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1.
JMIR Mhealth Uhealth ; 9(9): e29498, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499047

RESUMO

BACKGROUND: Diabetes has placed heavy social and economic burdens on society and families worldwide. Insufficient knowledge and training of frontline medical staff, such as nurses, interns, and residents, may lead to an increase in acute and chronic complications among patients with diabetes. However, interns have insufficient knowledge about diabetes management. The factors that affect interns' current level of diabetes-related knowledge are still unclear. Therefore, understanding the behavioral intentions of interns is essential to supporting the development and promotion of the use of virtual simulation teaching applications. OBJECTIVE: This study aimed to identify the determinants of nursing interns' intentions to use simulation-based education applications. METHODS: From December 1, 2020, to February 28, 2021, the web-based survey tool Sojump (Changsha Xingxin Information Technology Co) was used to survey nursing interns in hospitals across China. Two survey links were sent to 37 partner schools in 23 major cities in China, and they were disseminated through participants' WeChat networks. Multiple regression analysis was used to determine the association between demographic information and basic disease information and the use of the application for treating adult patients. RESULTS: Overall, 883 nursing interns from 23 provinces in China responded to the survey. Among them, the virtual simulation utilization rate was 35.6% (314/883) and the awareness rate was 10.2% (90/883). In addition, among the interns, only 10.2% (90/883) correctly understood the concept of virtual simulation, and most of them (793/883, 89.8%) believed that scenario-simulation training or the use of models for teaching are all the same. Multiple regression analysis showed that the educational level, independent learning ability, and professional identity of the interns were related to use of the application (P<.05). Skills and knowledge that the interns most wanted to acquire included the treatment of hypoglycemia (626/883, 70.9%), functional test simulation (610/883, 69.1%), and blood glucose monitoring technology (485/883, 54.9%). A total of 60.5% (534/883) of the interns wanted to acquire clinical thinking skills, while 16.0% (141/883) wanted to acquire operational skills. Nursing trainees believed that the greatest obstacles to virtual simulation included limited time (280/883, 31.7%), the degree of simulation (129/883, 14.6%), the demand for satisfaction (108/883, 12.2%), and test scores (66/883, 7.5%). CONCLUSIONS: The understanding and usage rate of diabetes virtual simulation teaching applications by Chinese nursing interns is very low. However, they have high requirements regarding this teaching method. Conducting high-quality randomized controlled trials and designing applications that are suitable for the needs of different nurse trainees will increase students' interest in learning and help improve diabetes knowledge among nursing interns.

2.
JAMA ; 326(10): 916-925, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519801

RESUMO

Importance: Standard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma. Objective: To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020). A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized. Interventions: Patients were randomized 1:1 to receive either camrelizumab 200 mg (n = 298) or placebo (n = 298), combined with up to 6 cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were given intravenously every 3 weeks. Main Outcomes and Measures: Coprimary end points were overall survival (significance threshold, 1-sided P < .02) and progression-free survival (significance threshold, 1-sided P < .005). Results: Of the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumab-chemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided P = .001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided P < .001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively. Conclusions and Relevance: Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03691090.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Método Duplo-Cego , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/secundário , Feminino , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Placebos , Intervalo Livre de Progressão , Qualidade de Vida , Análise de Sobrevida
3.
Future Oncol ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34269067

RESUMO

Definitive chemoradiotherapy is the standard of care for inoperable locoregionally advanced esophageal squamous cell carcinoma (ESCC). Immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibodies have led to a paradigm shift in advanced, metastatic ESCC treatment; however, the effect of incorporating checkpoint inhibitors in the definitive management of ESCC is unclear. Tislelizumab is an anti-PD-1 antibody specifically engineered to minimize FcÉ£R binding on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. The RATIONALE 311 study described here (BGB-A317-311; NCT03957590) is a registrational multicenter, double-blind, placebo-controlled, randomized, Phase III clinical trial designed to evaluate the efficacy and safety of tislelizumab combined with concurrent chemoradiotherapy in patients with inoperable localized ESCC.

