20 results on '"Hao, Xue-Zhi"'
Search Results
2. Influence of PD‐L1 expression on the efficacy of EGFR‐TKIs in EGFR‐mutant non‐small cell lung cancer.
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Lei, Si‐Yu, Xu, Hai‐Yan, Li, Hong‐Shuai, Yang, Ya‐Ning, Xu, Fei, Li, Jun‐Ling, Wang, Zhi‐Jie, Xing, Pu‐Yuan, Hao, Xue‐Zhi, and Wang, Yan
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LUNG cancer ,DRUG efficacy ,GENETIC mutation ,PROGRAMMED death-ligand 1 ,CONFIDENCE intervals ,EPIDERMAL growth factor receptors ,CLASSIFICATION ,LOG-rank test ,MULTIVARIATE analysis ,RETROSPECTIVE studies ,PATIENTS ,REGRESSION analysis ,PROTEIN-tyrosine kinase inhibitors ,TREATMENT effectiveness ,RISK assessment ,DESCRIPTIVE statistics ,ELECTRONIC health records ,PROGRESSION-free survival ,PROPORTIONAL hazards models ,EVALUATION ,SYMPTOMS - Abstract
Background: Evidence on the influence of programmed death‐ligand 1 (PD‐L1) expression on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) in EGFR‐mutant non‐small cell lung cancer (NSCLC) patients is at variance. Methods: A single‐center retrospective study was conducted to evaluate the influence of PD‐L1 expression on the efficacy of EGFR‐TKIs for NSCLC patients with EGFR mutation. Clinical information was retrieved from electronic medical records. The patients were divided into three subgroups according to PD‐L1 expression level: PD‐L1 < 1% (negative), PD‐L1 1%–49% and PD‐L1 ≥ 50%. The clinicopathological features, overall response rate (ORR), progression‐free survival (PFS) and comutation information were collected and compared between the three subgroups. Results: A total of 117 patients were included. For PD‐L1 < 1%, PD‐L1 1%–49% and PD‐L1 ≥ 50% group, there were 39 (33.3%), 51 (43.5%) and 27 (23.0%) patients respectively, and the ORR was 43.2%, 64.0%, and 51.9%, respectively (p = 0.162), and the median progression‐free survival (mPFS) was 22.0 months (95% CI: 14.0–29.9 months), 15.4 months (95% CI: 8.9–21.8 months) and 13.0 months (95% CI: 10.6–15.3 months), respectively (log‐rank, p = 0.01). The mPFS was negatively correlated with PD‐L1 expression level (r = −0.264, p = 0.041) and PD‐L1 expression was an independent risk factor for worse PFS of EGFR‐TKIs in multivariate Cox regression. Patients with concurrent TP53 mutation had shorter PFS (p = 0.039) and the patients harboring both mutant TP53 and positive PD‐L1 had the shortest PFS (p = 0.006). Conclusions: The efficacy of EGFR‐TKIs was influenced by the baseline PD‐L1 expression. Higher PD‐L1 expression was associated with shorter PFS. The combined indicators of TP53 and PD‐L1 identified subgroups showing divergent benefits from EGFR‐TKIs. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Afatinib and Dacomitinib Efficacy, Safety, Progression Patterns, and Resistance Mechanisms in Patients with Non-Small Cell Lung Cancer Carrying Uncommon EGFR Mutations: A Comparative Cohort Study in China (AFANDA Study).
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Li, Hong-Shuai, Wang, Shou-Zheng, Xu, Hai-Yan, Yan, Xiang, Zhang, Jin-Yao, Lei, Si-Yu, Li, Teng, Hao, Xue-Zhi, Zhang, Tao, Yang, Guang-Jian, Zhou, Li-Qiang, Liu, Peng, Wang, Yu-Ying, Hu, Xing-Sheng, Xing, Pu-Yuan, and Wang, Yan
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THERAPEUTIC use of antineoplastic agents ,LUNG cancer ,DRUG efficacy ,DISEASE progression ,STATISTICS ,GENETIC mutation ,CONFIDENCE intervals ,EPIDERMAL growth factor receptors ,PROTEIN kinase inhibitors ,MULTIVARIATE analysis ,AFATINIB ,COMPARATIVE studies ,DESCRIPTIVE statistics ,DATA analysis software ,PATIENT safety ,DRUG resistance in cancer cells ,LONGITUDINAL method - Abstract
Simple Summary: Afatinib has been approved for patients with lung cancer carrying uncommon epidermal growth factor receptor gene (EGFR) mutations. Dacomitinib, another second-generation inhibitor, has also shown promising potential for these mutations. This is the first and largest comparative study on second-generation inhibitors in patients with uncommon EGFR mutations to date. We found that dacomitinib demonstrated a more favorable activity with manageable toxicity compared with afatinib, which provided more evidence for dacomitinib application in this setting. (1) Background: Afatinib has been approved for patients with non-small cell lung cancer (NSCLC) carrying major uncommon epidermal growth factor receptor gene (EGFR) mutations. Dacomitinib, another second-generation tyrosine kinase inhibitor, has also shown promising potential for uncommon EGFR mutations. However, no comparative study has been conducted. (2) Methods: Two cohorts were employed: the AFANDA cohort, an ambispective cohort including 121 patients with uncommon EGFR mutations admitted to two tertiary hospitals in China, and an external validation afatinib cohort (ex-AC), extracted from the Afatinib Uncommon EGFR Mutations Database (N = 1140). The AFANDA cohort was divided into an afatinib cohort (AC) and a dacomitinib cohort (DC) for internal exploration. Objective response rate (ORR), progression-free survival (PFS), and adverse events (AEs) were assessed for comparison. Progression patterns and resistance mechanisms were explored. (3) Results: In total, 286 patients with advanced NSCLC carrying uncommon EGFR mutations treated with afatinib or