Physical exercise reverses immuno-cold tumor microenvironment via inhibiting SQLE in non-small cell lung cancer

Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are obscure.Immunometabolic regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].However,whether physical exercise can modulate cholesterol metabolism in tumor cells is currently unknown.

Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.

Patient-derived non-small cell lung cancer xenograft mirrors complex tumor heterogeneity

Objective:Patient-derived xenograft(PDX)models have shown great promise in preclinical and translational applications,but their consistency with primary tumors in phenotypic,genetic,and pharmacodynamic heterogeneity has not been well-studied.This study aimed to establish a PDX repository for non-small cell lung cancer(NSCLC)and to further elucidate whether it could preserve the heterogeneity within and between tumors in patients.Methods:A total of 75 surgically resected NSCLC specimens were implanted into immunodeficient NOD/SCID mice.Based on the successful establishment of the NSCLC PDX model,we compared the expressions of vimentin,Ki67,EGFR,and PD-L1 proteins between cancer tissues and PDX models using hematoxylin and eosin staining and immunohistochemical staining.In addition,we detected whole gene expression profiling between primary tumors and PDX generations.We also performed whole exome sequencing(WES)analysis in 17 first generation xenografts to further assess whether PDXs retained the patient heterogeneities.Finally,paclitaxel,cisplatin,doxorubicin,atezolizumab,afatininb,and AZD4547 were used to evaluate the responses of PDX models to the standard-of-care agents.Results:A large collection of serially transplantable PDX models for NSCLC were successfully developed.The histology and pathological immunohistochemistry of PDX xenografts were consistent with the patients’tumor samples.WES and RNA-seq further confirmed that PDX accurately replicated the molecular heterogeneities of primary tumors.Similar to clinical patients,PDX models responded differentially to the standard-of-care treatment,including chemo-,targeted-and immuno-therapeutics.Conclusions:Our established PDX models of NSCLC faithfully reproduced the molecular,histopathological,and therapeutic characteristics,as well as the corresponding tumor heterogeneities,which provides a clinically relevant platform for drug screening,biomarker discovery,and translational research.

Oncoprotein HBXIP promotes tumorigenesis through MAPK/ERK pathway activation in non-small cell lung cancer

Objective:The oncoprotein,hepatitis B X-interacting protein(HBXIP),has been reported to play an important role in human malignancies.However,its functions in non-small cell lung cancer(NSCLC)are poorly understood.The goal of the present study was to identify the role of HBXIP in the regulation of NSCLC development.Methods:The level of HBXIP expression in NSCLC tissue was assessed by immunohistochemical and Western blot analyses,and its relationships with clinicopathological features and outcomes were statistically evaluated.The effects of HBXIP on NSCLC cell progression were assessed through cell viability,colony formation,and flow cytometry analyses in vitro.The mechanism by which HBXIP regulated the MAPK pathway was studied by Western blot,immunofluorescence,and immunoprecipitation assays.In addition,in vivo experiments were performed to evaluate the progression of NSCLC and ERK signaling pathway activation after HBXIP knockdown.Results:HBXIP was overexpressed in human NSCLC and was correlated with the invasiveness of NSCLC.The high expression of HBXIP in NSCLC was significantly correlated with gender(P=0.033),N stage(P=0.002),and tumor-node-metastasis stage(P=0.008).In vitro experiments using an NSCLC cell line revealed that HBXIP knockdown resulted in the suppression of cell proliferation and colony formation,which was consistent with the enhanced cell cycle arrest in G1 phase.The results of a mechanistic investigation suggested that binding of HBXIP to MEK1 protein promoted MAPK/ERK signaling pathway activation in NSCLC by preventing the proteasome-mediated degradation of MEK1.In addition,the results obtained using in vivo subcutaneous tumor xenografts confirmed that HBXIP deficiency decreased MEK1 protein levels and NSCLC tumor growth.Conclusions:Taken together,our results showed that the HBXIP-MEK interaction promoted oncogenesis via the MAPK/ERK pathway,which may serve as a novel therapeutic target for cancers in which MAPK/ERK signaling is a dominant feature.