4.
Int J Radiat Oncol Biol Phys ; 110(5): 1396-1406, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33677048

RESUMO

PURPOSE: To evaluate the feasibility and efficacy of involved-field irradiation in definitive chemoradiation therapy for locoregional esophageal squamous cell carcinoma. METHODS AND MATERIALS: Patterns in recurrence and elective nodal failure were analyzed in patients from the previously published ESO-Shanghai 1 trial, who received definitive chemoradiation therapy with involved-field irradiation to 61.2 Gy in 34 fractions using intensity modulated radiation therapy planning. Nodal regions were delineated using the lymph node map from the sixth edition of the American Joint Committee on Cancer staging system. Elective nodal failure was defined as recurrence in the regional nodal area outside the planning target volume. Extensive elective nodal failure, defined as an extensive nodal area regardless of tumor location, was calculated for additional analysis. The incidental (ie, mean) irradiation dose of each node and each region was evaluated. RESULTS: With a median follow-up of 48.7 months among survivors, the 3-year actuarial rate for overall survival was 53.6%, and the median overall survival was 44.8 months (95% confidence interval, 34.6-55.0). Of the 436 patients included in this study, 258 patients (59.2%) experienced treatment failure. Elective nodal failure was experienced by 37 patients (8.5%), 7 (1.6%) of whom encountered nodal-only failure. The 3-year actuarial rates of elective nodal control and elective nodal-only control were 89.7% and 97.9%, respectively. The median incidental dose of these nodes was 33.2 Gy (interquartile range [IQR], 1.3-50.7 Gy). The median distance of each node to the planning target volume was 1.4 cm (IQR, 0.6-4.9 cm). Extensive elective nodal failure was experienced by 51 patients (11.6%), and 20 (4.6%) patients had nodal-only failure. The 3-year extensive elective nodal control and extensive elective nodal control-only rates were 86.0% and 94.3%, respectively. The median incidental dose of these nodes was 23.2 Gy (IQR, 1.1-53.5 Gy). The median distance of each node to the planning target volume was 2.0 cm (IQR, 0.6-5.5 cm). CONCLUSION: Involved-field irradiation can achieve a low rate of isolated nodal failure and a satisfactory survival outcome. The use of elective nodal irradiation may be unnecessary in definitive chemoradiation therapy for the treatment of locoregional esophageal squamous cell carcinoma.


Assuntos
Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Radioterapia de Intensidade Modulada/métodos , Idoso , China , Cisplatino/uso terapêutico , Intervalos de Confiança , Fracionamento da Dose de Radiação , Esquema de Medicação , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/radioterapia , Estudos de Viabilidade , Feminino , Fluoruracila/uso terapêutico , Humanos , Linfonodos/diagnóstico por imagem , Irradiação Linfática , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Paclitaxel/uso terapêutico , Estudos Prospectivos , Fatores de Tempo , Falha de Tratamento
5.
Thorac Cancer ; 12(9): 1373-1381, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33760397

RESUMO

BACKGROUND: This multicentre, open-label study evaluated the efficacy and safety of antiprogrammed death ligand 1 antibody SHR-1316 plus liposomal irinotecan and 5-fluorouracil as the first-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC). METHODS: Eligible patients received SHR-1316 (10 mg/kg), liposomal irinotecan (60 mg/m2 for the first cycle, 80 mg/m2 thereafter), and 5-fluorouracil (2400 mg/m2 ) every 14 days until disease progression, intolerable toxicity or withdrawal of consent. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. RESULTS: We enrolled 23 patients between 11 March 2019 and 31 May 2019. The median follow-up duration was 15.2 months (95% CI 14.2-16.2). The median PFS was 8.5 months (95% CI 1.2-15.8), and ORR and DCR were 52.2% (95% CI 30.1-74.3) and 73.9% (95% CI 54.5-93.3), respectively. The median OS was 11.6 months (95% CI 6.7-16.6). The most common treatment-related grade 3-4 adverse events (AEs) were neutropenia (17.4%), nausea (13.0%), and anorexia (13.0%). Treatment-related serious AEs occurred in two patients. No treatment-related deaths occurred. CONCLUSIONS: SHR-1316 plus liposomal irinotecan and 5-fluorouracil has a promising efficacy and manageable safety profile, and could be a new first-line treatment approach for patients with unresectable locally advanced or distant metastatic ESCC.

6.
Future Oncol ; 17(11): 1285-1293, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33626929

RESUMO

For patients with oligometastatic esophageal squamous cell carcinoma, the efficacy of local therapy is still controversial because of patient selection and lack of adequate controls in most studies. Here the authors design the ESO-Shanghai 13 trial, a prospective, multicenter, randomized, Phase II trial, to assess the impact of combined local therapy and systemic therapy on progression and survival compared with systemic therapy alone for patients with four or less metastases. A total of 102 patients will be recruited over 3 years from approximately five centers and randomized in a 1:1 ratio to receive either systemic therapy alone or systemic therapy and local therapy, such as radiation, surgery and thermal ablation. The primary endpoint is progression-free survival. The secondary endpoints are overall survival, local control, toxicity and quality of life. Clinical trial registration: NCT03904927 (ClinicalTrials.gov).

