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@#Chinese Medical Association guideline for clinical diagnosis and treatment of lung cancer (2022 edition) has been published this year. The 2022 edition has been updated in the aspects of lung cancer screening, pathology, standards of thoracic surgery, treatment of metastatic lung cancer. In this study, we tried to introduce those updated aspects in the guideline of 2022 edition.
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Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs. .
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Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients' survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.
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Lung cancer has the highest morbidity and mortality among malignant tumors worldwidely. Targeted therapy related to non-small cell lung cancer (NSCLC) is the research hotspot in recent year. The emergence of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has brought a huge change in the treatment of patients with EGFR mutation. The patients with EGFR exon20 insertion are specific cohort in NSCLC. Reviewing the clinical researches to EGFR exon20 insertion mutation positive NSCLC, as well as summarizing character, testing methods and treatment, will provide a help for clinical application, bringing more benefits for patients at the same time.
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Non-small cell lung cancer (NSCLC) is one of the malignant diseases with high morbidity, high mortality and poor prognosis in China and worldwide, and the progression of which is significantly related to abnormal angiogenesis. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), inhibits angiogenesis during tumor progression. It has been widely demonstrated to improve the survival of NSCLC patients. Therefore, bevacizumab is approved and recommended as the first-line treatment of advanced NSCLC by a number of countries and regions. In this paper, various large-scale clinical trials are analyzed to highlight the current clinical applications of bevacizumab in advanced NSCLC, especially patients with EGFR mutations. In addition, this review focuses on the efficacy, safety and predict factors of bevacizumab as anti-angiogenic therapy, in order to screen the patients who can acquire the maximal benefit.
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Objective The aim of the study is to investigate the therapeutic efficacy of next-generation anaplastic lynphoma kinase-tyrosine kinase inhibitor (ALK-TKI) in advanced non-small cell lung cancer (NSCLC).Methods The clinical data and outcomes of 22 patients with advanced non-small cell lung cancer who received the next generation of ALK-TKI from 2014 to 2017 in our hospital were retrospectively analyzed.Results 22 patients were included for survival analysis with 15 males and 7 females.The median age was 48 and all of them were adenocarcinoma patients.There were 12,2,7 and 1 patients received ceritinib,alectinib,brigatinib and lorlatinib,respectively.A total of 14 patients could be evaluated,including complete response (CR) in 2 cases,partial response (PR) in 3 cases,stable disease (SD) in 6 cases,progressive disease (PD) in 3 cases.The ORR and DCR were 35.7％ and 78.6％,respectively.The median progression free survival (PFS) of the 22 NSCLC patients was 8.7 months.Progression pattern can be analyzed in 17 patients.Among them,10 patients underwent primary progression (lung),occurring at the leading frequency (accounting for 58.8％) and followed by central nerve system (CNS) progression (accounting for 29.4％).Conclusions Next-generation ALK-TKI provide a reasonable choice for crizotinib-resistant patients.Primary progression (lung) is the leading cause for treatment failure.Multi-disciplinary integration may provide a potential choice for prolonging administration of next-generation ALK-TKI.
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Background and purpose:Checkpiont targeted immunotherapy in the field of solid tumor therapy has huge potential, triggering a boom in the study of immune targeted drugs. A study has provided a basis for the follow-up study of ipilimumab combined with chemotherapy in the treatment of non-small cell lung cancer(NSCLC) patients. This study counted the adverse event statistics that ipilimumab or placebo combined with paclitaxel and carboplatin as first-line therapy for the treatment of stage Ⅳ or recurrent squamous cell carcinoma to evaluate the safety of ipilimumab combined with chemotherapy in the treatment of advanced squamous cell carcinoma.Methods:This study selected 13 patients with ECOG scores≤1 and stage ⅣA or ⅣB squamous cell carcinoma in the Shanghai Chest Hospital, Shanghai Jiao Tong Uni-versity. Randomized controlled double blind trial was used in this study. The patients of experimental group were treated with ipilimumab combined with paclitaxel and carboplatin, while the patients of control group were treated with the placebo combined with paclitaxel and carboplatin. Adverse events (AEs) were counted in the process of treatment.Results:The most common AEs were the 1/2 grade AEs. Immune-related AEs (irAEs) reported in the ipilimumab group included level Ⅰ of diarrhea and pruritus, level Ⅱ of rash and pruritus and level Ⅲ of hypophysitis.Conclusion:The side effects of ipilimumab were mild, tolerable and manageable.
