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1.
Phys Imaging Radiat Oncol ; 20: 23-29, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34693040

RESUMO

Background and Purpose: Urethra-sparing radiation therapy for localized prostate cancer can reduce the risk of radiation-induced genitourinary toxicity by intentionally underdosing the periurethral transitional zone. We aimed to compare the clinical impact of a urethra-sparing intensity-modulated proton therapy (US-IMPT) plan with that of conventional clinical plans without urethral dose reduction. Materials and Methods: This study included 13 patients who had undergone proton beam therapy. The prescribed dose was 63 GyE in 21 fractions for 99% of the clinical target volume. To compare the clinical impact of the US-IMPT plan with that of the conventional clinical plan, tumor control probability (TCP) and normal tissue complication probability (NTCP) were calculated with a generalized equivalent uniform dose-based Lyman-Kutcher model using dose volume histograms. The endpoints of these model parameters for the rectum, bladder, and urethra were fistula, contraction, and urethral stricture, respectively. Results: The mean NTCP value for the urethra in US-IMPT was significantly lower than that in the conventional clinical plan (0.6% vs. 1.2%, p < 0.05). There were no statistically significant differences between the conventional and US-IMPT plans regarding the mean minimum dose for the urethra with a 3-mm margin, TCP value, and NTCP value for the rectum and bladder. Additionally, the target dose coverage of all plans in the robustness analysis was within the clinically acceptable range. Conclusions: Compared with the conventional clinically applied plans, US-IMPT plans have potential clinical advantages and may reduce the risk of genitourinary toxicities, while maintaining the same TCP and NTCP in the rectum and bladder.

2.
J Radiat Res ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34617104

RESUMO

The prediction of liver Dmean with 3-dimensional radiation treatment planning (3DRTP) is time consuming in the selection of proton beam therapy (PBT), and deep learning prediction generally requires large and tumor-specific databases. We developed a simple dose prediction tool (SDP) using deep learning and a novel contour-based data augmentation (CDA) approach and assessed its usability. We trained the SDP to predict the liver Dmean immediately. Five and two computed tomography (CT) data sets of actual patients with liver cancer were used for the training and validation. Data augmentation was performed by artificially embedding 199 contours of virtual clinical target volume (CTV) into CT images for each patient. The data sets of the CTVs and OARs are labeled with liver Dmean for six different treatment plans using two-dimensional calculations assuming all tissue densities as 1.0. The test of the validated model was performed using 10 unlabeled CT data sets of actual patients. Contouring only of the liver and CTV was required as input. The mean relative error (MRE), the mean percentage error (MPE) and regression coefficient between the planned and predicted Dmean was 0.1637, 6.6%, and 0.9455, respectively. The mean time required for the inference of liver Dmean of the six different treatment plans for a patient was 4.47±0.13 seconds. We conclude that the SDP is cost-effective and usable for gross estimation of liver Dmean in the clinic although the accuracy should be improved further if we need the accuracy of liver Dmean to be compatible with 3DRTP.

3.
J Radiat Res ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34590123

RESUMO

Compared to conventional X-ray therapy, proton beam therapy (PBT) has more clinical and physical advantages such as irradiation dose reduction to normal tissues for pediatric medulloblastoma. However, PBT is expensive. We aimed to compare the cost-effectiveness of PBT for pediatric medulloblastoma with that of conventional X-ray therapy, while focusing on radiation-induced secondary cancers, which are rare, serious and negatively affect a patient's quality of life (QOL). Based on a systematic review, a decision tree model was used for the cost-effectiveness analysis. This analysis was performed from the perspective of health care payers; the cost was estimated from medical fees. The target population was pediatric patients with medulloblastoma below 14 years old. The time horizon was set at 7.7 years after medulloblastoma treatment. The primary outcome was the incremental cost-effectiveness ratio (ICER), which was defined as the ratio of the difference in cost and lifetime attributable risk (LAR) between conventional X-ray therapy and PBT. The discount rate was set at 2% annually. Sensitivity analyses were performed to model uncertainty. Cost and LAR in conventional X-ray therapy and PBT were Japanese yen (JPY) 1 067 608 and JPY 2436061 and 42% and 7%, respectively. The ICER was JPY 3856398/LAR. In conclusion, PBT is more cost-effective than conventional X-ray therapy in reducing the risk of radiation-induced secondary cancers in pediatric medulloblastoma. Thus, our constructed ICER using LAR is one of the valid indicators for cost-effectiveness analysis in radiation-induced secondary cancer.

