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RESUMEN Fundamento: en estadios avanzados del cáncer de pulmón de células no pequeñas el tratamiento se basa fundamentalmente en la poliquimioterapia. Estudios previos relacionan el desarrollo de resistencia al cisplatino con el aumento de los niveles del glutatión celular, mientras que, la depleción de este tripéptido se ha asociado con una mayor sensibilidad a este fármaco. Objetivo: evaluar el efecto de la poliquimioterapia con cisplatino y vinblastina en los niveles intracelulares de glutatión y en el estado redox celular en pacientes con cáncer de pulmón de células no pequeñas en estadios avanzados. Métodos: se realizó un estudio de casos y controles en el que se incluyeron 38 pacientes con cáncer de pulmón de células no pequeñas en estadios IIIb-IV, que concluyeron el esquema de tratamiento con cisplatino y vinblastina y 25 individuos aparentemente sanos como grupo control en el período correspondiente al período de mayo del 2016 a mayo del 2018 en el Hospital Neumológico Benéfico Jurídico de la Habana. Las concentraciones intraeritrocitarias del glutatión reducido y oxidado fueron determinadas mediante un método de HPLC-UV. El estado redox celular se calculó mediante la ecuación de Nerst. Los resultados se expresaron como medias y desviación estándar. Se utilizó la prueba no paramétrica U-Mann Whitney para la comparación de las medias aritméticas de las variables de respuesta. Resultados: después del tratamiento se apreció una disminución de las concentraciones de glutatión reducido (920 µM vs. 1252 µM; p=0,036) así como, cambios en el estado redox celular (-338,4 mV vs. -353,2 mV; p=0,029) en contraste con los controles. Conclusiones: la quimioterapia combinada con cisplatino induce una disminución de los niveles glutatión reducido y cambios en el estado redox celular. Estos efectos pueden contribuir a una mayor supervivencia en los pacientes que responden al tratamiento.
ABSTRACT Background: in advanced stages of non-small cell lung cancer, treatment is fundamentally based on polychemotherapy. Previous studies relate the development of resistance to cisplatin with increased levels of cellular glutathione, while depletion of this tripeptide has been associated with greater sensitivity to this drug. Objective: to evaluate the effect of polychemotherapy with cisplatin and vinblastine on intracellular glutathione levels and cellular redox status in patients with non-small cell lung cancer in advanced stages. Methods: a case-control study was carried out that included 38 patients with non-small cell lung cancer in stages IIIb-IV, who completed the treatment scheme with cisplatin and vinblastine, and 25 apparently healthy individuals as a control group from May 2016 to May 2018 at the Benéfico Jurídico Pneumological Hospital in Havana. The intraerythrocyte concentrations of reduced and oxidized glutathione were determined by an HPLC-UV method. The cellular redox state was calculated using the Nerst equation. The results were expressed as means and standard deviation. The non-parametric U-Mann Whitney test was used to compare the arithmetic means of the response variables. Results: after treatment, a decrease in reduced glutathione concentrations (920 µM vs. 1252 µM; p=0.036) was observed, as well as changes in the cellular redox state (-338.4 mV vs.-53.2 mV; p=0.029) in contrast to controls. Conclusions: chemotherapy combined with cisplatin induces a decrease in reduced glutathione levels and changes in the cellular redox state. These effects may contribute to increased survival in patients who respond to treatment.
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RESUMEN Introducción: la concentración plasmática del factor de crecimiento epidérmico pudiera encontrarse alterada en pacientes con cáncer de pulmón de células no pequeñas y trombocitopenia/trombocitosis por quimioterapia. Objetivo: determinar la asociación existente entre la concentración plasmática plaquetaria y la concentración plasmática de factor de crecimiento epidérmico en pacientes con cáncer de pulmón de células no pequeñas tratados con quimioterapia, entre marzo de 2019 y febrero de 2020 en el Hospital Provincial Saturnino Lora. Métodos: se realizó un estudio observacional descriptivo transversal en el Hospital Provincial Saturnino Lora, provincia Santiago de Cuba, Cuba, entre marzo de 2019 y febrero de 2020. El universo estuvo constituido por 54 pacientes con diagnóstico de cáncer pulmonar de células no pequeñas tratados con quimioterapia. Por muestreo probabilístico aleatorio simple se seleccionó una muestra de 12 pacientes. Se midieron las variables: concentración plasmática plaquetaria (pre y post-quimioterapia), concentración plasmática de factor de crecimiento epidérmico (pre y post-quimioterapia), y modificación de la concentración plasmática de factor de crecimiento epidérmico (castración, no castración). Para el procesamiento de los datos se empleó el test estadístico T student y la correlación lineal de Pearson, así como la media y desviación estándar como medidas de resumen y dispersión, respectivamente. Resultados: entre las concentraciones plasmáticas plaquetaria y del factor de crecimiento epidérmico se halló una relación lineal de -0,37 previo a la quimioterapia y de -0,51, posterior a esta; no se encontraron diferencias estadísticamente significativas. Conclusiones: se concluye que la modificación de la concentración plasmática del factor de crecimiento epidérmico no guarda relación aparente con la modificación plasmática plaquetaria, con posible relación espuria, dada por la quimioterapia.
