RESUMO
Twenty-two novel longifolene-derived diphenyl ether-carboxylic acid compounds 7a-7v were synthesized from renewable biomass resources longifolene, and their structures were confirmed by FT-IR, 1H NMR, 13C NMR, and HRMS. The preliminary evaluation of in vitro antifungal activity displayed that compound 7b presented inhibition rates of 85.9%, 82.7%, 82.7%, and 81.4% against Alternaria solani, Cercospora arachidicola, Rhizoctonia solani, and Physalospora piricola, respectively, and compound 7l possessed inhibition rates of 80.7%, 80.4%, and 80.3% against R. solani, C. arachidicola, P. piricola, respectively, exhibiting excellent and broad-spectrum antifungal activities. Besides, compounds 7f and 7a showed significant antifungal activities with inhibition rates of 81.2% and 80.7% against A.solani, respectively. Meanwhile, a reasonable and effective 3D-QSAR mode (r2 = 0.996, q2 = 0.572) has been established by the CoMFA method. Furthermore, the drug-loading complexes 7b/MgAl-LDH were prepared and characterized. Their pH-responsive controlled-release behavior was investigated as well. As a result, complex 7b/MgAl-LDH-2 exhibited excellent controlled-releasing performance in the water/ethanol (10:1, v:v) and under a pH of 5.7.
Assuntos
Antifúngicos , Relação Quantitativa Estrutura-Atividade , Antifúngicos/farmacologia , Preparações de Ação Retardada , Ácidos Carboxílicos , Éter , Espectroscopia de Infravermelho com Transformada de Fourier , Etil-Éteres , Éteres Fenílicos , Relação Estrutura-AtividadeRESUMO
Twenty novel longifolene-derived tetraline fused thiazole-amide compounds were synthesized from longifolene, a renewable natural resource. Their structures were characterized by FT-IR, NMR, ESI-MS, and elemental analysis. The inâ vitro antiproliferative activity of these compounds against SK-OV-3 ovarian cancer cell lines, MCF-7 human breast cancer cell lines, HepG2 human liver cancer cell lines, A549 human lung adenocarcinoma cell lines, and T-24 human bladder cancer cell lines was tested by MTT assay. Compounds 6a-6c displayed significant and broad-spectrum antiproliferative activity against almost the tested cancer cell lines with IC50 in the range of 7.84 to 55.88â µM, of which compound 6c exhibited excellent antiproliferative activities with 7.84â µM IC50 against SKOV-3, 13.68â µM IC50 against HepG2, 15.69â µM IC50 against A549, 19.13â µM IC50 against MCF-7, and 22.05â µM IC50 against T-24, showing better and broad-spectrum antiproliferative effect than that of the positive control 5-FU. Furthermore, the action model was analyzed by the molecular docking study. Some intriguing structure-activity relationships were found and discussed herein by DFT theoretical calculation.
Assuntos
Antineoplásicos , Sesquiterpenos , Humanos , Amidas/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Simulação de Acoplamento Molecular , Estrutura Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Relação Estrutura-Atividade , Tiazóis/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
BACKGROUND: Chromatin organization is associated with tumorigenesis; however, information on its role in hepatocellular carcinoma (HCC) is limited. Moreover, although immune checkpoint inhibitors (ICIs) have proven effective against HCC, the optimal index remains unknown. In this study, we aimed to construct a chromatin organization-related gene signature (CORGS) for prognosis and predicting response to ICIs in HCC. METHODS: HCC-related data were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Construction (ICGC). Chromatin organization-related genes (CORGs) were retrieved from Gene Set Enrichment Analysis. Differentially expressed genes (DEGs) and prognostic genes were then applied to select candidate genes using advanced statistical methods, including learning vector quantization, random forest, and lasso regression. Subsequently, the CORGS was established based on chromatin organization-related hub genes using multivariate Cox regression analysis, evaluated with Kaplan-Meier survival curves, and verified in 64 samples of HCC patients from Fujian Provincial Hospital (FPH) via quantitative PCR. Subsequently, functional enrichment analysis, tumor somatic mutation analysis, and tumor immune analysis were performed to evaluate the potential value of the CORGS. RESULTS: Three hundred and thirty-nine CORGs were identified as DEGs, and 186 were associated with HCC prognosis (all P < 0.05). Four intersection genes were selected to establish the CORGS using TCGA cohort, which was found to serve as an independent risk factor for HCC patients. CORGS was then validated in an ICGC cohort. In addition, CORGS reliability was verified in 64 samples from HCC patients and 26 adjacent non-tumorous tissues, collected from the FPH. The CORGS was also associated with tumor immune microenvironment characteristics and ICI response. Moreover, data from "IMvigor 210" revealed that more patients in the low CORGS group responded to atezolizumab compared to high CORGS patients (P < 0.05). Finally, a nomogram of tumor characteristics and the CORGS was established, exhibiting superior discrimination and calibration compared to the current staging system and published models. CONCLUSIONS: CORGS may serve as an effective predictive biomarker for HCC as well as a potential index of the tumor immune microenvironment and ICI response.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Cromatina/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoterapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Prognóstico , Reprodutibilidade dos Testes , Microambiente Tumoral/genéticaRESUMO