7.
Oncologist ; 26(6): e925-e935, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33393167

RESUMO

LESSONS LEARNED: Apatinib has potential as an effective and safe second-line or higher treatment for patients with chemotherapy-refractory esophageal squamous cell carcinoma (ESCC). Clinical safety is of potential concern when administering apatinib to patients with uncontrolled esophageal lesions or severe invasion of trachea, bronchi, or major blood vessels. To the best of the authors' knowledge, this is the first prospective phase II study to investigate apatinib for patients with chemotherapy-refractory ESCC. Apatinib could provide an alternative option for ESCC after first-line or higher therapy in carefully selected patients. BACKGROUND: The aim of this study was to evaluate the efficacy and adverse effects of the oral vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase inhibitor apatinib in patients with chemotherapy-refractory esophageal squamous cell carcinoma (ESCC). METHODS: We enrolled patients with chemotherapy-refractory ESCC. All patients received continuous apatinib 500 mg once daily. RESULTS: Between July 2017 and August 2018, 40 patients were recruited, of whom 5 (12.5%) had uncontrolled primary tumors. Additionally, three patients with partial response (PR) and 23 with stable disease (SD) were observed for overall response rate (ORR) of 7.5% and disease control rate (DCR) of 65.0%. Median progression-free survival (PFS) was 3.8 months (95% confidence interval [CI], 2.2-5.4); median overall survival (OS) was 5.8 months (95% CI, 3.2-8.4). Common adverse effects were fatigue (15%), hypertension (12.5%), and palmar-plantar erythrodysesthesia syndrome (10%). Two cases of death from massive bronchopulmonary hemorrhage were observed, and esophageal fistula occurred in another two patients. Notably, both patients with esophageal fistula and one patient with massive fatal bronchopulmonary hemorrhage were individuals with uncontrolled primary tumors (3/5, 60%). Fatal bronchopulmonary hemorrhage in a second patient was associated with major blood vessel invasion. CONCLUSION: Apatinib has potential as an effective and safe treatment for patients with chemotherapy-refractory ESCC whose primary tumors are controlled and without severe invasion of trachea, bronchi, or major blood vessels.


Assuntos
Antineoplásicos , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias de Cabeça e Pescoço , Antineoplásicos/efeitos adversos , China , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Humanos , Estudos Prospectivos , Piridinas , Fator A de Crescimento do Endotélio Vascular
8.
J Thorac Oncol ; 16(2): 310-317, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33307192

RESUMO

INTRODUCTION: The optimal extent of lymphadenectomy during esophagectomy remains unclear. In this trial, we aim to clarify whether three-field (cervical-thoracic-abdominal) lymphadenectomy improved patient survival over two-field (thoracic-abdominal) lymphadenectomy for esophageal cancer. METHODS: Between March 2013 and November 2016, a total of 400 patients with middle and lower thoracic esophageal cancer were included and randomly assigned to undergo esophagectomy with either three- or two-field lymphadenectomy at a 1:1 ratio. Analyses were done according to the intention-to-treat principle. The primary end point was overall survival (OS), calculated from the date of randomization to the date of death from any cause. RESULTS: Demographic characteristics were similar in the two arms. The median follow-up time was 55 months (95% confidence interval [CI]: 52-58). OS (hazard ratio [HR] = 1.019, 95% CI: 0.727-1.428, p = 0.912) and the disease-free survival (DFS) (HR = 0.868, 95% CI: 0.636-1.184, p = 0.371) were comparable between the two arms. The cumulative 5-year OS was 63% in the three-field arm, as compared with 63% in the two-field arm; 5-year DFS was 59% and 53%, respectively. On the basis of whether the patients had mediastinal or abdominal lymph node metastasis or not, OS was also comparable between the two arms. In this cohort, only advanced tumor stage (pathologic TNM stages III-IV) was identified as the risk factor associated with reduced OS (HR = 3.330, 95% CI: 2.140-5.183, p < 0.001). CONCLUSIONS: For patients with middle and lower thoracic esophageal cancer, there was no improvement in OS or DFS after esophagectomy with three-field lymphadenectomy over two-field lymphadenectomy.


