BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are often associated with non-EGFR genetic alterations, which may be a reason for the poor efficacy of EGFR tyrosine kinase inhibitors (TKIs). Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations. METHODS: Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant non-EGFR genetic alterations were retrospectively collected. And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy. Demographic, clinical and pathological data were collected, and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression. Survival data were obtained through face-to-face or telephone follow-up. The differences between the two groups in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS 107 patients were included, including 63 cases in the combination group and 44 cases in the monotherapy group. The ORR were 78% and 50% (P=0.003), and DCR were 97% and 77% (P=0.002), respectively. At a median follow-up of 13.7 mon, a PFS event occurred in 38.1% and 81.8% of patients in the two groups, with median PFS of 18.8 mon and 5.3 mon, respectively (P<0.000,1). Median OS was unreached in the combination group, and 27.8 mon in the monotherapy group (P=0.31). According to the Cox multivariate regression analysis, combination therapy was an independent prognostic factor of PFS CONCLUSIONS: In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations, combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy, which should be the preferred treatment option.
Adenocarcinoma of Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Retrospective Studies

Objective:To explore the risk factors of acute renal injury (AKI) in exertional heat radiation disease (EHS) .Methods:In november 2019, the clinical data of 69 EHS patients admitted from July 2015 to September 2019 were reviewed. The general data, laboratory indexes, Glasgow score (GCS) at admission, 24-hour acute physiology and chronic health score Ⅱ (APACHE Ⅱ) , exposure time rate and physical labor intensity were collected. According to the occurrence of AKI, the patients were divided into AKI group and non-AKI group, 31 and 38 in each group. The differences of general data and laboratory indexes between the two groups were compared, and the t and Mann-Whitney U test were used to compare the two groups. The enumeration data are expressed by examples and constituent ratio (%) . Independent sample χ 2 test is used for inter-group comparison, and multiple test is used for multi-sample comparison. The correlation was analyzed by linear regression. Risk factors were analyzed by Logistic regression analysis. Results:At discharge, 31 of 69 EHS patients developed AKI. Compared with the non-AKI group, the heart rate, white blood cell count, lactic acid, D-dimer and myoglobin were higher; MAP, platelet count and PH were lower in the AKI group. The difference was statistically significant ( P<0.05) . APACHE Ⅱ score, core temperature, time to drop to 38.5 ℃, contact time rate, platelet count, pH, lactic acid, D-dimer and myoglobin were all correlated with creatinine ( r=0.57, 0.42, 0.80, 0.78, 0.57, 0.43, 0.51, 0.55, 0.79) . APACHE Ⅱ score, time to drop to 38.5C, Lac and MYO are the risk factors of AKI in EHS patients. Multivariate Logistic regression analysis showed that the time required to drop to 38.5C was an independent risk factor for the occurrence of AKI. Conclusion:AKI is a serious complication of EHS. EHS complicated with AKI, should be identified early and effective intervention measures should be taken.

Objective:To explore the risk factors of acute renal injury (AKI) in exertional heat radiation disease (EHS) .Methods:In november 2019, the clinical data of 69 EHS patients admitted from July 2015 to September 2019 were reviewed. The general data, laboratory indexes, Glasgow score (GCS) at admission, 24-hour acute physiology and chronic health score Ⅱ (APACHE Ⅱ) , exposure time rate and physical labor intensity were collected. According to the occurrence of AKI, the patients were divided into AKI group and non-AKI group, 31 and 38 in each group. The differences of general data and laboratory indexes between the two groups were compared, and the t and Mann-Whitney U test were used to compare the two groups. The enumeration data are expressed by examples and constituent ratio (%) . Independent sample χ 2 test is used for inter-group comparison, and multiple test is used for multi-sample comparison. The correlation was analyzed by linear regression. Risk factors were analyzed by Logistic regression analysis. Results:At discharge, 31 of 69 EHS patients developed AKI. Compared with the non-AKI group, the heart rate, white blood cell count, lactic acid, D-dimer and myoglobin were higher; MAP, platelet count and PH were lower in the AKI group. The difference was statistically significant ( P<0.05) . APACHE Ⅱ score, core temperature, time to drop to 38.5 ℃, contact time rate, platelet count, pH, lactic acid, D-dimer and myoglobin were all correlated with creatinine ( r=0.57, 0.42, 0.80, 0.78, 0.57, 0.43, 0.51, 0.55, 0.79) . APACHE Ⅱ score, time to drop to 38.5C, Lac and MYO are the risk factors of AKI in EHS patients. Multivariate Logistic regression analysis showed that the time required to drop to 38.5C was an independent risk factor for the occurrence of AKI. Conclusion:AKI is a serious complication of EHS. EHS complicated with AKI, should be identified early and effective intervention measures should be taken.