Forkhead box M1 (FOXM1) is a proliferative transcription factor and plays a vital role in many cancers. However, the function and molecular mechanism of FOXM1 in esophageal squamous cell carcinoma (ESCC) remain poorly understood. Hence, we aim to clarify the molecular basis of FOXM1-mediated ESCC progression. In this study, bioinformatics analysis showed that FOXM1 was mainly involved in key signal pathways, including cell proliferation, cell cycle, and homologous recombination in ESCC, and predicted that CDC6 might be a potential regulatory target gene of FOXM1. The results revealed that FOXM1 and CDC6 were significantly overexpressed in ESCC tissue and cell line, and their expression was positively correlated. Further studies showed that FOXM1 directly transcriptionally activated CDC6 by binding to its promoter region in ESCC cells. Moreover, FOXM1 mediated ESCC cell proliferation by regulating CDC6 expression, which may be related to promoting G1-S phase transition of cell cycle. Taken together, FOXM1-CDC6 axis mediates ESCC malignant proliferation and may serve as a potential biological target for ESCC treatment.
Assuntos
Proteínas de Ciclo Celular , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteína Forkhead Box M1 , Proteínas Nucleares , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica/genética , Proteínas Nucleares/genéticaRESUMO
A series of novel menthone derivatives bearing pyrimidine and urea moieties was designed and synthesized to explore more potent natural product-derived antitumor agents. The structures of the target compounds were confirmed by FTIR, NMR, and HRMS. The in vitro antitumor activity was tested by standard methyl thiazolytetrazolium assay and showed that 4i, 4g, 4s, and 4m are the best compounds with IC50 values of 6.04 ± 0.62µM, 3.21 ± 0.67µM, 19.09 ± 0.49µM, and 18.68 ± 1.53µM, against Hela, MGC-803, MCF-7, and A549, respectively. The results of the preliminary action mechanism studies showed that compound 4i, the representative compound, could induce cell apoptosis in Hela cells in a dose-dependent manner and might arrest the cell cycle in the G2/M phase. Furthermore, the results of network pharmacology prediction and Western blot experiments indicated that compound 4i might inhibit Hela cells through inhibit PI3K/Akt/mTOR signaling pathway. The binding modes and the binding sites interactions between compound 4i and the target proteins were predicted preliminarily by the molecular docking method.
RESUMO
ABSTRACT: On the basis of endocrine therapy for patients with low burden metastatic prostate cancer (LBMP), the clinical efficacy and quality of life were compared between prostate-only directed radiotherapy (PODT) and prostate and metastasis radiotherapy (PMRT).From November 2009 to November 2015, total 91 patients newly diagnosed with LBMP were retrospectively analyzed, of which 52 patients received PODT and 39 patients received PMRT. The biochemical failure free interval (IBF), prostate specific survival (PCSS), and overall survival (OS) time were compared between the 2 groups, and expanded prostate cancer index composite (EPIC) scale was used to evaluate the difference in quality of life between the 2 groups.The median IBF of the PODT group was 31 months, which was significantly lower than the 39 months of the PMRT group (Pâ<â.05); the 5-year OS and PCSS were 58.9%, 65.3% in PODT group, and 58.9%, 71.79% in PMRT group, respectively. There was no significant between the 2 groups (Pâ>â.05); the side effects of acute radiotherapy in PMRT group were significantly higher than PODT group (Pâ<â.05), especially in bone marrow suppression and gastrointestinal reactions; The scores of urinary system function and intestinal system function in PMRT group were significantly higher than PODT group at the end of radiotherapy, 3 months after radiotherapy, and 6 months after radiotherapy (Pâ<â.05). The score of sexual function in PMRT group was significantly lower than that in PODT group after radiotherapy (Pâ<â.05), and higher than that in PORT group at other follow-up time points (Pâ<â.05). The hormone function was decreased at each follow-up time point in 2 groups, and there was no significant difference between the 2 groups (Pâ>â.05).Patients with LBMP receiving PMRT can improve IBF, but cannot increase PCSS and OS, and increase the incidence of acute radiation injury.
