Accuracy of endoscopic ultrasound-guided needle aspiration specimens for molecular diagnosis of non-small-cell lung carcinoma

BACKGROUND Endoscopic ultrasonography-guided fine-needle aspiration(EUS-FNA)and endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)are highly sensitive for diagnosing and staging lung cancer.In recent years,targeted therapy has shown great significance in the treatment of non-small cell lung carcinoma(NSCLC).Using these minimally invasive techniques to obtain specimens for molecular testing will provide patients with a more convenient diagnostic approach.AIM To evaluate the feasibility and accuracy of tissue samples obtained using EUSFNA and EBUS-TBNA for molecular diagnosis of NSCLC.METHODS A total of 83 patients with NSCLC underwent molecular testing using tissues obtained from EUS-FNA or EBUS-TBNA at the Tianjin Medical University Cancer Hospital from January 2017 to June 2019.All enrolled patients underwent chest computed tomography or positron emission tomography/computed tomography prior to puncture.We detected abnormal expression of EGFR,KRAS,MET,HER2,ROS1 and anaplastic lymphoma kinase protein.Two patients failed to complete molecular testing due to insufficient tumor tissue.The clinical features,puncture records,molecular testing results and targeted treatment in the remaining 81 patients were summarized.RESULTS In a total of 99 tissue samples obtained from 83 patients,molecular testing was successfully completed in 93 samples with a sample adequacy ratio of 93.9%(93/99).Biopsy samples from two patients failed to provide test results due to insufficient tumor tissue.In the remaining 81 patients,62 cases(76.5%)were found to have adenocarcinoma,11 cases(13.6%)had squamous cell carcinoma,3 cases(3.7%)had adenosquamous carcinoma and 5 cases(6.2%)had NSCLC-not otherwise specified.The results of molecular testing showed EGFR mutations in 21 cases(25.9%),KRAS mutations in 9 cases(11.1%),ROS-1 rearrangement in 1 case(1.2%)and anaplastic lymphoma kinase-positive in 5 cases(6.2%).Twentyfour patients with positive results received targeted therapy.The total effectiveness rate of targeted therapy was 66.7%(16/24),and the disease control rate was 83.3%(20/24).CONCLUSION Tissue samples obtained by EUS-FNA or EBUS-TBNA are feasible for the molecular diagnosis of NSCLC and can provide reliable evidence for clinical diagnosis and treatment.

Glabridin and Anti-Non-Muscle Myosin IIA Therapy Disrupts Non-Small Cell Lung Carcinoma Motility

Lung cancer is the leading cause of cancer related death in the United States killing over 130,000 people each year. While a combination of chemo and radiation therapy may be effective, surgery is still required for many patients. Without surgery, the disease may progress and lead to metastases. We sought to determine if treatment with anti-non-muscle myosin IIA antibody would inhibit movement of the cells in the presence and absence of glabridin (an isoflavonoid compound shown to inhibit cell migration by inhibiting myosin). We compared inhibition by glabridin to that of an anti-non-muscle myosin IIA antibody and a combination therapy of both at 12 and 24 hours post wound creation. Cells that took up the anti-non-muscle myosin IIA antibody were greatly inhibited in motility and exhibited no significant change in wound healing. Glabridin treatment resulted in a dramatic increase in wound size within 12 hours and regeneration within 24 hours. The greatest decrease in motility was observed in cells treated with the combination of both glabridin and anti-non-muscle myosin IIA antibody. By 24 hrs, cell migration had halted due to death of the cells resulting from this combination. Further testing needs to be done to determine a safe mode of delivery of the combination therapy to ensure only local distribution. Controlled release drug delivery depot systems have been used as a means to provide local release of drugs intra-tumorally or adjacent to the cancerous tissue after surgical resection and have great potential.

EGFR mutation identifies distant squamous cell carcinoma as metastasis from lung adenocarcinoma

Lung cancer metastasis is typically determined by histologic similarity between distant and primary lesions. Herein, we present a 70-year-old Japanese woman with an adenocarcinoma in her lung and a squamous cell carcinoma in her femur; both tumors had an identical epidermal growth factor receptor mutation, G719 S. This indicated that both tumors had a common origin, despite their histologic dissimilarity. The tumor in the femur was thus identified genetically as a lung cancer metastasis. This case suggests that genetic analysis can determine whether a distant lesion is a lung cancermetastasis, particularly when the histology differs from that of the primary lesion.