Objective:To preliminarily explore the treatment effect of nivolumab on Chinese non-small-cell lung cancer (NSCLC) patients with brain metastases, and further enrich the evidences of programmed death-ligand 1 (PD-1) monoclonal antibody in the treatment of NSCLC patients with brain metastases.Methods:The clinical and pathological data of 22 NSCLC patients with brain metastases treated with nivolumab were collected. The electronic imaging data were collected to confirm the treatment effect and time point of disease progression, and the survival data of the patients were obtained through follow-up.Results:Twenty-one patients were evaluated for the intracranial treatment effect. The intracerebral objective response rate (IORR) was 28.6%, the intracranial disease control rate (IDCR) was 47.6%. The median intracranial progression-free-survival (iPFS) of all the 22 patients was 5.2 months. Both the 1-year and 2-year survival rates were 56.7%.Conclusions:The treatment effect of PD-1 monoclonal antibody on NSCLC patients with brain metastases is similar as those without brain metastases.

Objective:To preliminarily explore the treatment effect of nivolumab on Chinese non-small-cell lung cancer (NSCLC) patients with brain metastases, and further enrich the evidences of programmed death-ligand 1 (PD-1) monoclonal antibody in the treatment of NSCLC patients with brain metastases.Methods:The clinical and pathological data of 22 NSCLC patients with brain metastases treated with nivolumab were collected. The electronic imaging data were collected to confirm the treatment effect and time point of disease progression, and the survival data of the patients were obtained through follow-up.Results:Twenty-one patients were evaluated for the intracranial treatment effect. The intracerebral objective response rate (IORR) was 28.6%, the intracranial disease control rate (IDCR) was 47.6%. The median intracranial progression-free-survival (iPFS) of all the 22 patients was 5.2 months. Both the 1-year and 2-year survival rates were 56.7%.Conclusions:The treatment effect of PD-1 monoclonal antibody on NSCLC patients with brain metastases is similar as those without brain metastases.

Objective: To investigate the clinical effects of first generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) compared with platinum-based chemotherapy as first-line therapy in advanced lung adenocarcinoma patients with uncommon EGFR mutations. Methods: Clinical data of 4 276 patients diagnosed as advanced lung adenocarcinoma (ⅢB/Ⅳ) underwent EGFR gene detection at the Affiliated Cancer Hospital of Zhengzhou University from January 2012 to February 2018 were collected and 99 cases with uncommon EGFR mutations were selected. The clinical pathological features, treatment outcomes, treatment options and prognosis after first-line treatment of the 99 cases were analysed and compared with other patients with common EGFR mutations. Results: The objective response rates of patients with uncommon EGFR mutations receiving EGFR-TKIs or platinum-based chemotherapy were 33.0% and 27.1%, respectively. The disease control rates were 76.5% and 87.5%, respectively. The progression-free survival (PFS) of patients treated with EGFR-TKIs was 7.2 months, significantly superior than 4.9 months of patients receiving chemotherapy (P=0.009). The overall survival of patients treated with EGFR-TKIs was 14.3 months, significantly worse than 20.7 months of patients receiving chemotherapy (P=0.034). Multivariate analysis showed that distant metastases (P=0.001) and smoking history (P=0.013) were independent prognostic factors for OS of lung adenocarcinoma patients with EGFR uncommon mutations. Conclusions Compared with chemotherapy, the usage of first generation of EGFR-TKIs as first-line therapy can improve the short-term efficacy of advanced lung adenocarcinoma patients with EGFR uncommon mutations. However, platinum-based chemotherapy shows a longer overall survival.

Objective To compare the efficacy and tolerance of platinum-based doublet chemotherapy versus single-agent chemotherapy as second-line treatment in elderly patients with advanced non-small cell lung cancer(NSCLC).Methods A total of 85 elderly patients with advanced NSCLC after first-line treatment were retrospectively analyzed and divided into the combination therapy group(n=40,taking platinum-based doublet chemotherapy)and the single-agent chemotherapy group(n=45,receiving single-agent second-line chemotherapy).Results There were no significant differences in the objective response rate (ORR)and the disease control rate (DCR)between the combination therapy group and the single-agent chemotherapy group(27.5 ％ or 11/40 vs.20.0 ％ or 9/45,60.0％ or 24/40 vs.73.3％ or 33/45,x2 =0.662 and 1.704,P=0.416 and 0.192).The median progression-free survival(PFS)was 3.8 months for the combination therapy group and 2.8 months for the single-agent chemotherapy group(P =0.045).The rate of grade Ⅲ/Ⅳ hematological toxicity was higher in the combination therapy group than in the single-agent chemotherapy group.Conclusions Platinum-based doublet chemotherapy has longer PFS than the single-agent chemotherapy as secondline treatment in elderly patients with advanced non-small cell lung cancer,and more attention should be paid to its high hematological toxicity.