Assuntos
Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Radioterapia/efeitos adversos , Radioterapia/métodos , Idoso , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/mortalidade , Qualidade de Vida , Estudos RetrospectivosRESUMO
BACKGROUND: To investigate the clinical characteristics, influencing factors, and their impact on survival in patients with brain metastases from esophageal squamous cell carcinoma (BM-ESCC). METHODS: A total of 67 patients with patients with newly diagnosed BM-ESCC were retrospectively analyzed from December 2000 to December 2016, in order to examine the correlation between clinicopathological characteristics and brain metastases, and between brain metastases and survival. RESULTS: The number of BM-ESCC was positively correlated with T and N stages (P<0.05). The higher the T and N stages, the higher the incidence. The median survival time was 9.65 months. N stage was an independent risk factor for BM-ESCC. N0 + N1 was associated with a lower risk of brain metastases (P<0.05). Patients with 1 brain metastasis had a significantly longer survival than those with 2 and 3 brain metastases. N stage-stratified analysis revealed that N0 + N1 patients had a longer survival than N2 and N3 patients (P<0.05). Cox regression analysis revealed that mortality in T3 + T4 patients was 2.337 times that of Tis + T1 patients; mortality in N3 patients was 3.486 times that of N0 + N1 patients; and mortality in untreated patients was 2.772 times that of those treated with whole brain radiotherapy. CONCLUSIONS: The number of BM-ESCC is correlated to T and N stages. The higher the N stage, the higher risk of brain metastases. The higher of T and N stages in ESCC, the worse in prognosis. Whole brain radiotherapy could offer greater survival benefits.
Assuntos
Neoplasias Encefálicas , Neoplasias Esofágicas , Encéfalo , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/radioterapia , Carcinoma de Células Escamosas do Esôfago/secundário , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
Seventeen novel 2-(5-amino-1-(substituted sulfonyl)-1H-1,2,4-triazol-3-ylthio)-6- isopropyl-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one compounds were synthesized from the abundant and naturally renewable longifolene and their structures were confirmed by FT-IR, NMR, and ESI-MS. The in vitro cytotoxicity of the synthesized compounds was evaluated by standard MTT assay against five human cancer cell lines, i.e., T-24, MCF-7, HepG2, A549, and HT-29. As a result, compounds 6d, 6g, and 6h exhibited better and more broad-spectrum anticancer activity against almost all the tested cancer cell lines than that of the positive control, 5-FU. Some intriguing structure-activity relationships were found and are discussed herein by theoretical calculation.
Assuntos
Proliferação de Células/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Sesquiterpenos/farmacologia , Tetralonas/farmacologia , Células Hep G2 , Humanos , Células MCF-7 , Espectroscopia de Ressonância Magnética , Neoplasias/patologia , Sesquiterpenos/síntese química , Sesquiterpenos/química , Espectrometria de Massas por Ionização por Electrospray , Espectroscopia de Infravermelho com Transformada de Fourier , Tetralonas/síntese química , Tetralonas/química , Triazóis/síntese química , Triazóis/químicaRESUMO
OBJECTIVE: To investigate risk factors for locoregional recurrence (LRR) of pathologic stage IIIA-N2 non-small cell lung cancer (pIIIA-N2 NSCLC) and construct a prediction model for risk score to determine a patient's risk for LRR and guide the selection of postoperative radiotherapy (PORT). METHODS: The clinical, pathologic, and biological data of 107 patients with pIIIA-N2 NSCLC treated at Fujian Provincial Hospital between May 2012 and December 2018 were analyzed retrospectively. None of the patients had positive surgical margins, and none received preoperative treatment or PORT. The Kaplan-Meier method was used for a univariate analysis of possible factors for locoregional recurrence-free survival (LRFS). The Cox regression model was used in a multivariate analysis to identify independent risk factors for LRFS, which were used to construct a prediction model for risk score. The concordance index was calculated to evaluate discrimination. RESULTS: The median follow-up time was 31.2 months. During the follow-up, 69 (64.5%) patients had LRR and/or distant metastasis (DM). Among them, 46 (43%) patients had LRR (with or without DM), and 56 (52.3%) patients had DM (with or without LRR). The 1-year LRFS, distant metastasis-free survival, disease-free survival, and overall survival rates were 78.2%, 78%, 69.8%, and 90.2%, respectively; the 3-year rates were 50.6%, 41.2%, 31.2%, and 66.3%, respectively. Multivariate analysis showed that surgical approach (hazard