Synchronous multiple lung cancers with hilar lymph node metastasis of small cell carcinoma:A case report

BACKGROUND Synchronous multiple lung cancers are rare and refer to the simultaneous presence of two or more primary lung tumors,which present significant challenges in terms of diagnosis and treatment.CASE SUMMARY We report a case of multiple synchronous lung cancers with hilar lymph node metastasis of small cell carcinoma of unknown origin in a 73-year-old man.Transbronchial lung biopsy revealed squamous cell carcinoma.Although enlargement of lymph node 12u was detected,no distant metastases were observed.The patient was preoperatively diagnosed with T1cN0M0 and underwent thoracoscopic right upper lobectomy with nodal dissection(ND2a).Based on histopathological findings,the primary lesion was squamous cell carcinoma.A microinvasive adenocarcinoma was also observed on the cranial side of the primary lesion.Tumors were detected in two resected lymph nodes(#12u and#11s).Both tumors were pathologically diagnosed as small cell carcinomas.The primary lesion of the small cell carcinoma could not be identified even by whole-body imaging;however,chemotherapy was initiated for hilar lymph node metastasis of the small cell carcinoma of unknown origin.CONCLUSION Multiple synchronous lung cancers can be accompanied by hilar lymph node metastasis of small cell carcinomas of unknown origin.

Hepatoid adenocarcinoma of the lung:A case report

BACKGROUND Hepatoid adenocarcinoma of the lung(HAL)is a rare type of non-small cell lung cancer(NSCLC),histologically similar to hepatocellular carcinoma.HAL has high malignancy and poor prognosis,and a better treatment plan needs further study.CASE SUMMARY In order to deeply understand the occurrence and development of HAL,here we report a case of HAL with extensive metastasis of alpha fetoprotein negative KRAS A146T mutation.The patient refused chemotherapy and received one course of treatment(immune checkpoint inhibitors),and died three months later due to progressive disease.CONCLUSION HAL is a special type of NSCLC.The surgical treatment of HAL in the limited stage can achieve long-term survival,but most of them were in the advanced stage when they were found,and the prognosis was poor,which requires multidisciplinary comprehensive treatment.

Hypofractionated Radiotherapy for Stage I Non-small Cell Lung Carcinoma in Patients Aged 75 Years and Older

Purpose: We report our single-institution experience using hypofractionated radiotherapy in a patient population 75 years and older diagnosed with stage IA or IB (T1/T2 N0) Non-Small Cell Lung Carcinoma. Materials and methods: This is a single-institution, retrospective analysis examining disease free and overall survival and toxicity after hypofractionated radiation therapy in a patient population 75 years and older diagnosed with stage IA or IB (T1/T2 N0) NSCLC. Between 1991 and 2005, a total of 33 such patients were identified with a median age of 79 years. Patients were treated with a median total dose of 7000 cGy using median daily dose fractions of 250 cGy. Analysis of competing risks (local failure, distal failure or death as the first event) was performed and cumulative incidence functions (CIF) were estimated. Results: The median length of follow-up was 19.8 months (range: 4.3 - 103.8 months). Of the 33 patients treated, 21 (63.6% of total) had no evidence of disease recurrence on follow-up imaging over the course of the study. Of the 12 patients with disease recurrence, 6 (18.2% of total) had local failure as the first event and 6 (18.2% of total) had distant metastasis as the first event. Analysis of competing risks showed that at 5 years, the probability of local failure as the first detected event was 19.5% (95%CI: 7.6%, 35.6%);the probability of distal failure as the first detected event was 21.5% (95%CI: 7.9%,39.4%);and the probability of death without recording a failure was 44.1% (95%CI: 26.1%, 60.7%). There were no treatment related deaths reported. Conclusions: Elderly patients diagnosed with stage I non-small cell lung cancer may safely be offered hypofractionated radiotherapy as an effective option with curative intent.

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.