Objective To investigate the clinical effects of first generation epithelial growth factor receptor tyrosine kinase inhibitors ( EGFR?TKIs) compared with platinum?based chemotherapy as first?line therapy in advanced lung adenocarcinoma patients with uncommon EGFR mutations. Methods Clinical data of 4 276 patients diagnosed as advanced lung adenocarcinoma (ⅢB／Ⅳ) underwent EGFR gene detection at the Affiliated Cancer Hospital of Zhengzhou University from January 2012 to February 2018 were collected and 99 cases with uncommon EGFR mutations were selected. The clinical pathological features, treatment outcomes, treatment options and prognosis after first?line treatment of the 99 cases were analysed and compared with other patients with common EGFR mutations. Results The objective response rates of patients with uncommon EGFR mutations receiving EGFR?TKIs or platinum?based chemotherapy were 33.0%and 27.1%, respectively. The disease control rates were 76.5% and 87.5%, respectively. The progression?free survival (PFS) of patients treated with EGFR?TKIs was 7.2 months, significantly superior than 4.9 months of patients receiving chemotherapy (P＝0.009). The overall survival of patients treated with EGFR?TKIs was 14.3 months, significantly worse than 20.7 months of patients receiving chemotherapy (P＝0.034). Multivariate analysis showed that distant metastases ( P＝0.001) and smoking history ( P＝0.013) were independent prognostic factors for OS of lung adenocarcinoma patients with EGFR uncommon mutations. Conclusions Compared with chemotherapy, the usage of first generation of EGFR?TKIs as first?line therapy can improve the short?term efficacy of advanced lung adenocarcinoma patients with EGFR uncommon mutations. However, platinum?based chemotherapy shows a longer overall survival.

Objective To investigate the clinical effects of first generation epithelial growth factor receptor tyrosine kinase inhibitors ( EGFR?TKIs) compared with platinum?based chemotherapy as first?line therapy in advanced lung adenocarcinoma patients with uncommon EGFR mutations. Methods Clinical data of 4 276 patients diagnosed as advanced lung adenocarcinoma (ⅢB／Ⅳ) underwent EGFR gene detection at the Affiliated Cancer Hospital of Zhengzhou University from January 2012 to February 2018 were collected and 99 cases with uncommon EGFR mutations were selected. The clinical pathological features, treatment outcomes, treatment options and prognosis after first?line treatment of the 99 cases were analysed and compared with other patients with common EGFR mutations. Results The objective response rates of patients with uncommon EGFR mutations receiving EGFR?TKIs or platinum?based chemotherapy were 33.0%and 27.1%, respectively. The disease control rates were 76.5% and 87.5%, respectively. The progression?free survival (PFS) of patients treated with EGFR?TKIs was 7.2 months, significantly superior than 4.9 months of patients receiving chemotherapy (P＝0.009). The overall survival of patients treated with EGFR?TKIs was 14.3 months, significantly worse than 20.7 months of patients receiving chemotherapy (P＝0.034). Multivariate analysis showed that distant metastases ( P＝0.001) and smoking history ( P＝0.013) were independent prognostic factors for OS of lung adenocarcinoma patients with EGFR uncommon mutations. Conclusions Compared with chemotherapy, the usage of first generation of EGFR?TKIs as first?line therapy can improve the short?term efficacy of advanced lung adenocarcinoma patients with EGFR uncommon mutations. However, platinum?based chemotherapy shows a longer overall survival.

In recent years, along with rapid development of targeted therapy in non-small cell lung cancer, tradi-tional chemotherapy get less and less attention. Yet it still can not be ignored in the current that how to locate and use tradi-tional chemotherapy so patients could derive maximum beneift. For this purpose, through the literature review and analysis, we point out there are still many traditional chemotherapy irreplaceable places whatever patients’ driver gene status. And there are some new treatment modalities of traditional chemotherapy which have been developed to further improve patients’ survival. At the same time, through exposition of predictive bio-markers development in chemotherapy, we pointed out that the future of traditional chemotherapy must be part of“targeted therapy”.