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4.
Int J Clin Oncol ; 26(7): 1179-1187, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34086112

RESUMO

BACKGROUND: We investigated whether prophylactic percutaneous endoscopic gastrostomy (PEG) is used effectively for patients treated with definitive concurrent chemoradiotherapy (CCRT) and the predictors of the need for PEG. METHODS: 326 patients with laryngeal, oropharyngeal or hypopharyngeal cancers were retrospectively reviewed. RESULTS: The PEG tube use group had more favorable results than the total parenteral nutrition and nasogastric tube groups in terms of rate of serum albumin loss, incidence of severe fever and aspiration pneumonia, CCRT completion rate and hospitalization period. However, it was inferior to oral intake. Analysis of the relative risk of requiring enteral or parenteral nutrition revealed that performance status (PS) 2, primary site (supraglottis, oropharynx, or hypopharynx), N3 disease, and cisplatin were predictors of the need for nutritional support. CONCLUSIONS: Prophylactic PEG is effective for patients treated with definitive CCRT and is especially required for patients with PS2 or oropharyngeal cancer.


Assuntos
Gastrostomia , Neoplasias de Cabeça e Pescoço , Quimiorradioterapia/efeitos adversos , Nutrição Enteral , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Estudos Retrospectivos
5.
BMJ Case Rep ; 14(5)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34035012

RESUMO

Patients undergoing radical treatment particularly chemoradiotherapy for cancer of the upper aerodigestive tract frequently experience progressive deterioration in swallow during and immediately after treatment. It is important to identify patients at high risk of compromised feeding early, following diagnosis, so that alternate feeding routes, such as percutaneous endoscopic gastrostomies (PEGs), can be promptly and prophylactically instituted, in keeping with the UK Head and Neck Cancer Guidelines (2016).


Assuntos
Gastrostomia , Neoplasias de Cabeça e Pescoço , Quimiorradioterapia/efeitos adversos , Nutrição Enteral/efeitos adversos , Gastrostomia/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Síndrome
6.
Crit Rev Oncol Hematol ; 162: 103345, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33933569

RESUMO

PURPOSE: To evaluate efficacy and toxicity of weekly cisplatin chemoradiotherapy versus three-weekly cisplatin chemoradiotherapy and identify differences in clinical outcomes and severe toxicity rate. METHODS: PICOS/PRISMA methods were used to identify studies on PubMed, EMBASE and Cochrane Library, 2005-2019. RESULTS: Six randomized clinical trials (554 patients) were identified. Weekly cisplatin was not associated with significant overall survival (HR 1.13, 95 % CI 0.84-1.51) and progression-free survival (HR 1.23, 95 %CI 0.91-1.65) improvement compared with three-weekly regimen. Severe acute toxicity (RR 0.95), treatment compliance to chemotherapy (RR 1.67) and radiotherapy (RR 0.61) were similar between regimens. CONCLUSION: Weekly cisplatin is not associated with better clinical outcomes compared to three-weekly cisplatin. Three-weekly cisplatin chemoradiotherapy should be considered the standard approach in the management of locally advanced head and neck cancer. Methodologically robust RCTs designs are needed to improve the quality of evidence. Differences on long-term toxicity and cost-effectiveness remain to be tested.


Assuntos
Antineoplásicos , Neoplasias de Cabeça e Pescoço , Antineoplásicos/efeitos adversos , Quimiorradioterapia/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Itália , Oncologia
7.
Medicine (Baltimore) ; 100(21): e25980, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032710