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Lung cancer still remains the leading cause of cancer-related death worldwide. Recent development of molecular targeted therapies, especially the emergence of epidermal growth factor receptor (EGFR) inhibitors, has made an enormous progress for the treatment of non-small cell lung cancer (NSCLC). However, targeted therapy still faces many problems including acquired resistance. Several clinical trials have proved that targeted therapy can significantly improve the progression-free survival (PFS), but there are still many things needed to be improved. Thus, oncologists still have a long way to go for realizing precision medicine. The present article illustrates the impact of precision medicine on the treatment of lung cancer and describes how to improve the treatment level of lung cancer, aiming to give an inspiration to the medical oncologists.
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PURPOSE: c-Met and its ligand, hepatocyte growth factor (HGF), play a critical role in oncogenesis and metastatic progression. The aim of this study was to identify inhibited enzymogram and to test the antitumor activity of SIM-89 (a c-Met receptor tyrosine kinase inhibitor) in non-small cell lung cancer. MATERIALS AND METHODS: Z′-LYTE kinase assay was employed to screen the kinase enzymogram, and mechanism of action (MOA) analysis was used to identify the inhibited kinases. Cell proliferation was then analyzed by CCK8 assay, and cell migration was determined by transwell assay. The gene expression and the phosphorylation of c-Met were examined by realtime-PCR and western blotting, respectively. Finally, the secretion of HGF was detected by ELISA assay. RESULTS: c-Met, activated protein kinase (AMPK), and tyrosine kinase A (TRKA) were inhibited by SIM-89 with the IC₅₀ values of 297 nmol/L, 1.31 µmol/L, and 150.2 nmol/L, respectively. SIM-89 exerted adenosine triphosphate (ATP) competitive inhibition on c-Met. Moreover, the expressions of STAT1, JAK1, and c-Met in H460 cells were decreased by SIM-89 treatment, and c-Met phosphorylation was suppressed in A549, H441, H1299, and B16F10 cells by the treatment. In addition, SIM-89 treatment significantly decreased the level of HGF, which accounted for the activation of c-Met receptor tyrosine kinase. Finally, we showed cell proliferation inhibition and cell migration suppression in H460 and H1299 cells after SIM-89 treatment. CONCLUSION: In conclusion, SIM-89 inhibits tumor cell proliferation, migration and HGF autocrine, suggesting it's potential antitumor activity.
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Adenosine Triphosphate , Blotting, Western , Carcinogenesis , Carcinoma, Non-Small-Cell Lung , Cell Movement , Cell Proliferation , Enzyme-Linked Immunosorbent Assay , Gene Expression , Hepatocyte Growth Factor , Lung Neoplasms , Phosphorylation , Phosphotransferases , Protein Kinases , Protein-Tyrosine KinasesABSTRACT
Bronchoscopy is a minimally invasive method for obtaining peripheral pulmonary lesions (PPL). Traditional bronchoscopy-guided transbronchial lung biopsy (TBLB) is performed under X-ray guidance, and diagnostic rate is relatively low. A new, real-time electromagnetic navigation bronchoscopy (ENB) is a minimally invasive diagnostic technique which appeared in recent years. Studies suggest ENB is a feasible and safe method for diagnosis of PPL which shows higher diagnostic yields than traditional TBLB, and its potential application in localization and treatment of PPL. This article reviews the clinical application of the technique.
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Background and purpose:Cytokine-induced killer (CIK) has both the advantages of T lympho-cytes’ powerful anti-tumor activity and NK cells’ tumor killing capacity without MHC restriction. It could directly kill tumor cells, regulate and enhance immune function, without damaging the structure and functions of the immune sys-tem. Its effects on the treatment of malignant solid tumors has been widely recognized. This study aimed to evaluate the anti-proliferation effects of CIK cells obtained and cultivated from lung cancer patients’ lymph nodes. Meanwhile, the safety of clinical transfusion was observed.Methods:The peripheral blood and lymph nodes of 6 surgery patients with lung cancer from Shanghai Chest Hospital were used to cultivate CIK cells for 14 days. The phenotypes of CIK cells were detected by lfow cytometry. The anti-proliferation activities of CIK cells on A549 lung cancer cells were detected by CCK8 assay. The morphological changes of CIK cells were observed by invert microscope. The expression of CEA level and adverse events were evaluated after CIK transfusion.Results:The proportion of CD3+CD56+T lymphocyte in two groups were both more than 30%. The CCK8 assay showed that the suppression rate of lymph nodes group was higher than that of peripheral blood group at each effect/target ratio(P<0.05). The adverse effect of CIK transfusion was mild and tolerable. The expression of CEA level decreased in patients.Conclusion:Lymph nodes of surgery patients with lung cancer can be used for cultivation of CIK cells. The anti-tumor activity of CIK isolated from lymph nodes is better than that of CIK cells cultivated from peripheral blood. Preclinical experiments showed high safety.
