The Therapeutic Effects of the Radiotherapy Plus TCM Treatment Observed in Senile Non-Parvicellular Lung Cancer Patients at the Late Stage

47 senile non-parvicellular lung cancer patients at stage Ⅲ or Ⅳ were randomly divided into a treatment group (26 cases) treated by radiotherapy plus traditional Chinese medicine (TCM) and a control group (21 cases) treated only by radiotherapy for observation of the therapeutic effects.The patients in the treatment group orally took Chinese medicine during and after the radiotherapy.There was no obvious difference in short-term therapeutic effects between the two groups,but the long-term curative effects in the treatment group was obviously superior to that in the control group (P<0.05 or P<0.01).Conclusion:radiotherapy plus TCM can prolong the survival period for senile non-parvicellular lung cancer patients.

Efficacy Differences of First-line EGFR-TKIs Alone vs in Combination with Chemotherapy in Advanced Lung Adenocarcinoma Patients with Sensitive EGFR Mutation and Concomitant Non-EGFR Genetic Alterations

Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe a reason for the poor efficacy of EGFR tyrosine kinase inhibitors(TKIs).Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations.Materials and methods:Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant nonEGFR genetic alterations were retrospectively collected.And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy.Demographic,clinical and pathological data were collected,and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression.Survival data were obtained through face-to-face or telephone follow-up.The differences between the two groups in objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS)and overall survival(OS)were investigated.Results:107 patients were included,including 63 cases in the combination group and 44 cases in the monotherapy group.The ORR were 78%and 50%(P=0.003),and DCR were 97%and 77%(P=0.002),respectively.At a median follow-up of 13.7 mon,a PFS event occurred in 38.1%and 81.8%of patients in the two groups,with median PFS of18.8 mon and 5.3 mon,respectively(P<0.000,1).Median OS was unreached in the combination group,and 27.8 mon in the monotherapy group(P=0.31).According to the Cox multivariate regression analysis,combination therapy was an independent prognostic factor of PFS.Conclusion:In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations,combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy,which should be the preferred treatment option.

Gene Polymorphisms and Chemotherapy in Non-small Cell Lung Cancer

The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan,oxidized by CYP3A4 to produce inactive compounds,is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. CYP3A4*16B polymorphism was associated with decreased metabolism of irrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite,SN-38,which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin,carboplatin) are being used in combination with new cytotoxic drugs such as gemcitabine,paclitaxel,docetaxel,or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1,XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinucleotide repeat (CA-SSR) showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR promoter activity. EGFR gene mutations and polymorphisms were also associated with EGFR kinase inhibitors response and toxicity.

Systematic review and meta analysis of the TCM therapy of Fuzheng and Kangai combined with chemotherapy in treating advanced NSCLC

Objective:To systematically evaluate TCM of Fuzheng and Kangai combined with chemotherapy in the treatment of Advanced NSCLC,including the efficacy and effect on the quality of life of patients.Methods:Two researchers independently searched the literature of clinical trails from Jan.2010 until Jun.2020 in the Cochrane Library,Pubmed,Embase,CBM,CNKI,WanFang Data and VIP database.Also,they had been evaluated and extracted strictly by REVMAN 5.3.Results:A total of 1303 patients were included in 15 articles.The meta analysis shows that the TCM of Fuzheng and Kangai combined with chemotherapy can improve the objective response rate[OR=2.14,95%CI(1.67,2.74),P<0.00001],disease control rate[OR=2.54,95%CI(1.88,3.42),P<0.00001]and KPS score[OR=3.28,95%CI(1.92,5.60),P<0.0001],decrease the incidence rate of liver injury[OR=0.34,95%CI(0.21,0.54),P=0.003],hemoglobin reduction[OR=0.53,95%CI(0.28,1.01),P=0.05],leukopenia[OR=0.22,95%CI(0.13,0.39),P<0.00001],thrombocytopenia[OR=0.32,95%CI(0.21,0.50),P<0.00001],toxic effects on the digestive systems[OR=0.30,95%CI(0.19,0.46),P<0.00001].Conclusions:the experimental group was better than control one in short-term efficacy and KPS score.Furthermore,the experimental group can reduce the incidence rate of myelosuppression,toxicity of digestive system and liver.