RESUMO

BACKGROUND: Concurrent chemoradiotherapy is widely utilised as a standardized primary method of treatment for patients with advanced nasopharyngeal carcinoma (NPC). However, the combination of concurrent chemoradiotherapy and adjuvant chemotherapy for treating NPC patients remain unclear. Therefore, this study attempts to elucidate the efficiency and safety of concurrent chemoradiotherapy combined with adjuvant chemotherapy (gemcitabine plus cisplatin versus 5-fluorouracil plus cisplatin) for treating patients with NPC. MATERIALS AND METHODS: This study is a randomized, multicentral, open-labelled trial to assess the clinical efficiency and safety of using concurrent chemoradiotherapy combined with adjuvant chemotherapy as a therapeutic measure for advanced NPC patients. A total of 50 patients will be randomly assigned into 2 groups, namely treatment-group-one and treatment-group-two. Eligible patients will be administered with concurrent chemoradiotherapy and subsequentially with adjuvant chemotherapy (gemcitabine plus cisplatin or 5-fluorouracil plus cisplatin). Moreover, the primary endpoint is a comparison of progression-free survival between concurrent chemoradiotherapy and subsequentially adjuvant gemcitabine and cisplatin and chemoradiotherapy, which is proceeded by adjuvant 5-fluorouracil and cisplatin in advanced NPC patients. Overall survival, overall response rate, incidence of acute and late toxicity, and adverse events are the minor endpoints. Statistical analyses will be performed with SPSS 25.0 software. DISCUSSION: The current research evaluates the clinical efficiency and safety of utilising concurrent chemoradiotherapy combined with adjuvant chemotherapy as a therapeutic strategy to treat advanced NPC patients. The work done in this study will provide a clinical basis for concurrent chemoradiotherapy in combination with adjuvant chemotherapy for treating advanced NPC. TRIAL REGISTRATION: DOI 10.17605/OSF.IO/5UPVM.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimiorradioterapia/métodos , Carcinoma Nasofaríngeo/terapia , Radioterapia de Intensidade Modulada/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Esquema de Medicação , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Estudos Multicêntricos como Assunto , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Radioterapia de Intensidade Modulada/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Trials ; 22(1): 345, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001287

RESUMO

BACKGROUND: The Surgery As Needed for Oesophageal cancer (SANO) trial compares active surveillance with standard oesophagectomy for patients with a clinically complete response (cCR) to neoadjuvant chemoradiotherapy. The last patient with a clinically complete response is expected to be included in May 2021. The purpose of this update is to present all amendments to the SANO trial protocol as approved by the Institutional Research Board (IRB) before accrual is completed. DESIGN: The SANO trial protocol has been published ( https://doi.org/10.1186/s12885-018-4034-1 ). In this ongoing, phase-III, non-inferiority, stepped-wedge, cluster randomised controlled trial, patients with cCR (i.e. after neoadjuvant chemoradiotherapy no evidence of residual disease in two consecutive clinical response evaluations [CREs]) undergo either active surveillance or standard oesophagectomy. In the active surveillance arm, CREs are repeated every 3 months in the first year, every 4 months in the second year, every 6 months in the third year, and yearly in the fourth and fifth year. In this arm, oesophagectomy is offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant metastases. The primary endpoint is overall survival. UPDATE: Amendments to the study design involve the first cluster in the stepped-wedge design being partially randomised as well and continued accrual of patients at baseline until the predetermined number of patients with cCR is reached. Eligibility criteria have been amended, stating that patients who underwent endoscopic treatment prior to neoadjuvant chemoradiotherapy cannot be included and that patients who have highly suspected residual tumour without histological proof can be included. Amendments to the study procedures include that patients proceed to the second CRE if at the first CRE the outcome of the pathological assessment is uncertain and that patients with a non-passable stenosis at endoscopy are not considered cCR. The sample size was recalculated following new insights on response rates (34% instead of 50%) and survival (expected 2-year overall survival of 75% calculated from the moment of reaching cCR instead of 3-year overall survival of 67% calculated from diagnosis). This reduced the number of required patients with cCR from 264 to 224, but increased the required inclusions from 480 to approximately 740 patients at baseline. CONCLUSION: Substantial amendments were made prior to closure of enrolment of the SANO trial. These amendments do not affect the outcomes of the trial compared to the original protocol. The first results are expected late 2023. If active surveillance plus surgery as needed after neoadjuvant chemoradiotherapy for oesophageal cancer leads to non-inferior overall survival compared to standard oesophagectomy, active surveillance can be implemented as a standard of care.