ABSTRACT Introduction: the plasma concentration of epidermal growth factor may be altered in patients with non-small cell lung cancer and thrombocytopenia/thrombocytosis due to chemotherapy. Objective: to determine the association between platelet plasma concentration and epidermal growth factor plasma concentration in patients with non-small cell lung cancer treated with chemotherapy between March 2019 and February 2020 at Saturnino Lora Provincial Hospital. Methods: a cross-sectional, descriptive and observational study was conducted at Saturnino Lora Provincial Hospital, Santiago de Cuba province, Cuba, between March 2019 and February 2020. The target group comprised 54 patients diagnosed with non-small cell lung cancer treated with chemotherapy. A sample of 12 patients was chosen by simple probability-random sampling: platelet plasma concentration (pre- and post-chemotherapy), epidermal growth factor plasma concentration (pre- and post-chemotherapy), and modification of epidermal growth factor plasma concentration (castration, non-castration) were measured. For data processing, the statistical T-student test and Pearson's linear correlation were applied, as well as the mean and standard deviation as summary and dispersion measures, respectively. Results: a linear relationship of -0.37 before chemotherapy and -0.51 after the chemotherapy was found between platelet and epidermal growth factor plasma concentrations; no statistically significant differences were found. Conclusions: it is concluded that the modification of the plasma concentration of epidermal growth factor has no apparent relationship with the platelet plasma modification, with possible spurious relationship, given by chemotherapy.
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ABSTRACT Objective: To evaluate the efficacy of stereotactic body radiotherapy (SBRT) versus surgery for early-stage non-small cell lung cancer (NSCLC) by means of a meta-analysis of comparative studies. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines, searches were performed on PubMed, MEDLINE, Embase, and Cochrane Library for eligible studies. The meta-analysis compared the hazard ratios (HR) for overall survival (OS), cancer-specific survival (CSS), and local control (LC). Subgroup and meta-regression analyses evaluated the association of extent of surgical resection, study publication year, tumor staging, propensity score matching, proportion of chemotherapy use, and proportion of pathological lymph node involvement with CSS and OS. Results: Thirty studies involving 29,511 patients were included (surgery group: 17,146 patients and SBRT group: 12,365 patients). There was a significant difference in favor of surgery vs. SBRT in the 3-year OS (HR = 1.35; 95% CI: 1.22-1.44; I2 = 66%) and 3-year CSS (HR = 1.23; 95% CI: 1.09-1.37; I2 = 17%), but not in the 3-year LC (HR = 0.97; 95% CI: 0.93-1.08; I2 = 19%). In the subgroup analysis for OS, no significant difference between surgery and SBRT groups was observed in the T1N0M0 subgroup (HR = 1.26; 95% CI: 0.95-1.68; I2 = 0%). In subgroup analysis for CSS, no significant difference was detected between the sublobar resection subgroup and the SBRT group (HR = 1.21; 95% CI: 0.96-1.53; I2 = 16%). Conclusions: Surgery generally resulted in better 3-year OS and CSS than did SBRT; however, publication bias and heterogeneity may have influenced these findings. In contrast, SBRT produced LC results similar to those of surgery regardless of the extent of surgical resection. These findings may have important clinical implications for patients with comorbidities, advanced age, poor pulmonary reserve, and other factors that may contraindicate surgery.
RESUMO Objetivo: Avaliar a eficácia da stereotactic body radiotherapy (SBRT, radioterapia estereotáxica corporal) vs. cirurgia para câncer de pulmão de células não pequenas em estágio inicial por meio de uma meta-análise de estudos comparativos. Métodos: Seguindo as diretrizes Preferred Reporting Items for Systematic Reviews and Meta-Analyses e Meta-analysis of Observational Studies in Epidemiology, foram realizadas buscas no PubMed, MEDLINE, Embase e Cochrane Library por estudos elegíveis. A meta-análise comparou as razões de risco (RR) para sobrevida global (SG), sobrevida específica para câncer (SEC) e controle local (CL). As análises de subgrupo e metarregressão avaliaram a associação de extensão da ressecção cirúrgica, ano de publicação do estudo, estadiamento do tumor, correspondência de escore de propensão, porcentagem de quimioterapia e porcentagem de acometimento linfonodal com SEC e SG. Resultados: Trinta estudos envolvendo 29.511 pacientes foram incluídos (grupo cirurgia: 17.146 pacientes e grupo SBRT: 12.365 pacientes). Houve diferença significativa a favor da cirurgia vs. SBRT na SG em 3 anos (RR = 1,35; IC95%: 1,22-1,44; I2 = 66%) e na SEC em 3 anos (RR = 1,23; IC95%: 1,09-1,37; I2 = 17%), mas não no CL em 3 anos (RR = 0,97; IC95%: 0,93-1,08; I2 = 19%). Na análise de subgrupo para SG, nenhuma diferença significativa entre os grupos cirurgia e SBRT foi observada no subgrupo T1N0M0 (RR = 1,26; IC95%: 0,95-1,68; I2 = 0%). Na análise de subgrupo para SEC, nenhuma diferença significativa foi detectada entre o subgrupo ressecção sublobar e o grupo SBRT (RR = 1,21; IC95%: 0,96-1,53; I2 = 16%). Conclusões: A cirurgia geralmente resultou em melhor SG e SEC em 3 anos do que a SBRT; no entanto, viés de publicação e heterogeneidade podem ter influenciado esses achados. Já a SBRT produziu resultados de CL semelhantes aos da cirurgia, independentemente da extensão da ressecção cirúrgica. Esses achados podem ter implicações clínicas importantes para pacientes com comorbidades, idade avançada, baixa reserva pulmonar e outros fatores que possam contraindicar a cirurgia.