Assuntos
Neoplasias Esofágicas , Neoplasias Pulmonares , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Excisão de Linfonodo , Estadiamento de Neoplasias , Taxa de Sobrevida
9.
Int J Radiat Oncol Biol Phys ; 108(3): 707-715, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32417405

RESUMO

PURPOSE: This study aims to assess the safety and efficacy of stereotactic body radiation therapy (SBRT) for patients with oligometastatic esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS: From April 2015 to December 2018, a prospective, single-arm, phase 2 trial was conducted. The main inclusion criteria were ESCC patients with 3 or fewer metastases and a controlled primary malignancy after radical treatment, with all metastatic lesions amenable to SBRT. The enrolled patients were assigned to SBRT for all metastatic lesions and then received chemotherapy for at least 4 cycles starting from 0 to 15 days after SBRT. The primary endpoint was progression-free survival (PFS). Overall survival, local control, and toxicities were assessed in all patients. The study is listed at clinicaltrials.gov, number NCT03000816. RESULTS: Thirty-four patients with 40 oligometastatic lesions, including 25 in distant organs and 15 in nonregional lymph nodes, were treated with SBRT. All metastases belonged to genuine oligometastatic disease. Seventeen patients (50.0%) received a median of 4 cycles (interquartile range, 3-6 cycles) of chemotherapy after SBRT. At a median follow-up time of 18.2 months (interquartile range, 11.1-35.0 months), the median PFS time was 13.3 months (95% confidence interval, 10.7-15.9); the 1- and 2-year PFS rates were 55.9% and 33.8%, respectively. The 1- and 2-year overall survival rates were 76.2% and 58.0%, respectively. The 1- and 2-year local control rates were both 92.1%. Grade 3 acute toxicities were observed in only 1 patient. No grade ≥4 acute adverse events or grade ≥3 late adverse events due to SBRT occurred in this study. CONCLUSIONS: For well-selected patients with oligometastatic ESCC, SBRT with or without chemotherapy is a well-tolerated and efficacious treatment modality. The prognosis of oligometastatic ESCC is quite different from that of extensively metastatic ESCC, so treatment with an accurate stratification for patients with metastatic ESCC is necessary.


Assuntos
Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/radioterapia , Radiocirurgia/métodos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalos de Confiança , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/secundário , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/secundário , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimentos dos Órgãos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Intervalo Livre de Progressão , Estudos Prospectivos , Radiocirurgia/efeitos adversos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
10.
Radiat Oncol ; 15(1): 75, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32268925

RESUMO

BACKGROUND: The improvement of survival outcomes and the reduction of toxicities for esophageal squamous cell carcinoma (SCC) are still needed. We conducted a pilot study of concurrent chemoradiotherapy with weekly docetaxel and cisplatin for the treatment of esophageal SCC with T4 and/or M1 lymph node metastasis (LNM) or locoregional recurrence. METHODS: Fifty-four patients with advanced thoracic esophageal SCC having a stage T4 tumor or M1 LNM and/or locoregional recurrence were enrolled. Docetaxel and cisplatin were both administered weekly at a dose of 25 mg/m2 5-6 times in total concurrently with a specific dose of radiation. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), locoregional control and treatment-related toxicities. RESULTS: From October 2015 to December 2016, concurrent treatment with full-cycle docetaxel and cisplatin and radiotherapy was administered to 41 of 54 patients (75.9%). A total of 51 patients (94.4%) completed the radiation schedules. Twenty-one patients (44.4%) achieved a complete response, and 21 (44.4%) achieved a partial response after chemoradiotherapy. The median survival time was 18.2 months, and the median PFS time was 11.5 months. The 1-year and 3-year OS, locoregional control and PFS rates were 70.4, 80.6, 50.0 and 36.4%, 64.3, 31.5%, respectively. Grade 3 toxicities included neutropenia (13.0%), anemia (3.7%), thrombocytopenia (1.9%), fatigue (20.4%), anorexia (13.0%), esophagitis (11.1%), and pneumonitis (5.6%). Grade 4 neutropenia occurred in 16.7% of patients. Four patients (7.4%) died from grade 5 toxicities. There were no significant differences in both survival and grade 3 and higher toxicities between the newly diagnosed group and recurrent group. CONCLUSIONS: Concurrent chemoradiotherapy with weekly docetaxel and cisplatin is a well-tolerated and effective treatment regimen for esophageal SCC with T4 or M1 LNM and/or locoregional recurrence. Clinical trials with larger sample size and comparisons with conventional fluorouracil and cisplatin regimens are needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Neoplasias Esofágicas/terapia , Neoplasias de Células Escamosas/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Neoplasias Esofágicas/patologia , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
11.
Int J Radiat Oncol Biol Phys ; 107(1): 98-105, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31987968

