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ObjectiveThis study aims to investigate the inhibitory effect of Wutoutang on pannus formation in adjuvant-induced arthritis (AIA) rats with wind-cold-dampness Bi syndrome and its potential mechanism. MethodA total of 40 male SD specific pathogen-free (SPF) rats were selected and divided into blank group, wind-cold-dampness Bi syndrome group [Complete Freund's Adjuvant (CFA), 200 μg], Wutoutang group (15 g·kg-1·d-1), and indometacin group (10 mg·kg-1) according to random number table method. Except for the blank group, the other groups were given wind-cold-dampness stimulation before the CFA injection. After the rats were administered for 30 days, the basic conditions, onset time, arthritis index score, and foot swelling volume of AIA rats with wind-cold-dampness Bi syndrome were observed. Finally, peripheral arterial blood, ankle joint, and synovial tissue were taken. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGFA) protein content, and rheumatism, including anti-O (ASO), C-reactive protein (CRP), and rheumatoid factor (RF). Hematoxylin-eosin (HE) staining revealed the changes in joint histomorphology. Immunohistochemistry was used to detect the expression of HIF-1α and VEGFA, two important proteins in the ankle pathway. Quantitative real-time polymerase chain reaction (Real-time PCR) was used to reveal mRNA levels of HIF-1α, VEGFA, angiopoietin-1 (Ang-1), and angiopoietin-2 (Ang-2) in rat synovial tissue. ResultThe foot swelling volume and arthritis score of AIA rats with wind-cold-dampness Bi syndrome were substantially higher (P<0.01) compared with the blank group. Serum CRP, RF, and ASO levels were considerably elevated (P<0.01). HE staining showed obvious hyperplasia of ankle synovium and synovial inflammation, angiogenesis and pannus formation, and aggravated bone destruction, indicating successful modeling. After the intervention of Wutoutang, the onset time was delayed (P<0.01). Foot swelling volume and arthritis score were decreased (P<0.01). Serum CRP, RF, and ASO levels were significantly decreased (P<0.01). The inflammatory hyperplasia of synovial tissue, angiogenesis and pannus formation, and bone destruction were alleviated. The mRNA levels of HIF-1α, VEGFA, Ang-1, and Ang-2 in the synovial membrane were significantly decreased (P<0.05, P<0.01). The expressions of HIF-1α and VEGFA in serum and ankle joints were decreased (P<0.01). In the indomethacin group, the onset time of the disease was delayed (P<0.01). Foot swelling volume and arthritis score were decreased (P<0.01). Serum CRP, RF, and ASO levels were significantly decreased (P<0.01). HIF-1α/VEGFA/Ang signaling pathway was activated, and pathological tissue injury was improved. ConclusionWutoutang can delay the onset time of AIA rats with wind-cold-dampness Bi syndrome, reduce foot swelling volume, arthritis score, rheumatic activity, and improve joint histopathology. It can inhibit pannus formation, and its mechanism may be related to down-regulating the expression of the HIF-1α/VEGFA/Ang pathway.
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Objective:To investigate the predictive value of enhanced CT-based radiomics for brain metastasis (BM) and selective use of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC).Methods:Clinical data of 97 patients diagnosed with LS-SCLC confirmed by pathological and imaging examination in Shanxi Provincial Cancer Hospital from January 2012 to December 2018 were retrospectively analyzed. The least absolute shrinkage and selection operator (LASSO) Cox and Spearman correlation tests were used to select the radiomics features significantly associated with the incidence of BM and calculate the radiomics score. The calibration curve, the area under the receiver operating characteristic (ROC) curve (AUC), 5-fold cross-validation, decision curve analysis (DCA), and integrated Brier score (IBS) were employed to evaluate the predictive power and clinical benefits of the radiomics score. Kaplan-Meier method and log-rank test were adopted to draw survival curves and assess differences between two groups.Results:A total of 1272 radiomics features were extracted from enhanced CT. After the LASSO Cox regression and Spearman correlation tests, 8 radiomics features associated with the incidence of BM were used to calculate the radiomics score. The AUCs of radiomics scores to predict 1-year and 2-year BM were 0.845 (95% CI=0.746-0.943) and 0.878 (95% CI=0.774-0.983), respectively. The 5-fold cross validation, calibration curve, DCA and IBS also demonstrated that the radiomics model yielded good predictive performance and net clinical benefit. Patients were divided into the high-risk and low-risk cohorts based on the radiomics score. For patients at high risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 18.2% in the PCI group, and 61.8% and 75.4% in the non-PCI group, respectively ( P<0.001). In the PCI group, the 1-year and 2-year overall survival rates were 92.9% and 78.6%, and 85.3% and 36.8% in the non-PCI group, respectively ( P=0.023). For patients at low risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 0% in the PCI group, and 10.0% and 20.2% in the non-PCI group, respectively ( P=0.062). In the PCI group, the 1-year and 2-year overall survival rates were 100% and 77.0%, and 96.7% and 79.3% in the non-PCI group, respectively ( P=0.670). Conclusion:The radiomics model based on enhanced CT images yields excellent performance for predicting BM and individualized PCI.
