Improvement of Quality of Life with Shenfu Injection (参附注射液) in Non Small Cell Lung Cancer Patients Treated with Gemcitabine plus Cisplatin Regimen

Objective： To observe the effect of Shenfu injection （参附注射液, SFI） in treating non small cell lung cancer （NSCLC） patients on quality of life with gemcitabine （GEM） plus cisplatin （GP） regimen. Methods： Thirty-four patients were ready to receive GP regimen chemotherapy for treating NSCLC disease, according to lot-drawing, they were divided into SFI pre-treatment group （18 cases） and SFI post-treatment group （ 16 cases）. SFI pre-treatment group： During the first treatment course, chemotherapy was begun with SFI 60 ml, intravenous dripping on the 3rd day, once daily, consecutively for 10 days; on the 1st day, GP regimen （GEM 1250 mg/m^2 , intravenous dripping, on the 1st and 8th day; cisplatin 70 mg/m^2 on the 2nd day; 21 days as one cycle） was carried out; in the second treatment course GP regimen was merely given to serve as the self-control. SFI post-treatment group： the medicament sequence order was reversed from that of pre-treatment group. Using dual international quality of life （QOL） scores, the effect of SFI on the patients＂ QOL was observed through randomized self pre- and post- crossover control. Results： The QOL in the 34 patients after being treated by SFI in combination with GP chemotherapy regimen in one group, and GP chemotherapy regimen alone in the other, was improved in different degrees, with significant difference （P〈0.01）; comparision of SFI combined with GP chemotherapy regimen with GP chemotherapy alone showed that QOL in patients was significantly different （P〈0.01）. Conclusion： SFI could improve QOL in patients with NSCLC who were treated with GP regimen.

Perioperative considerations in patients with non small cell lung cancer and metastases in mediastinal lymph nodes

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,

CYFRA 21-1 as an early predictor of first line chemotherapy response in advanced non small cell lung cancer

Objective： In an era of ever evolving, promising new therapies for advanced non small cell lung cancer （NSCLC）, early predictors of response to therapy, are needed. We evaluated early variations in CYFRA 21-1 serum levels of patients with advanced NSCLC receiving first line chemotherapy and correlated the results with objective tumor response. Methods： 29 consecutive, previously untreated, patients of advanced non small cell lung cancer, with measurable disease on CT scan were evaluated. All patients were treated with conventional systemic chemotherapy, although the choice of chemotherapy was left to the discretion of the treating physicians. Serum samples were obtained immediately before the start of 1st and 2nd cycles of chemotherapy. CYFRA 21-1 was measured with an electrochemiluminescense immunoassay on an automatic analyzer （Elecsys 2000; Roche Diagnostics）. Response was evaluated using Response evaluation criteria in solid tumors （RECIST） criteria. Results： 10 patients had partial response, 9 patients had stable disease and 9 had progressive disease. None of the patients had complete response. 21/29 （72%） patients had an elevated baseline value of CYFRA 21-1.62% patients （18/29） had a decrease in CYFRA 21-1 after 1 cycle of chemotherapy. The average reduction in the 2nd reading was irrespective of whether baseline value was normal or not. The average reduction was statistically significant （P = 0.002; 95% CI, from 0.8369 to 3.49464; t test）. 8 out of 10 （80%） patients with partial response had a reduction in their 2nd reading of. CYFRA （P = 0.019; 95% CI, from 0.81965 to 7.20035; t test） which was significant. We also observed that 6/9 （66%） patients whose disease remains stable also had a decrease in their subsequent reading （P = 0.0106; 95% CI, from -0.44942 to 3.82720; t test）, though it was not significant statistically. Although 5 out of 9 （55%） patients, who had an increase in their CYFRA 21-1 level, had progressive disease, but it was not statistically significant （P = 0.537; 95% CI, from -1.20021 to 2.13354; ttest）. 14 out of 19 （73%） who either had partial response or had stable disease, had a reduction in their 2nd value of CYFRA 21-1 and was significant statistically （P = 0.004; 95% CI, from 0.74792 to 3.50208; t test）. We also observed that except for 1 patient, all patients who had a decrease of 42% or more in their subsequent CYFRA 21-1 level, were those who had either responded to chemotherapy or had stable disease （P = 0.001）, which was statistically significant. Conclusion： We can conclude that monitoring of serum marker CYFRA 21-1, early dudng first-line chemotherapy may be a useful prognostic tool for evaluation of early tumor response in patients with advanced NSCLC.