4.
Phys Imaging Radiat Oncol ; 18: 1-4, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34258400

RESUMO

The urethra position may shift due to the presence/absence of the catheter. Our proposed post-urination-magnetic resonance imaging (PU-MRI) technique is possible to identify the urethra without catheter. We aimed to verify the inter-operator difference in contouring the urethra by PU-MRI. The mean values of the evaluation indices of dice similarity coefficient, mean slice-wise Hausdorff distance, and center coordinates were 0.93, 0.17 mm, and 0.36 mm for computed tomography, and 0.75, 0.44 mm, and 1.00 mm for PU-MRI. Therefore, PU-MRI might be useful for identifying the prostatic urinary tract without using a urethral catheter. Clinical trial registration: Hokkaido University Hospital for Clinical Research (018-0221).

5.
Med Phys ; 48(9): 5311-5326, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34260755

RESUMO

PURPOSE: To show the feasibility of real-time CT image generation technique utilizing internal fiducial markers that facilitate the evaluation of internal deformation. METHODS: In the proposed method, a linear regression model that can derive internal deformation from the displacement of fiducial markers is built for each voxel in the training process before the treatment session. Marker displacement and internal deformation are derived from the four-dimensional computed tomography (4DCT) dataset. In the treatment session, the three-dimensional deformation vector field is derived according to the marker displacement, which is monitored by the real-time imaging system. The whole CT image can be synthesized by deforming the reference CT image with a deformation vector field in real-time. To show the feasibility of the technique, image synthesis accuracy and tumor localization accuracy were evaluated using the dataset generated by extended NURBS-Based Cardiac-Torso (XCAT) phantom and clinical 4DCT datasets from six patients, containing 10 CT datasets each. In the validation with XCAT phantom, motion range of the tumor in training data and validation data were about 10 and 15 mm, respectively, so as to simulate motion variation between 4DCT acquisition and treatment session. In the validation with patient 4DCT dataset, eight CT datasets from the 4DCT dataset were used in the training process. Two excluded inhale CT datasets can be regarded as the datasets with large deformations more than training dataset. CT images were generated for each respiratory phase using the corresponding marker displacement. Root mean squared error (RMSE), normalized RMSE (NRMSE), and structural similarity index measure (SSIM) between the original CT images and the synthesized CT images were evaluated as the quantitative indices of the accuracy of image synthesis. The accuracy of tumor localization was also evaluated. RESULTS: In the validation with XCAT phantom, the mean NRMSE, SSIM, and three-dimensional tumor localization error were 7.5 ± 1.1%, 0.95 ± 0.02, and 0.4 ± 0.3 mm, respectively. In the validation with patient 4DCT dataset, the mean RMSE, NRMSE, SSIM, and three-dimensional tumor localization error in six patients were 73.7 ± 19.6 HU, 9.2 ± 2.6%, 0.88 ± 0.04, and 0.8 ± 0.6 mm, respectively. These results suggest that the accuracy of the proposed technique is adequate when the respiratory motion is within the range of the training dataset. In the evaluation with a marker displacement larger than that of the training dataset, the mean RMSE, NRMSE, and tumor localization error were about 100 HU, 13%, and <2.0 mm, respectively, except for one case having large motion variation. The performance of the proposed method was similar to those of previous studies. Processing time to generate the volumetric image was <100 ms. CONCLUSION: We have shown the feasibility of the real-time CT image generation technique for volumetric imaging.


Assuntos
Marcadores Fiduciais , Neoplasias , Tomografia Computadorizada Quadridimensional , Humanos , Movimento (Física) , Imagens de Fantasmas
6.
J Radiat Res ; 62(5): 926-933, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34196697

