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1.
Artigo em Inglês | MEDLINE | ID: mdl-32240774

RESUMO

PURPOSE: A prospective trial of proton therapy for breast cancer revealed an increased rib fracture rate of 7%, which is higher than the expected rate based on the literature on photon therapies. We aim to evaluate the hypothesis that the increased relative biological effectiveness (RBE) at the distal edge of proton beams is the cause. METHODS AND MATERIALS: We combined the cohort from the prospective clinical trial and a retrospective cohort from a database. Monte Carlo simulations were performed to recalculate the physical dose and dose-averaged linear energy transfer (LETd). The first 10 ribs and fracture areas in patients with fractures were contoured and deformably registered. The LETd-weighted dose was used as a surrogate for biological effectiveness and compared with the conventional fixed RBE of 1.1. Dose to 0.5 cm3 of the ribs (D0.5) was selected to analyze the dose-response relationship using logistic regression. We chose an alpha/beta ratio of 3 to calculate the biological effective dose in Gy3(RBE). RESULTS: Thirteen of 203 patients in the cohorts exhibited a total of 25 fractures. The LETd in fractured areas is increased (6.1 ± 2.0 keV/µm, mean ± standard deviation), suggesting possible end-of-range radiobiological effects with increased RBE. The D0.5 of the fractured ribs is 80.3 ± 9.4 Gy3(RBE) with a generic factor of 1.1 and is relatively low compared with historical photon results. On the other hand, the D0.5 of the fractured ribs is 100.0 ± 12.5 Gy3(RBE) using the LETd-based model with a dose-response curve that is more consistent with historical photon data. CONCLUSIONS: The increased rib fracture rate seen in our trial is probably associated with the increased LETd and RBE at the distal edge of proton beams. This phenomenon warrants further investigation and possible integration of LETd into treatment planning and optimization in proton therapy.

2.
Cancer Epidemiol Biomarkers Prev ; 29(3): 558-564, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32051189

RESUMO

BACKGROUND: Infections account for about 15% of human cancers globally. Although abnormal hematologic profiles and bone marrow suppression are common in patients with dengue, whether dengue is associated with a higher risk of leukemia has not been investigated. METHODS: We conducted a nationwide population-based cohort study by analyzing the National Health Insurance Research Databases in Taiwan. Laboratory-confirmed dengue patients between 2002 and 2011 were identified; five matched non-dengue controls were randomly selected for each patient. Follow-up ended on December 31, 2015. Multivariate Cox proportional hazard regression models were used to evaluate the effect of dengue virus infection on the risk of leukemia. Cancers other than leukemia were used as falsification endpoints to evaluate the validity of this study. RESULTS: We identified 12,573 patients with dengue and 62,865 non-dengue controls. Patients with dengue had a higher risk of leukemia [adjusted HR, 2.03; 95% confidence interval (CI), 1.16-3.53]. Stratified analyses by different follow-up periods showed that dengue virus infection was significantly associated with a higher risk of leukemia only between 3 and 6 years after infection (adjusted HR, 3.22; 95% CI, 1.25-8.32). There was no significant association between dengue and the risk of other cancers. CONCLUSIONS: This study provides the first epidemiologic evidence for the association between dengue virus infection and leukemia. IMPACT: Considering the rapidly increasing global incidence of dengue and the burden of leukemia, further studies are required to verify this association and to unravel the potential mechanisms of pathogenesis.

3.
Am J Epidemiol ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31781756

RESUMO

Random-effects meta-analysis is one of the mainstream methods for research synthesis. The heterogeneity in meta-analyses is usually assumed to follow a normal distribution. This is actually a strong assumption, but one that often receives little attention and is used without justification. Although methods for assessing the normality assumption are readily available, they cannot be used directly because the included studies have different within-study standard errors. We present a standardization framework for evaluation of the normality assumption and examine its performance in random-effects meta-analyses with simulation studies and real examples. We use both a formal statistical test and a quantile-quantile plot for visualization. Simulation studies show that our normality test has well-controlled type I error rates and reasonable power. We also illustrate the real-world significance of examining the normality assumption with examples. Investigating the normality assumption can provide valuable information for further analysis or clinical application. We recommend routine examination of the normality assumption with the proposed framework in future meta-analyses.