RESUMO

PURPOSE: This prospective phase 2 study evaluated the efficacy and safety of intensity modulated radiation therapy plus etoposide/cisplatin (EP) for patients with unresectable thymic epithelial tumors (TETs). METHODS AND MATERIALS: Patients with limited advanced unresectable TETs whose lesions could be encompassed within radiation fields were enrolled in this study. Two cycles of EP (75 mg/m2 etoposide and 25 mg/m2 cisplatin on days 1-3 and days 29-31) were administered concurrently with radiation therapy, followed by 2 cycles after radiation therapy. The primary endpoint was the objective response rate. The secondary endpoints were the progression-free survival rate, overall survival rate, and incidence of adverse events. RESULTS: Fifty-six patients were enrolled between June 2011 and May 2018. Twenty-two and 34 patients had thymomas and thymic carcinomas, respectively. The median age was 52 (range, 21-76) years, and 30 patients (53.6%) were men. Eight patients (14.3%) had stage III tumors, 6 (10.7%) had stage IVA tumors, and 42 (75.0%) had stage IVB tumors. The objective response rate was 85.7% (95% confidence interval, 76.3%-95.2%). With a median follow-up of 46 (range, 7-101) months, the 1-, 2-, and 5-year progression-free survival rates were 66.1%, 48.0%, and 29.5%, and the 1-, 2-, and 5-year overall survival rates were 91.0%, 76.2%, and 56.2%, respectively. The most common grade 3 to 4 adverse event was leukopenia (42.9%). Pulmonary fibrosis was also observed (5.3%). CONCLUSIONS: Because intensity modulated radiation therapy with EP is effective and safe for limited advanced unresectable TETs, it could be a suitable treatment option for such patients.


Assuntos
Cisplatino/uso terapêutico , Etoposídeo/uso terapêutico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/radioterapia , Radioterapia de Intensidade Modulada , Neoplasias do Timo/tratamento farmacológico , Neoplasias do Timo/radioterapia , Adulto , Idoso , Cisplatino/efeitos adversos , Terapia Combinada , Intervalo Livre de Doença , Etoposídeo/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Estudos Prospectivos , Radioterapia de Intensidade Modulada/efeitos adversos , Segurança , Neoplasias do Timo/patologia , Neoplasias do Timo/cirurgia , Resultado do Tratamento , Adulto Jovem
12.
J Thorac Dis ; 11(10): 4205-4210, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31737304

RESUMO

Background: Liver and lung are the most common metastatic sites for esophageal cancer. Tumor location of esophageal cancer has been a prognostic factor of tumor, node and metastasis (TNM) staging system since 2009. However, the relationship between tumor location and metastatic sites remains unclear. Methods: Patients with esophageal cancer were derived from surveillance, epidemiology and end results (SEER) database from 2010 to 2013. Age, sex, histologic type and grade were included in the model for propensity score matching between patients with or without liver and lung metastasis. After propensity score matching, the relationship between tumor location and the probability of liver or lung metastasis was analyzed using chi-square analysis. Overall survival was analyzed between different locations within liver or lung metastasis patients. Results: A total of 6,812 patients were eligible. After matching, primary site was still an independent risk factor for both liver and lung metastasis. For patients with liver metastasis, lower esophagus was more likely to be the primary site than upper segment (P=0.014). In contrast, lung metastasis was more likely to be found in patients with upper esophageal cancer than lower segment (P=0.033). In liver metastasis group, those with upper esophageal cancer had the worst survival, followed by middle and lower segment and the results are opposite in lung metastasis group. Conclusions: These findings are useful in the evaluation when diagnose and follow up. Targeted examinations in accordance with tumor location will assist to find early metastasis and deliver treatment timely and properly.

