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1.
J Appl Toxicol ; 44(5): 784-793, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38262615

RESUMO

Successful treatment of pediatric cancers often results in long-term health complications, including potential effects on fertility. Therefore, assessing the male reproductive toxicity of anti-cancer drug treatments and the potential for recovery is of paramount importance. However, in vivo evaluations are time-intensive and require large numbers of animals. To overcome these constraints, we utilized an innovative organ culture system that supports long-term spermatogenesis by placing the testis tissue between a base agarose gel and a polydimethylsiloxane ceiling, effectively mirroring the in vivo testicular environment. The present study aimed to determine the efficacy of this organ culture system for accurately assessing testicular toxicity induced by cisplatin, using acrosin-green fluorescent protein (GFP) transgenic neonatal mouse testes. The testis fragments were treated with different concentrations of cisplatin-containing medium for 24 h and incubated in fresh medium for up to 70 days. The changes in tissue volume and GFP fluorescence over time were evaluated to monitor the progression of spermatogenesis, in addition to the corresponding histopathology. Cisplatin treatment caused tissue volume shrinkage and reduced GFP fluorescence in a concentration-dependent manner. Recovery from testicular toxicity was also dependent on the concentration of cisplatin received. The results demonstrated that this novel in vitro system can be a faithful replacement for animal experiments to assess the testicular toxicity of anti-cancer drugs and their reversibility, providing a useful method for drug development.


Assuntos
Cisplatino , Testículo , Humanos , Camundongos , Animais , Criança , Recém-Nascido , Masculino , Testículo/metabolismo , Técnicas de Cultura de Órgãos/métodos , Cisplatino/toxicidade , Espermatogênese , Proteínas de Fluorescência Verde/genética
2.
Sci Rep ; 13(1): 2233, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36788295

RESUMO

Neural regeneration is extremely difficult to achieve. In traumatic brain injuries, the loss of brain parenchyma volume hinders neural regeneration. In this study, neuronal tissue engineering was performed by using electrically charged hydrogels composed of cationic and anionic monomers in a 1:1 ratio (C1A1 hydrogel), which served as an effective scaffold for the attachment of neural stem cells (NSCs). In the 3D environment of porous C1A1 hydrogels engineered by the cryogelation technique, NSCs differentiated into neuroglial cells. The C1A1 porous hydrogel was implanted into brain defects in a mouse traumatic damage model. The VEGF-immersed C1A1 porous hydrogel promoted host-derived vascular network formation together with the infiltration of macrophages/microglia and astrocytes into the gel. Furthermore, the stepwise transplantation of GFP-labeled NSCs supported differentiation towards glial and neuronal cells. Therefore, this two-step method for neural regeneration may become a new approach for therapeutic brain tissue reconstruction after brain damage in the future.


Assuntos
Lesões Encefálicas Traumáticas , Células-Tronco Neurais , Camundongos , Animais , Hidrogéis , Neurônios , Lesões Encefálicas Traumáticas/terapia , Engenharia Tecidual/métodos , Alicerces Teciduais , Materiais Biocompatíveis , Diferenciação Celular
3.
Biol Pharm Bull ; 44(7): 910-919, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33896885

RESUMO

Glioblastoma multiforme (GBM) is the most prevalent malignant primary brain tumor with a high recurrence rate. Despite multimodal therapy including surgical resection, chemotherapy, and radiotherapy, the median survival time after the initial diagnosis of GBM is approximately 14 months. Since cancer stem cells (CSCs) are considered the leading cause of cancer recurrence, glioblastoma stem cell-targeted therapy is a promising strategy for the treatment of GBM. However, because CSC heterogeneity has been implicated in the difficulties of CSC-target therapy, more in-depth knowledge of CSC biology is still required to develop novel therapies. In this study, we established single cell-derived tumorspheres from human glioblastoma U87MG cells. One of these tumorspheres, P4E8 clone, showed CSC-like phenotypes, such as self-renewal capacity, expression of CSC markers, resistance to anti-cancer agents, and in vivo tumorigenicity. Therefore, we used P4E8 cells as a cell-based model of glioblastoma stem cells (GSCs). Gene expression analysis using microarray indicated that the most highly expressed genes in P4E8 cells compared to the parental U87MG were PC3-secreted microprotein (MSMP). Furthermore, MSMP was expressed in patient-derived GSCs and human glioma tissues at the protein level, implying that MSMP might contribute to glioma development and progression.