4.
Head Neck ; 41(9): 3201-3210, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31116482

RESUMO

BACKGROUND: We hypothesized that patients with head and neck squamous cell carcinoma (HNSCC) with smoking cessation during curative chemoradiotherapy (CRT) had fewer complications and lower tumor progression risks. METHODS: Sixty-three patients with nonmetastatic HNSCC who were smokers at diagnosis (carbon monoxide [CO] breath concentrations ≥3 ppm) and underwent curative CRT were prospectively enrolled. Successful smoking cessation throughout CRT was confirmed by CO breath concentrations <3 ppm at CRT completion. RESULTS: Forty-one patients (65%) successfully discontinued smoking throughout CRT. With a median 33-month follow-up, patients with successful smoking cessation during CRT had significantly fewer, greater, and lower probabilities of grade ≥3 acute toxicities (P = .01), progression-free survival (P = .03), and permanent gastrostomy or tracheostomy (P = .04), respectively, than those continuing smoking throughout CRT. In multivariate analysis, successful smoking cessation during CRT significantly reduced tumor progression risks (hazard ratio: 0.4, P = .05). CONCLUSION: Smoking cessation during curative CRT reduced treatment-related toxicities and tumor progression risks in patients with HNSCC.

5.
Res Synth Methods ; 10(2): 255-266, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30835918

RESUMO

A systematic review and meta-analysis is an important step in evidence synthesis. The current paradigm for meta-analyses requires a presentation of the means under a random-effects model; however, a mean with a confidence interval provides an incomplete summary of the underlying heterogeneity in meta-analysis. Prediction intervals show the range of true effects in future studies and have been advocated to be regularly presented. Most commonly, prediction intervals are estimated assuming that the underlying heterogeneity follows a normal distribution, which is not necessarily appropriate. In this article, we provide a simple method with a ready-to-use spreadsheet file to estimate prediction intervals and predictive distributions nonparametrically. Simulation studies show that this new method can provide approximately unbiased estimates compared with the conventional method. We also illustrate the advantage and real-world significance of this approach with a meta-analysis evaluating the protective effect of vaccination against tuberculosis. The nonparametric predictive distribution provides more information about the shape of the underlying distribution than does the conventional method.


Assuntos
Intervalos de Confiança , Metanálise como Assunto , Tuberculose/prevenção & controle , Vacinação/métodos , Algoritmos , Simulação por Computador , Interpretação Estatística de Dados , Humanos , Modelos Estatísticos , Distribuição Normal , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Literatura de Revisão como Assunto
6.
Anticancer Res ; 38(3): 1569-1577, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29491087

RESUMO

BACKGROUND: The association of extended lymph node (LN) dissection with improved outcomes in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who received preoperative chemoradiotherapy (CRT) followed by surgery is debatable. PATIENTS AND METHODS: We reviewed data from patients with esophageal cancer enrolled in three phase II clinical trials of preoperative paclitaxel and cisplatin-based CRT during 2000-2012. Patients with ESCC who underwent planned esophagectomy were enrolled. The number of resected LNs and other clinicopathological factors were analyzed regarding their impact on progression-free (PFS) and overall (OS) survival using Cox proportional hazards model. RESULTS: In total, 139 patients were included. The median PFS and OS were 24.4 and 31.8 months, respectively. The median number of resected and positive LNs were 19 (range=2-96) and 0 (range=0-9), respectively. The mean number of positive LNs did not differ significantly among quartile groups of total resected LNs (quartile 1: 2-12, 2: 13-19, 3: 20-29, and 4: 30-96). The resected LN number analyzed as dichotomies divided by the median or as continuous variables was not associated with PFS or OS. However, in an exploratory analysis, patients of quartiles 2 and 3 had longer PFS and OS than those with quartiles of 1 and 4 in multivariate analysis (p=0.019 and 0.005, respectively). CONCLUSION: Although extensive LN dissection was not associated with improved survival, resection of 13-29 LNs was associated with improved survival in patients with locally advanced ESCC receiving preoperative paclitaxel and cisplatin-based CRT.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Excisão de Linfonodo , Linfonodos/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/cirurgia , Quimiorradioterapia , Ensaios Clínicos Fase II como Assunto , Neoplasias Esofágicas/cirurgia , Esofagectomia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , /estatística & dados numéricos , Período Pré-Operatório , Modelos de Riscos Proporcionais
7.
J Surg Oncol ; 117(3): 497-505, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29284067