dacomitinib were enrolled, including 79 in the AFANDA cohort (44 in the DC, 35 in the AC) and 207 in the ex-AC. In internal exploration, the ORR of the DC was significantly higher than that of the AC (60.5 vs. 26.7%, p = 0.008), but there was no significant difference in median PFS between the DC and the AC (12.0 months vs. 10.0 months, p = 0.305). Multivariate analysis confirmed an independent favorable effect of dacomitinib on PFS (hazard ratio (HR), 1.909; p = 0.047). In external validation, multivariate analysis confirmed the independent prognostic role of dacomitinib in PFS (HR, 1.953; p = 0.029). Propensity score matching analysis confirmed the superiority of dacomitinib over afatinib in terms of PFS in both univariate and multivariate analyses. Toxicity profiling analysis suggested more G1 (p = 0.006), but fewer G3 (p = 0.036) AEs in the DC than in the AC. Progression patterns revealed that the incidence of intracranial progression in the AC was significantly higher than that in the DC (50 vs. 21.1%, p = 0.002). Drug resistance analysis indicated no significant difference in the occurrence of T790M between the AC and the DC (11.8 vs. 15.4%, p = 0.772). (4) Conclusions: Compared with afatinib, dacomitinib demonstrated a more favorable activity with manageable toxicity and different progression patterns in patients with NSCLC carrying uncommon EGFR mutations. [ABSTRACT FROM AUTHOR]
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- 2022
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4. Immunohistochemistry reliably detects ALK rearrangements in patients with advanced non-small-cell lung cancer
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Han, Xiao-Hong, Zhang, Ning-Ning, Ma, Li, Lin, Dong-Mei, Hao, Xue-Zhi, Liu, Yu-Tao, Wang, Lin, Liu, Peng, Yuan, Zheng, Li, Dan, Lin, Hua, Sun, Yan, and Shi, Yuan-Kai
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- 2013
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5. Long-term outcomes of gemcitabine and cisplatin in patients with recurrent or metastatic esophageal squamous cell carcinoma: a phase II trial
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HUANG, Jing, FAN, Qing-xia, CHEN, Li, LIU, Ai-na, CAI, Rui-gang, HAO, Xue-zhi, WANG, Jin-wan, and SUN, Yan
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- 2011
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6. Survival and pretreatment prognostic factors for extensive‐stage small cell lung cancer: A comprehensive analysis of 358 patients.
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Huang, Li‐Ling, Hu, Xing‐Sheng, Wang, Yan, Li, Jun‐Ling, Wang, Hong‐Yu, Liu, Peng, Xu, Jian‐Ping, He, Xiao‐Hui, Hao, Xue‐Zhi, Jiang, Pei‐Di, Liu, Yu‐Tao, Luo, Jian, Zhou, Sheng‐Yu, Wang, Jin‐Wan, Yang, Jian‐Liang, Qin, Yan, Yuan, Peng, Lin, Lin, and Shi, Yuan‐Kai
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STATISTICS ,ACQUISITION of data methodology ,SPECIALTY hospitals ,SMALL cell carcinoma ,MULTIVARIATE analysis ,LUNG tumors ,RETROSPECTIVE studies ,TUMOR classification ,CANCER patients ,CANCER treatment ,MEDICAL records ,DESCRIPTIVE statistics ,BONE metastasis ,SMOKING ,TUMOR markers ,DECISION making in clinical medicine ,PROPORTIONAL hazards models - Abstract
Background: Extensive‐stage small cell lung cancer (ES‐SCLC) is deemed as a fatal malignancy with a poor prognosis. Although immunotherapy has gradually played an important role in the treatment of ES‐SCLC since 2018, ES‐SCLC treatment data and patient outcome before 2018, when chemotherapy served as a fundamental therapeutic strategy, is still meaningful as a summary of the situation regarding previous medical treatment and is a baseline for comparative data. In addition, the prognostic factors of ES‐SCLC have failed to reach a consensus until now. Therefore, this study aimed to evaluate survival and identify the prognostic factors in an ES‐SCLC population. Methods: We retrospectively collected the detailed medical records of 358 patients with ES‐SCLC from January 1, 2011 to December 31, 2018 in a Chinese top‐level cancer hospital. The prognostic factors were evaluated by Cox univariate and multivariate analysis. Results: The median overall survival (OS) of ES‐SCLC patients (N = 358) was 14.0 months, the one‐ and two‐year OS rates were 56.2% and 21.7%, respectively. Moreover, we identified two demographic characters (age ≥ 70, smoking index ≥ 400), one tumor burden factor (bone multimetastasis), two tumor biomarkers (cyfra211, CA125) and two laboratory indexes (decreased Na, PLR < 76) as independent prognostic factors for OS in this patient population. Progression‐free survival (PFS) data of 238 patients was obtained for further analysis, and the median PFS was 6.2 months, and six‐month and one‐year PFS rates were 51.7% and 14.3%, respectively. Elevated cyfra211, decreased Hb and Na were identified as independent prognostic factors for PFS. Conclusions: This study provides real‐world evidence of the survival and prognosis of ES‐SCLC patients which will enable better evaluation and clinical decision‐making in the future. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Icotinib as Adjuvant Treatment for Stage II-IIIA Lung Adenocarcinoma Patients with EGFR Mutation (ICWIP Study): Study Protocol for a Randomised Controlled Trial.