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Background and purpose:For patients with advanced lung adenocarcinoma harboring an activating EGFR gene mutation, the current standard of care is EGFR-TKI alone. This study aimed to compare efficacy and safety of gefitinib plus chemotherapy with gefitinib or chemotherapy alone for treating advanced lung adenocarcinoma with an activatingEGFR gene mutation.Methods:This study included 61 patients with lung adenocarcinoma harboring an acti-vatingEGFR gene mutation (19 exons deletion and exon 21 L858R mutations) whose ECOG performance status was 0 or 1. Patients were randomly divided into 3 groups. Group A (n=20) were given carboplatin/pemetrexed of a 4-week cycle, six cycles at most, plus gefitinib (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1; gefitinib 250 mg/d, d 5-21), and then re-ceived pemetrexed of a 4-week cycle plus gefitinib as maintenance therapy; Group B (n=20) were given carboplatin/peme-trexed of a 4-week cycle, six cycles at most (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1), then received pemetrexed as maintenance therapy; Group C (n=21) were given gefitinib (gefitinib 250 mg/d). Patients continued to receive therapy until disease progression or unacceptable toxicity or death. The primary end point was middle PFS and 12 months PFS rate. The secondary end points included objective response rate and adverse events.Results:Groups A and C both lost 1 case during follow-up. Median PFS for patients was 20.1 months (95%CI:18.0-22.2) in group A, 5.5 months (95%CI:3.9-7.2) in group B, and 9.8 months (95%CI:6.8-12.8) in group C. PFS rates of 12 months for groups A, B and C were 78.9%, 15.0% and 40.0%, respectively. The overall objective response rates for groups A, B and C were 84.2%, 35.0% and 65.0%, respectively. Serious adverse events were reported by 36.8% for group A, 30.0% for group B, and 5.0% for group C. The most common grade 3/4 adverse events were neutropenia (3 cases in group A, 4 cases in group B), fatigue (2 cases in group A, 2 cases in group B) and liver function impairment (2 cases in group A, 1 case in group C).Conclusion:Among patients withEGFR mutant lung adenocarcinoma, combination of chemotherapy with gefitinib as first-line treatment demonstrates an improvement in PFS. Long-term survival results will be further followed up.
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Objective To evaluate the diagnostic value of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) in intrathoracic tuberculosis(TB).Methods We retrospectively analyzed patients underwent EBUS-TBNA with a final diagnosis of intrathoracic TB at Shanghai Chest Hospital from October 2009 to March 2013 and observed that the diagnostic efficacy by pathology and microbiology and safety of EBUS-TBNA for intrathoracic TB.Results 75 patients were diagnosed with pulmonary TB or intrathoracic tuberculous lymphadenitis,and accuracy was 80％ (60/75) by EBUS TBNA.A total of 60 patients had pathology,acid-fast bacilli(AFB) staining and mycobacterial culture test results,of whom 52 (86.67％)were diagnosed.Pathological findings were consistent with TB in 77.33％ patients (58/75),in 20.31％ (13/64) the smear were positive for AFB and in 46.67％ (28/60) were positive for cuhure.One hundred and twenty-nine mediastinal or hilar lymph nodes and 10 intrapulmonary lesions were biopsied in 75 patients,the average target number of per patient were 1.85.Pathological findings were consistent with TB in 66.19％ samples(92/139),in 13.91％ (16/115) were positive for AFB and in 38.32％ (41/107) were positive for culture.Multivariate regression revealed that short-axis diameter was an independent risk factor associated with positive pathology,smear and euhure.Additionally,more aspiration times cause higher pathology positive rate,pathology showing necrosis and positive smear were independent risk factors associated with positive cuhure.There were two patients occurred complications during operation.Conclusion EBUS-TBNA was a safe and effective method for the diagnosis of intrathoracic tuberculosis.