Effects of Electro-Acupuncture on Immune Function After Chemotherapy in 28 Cases

PURPOSE: To observe the effects of electroacupuncture therapy on T cells and activity of NK cell in the patient of Chemotherapy. METHOD: Electro-acupuncture therapy was simultaneously applied during chemotherapy, T cells and activity of NK cell of patients were determined before electroacupuncture treatment (before chemotherapy) and after 4-course electro-acupuncture treatments. RESULTS: Before chemotherapy, CD3 was low within the normal range, CD4 was much lower than the normal range, and CD8, CD4/CD8 and activity of NK cell were within the normal range. After one month of chemotherapy combined with electro-acupuncture, no decline of all the indices was found (P > 0.05). CONCLUSION: Electro-acupuncture can really increase the immune function of patients of chemotherapy.

Treatment Sequencing Strategies in Lung Cancer

Background and objective The advances in the lung cancer screening methods and therapeutics,together with awareness towards deleterious habits,such as smoking,is increasing the overall survival with better quality of life for the patients.However,lung cancer is still one of the most common and fatal neoplasm with a high incidence and consequently burden to public health worldwide.Thus,based on guidelines and recent phasesⅡandⅢclinical trials studies,this manuscript summarizes the current treatment sequencing strategies in lung cancer.Methods A comprehensive search of related articles was performed focused on phasesⅡandⅢclinical trials studies.Results The lung cancer management should take into consideration the tumor characteristics,histology,molecular pathology and be discussed in a multidisciplinary team.Lung cancer treatment options comprises surgery whenever possible,radiotherapy associate with/or chemotherapy and immunotherapy as monotherapy,or combined with chemotherapy and best palliative care.Conclusions The screening predictability in more patients,smoking reduction,early diagnosis,better disease understanding and individualized,more effective and tolerable therapeutics are related to an increasing in overall survival and quality of life.In the near future improvement of personalized therapy in precision medicine is expected,enhancing new predictive biomarkers,optimal doses and optimal treatment sequencing as well as anti-cancer vaccines development.

Investigation of therapeutic modalities of G719X, an uncommon mutation in the EGFR gene in non-small cell lung cancer

Objective G719 X is the most frequently seen uncommon mutation of the epidermal growth factor receptor(EGFR) gene, which is a point mutation at exon 18 with three common subtypes, G719 A/G719 C/G719 S. This study explored the clinicopathological characteristics of the G719 X mutation and investigated the efficacy of EGFR-tyrosine kinase inhibitor(TKI) treatment and chemotherapy in patients with the G719 X mutation; the survival rate after these different treatment modalities were then analyzed in order to provide evidence for clinical treatment.Methods Clinical data of 41 patients with the G719 X mutation admitted in the Beijing Chest Hospital, Capital Medical University from September 2014 to July 2018, were collected and the EGFR mutations were detected by amplification refractory mutation system-polymerase chain reaction(ARMS-PCR). The clinicopathological characteristics of the G719 X mutation were analyzed, and the relationship among the G719 X mutation, the efficacy of different treatment modalities, and the progression-free survival(PFS) was analyzed. Results Of the 41 cases, 24(58.5%) were G719 X single mutations and 17(41.5%) were compound mutations, including G719 X/S768 I, G719 X/L861 Q, G719 X/19 del, and G719 X/c-Met compound mutation. The objective response rate(ORR) of first-line EGFR-TKI therapy was 50%(6/12), the disease control rate(DCR) was 83.3%(10/12), and the median PFS(mPFS) was 9 months. After resistance to EGFR-TKI in the previous treatment, the ORR(71.4%, 5/7) and DCR(100%, 7/7) were still high following EGFR-TKIs, by an mPFS of 8 months. The ORR of chemotherapy was 33.3%(2/6), the DCR was 100%(6/6), and the mPFS was 6 months. Conclusion G719 X is an uncommon mutation of the EGFR gene and is sensitive to many EGFR-TKIs. It can be treated with the second-or third-generation EGFR-TKIs after resistance to the first-generation EGFR-TKIs. G719 X mutation also showed favorable effect to chemotherapy.

