenging cases.