Search

Exosomes are nano-vesicles that can shuttle active cargoes. Mesenchymal stem cells play a complex function in tumour progression.We investigated the effect of miR-486-5p, an exosome of human bone marrow-derived MSCs on lung cancer. We found that miR-486-5p, carried in mesenchymal stem cells and mesenchymal stem cell-derived exosomes, regulates MIER3 expression by binding to its 3’UTR, thereby inhibiting the epithelial-mesenchymal transition process of A549 cells. In vivo, we demonstrated that exosome treatment reduced the area of tumour necrosis, increased the expression of miR-486-5p and inhibited the epithelial–mesenchymal transition process in mice. In conclusion, mesenchymal stem cell-derived exosomal miR-486-5p directly and negatively targets MIER3 to inhibit lung cancer.

Kaplan-Meier estimate of overall survival

Purpose:Our primary purpose is to explore safety and efficacy of high-dose icotinib in comparison with routine-dose icotinib in patients with non–small cell lung cancer (NSCLC) harboring 21-L858R mutation.Patients and Methods:Patients with treatment-naïve, EGFR-mutant (21-L858R or exon 19 deletion at 2:1) NSCLC were enrolled. Patients with 21-L858R mutation were randomized to receive routine-dose icotinib (125 mg, thrice daily; L858R-RD) or high-dose icotinib (250 mg, thrice daily; L858R-HD), whereas patients with exon 19 deletion received only routine-dose icotinib (19-Del-RD) until progression, death, or unacceptable toxicity. The primary endpoint was median progression-free survival (mPFS), assessed by an independent review committee.Results:From May 2015 to November 2017, 253 patients (86 in L858R-RD; 90 in L858R-HD; and 77 in 19-Del-RD) were enrolled. The mPFS in L858R-HD group was similar to that in 19-Del-RD group (12.9 months and 12.5 months, respectively) and was significantly longer than that in L858R-RD group [12.9 months vs. 9.2 months, hazard ratio (HR): 0.75; 95% confidence interval (CI), 0.53–1.05]. A longer but statistically nonsignificant mPFS was observed between 19-Del-RD and L858R-RD groups (12.5 months vs. 9.2 months, HR: 0.80; 95% CI, 0.57–1.13). A higher objective response rate (ORR) was observed in L858R-HD group compared with L858R-RD group (73% vs. 48%), also between 19-Del-RD and L858R-RD groups (75% vs. 48%). Similar incidences of grade 3/4 toxicities were observed among the three treatment groups.Conclusions:High-dose icotinib improved mPFS and ORR in patients with NSCLC harboring 21-L858R mutation with acceptable tolerability, which could be a new therapeutic option for this patient population.

Objective To explore the difference and diagnostic value evaluation of serum tumor markers in different clinical stages of elderly non-small cell lung cancer (NSCLC) patients. Methods Select 100 elderly NSCLC patients admitted to our hospital from June 2018 to June 2021, collect the general data, pathology data and imaging data of the patients, and the patients were divided into I-IV clinical stages according to the International Union Against Cancer (UICC) 8th edition lung cancer TNM staging standard. Detect the subjects’ peripheral serum tumor markers, serum carcinoembryonic antigen (CEA), cytokeratin fragment 21-1 (CYFRA21-1), squamous cell carcinoma-associated antigen (SCCA), carbohydrate antigen 125 (CA125) and sugar Class antigen 199 (CA199). Compare the differences of serum CEA, CYFRA21-1, SCCA, CA125, CA199 levels in different clinical stages of elderly NSCLC patients, and the diagnostic value of the above indicators for elderly NSCLC patients was analyzed by receiver operating characteristic curve (ROC curve) and area under the curve (AUC). Results The smoking history, differentiation degree, lymph node metastasis and tumor diameter of elderly NSCLC patients with different clinical stages are significantly different; with the increase of NSCLC disease progression, the levels of serum CEA, CYFRA21-1, SCCA, CA125, and CA199 continue to increase, and serum tumors There is a significant correlation between the markers; serum CEA, CYFRA21-1, SCCA, CA125, CA199 have diagnostic value for the clinical staging of elderly NSCLC patients. Conclusions The elevation of serum CEA, CYFRA21-1, SCCA, CA125 and CA199 in elderly NSCLC patients is positively correlated with the degree of tumor malignancy. The detection of the above indicators is of great value for the early diagnosis and disease monitoring of elderly NSCLC.