Assuntos
Glioma/fisiopatologia , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Animais , Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica , Glioblastoma/fisiopatologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Recidiva Local de Neoplasia/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Transplante Heterólogo
4.
Yakugaku Zasshi ; 140(5): 701-710, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32378674

RESUMO

We previously reported that anticholinergic (AC) drug use increases with age in the elderly Japanese population. In this analysis, we investigated attribution for each AC drug type to total AC burden using different elderly age groups. Prescription records (from 09/23/2015 to 12/31/2016) for outpatients using any AC were extracted from pharmacy claims (primary source) and hospital-based databases. AC burden (number of AC drugs and AC score) and AC type were assessed using the Anticholinergic Cognitive Burden (ACB) scale, Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and Beers criteria. Age was categorized using three subgroups (65-74, 75-84, and ≥85 years). Overall, 125426, 140634, 35628, and 23149 of the pharmacy outpatients received ≥1 AC drug from the ACB scale, ADS, ARS, or Beers criteria, respectively. The number of AC drugs increased with age for the ACB scale and ADS groups; but decreased for the ARS and Beers criteria. Antihypertensives provided the biggest contribution to AC score using the ACB scale and ADS, and antihistamines for the ARS. Proportional attribution to AC score typically increased with age for antihypertensives (ADS highest proportion: 34.6% for ≥85 years) and cardiac agents, but decreased for antihistamines (ARS lowest proportion: 15.3% for ≥85 years), corticosteroids, and antiepileptics. Similar findings were typically observed for the hospital database. In conclusion, antihypertensives were the principal type of AC drugs using the ACB scale and ADS and their attribution to AC score increased with age. Antihistamines were the principal drug type for the ARS.


Assuntos
Antagonistas Colinérgicos/efeitos adversos , Uso de Medicamentos/estatística & dados numéricos , Polimedicação , Prescrições/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Povo Asiático , Antagonistas Colinérgicos/administração & dosagem , Antagonistas Colinérgicos/classificação , Transtornos Cognitivos/induzido quimicamente , Estudos Transversais , Feminino , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Japão/epidemiologia , Masculino , Estudos Retrospectivos , Risco
5.
J Stroke Cerebrovasc Dis ; 29(5): 104749, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32178931

RESUMO

OBJECTIVES: Evaluation of cognitive status is not performed routinely in the acute stroke setting. This study aimed to evaluate the frequency of early cognitive impairment in patients with minor ischemic stroke, analyze the factors associated with early cognitive impairment, and assess functional outcomes. METHODS: In this prospective study, 112 consecutive patients with acute minor ischemic stroke were enrolled. Neuroimages were assessed for semiquantitative evaluation of brain atrophy and small vessel disease (SVD) markers. Cognitive performance was measured within 5 days of onset using Montreal Cognitive Assessment (MoCA) scores. Functional outcome analyses were adjusted for demographic variables, premorbid cognitive status, education level, vascular risk factors, neuroimaging characteristics, stroke severity, and MoCA scores. RESULTS: The median MoCA score was 22, and 63% of patients had cognitive impairment. Factors independently associated with cognitive impairment were education (odds ratios [OR], .79; confidence intervals [CI], .63-.99), smoking (OR, .26; 95%CI, .073-.89), and temporal horn atrophy (OR, 4.73; 95% CI, 1.66-13.49). Factors independently associated with poor functional outcome were total MoCA score (OR, .78; 95%CI, .62-.95) and the sum of 4 MoCA subscores (visuospatial/executive, attention, language, and orientation; OR, .72; 95%CI, .53-.92). The cutoff value of the sum of 4 MoCA subscores for predicting poor outcome was 13 points with 76.5% sensitivity and 81.1% specificity. CONCLUSIONS: Early cognitive impairment was common after minor ischemic stroke and was associated with preexisting temporal horn atrophy but not SVD markers. The sum of 4 MoCA subscores was useful in predicting the functional outcome.


