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1.
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
2.
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.

3.
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.

4.
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
5.
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.

6.
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
7.
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
8.
Minim Invasive Ther Allied Technol ; 29(6): 334-343, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31516050

RESUMO

Purpose: This study evaluated the success rate and complications of percutaneous implantation of hepatic fiducial true-spherical gold markers for real-time adaptive radiotherapy (RAR), which constitutes real-time image-guided radiotherapy with gating.Material and methods: We retrospectively evaluated 100 patients who underwent 116 percutaneous intrahepatic implantations of 2-mm-diameter, spherical, gold fiducial markers before RAR from 1999 to 2016, with Seldinger's method. We defined technical success as marker placement at the intended liver parenchyma, without mispositioning, and clinical success as successful tracking of the gold marker and completion of planned RAR. Complications related to marker placement were assessed.Results: The technical success rate for true-spherical gold marker implantation was 92.2% (107/116). Nine of 116 markers migrated (intra-procedurally in seven patients, delayed in two patients). Migration out of the liver (n = 4) or intrahepatic vessels (n = 5) occurred without complications; these markers were not retrieved. The clinical success rate was 100.0% (115/115). Abdominal pain occurred in 16 patients, fever and hemorrhage in seven patients each, and pneumothorax and nausea in one patient each. No major complications were encountered.Conclusions: Percutaneous transhepatic implantation of true-spherical gold markers for RAR is feasible and can be conducted with a high success rate and low complication rate.


Assuntos
Neoplasias Hepáticas , Radioterapia Guiada por Imagem , Marcadores Fiduciais , Humanos , Estudos Retrospectivos
9.
J Appl Clin Med Phys ; 21(2): 38-49, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31886616

RESUMO

We developed a synchrotron-based real-time-image gated-spot-scanning proton-beam therapy (RGPT) system and utilized it to clinically operate on moving tumors in the liver, pancreas, lung, and prostate. When the spot-scanning technique is linked to gating, the beam delivery time with gating can increase, compared to that without gating. We aim to clarify whether the total treatment process can be performed within approximately 30 min (the general time per session in several proton therapy facilities), even for gated-spot-scanning proton-beam delivery with implanted fiducial markers. Data from 152 patients, corresponding to 201 treatment plans and 3577 sessions executed from October 2016 to June 2018, were included in this study. To estimate the treatment process time, we utilized data from proton beam delivery logs during the treatment for each patient. We retrieved data, such as the disease site, total target volume, field size at the isocenter, and the number of layers and spots for each field, from the treatment plans. We quantitatively analyzed the treatment process, which includes the patient load (or setup), bone matching, marker matching, beam delivery, patient unload, and equipment setup, using the data obtained from the log data. Among all the cases, 90 patients used the RGPT system (liver: n = 34; pancreas: n = 5; lung: n = 4; and prostate: n = 47). The mean and standard deviation (SD) of the total treatment process time for the RGPT system was 30.3 ± 7.4 min, while it was 25.9 ± 7.5 min for those without gating treatment, excluding craniospinal irradiation (CSI; head and neck: n = 16, pediatric: n = 31, others: n = 15); for CSI (n = 11) with two or three isocenters, the process time was 59.9 ± 13.9 min. Our results demonstrate that spot-scanning proton therapy with a gating function can be achieved in approximately 30-min time slots.


Assuntos
Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Terapia com Prótons/métodos , Radioterapia Guiada por Imagem/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Marcadores Fiduciais , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Neoplasias Hepáticas/radioterapia , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/radioterapia , Neoplasias da Próstata/radioterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Reprodutibilidade dos Testes , Síncrotrons , Fatores de Tempo , Adulto Jovem
10.
EJNMMI Res ; 9(1): 104, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31802264