ratio [HR], 0.348; 95% confidence interval [CI], 0.175-0.693; P = 0.003), metastatic N2 lymph node ratio (HR, 3.597; 95% CI, 1.832-7.062; P = 0.000), epidermal growth factor receptor status (HR, 3.666; 95% CI, 1.724-7.797; P = 0.001), and lymphocyte-to-monocyte ratio (HR, 2.364; 95% CI, 1.221-4.574; P = 0.011) were independent risk factors for LRFS. These independent risk factors were used to construct a prediction model for risk score and stratify patients into the low-risk group (risk score: 0-2), medium-risk group (risk score: 3-5), and high-risk group (risk score: 6-13). The 1-year LRFS rates of these groups were 91.9%, 85.3%, and 54.6%, respectively; the 3-year LRFS rates were 71.4%, 57.3%, and 13.6%, respectively. These between-group differences were significant (P = 0.000). The prediction model showed good discrimination (concordance index = 0.747, 95% CI, 0.678-0.816). CONCLUSION: Our prediction model for risk score based on characteristics of pIIIA-N2 NSCLC patients may help clinicians predict a patient's risk for LRR. Further investigations of PORT with patients in different risk groups are warranted.
RESUMO
OBJECTIVE: This study aimed to evaluate the clinical efficacy of different target volumes in pelvic radiotherapy in postoperative treatment of cervical cancer based on the Sedlis criteria. METHODS: Patients who admitted to our department for post-operative radiotherapy of cervical cancer from December 2001 to December 2011 and met the Sedlis criteria were retrospectively analysed. The incidences of acute and late radiation injuries, and overall, disease-free and tumour-specific survival with reduced-volume pelvic and whole-pelvis radiotherapy were evaluated and compared. RESULTS: A total of 371 patients were included in the study, including 239 receiving whole-pelvis radiotherapy and 132 receiving reduced-volume pelvic radiotherapy. The volume of contours for mean PTV volumes, bilateral femoral heads and small intestine volumes in reduced-volume pelvic radiotherapy were lower than whole-pelvis radiotherapy; the results were similar to the V10, V20, V30, V40 and V45 for pelvic bone marrow and small intestine dose volume (both p < 0.05). The acute radiation injury observed in the two groups was mainly haematologic toxicity and upper and lower gastrointestinal symptoms. The incidences of acute radiation injury, and late radiation injury of gastrointestinal and urinary tracts were both significantly lower with reduced-volume pelvic radiotherapy than with whole-pelvis radiotherapy (both p < 0.05). Moreover, there was no significant difference in the incidence of lower extremity oedema, or 2-year or 5-year overall, disease-free or tumour-specific survival between groups (all p > 0.05). CONCLUSION: Reduced-volume pelvic radiotherapy could relieve acute and late radiation injuries, especially myelosuppression, and did not affect long-term survival. Advanced in knowledge: Our study shows that reduced-volume base on National Comprehensive Cancer Network 2016 is more fit for cervical cancer than others.
Assuntos
Lesões por Radiação/prevenção & controle , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Neoplasias do Colo do Útero/radioterapia , Adenocarcinoma/mortalidade , Adenocarcinoma/radioterapia , Medula Óssea/efeitos da radiação , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Feminino , Humanos , Intestino Delgado/efeitos da radiação , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias do Colo do Útero/mortalidadeRESUMO
In order to develop novel chemotherapeutic agents with potent anticancer activities, a series of dehydroabietic acid (DHA) derivatives bearing an acylhydrazone moiety were designed and synthesized by the condensation between dehydroabietic acylhydrazide (3) and a variety of substituted arylaldehydes. The inhibitory activities of these compounds against CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical), and BEL-7402 (liver) human carcinoma cell lines were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro. The screening results revealed that many of the compounds showed moderate to high levels of anticancer activities against the tested cancer cell lines and some displayed similar potent inhibitory activities to the commercial anticancer drug cisplatin, while they exhibited lower cytotoxicity against normal human liver cell (HL-7702). Particularly, compound 4w, N'-(3,5-difluorobenzylidene)-2-(dehydroabietyloxy)acetohydrazide, with an IC50 (50% inhibitory concentration) value of 2.21 µM against HeLa cell, was about 17-fold more active than that of the parent compound, and showed remarkable cytotoxicity with an IC50 value of 14.46 µM against BEL-7402 cell. These results provide an encouraging framework that could lead to the development of potent novel anticancer agents.