Assuntos
Isquemia Encefálica/complicações , Cognição , Disfunção Cognitiva/etiologia , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Atrofia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Avaliação da Deficiência , Escolaridade , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fumar/efeitos adversos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Lobo Temporal/diagnóstico por imagem , Fatores de Tempo
6.
Anticancer Res ; 37(10): 5829-5835, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28982908

RESUMO

AIM: We report the long-term tumor control and toxicity outcomes of patients undergoing hypofractionated (2.2 Gy) image-guided intensity-modulated radiotherapy (IG-IMRT) using tomotherapy for clinically localized prostate cancer. PATIENTS AND METHODS: We examined the cases of 138 consecutive patients with stage T1-T3 prostate cancer that were treated with IG-IMRT from June 2007 to July 2009. The median follow-up time was 79 months (range=31-96 months). The planning target volume received a dose of 72.6-74.8 Gy in 33-34 fractions (2.2 Gy/fraction). Megavoltage computed tomographic (CT) scans were performed before each treatment and corrected to the registered positions on the planning CT scans using prostate soft-tissue matching. RESULTS: The 5-year biochemical and clinical relapse-free survival rates were 95% for the low-risk group, 92% for the intermediate-risk group, and 77% for the high-risk group. The 5-year incidence rates of grade 2 and 3 late gastrointestinal toxicities were 6.3% and 3.1%, respectively, and those of grade 2 and 3 late genitourinary toxicities were 7.9% and 0%, respectively. Multivariate analysis indicated that T-stage is a prognostic factor for biochemical relapse-free survival rates. CONCLUSION: This report involved the longest followed-up cohort of patients to have received hypofractionated (2.2 Gy) soft tissue-matched IG-IMRT using tomotherapy. The findings of this study indicate that hypofractionated IMRT is well tolerated and is associated with good long-term tumor-control outcomes in patients with localized prostate cancer.


Assuntos
Adenocarcinoma/radioterapia , Neoplasias da Próstata/radioterapia , Hipofracionamento da Dose de Radiação , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Lesões por Radiação/etiologia , Interpretação de Imagem Radiográfica Assistida por Computador , Radioterapia Guiada por Imagem/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
Regul Toxicol Pharmacol ; 86: 199-204, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28288808

RESUMO

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has been conducting a prospective evaluation period to validate the criteria for waiving some carcinogenicity studies in rats. Before the waiving strategy is practiced in ICH, it is crucial to elucidate whether non-neoplastic lesions are found only in 2-year rat carcinogenicity studies. To confirm possible importance of 2-year bioassays for evaluating chronic toxicity but not carcinogenicity, we retrospectively surveyed 59 pharmaceuticals approved by the Ministry of Health, Labour and Welfare (MHLW) from 2007 to 2010 in Japan for non-neoplastic lesions observed in carcinogenicity studies. Non-neoplastic histopathological lesions observed only in 2-year carcinogenicity studies but not in 6-month chronic toxicity studies using rats were compared with clinical adverse drug reactions (ADRs). Thirteen non-neoplastic lesions that may correlate with clinical ADRs were classified into three categories: Category 1, lesions not predictable from other nonclinical data except those from 2-year rat carcinogenicity studies; Category 2, lesions predictable mainly from chronic toxicity studies; Category 3, lesions predictable mainly from pharmacological actions. In the present survey, non-neoplastic lesions only found in 2-year rat carcinogenicity studies were neither significant in terms of frequency and severity nor useful for clinical risk management.


Assuntos
Bioensaio , Testes de Carcinogenicidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Testes de Toxicidade Crônica/métodos , Animais , Humanos , Japão , Estudos Prospectivos , Ratos , Fatores de Tempo
8.
Biologicals ; 44(5): 467-79, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27461129

RESUMO

The development of human cell therapy and gene therapy products has progressed internationally. Efforts have been made to address regulatory challenges in the evaluation of quality, efficacy, and safety of the products. In this forum, updates on the specific challenges in quality, efficacy, and safety of products in the view of international development were shared through the exchange of information and opinions among experts from regulatory authorities, academic institutions, and industry practitioners. Sessions identified specific/critical points to consider for the evaluation of human cell therapy and gene therapy products that are different from conventional biological products; common approaches and practices among regulatory regions were also shared. Certain elements of current international guidelines might not be appropriate to be applied to these products. Further, international discussion on the concept of potency and in vivo tumorigenicity studies, among others, is needed. This forum concluded that the continued collective actions are expected to promote international convergence of regulatory approaches of the products. The Pharmaceuticals and Medical Devices Agency and Japanese Society for Regenerative Medicine jointly convened the forum with support from the National Institutes of Biomedical Innovation, Health and Nutrition. Participants at the forum include 300 experts in and outside of Japan.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Terapia Genética/métodos , Terapia Baseada em Transplante de Células e Tecidos/instrumentação , Congressos como Assunto , Terapia Genética/instrumentação , Humanos
9.
Nihon Rinsho ; 74(1): 120-3, 2016 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-26793891

