Lung cancer is currently the leading cause of cancer death in Western nations.Non-small cell lung cancer(NSCLC)represents 80%of all lung cancers,and adenocarcinoma is the predominant histological type.Despite the inte...Lung cancer is currently the leading cause of cancer death in Western nations.Non-small cell lung cancer(NSCLC)represents 80%of all lung cancers,and adenocarcinoma is the predominant histological type.Despite the intensive research carried out on this field and therapeutic advances,the overall prognosis of these patients remains unsatisfactory,with a 5-year overall survival rate of less than 15%.Nowadays,pharmacogenetics and pharmacogenomics represent the key to successful treatment.Recent studies suggest the existence of two distinct molecular pathways in the carcinogenesis of lung adenocarcinoma:one associated with smoking and activation of the K-Ras oncogene and the other not associated with smoking and activation of the epidermal growth factor receptor(EGFR).The K-ras mutation is mainly responsible for primary resistance to new molecules which inhibit tyrosine kinase EGFR(erlotinib and gefitinib)and most of the EGFR mutations are responsible for increased tumor sensitivity to these drugs.This article aims to conduct a systematic review of the literature regarding the molecular pathways involving the EGFR,K-Ras and EGFR targeted therapies in NSCLC tumor behavior.展开更多
Since the latest revision of the TNM system reclassified T3N0 tumours into the ⅡB stage, N2 lesions became the major determinant of the ⅢA stage. Concerning the minority of patients with T3N1 tumours in this stage,
Introduction: Lung cancer is often diagnosed in a late stage, which might be related to lack of risk factors and symptoms awareness. Aim of this study was to evaluate these factors. Methods: A survey was conducted to ...Introduction: Lung cancer is often diagnosed in a late stage, which might be related to lack of risk factors and symptoms awareness. Aim of this study was to evaluate these factors. Methods: A survey was conducted to assess the awareness of lung cancer risk factors and symptoms. Kruskal-Wallis, Fisher and chi-square tests were used to compare the groups. Results: Altogether 403 participants (108 male;median age 29 (range 13 to 74) years;98 smokers, 90 ex-smokers and 212 non-smokers) completed the survey (321 filled in online questionnaire, 82 were interviewed face-to-face). Three per cent of the respondents were unable to name any lung cancer risk factor, 36% named one and 61% named two or more. Smoking was mentioned most commonly, others far less often. When presented with a list of lung cancer risk factors, 99.7% of respondents recognised two or more;most commonly smoking (99%) and second-hand smoking (95%). Concerning symptoms, 17% were unable to name any, 21% named one and 62% named two or more. Prolonged cough was mentioned most often (59%), followed by dyspnea (45%) and chest pain (30%). When presented with a list, 99% of respondents recognised two or more symptoms;most often prolonged cough (86%), weakness (85%) and chest pain (82%). There were no statistical differences in lung cancer symptom, risk factor or prognosis awareness among smokers, ex-smokers and non-smokers. There were some differences related to age, sex, education and type of used questionnaire. Conclusions: Awareness of lung cancer risks and symptoms is moderate in general population without major differences between smokers and non-smokers.展开更多