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Background and purpose:Multiple primary lung cancers (MPLC) is a rare entity, but recently there has been a gradual increase in the number of patients diagnosed with MPLC. The aim of this study is to investigate the diagnosis, treatment and prognosis of MPLC through analyzing the clinical data.Methods:Forty-one patients were diagnosed MPLC by Martini-Melamed criteria. Their clinicopathological data were retrospectively reviewed. Results:There were 3 patients with triple primary lung cancer and 38 patients with double primary lung cancer. There were 13 patients with synchronous MPLC, 26 patients with metachronous MPLC, 2 patients with synchronous and metachronous MPLC. Of 85 lesions, the surgical procedures were mainly lobectomy (78.8%, 67/85). Lesions (41.2%, 35/85) were frequently in right upper lobe. Pathological type was mainly adenocarcinoma (70.6%, 60/85),followed by squamous cell carcinoma (17.6%, 15/85). Of 60 adenocarcinoma specimens, the papillary predominant subtype was more common (50%, 30/60). Eighty percent (68/85) of the lesions were stage I. As to the initial cancer and repeated cancer, patients who shared the same pathological type (68.3%, 28/41) were more than the different (31.7%, 13/41), of which adenocarcinoma-adenocarcinoma was most common(82.1%, 23/28). Lesions located in contralateral lobes were in 37 patients (90.2%), and located in ipsilateral different lobes were in 4 patients (9.8%). The 2-year overall survival (OS) of them was 87.8%. Survival analysis showed that the prognosis of patients with same pathological type was better than patients with different pathological type (P=0.037), the prognosis of patients with no lymph node metastasis was better than patients with N1,N2 metastasis (P=0.02).Conclusion:Lesions in patients with multiple primary lung cancers are more frequently in the right upper lobes. The pathology type is mainly adenocarcinoma, of which the papillary predominant subtype was most common. Early diagnosis improves continuously, active treatment with operation can achieve better prognosis.
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10.3969/j.issn.1007-3969.2013.05.002
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Background and purpose: Brain metastases are common occurrences in patients with non-small cell lung cancer (NSCLC). Gefitinib is a specific inhibitor of epidermal growth factor receptor-associated tyrosine kinase, which has been commonly used in the treatment for advanced NSCLC. The aim of this study was to evaluate the antitumor efficacy of gefitinib in NSCLC patients with brain metastases. Methods: Fifty NSCLC patients with brain metastases were reviewed retrospectively. All of them were treated with gefitinib, given orally at a daily dose of 250 mg. These patients discontinued administration of gefitinib when disease progression, death or intolerable side effects appeared. X~2 test was applied in response analysis. Survival analysis was compared with Kaplan-Meier method and Log-rank test respectively. The multivariate analysis was perfonned with Cox's proportion risk model. Statistical significance was defined as P<0.05. Results: In terms of intracranial lesions, partial response (PR) was observed in 5 patients (10%), stable disease (SD) in 37 patients (74%) and progressive disease (PD) in 8 patients (16%), objective response rate (ORR) and disease control rate (DCR) were 10% and 84%, respectively. As for systemic disease, PR was observed in 5 patients (10%), SD in 30 patients (60%) and PD in 15 patients (30%), overall ORR and DCR were 10% and 70%, respectively. Overall DCR was related to the patients' PS score and the number of brain metastases (P=0.004, P=0.022), but there was no statistical difference in overall DCR among different subtypes of age, gender, smoking history, histology, the onset of brain metastases, chemotherapy, brain radiotherapy and side effects (P>0.05). The median time to disease progression (MTTP) was 7.0 months, which was related to the patients' PS score and smoking history (P=0.000, P=0.045). The median survival time (MST) was 10.8 months, and 1-and 2-year survival rates were 44% and 6% respectively. The univariate analysis showed that the survival time was related to the patients' PS score. smoking history and the number of brain metastases (P=0.011, P=0.028, P=0.044). The multivariate analysis indicated that both the patients' PS score and smoking history were two independent prognostic factors (P=0.005, P=0.006) and the relationship of the survival time and the number of brain metastases was near to statistical significance (P=0.075). Conclusion: The patients with non-smoking history and favorable performance status(PS 0-1) may have better survival benefit and those with single brain metastasis have a trend to survive longer. Gefitinib may be effective on brain metastases in NSCLC patients and appears to be a possible new treatment option.