RESUMO

BACKGROUND: We investigated the prognostic predictive value of the combination of fluorodeoxyglucose (FDG)- and fluoromisonidazole (FMISO)-PET in patients with non-small cell lung carcinoma (NSCLC) treated with stereotactic body radiation therapy (SBRT). PATIENTS AND METHODS: We prospectively examined patients with pathologically proven NSCLC; all underwent FDG and FMISO PET/CT scans before SBRT. PET images were acquired using a whole-body time-of-flight PET-CT scanner with respiratory gating. We classified them into recurrent and non-recurrent groups based on their clinical follow-ups and compared the groups' tumor diameters and PET parameters (i.e., maximum of the standardized uptake value (SUVmax), metabolic tumor volume, tumor-to-muscle ratio, and tumor-to-blood ratio). We performed univariate analysis to evaluate the impact of the PET variables on the patients' progression-free survival (PFS). We divided the patients by thresholds of FDG SUVmax and FMISO SUVmax obtained from receiver operating characteristic analysis for assessment of recurrence rate and PFS. RESULTS: Thirty-two NSCLC patients (19 male and 13 females; median age, 83 years) were enrolled. All received SBRT. At the study endpoint, 23 patients (71.9%) were non-recurrent and nine patients (28.1%) had recurrent disease. Significant between-group differences were observed in tumor diameter and all the PET parameters, demonstrating that those were significant predictors of the recurrence in all patients. In the 22 patients with tumors > 2 cm, tumor diameter and FDG SUVmax were not significant predictors. Thirty-two patients were divided into three patterns from the thresholds of FDG SUVmax (6.81) and FMISO SUVmax (1.89); A, low FDG and low FMISO (n = 14); B, high FDG and low FMISO (n = 8); C, high FDG and high FMISO (n = 10). No pattern A patient experienced tumor recurrence, whereas two pattern B patients (25%) and seven pattern C patients (70%) exhibited recurrence. A Kaplan-Meier analysis of all patients revealed a significant difference in PFS between patterns A and B (p = 0.013) and between patterns A and C (p < 0.001). In the tumors > 2 cm patients, significant differences in PFS were demonstrated between pattern A and C patients (p = 0.002). CONCLUSION: The combination of FDG- and FMISO-PET can identify patients with a baseline risk of recurrence and indicate whether additional therapy might be performed to improve survival.

11.
J Appl Clin Med Phys ; 20(8): 78-86, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31400082

RESUMO

PURPOSE: Interplay effects may influence dose distributions to a moving target when using dynamic delivery techniques such as intensity-modulated radiotherapy (IMRT). The aim of this study was to evaluate the impact of organ motion on volumetric and dosimetric parameters in stomach lymphomas treated with IMRT. METHODS: Ten patients who had been treated with IMRT for stomach lymphomas were enrolled. The clinical target volume (CTV) was contoured as the whole stomach. Considering interfractional uncertainty, the internal target volume (ITV) margin was uniformly 1.5 cm to the CTV and then modified based on the 4DCT images in case of the large respiratory motion. The planning target volume (PTV) was created by adding 5 mm to the ITV. The impact of organ motion on the volumetric and dosimetric parameters was evaluated retrospectively (4D simulation). The organ motion was reproduced by shifting the isocenter on the radiation treatment planning system. Several simulation plans were created to test the influence of the beam-on timing in the respiration cycle on the dose distribution. The homogeneity index (HI), volume percentage of stomach covered by the prescribed dose (Vp ), and D99 of the CTV were evaluated. RESULTS: The organ motion was the largest in the superior-inferior direction (10.1 ± 4.5 mm [average ± SD]). Stomach volume in each respiratory phase compared to the mean volume varied approximately within a ± 5% range in most of the patients. The PTV margin was sufficiently large to cover the CTV during the IMRT. There was a significant reduction in Vp and D99 but not in HI in the 4D simulation in free-breathing and multiple fractions compared to the clinically-used plan (P < 0.05) suggesting that interplay effects deteriorate the dose distribution. The absolute difference of D99 was less than 1% of the prescribed dose. CONCLUSIONS: There were significant interplay effects affecting the dose distribution in stomach IMRT. The magnitude of the dose reduction was small when patients were treated on free-breathing and multiple fractions.