Application value of ATP based bioluminescence tumor chemosensitivity assay in the chemotherapy for hydrothorax caused by non-small cell lung cancer

Objective： The aim of the study was to investigate the clinical value and application of ATP based bioluminescence tumor chemosensitivity assay （ATP-TCA） in the chemotherapy for hydrothorax caused by non-small cell lung cancer （NSCLC）. Methods： Hydrothorax specimens from 120 NSCLC patients were analyzed by ATP-TCA and the most sensitive chemotherapeutic drugs were used in NSCLC patients （treatment group）. At the same time, 56 NSCLC patients with hydrethorax were admitted in our Hospital （Department of Oncology, The No. 2 People＇s Hospital of Yibin, China） and given chemotherapy without guidance of the ATP-TCA （control group）. Before the third chemotherapeutic cycle, clinical outcomes were analyzed in the two groups. Results： Effective rate of hydrothorax in treatment group was 67%, while 46% in control group （P 〈 0.05）. In refractory hydrothorax patients, they were 69% and 40% （P 〈 0.05）, respectively.In vitro results correlated well with clinical outcomes （P 〈 0.01）. Conclusion： Effective rate of chemotherapy for hydrothorax in NSCLC is higher in treatment group than that in control group. ATP-TCA is especially helpful for refractory hydrothorax.

Effect of application of markers and immune function of patients with tumor of erlotinib combined with Addie injection in non-small cell lung cancer

Objective:To investigate the efficacy of erlotinib plus Addie injection in the treatment of non-small cell lung cancer patients of tumor markers and immune function.Methods: A total of 174 patients with non-small cell lung cancer who were treated in our hospital from February 2013 to February 2017 were selected. Randomly divided into 2 groups, 87 cases in each group, set as observation group and control group. The observation group received erlotinib combined with Addie injection and the control group only received erlotinib. After 6 weeks of treatment, tumor markers, vascular endothelial growth factor levels and immune function indexes were compared between the two groups after treatment.Results: The observation group after treatment of tumor markers in CEA (carcinoembryonic antigen), CA199 (carbohydrate antigen 19-9) and CYFRA21-1 (cytokeratin 19 fragment) and NSE (neuron specific enolase) than those in control group and the difference was statistically significant. After treatment, the levels of VEGFA (vascular endothelial factor-A), VEGFB (vascular endothelial factor-B) and VEGFC (vascular endothelial factor-C) in the observation group were lower than those in the control group and the difference was statistically significant. After treatment, the immune index CD3+ (total T lymphocyte), CD4+ (helper T lymphocyte) and CD4+/CD8+ levels in the observation group were higher than those in the control group, and the level of NK (natural killer cell) was higher than that of the control group and the difference was statistically significant. After treatment, the levels of IgG (re reactive antibody), IgM (initial immune response antibody) and IgA (mucosal immune secretory antibody) in the observation group were higher than those in the control group and the difference was statistically significant.Conclusion: Erlotinib combined with Addie injection in the treatment of non-small cell lung cancer clinical effect is good. It can improve the immune function and reduce the levels of VEGF and tumor markers. It is recommended to be widely used in clinic.

Effects of Yiqi Gu Ben Decoction combined with DC chemotherapy on serum tumor markers, inflammatory factors and immune function in patients with locally advanced non-small cell lung cancer

Objective: To investigate the effects of Yiqi Gu decoction combined with DC chemotherapy on serum tumor markers, inflammatory factors and immune function in patients with locally advanced non-small cell lung cancer. Methods: A total of 95 patients with locally advanced non-small cell lung cancer were selected as the research objects, according to the random data table they were divided into control group (n=48) and observation group (n=47), patients in the control group were given DC chemotherapy, On the basis of this treatment, the patients in the observation group were given Yiqi Gu decoction treatment, Comparison of the levels of serum tumor markers [antigen (CEA) and carbohydrate antigen 19-9 (CA19-9)], inflammatory factor [C reactive protein (CRP) and tumor necrosis factor-α (TNF-α)] and immune function (CD3+, CD4+, CD8+, CD4+/CD8+)Results: Before treatment, there were no significant difference in the levels of CEA, CA19-9, CRP, TNF-α, CD3+, CD4+, CD8+, CD4+/CD8+ between the two groups;After treatment, the CEA, CA19-9, CRP, TNF-α, CD8+ levels of two groups were significantly lower than those in the same group before treatment, and the decreased range in observation group was significantly higher than the control group, moreover the levels after treatment were obviously lower than control group;After treatment, the levels of CD3+, CD4+, CD4+/CD8+ in the observation group were (64.72±5.25)% , (39.51±5.14)% and (1.35±0.27), which were significantly higher than the same group before treatment, and significantly higher than the control group [(58.57±5.09)%, (31.34±5.06)%, (1.14±0.33)], differences were statistically significant. Conclusion: DC chemotherapy combined with Yiqi Guben Decoction in the treatment of locally advanced non-small cell lung cancer, can effectively reduce the serum tumor marker levels, decrease inflammatory stress, improve immune function, has an important clinical value.