Objective: To observe the benefit of mineralocorticoid receptor antagonist and sodium-glucose co-transport 2 inhibitor (SGLT2 inhibitor) in heart failure preserved ejection (HFpEF) in rural Tanzania. Background and Re...Objective: To observe the benefit of mineralocorticoid receptor antagonist and sodium-glucose co-transport 2 inhibitor (SGLT2 inhibitor) in heart failure preserved ejection (HFpEF) in rural Tanzania. Background and Result: The use of spironolactone and dapagliflozin was shown to be effective in improving the clinical outcome and reducing CV hospitalization rate and CV mortality in patients with heart failure preserved left ventricular ejection fraction (HFpEF). This is the case presentation of one patient with HFpEF with diastolic dysfunction grade 3, obesity grade 3, Type 2 Diabetes, and Atrial Fibrillation (permanent). In the case of a 76-year-old female after previous ineffective treatment, the initiation of Spironolactone and Dapagliflozin led to a rapid and marked improvement in the clinical conditions. Diastolic dysfunction was improved from stage III to stage I. Moreover, the initiation of spironolactone and dapagliflozin therapy avoided a referral for surgical intervention and interrupted a long series of hospitalizations for acute HF and prevented CV death. Conclusion: Based on our experience, we conclude that the treatment with spironolactone and dapagliflozin allows for better treatment optimization with a positive impact on the control of clinical outcomes and preventing CV death and CV hospitalization in HFpEF and related comorbidities in the African population, which is underrepresented in most of the trials.展开更多
Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial ...Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.展开更多
小细胞肺癌(small cell lung cancer,SCLC)约占肺癌诊断病例的15%。多数SCLC患者确诊即为广泛期,化疗是其首选治疗方案,但总体疗效有限,患者预后差,急需新的临床治疗方案。2019年以来以抗程序性死亡受体-1(programmed death-1,PD-1)/程...小细胞肺癌(small cell lung cancer,SCLC)约占肺癌诊断病例的15%。多数SCLC患者确诊即为广泛期,化疗是其首选治疗方案,但总体疗效有限,患者预后差,急需新的临床治疗方案。2019年以来以抗程序性死亡受体-1(programmed death-1,PD-1)/程序性死亡受体配体-1(programmed death ligand-1,PD-L1)抗体药物为代表的免疫检查点抑制剂显著改善广泛期SCLC患者的生存预后。美国食品药品管理局(Food and Drug Administration,FDA)批准免疫联合化疗成为广泛期SCLC临床免疫治疗新方案。然而,免疫联合治疗受益患者人群及治疗疗效有限,因此如何筛选潜在受益患者及进一步提高疗效是临床急需解决的问题。本文针对广泛期SCLC免疫治疗疗效预测生物标志物以及联合治疗增敏策略的研究进展进行综述。展开更多
Background Pemetrexed is a novel folic acid antagonist with multiple targets, which has been widely used in the treatment of non-small cell lung cancer （NSCLC）. The objective of this study was to compare the effects...Background Pemetrexed is a novel folic acid antagonist with multiple targets, which has been widely used in the treatment of non-small cell lung cancer （NSCLC）. The objective of this study was to compare the effects and toxicities in NSCLC patients treated with pemetrexed monotherapy versus pemetrexed plus a platinum combination agent, so as to provide a basis for standard second-line chemotherapy. Methods The clinical data of 52 patients with NSCLC who were admitted to Shanghai Chest Hospital from August 2006 to October 2008 were retrospectively analyzed. Ten of the 52 patients received pemetrexed monotherapy, and the other 42 patients received the pemetrexed plus platinum regimen. The primary end point was overall survival （OS）. The progression-free survival time （PFS） was analyzed and the effects and toxicities were assessed. Survival analysis was evaluated by Kaplan-Meier method. Single factor analysis and the COX regression model were done to analyze the relationship between the influential factors and the prognosis of disease. The elderly patients （〉60 years old） were analyzed separately as a subgroup. Results No statistically significant increase in OS （x^2=0.09, P=0.76）, PFS （x^2=0.15, P=0.70）, disease control rate （DCR） （x^2=0.06, P=0.81） or 1-year survival rate （x^2=0.33, P=0.57） was found between the two regimens. Single factor analysis showed that the factors including surgery history, PS score before treatment, clinical stage, and response to second-line treatment influenced the prognosis of NSCLC （all P 〈0.05）. COX regression analysis demonstrated that surgery history （P=-0.041） and performance status （PS） score before treatment （P=0.043） may be associated with survival. The toxicity of the two regimens was similar. In the subgroup of elderly patients, no