Monoclonal Antibodies: An Emerging Class of Therapeutics in Non Small Cell Lung Cancer

Lung cancer is the leading cause of cancer-related deaths in industrialized countries and non small cell lung cancer (NSCLC) accounts for 85% of all lung cancers. Cisplatin doublet based chemotherapy, which is the recommended regimen in first line therapy in advanced or metastatic NSCLC, improves survival but in low proportion. Monoclonal antibodies (mAbs) are a novel promising therapeutic class used with great results in inflammatory diseases such as rheumatoid arthritis. Antibodies are natural proteins with modular structure, specific pharmacodynamics and pharmacokinetics and possibly produced against any antigens, thus giving them several advantages over small drug therapeutics. In solid tumors, therapeutic mAbs improved progression free survival (PFS) and overall survival (OS) of patients with breast and colon cancers and had considerably changed the treatment in clinical practice. In NSCLC, bevacizumab, an anti-VEGF mAb, and cetuximab, an anti-EGFR mAb, are the most studied antibodies. Bevacizumab acts on angiognenesis and improved PFS of non squamous NSCLC but in low proportion as shown in two large phase III trials. It was approved by European Medicines Agency (EMEA) and Food and Drug administration (FDA) as a first line therapy in combination with cisplatin doublet chemotherapy. Cetuximab slightly enhanced OS but did not improve PFS in two large phase III trials. These results added to high adverse effect lead to cetuximab refusal by EMEA and FDA in NSCLC. At first glance, the results of mAbs in NSCLC are somewhat disappointing, in contrast to the benefits obtained with mAb treatments in other solid tumors. However, many other mAbs directed against novel targets, such as IGF1-R or CTLA-4, and new mAbs targeting VEGFR and EGFR pathways with different pharmacodymamical and pharmacokinetic properties are under evaluation and may change our vision of taking care of patients with NSCLC. In conclusion, it seems that mAbs therapy in NSCLC clearly marks the start of a new era in NSCLC treatment, with promises in improving patient survival and quality of life.

The ^(18)F-FDG uptake in non small cell lung carcinoma correlates with the DNA-grading of malignancy

In order to evaluate correlation of glucose metabolism and DNA ploidity of tumors, the uptake of 18F-Deoxyglucose (FDG) by PET prior to surgery and the DNA cotent and DNA-grading of malignancy (DNA-MG) of Schiff-stained nuclei obtained from fresh tumor fragments by means of image cytometry were studied, and thereafter the correlation between standardized uptake value (SUV) and (DNA-MG) was analysed in forty-nine patients with histologically proven non-small cell lung carcinoma (NSCLC). As a result of the DNA histograms of these 49 patients, 46 (93.88%) were aneuploid and only 3(6.12%) were tetraploid. A linear correlation of the SUV versus the (DNA-MG) (r=0.336, p=0.024) was found, demonstrating that 18F-FDG PET as a non-invasive metabolic imaging technique, may also provide inforrnation correlated to malignant DNA patterns which may be valuable in malignant differentiation and prognostic prediction.

Forecasting of Survival Rate in Patients with the Early Stage of Non Small Cell Lung Cancer