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Objective: To investigate the relationship between the examined number of lymph nodes at the N1 station and the clinicopathological characteristics and prognosis of patients with pT1-3N0M0 non-small cell lung cancer (NSCLC). Methods: A total of 337 patients with pT1-3N0M0 NSCLC who underwent radical lung cancer surgery at the Provincial Hospital Affiliated to Anhui Medical University from January 2013 to March 2015 were selected. The receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value for predicting 5-year survival in pT1-3N0M0 NSCLC patients by the examined number of lymph nodes at the N1 station. The relationships between the examined number of lymph nodes at the N1 station and the clinicopathological characteristics and prognosis of patients with pT1-3N0M0 NSCLC were analyzed according to the optimal cut-off group. Results: A total of 1 321 lymph nodes at N1 station were examined in 337 patients, with a mean of 3.9 nodes per patient. The median survival time was 42.0 months, with 1-, 3- and 5-year survival rates of 82.2%, 57.1% and 24.9%, respectively. ROC curve analysis showed that the optimal cut-off value of 4.5 lymph nodes examined at the N1 station was used to predict 5-year survival in patients with pT1-3N0M0 NSCLC. After rounding off the number, the number of lymph nodes examined at the N1 station was 5 as the cut-off value, and the patients were divided into the group with <5 lymph nodes examined (212 cases) and the group with ≥5 lymph nodes examined (125 cases). The proportion of patients received adjuvant chemotherapy was 19.2% in the group with ≥5 lymph nodes examined, which was higher than 9.0% in the group with <5 lymph nodes examined (P=0.007), and the differences in other clinicopathological characteristics between the two groups were not statistically significant (P>0.05). The median survival time for patients in the group with <5 lymph nodes examined was 38.0 months, with 1-, 3- and 5-year survival rates of 80.1%, 52.5% and 15.6%, respectively. The median survival time for patients in the group with ≥5 lymph nodes examined was 48.0 months, and the 1-, 3- and 5-year survival rates were 85.6%, 64.0% and 36.0%, respectively. The survival rate of patients in the group with ≥5 lymph nodes examined was better than that in the group with <5 lymph nodes examined (P=0.002). Multifactorial Cox regression analysis showed that T stage (OR=1.408, 95% CI: 1.118-1.670) and the examined number of lymph nodes at N1 station (OR=0.670, 95% CI: 0.526-0.853) were independent influence factors for the prognosis of pT1-3N0M0 NSCLC patients. Conclusion: The examined number of lymph nodes at the N1 station is associated with the prognosis of patients with pT1-3N0M0 NSCLC, and the examination of at least 5 lymph nodes at N1 station at the time of postoperative pathological examination improves the 5-year survival rate of patients.
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Carcinoma, Non-Small-Cell Lung/surgery , Humans , Lung Neoplasms/surgery , Lymph Nodes/surgery , Lymphatic Metastasis/pathology , Neoplasm Staging , Prognosis , Retrospective StudiesABSTRACT
Brain metastasis is a common complication of non-small cell lung cancer (NSCLC) patients. About 25%-55% of patients with NSCLC will develop brain metastases, and the occurrence of brain metastasis predicts a poor prognosis. Traditionally, radiotherapy, chemotherapy, targeted therapy and surgery are the main treatment options for NSCLC patients with brain metastases. In recent years, with the emergence of immune checkpoint inhibitors (ICI), the survival of NSCLC patients with brain metastases has been significantly improved. This article reviews the research progress of ICI treatment for NSCLC patients with brain metastases in order to provide new treatment strategies.