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Liu, Yu-Tao, Hao, Xue-Zhi, Liu, De-Ruo, Cheng, Gang, Zhang, Shu-Cai, Xiao, Wen-Hua, Hu, Yi, Liu, Jun-Feng, He, Ming, Ding, Cui-Min, Zhang, Li, Wang, Jun, Li, Hui, Dong, Gui-Lan, Zhi, Xiu-Yi, Li, Jian, and Shi, Yuan-Kai
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RANDOMIZED controlled trials ,NON-small-cell lung carcinoma ,ADENOCARCINOMA ,LUNGS ,PROTEIN-tyrosine kinases - Abstract
The efficacy and possible role of epidermal growth factor receptor tyrosine kinase inhibitors in treating early-stage non-small-cell lung cancer have yet to be established. Therefore, we aimed to explore the efficacy and safety of icotinib in completely resected EGFR-mutant stage II–IIIA lung adenocarcinoma patients who underwent standard chemotherapy. This is a randomised, double-blinded, placebo-controlled, multicentre, Phase III trial. A total of 124 patients aged 18– 75 years who qualified the inclusion criteria were recruited. These patients were randomised (1:1) to receive either icotinib (125 mg 3 times per day) or placebo (the same dosage and frequency) for 36 months, followed by a further 36 months of observational window. The primary endpoint is disease-free survival (DFS), while the secondary endpoints are overall survival, 3-year and 5-year DFS, safety and tolerability of the medication, and health-related quality-of-life. Analyses will be conducted in a full analysis set and a per-protocol set as well. To our knowledge, the present study is the first randomised, double-blinded, placebo-controlled, multicenter trial designed to explore efficacy and safety of icotonib in this population. The results obtained in the near future may provide potential guidance in clinical practice. Trial Registration: This trial was registered on www.ClinicalTrail.gov as NCT02125240. [ABSTRACT FROM AUTHOR]
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- 2020
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8. Analysis of clinicopathological features of the echinoderm microtubule-associated protein-like-4-anaplastic lymphoma kinase fusion gene in Chinese patients with advanced non-small-cell lung cancer
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Liu, Yu-Tao, Shi, Yuan-Kai, Hao, Xue-Zhi, Wang, Lin, Li, Jun-Ling, Han, Xiao-Hong, Li, Dan, Zhou, Yu-Jie, and Tang, Le
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Original Articles - Abstract
The echinoderm microtubule-associated protein-like-4-anaplastic lymphoma kinase (EML4-ALK) fusion gene defines a novel molecular subset of non-small-cell lung cancer (NSCLC). However, the clinicopathological features of patients with the EML4-ALK fusion gene have not been defined completely.Clinicopathological data of 200 Chinese patients with advanced NSCLC were analyzed retrospectively to explore their possible correlations with EML4-ALK fusions.The EML4-ALK fusion gene was detected in 56 (28.0%) of the 200 NSCLC patients, and undetected in 22 (11.0%) patients because of an insufficient amount of pathological tissue. The median age of the patients with positive and negative EML4-ALK was 48 and 55 years, respectively. Patients with the EML4-ALK fusion gene were significantly younger (P0.001). The detection rate of the EML4-ALK fusion gene in patients who received primary tumor or metastatic lymph node resection was significantly higher than in patients who received fine-needle biopsy (P= 0.003). The detection rate of the EML4-ALK fusion gene in patients with a time lag from obtainment of the pathological tissue to EML4-ALK fusion gene detection ≤48 months was significantly higher than in patients48 months (P= 0.020). The occurrence of the EML4-ALK fusion gene in patients with wild-type epidermal growth factor receptor (EGFR) was significantly higher than in patients with mutant-type EGFR (42.5% [37/87] vs. 6.3% [1/16], P= 0.005).Younger age and wild-type EGFR were identified as clinicopathological characteristics of patients with advanced NSCLC who harbored the EML4-ALK fusion gene. The optimal time lag from the obtainment of the pathological tissue to the time of EML4-ALK fusion gene detection is ≤48 months.