Correlation of peripheral blood NK cell content with tumor marker content and proliferation molecule expression in patients with non-small cell lung cancer

Objective:To study the correlation of peripheral blood NK cell content with tumor marker content and proliferation molecule expression in patients with non-small cell lung cancer (NSCLC).Methods: A total of 80 patients who were diagnosed with NSCLC in our hospital between June 2014 and October 2016 were selected as the NSCLC group of the research, and 96 healthy volunteers who received physical examination in our hospital during the same period were selected as the control group of the research. The peripheral blood NK cell content and serum tumor marker contents of two groups of subjects were determined, and the proliferation molecule expression levels in lung cancer focus tissue and focus tissue adjacent to carcinoma of NSCLC group were determined.Results:Peripheral blood NK cell content of NSCLC group was significantly lower than that of control group;serum CEA, CA125, Cyfra21-1 and HE4 contents were significantly higher than those of control group, and serum CEA, CA125, Cyfra21-1 and HE4 contents of NSCLC patients with high NK cell content were significantly lower than those of NSCLC patients with low NK cell content;c-myc, c-FLIP, Livin, Moesin and k-ras protein expression in lung cancer focus tissue were significantly higher than those in focus tissue adjacent to carcinoma, and c-myc, c-FLIP, Livin, Moesin and k-ras protein expression in lung cancer focus tissue with high NK cell content were significantly lower than those in lung cancer focus tissue with low NK cell content.Conclusion: Peripheral blood NK cell content significantly reduces in patients with NSCLC and is associated with the cancer cell proliferation activity.

Effects of combined treatment of bronchial arterial chemoembolization and radioactive particle implantation on tumor markers and T lymphocyte subsets in locally advanced non-small cell lung cancer

Objective: To investigate the effects of bronchial arterial chemoembolization combined with radioactive particle implantation on the level of serum tumor markers and T lymphocyte subsets in patients with locally advanced non-small cell lung cancer. Methods: A total of 91 cases of locally advanced non-small cell lung cancer patients according to the random data table were divided into the control group (n=45) and observation group (n=46) according to the random data table. Patients in the control group was treated with bronchial arterial chemoembolization, on the basis of the control group, patients in the observation group were treated with radioactive particle implantation, the serum tumor markers and T lymphocyte subsets of the two groups were compared before and after treatment. Results: The levels of CEA, NSE, CA125, CD4+, CD8+, CD4+/CD8+ and NK in the two groups before the treatment were not statistically significant. Compared with the group before treatment, levels of CEA, NSE, CA125and CD8+ of the two groups after treatment were significantly decreased, and after treatment the level of CEA, NSE, CA125and CD8+ in the observation group was significantly lower than those of the control group;The levels of CD4+, CD4+/CD8+ and NK in the two groups after treatment were significantly higher than those in the group before treatment, and the observation group levels were significantly higher than those of the control group. Conclusion: Bronchial artery embolization combined with radioactive particle implantation for locally advanced non-small cell lung cancer, can effectively reduce the serum tumor markers level, improve the level of T cell subsets of patients, has important clinical value.

Characteristics of tumor microenvironment and novel immunotherapeutic strategies for non-small cell lung cancer

Immune checkpoint inhibitor-based immunotherapy has revolutionized the treatment approach of non-small cell lung cancer(NSCLC).Monoclonal antibodies against programmed cell death-1(PD-1)and PD-ligand 1(PD-L1)are widely used in clinical practice,but other antibodies that can circumvent innate and acquired resistance are bound to undergo preclinical and clinical studies.However,tumor cells can develop and facilitate the tolerogenic nature of the tumor microenvironment(TME),resulting in tumor progression.Therefore,the immune escape mechanisms exploited by growing lung cancer involve a fine interplay between all actors in the TME.A better understanding of the molecular biology of lung cancer and the cellular/molecular mechanisms involved in the crosstalk between lung cancer cells and immune cells in the TME could identify novel therapeutic weapons in the old war against lung cancer.This article discusses the role of TME in the progression of lung cancer and pinpoints possible advances and challenges of immunotherapy for NSCLC.

