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BACKGROUND: Neoadjuvant therapy plus oesophagectomy has been accepted as the standard treatment for patients with potentially curable locally advanced oesophageal cancer. No completed randomized controlled trial (RCT) has directly compared neoadjuvant chemotherapy and neoadjuvant chemoradiation in patients with oesophageal squamous cell carcinoma (ESCC). The aim of the current RCT is to investigate the impact of neoadjuvant chemotherapy plus surgery and neoadjuvant chemoradiotherapy plus surgery on overall survival for patients with resectable locally advanced ESCC. METHODS: This open label, single-centre, phase III RCT randomized patients (cT2-T4aN + M0 and cT3-4aN0M0) in a 1:1 fashion to receive either the CROSS regimen (paclitaxel 50 mg/m2; carboplatin (area under the curve = 2), q1w, 5 cycles; and concurrent radiotherapy, 41.4 Gy/23 F, over 5 weeks) or neoadjuvant chemotherapy (paclitaxel 175 mg/m2; and cisplatin 75 mg/m2, q21d, 2 cycles). Assuming a 12% 5-year overall survival difference in favour of the CROSS regimen, 80% power with a two-sided alpha level of 0.05 and a 5% dropout each year for an estimated 3 years enrolment, the power calculation requires 456 patients to be recruited (228 in each group). The primary endpoint is 5-year overall survival, with a minimum 5-year follow-up. The secondary endpoints include 5-year disease-free survival, toxicity, pathological complete response rate, postoperative complications, postoperative mortality and quality of life. A biobank of pre-treatment and resected tumour tissue will be built for translational research in the future. DISCUSSION: This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies. TRIAL REGISTRATION: NCT04138212, date of registration: October 24, 2019.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Esofagectomia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Fracionamento da Dose de Radiação , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Masculino , Terapia Neoadjuvante , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Projetos de Pesquisa , Análise de Sobrevida , Resultado do TratamentoRESUMO
Background: While multiple system atrophy (MSA) presents with high heterogeneous motor and nonmotor symptoms, the associations between clinical phenotypes and prognosis are unclear. Objective: We aimed to evaluate clinical phenotypes of MSA using data-driven approach and measure the impact of phenotypes on survival and bedbound status. Methods: 193 MSA patients were recruited from Xuanwu Hospital Capital Medical University, whose history, motor and non-motor symptoms were examined using cluster analysis. Ninety-five participants were followed-up via telephone after a mean of 31.87 months. We employed Kaplan- Meier analysis to examine survival and performed Cox and logistic regression analyses to identify factors associated with survival and bedbound status. Results: We identified four clinical profiles of MSA: cerebellar symptom-dominant, sleep and mood disorder-dominant, rigid akinetic-dominant, and malignant diffuse. The overall median survival was 7.75 years (95% CI 7.19-8.31). After adjusting for years from symptom onset to diagnosis, age and sex, patients in the malignant diffuse and rigid akinetic-dominant clusters had greater risk of death than sleep and mood disorder-dominant cluster. Furthermore, patients in the malignant diffuse and rigid akinetic-dominant clusters had higher risk of being bedbound than cerebellar symptom-dominant cluster. Conclusions: The malignant diffuse and sleep and mood disorder-dominant were identified besides the two classical subtypes, parkinsonism, and cerebellar symptom-variant. Patients with rigid-akinetic motor profiles have a worse prognosis than cerebellar symptom-dominant profiles in general. Diffuse symptoms, especially postural instability, and cognitive alterations at diagnosis, indicate rapid functional loss and disease progression. The different profiles and prognoses might indicate varied underlying pathological mechanisms.
Multiple system atrophy (MSA) is a complex disease that can affect both movement and non-movement functions of patients. However, we do not know much about how these different symptoms relate to how the patient's health might change over time. In this study, we looked at 193 MSA patients to learn more about if the patients can be distinguished into different subgroups at diagnosis and if the subgroups might be associated with their survival and ability to move in the future. We found four main subgroups of patients: group 1 characterized by the dysfunction of cerebellum (a part of the brain), group 2 characterized by sleep and mood problems, group 3 characterized by rigidity and slow movements, and group 4 with diffuse symptoms mentioned above. After tracking 95 patients for nearly 32 months, we found that those characterized by rigidity and slow movements, and those with diffuse symptoms had a higher chance of dying compared to those characterized by sleep and mood problems. Group 3 and 4 also had a higher chance of becoming unable to move out of bed. This suggests that patients with severe symptoms of rigidity and slowness at diagnosis tend to have a worse outlook than those without. And if multiple MSA symptoms are found when the patient is diagnosed, especially trouble with thinking, are also signs that the disease is getting worse quickly. By understanding these disease patterns, we can better tailor treatments and provide better support for people with MSA.