Lung cancer is the most common cause of death from oncological diseases all over the world. Primary treatment of patients with the early stage of non-small cell lung cancer is a surgery. However, after surgery 30% - 85% of patients undergo disease progression. In order to improve the results of treatment of patients with non-small cell lung cancer it is necessary to separate a group of patients with dismal prognosis for whom adjuvant chemotherapy will permit improving the survival rate. The aim of our research was to create a forecasting model with a view to detect the patients with the early stage of non-small cell lung cancer and dismal prognosis. Our research covered 254 patients with the early stage of non-small cell lung cancer who underwent a cure from June 2008 till December 2012 in the department of thoracic surgery of Zaporizhzhia Regional Clinical Oncologic Dispensary. In order to identify the factors connected with the risks of low survival rate of patients with the early stage of non-small cell lung cancer after curative treatment (surgical treatment, adjuvant chemotherapy), a method of design of neural network models of classification was used. 39 factors were taken for input characteristics. During investigation two forecasting models were built. As follows from the analysis of first forecasting model with the increase of the patient’s BMI, the risk of low patient survival rate statistically and significantly (p = 0.03) decreases, OR = 0.89 (95% CI 0.80 - 0.99) for each kg/m2 index value. The risk of low patient survival rate also decreases (p = 0.02) if he has a squamous cell carcinoma, OR = 0.36 (95% CI 0.15 - 0.88) compared with other histological forms of tumor. The connection between the risk of low patient survival rate and the volume of surgical intervention was discovered (p = 0.01), OR = 3.19 (95% CI 1.29 - 7.86) for patients who underwent a pulmonectomy compared with patients who underwent an upper bilobectomy. As follows from the analysis of second forecasting model with the increase of the patient’s BMI the risk of low patient survival rate statistically and significantly (p = 0.01) decreases;OR = 0.84 (95% CI 0.74 - 0.96) for each kg/m2 index value. It is found that with the increasing level of EGFR expression in the primary tumor, the risk of low patient survival rate statistically and significantly increases (p = 0.04), OR = 1.39 (95% CI 1.01 - 1.90) for each graduation rate. The risk of low patient survival rate also increases when conducting the lymph dissection in the volume D0 - D1.

A Clinic-Epidemilogical Study of Cases of Locally Advanced Non Small Cell Lung Cancer (NSCLC) That Received Radiotherapy at NCI Cairo in the Period from 2001-2010

Purpose: This work was to study the clinic-epidemiological characteristics of patients with locally advanced NCSLC and to analyze their prognostic factors and also the results of different treatment modalities for local control and their effect on overall survival (OAS). Materials and Methods: This is a retrospective study including 121 patients with primary locally advanced NSCLC diagnosed between 2001 and 2010 at the radiotherapy department , National Cancer Institute, Cairo University, Egypt. Results: The study showed significant correlation between the tumor size 60, moderately differentiated tumors G2 and treatment outcomes;better locoregional control and better survival rates. On the opposite side poorly differentiated tumors G3, tumor size > 7 cm had the worst locoregional control and survival rates. The study also showed significant statistical correlation between treatment modality, locoregional control and survival rates. Patients who were treated by either concommitent chemo-radiotherapy or sequential chemo-radiotherapy had better local control compared to other patients who were treated by radical radiotherapy, and they also had the best survival rates among all the other treatment groups. The average 6 months OAS rates for all studied patients were 60.3% while 12 months survival rates were 38.8%. The median OAS was 7 months. Conclusions: From the present study, we concluded that concomitant chemo-radiotherapy is the treatment of choice for locally advanced non small cell lung cancer;also we concluded that better performance status and higher hemoglobin levels have better treatment outcome in these cases.

Pang Fuwan Uses Yao Medicine to Observe the Therapeutic Effects on the Physical and Mental Symptoms of Patients with Advanced Non-Small Cell Lung Cancer

Objective: Investigate the efficacy and safety of Yao Medicine in the treatment of advanced non-small-cell lung carcinoma, and explore the best therapeutic measure for clinical benefit. Methods: From July 2020 to July 2022, 84 patients with advanced non-small-cell lung carcinoma were selected and randomly divided into the Observation Group and control group, and the control group was treated with routine Western medicine, with 42 cases in each group. The activity of daily living (ADL) was assessed before and after treatment, meanwhile, the self-rating depression scale (SDS) and self-rating anxiety SAS (SAS) were used to assess the improvement of a bad mood, and quality of life SF-36 was used to assess the quality of life, to judge the efficacy and safety. Results: The effective rate of observation group was 91.67%. The effective rate of the control group was 76.19%. The effective rate of the observation group was significantly higher than that of the control group (P 0.05). There were no significant differences in the scores of SDS, SAS and quality of life between the two groups before treatment (P > 0.05), and after treatment, the scores of SDS, SAS and quality of life in the two groups were compared with those in the control group (P > 0.05), the scores of VAS, SDS and SAS decreased significantly, while ESCV, angle of straight leg elevation, ADL, physiological score, emotional score, social score and health status score increased significantly, the difference was statistically significant (P 0.05). Conclusion: Yao Medicine can improve the psychosomatic symptoms of patients with advanced non-small-cell lung carcinoma better, with better efficacy and higher safety.