Assuntos
Neoplasias Esofágicas , Terapia Neoadjuvante , Quimiorradioterapia/efeitos adversos , Neoplasias Esofágicas/terapia , Esofagectomia/efeitos adversos , Humanos , Terapia Neoadjuvante/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Conduta Expectante
9.
Anticancer Res ; 41(5): 2459-2465, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952471

RESUMO

BACKGROUND/AIM: For patients with locally recurrent rectal cancer (LRRC) extensive surgery is often the only curative option and patient selection is crucial. This study aimed to investigate whether magnetic resonance imaging (MRI) characteristics of the primary tumour can predict oncological outcome after surgery for locally recurrent rectal cancer (LRRC). PATIENTS AND METHODS: All patients undergoing surgery for LRRC with a curative intent at the Karolinska University Hospital 2003-2013 were included. MRI examinations of the primary tumour were re-evaluated. RESULTS: In total, 54 patients were included. A tumour volume decrease of <70% after preoperative radiotherapy or chemoradiotherapy (C)RT for the primary tumour was correlated with a lower proportion of R0 resection of the LRRC (OR=0.07, 95% CI=0.01-0.84). No association between MRI characteristics of the primary tumour and prognosis after LRRC surgery was found. CONCLUSION: Long-term outcomes after surgery for LRRC were not significantly associated with MRI characteristics of the index tumour. However, factors associated with increased risk of R1 resection of LRRC were identified.


Assuntos
Angiografia por Ressonância Magnética , Recidiva Local de Neoplasia/cirurgia , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Resultado do Tratamento
10.
Anticancer Res ; 41(5): 2583-2589, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952487

RESUMO

BACKGROUND/AIM: High-grade gliomas have a poor prognosis despite standard treatment. The aim of the study was to identify new prognostic factors to select patients who need more intense treatment. PATIENTS AND METHODS: Forty-three consecutive patients underwent surgery plus chemoradiotherapy for pathologically diagnosed high-grade gliomas (grade III, IV). RESULTS: The median survival time was 989 days, and the 1-year survival rate was 87.6%. Among patients with grade IV disease, the median survival time, 1-year, and 2-year survival rate were 814 days, 82.6%, and 58.7%, respectively. In the univariate analysis, unmethylated MGMT promoter (p=0.0495), brainstem infiltration (p=0.0004), basal ganglia as the primary lesion site (p=0.0056), 3-dimensional conformal radiotherapy (p=0.0286), and <50 Gy (p=0.0049) were associated with a poor prognosis. In the multivariate analysis, only brainstem infiltration retained significance (HR for death, 0.21; 95% CI=0.06-0.70; p=0.011). CONCLUSION: Brainstem infiltration is a novel prognostic factor for poor prognosis in patients with high-grade gliomas.


Assuntos
Tronco Encefálico/imunologia , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioma/tratamento farmacológico , Glioma/radioterapia , Proteínas Supressoras de Tumor/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Gânglios da Base/imunologia , Gânglios da Base/patologia , Tronco Encefálico/patologia , Quimiorradioterapia/efeitos adversos , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/imunologia , Glioma/imunologia , Glioma/patologia , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Regiões Promotoras Genéticas/genética
11.
Front Immunol ; 12: 618150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841399

RESUMO

Earlier evidence has proven that probiotic supplements can reduce concurrent chemoradiotherapy (CCRT)-induced oral mucositis (OM) in nasopharyngeal cancer (NPC). The incidence of severe OM (grade 3 or higher) was the primary endpoint in this study. We first enrolled 85 patients with locally advanced NPC who were undergoing CCRT. Of them, 77 patients were finally selected and randomized (1:1) to receive either a probiotic cocktail or placebo. To investigate the protective effects and the mechanism of probiotic cocktail treatment on OM induced by radiotherapy and chemotherapy, we randomly divided the rats into the control (C) group, the model (M) group, and the probiotic (P) group. After treatment, samples from the tongue, blood, and fecal and proximal colon tissues on various days (7th, 14th, and 21st days) were collected and tested for the inflammatory response, cell apoptosis, intestinal permeability, and intestinal microbial changes. We found that patients taking the probiotic cocktail showed significantly lower OM. The values of the incidence of 0, 1, 2, 3, and 4 grades of OM in the placebo group and in the probiotic cocktail group were reported to be 0, 14.7, 38.2, 32.4, and 14.7% and 13.9, 36.1, 25, 22.2, and 2.8%, respectively. Furthermore, patients in the probiotic cocktail group showed a decrease in the reduction rate of CD3+ T cells (75.5% vs. 81%, p < 0.01), CD4+ T cells (64.53% vs. 79.53%, p < 0.01), and CD8+ T cells (75.59 vs. 62.36%, p < 0.01) compared to the placebo group. In the rat model, the probiotic cocktail could ameliorate the severity of OM, decrease the inflammatory response, cause cell apoptosis and intestinal permeability, and restore the structure of gut microbiota to normalcy. In conclusion, the modified probiotic cocktail significantly reduces the severity of OM by enhancing the immune response of patients with NPC and modifying the structure of gut microbiota. Clinical Trial Registration: The Clinical Trial Registration should be the NCT03112837.


