EGFR Mutation Status and PD-L1 Expression in Patients ≤40 Years Old with NSCLC / 肿瘤防治研究

Objective To retrospectively analyze the clinical data of 47 young NSCLC patients mutation style of EGFR and PD-L1 expression in tumor cells, to understand their clinicopathological and molecular characteristics. Methods We enrolled 47 young (≤40 years old) patients confirmed as NSCLC who underwent surgical resection, and 94 old patients (≥60 years old) were matched as 1:2 by R language. EGFR mutation status was detected by ARMS-PCR, and the expression of PD-L1 was detected by immunohistochemistry. Results The median age of 47 young patients with NSCLC was 37 years old. The disease was more common in women and the majority type was adenocarcinoma. In youth group, the 19del and 20ins were more frequent, but the exon 21 L858R point mutation proportion was higher in elder group. The expression of PD-L1 was significantly increased in the solid predominant histological subtype. The PD-L1 expression in 19del patients was higher than that in the patients with L858R mutation in youth group. Conclusion The majority of young NSCLC patients are female, nonsmokers and suffered from adenocarcinoma cancer. The proportion of EGFR alteration in 19del and 20ins in youth group is higher than that in elder group. The positive rate of PD-L1 expression in solid predominant histological subtype is higher than that with other subtypes. The expression of PD-L1 in young patients with EGFR 19del is higher than that with L858R.

Expression of CD44 in Tumor Tissue and Serum of Small Cell Lung Cancer and Its Clinical Prognostic Significance / 中国肺癌杂志

BACKGROUND@#Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid growth, early metastasis and acquired therapeutic resistance, and the prognosis is extremely poor. Studies have proved that the stem cell marker CD44 is correlated with tumor recurrence and treatment resistance, however, there are limited reports yet concerning on the CD44 expression and its clinical prognostic significance in SCLC patients. The purpose of this study is to investigate the expression of CD44 in tumor tissues as well as serum of SCLC patients and explore its correlation with the clinical characteristics, therapeutic effect and prognosis.@*METHODS@#The tumor tissues and serum samples of 47 newly diagnosed SCLC patients were collected. Immunohistochemistry and enzyme-linked immunosorbent assay were applied to detect CD44. The relationship between CD44 level and the clinical characteristics as well as prognosis of the patients was analyzed.@*RESULTS@#The stem cell marker CD44 was detectable both in serum sample and tumor tissue of SCLC patients. The positive rate of CD44 in tumor tissue was significantly higher in patients with performance status (PS) 2 than that of patients with PS 0-1 (85.71% vs 30%, P=0.017). Patients were divided in to different groups according to the treatment efficacy. The CD44 immunohistochemical score and serum level in the disease progression group were significantly higher than those in the disease control group, and the differences were statistically significant (P=0.006, P=0.034), Univariate analysis depicted that the progression-free survival (PFS) of CD44 positive patients was significantly shorter than that of CD44 negative patients (5.23 mon vs 9.03 mon, P=0.036).@*CONCLUSIONS@#The positive expression of CD44 in tumor tissues of pre-treatment SCLC patients is correlated with poor PFS. The clinical significance of CD44 is worthy to be further studied.

A Single Center Analysis of Advanced Non-small Cell Lung Cancer Patients Treated with Immunotherapy in Real-world Practice / 中国肺癌杂志