Quantitative analysis of butyric acid-induced nuclear ultrastructural alterations in cells of human lung giant cell carcinoma in vitro

The effects of butyric acid(BA)on the nuclear ultrastructure of humanlung giant cell carcinoma(Strain PLA-801 D)were observed with digital imageprocessing.It was found that the length of the nuclear circumference of the tu-mor cells incubated with 2mmol of BA was approximately equal to that of thecontrol whereas the nuclear area was increased by 1.4times,which implies thatthe nuclear profile tends to become more regular after BA treatment.In addition,the optical density of the nuclei of the experimental group decreased significantlyas compared with that of the control,which indicates that the chromatin in thenuclei was decreased by BA.It was concluded on the basis of the findings thatBA may have a biological effect of reverse-transformation on the malignant cells.

The ^(18)F-FDG uptake in non small cell lung carcinoma correlates with the DNA-grading of malignancy

In order to evaluate correlation of glucose metabolism and DNA ploidity of tumors, the uptake of 18F-Deoxyglucose (FDG) by PET prior to surgery and the DNA cotent and DNA-grading of malignancy (DNA-MG) of Schiff-stained nuclei obtained from fresh tumor fragments by means of image cytometry were studied, and thereafter the correlation between standardized uptake value (SUV) and (DNA-MG) was analysed in forty-nine patients with histologically proven non-small cell lung carcinoma (NSCLC). As a result of the DNA histograms of these 49 patients, 46 (93.88%) were aneuploid and only 3(6.12%) were tetraploid. A linear correlation of the SUV versus the (DNA-MG) (r=0.336, p=0.024) was found, demonstrating that 18F-FDG PET as a non-invasive metabolic imaging technique, may also provide inforrnation correlated to malignant DNA patterns which may be valuable in malignant differentiation and prognostic prediction.

Gli1 promotes epithelial-mesenchymal transition and metastasis of non-small cell lung carcinoma by regulating snail transcriptional activity and stability

Metastasis is crucial for the mortality of non-small cell lung carcinoma(NSCLC) patients.The epithelial-mesenchymal transition(EMT) plays a critical role in regulating tumor metastasis.Glioma-associated oncogene 1(Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein,we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.

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.

Adenocarcinoma transformed into squamous cell carcinoma in non-small cell lung cancer

Non-small cell lung cancer(NSCLC)is the most common form of lung cancer which remains the deadliest malignancy worldwide(Siegel et al.,2019).In general,NSCLC can be divided into several subtypes,including adenocarcinoma(ADC),squamous cell carcinoma(SCC),adeno-squamous cell carcinoma(AD-SCC)and large cell carcinoma(LCC).

Study of the impact of CT/CT image fusion radiotherapy on V_(20) and radiation pneumonitis of non-small cell lung cancer

Objective:The aim of our study was to investigate the value of CT/CT image fusion radiation treatment planning in non-small cell lung cancer(NSCLC) and the impact on V20 and radiation pneumonitis(RP).Methods:Patients who were pathologically or cytologically diagnosed of stage IIIA and IIIB NSCLC were treated with three-dimensional conformal radiation therapy(4000 cGy).Forty patients got at least 25% tumor reduction were randomly divided into two groups:group A of regular shrink field radiotherapy(20 cases) and group B of CT/CT image fused shrink field radiotherapy(20 cases).Dosage reached 6600 cGy.Clinical data,V20 and RP were observed within 3 months after radiotherapy.Statistical analysis was conducted for the NSCLC patients.Results:22.5%(9/40) patients got RP during follow-up.Group A accounted for 6 cases(30%),and group B had 3 cases(15%).There was no marked difference between the two groups(P = 0.256),univariate analysis revealed that the IV20 of A and B groups,and IV20 and CV20 of all patients were statistically related to the incidence of RP(P < 0.05).With Wilcoxon method assay,the ipsilateral lung V20 and contralateral lung V20 had statistical significance between the two groups(P < 0.05).Conclusion:The CT/CT image infusion treatment planning could increase the radical dosage with better tumor control probability but won't increase adverse reaction.

Nedaplatin/Gemcitabine Versus Carboplatin/Gemcitabine in Treatment of Advanced Non-small Cell Lung Cancer: A Randomized Clinical Trial

Objective： To evaluate the efficacy and safety of nedaplatin/gemcitabine （NG） and carboplatin/gemcitabine （CG） in the management of untreated advanced non-small cell lung cancer （NSCLC）. Methods： Sixty-two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm （n=30） and the CG arm （n=32）. Only patients （24 and 25 in the NG and CG arms, respectively） who completed 〉2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate （ORR）. The secondary outcome measures included progression-free survival （PFS）, overall survival （OS） and adverse events. Results： There were no statistically significant differences in the efficacy measures （ORR, P=0.305; median PFS, P=0.298, median OS, P=0.961） or in the major adverse events （grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.222） between the two treatment arms. However, there was a trend towards higher ORR （37.5% vs. 24.0%）, longer PFS （6.0 vs. 5.0 months）, and less adverse events in the NG arm. Conclusion： NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.