Clinical Application of Circulating Tumor Cells in Evaluating the Effect of Chemotherapy in Advanced Non-Small Cell Lung Cancer

Objective:To explore the value of circulating tumor cells in evaluating the effect of chemotherapy for advanced non-small cell lung cancer.Methods:Sixty-two patients with advanced non-small cell lung cancer who received chemotherapy in the Affiliated Hospital of Hebei University from January 2018 to December 2021 were selected as the research subjects.The positive rate of CTCs after two weeks of chemotherapy and four weeks of chemotherapy as well as the evaluation of imaging efficacy were observed and analyzed.Results:Based on the clinical data of the patients,the positive rate of CTCs in male patients was 77.78%,that in female patients was 80.77%,that in patients≥60 years old was 78.13%,that in patients<60 years old was 76.67%,that in squamous cell carcinoma was 79.31%,that in adenocarcinoma was 78.79%,and that in highly differentiated,moderately differentiated,and poorly differentiated+undifferentiated CTCs was 66.67%,84.21%,and 90.91%,respectively;there was no statistical difference in the general data.The positive rate of CTCs was 88.71%before chemotherapy and 66.13%after two weeks of chemotherapy,in which the difference was statistically significant;the positive rate of CTCs four weeks after chemotherapy was 59.68%,which was statistically significant compared with that before chemotherapy;however,there was no significant difference between two weeks after chemotherapy and four weeks after chemotherapy.After chemotherapy,35 patients had CR+PR,19 patients had SD,and 8 patients had PD.The proportions of CR+PR,SD,and PD in the imaging evaluation results were 56.45%,30.65%,and 12.90%,respectively.After kappa consistency test,it was found that the consistency was good.Conclusion:CTCs can be used as one of the indicators to evaluate the effect of chemotherapy for advanced non-small cell lung cancer.The results are consistent with those of imaging evaluation.The detection of CTCs can be widely used as one of the clinical indicators.

Implication of serum levels of interleukin-18 and nitric oxide in tumor growth and metastasis of non-small cell lung cancer

To study the effect of IL-18 and nitric oxide(NO) on the growth and metastasis of non-small cell lung cancer (NSCLC).Methods Serum IL-18 and nitrate and nitrite levels in 82 patients with NSCLC and 20 healthy control subjects were measured by using ELISA and Griess.Results The levels of serum IL-18 were (334.2±31.0)ng/L in NSCLC patients and (151.3±22.0)ng/L in control subjects,respectively.The levels of nitrate and nitrite were (237.1±21.0)μmol/L in NSCLC patients and (44.2±15.0)μmol/L in control subjects.The levels of serum IL-18 and nitrate and nitrite were not related with age,gender,histological types in patients with NSCLC.The levels of serum IL-18 was closely associated with TNM stage,lymph node metastasis and distal metastasis,but not with its degree and organ types of metastasis.There was a negative correlation between the levels of serum IL-18 and nitrate and nitrite.Conclusion Serum IL-18 and nitrate and nitrite levels may be useful to evaluate the prognosis of the patients with NSCLC.16 refs,2 tabs.

HYPERMETHYLATION OF p14^(ARF) PROMOTER REGION AND EXPRESION OF p14^(ARF) GENE PRODUCT IN NON-SMALL CELL LUNG CANCER

Objective： This study was designed to investigate promoter methylation status and protein expression of p14^ARF gene in non-small cell lung cancer, and value the role of p14^ARF promoter methylation in carcinogenesis of non-small cell lung cancer. Methods： Promoter methylation status and protein expression of p14^ARF gene in 40 cases of non-small cell lung cancer were analyzed by methylation specific polymerase china reaction （MSP）, restriction enzyme-related polymerase chain reaction （RE-PCR） and immunohistochemistry （IHC）. Results： The positive rates of p14^ARF promoter methylation in tumor tissues and normal tissues adjacent to cancer were 17.5% （7/40） and 2.5% （1/40） respectively. There were statistically significant differences between them, P〈0.05. The results of RE-PCR were consistent with that of MSP. The expression rate of p14^ARF protein in tumor tissues was significantly lower than that in normal tissues adjacent to cancer, p〈0.01. Promoter methylation status and protein expression of p14^ARF gene in non-small cell lung cancer showed significantly an inverse correlation （r=-0.56, P〈0.01）, and both of them did not relate statistically with the clinicopathologic characteristics of patients such as histological classification, clinical stage, differentiation grade and lymph node involvement. Conclusion： Promoter methylation is a crucial mechanism of inactivation of p14^ARF gene. Promoter methylation of p14^ARF gene might he involved in carcinogenesis of non-small cell lung cancer, and is an early event in development process of non-small cell lung cancer. It might be used as a new target in gene treatments in the future.