Primary pulmonary lymphoepithelioma-like carcinoma misdiagnosed as lung squamous cell carcinoma:A case report

BACKGROUND Primary pulmonary lymphoepithelioma-like carcinoma(PPLELC)is an uncommon subtype of squamous cell carcinoma(SCC)of the lung,closely associated with Epstein-Barr virus(EBV)infection.The pathological features of PPLELC closely resemble those of SCC,which makes it prone to misdiagnosis.Surgical intervention constitutes the primary treatment approach for PPLELC.CASE SUMMARY This report describes a 44-year-old woman who was hospitalized for 1 mo due to left chest pain.Computed tomography revealed a mass shadow in the anterior basal segment of the left lower lobe,and a subsequent needle biopsy suggested SCC.The patient underwent radical tumor resection in the lower left lobe of the lung,and postoperative pathological examination indicated lymphoepithelial carcinoma,and the test for EBV encoded small RNA was positive.Following surgery,the patient was scheduled to receive four cycles of adjuvant chemotherapy,using the paclitaxel+carboplatin regimen,but the patient refused further treatment.CONCLUSION PPLELC is an exceptionally rare subtype of lung SCC and is prone to misdiagnosis.

Molecularly targeted therapies for advanced or metastatic non-small-cell lung carcinoma

Non-small-cell lung cancer(NSCLC)remains the leading cause of cancer-related death in both men and women in the United States.Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease.Improvements in overall survival and quality of life have been modest.Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics,thus changing the treatment paradigm for many NSCLC patients.In this review,we present a summary of many of the currently investigated biologic targets in NSCLC,discuss their current clinical trial status,and also discuss the potential for development of other targeted agents.

AN IMMUNOHISTOCHEMICAL STUDY OF OCCULT MICRO- METASTASES IN REGIONAL LYMPH NODES OF 94 PATIENTS WITH STAGE I NON-SMALL CELL LUNG CARCINOMA

In the study, 739 regional lymph nodes from 94 patients with stage I non- small cell lung carcinoma (NSCLC) were studied by immunohistochemical techniques. These lymph nodes contained no metastatic tumor as assessed by conventional histopatholgy were recut. A series of consecutive sections from the original blocks were immunostained with poly-and monoclonal antibodies to cytokeratins, carcinoembryonic antigen (CEA), and human milk fat globulin membrane antigen (HMFG-2). Single tumor cells or small clusters of tumor cells, not visible on routine examination, were readily detected. The actual number of lymph nodes that contained occult tumor cells was 123 (16.6%) from 53 patients (56.4%). The majority of 102 immunostalned positive nodes were distributed in the hllar (29% ) and peribronchlal (25%) regions. Our data indicate that (1) a series of consecutive sections and immunohistochemistry may greatly Increase the diagnostic yield of occult micrometastases in lymph nodes; (2) the high incidence of occult metastases in NSCLC may be of Importance in relation to their rapid dissemination and high death rates; (3) the high frequencyof occult nodal metastases in NSCLC raises questions in regard to our presently used criteria for staging, prognosis and treatment of ostensibly stage I disease; and (4) perhaps dissections of hllar and peribronchlal nodes will have an Importantly clinical significance in prevention of wide dissemination of tumor cells.

Two Molecular Markers of Early Non-Small Cell Lung Carcinoma Based on Gene Expression in Peripheral Blood

Background: Lung cancer is among the most common cancers. Search is ongoing to find biomarkers to improve the diagnosis lung cancer techniques in early stages. In this study we evaluate the sensitivity and specificity of the MUC1 and CEA gene expressions in the peripheral blood of non-small cell lung cancer (NSCLC). Material and Methods: This study was done in Masih Daneshvari Hospital, Tehran, Iran and was case/control study that conducted on 30 NSCLC patients and 30 healthy controls. Peripheral blood was collected and total RNA was extracted then cDNA was synthesized. Sample was separately assessed by real time PCR. Results: The expression of CEA gen was positive in 24 patients indicating 80% sensitivity for this marker. The expression of CEA gen was positive in 9 controls out of 30 each. A statistically significant difference was detected between patients and healthy controls with regard to CEA mRNA expression (P 0.001). The MUC1 gen expressed in 20 out of 30 patients, while it expressed in 3 controls. The difference in MUC1 mRNA expression was statistically significant between NSCLC patients and healthy controls (P 0.001). Conclusion: MUC1 and CEA are molecular biomarkers with relatively favorable sensitivity for primary diagnosis of NSCLC.