Paraneoplastic eosinophilia is a rare complication observed in 1% solid tumor cases and appears to have tumor type-dependent prognostic impact, in which the increased eosinophil count was generally associated with unfavorable prognosis. In the English literature, more than 20 patients have been reported of eosinophilia associated with primary non-small cell lung cancer (NSCLC) at diagnosis, all of whom underwent either surgery, chemotherapy, or symptomatic therapy. Herein, we describe clinical course a stage IV NSCLC patient with paraneoplastic eosinophilia and leukocytosis and receiving targeted therapy. A 64-year-old male former smoker was diagnosed with lung adenocarcinoma harboring EGFR L858R mutation and MET amplification. Blood eosinophilia was manifested at diagnosis and confirmed to be paraneoplastic by eliminating other potential causes. The disease progressed rapidly within a month on EGFR inhibitor icotinib and then within three months on icotinib plus crizotinib after rapid response within the first month. A multi-target kinase inhibitor anlotinib was added, and the disease progressed one month later despite initial self-reported asymptomatic high-performance status. The patient was lost to subsequent follow-ups. Radiographic evaluation of disease control or progression coincided with respective distinct alleviation or worsening of eosinophilia. Consistent with previous reports of poor clinical outcome associated with blood eosinophilia, our results suggested a negative prognostic impact in EGFR-/MET-altered NSCLC. This case is, to the best of our knowledge, the first to provide evidence for blood eosinophilia paralleling disease progression in an EGFR- and MET-altered lung adenocarcinoma under targeted therapy, which suggested negative prognostic impact of blood eosinophilia in driver-positive NSCLC.

Introduction Some ALK inhibitors with good inhibition of ROS1 in preclinical studies have been reported to be possibly beneficial in ROS1-positive NSCLC. In this work, we studied the efficacy and safety of ensartinib in the treatment of patients with ROS1-positive NSCLC. Methods The exploratory study was a phase 2, single-arm, multicenter design (NCT03608007). Patients with ROS1-positive NSCLC with a previous chemotherapy line number of less than or equal to 1 who received ensartinib at the dose of 225 mg once daily were enrolled. The primary end point was objective response rate evaluated by an investigator per Response Evaluation Criteria in Solid Tumors version 1.1. Results From June 2018 to July 2019, a total of 59 patients were enrolled at 23 centers in the People’s Republic of China. At the time of data cutoff, the median follow-up was 19.8 months (range: 0.8–22.5). The median objective response rate was 27.0 % (95 % confidence interval [CI]: 13.8–44.1) with 10 partial responses. Median duration of response was 4.8 months (95 % CI: 1.8–10.8). The median progression-free survival was 4.6 months (95 % CI: 4.0–6.4). The median overall survival was not estimable (95 % CI: 14.9–not estimable). Of four patients with brain metastases, intracranial disease control was reported in three (75.0 %, 95 % CI: 19.4–99.4). The most common treatment-related adverse events (TRAEs) were rash and liver enzyme abnormalities, with good prognosis after adjustment for dosage and concomitant medication. Most of the TRAEs were of grades 1 to 2, and incidence of grade greater than or equal to 3 TRAEs was 25.4 %. Conclusions Ensartinib had a modest efficacy in patients with ROS1-positive NSCLC with an acceptable safety profile.

Befotertinib (D-0316) is a novel, third-generation EGFR tyrosine kinase inhibitor (TKI). This study evaluated befotertinib in patients with locally advanced or metastatic NSCLC who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy.This was a single-arm, open-label, phase 2 study at 49 hospitals across mainland China. Patients with locally advanced or metastatic NSCLC harboring EGFR T790M mutations with disease progression after prior first- or second-generation EGFR TKI therapy received oral befotertinib of 50 mg (cohort A) or 75 to 100 mg (cohort B) once daily. The primary end point was objective response rate (ORR) assessed by an independent review committee in intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT03861156.A total of 176 patients and 290 patients were included in cohorts A (50 mg) and B (75-100 mg), respectively. At data cutoff (August 15, 2021), independent review committee-assessed ORR was 67.6% (95% confidence interval [CI]: 61.9%-72.9%) in cohort B. The investigator-assessed ORR was 54.0% (95% CI: 46.3%-61.5%) in cohort A and 65.9% (95% CI: 60.1%-71.3%) in cohort B. The median investigator-assessed progression-free survival was 11.0 (95% CI: 9.6-12.5) months in cohort A and 12.5 (95% CI: 11.1-13.8) months in cohort B. The median independent review committee-assessed progression-free survival in cohort B was 16.6 (95% CI: 15.0-not evaluable [NE]) months. The intracranial ORR was 26.7% (95% CI: 7.8%-55.1%) in cohort A by investigator assessment, while 57.1% (95% CI: 34.0%-78.2%) and 55.9% (95% CI: 37.9%-72.8%) in cohort B by investigator and independent review committee assessment, respectively. The median investigator-assessed intracranial progression-free survival was 16.5 (95% CI: 8.6-NE) months in cohort A, while the median intracranial progression-free survival was not evaluable in cohort B due to immature data regardless of investigator or independent review committee assessment. and NE (95% CI: 13.8-NE) in cohort B. The overall survival was immature. Grade 3 or higher treatment-related adverse events and treatment-related serious adverse events occurred in 20.5% and 11.4% of patients in cohort A and in 29.3% and 10.0% of patients in cohort B, respectively.Befotertinib of 75 to 100 mg has satisfying efficacy and manageable toxicity in patients with locally advanced or metastatic NSCLC harboring T790M mutation with resistance to first- or second-generation EGFR TKIs. A phase 3 randomized trial is underway (NCT04206072).