Assuntos
Abietanos/síntese química , Abietanos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Abietanos/química , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Estrutura MolecularRESUMO
How to define a clinical target volume (CTV) as small as possible for prostate cancer to reduce the dose received by normal organs is an interesting study. We conduct a research to analyze the clinical efficacy of intensity modulated radiotherapy (IMRT) using reduced CTV in the treatment of prostate cancer. From January 2006 to June 2010, 78 patients with prostate cancer were treated with IMRT according to this institutional protocol. Of them, 18 had stage II tumors, 39 had stage III tumors, and 21 had stage IVa tumors. Clinical outcomes included overall survival, biochemical recurrence, recurrence-free survival, and acute and chronic injuries caused by radiotherapy. Risk factors were evaluated using the Cox regression model. As of December 31, 2014, all patients completed radiotherapy as planned. Myelosuppression was mostly grade 1, acute urinary injury was mostly grades 1 and 2, and intestinal injury was mostly grade 1. The 5-year follow-up rate was 91.0%. The overall, progression-free, biochemical recurrence-free, and distant metastasis-free survival rates were 82.1%, 79.4%, 84.6%, and 94.9%, respectively. Tumor volumes defined by small target volumes and Radiation Therapy Oncology Group were 274.21â±â92.64 and 600.68â±â113.72, respectively, representing a significant difference (Pâ<â.05). Age, prostate-specific antigen level, eastern cooperative oncology Group score, Gleason score, and volume of CTV were independent risk factors for mortality and disease progression. Our findings indicated that IMRT with reduced CTV have less acute and chronic injuries caused by radiation, particularly grade 3 or higher urinary and intestinal injuries, while ensuring survival benefits and protecting the hematopoietic function.
Assuntos
Neoplasias da Próstata/radioterapia , Radioterapia de Intensidade Modulada , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Análise de Sobrevida , Resultado do Tratamento , Carga TumoralRESUMO
The aim of our study was to investigate the relationship between cancer-related fatigue and clinical parameters, and the effect factors of fatigue for the prostate cancer patients. Long-term follow-up is performed using the Fatigue Symptom Inventory before treatment (A), at the end of intensity-modulated radiotherapy (B), and 3 months (C), 12 months (D), 24 months (E), 36 months (F), and 48 months (G) after the end of intensity-modulated radiotherapy. Three dimensions of fatigue are assessed during follow-up: severity, perceived interference with quality of life, and duration in the past week. In all, 97 patients with locally advanced prostate cancer were enrolled in the study. Median follow-up time was 43.9 months. The fatigue index was significantly higher in the prostate-specific antigen >20âng/mL, Gleason score >8, the Eastern Cooperative Oncology Group scores, and the higher education. The most severe fatigue occurred at time points B and C. The score for duration of fatigue fluctuated across the time points, with significantly increased scores at time points D, E, and F.In conclusion, we show that cancer-related fatigue is the important symptom which affects the quality of life for the prostate cancer patients. For patients with locally advanced prostate cancer with a high Eastern Cooperative Oncology Group score, a Gleason score of >8 points, prostate-specific antigen levels of >20âng/mL, and high education, attention should be paid to the interference of fatigue with quality of life, especially general level of activity, ability to concentrate, and mood, after radiotherapy combined with hormonal therapy.