Assuntos
Linfoma/radioterapia , Movimentos dos Órgãos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Respiração , Neoplasias Gástricas/radioterapia , Humanos , Linfoma/fisiopatologia , Órgãos em Risco/efeitos da radiação , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Neoplasias Gástricas/fisiopatologia
12.
Phys Med ; 65: 33-39, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31430584

RESUMO

PURPOSE: To quantitatively evaluate and compare the image recognition performance of multiple fiducial markers available in real-time tumor-tracking radiation therapy (RTRT). METHODS: Clinically available markers including sphere shape, coil shape, cylinder shape, line shape, and ball shape (folded line shape) were evaluated in liver and lung models of RTRT. Maximum thickness of the polymethyl metacrylate (PMMA) phantom that could automatically recognize the marker was determined by template-pattern matching. Image registration accuracy of the fiducial marker was determined using liver RTRT model. Lung RTRT was mimicked with an anthropomorphic chest phantom and a one-dimensional motion stage in order to simulate marker motion in heterogeneous fluoroscopic images. The success or failure of marker tracking and image registration accuracy for the lung model were evaluated in the same manner as that for the liver model. RESULTS: All fiducial markers except for line shape and coil shape of thinner diameter were recognized by the PMMA phantom, which is assumed to have the typical thickness of an abdomen, with two-dimensional image registration accuracy of <2 pixels. Three-dimensional calculation error with the use of real-time stereoscopic fluoroscopy in RTRT was thought to be within 1 mm. In the evaluation using the lung model, the fiducial markers were recognized stably with sufficient accuracy for clinical application. The same was true for the evaluation using the liver model. CONCLUSIONS: The image recognition performance of fiducial markers was quantified and compared. The results presented here may be useful for the selection of fiducial markers.


Assuntos
Marcadores Fiduciais , Fluoroscopia , Processamento de Imagem Assistida por Computador , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Radioterapia Guiada por Imagem/normas , Fígado/diagnóstico por imagem , Fígado/efeitos da radiação , Pulmão/diagnóstico por imagem , Pulmão/efeitos da radiação , Imagens de Fantasmas , Polimetil Metacrilato , Fatores de Tempo
13.
Int J Radiat Oncol Biol Phys ; 105(3): 606-617, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31306735

RESUMO

PURPOSE: Preoperative treatment is recommended for borderline resectable pancreatic ductal adenocarcinoma. However, the standard treatment has not yet been determined. We conducted a multicenter phase 2 study to investigate the efficacy of neoadjuvant treatment of sequential chemoradiation followed by chemotherapy. METHODS AND MATERIALS: All enrolled patients were treated by preoperative chemoradiation (a total dose of 50.4 Gy in 28 fractions and orally administered S-1 at 80 mg/m2 on the day of irradiation) followed by chemotherapy (administration of gemcitabine at 1000 mg/m2/dose on days 1, 8, and 15 in 3 cycles of 4 weeks) and attempted curative resection. The primary outcome was an R0 resection rate among patients who completed preoperative treatment and pancreatectomy. The threshold of the R0 resection rate was defined as 74% based on a previous study of up-front surgery. RESULTS: Forty-five patients were included. Twenty-one patients could not undergo pancreatectomy because of progressive diseases (n = 14), adverse events (n = 5), or consent withdrawal (n = 2), and 4 patients underwent additional resection after dropping out. The resection rates were 53.3% and 62.2% in the per-protocol set (PPS) and full analysis set (FAS) populations, respectively. The R0 resection rates were 95.8% (95% confidence interval, 78.9%-99.9%) and 96.4% (81.7%-99.9%) in the PPS and FAS populations, respectively. The median overall survival and progression-free survival of all the included patients were 17.3 and 10.5 months, respectively. The median survival time of the patients with pancreatectomy was significantly longer than that of the patients without pancreatectomy in the PPS (27.9 vs 12.3 months; P = .001) and FAS populations (32.2 vs 11.8 months; P < .001). CONCLUSIONS: This study revealed that a long duration of preoperative treatment of sequential chemoradiation followed by systemic chemotherapy provides a high rate of R0 resection and sufficient survival time in patients undergoing pancreatectomy.