significant difference in OS （x^2=0.01, P=0.94）, PFS （x^2=0.14, P=0.70）, DCR （x^2=0.004, P=-0.95）, or 1-year survival rate （x^2=0.03, P=0.87） was found between the two regimens. The toxicity of combination therapy was significantly higher in terms of hematologic （x^2=g.95, P=-0.01） and gastrointestinal adverse events （x^2=7.66, P=0.03）. Conclusions There is no significant difference in survival or side effects between these two regimens. For elderly patients （〉60）, pemetrexed monotherapy shows similar efficacy and a better safety profile when compared with pemetrexed combination therapy.展开更多
Background Several clinical trials showed that erlotinib was effective after the failure of gefitinib in advanced non-small cell lung cancer （NSCLC）. The aim of this study was to evaluate the feasibility of erlotini...Background Several clinical trials showed that erlotinib was effective after the failure of gefitinib in advanced non-small cell lung cancer （NSCLC）. The aim of this study was to evaluate the feasibility of erlotinib treatment after the failure of gefitinib based on the data from our hospital. Methods The clinical data of 20 patients with advanced NSCLC who were admitted to Shanghai Chest Hospital from August 2007 to December 2008 were retrospectively analyzed. All of the patients were given erlotinib treatment after the failure of gefitinib. Survival analysis was made by Kaplan-Meier method. The Cox regression model was performed to analyze the relationship between the influential factors and the erlotinib progression-free survival （PFS）. Results Five patients had a partial response （PR）, nine patients had stable disease （SD） and six patients had progressive disease （PD） with gefitinib treatment. The median PFS was 277 days （95% CI 0-566）. No patient had a PR, seven had SD and fourteen PD with the erlotinib therapy. The median PFS was 31 days （95% CI 9.1-52.9）. The response rate （RR） was 0, and the disease control rate （DCR） was 35% （7/20）. Cox regression analysis demonstrated that sex （P=0.96）, age （P=0.89）, smoking history （P=0.78）, performance status （PS） （P=0.98）, gefitinib efficacy （P=-0.90） and whether chemotherapy was applied between using the two drugs （P=-0.45） had no significant correlation with erlotinib PFS. Fifteen patients had epidermal growth factor receptor （EGFR） mutation status determined. There were five cases got SD with the erlotinib treatment in ten mutation negative （wild-type） patients. No SD was recorded in the five mutation positive patients. Conclusions The efficacy of erlotinib treatment after gefitinib failure was limited. However, the patients who are EGFR mutation negative can probably benefit from erlotinib treatment after gefitinib failure.展开更多
文摘Lung cancer is currently the leading cause of cancer death in Western nations.Non-small cell lung cancer(NSCLC)represents 80%of all lung cancers,and adenocarcinoma is the predominant histological type.Despite the intensive research carried out on this field and therapeutic advances,the overall prognosis of these patients remains unsatisfactory,with a 5-year overall survival rate of less than 15%.Nowadays,pharmacogenetics and pharmacogenomics represent the key to successful treatment.Recent studies suggest the existence of two distinct molecular pathways in the carcinogenesis of lung adenocarcinoma:one associated with smoking and activation of the K-Ras oncogene and the other not associated with smoking and activation of the epidermal growth factor receptor(EGFR).The K-ras mutation is mainly responsible for primary resistance to new molecules which inhibit tyrosine kinase EGFR(erlotinib and gefitinib)and most of the EGFR mutations are responsible for increased tumor sensitivity to these drugs.This article aims to conduct a systematic review of the literature regarding the molecular pathways involving the EGFR,K-Ras and EGFR targeted therapies in NSCLC tumor behavior.