RESUMO

BACKGROUND: Population-based studies evaluating outcomes of different approaches for rectal cancer are scarce. METHODS: We conducted a retrospective cohort study using the Nationwide Inpatient Sample database between 2008 and 2012. We compared the outcomes and costs among rectal cancer patients undergoing robotic, laparoscopic, or open surgeries using propensity scores for adjusted and matched analysis. RESULTS: We identified 194 957 rectal cancer patients. Over the 5-year period, the annual admission number decreased by 13.9%, the in-hospital mortality rate decreased by 32.2%, while the total hospitalization cost increased by 13.6%. Compared with laparoscopic surgery, robotic surgery had significantly lower length of stay (LOS) (OR 0.69, 95%CI 0.57-0.84), comparable wound complications (OR 1.08, 95%CI 0.70-1.65) and higher cost (OR 1.42, 95%CI 1.13-1.79), while open surgery had significantly longer LOS (OR 1.38, 95%CI 1.19-1.59), more wound complications (OR 1.49, 95%CI 1.08-1.79), and comparable cost (OR 0.92, 95%CI 0.79-1.07). There were no difference in in-hospital mortality among three approaches. CONCLUSIONS: Laparoscopic surgery was associated with better outcomes than open surgery. Robotic surgery was associated with higher cost, but no advantage over laparoscopic surgery in terms of mortality and complications. Studies on cost-effectiveness of robotic surgery may be warranted.


Assuntos
Laparoscopia/estatística & dados numéricos , Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Idoso , Estudos de Coortes , Análise Custo-Benefício , Feminino , Humanos , Pacientes Internados/estatística & dados numéricos , Laparoscopia/economia , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Neoplasias Retais/economia , Neoplasias Retais/epidemiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/economia , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Estados Unidos/epidemiologia
8.
Sci Rep ; 7(1): 2006, 2017 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-28515452

RESUMO

Limited data are available for the epidemiology and outcome of colorectal cancer in relation to the three main surgical treatment modalities (open, laparoscopic and robotic). Using the US National Inpatient Sample database from 2004 to 2012, we identified 1,265,684 hospitalized colorectal cancer patients. Over the 9 year period, there was a 13.5% decrease in the number of hospital admissions and a 43.5% decrease in in-hospital mortality. Comparing the trend of surgical modalities, there was a 35.4% decrease in open surgeries, a 3.5 fold increase in laparoscopic surgeries, and a 41.3 fold increase in robotic surgeries. Nonetheless, in 2012, open surgery still remained the preferred surgical treatment modality (65.4%), followed by laparoscopic (31.2%) and robotic surgeries (3.4%). Laparoscopic and robotic surgeries were associated with lower in-hospital mortality, fewer complications, and shorter length of stays, which might be explained by the elective nature of surgery and earlier tumor grades. After excluding patients with advanced tumor grades, laparoscopic surgery was still associated with better outcomes and lower costs than open surgery. On the contrary, robotic surgery was associated with the highest costs, without substantial outcome benefits over laparoscopic surgery. More studies are required to clarify the cost-effectiveness of robotic surgery.


Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/história , Neoplasias Colorretais/mortalidade , Bases de Dados Factuais , Feminino , Pesquisas sobre Serviços de Saúde , História do Século XXI , Humanos , Incidência , Pacientes Internados , Masculino , Mortalidade , Fatores de Risco , Fatores Socioeconômicos , Resultado do Tratamento , Estados Unidos
9.
Asian J Androl ; 19(5): 596-601, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27506334

RESUMO

The benefit of androgen-deprivation therapy (ADT) in combination with dose-escalated radiotherapy (DERT) for localized prostate cancer has not been determined in randomized studies. In this study, the benefit of ADT was assessed in patients uniformly treated with dose-escalated intensity-modulated radiation therapy (IMRT) to the prostate and seminal vesicles but not pelvis. In all, 419 patients with localized prostate adenocarcinoma underwent definitive IMRT (cumulative dose 78 Gy), with 32.6%, 33.1%, 32.1%, and 2.1% having T1 through T4 disease, respectively, and 51.2% having high-risk disease. ADT was given to 76.1% of patients. With a median follow-up of 60 months, 5-year biochemical failure-free, disease-free, and overall survival rates were 87%, 86%, and 87%, respectively. T stage was an independent predictor of all three rates. Five-year pelvic nodal recurrence rate was 2.9%. ADT improved biochemical failure-free and disease-free survival but not overall survival. ADT showed benefit in high-risk disease but not intermediate-risk disease. Late gastrointestinal and genitourinary toxicities ≥ grade 2 occurred in 11.0% and 6.7%, respectively. In conclusion, DERT with 78 Gy yields good disease control and low rate of pelvic nodal recurrence. ADT improves disease-free survival in patients with high-risk but not intermediate-risk disease.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Pelve/efeitos da radiação , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/terapia , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Relação Dose-Resposta à Radiação , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Análise de Sobrevida , Falha de Tratamento , Resultado do Tratamento
10.
Oncotarget ; 7(28): 44224-44235, 2016 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-27317764

RESUMO

We investigated the outcomes and the associated clinical-pathological factors in patients with prostate cancer (PCa) undergoing salvage intensity modulated radiation therapy (IMRT) for post-radical-prostatectomy (RP) biochemical failure. We report clinical outcomes of post-RP salvage IMRT, and describe chronic toxicity in these patients.Fifty patients with PCa underwent post-RP salvage IMRT. The median dose of IMRT was 70 Gy to the prostatic and seminal vesicle bed. Clinical-pathological and toxicity information were collected. The prostate cancer-specific survival (PCSS), disease-free survival (DFS), and biochemical-failure-free survival (BFFS) were calculated. Prognostic factors were analyzed for their association with disease control.The median follow-up time was 74 months. The 5-year PCSS, DFS, and BFFS after salvage IMRT were 95%, 88%, and 60%, respectively. Two patients (4%) experienced late gastrointestinal toxicity ≥ grade 3, and 5 patients (10%) had late genitourinary toxicity ≥ grade 3. On multivariate analysis, post-RP prostate-specific antigen (PSA) nadir ≤0.1 ng/ml (P=0.018) and PSA ≤0.5 ng/ml at salvage IMRT (P=0.016) were independent factors predicting better BFFS. Patients with both post-RP PSA nadir ≤0.1 ng/ml and PSA ≤0.5 ng/ml at salvage IMRT had a 5-year BFFS of 83% as compared with 43% in other patients (P=0.001).In conclusion, with hormonal therapy in most PCa patients, the addition of salvage IMRT for post-RP biochemical failure can achieve a good outcome with low toxicity. Patients with a post-RP PSA nadir ≤0.1 ng/ml and PSA ≤0.5 ng/ml at salvage IMRT could benefit the most from salvage IMRT.