Assuntos
Quimiorradioterapia/efeitos adversos , Neoplasias Nasofaríngeas/complicações , Probióticos/uso terapêutico , Estomatite/etiologia , Estomatite/terapia , Animais , Quimiorradioterapia/métodos , Gerenciamento Clínico , Modelos Animais de Doenças , Suscetibilidade a Doenças , Duração da Terapia , Microbioma Gastrointestinal , Humanos , Masculino , Metagenoma , Metagenômica/métodos , Neoplasias Nasofaríngeas/terapia , Ratos , Índice de Gravidade de Doença , Estomatite/diagnóstico , Resultado do Tratamento
12.
Medicine (Baltimore) ; 100(16): e25342, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879663

RESUMO

BACKGROUND: The incidence of malnutrition in patients with esophageal cancer is high, which seriously affects the therapeutic effect and quality of life. Oral nutritional supplement is the first choice of nutritional support recommended by current guidelines, which can supplement the lack of energy and protein in patients with esophageal cancer, improve nutritional status and improve the quality of life, but there are few clinical studies. Therefore, the purpose of this randomized controlled trial is to evaluate the effect of oral nutritional supplement therapy on nutritional status and quality of life in patients with esophageal cancer treated undergoing radiotherapy and chemotherapy. METHODS: This is a prospective randomized controlled trial to study the effects of oral nutritional supplement therapy on nutritional status and quality of life in patients with esophageal cancer undergoing radiotherapy and chemotherapy. This study is approved by the Clinical Research Society of our hospital. Patients will be randomly divided into ONS group and traditional diet group. The nutritional status, quality of life score and adverse reactions will be observed before and after radiotherapy and chemotherapy. The data will be analyzed by SPSS 16.0. DISCUSSION: This study will evaluate the effect of oral nutritional supplement therapy on nutritional status and quality of life of patients with esophageal cancer undergoing radiotherapy and chemotherapy. The results of this experiment will establish clinical evidence for the application of oral nutritional supplement therapy in patients with esophageal cancer undergoing radiotherapy and chemotherapy. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/9ZW34.


Assuntos
Quimiorradioterapia/efeitos adversos , Suplementos Nutricionais , Neoplasias Esofágicas/terapia , Desnutrição/prevenção & controle , Apoio Nutricional/métodos , Adulto , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/fisiopatologia , Feminino , Humanos , Masculino , Desnutrição/etiologia , Pessoa de Meia-Idade , Estado Nutricional , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
13.
Nutrients ; 13(4)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33924581

RESUMO

BACKGROUND: The Prognostic Nutritional Index (PNI) is a parameter of nutritional and inflammation status related to toxicity in cancer treatment. Since data for head and neck cancer are scanty, this study aims to investigate the association between PNI and acute and late toxicity for this malignancy. METHODS: A retrospective cohort of 179 head and neck cancer patients treated with definitive radiotherapy with induction/concurrent chemotherapy was followed-up (median follow-up: 38 months) for toxicity and vital status between 2010 and 2017. PNI was calculated according to Onodera formula and low/high PNI levels were defined according to median value. Odds ratio (OR) for acute toxicity were calculated through logistic regression model; hazard ratios (HR) for late toxicity and survival were calculated through the Cox proportional hazards model. RESULTS: median PNI was 50.0 (interquartile range: 45.5-53.5). Low PNI was associated with higher risk of weight loss > 10% during treatment (OR = 4.84, 95% CI: 1.73-13.53 for PNI < 50 versus PNI ≥ 50), which was in turn significantly associated with worse overall survival, and higher risk of late mucositis (HR = 1.84; 95% CI:1.09-3.12). PNI predicts acute weight loss >10% and late mucositis. CONCLUSIONS: PNI could help clinicians to identify patients undergoing radiotherapy who are at high risk of acute and late toxicity.