Proportion and clinical features of never-smokers with non-small cell lung cancer

Background: The proportion of never?smokers with non?small cell lung cancer(NSCLC) is increasing, but that in Korea has not been well addressed in a large population. We aimed to evaluate the proportion and clinical features of never?smokers with NSCLC in a large single institution.Methods: We analyzed clinical data of 1860 consecutive patients who were newly diagnosed with NSCLC between June 2011 and December 2014.Results: Of the 1860 NSCLC patients, 707(38.0%) were never?smokers. The proportions of women(83.7% vs. 5.6%) and adenocarcinoma(89.8% vs. 44.9%) were higher among never?smokers than among ever?smokers. Significantly more never?smokers were diagnosed at a younger median age(65 vs. 68 years, P < 0.001) and earlier stage(stage I–II, 44.5% vs. 38.9%, P < 0.001) a= 0.015) compared with ever?smokers. Epidermal growth factor receptor mutations(57.8% vs. 24.4%, Pnd anaplastic lymphoma kinase rearrangements(7.8% vs. 2.8%, P < 0.001) were more common in never?smokers, whereas Kirsten rat sarcoma viral oncogene homolog mutations(5.8% vs. 9.6%, P ntly encountered in never?smokers than in ever?smokers. Never?smokers showed longer su= 0.021) were less frequervival after adjust?ing for the favorable effects of younger age, female sex, adenocarcinoma histology, better performance status, early stage disease, being asymptomatic at diagnosis, received antitumor treatment, and the presence of driver mutations(hazard ratio, 0.624; 95% confidence interval, 0.460–0.848; P = 0.003).Conclusions: More than one?third of the Korean patients with NSCLC were never?smokers. NSCLC in never?smokers had different clinical characteristics and major driver mutations and resulted in longer overall survival compared with NSCLC in ever?smokers.

Current treatment landscape for oligometastatic non-small cell lung cancer

The management of patients with advanced non-small cell lung carcinoma(NSCLC)has undergone major changes in recent years.On the one hand,improved sensitivity of diagnostic tests,both radiological and endoscopic,has altered the way patients are staged.On the other hand,the arrival of new drugs with antitumoral activity,such as targeted therapies or immunotherapy,has changed the prognosis of patients,improving disease control and prolonging survival.Finally,the development of radiotherapy and surgical and interventional radiology techniques means that radical ablative treatments can be performed on metastases in any location in the body.All of these advances have impacted the treatment of patients with advanced lung cancer,especially in a subgroup of these patients in which all of these treatment modalities converge.This poses a challenge for physicians who must decide upon the best treatment strategy for each patient,without solid evidence for one optimal mode of treatment in this patient population.The aim of this article is to review,from a practical and multidisciplinary perspective,published evidence on the management of oligometastatic NSCLC patients.We evaluate the different alternatives for radical ablative treatments,the role of primary tumor resection or radiation,the impact of systemic treatments,and the therapeutic sequence.In short,the present document aims to provide clinicians with a practical guide for the treatment of oligometastatic patients in routine clinical practice.

Application of non-small cell lung cancer pleural effusion cell blocks in molecular pathological detection

Objective: The tumor tissues used in molecular pathological detection were usually obtained by surgery, which would cause trauma and may not be suitable for the terminal cancer patients. This paper evaluated the value of the non-small cell lung cancer(NSCLC) pleural effusion cell blocks as tumor tissues replacement materials in the application of molecular pathological detection. Methods: Tumor cells were made into cell blocks through stratified centrifugal from 30 NSCLC patients with the pleural effusion. The immunohistochemistry, fluorescence in situ hybridization(FISH) and gene sequencing methods were employed in our experiments. Results: The tumor cells of cell block section were rich and could keep part of histological structure. Immunohistochemistry staining could assist diagnosis and tumor parting. Epidermal growth factor receptor(EGFR) FISH-positive was found in 33.33% of the group, high polysomy in 6 cases, amplification in 4 cases. EGFR gene mutations were found in 8 cases of 30 samples, with an incidence of 26.67%, 6 cases were detected in the exon 19, and 2 cases were detected in the exon 21. Conclusion: The NSCLC pleural effusion cell blocks are useful for the diagnosis and determining the primary source of tumor, instructed targeted therapy.