THE CLINICAL COURSE AND TREATMENT RESULTS OF LUNG METASTASES FROM BREAST CANCER

Objective: To analyze the clinical course and treatment result of lung metastases from breast cancer Method: 122 cases with lung metastases from breast cancer were treated with chemotherapy or chemotherapy plus endocrine therapy, response was assessed according to WHO criteria and survival rate estimated using the life Table Results: The median time from initial treatment of primary tumor to lung metastases was 22 months Sites of common consecutive metastases were lung, liver and bone The overall response rate was 48% with a CR rate of 15% Compared to non DDP encompassing regimen, the CR rate was higher in DDP based chemotherapy (7% versus 21%, P <0 05) with a longer median survival time (MST) The PR rate was higher in regimens containing anthracycline (48%) than in those without anthracycline (20%, P <0 01) The response rate was similar between chemotherapy and chemotherapy plus endocrine therapy ( P >0 05) No difference in MST was observed between patients receiving anthracycline and non anthracycline encompassing regimens The 1 , 3 , 5 , and 10 year survival rate was 77%, 22%, 11%, and 10%, respectively Conclusion: Size of primary tumor, the length of disease free interval, the number of lung metastases may provide additional information for predicting patients survival after treatment of lung metastases Combination chemotherapy, especially DDP based chemotherapy may prolong survival time of patients with lung metastases from breast cancer

Is there a role for surgery in stage ⅢA-N2 non-small cell lung cancer?

The role of surgery in stage ⅢA-N2 non-small cell lung cancer(NSCLC) remains controversial.Most important prognostic factors are mediastinal downstaging and complete surgical resection.Different restaging techniques exist to evaluate response after induction therapy and these are subdivided into non-invasive,invasive and alternative or minimally invasive techniques.In contrast to imaging or functional studies,remediastinoscopy provides pathological evidence of response after induction therapy.Although techn...

The clinical evaluation of Iressa first-line treatment of senium advanced-stage non-small cell lung cancer

Objective: To evaluate the response and the side effects of Iressa on the first line treatment in senium advanced stage non-small cell lung cancer. Methods: Sixteen non-small cell lung cancer patients were observed from November 2005 to September 2007, the date of patients belong to the Second Affiliated Hospital of Dalian Medical University. I was prescribed on the first line at oral dose of 250 mg daily as a continuous dose. Then the response and side-effects of Iressa were evalu-ated. Results: Among 16 patients, CR, PR, SD, PD were 0% (0/16), 37.5% (6/16), 50% (8/16), 12.5% (2/16) respectively. CR + PR + SD was 87.5% (14/16). Adverse events: rash 37.5% (6/16), dry skin 18.75% (3/16), itching of skin 12.5% (2/16), diarrhea 31.25 (5/16), and hepatic dysfunction (GPT increase) 12.5% (2/16). Conclusion: Iressa is active on the first line treatment in old age advanced stage non-small cell lung cancer. It is well tolerated with adverse events. The quality of life may be improved significantly.

工程化外泌体在肺癌治疗中的研究进展

非小细胞肺癌最佳的治疗方式为早期手术治疗,而大部分肺癌发现时已为晚期。治疗方式以药物及放射治疗为主。但上述治疗方式出现耐药或疗效不显著是不可避免的,因此,针对肺癌的治疗迫切需要更多的手段。研究证实,工程化外泌体在心血管系统疾病、肿瘤、组织再生与修复等领域具有良好的临床应用潜能。本文总结了国内外工程化外泌体在肺癌治疗中的应用。

Acidification and apoptosis of human lung cancer cells induced with antisense nucleotides against NHE-1 gene

To explore the role of Na+/H+ exchanger-1 (NHE-1 ) gene expression in intracellular PH (pHi) regulation and the modulation of apoptosis of human lung cancer cells. Methods: After the human lung cell line A549 cells were incubated with a 21-mer antisense phosphorothioate oligodeoxynucleotide (ASODN) complementary to NHE-1 gene, the acidification effects of AS-ODN on A549 cells was investigated with fluorescent probe labeling and the apoptotic rate of these cells determined with in situ cell apoptosis detection. Results: Intracellular acidification (pHi from 7. 12 to 6. 55) and cell apoptosis of A549 cells induced by AS-ODN were correlated to dose of the agent. The apoptotic rate was found to be 30. 1 %, 91. 2% and 99. 6% respectively at the end of incubation time of 24, 48 and 72 h with 20μmol/L AS--ODN. Under the electron microscope, morphological changes of cell apoptosis were seen. Conclusion: Intracellular acidification (pHi<6. 55) can trigger apoptosis of human lung cancer cells and NHE-1 gene expression plays an important role in the regulation of apoptosis of the human lung cancer cells through preventing intracellular acidification.