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Objective:To investigate the predictive value of 18F-FDG PET-CT in the conversion from thoracoscopic lobectomy to thoracotomy for non-small cell lung cancer (NSCLC). Methods:The clinical data, CT and PET-CT images of 193 patients with primary NSCLC undergoing thoracoscopic surgery from January 2014 to June 2021 at China-Japan Friendship Hospital were retrospectively analyzed. All patients were divided into 45 cases who were converted to thoracotomy (the conversional group) and 148 cases who were not converted to thoracotomy (the non-conversional group). Univariate analysis was performed on clinicopathological characteristics and image parameters. Multivariate logistic regression was used to analyze the factors affecting the conversion to thoracotomy. Taking the final conversion to thoracotomy or not as the gold standard, the predictive effect of variables in the conversion to thoracotomy was analyzed through the receiver operating characteristic (ROC) curve. Delong test was used to compare the area under the curve (AUC) predicted by all variables.Results:In the conversional group, the proportion of peribronchial lymph node (PLN), peribronchial cuffs of soft (PCS), pleural calcification, pulmonary nodule calcification, PLN or PCS calcification or increased density on chest CT was higher than that in the non-conversional group (all P<0.05); and the maximum standardized uptake value (SUV max) of PET in the conversional group was higher compared with that in the non-conversional group ( P<0.001). Univariate logistic regression analysis suggested age ( OR = 4.663,95% CI 2.191- 9.923, P < 0.001) and PLN or PCS density of chest CT scan ( OR = 2.824, 95% CI 1.791-7.303, P < 0.001) were independent influencing factors of the conversion from thoracoscopic lobectomy to thoracotomy. ROC analysis showed that the effect of the conversion to thoracotomy predicted by the combination of 18F-FDG PET and chest CT [AUC = 0.891 (95% CI 0.831-0.951); the optimal cut-off value of SUV max and CT was 3.45, 70 Hu: the sensitivity was 84.4%, the specificity was 83.8%] was better than that by chest CT alone [AUC = 0.678 (95% CI 0.591-0.766); the optimal cut-off value of CT was 70 Hu: the sensitivity was 62.2%, the specificity was 62.8%; P < 0.001] and by age [AUC = 0.625 (95% CI 0.532-0.719); the optimal cut-off value was 65.5 years: the sensitivity was 75.6%, the specificity was 60.1%; P < 0.001]. Conclusions:PLN or PCS density on chest scan and age are valuable in predicting the conversion from thoracoscopic lobectomy to thoracotomy for NSCLC patients. The combination of PET and CT has an additional role in predicting the conversion to thoracotomy during thoracoscopic lobectomy.
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The incidence of brain metastases in patients with non-small cell lung cancer (NSCLC) has increased as a result of improved local control rate and survival rate. Prophylactic cranial irradiation (PCI) has been proven to reduce the incidence of brain metastases and improve survival rate in patients with NSCLC. However, the value of PCI for NSCLC is still controversial. This paper reviews the progress of the efficacy and adverse reactions after PCI treatment for patients with NSCLC.
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Due to the high incidence and fatality rate of lung cancer, more and more attention is paid to the treatment model of lung cancer. Non-small cell lung cancer (NSCLC) accounts for about 4/5 of the total number of lung cancer patients, and the combination of anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) is found in 3%-7% of all cases. The treatment is mainly targeted therapy. The known targeted drugs for ALK fusion-positive NSCLC have been studied for the fourth generation, providing patients with a variety of medication options; in particular, the research on the fourth-generation drugs TPX-0131 and NUV-655 has brought new hopes to the majority of third-generation targeted drug-resistant patients. At present, China is also working hard to develop new domestic inhibitors, which will provide new drug options for Chinese patients with ALK-positive advanced NSCLC. This article will review its targeted therapy and the latest research, hoping to provide a reference for targeted drug selection.
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Objective:To investigate the effects of serum miRNA-126 (miR-126) and miRNA-449a (miR-449a) expression levels on the efficacy and prognostic evaluation of pemetrexed combined with cisplatin in treatment of non-small cell lung cancer (NSCLC).Methods:The data of 100 NSCLC patients admitted to Wuhan Hankou Hospital from January 2016 to January 2017 were retrospectively analyzed. Before treatment, the relative expression levels of miR-126 and miR-449a in serum of both groups were detected by using real-time fluorescence quantitative polymerase chain reaction. A total of 100 healthy volunteers during the same period were treated as the control group. The efficacy was evaluated after 2 courses of treatment, and the correlation of miR-126 and miR-449a relative expression levels with clinicopathological characteristics, efficacy and prognosis of patients was analyzed.Results:The relative expression levels of serum miR-126 and miR-449a in NSCLC patients were lower than those in the control group (1.23±0.34 vs. 2.22±0.57, 0.95±0.21 vs. 2.13±0.43), and the differences were statistically significant ( F = 14.92, 24.66; all P < 0.01). There were significant differences in the relative expression levels of serum miR-126 and miR-449a in NSCLC patients with different therapeutic effects ( F = 80.65, 22.43, all P < 0.01). Spearman correlation analysis showed that the relative expression levels of serum miR-126 and miR-449a were correlated with the therapeutic effect ( ρ = 0.782, 0.618, all P < 0.01). The relative expression levels of serum miR-126 and miR-449a in NSCLC patients with different gender and age had no statistically significant difference (all P > 0.05). The relative expression levels of serum miR-126 and miR-449a in NSCLC patients with different TNM staging, pathological type, tumor diameter, degree of differentiation showed significant differences (all P < 0.05). Univariate Cox regression analysis showed TNM staging, tumor diameter, degree of differentiation, relative expression levels of serum miR-126 and miR-449a were correlated with the survival of NSCLC patients (all P < 0.05). Multivariate Cox regression analysis revealed TNM staging, tumor diameter, degree of differentiation and the relative expression levels of miR-126 and miR-449a were independent factors affecting the survival of NSCLC patients after surgery. The overall survival of patients with the high expressions of miR-126 and miR-449a was better than that of patients with the low expressions (all P < 0.05). Conclusions:The relative expression levels of serum miR-126 and miR-449a can be used as a potential serologic indicator to analyze the prognosis of NSCLC patients treated with pemetrexed combined with cisplatin.