Effect of miR-375 on non-small cell lung carcinoma invasion,migration,and proliferation through the CIP2A pathway

Lung cancer is one of the malignant tumors with the fastest increase in morbidity and mortality and the greatest threat to people’s health and life.Worldwide,lung cancer is the leading cause of cancer death in men and the second leading cause of cancer deaths in women[1].Lung cancer is divided into two major groups,small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC)[2].SCLC accounts for approximately 20%of lung cancers.It has a high degree of malignancy and early metastasis,and is sensitive to chemotherapy and radiotherapy.The initial remission rate is high,but it is prone to secondary drug resistance and relapse.Chemotherapy is the mainstay.NSCLC includes three major histological subtypes,lung squamous cell carcinoma(SCC),lung adenocarcinoma(ADC),and large cell lung cancer(LCLC),accounting for approximately 80%of lung cancers.Cell division is slower,and the diffusion shift is relatively late[3].Nevertheless,while current research on the biological characteristics of different histological subtypes of NSCLC is expanding,its basic molecular mechanism is not yet clear.For example,smoking is more risky for SCC than ADC[4].Micro-RNA is an endogenous small RNA with a length of approximately 19–25 nucleotides.As a short non-coding RNA,its main function is to regulate the expression level of mRNA.miRNAs can be used as proto-oncogenes or tumor suppressors,and participate in various processes including proliferation,apoptosis,metabolism,and differentiation of cells through targeted binding to different transcripts[5].miRNAs are expressed in specific tissue and developmental stages under normal physiological conditions,but abnormal expression of miRNAs can lead to a series of pathological states,such as tumorigenesis and metastasis[6–7].miRNA regulates the function of tumor cells by regulating the expression of functional proteins.For example,miR-206 promotes breast cancer proliferation by inhibiting estrogen receptor alpha(ERα)while miR-34a downregulates E2 factor transcription factor 2(E2F2)expression to regulate the cell cycle and apoptosis[8–9].CIP2A,as an oncogenic protein during the malignant transformation and progression of cancer cells,has been shown to have a certain relationship with the efficacy of many drugs in cancer treatment.Oncoprotein CIP2A,also known as KIAA1524 or P90,was named in 2007 and is a cancerous inhibitor of PP2A due to its effect on cancer cells.The stability of PP2A and MYC is controlled to form a"carcinogenic connection"[10].In this study,we found that miR-375 regulated the expression of downstream protein kinase B(AKT),MYC,p-AKT and other related proteins through the CIP2A/PP2A signaling pathway,inhibiting the cancer phenotype of lung cancer,and affecting cell invasion,proliferation,apoptosis,and the cell morphology process.We found that the CIP2A gene is a direct binding target of miR-375.Thus,it has become a topic of great interest to explore whether and how miR-375 regulates ADC cells through the CIP2A signaling pathway.By up-regulating miR-375 in a lentivirus-transfected A549 cell line,we found that a series of phenotypes,including cell invasion,proliferation,and apoptosis were changed,and that CIP2A and its downstream signaling proteins were also changed.

Efficacy and Safety of Primary Radiotherapy in Combination with EGFR-TKIs for Non-Small Cell Lung Cancer Harboring EGFR Mutation

Objective: To evaluate the efficacy and safety of EGFR-TKI with the radiotherapy in EGFR mutant metastatic NSCLC. Methods: Retrospective analysis of 72 patients with stage IV lung cancer with EGFR-sensitive mutation. Patients in the A group were treated with the first-generation EGFR-TKI (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) combined with radiotherapy for primary tumors (34 cases). The B group was treated with the first-generation EGFR-TKI alone until the disease progressed (38 cases). PFS, OS, pulmonary infection and hematological toxicity during treatment were commented in both groups. Results: The objective remission rate was 47.1% (16/34) in the A group and 21.1% (8/38) in the B group. There was a significant difference between the two groups. There was no significant difference in hematological toxicity between the A group and the B group. There were 10 patients (29.4%) with degree II pulmonary infection in the A group and 3 patients (7.9%) in the B group. The difference between the two groups was statistically significant, suggesting that the incidence of pneumonia in the A group was higher than that in the B group. The median PFS (Progression-Free Survival)) and OS (Overall Survival) of the A group were significantly longer than those of the B group (16.5 months vs 9 months) and the median OS (36 months vs 19 months). The PFS and OS in the A group were significantly longer than those in the B group. Conclusion: EGFR-TKI combined with primary radiotherapy can significantly prolong the drug resistance time of EGFR mutant metastatic NSCLC.