13.
Front Oncol ; 9: 1116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31696059

RESUMO

Purpose: Our study aimed to provide data on effectiveness, safety of crizotinib treatment, brain metastases, progression patterns, and sequential therapy beyond crizotinib treatment in patients with advanced ALK-positive NSCLC in China. Methods: We reviewed the medical records of crizotinib-treated NSCLC patients with ALK-rearrangement between May 2014 and May 2018 at Fudan University Shanghai Cancer Center. All patients received crizotinib with 250 mg twice daily. Main outcome measures were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), the second PFS (PFS2), overall survival (OS), and adverse events. Results: One hundred and four patients with ALK-positive NSCLC were included in this retrospective study. ORR and DCR were 82.7 and 98.1%, respectively. The estimated PFS and OS were 13.0 months (95% CI 9.0-17.0 months) and 36.0 months (95% CI 31.0-41.0 months), respectively. Multivariable analysis showed that young age, presence of baseline adrenal gland metastases and non-adenocarcinoma were independent predictive factors for poorer PFS. Presence of baseline adrenal gland metastases, non-adenocarcinoma, intrathoracic progression and shorter crizotinib treatment time were associated with worse OS. Patients without baseline brain metastases (BBM) who were administered with crizotinib as first-line therapy can achieve a significantly longer PFS than those who received crizotinib as second or later line therapy (p = 0.006). For patients with BBM receiving sequential therapy beyond the first disease progression after crizotinib treatment (1st PD), crizotinib beyond progressive disease (CBPD) plus local therapy can lead to a significantly longer PFS2 (67.0 vs. 21.0 weeks; p = 0.046). Additionally, the OS was significantly longer in patients achieving 1st PD who received CBPD plus local therapy than those who did not receive CBPD or local therapy (35.0 vs. 24.0 months, p = 0.041). Presence of brain metastases at any time was in association with worse PFS. No unexpected adverse effects were reported. Conclusions: Crizotinib was effective and well tolerated in Chinese patients with ALK-positive, advanced NSCLC in real-world clinical practice. For patients without BBM, crizotinib as first-line therapy can lead to a longer PFS than second-or later line therapy. CBPD plus local therapy after 1st PD beyond crizotinib is feasible and effective in clinical routine practice.

14.
Pathol Res Pract ; 215(12): 152645, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31704154

RESUMO

BACKGROUND: Forkhead box protein P1 (FOXP1) has been suggested as a prognostic marker in several malignant tumors. However, the significance of FOXP1 in esophageal squamous cell carcinoma (ESCC) is still unclear. The purpose of this study was to investigate the expression pattern of FOXP1 in normal esophageal tissue and ESCC and to analyze the clinicopathological significance and prognostic value of FOXP1 in ESCC. METHODS: FOXP1 was detected by immunohistochemistry using tissue microarrays containing tumor tissues and adjacent normal tissues from 270 ESCC patients with oncological follow-up data. RESULTS: Normal esophageal tissues predominantly showed an exclusive nuclear FOXP1 (n-FOXP1) expression pattern, and no exclusive cytoplasmic FOXP1 (c-FOXP1) staining was found. In ESCC, the expression rates of exclusive n-FOXP1-positive, exclusive c-FOXP1-positive, both nuclear and cytoplasmic positive and complete negative were 14.4%, 28.9%, 10.4% and 46.3%, respectively. High n-FOXP1 expression was significantly correlated with decreased postoperative recurrence and distant metastasis (P < 0.05). Furthermore, elevated c-FOXP1 expression was significantly associated with regional lymph node metastasis and distant metastasis (P < 0.05). High c-FOXP1 expression had an effect on shorter overall survival (OS) time, but the difference was not statistically significant (P > 0.05). Kaplan-Meier analysis showed that ESCC patients with high n-FOXP1 expression survived significantly longer than patients with low n-FOXP1 expression. Multivariate analysis confirmed that patients with high n-FOXP1 staining exhibit good prognosis and n-FOXP1 was an independent factor for ESCC prognosis. CONCLUSIONS: Our results suggest that FOXP1 plays an essential role in ESCC progression and prognosis and may be a useful biomarker for predicting survival.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Esofágicas/química , Carcinoma de Células Escamosas do Esôfago/química , Fatores de Transcrição Forkhead/análise , Proteínas Repressoras/análise , Núcleo Celular/química , Citosol/química , Progressão da Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/secundário , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Fatores de Risco , Fatores de Tempo , Análise Serial de Tecidos , Resultado do Tratamento , Regulação para Cima
15.
16.
Ann Surg Oncol ; 26(8): 2367-2374, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31187360

RESUMO

BACKGROUND: The value of adjuvant therapy for esophageal squamous cell carcinoma (ESCC) has been controversial, at least partially due to the lack of efficient criteria for selecting suitable patients. This study aimed to explore the existence of parameters related to lymph node (LN) status that can predict the value of adjuvant therapy in ESCC. METHODS: The study included 298 patients with ESCC who had undergone radical esophagectomy with lymphadenectomy. Adjuvant therapy was defined as reception of adjuvant chemotherapy, radiotherapy, or chemoradiotherapy. For the study, LN ratio (LNR), total number of resected LNs (TLNs), and pN stage were selected for Cox regression analyses, including their correlations and prognostic values for survival. Log-rank tests were used to compare the survival rates of the patients with and without adjuvant therapy stratified by pN stage, TLNs, LNR, or their combinations. RESULTS: The independent prognostic factors for survival were TLNs, LNR, and pN stage. Whereas pN stage was significantly related to TLNs and LNR, TLNs were not correlated with LNR. The survival rates between the patients with and those without adjuvant therapy stratified by pN stage, TLNs, or LNR did not differ significantly. We used the median values of TLNs and LNR to group the patients into four groups. The patients in the group with fewer TLNs and higher LNR who had undergone adjuvant therapy showed a significantly better survival than those without adjuvant therapy (p = 0.030). CONCLUSIONS: In contrast to TLNs, LNR, and pN stage as single factors, the combination of TLNs and LNR can predict the value of adjuvant therapy.