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Objective:To investigate the epidemiological characteristics and prognostic affecting factors of non-small cell lung cancer (NSCLC) in Shanxi from 2015 to 2019.Methods:A total of 17 082 patients with NSCLC in Shanxi Provincial Cancer Hospital from January 2015 to December 2019 were selected as the research subjects. The medical records of all patients were retrieved, and the epidemiological characteristics of the patients' age, gender, occupation and smoking history were analyzed. All patients were given conventional treatment and followed up for 18 months. According to the follow-up results, they were divided into the death group (4 391 cases) and the survival group (12 691 cases). The single factor and multivariate logistic regression analysis was used to analyze the factors affecting the prognosis of patients.Results:Among 17 082 patients with NSCLC, there were 3 058 cases (17.91%) in 2015, 3 129 cases (18.32%) in 2016, 3 325 cases (19.46%) in 2017, 3 564 cases (20.86%) in 2018, and 4 006 cases (23.45%) in 2019, and the number of confirmed cases in different years showed an upward trend ( χ2 = 21.593, P < 0.05). The incidence rate of males was slightly higher than that of females [51.76% (8 841/17 082) vs. 48.24% (8 241/17 082)], 64.12% (10 953/17 082) occurred in the 61-80 years old population, and the occupational distribution was predominantly workers [34.08% (5 821/17 082)] and farmers [30.00% (5 124/17 082)]; there were 56.69% (9 683/17 082) patients with a history of smoking. Multivariate logistic regression analysis showed that lymph node metastasis, tumor staging Ⅲ-Ⅳ, sensitive mutations of epidermal growth factor receptor, and initial pleural effusion were independent factors influencing the poor prognosis of patients with NSCLC (all P < 0.05). Conclusions:The incidence of NSCLC in Shanxi from 2015 to 2019 is on the rise. The incidence of this disease is related to gender, age and occupation. There are many factors affecting the prognosis of patients, and targeted interventions can help improve the prognosis.
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Objective:To investigate the clinical characteristics of non-small cell lung cancer (NSCLC) patients with different epidermal growth factor receptor (EGFR) gene mutations and the comparison of therapeutic effects.Methods:The clinical data of 324 patients with NSCLC admitted to the 904th Hospital of the Joint Service Support Force of PLA from April 2018 to June 2020 were retrospectively analyzed. Gene sequencing method was used to detect EGFR gene and mutations of exons 19 and 21. NSCLC patients with EGFR gene mutations were divided into group A (mutation of exon 19 of EGFR gene) and group B (mutation of exon 21 of EGFR gene). Both groups were treated with gefitinib combined with TP (paclitaxel + cisplatin) regimen for 3 months. The clinical features, efficacy and adverse reactions of the two groups were compared.Results:Among 234 NSCLC patients, 107 cases (45.73%) had EGFR gene mutations. Among them, there were 49 cases in group A (including delE746-A750 mutation in 32 cases, delL747-P753insS 3 mutation in 8 cases, delL747-A750 1 mutation in 6 cases, delL747-T751 1 mutation in 3 cases), and there were 58 cases in group B (all L858R mutations), and no double mutations in exons 19 and 21 were found in both groups. There were no significant differences in gender, TNM staging, pathological type, smoking history, age, degree of differentiation, tumor location, tumor diameter, and lymph node metastasis in the two groups (all P > 0.05). The difference in the clinical control rates of group A and group B was not statistically significant [91.8% (45/49) vs. 89.7% (52/58), χ2=0.15, P = 0.699]. The incidence of grade Ⅲ-Ⅳ adverse reactions in the two groups during treatment had no statistically significant differences (all P > 0.05). Conclusions:EGFR mutation rate in NSCLC patients is relatively high, most of which are EGFR exons 19 and 21 mutations. Gefitinib combined with TP regimen in the treatment of EGFR exons 19 and 21 mutations in NSCLC patients has good curative effects and high safety.