RESUMO

The purpose of this work is to show the usefulness of a prediction method of tumor location based on partial least squares regression (PLSR) using multiple fiducial markers. The trajectory data of respiratory motion of four internal fiducial markers inserted in lungs were used for the analysis. The position of one of the four markers was assumed to be the tumor position and was predicted by other three fiducial markers. Regression coefficients for prediction of the position of the tumor-assumed marker from the fiducial markers' positions is derived by PLSR. The tracking error and the gating error were evaluated assuming two possible variations. First, the variation of the position definition of the tumor and the markers on treatment planning computed tomograhy (CT) images. Second, the intra-fractional anatomical variation which leads the distance change between the tumor and markers during the course of treatment. For comparison, rigid predictions and ordinally multiple linear regression (MLR) predictions were also evaluated. The tracking and gating errors of PLSR prediction were smaller than those of other prediction methods. Ninety-fifth percentile of tracking/gating error in all trials were 3.7/4.1 mm, respectively in PLSR prediction for superior-inferior direction. The results suggested that PLSR prediction was robust to variations, and clinically applicable accuracy could be achievable for targeting tumors.

7.
J Radiat Res ; 62(4): 626-633, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-33948661

RESUMO

In spot scanning proton therapy (SSPT), the spot position relative to the target may fluctuate through tumor motion even when gating the radiation by utilizing a fiducial marker. We have established a procedure that evaluates the delivered dose distribution by utilizing log data on tumor motion and spot information. The purpose of this study is to show the reliability of the dose distributions for liver tumors treated with real-time-image gated SSPT (RGPT). In the evaluation procedure, the delivered spot information and the marker position are synchronized on the basis of log data on the timing of the spot irradiation and fluoroscopic X-ray irradiation. Then a treatment planning system reconstructs the delivered dose distribution. Dose distributions accumulated for all fractions were reconstructed for eight liver cases. The log data were acquired in all 168 fractions for all eight cases. The evaluation was performed for the values of maximum dose, minimum dose, D99, and D5-D95 for the clinical target volumes (CTVs) and mean liver dose (MLD) scaled by the prescribed dose. These dosimetric parameters were statistically compared between the planned dose distribution and the reconstructed dose distribution. The mean difference of the maximum dose was 1.3% (95% confidence interval [CI]: 0.6%-2.1%). Regarding the minimum dose, the mean difference was 0.1% (95% CI: -0.5%-0.7%). The mean differences of D99, D5-D95 and MLD were below 1%. The reliability of dose distributions for liver tumors treated with RGPT-SSPT was shown by the evaluation of the accumulated dose distributions.

8.
Hepatol Res ; 51(8): 870-879, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33894086

RESUMO

AIM: To report the outcomes of stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system for hepatocellular carcinoma patients. METHODS: From January 2005 to July 2018, 63 patients with 74 lesions with a maximum diameter ≤52 mm were treated by stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system. No patient with a Child-Pugh Score ≥9 was included, and 85.6% had a score of 5 or 6. Using the biological effective dose (BED) with an α/ß ratio of 10 (BED10 ), the median dose in BED10 at the reference point was 76.8 Gy (range 60-122.5 Gy). Overall survival (OS) and local control rates were assessed using the Kaplan-Meier method. RESULTS: With a median follow-up period of 24.6 months (range 0.9-118.4 months), the 1-year and 2-year OS rates were 86.8% (95% confidence interval [95% CI] 75.8-93.3) and 71.1% (57.8-81.6), respectively. The 2-year OS was 89.6% in patients with the baseline modified albumin-bilirubin (mALBI) grade =1, and 61.7% in patients with grade ≥2a. In the multivariate analysis, the mALBI grade (=1 vs. ≥2a) was a significant factor for OS (p = 0.028, 95% CI 1.11-6.18). The 1-year and 2-year local control rates were 100% (100-100%) and 92.0% (77.5-97.5%). The local control rates were significantly higher in the BED10 ≥100 Gy group than in the BED10 <100 Gy group (2-year 100% vs. 86.5%, p = 0.049) at the reference point. CONCLUSION: This retrospective study of stereotactic body radiotherapy using real-time tumor-tracking radiotherapy for hepatocellular carcinoma showed favorable outcomes with lower incidence of toxicities, especially in patients treated with BED10 ≥100 Gy to the reference point.