免疫细胞及炎症因子对晚期肺癌一线化疗效果的预测价值

【目的】探讨T淋巴细胞亚群、肿瘤浸润T淋巴细胞(Tils)及炎症因子对晚期肺癌一线化疗效果的预测价值。【方法】检测98例首诊TNM分期为Ⅲ/Ⅳ期的非小细胞肺腺癌患者的血清白细胞介素1α(IL-1α)、IL-6、IL-17、γ-干扰素(INF-γ)水平及T淋巴细胞亚群CD4^(+)T、CD8^(+)T、调节性T细胞、CD57^(+)细胞、Granzyme B^(+)细胞、CD45RO^(+)细胞比例;所有患者均接受紫杉醇注射液+顺铂化疗,治疗4个周期后评定疗效,并据此分为有效组和无效组,分析化疗无效的影响因素及预测疗效的有效标志物。【结果】化疗后,98例患者中69例化疗有效,29例无效。无效组患者淋巴结转移占比及调节性T细胞、IL-1α表达水平均高于有效组(P<0.05),CD57^(+)细胞、CD45RO^(+)细胞比例均低于有效组(P<0.05)。多因素逐步Logistic回归分析结果显示,调节性T细胞、IL-1α水平高是肺癌患者化疗无效的危险因素(P<0.05),CD57^(+)细胞、CD45RO^(+)细胞比例高是保护因素(P<0.05)。受试者工作特征(ROC)曲线分析显示,调节性T细胞、CD57^(+)细胞、CD45RO^(+)细胞、IL-1α水平预测化疗效果的灵敏度分别为82.76%、86.21%、89.66%、93.10%,四者联合的灵敏度、特异度和曲线下面积(AUC)分别为82.76%、97.10%、0.957。【结论】T淋巴细胞亚群、Tils及炎症因子水平与晚期肺癌治疗效果密切相关,其可作为预测疗效的敏感指标。

王文萍从痰瘀论治肺癌经验

王文萍教授认为,肺癌病机为痰瘀互结,临证以活血化瘀、调畅气机为主,软坚散结、化痰祛瘀为辅,方用血府逐瘀汤合二陈汤化裁治疗肺癌,同时注重对患者进行心理疏导,减轻其精神压力,以达到标本兼治的目的。本文从病因病机、治法治则、遣方用药总结王文萍教授治疗肺癌的临证经验,并附验案一则,以期较为全面地分析王文萍从痰瘀论治肺癌的学术思想。

肿瘤相关巨噬细胞:调节肿瘤微环境的新靶点

肿瘤相关巨噬细胞(tumor-associated macrophage,TAM)在肺癌免疫微环境中扮演着重要的角色。它们通过自身的表型和吞噬功能的变化,在肺癌的发生和进展中发挥作用,通过促进肺癌免疫抑制型微环境的形成和肿瘤异常血管的生长加速肺癌的侵袭和扩散。巨噬细胞在应对不同刺激时,可以极化为具有不同功能和特征的亚型,分为抗肿瘤M1型和促肿瘤的M2型。在肿瘤组织中,TAM通常极化为交替活化型的M2表型,表现出对肿瘤免疫的抑制作用。本文综述了抗血管生成药物在调节TAM表型方面的作用,它们可以通过将M2型TAM重编程为M1型来发挥抗肿瘤作用。同时,TAM的功能改变在抗血管生成治疗和免疫治疗策略中也起到重要作用。研究证实,TAM通过极化及功能改变可能成为调节肿瘤微环境的新靶点,开辟肺癌治疗的新途径。