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Objective:To investigate the clinical efficacy and safety of Xiaoaiping injection combined with chemotherapy in treatment of non-small cell lung cancer (NSCLC) patients.Methods:Based on LinkDoc database, a total of 1 144 patients first diagnosed as stage Ⅲ B-Ⅳ NSCLC in 4 medical centers including Henan Cancer Hospital from 2014 to 2018 were enrolled. The baseline data of included patients was used to make propensity score matching. The patients were divided into the experimental group (Xiaoaiping injection combined with chemotherapy) and the control group (chemotherapy alone), 572 cases in each group. The objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), time to progression (TTP) and adverse reactions of the two groups were observed and compared. Results:Based on the statistical results of patients with records of efficacy evaluation, the ORR of the experimental group and the control group was 26.54% (86/324) and 26.07% (79/303), respectively, and there was no statistically significant difference ( χ2 = 0.02, P = 0.894); the DCR of both groups was 61.42% (199/324) and 62.38% (189/303), respectively, and there was no statistically significant difference ( χ2 = 0.06, P = 0.805). The median OS time of the experimental group and the control group was 21.2 months and 16.5 months, respectively, and there was a statistically significant difference ( χ2 = 7.53, P = 0.006). The median PFS time was 9.3 months and 8.9 months, respectively, and there was no statistically significant difference ( χ2 = 2.25, P = 0.134). The median TTP was 1.8 months (1.2 months, 5.1 months) and 1.7 months (1.2 months, 5.8 months), respectively, and there was a statistically significant difference ( Z = 3.89, P = 0.049). The incidence of bone marrow suppression was 75.52% (432/572) and 64.51% (369/572),respectively in the experimental group and the control group, and there was a statistically significant difference ( χ2 = 16.53, P <0.001); the incidence of liver dysfunction was 39.86% (228/572) and 29.55% (169/572), respectively, and there was a statistically significant difference ( χ2 = 13.43, P < 0.001); the incidence of abnormal kidney function was 2.45% (14/572) and 3.15% (18/572), respectively, and there was no statistically significant difference ( χ2 = 0.51, P = 0.473). Conclusions:Xiaoaiping injection combined with chemotherapy can prolong the survival time of patients with advanced NSCLC. It is necessary to pay attention to the potential risks of bone marrow suppression and liver damage.
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Objective:To investigate the effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSC) and their conditioned medium on proliferation, migration and apoptosis of human non-small cell lung cancer (NSCLC) polyploid A549 cells.Methods:A549 cells in logarithmic phase were selected. After induction treatment with 1 μmol/L docetaxel for 24 h, DMEM/F12 medium with 10% fetal bovine serum was used to culture the cells for 3 d, finally the polyploid A549 cells model was successfully established. After finishing the separation and culture of hUC-MSC, hUC-MSC conditioned medium was prepared. Normally cultured polyploid A549 cells were treated as the control group, conditioned medium cultured polyploid A549 cells were treated as the conditioned medium group. hUC-MSC was co-cultured with polyploid A549 cells, and the ratio of the total number of cells was 2:1 and 5:1, respectively, which were recorded as MSC 1 group and MSC 2 group. Cells in each group were continually cultured for 48 h or 72 h. Proliferation and apoptosis of polyploid A549 cells in each group were detected by using flow cytometry, cell migration ability was detected by using Transwell assay, and the expressions of migration and apoptosis-related proteins were detected by using Western blotting.Results:Polyploid A549 cells model was successfully established and hUC-MSC was cultured separately. The result of cell proliferation detected by flow cytometry showed that at 48 h, the mean fluorescence intensity of the control group, conditioned medium group, MSC 1 group and MSC 2 group was 1 695±305, 2 020±85, 1 259±35 and 1 356±33, respectively, and the difference was statistically significant ( F = 14.00, P < 0.05); at 72 h, the mean fluorescence intensity of the control group, conditioned medium group, MSC 1 group and MSC 2 group was 1 052±77, 1 309±24, 864±201 and 1 103±237, respectively, and the difference was statistically significant ( F = 3.90, P > 0.05). The result of Transwell assay showed that at 48 h, the number of cell migration in the control group, conditioned medium group, MSC 1 group and MSC 2 group was 52±9, 57±12, 68±8 and 75±11, respectively, and the difference was statistically significant( F = 32.16, P < 0.05); the number of cell migration in each experimental group was all higher than that in the control group (all P < 0.05). The percentage of apoptotic cells in the control group, conditioned medium group, MSC 1 group and MSC 2 group was (15.53±4.27)%, (13.77±1.75)%, (3.60±0.50)% and (2.33±0.06)%, respectively, and the difference was statistically significant ( F = 182.36, P < 0.05); there was no statistically significant difference between the control group and conditioned medium group ( P > 0.05); there were statistically significant differences between MSC 1 group and the control group, MSC 2 group and the control group (both P < 0.05). Western blotting results showed that compared with the control group, the expression of migration-related protein matrix metallopeptidase 9 (MMP-9) was increased, the expression of pro-apoptotic protein bax was reduced, the expression of anti-apoptotic protein bcl-xL was increased in conditioned medium group, MSC 1 group and MSC 2 group. Conclusions:hUC-MSC can improve the migration and anti-apoptotic ability of polyploid A549 cells, suggesting that hUC-MSC may affect the survival of tumor cells during the process of chemotherapy damage and repair.