RESUMO

The purpose of this paper is to provide overview of the latest research trend on technique of radiation therapy of prostate cancer. Three-dimensional conformal radiation therapy(3D -CRT) has achieved better outcome of treatment for prostate cancer than 2-dimensional radiation therapy. Intensity-modulated radiation therapy(IMRT) is considered to be superior to 3D-CRT at certain points. Image-guided (IG) radiation therapy (IGRT), mainly IG-IMRT, is investigated what kind of influence it has on an outcome, both tumor control rate and adverse events. Particle therapy is a most ideal therapy theoretically. There is, however, few evidence which revealed that the therapy is superior to any other modalities.


Assuntos
Hemorragia/etiologia , Neoplasias da Próstata/radioterapia , Lesões por Radiação/etiologia , Humanos , Masculino , Neoplasias da Próstata/patologia , Radioterapia/efeitos adversos , Dosagem Radioterapêutica
12.
Anticancer Res ; 34(12): 7373-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25503175

RESUMO

AIM: To investigate the frequency and characteristics of interfractional rectal displacement in patients with prostate cancer treated with image-guided intensity-modulated radiation therapy (IG-IMRT) using helical tomotherapy. PATIENTS AND METHODS: Data for a total of 256 patients were analyzed. Megavoltage computed tomography (MVCT) images were acquired before radiation therapy and interfractional rectal displacement was assessed with soft-tissue matching by comparing treatment planning images within 9,445 fractions. Anterior rectal region displacement larger than 5 mm, requiring repeated precaution, was defined as the action level of rectal displacement (ARD). RESULTS: ARD was identified in 676 (7.2%) out of 9,445 fractions and at least once in 75% (190/256) of patients. Univariate analysis identified three predisposing factors for ARD: body mass index (BMI), rectal volume and prostate volume. Multivariate logistic regression analysis revealed that lower BMI and large rectal volume were statistically significant predictors of ARD. The highest incidence of ARD (13.6% and 9.1%) was found during the initial two weeks of treatment (first five and next five fractions), after which the incidence decreased to 5.96% (p<0.0001). CONCLUSION: ARD was identified in 7.9% of fractions and in 74.8% of patients and was most likely to occur in patients with a low BMI and/or large rectal volume. ARD occurred predominantly during the initial two weeks of treatment and became less likely over time.


Assuntos
Neoplasias da Próstata/radioterapia , Radioterapia Guiada por Imagem/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Prolapso Retal/patologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Reto/patologia
13.
Anticancer Res ; 34(12): 7383-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25503177

RESUMO

AIM: To analyze intrafractional organ motion in patients with lung cancer treated with image-guided stereotactic body radiotherapy using helical tomotherapy (SBRT-HT). PATIENTS AND METHODS: Data from 25 patients with lung cancer who received 50 Gy/5 fractions of SBRT-HT were analyzed. Slow-scan megavoltage computed tomography (MVCT) images were acquired before (pre-MVCT) and after (post-MVCT) each fraction. We analyzed the imaging quality of the 124 post-MVCT images to identify tumor contours using low-density settings. Next we examined tumor contour deviations from the planning target volume (PTV) in post-MVCT images for intrafractional tumor displacement. RESULTS: Image quality was determined as good in 111/124 images from 22 patients (92%). None of the upper lung tumor images were of poor quality (74 images in 15 patients), whereas lower lung tumors yielded 14 poor-quality images out of the 50 images (3/10 patients). The difference in image quality between upper and lower lung tumors was statistically significant (p<0.01), especially when accompanied by interstitial lung shadows. Deviations in tumor position in post-MVCT images were analyzed in 110 images from 23 patients and revealed 99 images (90%) with tumor contours confined to PTV. In upper lung tumors, 4/74 images in 15 patients (5.4%) showed tumor contour deviations outside PTV. Lower lung tumors showed a higher rate of deviation with 7/36 images in 8 patients (19.4%) showing tumor contour deviations outside PTV (p<0.05). The maximum deviation was 1 mm for upper lung tumors and 2 mm for lower lung tumors. CONCLUSION: Upper lung tumors are good candidates for MVCT image-guided SBRT-HT. However, lower lung tumors, especially those adjacent to the diaphragm or pleura, can be difficult to assess, warranting precise dose delivery by MVCT image-guided SBRT-HT.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Tomografia Computadorizada Espiral/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
J Radiat Res ; 55(6): 1033-47, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25204643