Analysis and Review of Downregulated Actin Cytoskeletal Proteins in Non-Small Cell Lung Cancer

Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties of NSCLC proteins is a potential alternative for developing treatment strategies. Towards this, 35 downregulated actin cytoskeletal proteins on NSCLC prognosis and treatment were studied by examining their protein-protein interactions, gene ontology enrichment terms, and signaling pathways. Using PubMed, various proteins in NSCLC were identified. The protein-protein interactions and functional associations of these proteins were examined using the STRING database. The focal adhesion signaling pathway was selected from all available KEGG and Wiki pathways because of its role in regulating gene expression, facilitating cell movement and reproduction, and significantly impacting NSCLC. The protein-protein interaction network of the 35 downregulated actin cytoskeleton proteins revealed that ACTG1, ACTR2, ACTR3, ANXA2, ARPC4, FLNA, TLN1, CALD1, MYL6, MYH9, MYH10, TPM1, TPM3, TPM4, PFN1, IQGAP1, MSN, and ZXY exhibited the highest number of interactions. Whereas HSPB1, CTNNA1, KRT17, KRT7, FLNB, SEPT2, and TUBA1B displayed medium interactions, while UTRN, TUBA1B, and DUSP23 had relatively fewer interactions. It was discovered that focal adhesions are critical in connecting membrane receptors with the actin cytoskeleton. In addition, protein kinases, phosphatases, and adapter proteins were identified as key signaling molecules in this process, greatly influencing cell shape, motility, and gene expression. Our analysis shows that the focal adhesion pathway plays a crucial role in NSCLC and is essential for developing effective treatment strategies and improving patient outcomes.

Efficacy and Safety of Primary Radiotherapy in Combination with EGFR-TKIs for Non-Small Cell Lung Cancer Harboring EGFR Mutation

Objective: To evaluate the efficacy and safety of EGFR-TKI with the radiotherapy in EGFR mutant metastatic NSCLC. Methods: Retrospective analysis of 72 patients with stage IV lung cancer with EGFR-sensitive mutation. Patients in the A group were treated with the first-generation EGFR-TKI (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) combined with radiotherapy for primary tumors (34 cases). The B group was treated with the first-generation EGFR-TKI alone until the disease progressed (38 cases). PFS, OS, pulmonary infection and hematological toxicity during treatment were commented in both groups. Results: The objective remission rate was 47.1% (16/34) in the A group and 21.1% (8/38) in the B group. There was a significant difference between the two groups. There was no significant difference in hematological toxicity between the A group and the B group. There were 10 patients (29.4%) with degree II pulmonary infection in the A group and 3 patients (7.9%) in the B group. The difference between the two groups was statistically significant, suggesting that the incidence of pneumonia in the A group was higher than that in the B group. The median PFS (Progression-Free Survival)) and OS (Overall Survival) of the A group were significantly longer than those of the B group (16.5 months vs 9 months) and the median OS (36 months vs 19 months). The PFS and OS in the A group were significantly longer than those in the B group. Conclusion: EGFR-TKI combined with primary radiotherapy can significantly prolong the drug resistance time of EGFR mutant metastatic NSCLC.