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Objective:To investigate the radiation dose and fractionation regimens for limited stage small cell lung cancer (LS-SCLC) in Chinese radiation oncologists.Methods:Over 500 radiation oncologists were surveyed through questionnaire for radiation dose and fractionation regimens for LS-SCLC and 216 valid samples were collected for further analysis. All data were collected by online questionnaire designed by WJX software. Data collection and statistical analysis were performed by SPSS 25.0 statistical software. The differences in categorical variables among different groups were analyzed by Chi-square test and Fisher's exact test. Results:Among 216 participants, 94.9% preferred early concurrent chemoradiotherapy, 69.4% recommended conventional fractionation, 70.8% preferred a total dose of 60 Gy when delivering conventional radiotherapy and 78.7% recommended 45 Gy when administering hyperfractionated radiotherapy.Conclusions:Despite differences in LS-SCLC treatment plans, most of Chinese radiation oncologists prefer to choose 60 Gy conventional fractionated radiotherapy as the main treatment strategy for LS-SCLC patients. Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN) and Chinese Medical Association guidelines or expert consensus play a critical role in guiding treatment decision-making.
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Objective:To investigate the value of derived neutrophil-to-lymphocyte ratio (dNLR) in predicting the prognosis of extensive-stage small cell lung cancer (ES-SCLC) patients treated with the first-line atezolizumab immunotherapy and chemotherapy.Methods:From the Project Data Sphere platform, the clinical data and laboratory test data of 53 ES-SCLC patients who received the first-line atezolizumab immunotherapy and chemotherapy in the global multicenter phase Ⅱ prospective study NCT03041311 from February 2017 to February 2022 were collected. The Contal-O'Quigley method was used to calculate the optimal cut-off value of baseline dNLR for determining the overall survival (OS) of patients. The dNLR higher than or equal to the optimal cut-off value was defined as high dNLR, and less than the optimal cut-off value was defined as low dNLR. According to optimal cut-off value, the dNLR levels at baseline and after 4 cycles of chemotherapy were determined, and dynamic dNLR grouping was performed (low risk: low dNLR at baseline and after 4 cycles of chemotherapy; intermediate risk: high dNLR at baseline or after 4 cycles of chemotherapy; high risk: high dNLR at baseline and after 4 cycles of chemotherapy). The differences in clinicopathological features between the baseline high dNLR group and low dNLR group were analyzed. Kaplan-Meier method was used to draw the OS and progression-free survival (PFS) curves, and log-rank test was used to compare the differences between the two groups. Univariate Cox proportional hazards model was used to analyze the influencing factors of OS and PFS. The time-dependent receiver operating characteristic (ROC) curve was used to evaluate the predictive value of baseline dNLR grouping and dynamic dNLR grouping for 1-year OS rate in ES-SCLC patients receiving the first-line atezolizumab immunotherapy and chemotherapy.Results:Among the 53 patients, 34 (64.20%) were male and 19 (35.80%) were female; 27 (50.90%) were < 65 years old and 26 (49.10%) were ≥65 years old. The optimal cut-off value of baseline dNLR for determining the OS was 1.79. There were 17 cases in low dNLR group and 36 cases in high dNLR group at baseline. The proportion of patients with elevated serum lactate dehydrogenase (LDH) in the baseline high dNLR group was higher than that in the baseline low dNLR group [58.33% (21/36) vs. 17.65% (3/17), χ2 = 7.72, P = 0.005]. The 1-year OS rates of the baseline high and low dNLR groups were 44.0% and 81.9%, and the 1-year PFS rates were 2.5% and 17.6%. The differences in OS and PFS between the two groups were statistically significant (both P < 0.05). There were 38 patients with complete dynamic dNLR data, including 9 cases of low-risk, 19 cases of medium-risk and 10 cases of high-risk, and the 1-year OS rates of the three groups were 90.0%, 67.5% and 33.3%, the difference in OS between the three groups was statistically significant ( P = 0.011). Univariate Cox regression analysis showed that baseline dNLR (low dNLR vs. high dNLR) was the influencing factor for OS of patients ( HR = 0.163, 95% CI 0.057-0.469, P = 0.001) and PFS ( HR = 0.505, 95% CI 0.268-0.952, P = 0.035). Time-dependent ROC curve analysis showed that the area under the curve (AUC) of baseline dNLR grouping and dynamic dNLR grouping for predicting 1-year OS rate of ES-SCLC patients receiving the first-line atezolizumab combined with chemotherapy was 0.674 (95% CI 0.575-0.887) and 0.731 (95% CI 0.529-0.765). Conclusions:Baseline and dynamic dNLR grouping may be effective markers for predicting the prognosis of ES-SCLC patients receiving the first-line atezolizumab immunotherapy and chemotherapy.