BACKGROUND@#In recent years, a number of clinical trials have shown that immunocheckpoint inhibitors (ICI) have brought survival benefits to patients with advanced non-small cell lung cancer (NSCLC), however, such clinical trials comprise cohorts selected based on strict and complex entry and exclusion criteria, and the results cannot fully reflect the real world situation. The purpose of this study was to investigate the clinical efficacy and safety of immunotherapy in the real world, as well as possible prognostic factors.@*METHODS@#Patients with advanced NSCLC receiving immunotherapy in Beijing Chest Hospital from January 2017 to July 2019 were retrospectively collected, and the following information were collected: curative effect, progression-free surival (PFS) and adverse reactions. The occurrence of adverse reactions and clinical curative effect and prognosis factors that may be relevant were explored.@*RESULTS@#34 patients were enrolled in this study, median PFS was 5.66 months (95%CI: 4.48-6.84), grade 1-2 and 3-4 incidence of adverse events was 61.71% (22/34) and 14.71% (5/34), there were 3 patients (8.82%) experienced fatal immune related adverse events (irAE), 2 cases were immune associated pneumonia, 1 case was immune related myocarditis. Univariate analysis showed that tumor-node-metastasis (TNM) stage and metastatic site were correlated with median PFS (P<0.05), and multivariate analysis showed that patients with extrapulmonary metastasis (OR=6.42, P=0.029) and pleural metastasis (OR=14.14, P=0.006) had shorter median PFS.@*CONCLUSIONS@#In the real world, immunotherapy has good efficacy in patients with advanced NSCLC, but the incidence of severe irAE is also higher. Distant metastasis and pleural metastasis are poor prognostic factors for advanced NSCLC patients receiving immunotherapy.

Optimization of culture conditions for Clostridium cellulolyticum / 生物工程学报

Clostridium cellulolyticum, as one of obligate anaerobic bacteria capable of secreting cellulosome, has not been efficiently cultured due to its strict requirement of growing conditions. In this study, culture conditions of C. cellulolyticum were optimized using response surface methodology. Plackett-Burman design was first used to screen the dominant impact factors for the growth of C. cellulolyticum, which were determined as yeast extract concentration, cellobiose concentration and culture temperature. The steepest ascent path design was then applied to gain the suitable range close to the optimal culture conditions for obtaining high cell density. The central composite design and the response surface analysis were finally used to determine the optimal levels of the influential factors, which were 3 g/L for yeast extract concentration, 7 g/L cellobiose concentration and 34 degrees C for culture temperature. The optimized medium was used for flask culture, and OD600 of C. cellulolyticum was increased from 0.303 to 0.586. With a pH-controlled fermentor at batch mode, OD600 reached 3.432, which was 2.8 times higher than elsewhere reported. These results support further study on the high-density culture of C. cellulolyticum and its application.

Analysis of prognosis and therapy strategy in patients with lung cancer aged 80 years and over / 中华老年医学杂志

Objective To analyze the prognostic factors and trerapy strategy of lung cancer in the patients aged 80 years and over.Methods Totally 107 patients aged ≥ 80 years with lung cancer were retrospectively reviewed.Patients' clinical characteristics and treatment were analyzed.Results Median survival time of the patients was 6.9 months.92.9％ (13/14) of small cell lung cancer patients and 34.4％ (31/90) of non small cell lung cancer patients were treated.Life cycle of patients who accepted effective treatments and supportive treatments were 16.5 months and 8.7 months,respectively (P=0.008).In the early stage of tumors,survival time of patients undergoing surgery was 36.7 months,15.5 months in patients without surgery (P=0.023),while in the late stage,survival time of patients receiving combined chemotherapy was 13.4 months,4.6 months in patients receiving single agent chemotherapy(P=0.002).In small cell lung cancer,survival time of patients who received radiotherapy was 12.8 months,6.4 months in patients who did not receive radiotherapy (P=0.049).Performance status (PS),clinical stage,early surgery,late chemotherapy and radiotherapy(x2=38.236,18.831,5.187,9.827,4.186,P＜0.05),but not sex and pathology type affected the prognosis.PS score (P=0.003)and clinical stage(P=0.046) were the independent influencing factors.Conclusions Performance status and clinical stage are the independent influencing factors of lung cancer in the patients aged over 80 years.Patients may improve survival if receiving surgery,chemotherapy and/or radiotherapy when they have good PS,otherwise patients may choose best supportive care.