Cross-talk between Smad4 and P38 Proteins in Non-small Cell Lung Cancer

Objective： Impaired signal transduction is associated with tumorigenesis and progression of various kinds of human cancers. Transforming growth factor （TGF）-beta/Smad and ras-mitogen activated protein kinase （MAPK） are two major signal transduction pathways for adjusting cell proliferation and differentiation. Little is known about TGF-beta/Smad4 in non-small cell lung cancer （NSCLC）. Hereby, we investigated the expression of Smad4 in NSCLC, its correlation with MAPK proteins （including p38, ERK1 and JNK1 proteins） and their clinical significance in NSCLC. Methods： The expressions of Smad4, p38, ERK1 and JNK1 were detected at protein level with Western blotting and immunohistochemistry, at transcription level with RT-PCR. Statistical analysis was performed for the comparisons of expressions of Smad4, p38, ERK1 and JNK1, and their correlation with various clinicopathological parameters and the prognosis of NSCLC. Results： The levels of protein and mRNA expression of Smad4 in lung cancer tissues were significantly lower than in normal tissues （P〈0.05）. All these four proteins were associated with TNM staging. There was a strongly negative correlation between p38 and Smad4. Expressions of Smad4, p38 and JNK1, as well as tumor differentiation and staging were significantly correlated with the prognosis of NSCLC by univariate analysis. By multivariate analysis, only Smad4, p38, tumor differentiation and staging were correlated with the prognosis. Taken together, the negative expression of p38 and positive expression of Smad4 were associated with a better prognosis of NSCLC. Conclusion： Smad4 could be of vital importance for the initiation and development of NSCLC. The expression of Smad4 might be inhibited by p38, supporting a cross-talk between main proteins of TGF-beta/Smad and ras-MAPK signal transduction pathways. Smad4 and p38 could be possible prognostic factors for NSCLC.

ADJUVANT CHEMOTHERAPY FOLLOWING RADICAL SURGERYFOR NON-SMALL CELL LUNG CANCER:A RANDOMIZED STUDY

Objective: To evaluate the efficacy of adjuvant chemotherapy after radical surgery for non-small cell lung cancer (NSCLC). Methods: Seventy patients with NSCLC (stage I–III) undergone radical surgery were randomized into two groups: 35 patients received adjuvant chemotherapy with cyclophosphamide (CTX) 300 mg/m2, vincristine (VCR) 1.4% mg/m2, adriamycin (ADM) 50 mg/m2, lomustine (CCNU) 50 mg/m2 dl, cisplatin (DDP) 20 mg/m2, d1–5, for 4 cycles, and followed by oral Ftorafur (FT-207) 600–900 mg/d for 1 year (adjuvant chemotherapy group). The other 35 patients received surgical treatment only (surgery group). Results: The overall 5-year survival rate was 48.6% in the adjuvant chemotherapy group, and 31.4% in the surgery group, respectively. The difference between the two groups was not statistically significant (P>0.05). The 5-year survival rate of patients in stage III was 44.0% and 20.8% received surgery with and without adjuvant chemotherapy, respectively. The difference between the two groups was statistically significant (P<0.025). The 5-year survival rate of patients in stage I–II in the two groups was 60.0% and 54.5%, respectively (P>0.75). Conclusion: Postoperative adjuvant chemotherapy in NSCLC can improve survival, for those patients in stage III, it suggests significantly 5-year survival rate in the adjuvant chemotherapy group was higher than that in the surgery alone group.

Differential alterations of positive and negative regulators of beta catenin enhance endogenous expression and activity of beta catenin in A549 non small cell lung cancer(NSCLC)cells

Beta catenin has been well documented in previous studies to be involved in non small cell lung cancer(NSCLC).Beta catenin abundance and transcriptional activity are significantly regulated by several factors.Though it is well known that Akt and Gsk3 beta are respective positive and negative regulators of beta catenin,however,no single study has so far documented how the expression and activity of both positive as well as negative regulators play favorable role on beta catenin expression and activity in NSCLC.In this study,we compared expression and activity of beta catenin and its regulators in normal lung cell WI38 and NSCLC cell A549 by western blot,qRT-PCR and luciferase assay.We observed that beta catenin positive regulators(Akt and Hsp90)and negative regulators(Gsk3 beta and microRNA-214)have differential expression and/or activity in NSCLC cell A549.However the differentially altered statuses of both the positive and negative regulators rendered cumulative positive effect on beta catenin expression and activity in A549.Our study thus suggests that chemotherapeutic modulations of regulating factors are crucial when abrogation and/or inhibition of key oncogenic proteins are necessary for cancer chemotherapy.