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Objective:To explore the prognostic value of pretreatment albumin in extranodal nasal type NK/T cell lymphoma (ENKTL).Methods:The clinical data of 184 ENKTL patients in Shanxi Province Cancer Hospital from January 2002 to December 2018 were retrospectively analyzed. The Contal-O'Quigley change point method was used to determine the optimal cut-off value of albumin for predicting the prognosis of patients. The propensity score matching (PSM) was used to minimize selection biases. The Kaplan-Meier method was used for survival analysis, and Cox proportional hazards model was used to determine the factors affecting survival. The time-dependent receiver operating characteristic curve, Akaike information criterion and integrated Brier score were used to evaluate the efficacy of international prognostic index (IPI), Korean prognostic index (KPI) and prognostic index of NK cell lymphoma (PINK) models incorporating albumin for predicting the prognosis of patients.Results:The optimal cut-off value of pretreatment albumin for predicting the prognosis of ENKTL patients was 37.5 g/L. The 3-year and 5-year overall survival (OS) rates in >37.5 g/L group (126 cases) were 66.2% and 60.3%, and the progression-free survival (PFS) rates were 58.8% and 49.6%; the 3-year and 5-year OS rates in ≤37.5 g/L group (58 cases) were 35.0% and 32.4%, and the PFS rates were 32.5% and 30.0%. The OS and PFS in > 37.5 g/L group were better than those in ≤37.5 g/L group (both P<0.001). After PSM, the OS and PFS in >37.5 g/L group were still better than those in ≤37.5 g/L group (both P = 0.002). Multivariate analysis showed that albumin was an independent influencing factor for OS ( RR = 0.419, 95% CI 0.266-0.660, P < 0.001) and PFS ( RR = 0.493, 95% CI 0.322-0.755, P < 0.001). After PSM, albumin was still an independent influencing factor for OS ( RR = 0.305, 95% CI 0.156-0.598, P = 0.001) and PFS ( RR = 0.341, 95% CI 0.185-0.627, P = 0.001). The prognostic prediction performance of the IPI, KPI and PINK models incorporating albumin were all improved. Conclusions:Pretreatment albumin is an important prognostic indicator for ENKTL.