文摘Since the latest revision of the TNM system reclassified T3N0 tumours into the ⅡB stage, N2 lesions became the major determinant of the ⅢA stage. Concerning the minority of patients with T3N1 tumours in this stage,
文摘Introduction: Lung cancer is often diagnosed in a late stage, which might be related to lack of risk factors and symptoms awareness. Aim of this study was to evaluate these factors. Methods: A survey was conducted to assess the awareness of lung cancer risk factors and symptoms. Kruskal-Wallis, Fisher and chi-square tests were used to compare the groups. Results: Altogether 403 participants (108 male;median age 29 (range 13 to 74) years;98 smokers, 90 ex-smokers and 212 non-smokers) completed the survey (321 filled in online questionnaire, 82 were interviewed face-to-face). Three per cent of the respondents were unable to name any lung cancer risk factor, 36% named one and 61% named two or more. Smoking was mentioned most commonly, others far less often. When presented with a list of lung cancer risk factors, 99.7% of respondents recognised two or more;most commonly smoking (99%) and second-hand smoking (95%). Concerning symptoms, 17% were unable to name any, 21% named one and 62% named two or more. Prolonged cough was mentioned most often (59%), followed by dyspnea (45%) and chest pain (30%). When presented with a list, 99% of respondents recognised two or more symptoms;most often prolonged cough (86%), weakness (85%) and chest pain (82%). There were no statistical differences in lung cancer symptom, risk factor or prognosis awareness among smokers, ex-smokers and non-smokers. There were some differences related to age, sex, education and type of used questionnaire. Conclusions: Awareness of lung cancer risks and symptoms is moderate in general population without major differences between smokers and non-smokers.
文摘Objective: To observe the benefit of mineralocorticoid receptor antagonist and sodium-glucose co-transport 2 inhibitor (SGLT2 inhibitor) in heart failure preserved ejection (HFpEF) in rural Tanzania. Background and Result: The use of spironolactone and dapagliflozin was shown to be effective in improving the clinical outcome and reducing CV hospitalization rate and CV mortality in patients with heart failure preserved left ventricular ejection fraction (HFpEF). This is the case presentation of one patient with HFpEF with diastolic dysfunction grade 3, obesity grade 3, Type 2 Diabetes, and Atrial Fibrillation (permanent). In the case of a 76-year-old female after previous ineffective treatment, the initiation of Spironolactone and Dapagliflozin led to a rapid and marked improvement in the clinical conditions. Diastolic dysfunction was improved from stage III to stage I. Moreover, the initiation of spironolactone and dapagliflozin therapy avoided a referral for surgical intervention and interrupted a long series of hospitalizations for acute HF and prevented CV death. Conclusion: Based on our experience, we conclude that the treatment with spironolactone and dapagliflozin allows for better treatment optimization with a positive impact on the control of clinical outcomes and preventing CV death and CV hospitalization in HFpEF and related comorbidities in the African population, which is underrepresented in most of the trials.
基金supported by grants from Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2017B030314120)General Research Project of Guangzhou Science and Technology Bureau (Grant No. 201607010391)+1 种基金National Key Research and Development Program of China (Grant No. 2016YFC1303800)Guangdong Provincial Applied S&T R&D Program (Grant No. 2016B020237006)
文摘Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.