9.
J Radiat Res ; 62(3): 483-493, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33899102

RESUMO

We developed a confidence interval-(CI) assessing model in multivariable normal tissue complication probability (NTCP) modeling for predicting radiation-induced liver disease (RILD) in primary liver cancer patients using clinical and dosimetric data. Both the mean NTCP and difference in the mean NTCP (ΔNTCP) between two treatment plans of different radiotherapy modalities were further evaluated and their CIs were assessed. Clinical data were retrospectively reviewed in 322 patients with hepatocellular carcinoma (n = 215) and intrahepatic cholangiocarcinoma (n = 107) treated with photon therapy. Dose-volume histograms of normal liver were reduced to mean liver dose (MLD) based on the fraction size-adjusted equivalent uniform dose. The most predictive variables were used to build the model based on multivariable logistic regression analysis with bootstrapping. Internal validation was performed using the cross-validation leave-one-out method. Both the mean NTCP and the mean ΔNTCP with 95% CIs were calculated from computationally generated multivariate random sets of NTCP model parameters using variance-covariance matrix information. RILD occurred in 108/322 patients (33.5%). The NTCP model with three clinical and one dosimetric parameter (tumor type, Child-Pugh class, hepatitis infection status and MLD) was most predictive, with an area under the receiver operative characteristics curve (AUC) of 0.79 (95% CI 0.74-0.84). In eight clinical subgroups based on the three clinical parameters, both the mean NTCP and the mean ΔNTCP with 95% CIs were able to be estimated computationally. The multivariable NTCP model with the assessment of 95% CIs has potential to improve the reliability of the NTCP model-based approach to select the appropriate radiotherapy modality for each patient.


Assuntos
Hepatopatias/etiologia , Neoplasias Hepáticas/complicações , Modelos Biológicos , Probabilidade , Lesões por Radiação/complicações , Intervalos de Confiança , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada
10.
PLoS One ; 16(3): e0249010, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33780512

RESUMO

Tracheal suctioning is an important procedure to maintain airway patency by removing secretions. Today, suctioning operators include not only medical staff, but also family caregivers. The use of a simulation system has been noted to be the most effective way to learn the tracheal suctioning technique for operators. While the size of the trachea varies across different age groups, the artificial trachea model in the simulation system has only one fixed model. Thus, this study aimed to construct multiple removable trachea models according to different age groups. We enrolled 20 patients who had previously received proton beam therapy in our institution and acquired the treatment planning computed tomography (CT) image data. To construct the artificial trachea model for three age groups (children, adolescents and young adults, and adults), we analyzed the three-dimensional coordinates of the entire trachea, tracheal carina, and the end of the main bronchus. We also analyzed the diameter of the trachea and main bronchus. Finally, we evaluated the accuracy of the model by analyzing the difference between the constructed model and actual measurements. The trachea model was 8 cm long for children and 12 cm for adolescents and young adults, and for adults. The angle between the trachea and bed was about 20 degrees, regardless of age. The mean model accuracy was less than 0.4 cm. We constructed detachable artificial trachea models for three age groups for implementation in the endotracheal suctioning training environment simulator (ESTE-SIM) based on the treatment planning CT image. Our constructed artificial trachea models will be able to provide a simulation environment for various age groups in the ESTE-SIM.


Assuntos
Órgãos Artificiais , Simulação por Computador , Traqueia/fisiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Sucção , Tomografia Computadorizada por Raios X , Traqueia/diagnóstico por imagem , Adulto Jovem
11.
Phys Med ; 82: 54-63, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33588228

RESUMO

The 4D Treatment Planning Workshop for Particle Therapy, a workshop dedicated to the treatment of moving targets with scanned particle beams, started in 2009 and since then has been organized annually. The mission of the workshop is to create an informal ground for clinical medical physicists, medical physics researchers and medical doctors interested in the development of the 4D technology, protocols and their translation into clinical practice. The 10th and 11th editions of the workshop took place in Sapporo, Japan in 2018 and Krakow, Poland in 2019, respectively. This review report from the Sapporo and Krakow workshops is structured in two parts, according to the workshop programs. The first part comprises clinicians and physicists review of the status of 4D clinical implementations. Corresponding talks were given by speakers from five centers around the world: Maastro Clinic (The Netherlands), University Medical Center Groningen (The Netherlands), MD Anderson Cancer Center (United States), University of Pennsylvania (United States) and The Proton Beam Therapy Center of Hokkaido University Hospital (Japan). The second part is dedicated to novelties in 4D research, i.e. motion modelling, artificial intelligence and new technologies which are currently being investigated in the radiotherapy field.