Assuntos
Quimiorradioterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , Mucosite/epidemiologia , Avaliação Nutricional , Radiodermatite/epidemiologia , Idoso , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Quimioterapia de Indução/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mucosite/etiologia , Valor Preditivo dos Testes , Prognóstico , Radiodermatite/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Medição de Risco , Perda de Peso/efeitos dos fármacos , Perda de Peso/efeitos da radiação
14.
Anticancer Res ; 41(4): 2141-2145, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813425

RESUMO

BACKGROUND/AIM: We compared the outcome of docetaxel, cisplatin, and 5-fluorouracil as combination chemoradiotherapy (DCF-RT) for unresectable locally advanced thoracic esophageal cancer (EC) with that of cisplatin (CDDP) and 5-fluorouracil (5-FU) as combination chemoradiotherapy (CF-RT) in clinical settings. PATIENTS AND METHODS: Seventy-three patients with unresectable locally advanced thoracic EC were included in this study. CF (n=38) consisted of intravenous CDDP at 70 mg/m2 (day 1) and 5-FU at 700 mg/m2 (days 1 to 4), repeated every four weeks for two cycles. DCF (n=35) consisted of intravenous docetaxel at 50 mg/m2 (day 1), CDDP at 60 mg/m2 (day 1), and 5-FU at 600 mg/m2 (days 1 to 4), repeated every four weeks for two cycles. Patients were irradiated with 60 Gy in 30 fractions. RESULTS: The overall complete response (CR) rate of DCF-RT was significantly higher than that of CF-RT (36.7% vs. 3.7%, p=0.003). The 3-year overall survival (OS) rate of DCF-RT was significantly higher than that of CF-RT (32.8% vs. 8.5%, p<0.001). CONCLUSION: DCF-RT demonstrated a higher CR rate and OS for unresectable locally advanced thoracic EC than CF-RT.


Assuntos
Quimiorradioterapia , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Neoplasias Esofágicas/terapia , Fluoruracila/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/efeitos adversos , Progressão da Doença , Docetaxel/efeitos adversos , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Fluoruracila/efeitos adversos , Humanos , Japão/epidemiologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
15.
Anticancer Res ; 41(4): 1753-1760, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813379

RESUMO

BACKGROUND/AIM: The chromosome translocation t(8;19)(p11;q13) has been reported in only six acute myeloid leukemia (AML) patients. We here present the genetic and clinical features of the seventh AML case with this aberration. MATERIALS AND METHODS: Cytogenetic and molecular genetic investigations were performed on leukemic bone marrow cells from a patient with therapy-related AML. RESULTS: A t(8;19)(p11;q13) was found leading to an in-frame fusion of exon 16 of the lysine acetyltransferase 6A gene (KAT6A) from 8p11 with exon 2 of the leucine twenty homeobox gene (LEUTX) from 19q13 resulting in expression of the otherwise silent LEUTX gene in the leukemic cells. The KAT6A-LEUTX protein is predicted to act as a histone acetyltransferase at its amino-terminal-KAT6A moiety but as a homeobox transcription factor at the LEUTX-carboxyl-terminal moiety. CONCLUSION: The present case is the second therapy-related AML, and the third AML overall, in which both a t(8;19)(p11;q13) and its molecular result, a KAT6A-LEUTX fusion gene, are described. The t(8;19)(p11;q13)/KAT6A-LEUTX deregulates transcription and induces leukemogenesis.


Assuntos
Biomarcadores Tumorais/genética , Quimiorradioterapia/efeitos adversos , Cromossomos Humanos Par 19 , Cromossomos Humanos Par 8 , Fusão Gênica , Histona Acetiltransferases/genética , Proteínas de Homeodomínio/genética , Leucemia Mieloide Aguda/etiologia , Translocação Genética , Idoso , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Resultado do Tratamento , Neoplasias do Colo do Útero/terapia
17.
BMC Cancer ; 21(1): 265, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33706745