RESUMO

With the advent of modern radiation techniques, we have been able to deliver a higher prescribed radiotherapy dose for localized prostate cancer without severe adverse reactions. We reviewed and analyzed the change of toxicity profiles of external beam radiation therapy (EBRT) from the literature. Late rectal bleeding is the main adverse effect, and an incidence of >20% of Grade ≥2 adverse events was reported for 2D conventional radiotherapy of up to 70 Gy. 3D conformal radiation therapy (3D-CRT) was found to reduce the incidence to ∼10%. Furthermore, intensity-modulated radiation therapy (IMRT) reduced it further to a few percentage points. However, simultaneously, urological toxicities were enhanced by dose escalation using highly precise external radiotherapy. We should pay more attention to detailed quality of life (QOL) analysis, not only with respect to rectal bleeding but also other specific symptoms (such as urinary incontinence and impotence), for two reasons: (i) because of the increasing number of patients aged >80 years, and (ii) because of improved survival with elevated doses of radiotherapy and/or hormonal therapy; age is an important prognostic factor not only for prostate-specific antigen (PSA) control but also for adverse reactions. Those factors shift the main focus of treatment purpose from survival and avoidance of PSA failure to maintaining good QOL, particularly in older patients. In conclusion, the focus of toxicity analysis after radiotherapy for prostate cancer patients is changing from rectal bleeding to total elaborate quality of life assessment.


Assuntos
Neoplasias da Próstata/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Disfunção Erétil/etiologia , Incontinência Fecal/etiologia , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Doenças Urogenitais Masculinas/etiologia , Prognóstico , Qualidade de Vida , Lesões por Radiação/etiologia , Radioterapia Conformacional/efeitos adversos , Doenças Retais/etiologia
15.
J Med Case Rep ; 8: 136, 2014 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-24886457

RESUMO

INTRODUCTION: Radiotherapy is a standard treatment for prostate cancer, and image-guided radiotherapy is increasingly being used to aid precision of dose delivery to targeted tissues. However, precision during radiotherapy cannot be maintained when unexpected intrafraction organ motion occurs. CASE PRESENTATION: We report our experience of internal organ motion caused by persistent gas production in a patient taking an alpha-glucosidase inhibitor. A 68-year-old Japanese man with prostate cancer visited our institution for treatment with helical tomotherapy. He suffered from diabetes mellitus and took an alpha-glucosidase inhibitor. Routine treatment planning computed tomography showed a large volume of rectal gas; an enema was given to void the rectum. Subsequent treatment planning computed tomography again showed a large volume of gas. After exercise (walking) to remove the intestinal gas, a third scan was performed as a test scan without tight fixation, which showed a sufficiently empty rectum for planning. However, after only a few minutes, treatment planning computed tomography again showed extreme accumulation of gas. Therefore, we postponed treatment planning computed tomography and consulted his doctor to suspend the alpha-glucosidase inhibitor, which was the expected cause of his persistent gas. Four days after the alpha-glucosidase inhibitor regimen was suspended, we took a fourth treatment planning computed tomography and made a treatment plan without gas accumulation. Thereafter, the absence of rectal gas accumulation was confirmed using daily megavolt computed tomography before treatment, and the patient received 37 fractions of intensity-modified radiotherapy at 74 Gy without rectal gas complications. In this case study, the alpha-glucosidase inhibitor induced the accumulation of intestinal gas, which may have caused unexpected organ motion, untoward reactions, and insufficient doses to clinical targets. CONCLUSIONS: We suggest that patients who are taking an alpha-glucosidase inhibitor for diabetes should discontinue use of that particular medicine prior to beginning radiotherapy.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Flatulência/induzido quimicamente , Inibidores de Glicosídeo Hidrolases/efeitos adversos , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Idoso , Diabetes Mellitus Tipo 2/complicações , Flatulência/diagnóstico por imagem , Humanos , Masculino , Neoplasias da Próstata/complicações , Reto/diagnóstico por imagem , Tomografia Computadorizada por Raios X
16.
J Radiat Res ; 55(3): 575-82, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24457315