Role of positron emission tomography-computed tomography in non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small cell carcinoma and small cell carcinoma are the main histological subtypes and constitutes around 85% and 15% of all lung cancer respectively. Multimodality treatment plays a key role in the successful management of lung cancer depending upon the histological subtype, stage of disease, and performance status. Imaging modalities play an important role in the diagnosis and accurate staging of the disease, in assessing the response to neoadjuvant therapy, and in the follow-up of the patients. Last decade has witnessed voluminous upsurge in the use of positron emission tomography-computed tomography(PET-CT); role of PET-CT has widened exponentially in the management of lung cancer. The present article reviews the role of 18-fluoro-deoxyglucose PET-CT in the management of non small cell lung cancer with emphasis on staging of the disease and the assessment of response to neoadjuvant therapy based on available literature.

Therapeutic guidance of tumor mutation burden on immune checkpoint inhibitors in advanced non-small cell lung cancer:a systematic review and comprehensive meta-analysis

Background:Tumor mutation burden(TMB)remains a promising but ambiguous predictive biomarker for the efficacy of immune checkpoint inhibitors(ICIs).We investigated the predictive value of TMB in patients with advanced non-small cell lung cancer(NSCLC)treated by ICI-containing therapies under strictly matched clinical settings.Methods:PubMed,Embase,Cochrane Central,ClinicalTrials.gov,and bioRxiv databases were searched till October 16,2021.All randomized controlled trials(RCTs)that compared patients with high TMB(TMB-H)and low TMB(TMB-L)and provided hazard ratio(HR)and corresponding 95%confidence interval(CI)in advanced NSCLC patients receiving ICIs were included,and mirror-based meta-analysis was performed(Part1).Bayesian network meta-analysis was conducted to investigate the efficacy of distinct first-line regimens in TMB-H and TMB-L groups(Part2).Public cohorts were used for validation and further exploration(Part3).Results:Twelve RCTs(n=5527)and 5 public cohorts(n=573)were included.In Part1,TMB-H patients generally exhibited a more significant progression-free survival(PFS)benefit from ICI-containing therapies compared to TMB-L patients(HR=0.58,95%CI:0.49-0.67,P<0.0001).In Part2,anti-PD-1 plus chemotherapy ranked best for PFS in both TMB-H and TMB-L groups.Anti-PD-L1 plus anti-CTLA-4 therapies indicated better PFS and overall survival(OS)benefit than single ICI and chemotherapy in the TMB-H group,but ranked worst in the TMB-L group.Finally,TMB was validated to be an independent predictive biomarker from programmed cell death-ligand 1(PD-L1)expression in Part3,which could further distinguish beneficiaries of ICI-containing therapies with PD-L1<50%.Conclusion:TMB-H could be a predictive biomarker independent of PD-L1 expression to identify beneficiaries of ICI-containing therapy in advanced NSCLC patients.

CLINICAL EFFICACY OF VINORELBINE PLUS CISPLATIN IN ADVANCED NON-SMALL CELL LUNG CANCER

A clinical study of the efficacy of vinorelbine plus cisplatin regimen in the management of advanced NSCLC was performed in 35 patients. Five of the 35 patients failed to finish one cycle of chemotherapy with this regimen because of severe and intractable leukopenia or rapid progress of the disease. Tumor response and toxicity were evaluated in the remaining 30 cases. Results showed that, with this regimen, the objective response rate (CR+PR) was 46.7%. The most common toxicity was leukopenia; other side effects included alopecia, gastrointestinal reactions, slight and transient renal and hepatic impairment and peripheral neuropathy. It suggested that vinorelbine plus cisplatin is a safe and effective regimen in the management of advanced NSCLC.

Clinical pathology of nodal micrometasteses in non-small cell lung cancer

Objective： To explore whether the conventional pathologic stages of some non-small cell lung cancer （NSCLC） patients were underestimated. Methods： 195 lymph node samples were taken from 25 NSCLC patients during the operations. Firstly, each resulting tissue block was processed for routine paraffin embedding. Then the 6- 10 serial sections were chosen, each 5/am thick, from every paraffin block of the lymph node. Finally, the first and the second last sections of each lymph node were stained by hematoxylin eosin （HE）, and the other serial sections were used for the immunohistochemical （IHC） staining examination with the monoclonal antibody against cyokeratin 19. Results： With HE staining, 30 of the 195 regional lymph nodes revealed dominant nodal metastases, and none showed micrometastases. IHC staining was performed on 135 lymph nodes that were identified as free of metastases by HE staining, 31 showed micrometastases; none showed gross nodal metastases. There was a significant difference between HE staining staging and IHC staining staging （P〈0.05）. Conclusion： Conventional HE staining can accurately detect gross nodal metastases in the lymph nodes of NSCLC patients, but is unfit for detecting lymph nodal micrometastases. IHC staining analysis can significantly facilitate the detection of occult micrometastatic tumor cells in lymph nodes, and its assessment of nodal micrometastases can provide a refinement of TNM stage for NSCLC patients. Our results provide a rationale for extensive lymph nodes sampling