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Objective:To investigate the relationship between absolute lymphocyte count (ALC) and prognosis of extranodal nasal NK/T cell lymphoma (ENKTL).Methods:The data of 184 patients with ENKTL who were admitted to Shanxi Provincial Cancer Hospital and the Second People's Hospital of Datong in Shanxi Province from January 2002 to December 2018 were retrospectively analyzed. Contal-O'Quigley variable point method was used to calculate the optimal cut-off value of ALC for predicting the prognosis of ENKTL, and the patients were divided into two groups based on this value. Kaplan-Meier method was used to analyze the survival of the two groups of patients. Cox proportional hazard regression model was used for univariate and multivariate survival analyses.Results:According to the Contal-O'Quigley variable point method, the best cut-off value of ALC for predicting ENKTL prognosis was 1.5×10 9/L. According to this value, patients were divided into ALC>1.5×10 9/L group (98 cases) and ALC≤1.5×10 9/L group (86 cases). Compared with the ALC≤1.5×10 9/L group, the proportions of patients with Eastern Cooperative Oncology Group (ECOG) score ≥2 points, serum lactate dehydrogenase (LDH)> 245 U/L, Korean prognostic index (KPI) score 2-4 points and international prognostic index (IPI) score 2-5 points were lower in the ALC>1.5×10 9/L group, but the proportion of patients with hemoglobin > 120 g/L was higher (all P < 0.05). The overall survival (OS) and progression-free survival (PFS) in the ALC>1.5×10 9/L group were better than those in the ALC≤1.5×10 9/L group (3-year OS rate: 65.7% vs. 45.4%, 5-year OS rate: 61.0% vs. 36.6%; 3-year PFS rate: 61.7% vs. 41.0%, 5-year PFS rate: 51.9% vs. 32.2%; all P < 0.05). Multivariate Cox regression analysis showed that ECOG score, serum LDH level, ALC, radiotherapy and L-asparaginase-containing chemotherapy were independent influencing factors of OS and PFS (all P < 0.05), and for OS, when ALC>1.5×10 9/L compared with≤1.5×10 9/L, RR was 0.634 (95% CI 0.398-1.008, P=0.050), and for PFS, RR was 0.625 (95% CI 0.406-0.962, P=0.033). Conclusion:Patients with high ALC have good prognosis, and therefore ALC may be a powerful prognostic factor of ENKTL.
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Objective:To summarize the experience of radiation oncology residency training programs in western coutries, and provide evidence to improve the present Phase-I Radiation Oncology Residency Training Programs in China.Methods:An electronic questionnaire-based survey was conducted among residents and staffs in 6 top cancer centers in China and 5 centers from Europe and North America to collect their feedback regarding the description and comparison of different programs.Results:A total of 70 responses and 4 papers explaining relevant training programs from 26 residents and 23 teachers in Chinese hopsitals and 20 residents and 1 teacher from Europe and North America were received. The Radiation Oncology Residency Training Programs in China were designed into 2 phases, and the results in the current study were involved with the first phase. Program designs were similar in the following aspects: goal, clinical practice-based training, rotation curriculum, interim and final assessment. However, the total timeframe in the investigated Chinese Phase-I programs was shorter than that in western hospitals (2 to 3 years vs. 4 to 5 years). Chinese programs covered major common diseases, whereas rotation design was performed based on each individual disease in western programs. In Chinese programs, the working hours were mainly 40-60 h every week. Although the working hours were commensurate with local workforce regulations, the residents from MSK program had an outstanding longer working time of 60-80 h every week and treated more patients compared with other programs. Conclusions:The investigated Phase-I Radiation Oncology Residency Training Programs in 6 top cancer centers in China share common features in goals, training modes and assessments with western programs. However, our programs have shorter timeframe and less detailed requirements in individual disease than the western programs.
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Tumor radiotherapy is established on the basis of clinical oncology, radio-physics and radiobiology, and has become one of the three major therapeutic methods for malignant tumors. With the pace of socialist construction in China, the subject of radiotherapy in Shanxi province has developed from scratch and from small to large for more than 60 years. Remarkable achievements have been made in the establishment of departments, the updating of technical equipment, the increase of employees and clinical scientific research. This article reviews and summarizes the development history of tumor radiotherapy in Shanxi province.
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Objective To evaluate the prognostic value of anemia in patients diagnosed with extranodal nasal-type natural killer (NK)/T cell lymphoma (NKTCL).Methods Clinical data of 1 225 NKTCL patients receiving the first course of treatment from 10 medical institutions in China were retrospectively analyzed.According to the diagnostic criteria in China,anemia was defined as the hemoglobin (Hb) level< 120 g/L for the male and< 110 g/L for the female from the sea-level area.The severity of anemia was classified into the extremely severe anemia (Hb ≤ 30 g/L),severe anemia (31-60 g/L),moderate anemia (61-90 g/L) and mild anemia (>90 g/L).Results Among 1 225 patients,199(16.2%) were complicated with anemia,who had more adverse prognostic factors compared with their counterparts without anemia.Among NKTCL patients with anemia,the proportion of patients with stage Ⅱ-ⅣV,a median age> anemia,Eastern Cooperative Oncology Group (ECOG) score of 2-4 and NK/T-cell lymphoma prognostic index (NKTCLPI) ≥ 2 was relatively high.Patients with anemia obtained worse clinical prognosis than those without anemia.The 5-year overall survival (OS) and progression-free survival (PFS) in NKTCL patients with anemia were calculated as 49.4% and 35.4%,significantly lower compared with 63.3% and 56.0% in their counterparts without anemia (both P<0.01).Single factor analysis demonstrated that anemia,age,ECOG score,group B symptom,lactate dehydrogenase,primary tumor site,primary tumor invasion and staging were the prognostic factors of OS and PFS.Multivariate analysis revealed that anemia was still the independent prognostic factor.Conclusions Anemia is not common in patients with NKTCL and these patients obtain poor clinical prognosis.Anemia is an independent prognostic factor for patients with NKTCL.