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INTRODUCTION: The motor subtypes of Parkinson's disease (PD) are widely accepted and implemented. However, the motor subtypes have been thought to represent different stages of PD recently because some patients experience tremor-dominant (TD) conversion to the non-tremor-dominant subtype, such as postural instability-gait difficulty (PIGD). In this study, we explore the monoaminergic denervation features of the striatal and extra-striatal areas in patients with different subtypes of PD with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-DTBZ) PET/CT. METHODS: Sixty-five patients diagnosed with PD were included and classified as TD (n = 25) and PIGD (n = 40). We evaluated the difference of monoaminergic features of each subregion of brain between motor subtypes of PD, as well as associations between these features and Parkinsonian motor symptoms. RESULTS: The striatal standardized uptake value ratios (SUVR) showed that dopaminergic disruption of patients with PIGD was more symmetrical in the posterior ventral putamen (p < 0.001) and more severe in the ipsilateral posterior dorsal putamen (p < 0.001 corrected) compared with that of patients with TD. The severity of PIGD scores was associated with striatal dopaminergic depletion, while tremor was associated with monoaminergic changes in extra-striatal areas, including pallidus, thalamus, and raphe nuclie. CONCLUSION: These results indicate that patients with different motor subtypes may have different underlying mechanisms of PD pathogenesis. Therefore, accurate diagnosis of PD subtypes can aid prognosis evaluation and treatment decision-making.
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Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Tremor/etiologia , Tremor/complicações , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/efeitos adversos , Putamen/diagnóstico por imagem , Putamen/patologia , Encéfalo/patologia , DopaminaRESUMO
OBJECTIVE: To evaluate the value of intraoperative radiation therapy with electrons (ELIOT) in treatment of malignant bone or soft tissue tumors around the joints. METHODS: From October 2008 to April 2012, nineteen patients with malignant bone or soft tissue tumors around the joints were treated with ELIOT. The tumors were located around the knee joint in 8 patients, around the hip joint in 6 patients, around the elbow joint in 4 patients and around the shoulder joint in one patient. All of the patients underwent limb salvage surgeries. R0 resections were performed in 18 patients, while R1 resection was performed in one patient. The doses of intraoperative radiation ranged from 10 Gy to 22 Gy. The median dose was 19 Gy. More than one ELIOT fields were used in 10 patients because of the large tumor size. RESULTS: Seven patients suffered wound complications. No grade ≥ 3 acute toxicities were observed. One patient developed radiation ulcer and arterial fistula 15 months after surgery and ELIOT, and resulted in amputation finally (grade 4 late toxicity). The mean Musculoskeletal Tumor Society (MSTS) 93 score was 26.26 ± 4.04 (87.5% ± 13.5%), with excellent to good extremity functions in 18 patients (94.7%). Four patients had local recurrences. The estimated locoregional control rates at 1, 2, and 3 years were 81.9%, 73.7%, and 73.7%, respectively. Seven patients died of the diseases. The estimated overall survivals of the entire group of patients at 1, 2, and 3 years were 76.3%, 61.2%, and 51.0%, respectively. CONCLUSIONS: ELIOT is a safe and well-tolerable technique and could be widely used for patients with malignant bone or soft tissue tumors around the joints with acceptable rates of acute and late toxicity. There is positive significance for controlling the tumor local recurrence, preserving the joint function and improving survival quality.
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Neoplasias Ósseas/radioterapia , Elétrons/uso terapêutico , Salvamento de Membro , Neoplasias de Tecidos Moles/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/cirurgia , Articulação do Cotovelo , Feminino , Seguimentos , Articulação do Quadril , Humanos , Período Intraoperatório , Articulação do Joelho , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Aceleradores de Partículas , Radioterapia Adjuvante , Neoplasias de Tecidos Moles/cirurgia , Taxa de Sobrevida , Adulto JovemRESUMO
OBJECTIVE: To analyze the complications and short-term outcomes of patients receiving intraoperative electron radiotherapy (IOERT) for locally advanced and recurrent periarticular soft tissue sarcomas of the extremities. METHODS: Twenty-one adult patients with locally advanced and/or recurrent periarticular soft tissue sarcomas of the extremities treated with IOERT were included in this study. Among them 14 patients had recurrent diseases after prior operation and 7 patients with locally advanced disease with primary treatment. The total dose of radiation ranged from 11 Gy to 21 Gy of 6 - 12 MeV beta ray given by intraoperative radiotherapy after complete tumor resection with negative margins. Five patients were given external beam radiotherapy (EBRT) with a total dose of 40 - 50 Gy, and 10 patients received chemotherapy. RESULTS: The median follow-up time was 15 months. Five patients (23.8%) had tumor relapse, including one patients with local recurrence, one patient with regional recurrence, two patients with distant metastasis and one patient with local recurrence and distant metastasis. The actuarial local control rate at 1 year was 95.2% (20/21), and at 2 years was 90.5% (19/21). Acute skin toxicity (RTOG) within 3 months after surgery included grade I in 6 patients and grade II in 3 patients. Two year late skin toxicity (RTOG/EORTC) included grade I in 4 patients and grade II in 2 patients. Fibrosis included grade I in 3 patients and grade II in 3 patients. Six patients had joint dysfunction (3 patients with grade I and 3 with grade II) and 6 patients had healing problems. One patient got ipsilateral schiatic neuritis 9 months after IOERT. No adverse events occurred during surgery. CONCLUSIONS: IOERT brings tolerable complications of acute and late toxicities and favorable local control rate. IOERT should be followed by postoperative radiotherapy or increase the intraoperative radiation dose for locally advanced and recurrent sarcomas to get a better local control. Otherwise, distant metastasis is one of the main reasons of treatment failure, so chemotherapy should be added to the treatment regimen.