Assuntos
Carcinoma de Células Escamosas/secundário , Quimiorradioterapia Adjuvante/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/secundário , Linfonodos/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
17.
Target Oncol ; 14(3): 315-323, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30976989

RESUMO

BACKGROUND: Approximately 1-2% of patients with non‒small-cell lung cancer (NSCLC) harbor ROS1 rearrangements. Crizotinib, an oral small-molecule tyrosine kinase inhibitor (TKI) that targets anaplastic lymphoma kinase (ALK), MET, and ROS1, has shown marked antitumor activity in patients with ROS1-positive advanced NSCLC. OBJECTIVE: Our objective was to analyze the efficacy and safety of crizotinib treatment in Chinese patients with advanced NSCLC with ROS1 rearrangement in real-world clinical practice. METHODS: We included 35 patients with ROS1-positive NSCLC in this retrospective analysis. All received crizotinib 250 mg twice daily between March 2016 and April 2018 at the Fudan University Shanghai Cancer Center. All had histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangements, which were identified by fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction, or next-generation sequencing. The main outcome measures were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events. RESULTS: The median age of the patients was 51.0 years; 23 (65.7%) were female and 28 (80.0%) were never smokers. All were diagnosed as having adenocarcinoma; eight patients (22.9%) had brain metastases at baseline. The ORR and DCR were 71.4% and 94.3%, respectively. The estimated median PFS was 11.0 months (95% confidence interval [CI] 7.8-14.2). The estimated median OS was 41.0 months (95% CI 22.5-59.5). Elevated transaminases (54.3%), vision disorder (25.7%), elevated blood creatinine (22.9%), diarrhea (20.0%), and vomiting (20.0%) were the most commonly reported adverse effects. CONCLUSION: Crizotinib was effective and well tolerated in Chinese patients with ROS1-positive advanced NSCLC in real-world clinical practice. The progression sites and patterns, as well as treatments after first disease progression on crizotinib were diverse. Crizotinib beyond progressive disease and local therapy after failure of crizotinib treatment were feasible and effective in clinical practice.


Assuntos
Antineoplásicos/uso terapêutico , Grupo com Ancestrais do Continente Asiático/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Crizotinibe/uso terapêutico , Rearranjo Gênico , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Terapia de Salvação , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
18.
J Cell Biochem ; 120(8): 12259-12272, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31017699

RESUMO

Emerging evidence indicates that microRNAs (miRNAs) play an important role in tumor carcinogenesis and progression by targeting gene expression. The goal of this study was to comprehensively analyze the vital functional miRNAs and their target genes in esophageal squamous cell carcinoma (ESCC) and to explore the clinical significance and mechanisms of miR-1 in ESCC. First, the miRNA and messenger RNA (mRNA) expression profiles of ESCC were determined with microarray technology. Using an integrated analysis of miRNAs and their target genes with multistep bioinformatics methods, the miRNA-mRNA regulatory network in ESCC was constructed. Next, miR-1 expression in 292 ESCC patients and its relationship with clinicopathological features and prognosis were detected by in situ hybridization. Furthermore, the biological functions of miR-1 were determined with in vitro and in vivo functional experiments. Finally, real-time quantitative reverse transcription polymerase chain reaction, Western blot analysis, and luciferase reporter assays were performed to verify the target genes of miR-1. In this study, 67 miRNAs and 2992 genes were significantly differentially expressed in ESCC tissues compared with their expression in adjacent normal tissues, and an miRNA-mRNA regulatory network comprising 59 miRNAs and 162 target mRNAs was identified. Low miR-1 expression was correlated with pathological T stage, lymph node metastasis, vessel invasion, and poor clinical outcome. miR-1 suppressed ESCC cell proliferation and invasion and promoted ESCC cell apoptosis. Fibronectin 1 (FN1) was verified as a direct target of miR-1. Taken together, the present results suggest that miR-1 may be a valuable prognostic predictor for ESCC, and the miR-1/FN1 axis may be a therapeutic target.