Assuntos
Calicreínas/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Terapia de Salvação/efeitos adversos , Terapia de Salvação/métodos , Resultado do Tratamento
11.
Chronobiol Int ; 33(2): 210-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26818960

RESUMO

This retrospective study tested the hypothesis that disease control and treatment-related toxicity in patients undergoing high-dose radiotherapy (HDRT) for prostate cancer varies in a circadian manner. Patients with localized prostate adenocarcinoma receiving HDRT (median 78 Gy) to the prostate and involved seminal vesicle(s) without elective pelvic irradiation were divided into a daytime treatment (before 5 PM) group (n = 267) and evening treatment (after 5 PM) group (n = 142). Biochemical failure (Phoenix definition), acute and late gastrointestinal (GI) and genitourinary toxicities (Common Terminology Criteria for Adverse Events version 4), biochemical failure-free survival (BFFS) and freedom from late toxicity were assessed. Analyses were performed by binary logistic regression and Cox proportional hazard regression. The median follow-up was 68 months, and 75% of patients were ≥70 years old. Evening HDRT was significantly associated with worse freedom from ≥grade 2 late GI complications (hazard ratio = 2.96; p < 0.001). The detrimental effect of evening HDRT was significant in patients older than 70 years old (p < 0.001) but not in younger patients (p = 0.63). In a subgroup of propensity score-matched cohort with T2b-T3 disease (n = 154), the 5-year BFFS was worse in the evening group than the daytime group (72% vs. 85%, hazard ratio = 1.95, p = 0.05). Our study indicates that evening HDRT may lead to more GI complications, especially in older patients, and worse BFFS in patients with T2b-T3 disease.


Assuntos
Adenocarcinoma/radioterapia , Ritmo Circadiano/fisiologia , Próstata/metabolismo , Neoplasias da Próstata/radioterapia , Adenocarcinoma/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
12.
World J Surg Oncol ; 13: 312, 2015 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-26545980

RESUMO

BACKGROUND: The prognostic factors for the recurrence of lymph node (LN) metastasis after dose-escalated radiotherapy (RT) in prostate cancer patients have not been well investigated. We report the prognostic factors and outcomes in patients receiving salvage treatment for LN recurrence after high-dose intensity-modulated RT (IMRT). METHODS: We studied a cohort of 419 patients with localized prostate adenocarcinoma undergoing definitive IMRT (78 Gy). LN recurrence was diagnosed by size criteria using computed tomography (CT) or magnetic resonance imaging, or abnormal uptake of (18)F-fluorocholine by LNs on positron emission tomography/CT. Overall survival and LN recurrence-free survival (LNRFS) were calculated, and prognostic factors were evaluated. RESULTS: With a median follow-up of 60 months, 18 patients (4.3 %) had LN recurrence and a significantly lower 5-year overall survival rate (60 vs. 90 %, p = 0.003). Univariate analysis showed that T3/T4 stage (p = 0.003), Gleason score >7 (p < 0.001), and estimated risk of pelvic LN involvement of >30 % by the Roach formula (p = 0.029) were associated with significantly lower LNRFS. On multivariate analysis, high Gleason score (hazard ratio = 5.99, p = 0.007) was the only independent factor. The 1/2-year overall survivals after LN recurrence were 67/54 %. Patients with isolated LN recurrence (p = 0.003), prostate-specific antigen (PSA) doubling time >5 months (p = 0.009), interval between PSA nadir and biochemical failure >12 months (p = 0.035), and PSA <10 ng/ml at LN recurrence (p = 0.003) had significantly better survival. Patients with isolated LN recurrence had significantly better survival when treated with combined RT and hormones than when treated with hormones alone (p = 0.011). CONCLUSIONS: Gleason score of >7 may predict LN recurrence in prostate cancer patients treated with definitive IMRT. Small number of patients limits the extrapolation of this risk with the primary treatment strategy. Combined RT and hormones may prolong survival in patients with isolated LN recurrence.