Assuntos
Inteligência Artificial , Tomografia Computadorizada Quadridimensional , Humanos , Japão , Polônia , Planejamento da Radioterapia Assistida por Computador
12.
Phys Med Biol ; 66(6): 065029, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33626513

RESUMO

Integrated-type proton computed tomography (pCT) measures proton stopping power ratio (SPR) images for proton therapy treatment planning, but its image quality is degraded due to noise and scatter. Although several correction methods have been proposed, techniques that include estimation of uncertainty are limited. This study proposes a novel uncertainty-aware pCT image correction method using a Bayesian convolutional neural network (BCNN). A DenseNet-based BCNN was constructed to predict both a corrected SPR image and its uncertainty from a noisy SPR image. A total 432 noisy SPR images of 6 non-anthropomorphic and 3 head phantoms were collected with Monte Carlo simulations, while true noise-free images were calculated with known geometric and chemical components. Heteroscedastic loss and deep ensemble techniques were performed to estimate aleatoric and epistemic uncertainties by training 25 unique BCNN models. 200-epoch end-to-end training was performed for each model independently. Feasibility of the predicted uncertainty was demonstrated after applying two post-hoc calibrations and calculating spot-specific path length uncertainty distribution. For evaluation, accuracy of head SPR images and water-equivalent thickness (WET) corrected by the trained BCNN models was compared with a conventional method and non-Bayesian CNN model. BCNN-corrected SPR images represent noise-free images with high accuracy. Mean absolute error in test data was improved from 0.263 for uncorrected images to 0.0538 for BCNN-corrected images. Moreover, the calibrated uncertainty represents accurate confidence levels, and the BCNN-corrected calibrated WET was more accurate than non-Bayesian CNN with high statistical significance. Computation time for calculating one image and its uncertainties with 25 BCNN models is 0.7 s with a consumer grade GPU. Our model is able to predict accurate pCT images as well as two types of uncertainty. These uncertainties will be useful to identify potential cause of SPR errors and develop a spot-specific range margin criterion, toward elaboration of uncertainty-guided proton therapy.


Assuntos
Teorema de Bayes , Aprendizado Profundo , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Cabeça/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imagens de Fantasmas , Tomografia Computadorizada por Raios X/métodos , Algoritmos , Calibragem , Humanos , Método de Monte Carlo , Redes Neurais de Computação , Terapia com Prótons , Prótons , Reprodutibilidade dos Testes , Incerteza
13.
Hepatol Res ; 51(4): 461-471, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33217113

RESUMO

AIM: To prospectively evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for patients with previously untreated solitary primary hepatocellular carcinoma (HCC). METHODS: The main eligibility criteria included the following: (1) primary solitary HCC; (2) no prior treatment for HCC; (3) Child-Turcotte-Pugh score of seven or less; and (4) unsuitability for or refusal of surgery and radiofrequency ablation (RFA). The prescribed dose of SBRT was 40 Gy in five fractions. The primary endpoint was 3-year overall survival (OS); the secondary endpoints included local progression-free survival (LPFS), local control (LC), and adverse events. The accrual target was 60 patients, expecting a 3-year OS of 70% with a 50% threshold. RESULTS: Between 2014 and 2018, 36 patients were enrolled; enrollment was closed early because of slow accrual. The median tumor size was 2.3 cm. The median follow-up at the time of evaluation was 20.8 months. The 3-year OS was 78% (95% confidence interval [CI]: 53%-90%). The 3-year LPFS and LC proportion were 73% (95% CI: 48%-87%) and 90% (95% CI: 65%-97%), respectively. Grade 3 or higher SBRT-related toxicities were observed in four patients (11%), and grade five toxicities were not observed. CONCLUSIONS: This study showed acceptably low incidence of SBRT-related toxicities. LC and OS after SBRT were comparable for previously untreated solitary HCC for patients unfit for resection and RFA. Although a definitive conclusion cannot be drawn by this study, the promising results indicate that SBRT may be an alternative option in the management of early HCC.