Assuntos
Adenocarcinoma/terapia , Antimetabólitos Antineoplásicos/administração & dosagem , Quimiorradioterapia/métodos , Desoxicitidina/análogos & derivados , Terapia Neoadjuvante , Ácido Oxônico/administração & dosagem , Neoplasias Pancreáticas/terapia , Tegafur/administração & dosagem , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Desoxicitidina/administração & dosagem , Fracionamento da Dose de Radiação , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Complicações Pós-Operatórias , Critérios de Avaliação de Resposta em Tumores Sólidos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento
14.
Radiother Oncol ; 135: 100-106, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31015154

RESUMO

PURPOSE: To predict the probability of radiation-induced liver toxicity (RILT) and implement the normal tissue complication probability (NTCP) model-based approach considering confidence intervals (CIs) to select patients for new treatment techniques, such as proton beam therapy, based on a certain NTCP reduction (ΔNTCP) threshold for primary liver cancer patients. METHODS AND MATERIALS: Common Toxicity Criteria for Adverse Events (CTCAE) grade ≥2 RILT was scored. The Lyman NTCP models predicting the probability of CTCAE grade ≥2 RILT as a function of the fraction-size adjusted mean liver dose (MLD), using reference fraction size = 2 Gy/fraction and α/ß ratio = 2 Gy, were fitted using the maximum likelihood method. At certain combinations of MLDs, ΔNTCP with a CI was evaluated by the delta method. RESULTS: Of the 239 patients, the incidence of CTCAE grade ≥2 RILT was 55% (46% in the Child-Pugh (CP)-A vs. 81% in the CP-B/C, p < 0.001). Among 180 CP-A patients, 40% who had viral hepatitis infections experienced toxicity vs. 32% in the nonhepatitis subgroup. The MLD was 18 Gy in the toxicity group vs. 16.1 Gy in the nontoxicity group (p = 0.002). The estimated NTCP model parameters specific to the patient subgroups and the ΔNTCP with CI assuming a particular CP classification and viral hepatitis infection status were considerably different which possible changed treatment decision. CONCLUSIONS: Patients with CP-A and viral hepatitis infection or CP-B/C cirrhosis had greater susceptibility to CTCAE grade ≥2 RILT. The estimated NTCP and ΔNTCP for individual patients along with a consideration of uncertainties improve the reliability of the NTCP model-based approach.


Assuntos
Neoplasias Hepáticas/radioterapia , Fígado/efeitos da radiação , Lesões por Radiação/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Incerteza
15.
Technol Cancer Res Treat ; 17: 1533033818809983, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30407123

RESUMO

BACKGROUND: Precise local radiotherapy for adrenal metastasis can prolong the useful life of patients with oligometastasis. The aim of this retrospective, 2-center study was to establish the safety and effectiveness of real-time tumor-tracking radiotherapy and general stereotactic body radiotherapy in treating patients with adrenal metastatic tumors. MATERIALS AND METHODS: Thirteen lesions in 12 patients were treated with real-time tumor-tracking radiotherapy (48 Gy in 8 fractions over 2 weeks) and 8 lesions in 8 patients were treated with general stereotactic body radiotherapy (40-50 Gy in 5-8 fractions over 2 weeks or 60-70 Gy in 10 fractions over 2 weeks). Overall survival rates, local control rates, and adverse effects were analyzed. RESULTS: The actuarial overall survival rates for all patients at 1 and 2 years were 78.5% and 45.8%, respectively, with a median follow-up of 17.5 months, and the actuarial local control rates for all tumors at 1 and 2 years were 91.7% and 53.0%, respectively, with a median follow-up of 9 months. A complete local tumor response was obtained in 3 tumors treated by real-time tumor-tracking radiotherapy (lung adenocarcinomas with diameters of 35, 40, and 60 mm). There was a statistically significant difference in the local control between the groups treated by real-time tumor-tracking radiotherapy (100% at 1 year) and general stereotactic body radiotherapy (50% at 1 year; P < .001). No late adverse reactions at Grade 2 or higher were reported for either treatment group. CONCLUSIONS: This study showed that although both treatments are safe and effective, the real-time tumor-tracking radiotherapy is more effective than general stereotactic body radiotherapy in local control for adrenal metastasis.


Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/radioterapia , Neoplasias das Glândulas Suprarrenais/secundário , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida
16.
In Vivo ; 32(5): 1183-1191, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30150442

RESUMO

BACKGROUND: Local antitumor efficacy and the outcome of neoadjuvant chemoradiotherapy (NACRT) with low-dose gemcitabine and wide irradiation area for borderline resectable and unresectable pancreatic cancer were evaluated. PATIENTS AND METHODS: Thirty-four cases of borderline resectable and unresectable pancreatic cancer were recruited. Three-dimensional conformal radiotherapy to the pancreatic bed and the region scheduled for lymph node dissection was performed to a total dose of 50.4 Gy28 fractions with gemcitabine at a dose of 150 mg/m2 weekly. Clinical and pathological results were examined. RESULTS: Twenty-seven patients (79.4%) completed the protocol. Grade 3/4 leucopenia (n=10), and grade 3 anorexia (n=1) occurred. Seven cases were excluded (two refused treatment; five had progressive disease), 20 underwent laparotomy, and 16 resected (47.1%) cases achieved R0 resection. Median survival time, and 3-year and 5-year survival rates were 39.0 months, and 56.3% and 28.1% in resected cases, respectively. CONCLUSION: NACRT with low-dose gemcitabine and wide irradiation area achieved 100% R0 resection and acceptable prognosis.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Adulto , Idoso , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Desoxicitidina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Pancreatectomia , Recidiva , Análise de Sobrevida , Resultado do Tratamento
17.
Medicine (Baltimore) ; 97(31): e11309, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30075497

RESUMO

Recently, several reports demonstrated the efficacy of neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACRT) for patients with borderline resectable (BRPC) and locally advanced unresectable pancreatic carcinoma (LAPC). The aim of this study was to evaluate the treatment response after NACRT, especially for nerve plexuses, and the optimal resection area for superior mesenteric artery nerve plexuses in BRPC and LAPC patients after NACRT.A total of 17 patients with BRPC and LAPC received preoperative gemcitabine-based NACRT. The numbers of BRPC and LAPC patients were 13 and 4, respectively. We evaluated nerve plexus invasion by CT before and after NACRT, decided on the resection area of plexus invasion in SMA before NACRT, and compared the preoperative evaluation and clinicopathological findings.In the plexus of the supra-mesenteric artery (pl-SMA), arterial nerve plexus invasion, in cases <90°, all patients showed the absence of residual cancer in the resected specimen after NACRT. In cases between 90° and 180°, 1 of 2 patients (50%) showed nerve plexus invasion. In cases over 180°, all patients showed nerve plexus invasion. We could perform R0 resection in all 10 cases, and pl-SMA invasion disappeared in 6 of 7 BRPC patients.We demonstrated the relationship between the angle of nerve plexus tumor invasion and treatment effect after NACRT. We could perform R0 resection in all pl-SMA invasion cases, deciding on the resection area of pl-SMA based on CT before NACRT.


Assuntos
Plexo Celíaco/cirurgia , Artéria Mesentérica Superior/cirurgia , Neoplasias Pancreáticas/terapia , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Quimiorradioterapia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Dissecação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Resultado do Tratamento
18.
Lung Cancer ; 122: 107-112, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30032817