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Objective To analyze the clinical features and prognosis of extra-nodal nasal NK/T cell lymphoma originated from the larynx. Methods Clinical data of 15 cases of extra-nodal nasal NK/T-cell lymphoma originated from the larynx were retrospectively analyzed. The overall survival ( OS ) and progression-free survival ( PFS) were calculated by Kaplan-Meier survival analysis. The effect of different clinical factors on the clinical prognosis was assessed by univariate analysis. Results Among 15 patients,13 cases were male and 2 female. The median age of onset was 40 years. In 8 cases,the lesions were confined to the larynx,and only 4 cases suffered from cervical lymph node involvement. According to Ann Abor staging, 11 cases were classified as grade I,3 as gradeⅡand 1 as gradeⅢ.The median OS was 28. 0 months and the 5-year OS was 32. 0%.The median PFS was 24. 7 months and the 5-year PFS was 33. 3%.Among 14 patients with stage Ⅰ/Ⅱ,the clinical prognosis of patients receiving combined chemo-radiotherapy was significantly better than those of their counterparts undergoing radiotherapy or chemotherapy alone ( median OS:37. 2 vs. 11. 2 vs.3. 7 months,P=0. 004) . Conclusion Extra-nodal nasal NK/T cell lymphoma originated from the larynx is extremely rare, predominantly in middle-aged male patients. The general condition is relatively favorable. Patients present with multiple lesions in the early stage and relatively poor prognosis. The clinical efficacy of chemotherapy combined with radiotherapy is probably higher compared with that of radiotherapy or chemotherapy alone.
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Objective To investigate the effect of pretreatment serum hemoglobin (Hb) level on the prognosis of early-stage extranodal nasal-type NK/T-cell lymphoma.Methods A retrospective analysis was performed on the clinical data of 175 patients with stage Ⅰ or Ⅱ extranodal nasal-type NK/T-cell lymphoma who were admitted to The Tumor Hospital Affiliated to Shanxi Medical University from 2000 to 2015.The inclusion criteria included Ann Arbor Ⅰ/Ⅱ stage, the primary tumor located in the upper aerodigestive tract, without other malignant diseases, and complete clinical information and follow-up data.Of the 175 patients, 67 received chemotherapy alone, 8 received radiotherapy alone,100 received radiotherapy and chemotherapyed.The survival rate was calculated using the Kaplan-Meier method.The log-rank test was used for univariate prognostic analysis.The Cox regression model was used for multivariate prognostic analysis.Results The univariate analysis showed that pretreatment serum Hb level (≥120 g/L), lactate dehydrogenase (LDH) level (normal), Eastern Cooperative Oncology Group (ECOG) score (0-1), Ann Arbor stage (IE), and radiotherapy were associated with significantly improved progression-free survival (PFS) and overall survival (OS)(P=0.000-0.046).The multivariate analysis showed that pretreatment serum Hb level, LDH level, ECOG score, and Ann Arbor stage were independent prognostic factors for PFS and OS (P=0.000-0.040).Conclusion Patients with a high pretreatment serum Hb level (≥120 g/L) have a better prognosis than those with a low pretreatment serum Hb level (<120 g/L).