RESUMO

BACKGROUND: Gliosarcoma (GSM) is a distinct and aggressive variant of glioblastoma multiforme (GBM) with worse prognosis and few treatment options. It is often managed with the same treatment modalities with temozolomide (TMZ) as in GBM. However, the therapeutic benefits on GSM from such treatment regimen is largely unknown. Patient-derived xenograft (PDX) models have been used widely to model tumor progression, and subsequently to validate biomarkers and inform potential therapeutic regimens. Here, we report for the first time the successful development of a PDX model of secondary GSM. METHODS: Tissue obtained from a tumor resection revealed a secondary GSM arising from GBM. The clinical, radiological, and histopathological records of the patient were retrospectively reviewed. Samples obtained from surgery were cultured ex vivo and/or implanted subcutaneously in immunocompromised mice. Histopathological features between the primary GBM, secondary GSM, and GSM PDX are compared. RESULTS: In explant culture, the cells displayed a spindle-shaped morphology under phase contrast microscopy, consistent with the sarcomatous component. GSM samples were subcutaneously engrafted into immunocompromised mice after single-cell suspension. Xenografts of serial passages showed enhanced growth rate with increased in vivo passage. We did not observe any histopathological differences between the secondary GSM and its serial in vivo passages of PDX tumors. CONCLUSIONS: Our PDX model for GSM retained the histopathological characteristics of the engrafted tumor from the patient. It may provide valuable information to facilitate molecular and histopathological modelling of GSM and be of significant implication in future research to establish precise cancer medicine for this highly malignant tumor.


Assuntos
Neoplasias Encefálicas/terapia , Quimiorradioterapia/efeitos adversos , Glioblastoma/terapia , Gliossarcoma/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Animais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/cirurgia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Proteínas de Ciclo Celular/análise , Proteínas de Ciclo Celular/genética , Quimiorradioterapia/métodos , Craniotomia , Feminino , Glioblastoma/diagnóstico , Glioblastoma/genética , Glioblastoma/patologia , Gliossarcoma/etiologia , Gliossarcoma/genética , Gliossarcoma/patologia , Humanos , Imageamento por Ressonância Magnética , Camundongos , Pessoa de Meia-Idade , Mutação , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/patologia , Cultura Primária de Células , Temozolomida/uso terapêutico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Am J Clin Oncol ; 44(6): 275-282, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33782335

RESUMO

OBJECTIVES: Preoperative radiotherapy improves outcomes for operable esophageal cancer patients, though the proximity of the heart to the esophagus puts patients at risk of radiation-induced cardiovascular disease. This study characterizes the impact of radiotherapy and different radiation techniques on cardiovascular morbidity among a cohort of esophageal cancer patients. MATERIALS AND METHODS: We identified 1125 patients aged 65 and older diagnosed between 2000 and 2011 with esophageal cancer who received surgery alone, or surgery preceded by either preoperative chemotherapy or preoperative chemoradiation from the Surveillance Epidemiology and End Results (SEER)-Medicare database. We used Medicare claims to identify severe perioperative and late cardiovascular events. Multivariable logistic regression and Fine-Gray models were used to determine the effect of presurgery treatment on the risk of perioperative and late cardiovascular disease. RESULTS: Preoperative chemotherapy or chemoradiation did not significantly increase the risk of perioperative cardiovascular complications compared with surgery alone. Patients treated with preoperative chemoradiation had a 36% increased risk of having a late cardiovascular event compared with patients treated with surgery alone (subdistribution hazard ratio [SDHR]: 1.36; P=0.035). There was no significant increase in late cardiovascular events among patients treated with preoperative chemotherapy (SDHR: 1.18; P=0.40). Among patients treated with preoperative chemoradiation, those receiving intensity modulated radiotherapy had a 68% decreased risk of having a late cardiovascular event compared with patients receiving conventional radiation (SDHR: 0.32; P=0.007). CONCLUSIONS: This study demonstrates an increased risk of cardiovascular complications among operative esophageal cancer patients treated with preoperative chemoradiation, though these risks might be reduced with more cardioprotective radiation techniques such as intensity modulated radiotherapy.


Assuntos
Adenocarcinoma/radioterapia , Doenças Cardiovasculares/epidemiologia , Quimiorradioterapia/efeitos adversos , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/patologia , Quimiorradioterapia/mortalidade , Terapia Combinada , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Feminino , Seguimentos , Humanos , Masculino , Medicare , Prognóstico , Radioterapia de Intensidade Modulada/mortalidade , Taxa de Sobrevida , Estados Unidos/epidemiologia
19.
Radiother Oncol ; 158: 191-199, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33667583