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Objective:To investigate the mutation of epidermal growth factor receptor (EGFR), the expression of programmed death ligand 1 (PD-L1), cell proliferation-associated antigen (Ki-67) in elderly patients with non-small cell lung cancer (NSCLC), and their correlation with clinical feature such as gender, histological type and TNM stage.Methods:The tissue samples of 340 elderly NSCLC patients with definite histopathological diagnosis were collected from January 2020 to December 2020 in Huadong Hospital Affiliated to Fudan University, including 195 males and 145 females, age between 68.9±6.0 years. Patients were grouped according to clinical features such as gender, histological type and TNM stage. The expression of EGFR mutation, PD-L1 and Ki-67 were detected by Super-ARMS and immunohistochemistry. The correlation between tnem and clinical features was statistically analyzed, and the correlation between EGFR mutation and PD-L1/Ki-67 expression was further analyzed separately.Results:In elderly NSCLC patients′ tissues, the positive rate of EGFR mutation was 48.53% (165/340). L858R and 19del mutations were the most common types, which were 56.36% (93/165), 30.30% (50/165) respectively. The mutation rate of EGFR was higher in women, lung adenocarcinoma, well-differentiated, and low-stage patients, which were 65.52% (95/145), 53.77% (164/305), 56.75% (143/252), 52.53% (135/257) respectively. In addition, the positive rate of PD-L1 expression was higher in elderly patients with non-adenocarcinoma lung cancer and poorly differentiated adenocarcinoma, which were 37.14% (13/35), 24.53% (13/53) respectively. The negative rate of PD-L1 expression was higher in elderly patients with NSCLC in stage Ⅰ+Ⅱ, no lymph node metastasis and weakly positive Ki-67, which were 89.11% (229/257), 87.63% (248/283), 94.71% (197/208) respectively. Correlation analysis showed that EGFR mutation was negatively correlated with the expression of PD-L1 and Ki-67 (PD-L1: r=-0.22, P<0.001; Ki-67: r=-0.32, P<0.001). Conclusion:There is a negatively correlation between EGFR mutation and the expression of PD-L1 and Ki-67 in elderly NSCLC, suggesting that the combined detection of EGFR mutation and PD-L1 expression could provide the basis for precise targeted therapy for elderly NSCLC patients.
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Objective:To study the effectiveness and safety of programmed cell death receptor 1(PD-1) monoclonal antibody combined with chemotherapy in the preoperative neoadjuvant treatment of stage ⅢA non-small cell lung cancer(NSCLC).Methods:A total of 65 patients with stage ⅢA NSCLC who underwent preoperative neoadjuvant treatment in our hospital from January 2019 to October 2020 were selected. According to the preoperative neoadjuvant treatment plan, they were divided into control group(31 cases) and observation group(34 cases). Patients in the control group were treated with albumin-bound paclitaxel and cisplatin for injection, and the patients in the observation group were treated with immunotherapy(carrelizumab/sintilizumab) on the basis of the control group, all underwent 2 cycles of preoperative neoadjuvant treatment. Compared the clinical efficacy of imaging, T lymphocyte subsets, drug side effects, surgical resection rate, major pathological remission(MPR), complete pathological remission(pCR) and postoperative complications of the two groups of patients, and analyzed the factors those affected MPR.Results:The clinical efficacy of PR and ORR of imaging in the observation group was better than that of the control group( P<0.05). The positive rate of CD3 + cells, the positive rate of CD4 + cells, the positive rate of CD8 + cells and the ratio of CD4 + /CD8 + cells in the observation group after treatment were higher than those in the control group( P<0.05). The drug toxicity of the observation group was higher than that of the control group in RCCEP/rash, abnormal thyroid function, and abnormal myocardial enzymes( P<0.05). Compared among the observation group(carrelizumab group/sintilizumab group), the toxicity of carrelizumab group was higher than that of sintilizumab group in RCCEP/skin rash, bone marrow suppression and abnormal myocardial enzymes( P<0.05). The MPR and pCR of the observation group were higher than those of the control group( P<0.05). There was no significant difference in surgical resection rate, surgical methods and postoperative complications between the two groups( P>0.05). The results of univariate analysis showed that ECOG score, pathological type, neoadjuvant treatment plan were related to MPR( P<0.05). The results of binary logistic regression analysis showed that ECOG score and neoadjuvant treatment plan were independent risk factors affecting MPR( P<0.05). Conclusion:PD-1 monoclonal antibody combined with chemotherapy can enable patients to obtain better MPR and pCR, and can improve the immune function of patients. But the side effects caused by immunotherapy drugs are worthy of attention, and the side effects are different between different immune drugs.