Assuntos
Adenocarcinoma/radioterapia , Recidiva Local de Neoplasia/radioterapia , Neoplasias da Próstata/radioterapia , Radioterapia de Intensidade Modulada/mortalidade , Terapia de Salvação/mortalidade , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Seguimentos , Humanos , Masculino , Gradação de Tumores , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Taxa de Sobrevida
13.
Radiother Oncol ; 115(1): 9-15, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25819996

RESUMO

BACKGROUND AND PURPOSE: To assess the usefulness of pathological stage according to the 7th edition of the Union for International Cancer Control-American Joint Committee on Cancer (UICC-AJCC) as a prognostic tool in patients undergoing neoadjuvant chemoradiation followed by esophagectomy (trimodality therapy, TMT) for locally advanced esophageal squamous cell carcinoma. MATERIAL AND METHODS: One hundred twenty-five eligible patients completing TMT were enrolled for analysis. The clinical (cTNM7) and pathological (ypTNM7) stage groups of their tumors were prospectively classified, and re-grouped by the 6th edition (ypTNM6). Survival was analyzed using the Kaplan-Meier method. The Cox proportional hazard model and the Akaike information criterion (AIC) were used to compare the performance of staging systems. RESULTS: With a median follow-up of 24.6 months, 54 patients (43.2%) died. Forty patients (32%) achieved pathological complete remission (pCR). The median survival was 31.8 months. On multivariate analysis, ypTNM7 (but not pCR or pN) was the only independent factor affecting overall survival (p<0.001). The ypTNM7 was superior to cTNM7 or ypTNM6 in predicting both overall and recurrence-free survival after TMT based on AIC values and Cox proportional hazard model analysis. CONCLUSIONS: In patients with locally advanced esophageal squamous cell carcinoma undergoing TMT, ypTNM7 is the best predictor of survival.


Assuntos
Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Neoplasias Esofágicas/terapia , Terapia Neoadjuvante , Adulto , Idoso , Carcinoma de Células Escamosas do Esôfago , Esofagectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais
14.
World J Surg Oncol ; 12: 329, 2014 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-25373828

RESUMO

BACKGROUND: We aimed to evaluate early clinical and pathological results for treating locally advanced rectal cancer with bevacizumab and neoadjuvant concurrent chemoradiotherapy using the technique of prone-position volumetric modulated arc therapy and to compare the toxicity of volumetric modulated arc therapy with that of supine-position four-field box radiotherapy. METHODS: Twelve patients with stage IIA to IVA rectal adenocarcinoma, treated with neoadjuvant concurrent chemoradiotherapy (45 Gy in 25 fractions to the rectal tumor and pelvic lymphatics) and bevacizumab, were prospectively enrolled. Chemotherapy included FOLFOX (leucovorin, fluorouracil, and oxaliplatin) (n=11) and 5-fluorouracil (n=1). All patients received prone-position volumetric modulated arc therapy. A historical cohort treated with supine-position box radiotherapy, including six other patients treated with bevacizumab-based concurrent chemoradiotherapy in our hospital, was used for comparison. Setup errors, toxicities, and potential biomarkers were evaluated. RESULTS: All patients completed neoadjuvant concurrent chemoradiotherapy and underwent total mesorectal excision. Four (33.3%) patients had pathological complete response. Significantly more grade 2 or 3 diarrhea was associated with the supine-box technique (5/6 versus 2/12, P=0.01). The magnitude of setup errors was similar between the supine-box and prone volumetric modulated arc therapy techniques. The estimated 2-year survival and 2-year failure-free survival rates were 100% and 72.9% in the prone volumetric modulated arc therapy group and 66.7% and 66.7% in the supine box group, respectively. CONCLUSIONS: The early clinical outcome has been encouraging. Volumetric modulated arc therapy in prone-positioned patients was technically advantageous and reduced bowel toxicity.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Retais/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Estudos de Coortes , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Prognóstico , Radioterapia de Intensidade Modulada , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Indução de Remissão , Taxa de Sobrevida
15.
Psychiatry Clin Neurosci ; 65(1): 95-7, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21265942