Association between polymorphisms of ERCC1 and response in patients with advanced non-small cell lung cancer receiving cisplatin-based chemotherapy / 中国肺癌杂志

<p><b>BACKGROUND AND OBJECTIVE</b>Results of studies on genetic polymorphisms of ERCC1 gene in DNA repair pathway which may affect response to platinum-based chemotherapy and survival in patients with non-small cell lung cancer are conflicting. The aim of this study is to prospectively assess the association between single nucleotide polymorphisms of C8092A and codon118 in ERCC1 and drug response in 90 patients with advanced non-small cell lung cancer treated with cisplatin-based chemotherapy.</p><p><b>METHODS</b>All patients were treated with cisplatin-based chemotherapy. Genotypes of ERCC1 C8092A and codon118 were examined by sequencing, and the association between genotypes and response was evaluated.</p><p><b>RESULTS</b>Genotype frequencies of ERCC1 C8092A were CC 40.0% (36/90), CA 48.9% (44/90) and AA 11.1% (10/90), frequencies of codon118 were CC 58.9% (53/90), CT 34.4% (31/90) and TT 6.7% (6/90). There was no significant difference in response rate of patients carrying with CC, compared with CA plus AA in C8092A (33.3% vs 29.6%, P = 0.71). Response rate of patients carrying with CC in ERCC1 118 was 32.1%, 24.3% with CT plus CC (P = 0.43). There was no difference in progression free survival between patients carrying with CC and CT plus TT in C8092A (5.2 months vs 5.4 months, P = 0.62). There was no difference in progression free survival between patients carrying with CC and CA plus AA (5.5 months vs 5.3 months, P = 0.59).</p><p><b>CONCLUSION</b>The results suggest that there is no association between polymorphisms in ERCC1 C8092A and codon118 and response in patients with advanced non-small cell lung cancer receiving cisplatin-based chemotherapy.</p>

Clinical value of serum TPS, CEA, Pro-GRP and CYFRA21-1 in patients with lung cancer / 中国肺癌杂志

<p><b>BACKGROUND AND OBJECTIVE</b>Serum tumor markers play important roles in diagnosis, response and prognosis monitoring for lung cancer. The clinical significance of serum level of tissue polypeptide specific antigen (TPS) was investigated in diagnosis, response monitoring and prognosis in patients with lung cancer, compared with carcinoembryonic antigen (CEA), precursor of gastrin-releasing peptide (Pro-GRP) and cytokeratin-19-fragments (CYFRA21-1).</p><p><b>METHODS</b>Blood samples of eighty-two patients with lung cancer before treatment and some after chemotherapy were measured by ELISA for four tumor markers.</p><p><b>RESULTS</b>Compared with lung benign diseases group and health control group, the positive rates and levels of TPS, CEA and Pro-GRP in patients with lung cancer were higher, with statistically significant difference. TPS in extensive-small cell lung cancer was significant higher than that in limited-small cell lung cancer. The positive rates and levels of TPS, CEA and Pro-GRP in patients after treatment had significant decreases compared with before treatment. TPS was an independent prognostic factor of non-small cell lung cancer.</p><p><b>CONCLUSION</b>TPS is valuable to diagnosis, response monitoring for patients with lung cancer, moreover, it maybe a useful factor of prognosis of non-small cell lung cancer.</p>

A randomized study comparing topotecan plus cisplatin versus etoposide plus carboplatin for previously untreated small cell lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>Topotecan is one of active agents for relapsed small cell lung can-cer (SCLC), some studies have shown that it is effective against SCLC as the first-line drug. This study is to assess the efficacy, toxicity and survival rate of topotecan plus cisplatin (TP) versus etoposide plus carboplatin (CE) in patients with previously untreated SCLC.</p><p><b>METHODS</b>Sixty-four patients with previously untreated SCLC were randomly assigned to receive either TP or CE. Topotecan 0.75 mg/(m²×d) via a 30-min intravenous infusion on days 1 to 5 and cisplatin 25 mg/(m²×d) on days 1 to 3 with hydration were given to patients in TP group. Carboplatin 300 mg/m² on day 1 and etoposide 100 mg/d on days 1 to 5 were given to patients in CE group. Treatment was repeated every 21 days. Responses and toxicities were evaluated in patients who received two cycles of chemotherapy. Patients with limited disease SCLC received thoracic irradiation or operation after the completion of chemotherapy.</p><p><b>RESULTS</b>Overall response rate was 75.0% in TP group and 68.8% in CE group. The median survival time was 10.5 months in TP group and 9.6 months in CE group. 1-, 2- and 3-year survival rate were 40.6%, 18.8% and 9.4% in TP group and 34.4%, 15.6% and 9.4% in CE group respectively. There were no significant differences in response rate, median survival time and survival rate between two groups (P > 0.05). Myelosuppression, nausea and vomiting, and alopecia were the most common toxicities, there was no significant difference in grade III and IV toxicities between two groups (P > 0.05).</p><p><b>CONCLUSIONS</b>TP has similar response rate and survivals with CE, and its toxicities are acceptable. TP regimen is an effective first-line treatment for SCLC.</p>