15.
J Appl Clin Med Phys ; 22(1): 174-183, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33338323

RESUMO

PURPOSE: To investigate potential advantages of adaptive intensity-modulated proton beam therapy (A-IMPT) by comparing it to adaptive intensity-modulated X-ray therapy (A-IMXT) for nasopharyngeal carcinomas (NPC). METHODS: Ten patients with NPC treated with A-IMXT (step and shoot approach) and concomitant chemotherapy between 2014 and 2016 were selected. In the actual treatment, 46 Gy in 23 fractions (46Gy/23Fx.) was prescribed using the initial plan and 24Gy/12Fx was prescribed using an adapted plan thereafter. New treatment planning of A-IMPT was made for the same patients using equivalent dose fractionation schedule and dose constraints. The dose volume statistics based on deformable images and dose accumulation was used in the comparison of A-IMXT with A-IMPT. RESULTS: The means of the Dmean of the right parotid gland (P < 0.001), right TM joint (P < 0.001), left TM joint (P < 0.001), oral cavity (P < 0.001), supraglottic larynx (P = 0.001), glottic larynx (P < 0.001), , middle PCM (P = 0.0371), interior PCM (P < 0.001), cricopharyngeal muscle (P = 0.03643), and thyroid gland (P = 0.00216), in A-IMPT are lower than those of A-IMXT, with statistical significance. The means of, D0.03cc , and Dmean of each sub portion of auditory apparatus and D30% for Eustachian tube and D0.5cc for mastoid volume in A-IMPT are significantly lower than those of A-IMXT. The mean doses to the oral cavity, supraglottic larynx, and glottic larynx were all reduced by more than 20 Gy (RBE = 1.1). CONCLUSIONS: An adaptive approach is suggested to enhance the potential benefit of IMPT compared to IMXT to reduce adverse effects for patients with NPC.


Assuntos
Neoplasias Nasofaríngeas , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
16.
J Radiat Res ; 62(2): 329-337, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33372202

RESUMO

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.


Assuntos
Neoplasias Faríngeas/radioterapia , Terapia com Prótons/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Faríngeas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Raios X , Adulto Jovem
17.
J Appl Clin Med Phys ; 21(12): 10-19, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33151643

RESUMO

A synchrotron-based real-time image gated spot-scanning proton beam therapy (RGPT) system with inserted fiducial markers can irradiate a moving tumor with high accuracy. As gated treatments increase the beam delivery time, this study aimed to investigate the frequency of intra-field adjustments corresponding to the baseline shift or drift and the beam delivery efficiency of a synchrotron-based RGPT system. Data from 118 patients corresponding to 127 treatment plans and 2810 sessions between October 2016 and March 2019 were collected. We quantitatively analyzed the proton beam delivery time, the difference between the ideal beam delivery time based on a simulated synchrotron magnetic excitation pattern and the actual treatment beam delivery time, frequency corresponding to the baseline shift or drift, and the gating efficiency of the synchrotron-based RGPT system according to the proton beam delivery machine log data. The mean actual beam delivery time was 7.1 min, and the simulated beam delivery time in an ideal environment with the same treatment plan was 2.9 min. The average difference between the actual and simulated beam delivery time per session was 4.3 min. The average frequency of intra-field adjustments corresponding to baseline shift or drift and beam delivery efficiency were 21.7% and 61.8%, respectively. Based on our clinical experience with a synchrotron-based RGPT system, we determined the frequency corresponding to baseline shift or drift and the beam delivery efficiency using the beam delivery machine log data. To maintain treatment accuracy within ± 2.0 mm, intra-field adjustments corresponding to baseline shift or drift were required in approximately 20% of cases. Further improvements in beam delivery efficiency may be realized by shortening the beam delivery time.


Assuntos
Neoplasias , Terapia com Prótons , Marcadores Fiduciais , Humanos , Neoplasias/radioterapia , Cintilografia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Síncrotrons
18.
Commun Biol ; 3(1): 620, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33110168

RESUMO

Enhanced invasiveness, a critical determinant of metastasis and poor prognosis, has been observed in cancer cells that survive cancer therapy, including radiotherapy. Here, we show that invasiveness in radiation-surviving cancer cells is associated with alterations in lysosomal exocytosis caused by the enhanced activation of Arl8b, a small GTPase that regulates lysosomal trafficking. The binding of Arl8b with its effector, SKIP, is increased after radiation through regulation of BORC-subunits. Knockdown of Arl8b or BORC-subunits decreases lysosomal exocytosis and the invasiveness of radiation-surviving cells. Notably, high expression of ARL8B and BORC-subunit genes is significantly correlated with poor prognosis in breast cancer patients. Sp1, an ATM-regulated transcription factor, is found to increase BORC-subunit genes expression after radiation. In vivo experiments show that ablation of Arl8b decreases IR-induced invasive tumor growth and distant metastasis. These findings suggest that BORC-Arl8b-mediated lysosomal trafficking is a target for improving radiotherapy by inhibiting invasive tumor growth and metastasis.