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- 2014
9. Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer
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Xing, Pu-Yuan, Li, Jun-Ling, Wang, Yan, Hao, Xue-Zhi, Wang, Bin, Yang, Lin, Shi, Yuan-Kai, and Zhang, Xiang-Ru
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Original Article - Abstract
To observe the efficacy and safety of albumin-bound paclitaxel (ABP) monotherapy in treating recurrent advanced non-small-cell lung cancer (NSCLC).We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed.Of these 21 patients, the best overall response was partial response (PR) in 6 patients (28.6%), stable disease (SD) in 10 patients (47.6%), and progressive disease (PD) in 5 patients (23.8%). The overall response rate (ORR) was 28.6% and the disease control rate (DCR) (PR + SD) was 76.2%. The median progression-free survival (PFS) was 4.0 months (95% CI, 5.0-7.0 months). The main grade 3/4 toxicities included neutropenia (11.1%), peripheral nerve toxicity (5.6%), muscle and joint aches (5.6%), and fatigue (5.6%).The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.
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- 2013
10. Efficacy and safety of the combination of paclitaxel and platinum in advanced thymic carcinoma.
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Xu, Jian‐ping, Hao, Xue‐zhi, Zhang, Xiang‐ru, Yang, Sheng, and Shi, Yuan‐kai
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COMBINATION drug therapy , *CISPLATIN , *CYTOLOGICAL techniques , *DRUG side effects , *LIVER diseases , *NEUTROPENIA , *PACLITAXEL , *THROMBOCYTOPENIA , *THYMOMA , *CARBOPLATIN , *TUMOR grading , *PHARMACODYNAMICS - Abstract
This study aimed to assess the efficacy and safety of a combination of paclitaxel and cisplatin/carboplatin for the treatment of advanced thymic carcinoma. Thirty-seven patients (23 men and 14 women, median age 47 years, performance status score ≤2) with pathologically or cytologically diagnosed advanced thymic carcinoma were recruited. Patients received 175 mg/m2 paclitaxel on day 1 and 75 mg/m2 cisplatin or 300 mg/m2 carboplatin on day 2 of a 21 day cycle for at least two cycles to evaluate efficacy and adverse events. No complete response ( CR) was observed; 11 patients had a partial response ( PR), 16 patients had no change ( NC), and 10 had progressive disease, resulting in an overall response rate of 29.7%, a stable rate of 43.2%, and a disease control rate ( CR + PR + NC) of 72.9%. Grade I/ II and III/ IV neutropenia were observed in 21 (56.7%) and 13 (35.1%) patients, respectively. Four (10.8%) patients developed grade I/ II thrombocytopenia. Grade I/ II and III/ IV nausea and vomiting were observed in 19 (51.2%) and five (13.5%) patients, respectively. Grade I/ II liver dysfunction was observed in seven (18.9%) patients. Two patients with grade III liver dysfunction recovered after hepatoprotective treatment. The combination of paclitaxel and platinum was effective and well tolerated in patients with advanced thymic carcinoma. [ABSTRACT FROM AUTHOR]
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- 2016
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11. Survival of patients with advanced lung adenocarcinoma before and after approved use of gefitinib in China.
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Liu, Yu‐Tao, Hao, Xue‐Zhi, Li, Jun‐Ling, Hu, Xing‐Sheng, Wang, Yan, Wang, Zi‐Ping, Wang, Hong‐Yu, Wang, Bin, Han, Xiao‐Hong, Zhang, Xiang‐Ru, and Shi, Yuan‐Kai
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ANTINEOPLASTIC agents , *GEFITINIB , *ACADEMIC medical centers , *ADENOCARCINOMA , *CHI-squared test , *CONFIDENCE intervals , *LUNG cancer , *LUNG tumors , *MULTIVARIATE analysis , *REGRESSION analysis , *RESEARCH funding , *SURVIVAL , *PROPORTIONAL hazards models , *RETROSPECTIVE studies , *DATA analysis software , *DESCRIPTIVE statistics , *KAPLAN-Meier estimator , *LOG-rank test , *THERAPEUTICS - Abstract
Background To compare the overall survival ( OS) of patients with advanced lung adenocarcinoma in China before and after the approved use of gefitinib, and analyze clinical factors that may affect OS. Methods Clinical data of 558 patients with advanced lung adenocarcinoma who received chemotherapy from January 2002 to December 2010 were retrospectively analyzed. According to the matched-pair case-control study design, 255 patients who only received chemotherapy and 255 patients who received gefitinib treatment after its approval were stringently matched by age, gender, and smoking history and enrolled in the study. Clinical factors including age, gender, smoking history, Eastern Cooperative Oncology Group ( ECOG) performance status ( PS), tumor stage, organ metastasis, and the number of prior chemotherapies were analyzed to determine their correlations with OS. Results The median survival time ( MST) of the 510 enrolled patients with advanced lung adenocarcinoma was 22.8 months. The MST of the patients who received gefitinib treatment was significantly longer than that of patients who did not receive gefitinib treatment (33.5 vs. 14.1 months, P < 0.001). The OS in patients who received gefitinib treatment was significantly longer than in patients who did not receive gefitinib treatment in almost all clinical factor-based subgroups, including age, gender, smoking history, ECOG PS 0-1, tumor stage, the presence or absence of lung, pleural, bone, brain, adrenal gland and liver metastasis, and the number of prior chemotherapies (all P < 0.001), except in the ECOG PS ≥2 subgroup. Conclusions Gefitinib treatment significantly improved the survival of patients with advanced lung adenocarcinoma in China. [ABSTRACT FROM AUTHOR]
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- 2015
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12. Analysis of clinicopathological features of the echinoderm microtubule-associated protein-like-4-anaplastic lymphoma kinase fusion gene in Chinese patients with advanced non-small-cell lung cancer.