Clinical study of combined chemotherapy of domestic paclitaxel and vinorelbine plus platinum for advanced non-small cell lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>To evaluate the efficacy and toxicity of combined chemotherapy of domestic paclitaxel and vinorelbine plus cisplatin and carboplatin in the treatment of advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>A total of 181 initially treated patients with advanced NSCLC were enrolled in this study and treated by NP (vinorelbine plus cisplatin), TC (domestic paclitaxel plus carboplatin) and TP (domestic paclitaxel plus cisplatin). The efficacy and side effects were analysed after at least two cycles of chemotherapy.</p><p><b>RESULTS</b>The overall response rates (CR+PR) were 42.4% in the NP arm, 40.3% in the TC arm and 43.3% in the TP arm respectively. No significant statistical difference was found among the three groups ( Chi-square= 0.108 6 , P > 0.05). The median survival times were 8.4 months, 9.4 months and 8.9 months respectively in the NP, TC and TP groups ( P > 0.05). The 1-, 2-, 3-year survival rates were 39.0%, 16.9%, 5.1% in the NP group and 41.9%, 21.0%, 6.5% in the TC group and 40.0%, 18.3%, 5.0% in the TP group respectively. No significant statistical difference was found among the three groups ( Chi-square=0.140 4, P > 0.05). The major side effects were myelosuppression, alopecia and nausea/vomiting in the three groups. There were no chemotherapy-related death among the three groups.</p><p><b>CONCLUSIONS</b>The combined regimens of NP, TC and TP are effective and well-tolerated regimens for advanced NSCLC.</p>

Diagnositic values of combined determination of carbohydrate antigen and tissue polypeptide antigen and neuron-specific enolase and carcinoembryonic antigen in the malignant pleural effusion / 中国肺癌杂志

<p><b>BACKGROUND</b>To evaluate the values of a new tumor marker carbohydrate antigen (CA242) and combined determination of CA242, tissue polypeptide antigen (TPA), neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) in the diagnosis of malignant pleural effusion associated with lung cancer.</p><p><b>METHODS</b>The concentration of CA242, TPA, NSE and CEA in the serum and the pleural effusion was measured in 57 patients with malignant pleural effusion associated with primary lung cancer and 30 patients with tuberculous pleural effusion by enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>The levels of the four tumor markers in the serum and pleural effusion from patients with lung cancer were significantly higher than those with tuberculous pleural effusion (P < 0.01). The sensitivity of CA242 in the serum and the pleural effusion for lung cancer was 53.6% (31/57) and 61.4% (35/57) respectively; the sensitivity of CA242 for lung adenocarcinoma was 65.7% (23/36) and 66.7% (24/36) respectively. The specificity was 90.0%. Combined determination of the four tumor markers in serum and pleural effusion: If two or more of them were positive for evidence for diagnosis of lung cancer, the specificity for the serum and the pleural effusion was 96.7% (29/30) and 100.0% (30/30) respectively, with the sensitivity of 75.4% (43/57) and 77.2% (44/57) respectively.</p><p><b>CONCLUSIONS</b>The determination of the new tumor marker CA242 in serum and pleural effusion might be useful for the diagnosis of malignant pleural effusion associated with lung cancer, especially for adenocarcinoma. The combined determination of the four tumor markers can increase the specificity and the sensitivity in the diagnosis of malignant pleural effusion.</p>