Assuntos
Biomarcadores Tumorais/genética , Progressão da Doença , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs/metabolismo , Animais , Apoptose/genética , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Fibronectinas/genética , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Modelos de Riscos Proporcionais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Front Genet ; 10: 47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30833958

RESUMO

Background: Esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis and occurs with high frequency in China. The germline mutation profile in ESCC remains unclear, and therefore, the discovery of oncogenic alterations in ESCC is urgently needed. This study investigates the germline mutation profile and reveals associations among genotype-environment interactions in ESCC. Methods: Whole exome sequencing and follow-up analysis were performed in 77 matched tumor-normal ESCC specimens to examine the germline profiles. Additionally, associations among genotype-environment interactions were investigated. Results: We identified 84 pathogenic/likely pathogenic mutations and 51 rare variants of uncertain significance (VUS). Twenty VUS with InterVar evidence of a score of moderate pathogenicity (PM) 2/PM2+ supporting pathogenicity (PP) 1 were found to have pathogenic significance. CYP21A2 was the most frequently mutated gene, and the p.Gln319* variant was identified in 6.5% (5/77) of patients. The TP53 p.V197E mutation, located within the DNA binding domain, was found in 1.3% (1/77) of patients. In total, the 11.7% (9/77) of individuals with homologous recombination (HR) VUS were more likely to have well-differentiated tumors than those without (P = 0.003). The degree of lymph node metastasis was correlated with homologous recombination deficiency (HRD) and VUS group (P < 0.05). Moreover, the 10.4% (8/77) of individuals with mismatch repair (MMR) VUS had a higher tumor mutational burden (TMB), although the correlation was not significant. Conclusions: Our study identified the germline mutation profiles in ESCC, providing novel insights into the molecular pathogenesis of this disease. Our results may also serve as a useful resource for the exploration of the underlying mechanism of ESCC and may provide information for the prevention, diagnosis and risk management of ESCC.

20.
J Clin Oncol ; 37(20): 1695-1703, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-30920880

RESUMO

PURPOSE: This trial aimed to assess the efficacy and safety of the paclitaxel plus fluorouracil regimen versus the cisplatin plus fluorouracil regimen in definitive concurrent chemoradiotherapy (dCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Patients with locally advanced ESCC were enrolled and randomly assigned to either the paclitaxel plus fluorouracil group or the cisplatin plus fluorouracil group. The patients in the paclitaxel plus fluorouracil group were treated with paclitaxel and fluorouracil one cycle per week in dCRT for five cycles followed by paclitaxel and fluorouracil one cycle per month in consolidation chemotherapy for two cycles. The patients in the cisplatin/5-fluorouracil group were treated with cisplatin and fluorouracil one cycle per month in dCRT for two cycles followed by two cycles in consolidation chemotherapy. The radiotherapy dose was 61.2 Gy delivered in 34 fractions. The primary end point was 3-year overall survival (OS). RESULTS: Four hundred thirty-six patients with ESCC in six centers were recruited at a 1:1 ratio between April 2012 and July 2015. The median follow-up of the surviving patients was 48.7 months (interquartile range, 42.6-60.9). The 3-year OS was 55.4% in the paclitaxel plus fluorouracil group and 51.8% in the cisplatin plus fluorouracil group (hazard ratio, 0.905 [95% CI, 0.698 to 1.172]; P = .448). The 3-year progression-free survival was also not significantly different between the paclitaxel plus fluorouracil group and the cisplatin plus fluorouracil group (43.7% v 45.5%, respectively; hazard ratio, 0.973 [95% CI, 0.762 to 1.243]; P = .828). Compared with the cisplatin plus fluorouracil group, the paclitaxel plus fluorouracil group had significantly lower incidences of acute grade 3 or higher anemia, thrombocytopenia, anorexia, nausea, vomiting, and fatigue (P < .05), but higher incidences of acute grade 3 or higher leukopenia, radiation dermatitis, and radiation pneumonitis (P < .05). CONCLUSION: The paclitaxel plus fluorouracil regimen did not significantly prolong the OS compared with the standard cisplatin plus fluorouracil regimen in dCRT in patients with locally advanced ESCC.


Assuntos
Carcinoma de Células Escamosas/terapia , Cisplatino/administração & dosagem , Neoplasias Esofágicas/terapia , Fluoruracila/administração & dosagem , Paclitaxel/administração & dosagem , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimiorradioterapia , China , Quimioterapia de Consolidação , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fótons , Modelos de Riscos Proporcionais , Resultado do Tratamento , Adulto Jovem
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