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Elétrons/uso terapêutico , Extremidades , Recidiva Local de Neoplasia/radioterapia , Sarcoma/radioterapia , Adolescente , Adulto , Idoso , Atrofia/etiologia , Elétrons/efeitos adversos , Feminino , Fibrose/etiologia , Seguimentos , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Neoplasia Residual/radioterapia , Dosagem Radioterapêutica , Radioterapia Adjuvante/efeitos adversos , Sarcoma/tratamento farmacológico , Sarcoma/cirurgia , Pele/patologia , Adulto JovemRESUMO
The gene fragment of PFC0460w was amplified from RNA of Plasmodium falciparum 3D7 strain with RT-PCR, and cloned into pGEM-T easy vector. The recombinant plasmid was transformed into E. coli DH5alpha and the positive clones were selected, which were identified by PCR and sequencing. The results showed that there were three sequences of PFC0460w fragment, respectively with length of 618, 597 and 543 bp. The 618 bp fragment was completely consistent with the sequence published in PlasmoDB (GenBank No. XM_001351147), and the 597 bp and 543 bp fragments were submitted to GenBank with Accession No. of JF799872 and JF799873, respectively. 205 amino acids were encoded by the 618 bp fragment, and five kinds of protein structure were predicted by Robetta.
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Biologia Computacional , Genes de Protozoários , Plasmodium falciparum/genética , Animais , Clonagem Molecular , Vetores Genéticos , Dados de Sequência Molecular , PlasmídeosRESUMO
BACKGROUND: Recurrence of thymomas even after complete resection is common, but the relapse patterns remain controversial. This study aimed to define the patterns and predictors of relapse after complete resection of thymoma. METHODS: A single-institution retrospective study was performed with 331 patients who underwent radical resection of thymoma between 1991 and 2012. RESULTS: After a median follow-up of 59 months, the recurrence rate was 6.9% (23/331). Relapse occurred in 23 patients with the pleura (14) and tumor bed (6) as the most common sites of recurrence. According to the definitions of the International Thymic Malignancy Interest Group, 10 (43.5%) patients had local relapse, 15 (65.2%) had regional relapse, 10 (43.5%) had distant relapse. The difference in survival following relapse between lung and regional relapse was statistically significant (P=0.027) but that between lung and distant relapse was not (P=0.808). The recurrence rates correlated with the initial Masaoka stage. Further, recurrence also correlated with World Health Organization (WHO) tumor type. The recurrence-free survival rates in patients with tumor size ⩾8 cm were worse than those of patients with tumor size <8 cm (P=0.007). Tumor size was also correlated with stage (r=0.110). As tumor becomes larger, the stage is more advanced (P=0.023). Multivariate analysis showed that Masaoka stage (P=0.005), tumor size (P=0.033), and WHO histological type (P=0.046) were predictive factors of relapse. CONCLUSION: Regional recurrence is the most common relapse pattern but local and distant relapse are also common. Advanced Masaoka stage, larger tumor size, and type B3 are risk factors of recurrence. Lung relapse should be considered distant relapse. Further, tumor size was correlated with Masaoka stage and therefore should be considered in the staging system.
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Timoma/radioterapia , Neoplasias do Timo/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva , Estudos Retrospectivos , Fatores de Risco , Tórax , Timoma/diagnóstico , Neoplasias do Timo/diagnósticoRESUMO
BACKGROUND: Lymph node ratio (LNR) has recently been reported as a potential prognostic marker in many malignant diseases. We aimed to analyze the potential prognostic effect of LNR on hypopharyngeal squamous cell carcinoma (HPSCC) after neoadjuvant therapy in our institution. METHODS: We performed a retrospective study of 279 patients with HPSCC who underwent radiotherapy with or without chemotherapy followed by neck dissection between November 1965 and December 2008. Patients were divided into four groups according to quartiles based on LNR. RESULTS: The mean LNR was 10.4% (range 0-100%, median 4.3%). Males and advanced clinical N classification significantly increased the LNR (P = 0.014 and P < 0.001, respectively). Compared with those with LNR <0.14, LNR ≥0.14 was associated with reduced overall, disease-specific and disease-free survival (all at P < 0.001). Multivariate analysis revealed that LNR is an independent predictor of prognosis. CONCLUSION: Our results suggest that LNR is a strong predictor of HPSCC after chemoradiotherapy.