RESUMO

To analyze outcomes and toxicities of stereotactic body radiotherapy with helical tomotherapy (HT-SBRT) for inoperable lung tumors, the medical records of 30 patients with 31 lung tumors treated with HT-SBRT were reviewed. The 3-year local control, cause-specific survival and overall survival rates (LC, CCS and OS, respectively) were analyzed using the Kaplan-Meier method. Toxicities were graded using Common Terminology Criteria for Adverse Events ver. 4. To investigate the factors associated with Grade 5 radiation pneumonitis (G5 RP), several parameters were analyzed: (i) patient-specific factors (age, gross tumor volume and PTV, and the interstitial pulmonary shadow on pretreatment CT); and (ii) dosimetry-specific factors (conformity index, homogeneity index, mean lung dose, and V5, V10, V15, V20 and V25 of the total lungs). The median duration of observation for all patients was 36.5 months (range, 4-67 months). The 3-year LC, CCS and OS were 82, 84 and 77%, respectively. Regarding Grade 3 or higher toxicities, two patients (6.7%) developed G5 RP. GTV was significantly associated with G5 RP (P = 0.025), and there were non-significant but slight associations with developing G5 RP for V5 (P = 0.067) and PTV (P = 0.096). HT-SBRT led to standard values of LC, CCS and OS, but also caused a markedly higher incidence of G5 RP. It is essential to optimize patient selection so as to avoid severe radiation pneumonitis in HT-SBRT.


Assuntos
Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Pneumonite por Radiação/classificação , Pneumonite por Radiação/mortalidade , Radiocirurgia/mortalidade , Radioterapia de Intensidade Modulada/mortalidade , Idoso , Idoso de 80 Anos ou mais , Causalidade , Terapia Combinada/mortalidade , Comorbidade , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento
17.
Anticancer Res ; 33(12): 5507-10, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24324089

RESUMO

AIM: To evaluate the incidence of rectal toxicity in patients undergoing hypofractionated (2.2 Gy) image-guided intensity-modulated radiotherapy (IG-IMRT) for prostate cancer. PATIENTS AND METHODS: We examined 117 consecutive patients with prostate cancer who underwent IG-IMRT from June 2007 to July 2009. The median follow-up time was 32 months (range 20-42 months). The clinical target volume (CTV) consisted of the prostate and seminal vesicles, and the planning target volume (PTV) consisted of the CTV plus a 5-mm expansion, not avoiding the rectum. The PTV received a dose of 72.6-74.8 Gy in 33-34 fractions (2.2 Gy/fraction). Megavoltage computed tomographic (MVCT) scans were performed before each treatment and corrected to the registered position for planning CT scans using prostate soft tissue matching. RESULTS: Late rectal bleeding of grades 1, 2, and 3 (Common Terminology Criteria for Adverse Events v3.0) occurred in 19 (16%), five (4%), and four (3%) patients, respectively. Late urinary toxicities of grades 1 and 2 occurred in five (4.3%) and eight (6.8%) patients, respectively. We found a paradoxically increased risk of rectal bleeding with more accurate irradiation of the rectum using soft tissue matching, whereas only a small percentage was reported in other IMRT series. CONCLUSION: IG-IMRT using daily MVCT scans allowed for exact dose delivery, which resulted in an increased rectal dose and exceptionally high incidence of rectal toxicity. Therefore, careful PTV contouring and dose schedule settings are important for safe administration of IG-IMRT.


Assuntos
Fracionamento da Dose de Radiação , Rim/efeitos da radiação , Pessoa de Meia-Idade , Neoplasias da Próstata/radioterapia , Humanos , Incidência , Masculino
18.
Anticancer Res ; 33(12): 5675-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24324116