RESUMO

This study examined prolactin levels, sexual function and clinical improvement after switching to aripiprazole from risperidone. Nine schizophrenic male Chinese patients who reported risperidone-induced sexual dysfunction were studied. Clinical Global Impression Scale Scores for Severity (CGI-S), Clinical Global Impression Scale Scores for Improvement (CGI-I), Arizona Sexual Experience Scale results and serum prolactin concentrations were determined over 16 weeks. After treatment with aripiprazole, all patients showed reduced serum prolactin (26.54 ± 17.03 ng/mL to 3.71 ± 1.87 ng/mL, P=0.008) and five reported improved sexual function. Mean baseline CGI-S (5.11 ± 0.93) decreased to 3.78 ± 1.39 (P=0.010) by week 16. Compared to baseline (4.0), the mean CGI-I significantly declined by the end of the study (3.44 ± 0.53, P=0.025).


Assuntos
Antipsicóticos/efeitos adversos , Piperazinas/efeitos adversos , Prolactina/sangue , Quinolonas/efeitos adversos , Risperidona/efeitos adversos , Esquizofrenia/tratamento farmacológico , Disfunções Sexuais Fisiológicas/induzido quimicamente , Adulto , Antipsicóticos/uso terapêutico , Aripiprazol , Humanos , Masculino , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Escalas de Graduação Psiquiátrica , Quinolonas/uso terapêutico , Risperidona/uso terapêutico
16.
J Cell Biochem ; 107(5): 933-43, 2009 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-19459161

RESUMO

Astrocytes, the most abundant glial cell population in the central nervous system (CNS), play physiological roles in neuronal activities. Oxidative insult induced by the injury to the CNS causes neural cell death through extrinsic and intrinsic pathways. This study reports that reactive oxygen species (ROS) generated by exposure to the strong oxidizing agent, hexavalent chromium (Cr(VI)) as a chemical-induced oxidative stress model, caused astrocytes to undergo an apoptosis-like cell death through a caspase-3-independent mechanism. Although activating protein-1 (AP-1) and NF-kappaB were activated in Cr(VI)-primed astrocytes, the inhibition of their activity failed to increase astrocytic cell survival. The results further indicated that the reduction in mitochondrial membrane potential (MMP) was accompanied by an increase in the levels of ROS in Cr(VI)-primed astrocytes. Moreover, pretreatment of astrocytes with N-acetylcysteine (NAC), the potent ROS scavenger, attenuated ROS production and MMP loss in Cr(VI)-primed astrocytes, and significantly increased the survival of astrocytes, implying that the elevated ROS disrupted the mitochondrial function to result in the reduction of astrocytic cell viability. In addition, the nuclear expression of apoptosis-inducing factor (AIF) and endonuclease G (EndoG) was observed in Cr(VI)-primed astrocytes. Taken together, evidence shows that astrocytic cell death occurs by ROS-induced oxidative insult through a caspase-3-independent apoptotic mechanism involving the loss of MMP and an increase in the nuclear levels of mitochondrial pro-apoptosis proteins (AIF/EndoG). This mitochondria-mediated but caspase-3-independent apoptotic pathway may be involved in oxidative stress-induced astrocytic cell death in the injured CNS.


Assuntos
Astrócitos/citologia , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Acetilcisteína/farmacologia , Animais , Fator de Indução de Apoptose/metabolismo , Astrócitos/efeitos dos fármacos , Astrócitos/enzimologia , Caspase 3 , Morte Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Células Cultivadas , Cromo/toxicidade , Citoproteção/efeitos dos fármacos , DNA/metabolismo , Endodesoxirribonucleases/metabolismo , Ativação Enzimática/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , NF-kappa B/metabolismo , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ligação Proteica/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fator de Transcrição AP-1/metabolismo
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