RESUMO

BACKGROUND AND PURPOSE: Despite definitive chemoradiotherapy (CRT) being a recommended therapeutic method for patients with T4b esophageal squamous cell carcinoma (ESCC), treatment response and complications remain unclear. Esophageal fistula is a severe CRT-related complication when treating locally advanced ESCC, but data on risk factors that lead to esophageal fistula formation are limited. The aim of this analysis is to characterize the outcomes of T4b ESCC treated by CRT and investigate the risk factors of esophageal fistula. MATERIALS AND METHODS: We retrospectively analyzed 136 patients with clinically unresectable T4b ESCC who were treated with CRT. Response, survival, and complication rates, particularly the rate of esophageal fistula and its associated risk factors were analyzed. RESULTS: The median progression-free survival and overall survival (OS) of all patients were 7.9 (95% confidence interval [CI]: 6.1-9.7) and 12.2 months (95% [CI]: 8.9-15.4), respectively. The Kaplan-Meier curves showed that the 3- and 5-year OS rates were 29.9% and 20.2%, respectively. The incidence rate of esophageal fistulas was 30.1%. The median OS for patients with esophageal fistula was only 6.9 (95%[CI] = 6.0-7.8) months. The risk for developing esophageal fistulas was significantly high for ulcerative-type tumors (odds ratio [OR] = 3.202; 95%[CI] = 1.036-7.850, P = 0.011) and for those invading the bronchus/trachea (OR = 3.378; 95%[CI] = 1.223-9.332, P = 0.048). CONCLUSION: We demonstrated that CRT for T4b ESCC patients has a curative potential, despite a high incidence of esophageal fistula, which was the main cause of treatment failure. The higher risk for fistula formation were tumors with ulceration or bronchus/trachea invasion.


Assuntos
Fístula Esofágica , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias de Cabeça e Pescoço , Quimiorradioterapia/efeitos adversos , Fístula Esofágica/epidemiologia , Fístula Esofágica/etiologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Humanos , Incidência , Estudos Retrospectivos , Resultado do Tratamento
20.
BMC Cancer ; 21(1): 314, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761922

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICI) have become standard treatment in different tumor entities. However, safe treatment with ICI targeting the PD-1/PD-L1 axis requires early detection of immune-related adverse events (irAE). There exist different questionnaires of drug manufacturers for the detection of irAE that have not been validated so far. METHODS: The prospective non-interventional ST-ICI trial studied treatment with PD-1/PD-L1 ICI alone or combined with radiotherapy. In the current analysis, the detection rate of self-reported irAE with a patient questionnaire containing 41 different questions was compared to clinician-reported irAE. RESULTS: Between April 2017 and August 2019, a total of 104 patients were prospectively enrolled. NSCLC (44%) and HNSCC (42%) were the most frequent tumor entities. A total of 784 questionnaires were collected. A total of 29 irAE were reported by clinicians. The most frequent irAE was hypothyroidism (9%), followed by skin reactions (5%), hepatitis (4%), diarrhea (3%), and pneumonitis (3%). Questions that became significantly more often positive at time points of clinician-reported irAE were "weight change", "difficulty to grip things", "bloody or mucous stool" and "insomnia". Self-reported organ-specific questions detected at least 50% of clinician-reported irAE of gastrointestinal, lung, endocrine, and skin irAE. It was not possible to detect hepatic irAE with the questionnaire. CONCLUSION: Questionnaires can help to detect gastrointestinal, lung, endocrine, or skin irAE, but not hepatic irAE. Questions on "weight change" and "insomnia" may help to increase the detection rate of irAE, besides organ-specific questions. These results are a valuable contribution to the future development of a specific and practicable questionnaire for early self-reported detection of irAE during ICI therapy in cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03453892 . Registered on 05 March 2018.


Assuntos
Quimiorradioterapia/efeitos adversos , Monitoramento de Medicamentos/métodos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/terapia , Autorrelato/estatística & dados numéricos , Idoso , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Quimiorradioterapia/métodos , Diarreia/induzido quimicamente , Diarreia/diagnóstico , Diarreia/epidemiologia , Diarreia/imunologia , Erupção por Droga/diagnóstico , Erupção por Droga/epidemiologia , Erupção por Droga/imunologia , Monitoramento de Medicamentos/estatística & dados numéricos , Feminino , Hepatite/diagnóstico , Hepatite/epidemiologia , Hepatite/imunologia , Humanos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/diagnóstico , Hipotireoidismo/epidemiologia , Hipotireoidismo/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Pneumonia/induzido quimicamente , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Pneumonia/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Estudos Prospectivos
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