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Objective:To analyze the drug sensitivity of human lung adenocarcinoma stem cells (LASC) to cisplatin (DDP) and carboplatin (CBP). Methods:Human lung adenocarcinomaic cells SPC-A1,AG,and CPA-Y2 were treated with DDP and CBP. The cell viability of cells was detected by CCK-8 assay. The phenotypic characteristics of drug surviving cells(DSCs)were determined by immunofluorescence staining. The LASC population was then separated by magnetic-activated cell sorting method. The LASC in DSCs was traced by using green fluorescence protein (GFP). The drug sensitivity of DSCs to DDP and CBP was analyzed.Results:The LASC exhibited the phenotypes of bronchioalveolar stem cells (BASC, OCT4~+CCSP~+SP-C~+). After mixture of CD221~+LASC with CD221~-lung adenocarcinoma differentiated cells, the DSC population showed OCT4~+BASC phenotypes. These DSCs were significantly resistant to DDP and CBP.Conclusion:LASC has a high resistance to DDP and CBP. This may be the reason for tumor recurrence after chemotherapy.
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<p><b>BACKGROUND AND OBJECTIVE</b>The aim of this study is to evaluate diagnostic yield and the safety of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis ofbronchogenic carcinoma.</p><p><b>METHODS</b>Between July, 2009 and February, 2010, 95 patients with mediastinal/hilar lymphadenopathy and/or intrathoracic peritracheal or peribronchial masses previously detected with CT scan underwent EBUS-TBNA. No rapid onsite cytology was performed.</p><p><b>RESULTS</b>In all 95 patients, 60 cases were newly diagnosed lung cancer through the pathological examination and clinical follow-up certification. In 60 lung cancer cases, 112 samples were obtained from lymph nodes (LNs) and 11 samples were obtained from intrapulmonary lesions. Fifty-eight cases of patients were diagnosed, false negative in 2 cases. Sensitivity and specificity of EBUS-guided TBNA method in distinguishing benign from malignant LNs or thoracic masses were 96.67% and 100%, respectively. There was any major complication in this series, the procedure was uneventful.</p><p><b>CONCLUSION</b>EBUSTBNA seemed a safe and effective technique in making bronchogenic carcinoma diagnosis for mediastinal/hilar LNs and intra-pulmonary masses.</p>
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Biopsy, Fine-Needle , Methods , Bronchi , Diagnostic Imaging , Pathology , Carcinoma, Bronchogenic , Diagnosis , Endosonography , Methods , Lung Neoplasms , DiagnosisABSTRACT
Background and purpose: The overall survival time of extensive-stage small cell lung cancer is not satisfactory. No chemotherapy schemes more effective than etoposide combined with cisplatin, and other optimum combinations should be under evaluation. The aim of this study was to investigate the survival advantage of IEP followed by EP chemotherapy in the treatment of extensive-stage small cell lung cancer compared with EP chemotherapy alone. Methods: From Jan 2004 to Sep 2007, 68 extensive-stage small cell lung cancer patients were enrolled in this project and were randomly divided into research group and control group in the ratio of 1:1. In the research group, 34 patients accepted IEP chemotherapy at least two times followed by EP chemotherapy maintenance therapy. 34 patients as control group accepted EP chemotherapy only. Statistical significance was defined as P<0.05. Results: The median overall survival time of the research group was 15.32 months and the control group was 9.30 months. There were no significant differences between the two groups (P=0.0787). The median time to progression of the research group was 7.83 months and 6.92 months for the control group, respectively. There were no significant differences between the two groups (P=0.0164). It is suggested that IEP followed by EP chemotherapy in treatment of extensive-stage small cell lung cancer could get a better progression free survival, but the overall survival time has not been improved. Conclusion: We conclude that those patients with extensive-stage small cell lung cancer could get better progression free survival by accepting IEP chemotherapy.
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After many targeted drugs have entered into the treatment guideline or all stage clinical trial of non-small-cell lung cancer (NSCLC), many researchers undertake deep investigation on the role of molecular gene marker in targeted therapy of NSCLC. It is a good outset that mutation detection of epidermal growth factor receptor (EGFR) gene direct the selection of EFGR tyrosine kinase inhibitors (EGFR-TKI). To choose individualized therapy regimens according to molecular gene marker will be the important research direction, but also be the critical measure to improve the management level of NSCLC and prolong patient"s survival. Accompanied with deep investigation of targeted therapy, there will be more molecular gene markers to direct the formulation of individualized therapy regimens.