ADVANCE NON SMALL CELL LUNG CANCER ACCEPTING CHEMOTHERAPY COMBINED WITH SHENMAI INJECTION

The aim of the study was to observe the changes of vascular endothelial growth factor(VEGF)and the efficacy of patients with advanced non-small-cell lung cancer(NSCLC)after the treatment of chemotherapy with Shenmai Injection.This study is a randomized controlled,prospective,single blind trial.63 eligible patients with NSCLC were

ANALYSIS OF TYPE I AND TYPE Ⅱ CYTOKINES PROFILE OF LYMPHOCYTE IN PLEURAL EFFUSION OF NON SMALL CELL LUNG CANCER PATIENTS

Objective To analyze mRNA expressions of 7 cytokines which influence the immune response in lymphocytes in pleural effusion of non small cell lung cancer patients to evaluate the effect of local tumor microenvironment on anti tumor immune response and to explore the mechanism of tumor escape.Methods Detecting the mRNA expression of IL 2,INF γ,IL 12,IL 18,IL 10,IL 4 and TGF β 1 in lymphocytes in pleural effusion of non small cell lung cancer patients and tuberculotic pleurisy patients on the single cell level by using in situ hybridization.Results In the pleural effusion of non small cell lung cancer, the mRNA expressions of IL 10,TGF β1 and IL 4 were significantly higher than those of IL 2,IL 12,IL 18 and INF γ,as well as these of control group.The cytokine expression levels of tuberculotic pleurisy patients were very low, and there were no significant differences between different cytokines.Conclusion Type 2 cytokines are expressed predominantly in the pleural effusion of non small cell lung cancer.The increased co expression of IL 10 and TGF β1 indicates that they might act jointly and play a critical role in the immunosuppression of non small cell lung cancer.

Prognostic Significance of Standardized Uptake Value of PET Scan in Non-Small Cell Lung Cancer

Background: To determine if the maximum standardized uptake value (SUVmax) of the primary tumor as determined by preoperative (18)F-fluoro-2-deoxyglucose ((18)F-FDG) positron emission tomography (PET) is an independent predictor of overall survival, mediastinal lymph node metastasis, and stage in patients with non-small cell lung cancer (NSCLC). Methods: A retrospective review of 1033 patients with stage I-IV histologically proven NSCLC who had an (18)F-FDG PET done between 2005 and 2011 for staging before receiving therapy was performed. SUVmax of primary NSCLC was measured and correlated with tumor characteristics, lymph node involvement, cancer stage and overall survival. The patients were divided into three groups according to their SUVmax value: group I SUVmax < 5;group II SUVmax 5 - 10;and group III SUVmax > 10. The primary outcome was survival and recurrence rate, compared using Log Rank Test. Results: The median duration of follow up was 675 days (22.5 months). The overall survival at two years for group I was 88%, group II 60% and group III 53%, significantly different among the three groups (p-value < 0.0001). Earlier stage lung cancer was found in patients with lower SUVmax values: in group I, 73% of patients had stage I cancer and only 4% had stage IV. The rate of ipsilateral mediastinal lymph node involvement (N2) in group I was 12.9% compared to 44.4% in group III (p-value < 0.0001). The overall survival was significantly different between group I and group II (Hazard Ratio (HR) 3.6;95% C.I 2.2 - 5.7 and a p-value < 0.0001) and between group II and group III (HR 1, 4;1.1 - 1.8 and a p-value = 0.013). Conclusion: There was a statistically significant difference in the overall survival, mediastinal lymph node metastases, and higher cancer stage with greater values of SUVmax on PET scan in patients with NSCLC.

Therapeutic management options for stage Ⅲ non-small cell lung cancer

Lung cancer is the leading cause of cancer death worldwide.Majority of newly diagnosed lung cancers are non-small cell lung cancer(NSCLC), of which up to half are considered locally advanced at the time of diagnosis.Patients with locally advanced stage Ⅲ NSCLC consists of a heterogeneous population, making management for these patients complex.Surgery has long been the preferred local treatment for patients with resectable disease.For select patients, multimodality therapy involving systemic and radiation therapies in addition to surgery improves treatment outcomes compared to surgery alone.For patients with unresectable disease, concurrent chemoradiation is the preferred treatment.More recently, research into different chemotherapy agents, targeted therapies, radiation fractionation schedules, intensity-modulated radiotherapy, and proton therapy have shown promise to improve treatment outcomes and quality of life.The array of treatment approaches for locally advanced NSCLC is large and constantly evolving.An updated review of past and current literature for the roles of surgery, chemotherapeutic agents, radiation therapy, and targeted therapy for stage Ⅲ NSCLC patients are presented.