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Lung cancer is one of the most common malignant neoplastic diseases in the elderly.Immunotherapy represented by immune checkpoint inhibitors mobilizes the body's immune system to achieve antitumor effects.Immune checkpoint inhibitors and their combination with other drugs have played an increasingly important role in the treatment of patients with advanced non-small cell lung cancer.In this review, we summarize the therapeutic effects, adverse reactions and hyperprogressive disease of immune checkpoint inhibitors in the elderly with advanced non-small cell lung cancer, in order to provide insight on immunotherapy strategies for non-small cell lung cancer in the elderly.
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Objective:To explore the value of SPECT/CT imaging on programmed death receptor 1 ligand (PD-L1) expression in patients with non-small cell lung cancer (NSCLC) based on 99Tc m labeled anti-PD-L1 nanoantibodies (NM-01). Methods:From January 2019 to March 2020, a total of 14 patients (11 males, 3 females; age: (61.9±11.0) years) with pathologically confirmed NSCLC in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine were prospectively enrolled. NM-01 were labeled with 99Tc m, and patients were recruited for SPECT/CT imaging 2 h after injection with 99Tc m-NM-01((359.1±68.0) MBq). The differences of SUV max in primary and metastatic lesions between PD-L1 positive and negative patients were compared by independent sample t test. The correlation between the SUV max and PD-L1 expression of primary lesions was analyzed by Pearson correlation analysis. Results:Of 14 patients, 6 were PD-L1 positive and 8 were PD-L1 negative. 99Tc m-NM-01 showed obviously increased uptake in kidneys and liver, while mildly increased uptake in spleen and bone marrow. The SUV max of primary lesions was 4.69±1.88 and the SUV max of metastatic lesions was 2.04±1.32. The SUV max of primary lesions in PD-L1 positive patients was significantly higher than that of PD-L1 negative patients (5.99±1.99 vs 3.72±1.10; t=5.98, P=0.039). There was no significant difference in the SUV max of metastatic lesions between PD-L1 positive and negative patients (1.66±1.03 vs 2.35±1.46; t=-1.77, P=0.084). The SUV max of primary lesions was positively correlated with PD-L1 expression ( r=0.648, P=0.042). Conclusion:99Tc m-NM-01 can demonstrate the expression of PD-L1 in primary and metastatic lesions in NSCLC.
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Radiotherapy combined with immunotherapy for non-small cell lung cancer (NSCLC), especially with PD-1/PD-L1 immune checkpoint inhibitors, have fallen under the spotlight in recent years. How to explore the optimal combination modality of radiotherapy and immunotherapy to maximize the benefits for all-stage patients is one of the developing directions of clinical research. This article expounds the effect of radiotherapy on tumor immunology, research progress on radiotherapy combined with immunotherapy for various stages of NSCLC, and the problems existing in radiotherapy combined with immunotherapy.
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Objective:To analyze the failure patterns and influencing factors of stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer (ES-NSCLC).Methods:113 cases of ES-NSCLC treated with SABR from 2012 to 2020 in our hospital were retrospectively analyzed. The failure patterns, recurrence time, recurrence site and influencing factors were analyzed. Kaplan-Meier method was used to calculate the local recurrence rate, regional lymph node recurrence rate and distant metastasis rate. Univariate analysis was performed by Log-rank test, and multivariate analysis was performed by Cox model.Results:The median follow-up time was 58 months (range: 6-108 months), and a total of 45 patients (39.8%) recurred. The median recurrence time was 36 months. Distant metastasis (DM) occurred in 31 patients (27.4%) and DM alone in 24 patients (21.2%). Local recurrence (LR) was developed in 12 patients (10.6%) and LR alone in 7(6.2%). Regional lymph node recurrence (RR) occurred in 11 patients (9.7%) and RR alone in 6 patients (5.3%). LR combined with RR was observed in 1 case (0.9%), LR combined with DM in 3(2.7%), LR combined with RR and DM in 1(0.9%), and RR combined with DM in 3(2.7%). The 1-, 2-, 3-, 4-and 5-year recurrence rates were 5.4%, 16.6%, 27.5%, 44% and 51.2%, respectively. Univariate and multivariate analyses suggested that EGFR mutation was an influencing factor of high recurrence rate.Conclusion:ES-NSCLC patients treated with SABR alone have a high recurrence rate, and DM is the most common mode of failure. Follow-up consolidation therapy is recommended, especially for EGFR mutation-positive NSCLC patients.
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Advanced non-small cell lung cancer (NSCLC) patients are commonly with brain metastases, leading to poor survival and quality of life. Epidermal growth factor receptor (EGFR) is common sensitive mutation type in NSCLC. Compared with other molecular types, it has different molecular biological characteristics. For patients with brain metastases and EGFR-mutated advanced NSCLC, EGFR-tyrosine kinase inhibitors can prolong overall survival and improve intracranial and extracranial control rate. To understand the characteristics of brain metastases of patients with sensitively EGFR-mutated NSCLC, the incidence, onset time, site, number and size of lesions, symptoms, targeted treatment effect and disease outcomes were reviewed, which can provide reference for interventional timing and local treatment technology selection of local treatment for brain parenchymal metastases.