RESUMO

OBJECTIVES: Even with advanced image guidance, biopsies occasionally fail to diagnose small lung lesions, which are highly suggestive of primary lung cancer by radiological examination. The aim of this study was to evaluate the outcome of stereotactic body radiotherapy (SBRT) to treat small lung lesions clinically diagnosed as primary lung cancer. MATERIALS AND METHODS: This is a prospective, multi-institutional observation study. Strict inclusion and exclusion criteria were determined in a nation-wide consensus meeting and used to include patients who were clinically diagnosed with primary lung cancer using precise imaging modalities, for whom further surgical intervention was not feasible, who refused watchful waiting, and who were highly tolerable of SBRT with informed consent. SBRT was performed with 48 Gy in 4 fractions at the tumor isocenter. RESULTS: From August 2009 to August 2014, 62 patients from 11 institutions were enrolled. Their median age was 80 years. The tumors ranged in size from 9 to 30 mm in diameter (median, 18 mm). The median follow-up interval was 55 months. The 3-year overall survival rate was 83.3% (95% confidence interval (CI) 71.1-90.7%) for all the patients and 94.7% (95% CI 68.1-99.2%) for the patients younger than 75 years. Local failure, regional lymph node metastases and distant metastases occurred in 4 (6.4%), 3 (4.8%) and 11 (17.7%) patients, respectively. Grades 3 and 4 toxicities were observed in 8 (12.9%) patients and 1 (1.6%) patient, respectively. No grade 5 toxicities were observed. CONCLUSIONS: SBRT is safe and effective for patients with small lung lesions clinically diagnosed as primary lung cancer that satisfied the proposed strict indication criteria as previously reported. A prospective interventional study is required to ascertain if SBRT is an alternative strategy for these patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Dosagem Radioterapêutica , Análise de Sobrevida , Resultado do Tratamento
19.
J Radiat Res ; 59(suppl_1): i50-i57, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29538699

RESUMO

Modern radiotherapy technologies such as proton beam therapy (PBT) permit dose escalation to the tumour and minimize unnecessary doses to normal tissues. To achieve appropriate patient selection for PBT, a normal tissue complication probability (NTCP) model can be applied to estimate the risk of treatment-related toxicity relative to X-ray therapy (XRT). A methodology for estimating the difference in NTCP (∆NTCP), including its uncertainty as a function of dose to normal tissue, is described in this study using the Delta method, a statistical method for evaluating the variance of functions, considering the variance-covariance matrix. We used a virtual individual patient dataset of radiation-induced liver disease (RILD) in liver tumour patients who were treated with XRT as a study model. As an alternative option for individual patient data, dose-bin data, which consists of the number of patients who developed toxicity in each dose level/bin and the total number of patients in that dose level/bin, are useful for multi-institutional data sharing. It provides comparable accuracy with individual patient data when using the Delta method. With reliable NTCP models, the ∆NTCP with uncertainty might potentially guide the use of PBT; however, clinical validation and a cost-effectiveness study are needed to determine the appropriate ∆NTCP threshold.


Assuntos
Neoplasias Hepáticas/terapia , Fígado/patologia , Fígado/efeitos da radiação , Probabilidade , Terapia com Prótons/efeitos adversos , Lesões por Radiação/etiologia , Incerteza , Terapia por Raios X , Algoritmos , Humanos
20.
J Radiat Res ; 59(suppl_1): i63-i71, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29309691

RESUMO

This is a report of a single-institution prospective study evaluating the safety of a spot-scanning dedicated, small 360-degree gantry, synchrotron-based proton beam therapy (PBT) system. Data collection was performed for 56 patients with 59 treatment sites who received proton beam therapy at Hokkaido University Hospital between March 2014 and July 2015. Forty-one patients were male and 15 were female. The median age was 66 years. The primary lesion sites were prostate (n = 17), bone/soft tissue (n = 10), liver (n = 7), lung (n = 6), central nervous system (n = 5), colon (n = 2), pancreas (n = 2), kidney (n = 2) and others (n = 5). Chemotherapy was administered in 11 patients. The prescribed total dose was from 20 to 76 GyE (Radiobiological equivalent dose, RBE = 1.1), with the median dose of 65 GyE in 4 to 35 fractions. No PBT-related Common Terminology Criteria for Adverse Events Grade 4 or 5 toxicities were observed; the incidence of early PBT-related Grade 4 adverse events was 0% (95% confidence interval 0 to 6.38%). The most common Grade 3 toxicities were hematologic toxicity (12.5%) unlikely to be related to the PBT. One patient developed a left femoral neck fracture (Grade 3) at 14.5 months after PBT for chondrosarcoma of the left pelvis. The pathological findings showed no other malignancies, suggesting that it was possibly related to the PBT. In conclusion, the spot-scanning dedicated, synchrotron-based PBT system is feasible, but further studies on its long-term safety and efficacy are warranted.


Assuntos
Terapia com Prótons/efeitos adversos , Síncrotrons , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Demografia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
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