RESUMO

AIM: To analyze an intrafractional organ motion for patients with prostate cancer using soft tissue matching by megavolt computed tomography (MVCT) images during the course of image-guided intensity-modulated radiotherapy (IGRT-IMRT) using helical tomotherapy. PATIENTS AND METHODS: Data from a total of 10 patients with prostate cancer who received IGRT-IMRT were analyzed, and MVCT images were acquired before and after radiation therapy. Intra-fractional movement and PTV margins for soft tissue matching were calculated by comparing treatment planning images with 740 MVCT images for right-left (RL), superior-inferior (SI), and anteroposterior (AP) dimensions. A total of 74 Gy/37 fractions were administered. A margin to compensate for these variations was calculated using the van Herk's equation. RESULTS: The intrafractional motion was 0.03 (-1.3 to 1.4) ±0.39 mm in the RL dimension, 0.08 (-1.8 to 0.28) ±0.73 mm in the SI dimension, and 0.52 (-1.8 to 1.8) ±0.63 mm in the AP dimension. The required PTV margin was 0.60 mm, 1.10 mm, and 0.78 mm in the RL, SI, and AP dimensions, respectively. Only one patient exhibited a deviation greater than 5 mm only once in 37 fractions (1/370=0.2%) caused by anal contraction. CONCLUSION: The PTV margin in soft tissue matching IGRT-IMRT by helical tomotherapy for a patient with prostate cancer was 3 mm or less, and our tentative PTV margin of 3-5 mm is sufficient for most patients, if adequate instruction for avoiding anal contraction is given.


Assuntos
Fracionamento da Dose de Radiação , Neoplasias da Próstata/radioterapia , Radioterapia Guiada por Imagem , Radioterapia de Intensidade Modulada/métodos , Humanos , Masculino
19.
Anticancer Res ; 33(6): 2453-6, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23749895

RESUMO

AIM: To evaluate an appropriate planning target volume (PTV) margin in for one to three vertebral metastases using megavolt computed tomography (MVCT) images during the course of image-guided and stereotactic intensity-modulated radiotherapy (IGRT-IMRT) by use of helical tomotherapy. PATIENTS AND METHODS: A total of 25 lesions in 24 patients with vertebral metastases who received IGRT-IMRT were analyzed. MVCT images were acquired before and after radiation therapy. Intra-fractional movement and PTV margin were calculated by comparing treatment planning images and these 310 MVCT images for right-left (RL), superior-inferior (SI), and anteroposterior (AP) dimensions. Five patients were treated by 35 Gy/5 fractions, 17 by 30 Gy/5 fractions, one by 25 Gy/5 fractions, and one by 60 Gy/30 fractions. A margin to compensate for these variations was calculated with the formula of vanHerk's equation. RESULTS: The intra-fractional motion was 0.02 (-1.3 to 1.4) ± 0.34 mm in the RL direction, -0.09 (-1.8 to 0.28) ± 0.44 mm in the SI direction, and 0.20 (-1.8 to 1.8) ± 0.36 mm in the AP direction. The required PTV margin was 0.98 mm in the RL direction, 0.69 mm in the SI direction, and 1.26 mm in the AP direction. No patient showed a deviation greater than 2 mm. CONCLUSION: The PTV margin in hypofractionated IGRT-IMRT, using helical tomotherapy for a few vertebral metastases, was 2 mm or less and our tentative PTV margin of 5 mm was sufficient and reducible.


Assuntos
Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Neoplasias da Coluna Vertebral/radioterapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia Conformacional , Neoplasias da Coluna Vertebral/secundário , Tomografia Computadorizada por Raios X
20.
Anticancer Res ; 33(4): 1679-84, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23564815

RESUMO

AIM: To examine the compatibility of the measured and calculated dose for the treatment of lung lesions by helical tomotherapy. MATERIALS AND METHODS: The administered dose was measured a total of 55 times at 22 points with a radiophotoluminescence glass dosimeter (RPLGD) inserted in the position of an anthropomorphic Rando Phantom. Two Gy were prescribed and calculated with a tomotherapy planning machine for a 3-cm diameter spherical planning target volume (PTV) created in the lung area. Compatibility (measured dose/calculated dose and σ value=(D(meas)-D(calc))/D(prescribed)) × 100 (%)) was analyzed according to dosimeter location. RESULTS: Deviations between measured and calculated doses for the lung lesion were within 4% for planning target volume, indicating that adequate dose delivery to the PTV was achievable. On the other hand, we found dose deviations up to 15% for the lower prescribed dose range (64% or less) for the measured dose/calculated comparison and a 6% deviation according to the σ value in or near inhomogeneous tissue. CONCLUSION: Although the measured dose satisfied the clinical requirement in almost all areas including PTV, we should note that there may be discrepancies between expected calculated dose and irradiated dose in or near inhomogeneous area.


Assuntos
Pneumopatias/radioterapia , Imagens de Fantasmas , Monitoramento de Radiação/instrumentação , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Dosimetria Termoluminescente , Adulto , Relação Dose-Resposta à Radiação , Feminino , Humanos , Monitoramento de Radiação/métodos
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