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Liu, Yu‐Tao, Shi, Yuan‐Kai, Hao, Xue‐Zhi, Wang, Lin, Li, Jun‐Ling, Han, Xiao‐Hong, Li, Dan, Zhou, Yu‐Jie, and Tang, Le
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LUNG cancer & genetics ,ACADEMIC medical centers ,AGE distribution ,BIOPSY ,CELL receptors ,CHI-squared test ,EPIDERMAL growth factor ,RESEARCH funding ,T-test (Statistics) ,U-statistics ,FLUORESCENCE in situ hybridization ,GENOMICS ,SYMPTOMS ,DISEASE progression ,DATA analysis software ,DESCRIPTIVE statistics - Abstract
Background The echinoderm microtubule-associated protein-like-4-anaplastic lymphoma kinase ( EML4- ALK) fusion gene defines a novel molecular subset of non-small-cell lung cancer ( NSCLC). However, the clinicopathological features of patients with the EML4- ALK fusion gene have not been defined completely. Methods Clinicopathological data of 200 Chinese patients with advanced NSCLC were analyzed retrospectively to explore their possible correlations with EML4- ALK fusions. Results The EML4- ALK fusion gene was detected in 56 (28.0%) of the 200 NSCLC patients, and undetected in 22 (11.0%) patients because of an insufficient amount of pathological tissue. The median age of the patients with positive and negative EML4- ALK was 48 and 55 years, respectively. Patients with the EML4- ALK fusion gene were significantly younger ( P < 0.001). The detection rate of the EML4- ALK fusion gene in patients who received primary tumor or metastatic lymph node resection was significantly higher than in patients who received fine-needle biopsy ( P = 0.003). The detection rate of the EML4- ALK fusion gene in patients with a time lag from obtainment of the pathological tissue to EML4- ALK fusion gene detection ≤48 months was significantly higher than in patients >48 months ( P = 0.020). The occurrence of the EML4- ALK fusion gene in patients with wild-type epidermal growth factor receptor ( EGFR) was significantly higher than in patients with mutant-type EGFR (42.5% [37/87] vs. 6.3% [1/16], P = 0.005). Conclusions Younger age and wild-type EGFR were identified as clinicopathological characteristics of patients with advanced NSCLC who harbored the EML4- ALK fusion gene. The optimal time lag from the obtainment of the pathological tissue to the time of EML4- ALK fusion gene detection is ≤48 months. [ABSTRACT FROM AUTHOR]
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- 2014
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13. The Molecular Detection and Clinical Significance of ALK Rearrangement in Selected Advanced Non-Small Cell Lung Cancer: ALK Expression Provides Insights into ALK Targeted Therapy.
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Zhang, Ning-Ning, Liu, Yu-Tao, Ma, Li, Wang, Lin, Hao, Xue-Zhi, Yuan, Zheng, Lin, Dong-Mei, Li, Dan, Zhou, Yu-Jie, Lin, Hua, Han, Xiao-Hong, Sun, Yan, and Shi, Yuankai
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LUNG cancer diagnosis ,LUNG cancer treatment ,ANAPLASTIC lymphoma kinase ,MOLECULAR diagnosis ,GENE rearrangement ,GENE expression ,HEALTH outcome assessment - Abstract
Background: This study aimed to elucidate clinical significance of anaplastic lymphoma kinase (ALK) rearrangement in selected advanced non-small cell lung cancer (NSCLC), to compare the application of different ALK detection methods, and especially evaluate a possible association between ALK expression and clinical outcomes in crizotinib-treated patients. Methods: ALK status was assessed by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC) and quantitative RT-PCR (qRT-PCR) in 173 selected advanced NSCLC patients. Clinicopathologic data, genotype status and survival outcomes were analyzed. Moreover, the association of ALK expression with clinical outcomes was evaluated in ALK FISH-positive crizotinib-treated patients including two patients with concurrent epidermal growth factor receptor (EGFR) mutation. Results: The positivity detection rate of ALK rearrangement by FISH, IHC and qRT-PCR was 35.5% (59/166), 35.7% (61/171), and 27.9% (34/122), respectively. ALK rearrangement was observed predominantly in young patients, never or light smokers, and adenocarcinomas, especially with signet ring cell features and poor differentiation. Median progression-free survival (PFS) of crizotinib-treated patients was 7.6 months. The overall survival (OS) of these patients was longer compared with that of crizotinib-naive or wild-type cohorts, but there was no significant difference in OS compared with patients with EGFR mutation. ALK expression did not associate with PFS; but, when ALK expression was analyzed as a dichotomous variable, moderate and strong ALK expression had a decreased risk of death (P = 0.026). The two patients with concomitant EGFR and ALK alterations showed difference in ALK expression, response to EGFR and ALK inhibitors, and overall survival. Conclusions: Selective enrichment according to clinicopathologic features in NSCLC patients could highly improve the positivity detection rate of ALK rearrangement for ALK-targeted therapy. IHC could provide more clues for clinical trial design and therapeutic strategies for ALK-positive NSCLC patients including patients with double genetic aberration of ALK and EGFR. [ABSTRACT FROM AUTHOR]
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- 2014
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14. Efficacy of dacomitinib in patients with EGFR‐mutated NSCLC and brain metastases.