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Objective To explore the association between epidermal growth factor receptor (EGFR) mutation subtypes and the prognosis of brain metastasis in patients with lung adenocarcinoma.Methods A retrospective analysis was performed on the clinical data of 256 patients who were admitted to our hospital and confirmed with brain metastases of lung adenocarcinoma by EGFR mutation detection from 2010 to 2015.The prognostic factors for brain metastases were analyzed.The survival rate was calculated by the Kaplan-Meier method and analyzed by the log-rank test.The univariate and multivariate prognostic analyses were performed by the log-rank test and the Cox proportional hazards model.Results The median survival time was 10.13 months in all patients.The univariate analysis showed that sex,EGFR mutation status,exon 19 deletion,the Karnofsky Performance Status (KPS) score of brain metastases,and targeted therapy were prognostic predictors (P=0.006,0.001,0.010,0.000,0.003).The multivariate analysis showed that the KPS score and exon 19 deletion were prognostic factors for brain metastases (P=O.000,0.045).When grouped into the recursive partitioning analysis classes,all the patients were split into three subgroups with significantly different prognosis (P =0.000).Conclusions Exon 19 deletion is a prognostic predictor of brain metastases in patieuts with lung adenocarcinoma,which can be integrated into the prognosis scoring system for brain metastases of lung adenocarcinoma.EGFR tyrosine kinase inhibitors improve the survival in patients with brain metastases of lung adenocarcinoma and EGFR mutation,particularly,in those with exon 19 deletion.
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Objective There is still a lack of effective clinical prognostic factors for predicting outcomes and guiding treatments in extranodal nasal-type NK/T-cell lymphoma (NKTCL).This study was aimed to investigate the clinical features and prognostic role of primary tumor burden (PTB).Methods A total of 1383 patients were recruited from ten hospitals, including 947 stage Ⅰ patients (68.5%), 326 stage Ⅱ patients (23.6%), and 110 stage Ⅲ-IV patients (8.0%).There were 751 patients (54.3%) presenting with high PTB (H-PTB).The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was conducted for survival difference analysis.Meanwhile, a multivariate analysis was performed using the Cox regression model.Results H-PTB was associated with high invasive potential, high frequency of B symptoms, advanced stage, regional lymph node involvement, lactate dehydrogenase elevation, and poor performance status.The patients with H-PTB had significantly lower 5-year overall survival (OS) and progression-free survival (PFS) rates than those with low PTB (L-PTB)(OS:50.2% vs.72.1%, P=0.000;PFS:41.8% vs.62.5, P=0.000).PTB was an independent prognostic factor for both OS (HR=1.851) and PFS (HR=1.755) according to the Cox multivariate analysis.Moreover, H-PTB was associated with significantly lower locoregional control (LRC) in early-stage NKTCL, and the 5-year LRC rate was 71.6% in patients with H-PTB and 84.3% in those with L-PTB (P=0.000).Conclusions H-PTB is associated with multiple adverse clinical features in NKTCL, and it is an independent indicator for poor outcomes and LRC.H-PTB can be used as a reliable indicator for risk stratification and treatment decision.
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Objective To compare the clinical effect of whole brain radiotherapy (WBRT) for brain metastases from lung adenocarcinoma between patients with and without epithelial growth factor receptor (EGFR) mutations.Methods A retrospective analysis was performed for 89 patients with brain metastases from lung adenocarcinoma who were treated in our hospital from August 2010 to May 2015.EGFR testing was performed in all patients.WBRT (6-MV external X-ray beam) was performed at 30 Gy in 10 fractions or 40 Gy in 20 fractions;for patients with ≤3 brain metastases, simultaneous integrated boost intensity-modulated radiotherapy was performed at 40-45 Gy in 10 fractions or 50-60 Gy in 20 fractions.The response rate, intracranial progression-free survival (IPFS), and overall survival (OS) were compared between patients with EGFR mutations and patients with wild-type EGFR.The Kaplan-Meier method was used to calculate IPFS and OS, the log-rank test was used for survival difference analysis and univariate prognostic analysis, and the Cox model was used for multivariate prognostic analysis.Results For these 89 patients, the overall response rate was 62%, the median IPFS was 7.0 months (95%CI:6.060-7.940), and the median OS was 12.0 months (95%CI:9.539-14.465).The univariate and multivariate analyses showed that the response rate was associated with Karnofsky Performance Scale (KPS) score and EGFR mutation status (P=0.009 and 0.035);KPS score and EGFR mutation status were significant prognostic factors for IPFS (P=0.048 and 0.000);KPS score and primary tumor control were significant prognostic factors for OS (P=0.000 and 0.031).Conclusions After WBRT for brain metastases from lung adenocarcinoma, the patients with EGFR mutations have a higher response rate and a longer IPFS compared with those with wild-type EGFR, but there is no significant in OS between the two groups of patients.