High plasma fibrinogen concentration and platelet count unfavorably impact survival in non–small cell lung cancer patients with brain metastases

High expression of fibrinogen and platelets are often observed in non–small cell lung cancer(NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as well as to determine the overall survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age ≥ 65 years(P = 0.011), smoking status(P = 0.009), intracranial symptoms(P = 0.022), clinical T category(P = 0.010), clinical N category(P = 0.003), increased partial thromboplastin time(P < 0.001), and platelet count(P < 0.001). Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration(median, 17.3 months versus 11.1 months; P ≤ 0.001). A similar result was observed for platelet counts(median, 16.3 months versus 11.4 months; P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases(R2 = 1.698, P < 0.001 and R2 = 1.699, P < 0.001, respectively). Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

Clinical characteristics and response to tyrosine kinase inhibitors of patients with non-small cell lung cancer harboring uncommon epidermal growth factor receptor mutations

Objective： To investigate the clinical features of patients with non-small cell lung cancer（NSCLC） harboring uncommon epidermal growth factor receptor（EGFR） mutations, and the treatment outcomes of EGFR tyrosine kinase inhibitors（TKIs） in these patients.Methods： We retrospectively analyzed the data of 128 NSCLC patients pathologically diagnosed with uncommon EGFR mutation in the Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences ＆ Peking Union Medical College and Beijing Hospital from January 2010 to December 2015, including 40 advanced patients who received EGFR-TKI.Results： Among the total 128 patients, 11 patients were non-adenocarcinoma, including squamous carcinoma（3.9%）, adenosquamous carcinoma（2.3%）, large cell carcinoma（0.8%）, and composite neuroendocrine carcinoma（1.6%）. Single mutations accounted for 75.0%（96/128）, including G719X（29.7%）, S768I（18.0%）, 20 exon insertion（13.3%）, L861Q（12.5%）, De novo T790M（0.8%）, and T725（0.8%）. Thirty-two patients harbored complex mutations. Forty advanced patients received EGFR-TKI, the objective response rate（ORR） was 20.0%,the disease control rate（DCR） was 85.0%, and the progression-free survival（PFS） was 6.4 [95% confidence interval（95% CI）, 4.8–7.9] months. The exploratory analysis of tumor response and PFS in 33 patients with G719X/S768I/L861 Q subtypes showed that ORR was 21.2%（7/33）, the DCR was 93.9%（31/33）, and PFS was 7.6（95% CI, 5.8–9.4） months. Patients with exon 20 insertion mutation and De novo T790 M experienced rapid disease progression with PFS no more than 2.7 months.Conclusions： Uncommon EGFR-mutant NSCLCs are heterogeneous, EGFR-TKIs can have different efficacy in this specific subtype, and thus further individual assessment is required for each case.

Nedaplatin/Gemcitabine Versus Carboplatin/Gemcitabine in Treatment of Advanced Non-small Cell Lung Cancer: A Randomized Clinical Trial

Objective： To evaluate the efficacy and safety of nedaplatin/gemcitabine （NG） and carboplatin/gemcitabine （CG） in the management of untreated advanced non-small cell lung cancer （NSCLC）. Methods： Sixty-two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm （n=30） and the CG arm （n=32）. Only patients （24 and 25 in the NG and CG arms, respectively） who completed 〉2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate （ORR）. The secondary outcome measures included progression-free survival （PFS）, overall survival （OS） and adverse events. Results： There were no statistically significant differences in the efficacy measures （ORR, P=0.305; median PFS, P=0.298, median OS, P=0.961） or in the major adverse events （grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.222） between the two treatment arms. However, there was a trend towards higher ORR （37.5% vs. 24.0%）, longer PFS （6.0 vs. 5.0 months）, and less adverse events in the NG arm. Conclusion： NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.