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Zhang, Jinyao, Wang, Yan, Liu, Ziling, Wang, Lin, Yao, Yu, Liu, Yutao, Hao, Xue Zhi, Wang, Jianyang, Xing, Puyuan, and Li, Junling
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Background Patients and Methods Results Conclusion Dacomitinib is a second‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) which is superior to first‐generation EGFR TKI in ARCHER 1050. However, the activity of dacomitinib in the central nervous system (CNS) is not known as ARCHER 1050 did not include patients with baseline brain metastases. This study aimed to describe dacomitinib's activity in the CNS in a real‐world setting.Thirty‐two patients who were receiving dacomitinib for advanced non‐small‐cell lung cancer (NSCLC) with EGFR mutations and brain metastasis were included in this study. Patients who received prior EGFR TKIs were excluded from this trial. Case report forms were collected to determine treatment outcomes.Among 32 patients with EGFR‐mutated NSCLC and brain disease, eight were included in the CNS evaluable for response group. The intracranial objective response rate (iORR) was 87.5% (95% confidence interval [CI] 47.3–99.7%) and the intracranial disease control rate (iDCR) was 100% (95% CI 63.1–100%). In 30 evaluable patients with measurable or nonmeasurable brain lesions, the iORR was 66.7% (95% CI 47.2–82.7%) and the iDCR was 100% (95% CI 88.4–100%). Median intracranial duration of response (iDoR) and intracranial progression‐free survival (iPFS) were not reached, with a one‐year iDoR rate of 72.2% (95% CI 48.7–95.7%) and a 1‐year iPFS rate of 71.2% (95% CI 51.0–91.4%), respectively. The majority of patients experienced low‐grade (G1/2) toxicities, which are reversible.This study suggests that dacomitinib demonstrated CNS efficacy in patients with EGFR TKI‐naïve EGFR‐mutated NSCLC in the real‐world setting. The safety profile was tolerable and manageable. [ABSTRACT FROM AUTHOR]
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- 2021
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15. Efficacy and safety of concomitant immunotherapy and denosumab in patients with advanced non-small cell lung cancer carrying bone metastases: A retrospective chart review.
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Li HS, Lei SY, Li JL, Xing PY, Hao XZ, Xu F, Xu HY, and Wang Y
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- Denosumab adverse effects, Humans, Immunologic Factors therapeutic use, Immunotherapy, Neoplasm Recurrence, Local, Phosphates, Retrospective Studies, Bone Neoplasms drug therapy, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms pathology
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Background: Synergistic anti-tumor effects were observed in vivo and in vitro when immune checkpoint inhibitors (ICIs) were combined with denosumab. However, the clinical benefit and safety of this synergy have not been adequately evaluated in non-small cell lung cancer (NSCLC)., Methods: Consecutive charts of NSCLC patients with bone metastases between December 2020 and December 2021 in the Chinese National Cancer Center were reviewed. The entire cohort was divided into one experimental group (denosumab + ICIs [DI]) and three control groups (denosumab + non-ICIs [DnI], phosphates + ICIs [PI], phosphates + non-ICIs [PnI]). Real-world objective response rates (ORRs), median progression-free survival (mPFS), skeletal-related events (SREs), and adverse events (AEs) were compared between groups., Results: A total of 171/410 (41.7%) patients with advanced or recurrent NSCLC carrying bone metastases who received bone-targeted therapy were eligible for analysis. Although the DI group showed a better benefit trend, differences were not statistically significant concerning the therapeutic efficacy among the DI group (n = 40), PI group (n = 74), DnI group (n = 15), and PnI group (n = 42) (ORRs: 47.5%, 43.2%, 33.3%, and 40.5%, respectively, p = 0.799; and mPFS: 378, 190, 170, and 172 days, respectively, p = 0.115; SREs: 5%, 10.8%, 13.3%, and 11.9%, respectively, p = 0.733). Nevertheless, further analysis in the NON-DRIVER cohort revealed a greater benefit for the DI group ( p = 0.045). Additionally, the AEs of the DI group were not significantly different from those of the PI, DnI, and PnI groups (AEs: 27.5%, 39.2%, 26.7%, and 28.6%, respectively, p = 0.742). Furthermore, the multivariate analysis revealed the independent prognostic role of DI treatment for PFS in the overall cohort. Within the DI group, we did not observe differences in benefit among different mutational subgroups ( p = 0.814), but patients with single-site bone metastasis ( p = 0.319) and high PD-L1 expression ( p = 0.100) appeared to benefit more, though no significant differences were observed., Conclusions: Denosumab exhibited synergistic antitumor efficacy without increasing toxicity when used concomitantly with ICIs in patients with advanced non-small cell lung cancer carrying bone metastases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Lei, Li, Xing, Hao, Xu, Xu and Wang.)
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- 2022
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16. A real-world study of dacomitinib in later-line settings for advanced non-small cell lung cancer patients harboring EGFR mutations.