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Objective@#To investigate the relationship between the status of epidermal growth factor receptor (EGFR) mutations and brain metastases in patients with lung adenocarcinoma.@*Methods@#From August 2010 to May 2015, a total of 1 063 lung adenocarcinoma patients with identified status of EGFR mutations in Shanxi Cancer Hospital were enrolled, of which 456 patients had EGFR mutations. Multivariate Logistic regression model was used to analyze the correlation between EGFR mutation status and brain metastases in patients with lung adenocarcinoma.@*Results@#In 125 patients with brain metastases before initial treatment, 65 patients had EGFR mutations, including 36 patients with deletion mutations in exon 19. The frequency of EGFR 19 exon mutation was 28.8% (36/125). Among 456 patients with EGFR mutations, 65(14.3%) patients were with brain metastases, in which 36(55.0%) had deletion mutations in exon 19. The multivariate analysis showed that age, Eastern Cooperative Oncology Group (ECOG) score, EGFR mutations and N staging were associated with brain metastases(P<0.05). Further subgroup multivariate analyses showed that age, ECOG score, mutation status in exon 19 and N staging were associated with brain metastases (P<0.05).@*Conclusions@#EGFR mutation status is related to brain metastases. Mutations in EGFR exon 19 is an independent risk factor for brain metastases.
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Objective:To study the radiation-sensitizing effects of nimotuzumab and X-ray radiotherapy on human esophageal carcino-ma KYSE450 cells. Methods:Human esophageal carcinoma cells KYSE450 were treated with nimotuzumab, irradiation, and the combi-nation of both. Cell growth inhibition was evaluated by MTT assay, and cell cycle distribution and apoptosis were analyzed by flow cy-tometry assay. Cell radiosensitivity was tested by clonogenic assay, and the survival curve was fitted using multi-target single-hit mod-el. The combination and accelerated radiation groups were tested by microarray technology, and the differentially expressed genes were screened among the two groups. Results:The growth of KYSE450 cells was inhibited in three groups, namely, the group treated with nimotuzumab, the group treated with irradiation, and the group treated with both. The group treated with both nimotuzumab and irradiation resulted in the highest inhibition rate (35.25%±5.62%) compared with that of the nimotuzumab (16.12%±8.73%) and ir-radiation groups (27.64%± 6.66%) (F=10.953, P<0.001). The highest rates of G2 phase arrest and cell apoptosis were observed in the group treated with the combination of nimotuzumab (29.37%±7.29%) (F=17.299, P<0.001) and irradiation (18.80%±2.03%) (F=85.691, P<0.001). Multi-target single-hit model showed that the values of SF2, Do, and Dq in the group with both treatments were smaller than those of the irradiation group with sensitization enhancement ratio of 1.63, which confirmed the radiosensitization effect of ni-motuzumab on KYSE450 cells. Microarray technology analysis found that nimotuzumab can enhance the radiosensitivity of esophageal squamous cell carcinoma by cutting the genes of EGF/PDGF signaling pathways. Conclusion:This experiment shows that nimotuzumab can effectively inhibit the growth of human esophageal cancer cell KYSE450. Nimotuzumab can also promote apoptosis and G2 phase arrest when combined with X-ray radiotherapy, thereby enhancing the radiosensitivity of KYSE450 cells. This effect is associated with cutting the genes of EGFR signaling pathways.
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Brain metastases (BM) are one of the main cause of death in patients with non small cell lung cancer ( NSCLC ).The prognosis is still poor, despite standard therapy based on surgery and radiotherapy.In recent years,with the deepening understanding of molecular mechanisms in lung cancer, epidermal growth factor receptor (EGFR) mutation might be considered as an effective therapeutic target for NSCLC with BM.Therefore,we review the current knowledge about the correlation between EGFR mutation with prevalence and prognosis in BM.