Assuntos
Fatores de Ribosilação do ADP/metabolismo , Sobrevivência Celular/efeitos da radiação , Lisossomos/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Fatores de Ribosilação do ADP/genética , Proteínas Adaptadoras de Transdução de Sinal , Antibacterianos/farmacologia , Biomarcadores Tumorais , Linhagem Celular Tumoral , Movimento Celular , Doxiciclina/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Proteínas do Tecido Nervoso/genética , Subunidades Proteicas , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismo
19.
Talanta ; 218: 121102, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32797869

RESUMO

A flow enzyme-linked immunosorbent assay (ELISA) method based on light absorption by enzymatically generated aniline oligomer in the presence of horseradish peroxidase (HRP), H2O2, and aniline is proposed. Aniline oligomer is rapidly formed through the polymerization reaction via the enzymatic reaction, and its fast reaction rate is beneficial for flow ELISA. An anti-3-phenoxybenzoic acid monoclonal antibody (mAb) was produced by mice, and was used for the flow competitive ELISA for the determination of 3-phenoxybenzoic acid (3PBA), which was performed on an acrylic plate having a Y-shaped channel. ABS resin beads (d = 1 mm) were filled in the channel to increase the surface area for the adsorption of the mAb. A clank-type detection chamber (optical length: 1 cm) made of polydimethylsiloxane (PDMS) containing carbon black, which can significantly decrease light scattering, was fabricated with a 3D printer. The PDMS detection chamber was connected to the outlet of the acrylic flow chip with a tube. A blue LED was used as a light source for the flow ELISA. The inhabitation concentration at 50% and the detection range (absorbance change from 90 to 10%) for the proposed flow competitive ELISA were 0.5 ppm and 0.05-5 ppm, respectively. We also performed the flow competitive ELISA in an artificial and real urine, and no significant matrix effect of the urine samples on the ELISA was found.


Assuntos
Análise de Injeção de Fluxo , Peróxido de Hidrogênio , Compostos de Anilina , Animais , Anticorpos Monoclonais , Benzoatos , Ensaio de Imunoadsorção Enzimática , Camundongos
20.
Phys Med Biol ; 65(21): 215007, 2020 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-32604078

RESUMO

This study proposes a near-real-time spot-scanning proton dose calculation method with probabilistic uncertainty estimation using a three-dimensional convolutional neural network (3D-CNN). CT images and clinical target volume contours of 215 head and neck cancer patients were collected from a public database. 1484 and 488 plans were extracted for training and testing the 3D-CNN model, respectively. Spot beam data and single-field uniform dose (SFUD) labels were calculated for each plan using an open-source dose calculation toolkit. Variable spot data were converted into a fixed-size volume hereby called a 'peak map' (PM). 300 epochs of end-to-end training was implemented using sets of stopping power ratio and PM as input. Moreover, transfer learning techniques were used to adjust the trained model to SFUD doses calculated with different beam parameters and calculation algorithm using only 7.95% of training data used for the base model. Finally, accuracy of the 3D-CNN-calculated doses and model uncertainty was reviewed with several evaluation metrics. The 3D-CNN model calculates 3D proton dose distributions accurately with a mean absolute error of 0.778 cGyE. The predicted uncertainty is correlated with dose errors at high contrast edges. Averaged Sørensen-Dice similarity coefficients between binarized outputs and ground truths are mostly above 80%. Once the 3D-CNN model was well-trained, it can be efficiently fine-tuned for different proton doses by transfer learning techniques. Inference time for calculating one dose distribution is around 0.8 s for a plan using 1500 spot beams with a consumer grade GPU. A novel spot-scanning proton dose calculation method using 3D-CNN was developed. The 3D-CNN model is able to calculate 3D doses and uncertainty with any SFUD spot data and beam irradiation angles. Our proposed method should be readily extendable to other setups and plans and be useful for dose verification, image-guided proton therapy, or other applications.


Assuntos
Redes Neurais de Computação , Terapia com Prótons , Incerteza , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Tomografia Computadorizada por Raios X
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