文摘小细胞肺癌(small cell lung cancer,SCLC)约占肺癌诊断病例的15%。多数SCLC患者确诊即为广泛期,化疗是其首选治疗方案,但总体疗效有限,患者预后差,急需新的临床治疗方案。2019年以来以抗程序性死亡受体-1(programmed death-1,PD-1)/程序性死亡受体配体-1(programmed death ligand-1,PD-L1)抗体药物为代表的免疫检查点抑制剂显著改善广泛期SCLC患者的生存预后。美国食品药品管理局(Food and Drug Administration,FDA)批准免疫联合化疗成为广泛期SCLC临床免疫治疗新方案。然而,免疫联合治疗受益患者人群及治疗疗效有限,因此如何筛选潜在受益患者及进一步提高疗效是临床急需解决的问题。本文针对广泛期SCLC免疫治疗疗效预测生物标志物以及联合治疗增敏策略的研究进展进行综述。
文摘Background Pemetrexed is a novel folic acid antagonist with multiple targets, which has been widely used in the treatment of non-small cell lung cancer （NSCLC）. The objective of this study was to compare the effects and toxicities in NSCLC patients treated with pemetrexed monotherapy versus pemetrexed plus a platinum combination agent, so as to provide a basis for standard second-line chemotherapy. Methods The clinical data of 52 patients with NSCLC who were admitted to Shanghai Chest Hospital from August 2006 to October 2008 were retrospectively analyzed. Ten of the 52 patients received pemetrexed monotherapy, and the other 42 patients received the pemetrexed plus platinum regimen. The primary end point was overall survival （OS）. The progression-free survival time （PFS） was analyzed and the effects and toxicities were assessed. Survival analysis was evaluated by Kaplan-Meier method. Single factor analysis and the COX regression model were done to analyze the relationship between the influential factors and the prognosis of disease. The elderly patients （〉60 years old） were analyzed separately as a subgroup. Results No statistically significant increase in OS （x^2=0.09, P=0.76）, PFS （x^2=0.15, P=0.70）, disease control rate （DCR） （x^2=0.06, P=0.81） or 1-year survival rate （x^2=0.33, P=0.57） was found between the two regimens. Single factor analysis showed that the factors including surgery history, PS score before treatment, clinical stage, and response to second-line treatment influenced the prognosis of NSCLC （all P 〈0.05）. COX regression analysis demonstrated that surgery history （P=-0.041） and performance status （PS） score before treatment （P=0.043） may be associated with survival. The toxicity of the two regimens was similar. In the subgroup of elderly patients, no significant difference in OS （x^2=0.01, P=0.94）, PFS （x^2=0.14, P=0.70）, DCR （x^2=0.004, P=-0.95）, or 1-year survival rate （x^2=0.03, P=0.87） was found between the two regimens. The toxicity of combination therapy was significantly higher in terms of hematologic （x^2=g.95, P=-0.01） and gastrointestinal adverse events （x^2=7.66, P=0.03）. Conclusions There is no significant difference in survival or side effects between these two regimens. For elderly patients （〉60）, pemetrexed monotherapy shows similar efficacy and a better safety profile when compared with pemetrexed combination therapy.
文摘Background Several clinical trials showed that erlotinib was effective after the failure of gefitinib in advanced non-small cell lung cancer （NSCLC）. The aim of this study was to evaluate the feasibility of erlotinib treatment after the failure of gefitinib based on the data from our hospital. Methods The clinical data of 20 patients with advanced NSCLC who were admitted to Shanghai Chest Hospital from August 2007 to December 2008 were retrospectively analyzed. All of the patients were given erlotinib treatment after the failure of gefitinib. Survival analysis was made by Kaplan-Meier method. The Cox regression model was performed to analyze the relationship between the influential factors and the erlotinib progression-free survival （PFS）. Results Five patients had a partial response （PR）, nine patients had stable disease （SD） and six patients had progressive disease （PD） with gefitinib treatment. The median PFS was 277 days （95% CI 0-566）. No patient had a PR, seven had SD and fourteen PD with the erlotinib therapy. The median PFS was 31 days （95% CI 9.1-52.9）. The response rate （RR） was 0, and the disease control rate （DCR） was 35% （7/20）. Cox regression analysis demonstrated that sex （P=0.96）, age （P=0.89）, smoking history （P=0.78）, performance status （PS） （P=0.98）, gefitinib efficacy （P=-0.90） and whether chemotherapy was applied between using the two drugs （P=-0.45） had no significant correlation with erlotinib PFS. Fifteen patients had epidermal growth factor receptor （EGFR） mutation status determined. There were five cases got SD with the erlotinib treatment in ten mutation negative （wild-type） patients. No SD was recorded in the five mutation positive patients. Conclusions The efficacy of erlotinib treatment after gefitinib failure was limited. However, the patients who are EGFR mutation negative can probably benefit from erlotinib treatment after gefitinib failure.