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Objective To explore the necessity of EGFR?targeted therapy combined with synchronized whole brain radiotherapy ( WBRT ) for non?small?cell lung cancer ( NSCLC ) with mutated EGFR and brain metastasis by comparing the effects on prognosis between WBRT combined with tyrosine kinase inhibitor ( TKI) and TKI alone. Methods A retrospective analysis was performed in 43 patients with EGFR mutation?positive NSCLC and brain metastasis. In those patients, 24 patients received WBRT plus TKI and 19 patients TKI alone. Results The overall response rate ( RR) and 6?month intracranial disease control rate ( CR) were significantly higher in the WBRT+TKI group than in the TKI group ( 79% vs. 37%, P=0. 002;79% vs. 63%, P=0. 008). The median intracranial progression?free survival (IPFS) time was significantly longer in the WBRT+TKI group than in the TKI group ( 23. 7 vs. 8. 3 months, P=0. 025) . The multivariate analysis indicated that the control of lung cancer, WBRT+TKI, and single brain metastasis were favorable factors for substantially longer IPFS time ( P=0. 033,0. 019,0. 019) . In 23 patients with exon 19 deletion, 12 patients received WBRT+TKI and 11 patients TKI alone;compared with the TKI group, the WBRT+TKI group had significantly higher RR and 6?month CR as well as significantly longer IPFS ( 100%vs. 35%, P=0. 000;100% vs. 55%, P=0. 008;23. 7 vs. 8. 4 months, P=0. 003). In 20 patients without exon 19 deletion, however, there were no significant differences in RR or 6?month CR between the WBRT+TKI group (n=12) and the TKI group (n=8)(64% vs. 50%, P=1. 000;58% vs. 75%, P=0. 642).The median IPFS was 14. 4 and 8. 4 months ( P=0. 864) . Conclusions WBRT combined with TKI is superior to TKI alone in the treatment of NSCLC with brain metastasis. Patients with exon 19 deletion have substantially better treatment outcomes.
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Objective To analyze and compare the clinical characteristics of primary sclerosing cholangitis (PSC) with IgG4-related sclerosing cholangitis (IgG4-SC).Methods The clinical data of 32 PSC patients and 72 IgG4-SC patients who were hospitalized in Peking Union Medical College Hospital (PUMCH) from January 2004 to December 2014 were retrospectively analyzed.Results Of the 32 PSC patients,there were 16 male and 16 female.Of the 72 IgG4-SC patients,there were 61 male and 11 female,(ratio =5.5∶ 1).The average ages were 44.9 (11 ~ 77) and 59.8 (28 ~ 83) years,respectively (P <0.05).The most common symptoms of PSC and IgG4-SC were abdominal pain and jaundice,and the incidences of abdominal pain and jaundice were 50.0% and 68.1%,78.1% and 81.9%,respectively.The serum IgG4 level of the IgG4-SC patients was significantly higher than the PSC patients (P < 0.05).The total protein in serum of the IgG4-SC patients was higher than the PSC patients (P < 0.05).The rate of bile duct wall thickening as detected on endoscopic ultrasonography (EUS) was higher than by abdominal ultrasound and abdominal CT,which were 91.2%,11.5% and 33.3%,respectively (P <0.05).12 PSC patients were followed up for over 2 years,including 2 patients who underwent liver transplantation after failure of conservative treatment,5 patients who died from hepatic failure and infection,and 3 with stable condition.43 IgG4-SC patients were followed up for over 2 years,including 16 patients with relapse.The recurrence rate was 37.2% (16/43).The more the extrabiliary organs or bile duct segments were involved,the higher was the recurrence rate.Conclusions Both PSC and IgG4-SC are cholestatic diseases,and they have many similarities in clinical and imaging manifestations.However,they still have unique features.IgG4-SC is sensitive to glucocorticoids therapy and has good prognosis.Thus,it is important to differentiate PSC from IgG4-SC.
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Objective To evaluate the prognosis influencing factors of early non-small cell luny cancer (NSCLC) after radiotherapy.Methods 81 early NSCLC patients received definitive radiotherapy and were eligible.Among these patients,60 were diagnosed as squamous cell carcinoma,16 were adenocarcinoma and 5 were diagnosed through imaging instead of pathology.45 patients received conventional radiotherapy,36 patients received three dimensional conformal radiotherapy (3D-CRT),All of them received a total dose of 50-96 Gy with a median dose of 67.8 Gy. Kaplan-Meier survival curves and Cox regression model analysis were applied to evaluate the survival and prognostic factors. Results The median survival time was 34 months.The 1-,3- and 5-year survival rates (OS) were 88.7 %,41.9 %,21.8 %,respectively.Karnofsky performance status≥80,Clinical stage, diameter≤4 cm and the therapeutic effect were associated with improving overall survival.Cox hazards model showed that Karnofsky performance status≥ 80 and diameter≤4 cm were likely to be independent positive prognostic factors. Conclusion Karnofsky performance status and tumor diamater can be used to evaluate the prognosis of early NSCLC after radiotherapy.