A Case Report of a Rare Sarcomatoid Poorly Differentiated Adenocarcinoma Harboring Concurrent Mutations in the ROS1, EGFR, ARID1A, and NFKBIA Genes in the Lung

ROS1 and EGFR are primary oncogenic drivers in non-small cell lung cancer (NSCLC) pathogenesis. However, EGFR mutations and ROS1 fusions are generally mutually exclusive in NSCLC, leading to a negligible probability of their co-occurrence. Consequently, clinical data and treatment strategies for their simultaneous presence are remarkably scarce. This report details the first recorded case of a sarcomatoid, poorly differentiated lung adenocarcinoma harboring both a ROS1 fusion and an EGFR mutation, alongside ARID1A and NFKBIA gene mutations. Moreover, this case study encompasses a review of instances featuring concurrent ROS1 and EGFR mutations. The identified genetic alterations in ROS1, EGFR, ARID1A, and NFKBIA are pivotal in the etiology of NSCLC. These mutations significantly influence disease progression and are essential for the development of personalized therapeutic approaches. Recognizing the unique genetic profiles in patients permits healthcare providers to devise customized treatment regimens that target these specific mutations, thereby enhancing patient outcomes in NSCLC.

Alectinib-Induced Immune Hemolytic Anemia in a Patient with Lung Adenocarcinoma: Case Report and Literature Review

Alectinib is a selective Anaplastic Lymphoma Kinase (ALK) tyrosine kinase inhibitor used as standard therapy for ALK-rearranged lung adenocarcinoma. Hemolytic anemia is considered a rare but significant adverse event of alectinib. Here, we report the case of a 78-year-old female with advanced ALK rearrangement-positive lung adenocarcinoma who developed grade 4 drug-induced hemolytic anemia after receiving alectinib as first-line therapy. We discontinued alectinib treatment and switched to brigatinib. As a result, anemia improved without recurrence of lung adenocarcinoma over one year.

Expressions of FEZ1 and Survivin, and their significance in small cell lung cancer and squamous cell lung carcinoma

Objective： To detect the expressions of FEZ1 and Survivin in small cell lung cancer （SOLO） and poorly differentiated squamous cell carcinoma （PDSCC）, and to approach a theoretical basis for clinical diagnosis and treatment. Methods： Immunohistochemical and flow cytometry method were used to detect the expressions of FEZ1 and Survivin. Apoptosis ratio and cell proliferation index in normal lung tissue, SCLC and PDSCC were analyzed. Results： The expressions of FEZ1 and Survivin were significantly different between SCLC and PDSCC （P 〈 0.05）. The apoptosis ratio and proliferation index of normal lung tissue were lower than those of PDSCC and SOLO, with a significant difference （P 〈 0.05）. Conclusion： The expressions of FEZ1 and Survivin are significantly different between SCLC and PDSCC, indicating that detecting the expressions of the two indexes may be helpful for clinical diagnosis.

Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

Enhanced recovery after surgery in elderly patients with non-small cell lung cancer who underwent video-assisted thoracic surgery

BACKGROUND This study was designed to investigate the clinical outcomes of enhanced recovery after surgery(ERAS)in the perioperative period in elderly patients with nonsmall cell lung cancer(NSCLC).AIM To investigate the potential enhancement of video-assisted thoracic surgery(VATS)in postoperative recovery in elderly patients with NSCLC.METHODS We retrospectively analysed the clinical data of 85 elderly NSCLC patients who underwent ERAS(the ERAS group)and 327 elderly NSCLC patients who received routine care(the control group)after VATS at the Department of Thoracic Surgery of Peking University Shenzhen Hospital between May 2015 and April 2017.After propensity score matching of baseline data,we analysed the postoperative stay,total hospital expenses,postoperative 48-h pain score,and postoperative complication rate for the 2 groups of patients who underwent lobectomy or sublobar resection.RESULTS After propensity score matching,ERAS significantly reduced the postoperative hospital stay(6.96±4.16 vs 8.48±4.18 d,P=0.001)and total hospital expenses(48875.27±18437.5 vs 55497.64±21168.63 CNY,P=0.014)and improved the satisfaction score(79.8±7.55 vs 77.35±7.72,P=0.029)relative to those for routine care.No significant between-group difference was observed in postoperative 48-h pain score(4.68±1.69 vs 5.28±2.1,P=0.090)or postoperative complication rate(21.2%vs 27.1%,P=0.371).Subgroup analysis showed that ERAS significantly reduced the postoperative hospital stay and total hospital expenses and increased the satisfaction score of patients who underwent lobectomy but not of patients who underwent sublobar resection.CONCLUSION ERAS effectively reduced the postoperative hospital stay and total hospital expenses and improved the satisfaction score in the perioperative period for elderly NSCLC patients who underwent lobectomy but not for patients who underwent sublobar resection.

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.

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.

IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT population.Results: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation:A multicenter,case-series study in China

Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.