Intraoperative photodynamic therapy for tracheal mass in non-small cell lung cancer:A case report

BACKGROUND Tracheal neoplasms represent less than 0.1%of all malignancies and have no established treatment guidelines.Surgical resection with reconstruction is the primary treatment.This study demonstrates successful treatment of concurrent lung and tracheal tumors using surgical excision and intraoperative photodynamic therapy(PDT),highlighting the effectiveness and safety of this approach.CASE SUMMARY A 74-year-old male with a history of smoking and chronic obstructive pulmonary disease was diagnosed with tracheal squamous cell carcinoma and right lower lobe adenocarcinoma.A multidisciplinary team created a treatment plan involving tumor resection and PDT.The tracheal tumor was removed through a tracheal incision and this was followed by intraluminal PDT.The trachea was repaired and a right lower lobectomy was performed.The patient received a second PDT treatment postoperatively and was discharged 10 d after the tracheal surgery,without complications.He then underwent platinum-based chemotherapy for lymphovascular invasion of lung cancer.Three-month postoperative bronchoscopy revealed normal tracheal mucosa with a scar at the resection site and no evidence of tumor recurrence in the trachea or lung.CONCLUSION Our case of concurrent tracheal and lung cancers was successfully treated with surgical excision and intraoperative PDT which proved safe and effective in this patient.

Favorable response of primary pulmonary lymphoepithelioma-like carcinoma to sintilimab combined with chemotherapy: A case report

BACKGROUND There is no established treatment for primary pulmonary lymphoepithelioma-like carcinoma(LELC)until now.CASE SUMMARY In this study,the patient responded well to sintilimab combined with paclitaxel and carboplatin,showing no obvious side effects.Meantime,the values of carbohydrate antigen 15-3(CA15-3)and carbohydrate antigen 72-4(CA72-4)gradually returned to normal.CONCLUSION Immunotherapy combined with chemotherapy in advanced-stage LELC may be more effective than immunotherapy or chemotherapy alone.CA15-3 and CA72-4 are biomarkers for evaluating therapeutic effects for LELC.

Initial outcome of induction chemotherapy followed by radiotherapy and concurrent weekly paclitaxel for stage Ⅲ non-small cell lung cancer

Objective： The aim of our study was to evaluate the toxicity and efficacy of induction chemotherapy （ICT） followed by three-dimensional conformal radiotherapy （3D CRT） and concurrent weekly paclitaxel on unresectable non-small cell lung cancer （NSCLC）. Methods： Stage III NSCLC patients with favorable conditions were treated with 2 to 4 cycles of carboplatin （AUC = 5-6, dl） combined with paclitaxel （175 mg/m〈 dl）, then followed by weekly paclitaxel （40 mg/m2） and concurrent 3D CRT within 3-4 weeks. The prescription dose was given as high as possible under the condition that V20 〈 31% and spinal cord dose 〈 50 Gy. Results： Thirty-one patients were enrolled. ICT was well tolerated. During the concurrent chemoradiotherapy, the treatment of 3 patients was ended ahead of the schedule because of severe pulmonary and heart toxicities; the treatment of 2 patients was delayed for 7 and 12 days because of fatigue. Myelosuppression was mild （16/31）： all were grade 1-2 except 1 was grade 3. Lymphocytopenia was more obvious （29/31, grade 3 in 21）. Three patients developed grade 3 radiation-induced esophagitis, and 2 developed grades 3-4 radiation-induced pneumonitis. Two developed grade 3 esophageal stricture. No grades 3-4 pulmonary fibrosis was observed. The overall response rate was 74.1%. The 1-, 2-, 3-year overall survival rates were 74.2%, 41.9%, and 34.6%, respectively, with the median survival time of 18.5 months. The 1-, 2-, 3-year local progression-freely survival rates were 64.5%, 32.3%, and 20.5%, respectively, with the median local progression-freely survival time of 14.3 months. Conclusion： The program of ICT followed by weekly paclitaxel and 3D CRT is accomplished in most of the favorable stage III NSCLC patients. The toxicity is tolerable, and the response rate is inspiriting.