可切除非小细胞肺癌新辅助免疫治疗研究进展

近年来,免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)对晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者预后的改善已成为共识,越来越多的临床研究也逐渐证明了免疫治疗对于可切除NSCLC患者的重要价值。然而,目前关于新辅助治疗背景下免疫联合策略的探索、治疗相关副作用、预后生物标志物等问题仍存在争议。本文综述了可切除NSCLC患者新辅助免疫治疗的最新进展,引发了新的思考,并讨论了其在临床应用中的优势及挑战。

基于“肺合大肠”理论探讨肺纤维化中医病机

肺纤维化是一种以肺泡上皮细胞损伤、成纤维细胞病理性增殖转型、细胞外基质过度沉积导致肺组织结构破坏及功能丧失的呼吸系统疾病,病死率高且尚无较好治疗方法。本文以“肺合大肠”的中医认识即“肺与大肠相表里”理论为基础,以“肺合大肠”的现代医学认识即“肠-肺轴”理论为关键点,结合二者探讨相关机制,初步阐述中医药调控“肠-肺轴”治疗肺纤维化的内涵,为临床通过“肠-肺轴”治疗肺纤维化提供新思路。

G719X/L861Q/S768I突变非小细胞肺癌诊断及靶向治疗进展

肺癌在全球癌症死亡原因中占比最高,对人类健康造成了极大威胁。30%-40%的非小细胞肺癌(non-small cell lung cancer,NSCLC)的发生是由于表皮生长因子受体(epidermal growth factor receptor,EGFR)发生点突变、外显子插入、外显子缺失导致。除常见的19号外显子缺失突变和21号外显子L858R突变外,18号外显子G719X突变、21号外显子L861Q突变、20号外显子S768I突变是最主要的罕见突变。目前,针对主要罕见突变的诊断方法主要是下一代测序技术(next-generation sequencing,NGS)、数字聚合酶链式反应(digital polymerase chain reaction,dPCR)、微滴式数字PCR(droplet digital PCR,ddPCR)等。关于G719X/L861Q/S768I突变NSCLC的靶向治疗,第一代EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)疗效较差,第二代和第三代EGFR-TKIs疗效相当,新型第三代EGFR-TKIs和联合治疗展现出不错的治疗前景。本文对G719X/L861Q/S768I突变NSCLC诊断及靶向治疗进展进行了归纳,以期为后续临床用药及研究提供参考。

EGFR外显子20插入突变:研究现状与治疗新策略

作为非小细胞肺癌(non-small cell lung cancer,NSCLC)中重要的致癌驱动基因,表皮生长因子受体外显子20插入突变(epidermal growth factor receptor exon 20 insertion,EGFR ex20ins)具有独特蛋白构象,并且对传统EGFR酪氨酸激酶抑制剂(EGFR-tyrosine kinase inhibitors,EGFR-TKIs)原发耐药。近年来,靶向EGFR ex20ins的药物探索从未停止。莫博赛替尼与埃万妥单抗率先被美国食品药品监督管理局(Food and Drug Administration,FDA)获批用于EGFR ex20ins突变NSCLC患者,随后舒沃替尼等药物取得突破,联合治疗方案的探索也有所收获。多管齐下有望克服EGFR ex20ins耐药。因此,深入了解EGFR ex20ins的分子机制并评估新型药物的有效性与差异性至关重要。本文将对相关最新研究成果进行全面总结,以期为EGFR ex20ins突变患者精准治疗提供有价值的参考。

粒细胞样髓源性抑制细胞在非小细胞肺癌中的研究进展

粒细胞样髓源性抑制细胞(granulocytic myeloid-derived suppressor cells,G-MDSCs)是MDSCs的主要亚群之一,在多数癌症中广泛富集,通过表达精氨酸酶1(arginase-1,Arg-1)及活性氧(reactive oxygen species,ROS)等机制抑制淋巴T细胞杀伤功能,重塑肿瘤免疫微环境,促进肿瘤的发生发展。近年来,越来越多的研究发现G-MDSCs与非小细胞肺癌患者的预后和免疫治疗疗效具有显著相关性,使用特异性靶向G-MDSCs的募集、分化和功能的药物能够有效抑制肿瘤的进展。本文主要就G-MDSCs在非小细胞肺癌中的免疫抑制作用及其相关通路靶向药物的研究进展进行综述。