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Li HS, Zhang JY, Yan X, Xu HY, Hao XZ, Xing PY, and Wang Y
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- ErbB Receptors, Humans, Mutation, Protein Kinase Inhibitors adverse effects, Quinazolinones, Retrospective Studies, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology
- Abstract
Objective: Dacomitinib has been approved for the first-line treatment of non-small cell lung cancer (NSCLC) carrying classical epidermal growth factor receptor (EGFR) mutations; however, real-world data on its later-line application are lacking., Materials and Methods: Patients' data were retrospectively collected from the Chinese National Cancer Center and the PLA hospital between August 2019 and August 2021. Kaplan-Meier method and Log-rank test were utilized to assess progression-free survival (PFS) and overall survival (OS). Univariate and multivariate Cox regression analysis was conducted to determine prognostic indicators., Results: In total, 56 NSCLC patients harboring EGFR mutations treated with later-line single dacomitinib or combinatory dacomitinib were enrolled. A total of 53 patients (94.6%) had treatment-related adverse events; eight patients (14.3%) had grade 3 or 4 events. Among 49 evaluable patients, 26.5% (13 patients) had a confirmed partial response and 73.5% (36 patients) had disease control; the median duration of follow-up was 9.6 months (95% confidence interval [CI], 8.4-10.8 months), the median progression-free survival was 5.4 months (95% CI, 3.5-7.3 months), and the half-year, 1-year, and 2-year OS rate were 79.2%, 70.6%, and 64.1%, respectively. Univariate analysis suggested that smoking, line of dacomitinib, and interval between last EGFR-tyrosine kinase inhibitor (TKI) and dacomitinib were associated with PFS and OS; chemotherapy between last EGFR-TKI and dacomitinib, and EGFR-TKI generation followed by dacomitinib were respectively associated with PFS and OS; multivariate analysis indicated chemotherapy between last EGFR-TKI and dacomitinib negatively affect PFS, and smoking and third-generation EGFR-TKI followed by dacomitinib negatively affect OS., Conclusions: This real-world study has shown that dacomitinib is active and well-tolerated in NSCLC patients harboring different EGFR mutations in later-line settings, even for those with brain metastases. Patients who benefited more from the first TKI were more likely to benefit from dacomitinib, and earlier application of dacomitinib after front-line TKI resistance may be considered., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2022
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17. Depth of Response was Associated with Progression-Free Survival in Patients with Advanced Non-small Cell Lung Cancer treated with EGFR-TKI.
- Author
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Liu YT, Zhang K, Li CC, Hu XS, Jiang J, Hao XZ, Wang Y, Li JL, Xing PY, Yang S, Zhang X, Wang GQ, Cai SL, and Shi YK
- Abstract
Background : Response Evaluation Criteria in Solid Tumors (RECIST) has been widely utilized to evaluate new therapeutic strategies in cancer. However, RECIST fails to assess the heterogeneity of response in highly active therapies. Depth of response (DepOR), defined as the maximum percentage change in tumor size compared with baseline, may provide a new strategy to evaluate disease response. In the present study, we studied the association between DepOR and progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Methods : Advanced NSCLC patients harboring EGFR driver mutation (L858R or exon 19 deletion) treated with EGFR-TKI from August 2014 to July 2017 from two sites were retrospetively collected for analysis. Patients were divided into four groups by DepOR (Q1 = 1-25%, Q2 = 26-50%, Q3 = 51-75%, Q4 = 76-100%). Kaplan-Meier curves were plotted for PFS against DepOR and the hazard ratio (HR) was determined through univariable and multivariable cox regression models. Results : In total, 265 patients were included for analysis. The number of patients in Group Q1-Q4 were 91 (34.3%), 73 (27.5%), 65 (24.5%) and 36 (13.6%), respectively. A greater DepOR was significantly associated with a longer PFS (Log-rank P <0.0001). The HRs (95% CI) for PFS comparing patients with different DepOR status were 0.58 (0.42-0.80) for Q2, 0.49 (0.35-0.69) for Q3, and 0.33 (0.22-0.50) for Q4, all compared with patients in Q1. DepOR as a continuous variable was also associated with prolonged PFS (HR, 0.20; 95% CI, 0.13-0.33; P<0.001). Additionally, in the multivariable cox regression model, abnormal LDH, brain metastasis and male were found to be associated with worse PFS outcomes (P<0.05). Conclusion : A greater DepOR is significantly associated with PFS benefit in advanced NSCLC treated with EGFR-TKI, suggesting that it may be a useful clinical outcome to evaluate the response of targeted therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)
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- 2019
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18. Circular RNA profiling identified as a biomarker for predicting the efficacy of Gefitinib therapy for non-small cell lung cancer.