Assuntos
Fadiga/etiologia , Gosserrelina/administração & dosagem , Estadiamento de Neoplasias , Neoplasias da Próstata/terapia , Qualidade de Vida , Radioterapia de Intensidade Modulada/métodos , Idoso , Antineoplásicos Hormonais/administração & dosagem , Relação Dose-Resposta a Droga , Seguimentos , Humanos , Injeções Subcutâneas , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/complicações , Neoplasias da Próstata/diagnóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
With great improvements in survival in patients with locally advanced prostate cancer, quality of life (QOL) is becoming an important factor in the selection of treatment. The aim of this study was to evaluate changes in health-related QOL in patients with locally advanced prostate cancer after intensity-modulated radiotherapy (IMRT) combined with androgen deprivation therapy. Patients were treated with IMRT combined with androgen deprivation. Total dose to the prostate was 68.2 Gy (2.2 Gy per fraction), and patients received 50 mg of oral Casodex once daily and 3.6 mg of subcutaneous Zoladex once every 28 days for 2.5 years. QOL was measured using the Expanded Prostate Cancer Index Composite. The time points were baseline, end of radiotherapy, and 3, 12, 36, 48, and 60 months after radiotherapy. From 2002 to 2007, a total of 87 patients were enrolled. Median follow-up time was 76.8 months. Compared with baseline, all four domain summary scores were decreased to varying degrees. Statistically significant changes in the urinary, bowel, and hormonal domain scores were observed (P < 0.05). The changes in scores for urinary incontinence and dysuria were -13.0 ± 8.3 and -6.12 ± 3.9, respectively (P < 0.05). QOL was decreased in patients with locally advanced prostate cancer after IMRT combined with androgen deprivation therapy in all four primary domains, especially in urinary, bowel, and hormonal domains. Nevertheless, the treatment was well tolerated in most patients during the 5 years of follow-up.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Qualidade de Vida , Radioterapia de Intensidade Modulada , Idoso , Idoso de 80 Anos ou mais , Anilidas/administração & dosagem , Anilidas/efeitos adversos , Anilidas/uso terapêutico , Gosserrelina/administração & dosagem , Gosserrelina/efeitos adversos , Gosserrelina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Nitrilas/uso terapêutico , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Compostos de Tosil/administração & dosagem , Compostos de Tosil/efeitos adversos , Compostos de Tosil/uso terapêutico , Resultado do Tratamento , Incontinência Urinária/induzido quimicamente , Incontinência Urinária/etiologiaRESUMO
AIM: The aim of this study was to evaluate acute adverse events and efficacy of three-dimensional intensity- modulated radiotherapy (IMRT) combined with endocrine therapy for intermediate and advanced prostate cancer. METHODS: Sixty-seven patients were treated with three-dimensional IMRT combined with maximum androgen blockade. The correlation between radiation-induced rectal injury and clinical factors was further analyzed. RESULTS: After treatment, 21 patients had complete remission (CR), 37 had partial remission (PR), and nine had stable disease (SD), with an overall response rate of 86.5%. The follow-up period ranged from 12.5 to 99.6 months. Thirty-nine patients had a follow-up time of ≥ five years. In this group, three-year and five-year overall survival rates were 89% and 89.5%, respectively; three-year and five-year progression-free survival rates were 72% and 63%. In univariate analyses, gross tumor volume was found to be prognostic for survival (χ2 = 5.70, P = 0.037). Rates of leucopenia and anemia were 91.1% and 89.5%, respectively. Two patients developed acute liver injury, and a majority of patients developed acute radiation proctitis and cystitis, mainly grade 1/2. Tumor volume before treatment was the only prognostic factor influencing the severity of acute radiation proctitis (P < 0.05). CONCLUSIONS: IMRT combined with endocrine therapy demonstrated promising efficacy and was well tolerated in patients with intermediate and advanced prostate cancer.
Assuntos
Anilidas/efeitos adversos , Quimiorradioterapia/efeitos adversos , Gosserrelina/efeitos adversos , Recidiva Local de Neoplasia/terapia , Nitrilas/efeitos adversos , Neoplasias da Próstata/terapia , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Compostos de Tosil/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Cistite , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Proctite , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Lesões por Radiação/diagnóstico , Radioterapia Guiada por Imagem/efeitos adversos , Taxa de SobrevidaRESUMO
OBJECTIVES To evaluate the consistency between the clinical staging of non-surgically treated oesophageal carcinoma (preliminary draft) and the surgical-pathological staging of the oesophageal carcinoma. METHODS Comprehensive clinical data from 112 patients with oesophageal cancer were collected from January 2009 to June 2010. Based on the clinical staging standard for oesophageal carcinomas treated with non-surgical methods, the preoperative TNM staging was performed and the results were compared with pTNM. The Kappa statistic was used to analyse the degree of consistency. RESULTS The Kappa values from the T staging, N staging and TNM staging of surgical-pathological results were 0.545, 0.615 and -0.090, respectively. CONCLUSIONS Consistency was observed between the non-surgical T staging and N staging and the postoperative pathological T staging and N staging, but the degree of consistency was only moderate. Additionally, no consistency was observed between the TNM staging results from the two staging systems. Whether the non-surgical staging system can replace the pathological staging system and its significance in evaluating the prognosis remain to be determined.