Coexisting opportunities and challenges:In which scenarios can minimal/measurable residual disease play a role in advanced non-small cell lung cancer?

Curative therapy was not previously available for patients with advanced non-small cell lung cancer(NSCLC);thus,the concept of minimal/measurable(or molecular)residual disease(MRD)was not applicable to these patients.However,advances in targeted and immunotherapy have revolutionized the treatment landscape for patients with advanced NSCLC,with emerging evidence of long-term survival and even the hope of complete remission(CR)by imaging examination.The latest research shows that patients with oligometastatic lung cancer can benefit from local treatment.After removing the lesions,the choice of follow-up therapy and monitoring of the lesions could remain uncertain.MRD plays a role in identifying early-stage NSCLC patients with high risks of recurrence and determining adjuvant therapy after radical treatment.In recent years,evidence has been accumulating regarding the use of circulating cell-free tumor DNA(ctDNA)to assess MRD in solid tumors.This study discussed the possible applications of ctDNA-based MRD monitoring in advanced NSCLC and described the current challenges and unresolved problems in the application of MRD in advanced NSCLC.

Early detection of circulating tumor DNA and successful treatment with osimertinib in thr790met-positive leptomeningeal metastatic lung cancer:A case report

BACKGROUND Patients diagnosed with non-small-cell lung cancer with activated epidermal growth factor receptor mutations are more likely to develop leptomeningeal(LM)metastasis than other types of lung cancers and have a poor prognosis.Early diagnosis and effective treatment of leptomeningeal carcinoma can improve the prognosis.CASE SUMMARY A 55-year-old female with a progressive headache and vomiting for one month was admitted to Peking University First Hospital.She was diagnosed with lung adenocarcinoma with osseous metastasis 10 months prior to admittance.epidermal growth factor receptor(EGFR)mutation was detected by genomic examination,so she was first treated with gefitinib for 10 months before acquiring resistance.Cell-free cerebrospinal fluid(CSF)circulating tumor DNA detection by next-generation sequencing was conducted and indicated the EGFR-Thr790Met mutation,while biopsy and cytology from the patient’s CSF and the first enhanced cranial magnetic resonance imaging(MRI)showed no positive findings.A month later,the enhanced MRI showed linear leptomeningeal enhancement,and the cytology and biochemical examination in CSF remained negative.Therefore,osimertinib(80 mg/d)was initiated as a second-line treatment,resulting in a good response within a month.CONCLUSION This report suggests clinical benefit of osimertinib in LM patients with positive detection of the EGFR-Thr790Met mutation in CSF and proposes that the positive findings of CSF circulating tumor DNA as a liquid biopsy technology based on the detection of cancer-associated gene mutations may appear earlier than the imaging and CSF findings and may thus be helpful for therapy.Moreover,the routine screening of chest CT with the novel coronavirus may provide unexpected benefits。

Effect of intensity modulated radiation therapy combined with paclitaxel+ endostar chemotherapy on serum malignant molecule levels in patients with locally advanced non-small cell lung cancer

Objective: To discuss the effect of intensity modulated radiation therapy combined with paclitaxel + endostar chemotherapy on serum malignant molecule levels in patients with locally advanced non-small cell lung cancer. Methods: Patients with locally advanced NSCLC who were treated in the hospital between February 2015 and January 2017 were collected and divided into control group (n=59) and research group (n=59) by random number table. Control group received the routine paclitaxel + endostar chemotherapy after the operation, and research group underwent intensity modulated radiation therapy combined with paclitaxel +endostar chemotherapy after the operation. The differences in serum levels of NSCLC-related tumor markers and angiogenesis indexes were compared between the two groups before and after treatment. Results: Before treatment, the differences in serum levels of NSCLC-related tumor markers and angiogenesis indexes were not statistically significant between the two groups. After treatment, serum TK1, CYFRA21-1, Pro-GRP, CEA, CA125 and SCC-Ag levels of research group were lower than those of control group;serum EGFR, COX-2, VEGF, HIF-1 and MMP-2 levels of research group were lower than those of control group. Conclusion:Postoperative intensity modulated radiation therapy combined with paclitaxel + endostar chemotherapy can effectively reduce the serum malignant molecule levels and optimize the illness in patients with local advanced NSCLC.