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Liu YT, Han XH, Xing PY, Hu XS, Hao XZ, Wang Y, Li JL, Zhang ZS, Yang ZH, and Shi YK
- Abstract
Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become important treatment options for non-small cell lung cancer (NSCLC) patients with EGFR sensitive mutation. However, the detection of EGFR driver mutation is impeded by the lack of adequate tumor tissues, histopathological type, long detection period, and the heterogeneity of a tumor. Therefore, it is necessary to develop a more convenient method to guide the clinical use of EGFR-TKI. Circular RNAs (circRNAs) are characterized as a closed structure with covalently joined ends resistant to exonucleases may be a potential biomarker. In the present study, we aimed to screen circRNAs that may be associated with the efficacy of EGFR-TKI., Methods: The expression of circRNAs sequenced by circular microarray in plasma samples between gefitinib effective and ineffective groups were compared. RT-qPCR further validated the results in an independent cohort. Kaplan-Meier curves were used to analyze the association between circRNA and progression-free survival (PFS) of NSCLC patients treated with gefitinib., Results: In total, 52 NSCLC patients treated with gefitinib were included for analysis. 1,377 circRNAs were differentially expressed in gefitinib effective and ineffective groups, among which 989 circRNAs were up-regulated, and 388 circRNAs were down-regulated in the effective group. Furthermore, two differentially expressed circRNAs, hsa_circ_0109320 and hsa_circ_0134501, were validated by RT-qPCR in an independent cohort of 38 gefitinib-treated NSCLC patients. Elevated hsa_circ_0109320 was associated with longer PFS in gefitinib-treated NSCLC patients., Conclusions: Taken together, hsa_circ_0109320 may be a potential biomarker for the efficacy of EGFR-TKI in NSCLC patients. This provides a new molecular typing method for individualized precision treatment., Competing Interests: Conflicts of Interest: ZH Yang is employee of Beijing CapitalBio Technology Company. The other authors have no conflicts of interest to declare.
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- 2019
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19. The molecular detection and clinical significance of ALK rearrangement in selected advanced non-small cell lung cancer: ALK expression provides insights into ALK targeted therapy.
- Author
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Zhang NN, Liu YT, Ma L, Wang L, Hao XZ, Yuan Z, Lin DM, Li D, Zhou YJ, Lin H, Han XH, Sun Y, and Shi Y
- Subjects
- Adult, Aged, Anaplastic Lymphoma Kinase, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung mortality, Crizotinib, ErbB Receptors genetics, ErbB Receptors metabolism, Female, Gene Expression, Genotype, Humans, Lung Neoplasms drug therapy, Lung Neoplasms mortality, Male, Middle Aged, Molecular Targeted Therapy, Mutation, Neoplasm Staging, Protein Kinase Inhibitors therapeutic use, Pyrazoles therapeutic use, Pyridines therapeutic use, Receptor Protein-Tyrosine Kinases antagonists & inhibitors, Risk Factors, Treatment Outcome, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms genetics, Lung Neoplasms pathology, Receptor Protein-Tyrosine Kinases genetics, Recombination, Genetic
- Abstract
Background: This study aimed to elucidate clinical significance of anaplastic lymphoma kinase (ALK) rearrangement in selected advanced non-small cell lung cancer (NSCLC), to compare the application of different ALK detection methods, and especially evaluate a possible association between ALK expression and clinical outcomes in crizotinib-treated patients., Methods: ALK status was assessed by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC) and quantitative RT-PCR (qRT-PCR) in 173 selected advanced NSCLC patients. Clinicopathologic data, genotype status and survival outcomes were analyzed. Moreover, the association of ALK expression with clinical outcomes was evaluated in ALK FISH-positive crizotinib-treated patients including two patients with concurrent epidermal growth factor receptor (EGFR) mutation., Results: The positivity detection rate of ALK rearrangement by FISH, IHC and qRT-PCR was 35.5% (59/166), 35.7% (61/171), and 27.9% (34/122), respectively. ALK rearrangement was observed predominantly in young patients, never or light smokers, and adenocarcinomas, especially with signet ring cell features and poor differentiation. Median progression-free survival (PFS) of crizotinib-treated patients was 7.6 months. The overall survival (OS) of these patients was longer compared with that of crizotinib-naive or wild-type cohorts, but there was no significant difference in OS compared with patients with EGFR mutation. ALK expression did not associate with PFS; but, when ALK expression was analyzed as a dichotomous variable, moderate and strong ALK expression had a decreased risk of death (P = 0.026). The two patients with concomitant EGFR and ALK alterations showed difference in ALK expression, response to EGFR and ALK inhibitors, and overall survival., Conclusions: Selective enrichment according to clinicopathologic features in NSCLC patients could highly improve the positivity detection rate of ALK rearrangement for ALK-targeted therapy. IHC could provide more clues for clinical trial design and therapeutic strategies for ALK-positive NSCLC patients including patients with double genetic aberration of ALK and EGFR.
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- 2014
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20. Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer.
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Xing PY, Li JL, Wang Y, Hao XZ, Wang B, Yang L, Shi YK, and Zhang XR
- Abstract
Objective: To observe the efficacy and safety of albumin-bound paclitaxel (ABP) monotherapy in treating recurrent advanced non-small-cell lung cancer (NSCLC)., Methods: We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed., Results: Of these 21 patients, the best overall response was partial response (PR) in 6 patients (28.6%), stable disease (SD) in 10 patients (47.6%), and progressive disease (PD) in 5 patients (23.8%). The overall response rate (ORR) was 28.6% and the disease control rate (DCR) (PR + SD) was 76.2%. The median progression-free survival (PFS) was 4.0 months (95% CI, 5.0-7.0 months). The main grade 3/4 toxicities included neutropenia (11.1%), peripheral nerve toxicity (5.6%), muscle and joint aches (5.6%), and fatigue (5.6%)., Conclusions: The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.
- Published
- 2013
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