POST-OPERATIVE STAGING AND SURVIVAL BASED ON THE REVISED TNM STAGING SYSTEM FOR NON-SMALL CELL LUNG CANCER

Objective: To study the factors affecting post-operative staging and survival in non-small cell lung cancer (NSCLC) patients based on the revised TNM staging system adopted by the UICC in 1977. Methods: Data were collected from 1757 consecutively operated NSCLC patients, including those receiving complete tumor excision, tumor debulking and exploratory thoractomy from April 1969 through Dec. 1993. the end point of follow-up was Nov. 30, 1998. Cumulative survival and its influencing factors were analyzed by Kaplan-Meier and Cox model of SPSS software. Results: In this series, 30 patients (1.7%) were lost from follow-up. The 5-year cumulative survival was 88.0% for patients in stage I A, and 53.9% in stage IB, 33.5% in stage II, 14.7% in stage III A, 5.5% in stage IIIB and 7.0% in stage IV. The overall 5-year survival rate was 28.2%. The 5-year survivals were 39.8%, 14.4% and 4.2% in patients treated with completely tumor resection, tumor debulking and explorative thoractomy, respectively. The 10-year survival rate was 31.4%, 9.5% and 0, respectively. Factors affecting long-term cumulative survival, in the order of decreasing significance, were the type of operation, lymph node status, staging, size and pathological type of the primary tumor. Conclusion: the revised staging system for NSCLC is superior to that used since 1986 as far as the end results of treatment in patients in different stage and the staging specificity are concerned. The T3N1M0 classification and the definition of Ml need to be further studied.

Endostar combined GC in the treatment of advanced non-small cell lung cancer:a case report

A 43-year-old female with a 3-month history of paroxysmal irritating cough presented progressive chest tightness and shortness of breath.Laboratory data showed elevated carcino-embryonic antigen(CEA).Further imaging studies revealed a soft tissue mass shadow was in right middle lobe lung with mediastinal and sub-carinal lymph nodes enlarged.Biopsy diagnosis:moderately and poorly differentiated adenocarcinoma of the lung.Clinical diagnosis:central non-small cell lung cancer(NSCLC) of right middle lobe(CIVT4N2M1),lung adenocarcinoma G2-3,malignant pleural effusion,pericardial effusion,hilar and mediastina lymph node metastases.After 4 cycles of endostar plus GC therapy,imaging studies revealed showed soft tissue mass in right middle lobe disappeared,and evaluation of short-term result was complete remission(CR).PFS has been seven months till now.Therefore,this report provided strong evidence that endostatin combined GC treatment for advanced NSCLC is safe and effective,which can prolong survival and improve quality of life.

Role of imaging biomarkers in mutation-driven non-small cell lung cancer

Lung cancer remains the leading cause of cancer-related deaths worldwide.The treatment of non-small cell lung cancer(NSCLC),which accounts for a vast majority of lung cancers,has shifted to personalized,targeted therapy following discoveries of several targetable oncogenic mutations.Targeting of specific mutations has improved outcomes in many patients.This success has led to several target-specific agents replacing chemotherapy as first-line treatment in certain mutated NSCLC.Several researchers have reported that there may be imaging biomarkers that may be predictive of the presence of these mutations.These features,when present,have the potential in triaging patients into the most appropriate diagnostic and treatment algorithms.Distinct imaging features and patterns of metastases that have been associated with NSCLC with various targetable oncogenic mutations are presented in this review.

Histological transformation of non-small cell lung cancer:Clinical analysis of nine cases

BACKGROUND Histological transformation is one of the numerous mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors(EGFRTKIs).Given its rarity,the underlying transformational mechanisms,clinical features,and therapeutic prognoses are only studied through limited case reports.AIM To analyze the clinical characteristics and underlying mechanisms in non-small cell lung cancer(SCLC)patients with histological transformation after treatment with EGFR-TKIs.METHODS We retrospectively investigated nine patients diagnosed with non-SCLC transforming to SCLC,large-cell neuroendocrine carcinoma(LCNEC),or squamous cell carcinoma on re-biopsy after first-or third-generation EGFR-TKIs.RESULTS The median age of nine patients was 60 years.Among them,six patients had the EGFR 19del mutation,one had the L858R mutation,and one had wild-type EGFR.The level of plasma NSE was measured in six patients with SCLC or LCNEC transformation when transformation occurred,and five patients had elevated plasma NSE levels.All patients received standard chemotherapy after transformation with the exception of one patient who received chemotherapy and anlotinib.CONCLUSION Tumor re-biopsy should be performed routinely when EGFR-TKI therapy fails in lung cancer patients to avoid ignoring histological transformation and to select a subsequent therapeutic strategy.The transformed tumor retained the original EGFR mutation,indicating that histological transformation represents an evolution from the initial tumor.