Purpose: Our primary purpose is to explore safety and efficacy of high-dose icotinib in comparison with routine-dose icotinib in patients with non–small cell lung cancer (NSCLC) harboring 21-L858R mutation. Patients and Methods: Patients with treatment-naïve, EGFR-mutant (21-L858R or exon 19 deletion at 2:1) NSCLC were enrolled. Patients with 21-L858R mutation were randomized to receive routine-dose icotinib (125 mg, thrice daily; L858R-RD) or high-dose icotinib (250 mg, thrice daily; L858R-HD), whereas patients with exon 19 deletion received only routine-dose icotinib (19-Del-RD) until progression, death, or unacceptable toxicity. The primary endpoint was median progression-free survival (mPFS), assessed by an independent review committee. Results: From May 2015 to November 2017, 253 patients (86 in L858R-RD; 90 in L858R-HD; and 77 in 19-Del-RD) were enrolled. The mPFS in L858R-HD group was similar to that in 19-Del-RD group (12.9 months and 12.5 months, respectively) and was significantly longer than that in L858R-RD group [12.9 months vs. 9.2 months, hazard ratio (HR): 0.75; 95% confidence interval (CI), 0.53–1.05]. A longer but statistically nonsignificant mPFS was observed between 19-Del-RD and L858R-RD groups (12.5 months vs. 9.2 months, HR: 0.80; 95% CI, 0.57–1.13). A higher objective response rate (ORR) was observed in L858R-HD group compared with L858R-RD group (73% vs. 48%), also between 19-Del-RD and L858R-RD groups (75% vs. 48%). Similar incidences of grade 3/4 toxicities were observed among the three treatment groups. Conclusions: High-dose icotinib improved mPFS and ORR in patients with NSCLC harboring 21-L858R mutation with acceptable tolerability, which could be a new therapeutic option for this patient population.

Exosomes are membrane-enclosed nanovesicles that shuttle active cargoes, such as mRNAs and microRNAs (miRNAs), between different cells. Mesenchymal stem cells (MSCs) are able to migrate to the tumor sites and exert complex functions over tumor progress. We investigated the effect of human bone marrow-derived MSCs (BMSCs)-derived exosomal miRNA-486-5p on lung cancer. Frist, during the co-culture experiments, we found that both MSCs and MSCs-derived exosomal can inhibit the proliferation and EMT process of A549 cells.Then we verified that the exosomes carry miRNA-486-5p, and overexpression of miRNA-486-5p inhibits the proliferation and EMT process of A549 cells. In addition, miRNA-486-5p carried by MSCs-derived exosomes regulates MIER3 expression through binding to its 3’UTR. Furthermore, the silenced MIER3 inhibits the proliferation of A549 cells and the EMT process. Finally, we verified that the tumor necrosis area of mice was reduced, miRNA-486-5p expression increased, and the EMT process was inhibited after exosome treatment in vivo. In conclusion, MSC-derived exosomal miRNA-486-5p directly and negatively targets MIER3 to suppress lung cancer.

VEGF inhibitors can enhance the efficacy of immunotherapy. However, despite high initial response rates, almost all patients eventually develop treatment resistance to EGFR tyrosine-kinase inhibitors. We aimed to evaluate the efficacy and safety of sintilimab with or without IBI305 plus pemetrexed and cisplatin, compared with pemetrexed and cisplatin alone, for the treatment of patients with locally advanced or metastatic EGFR-mutated non-small-cell lung cancer (NSCLC) who had disease progression after receiving EGFR tyrosine-kinase inhibitor therapy.This randomised, double-blind, multicentre, phase 3 trial was conducted at 52 hospitals in China. Eligible participants were adults aged 18-75 years with locally advanced or metastatic NSCLC and EGFRBetween July 11, 2019, and July 31, 2021, 936 patients were screened and 444 were randomly assigned (148 to the sintilimab plus IBI305 plus chemotherapy group, 145 to the sintilimab plus chemotherapy group, and 151 to the chemotherapy alone group). Data cutoff for this interim analysis was July 31, 2021. After a median follow-up of 9·8 months (IQR 4·4-13·3), progression-free survival was significantly longer in the sintilimab plus IBI305 plus chemotherapy group versus the chemotherapy alone group (median 6·9 months [95% CI 6·0-9.3] vs 4·3 months [4·1-5·4]; hazard ratio 0·46 [0·34-0·64]; p0·0001). The most common grade 3 or 4 treatment-related adverse events were decreased neutrophil count (30 [20%] in the sintilimab plus IBI305 plus chemotherapy group vs 26 [18%] in the sintilimab plus chemotherapy group vs 27 [18%] in the chemotherapy alone group), decreased white blood cell count (17 [11%] vs 12 [8%] vs 13 [9%]), and anaemia (18 [12%] vs ten [7%] vs 15 [10%]). Potentially treatment-related deaths occurred in six patients (intestinal obstruction, gastrointestinal haemorrhage, and myelosuppression in one patient each, and three deaths of unknown cause) in the sintilimab plus IBI305 plus chemotherapy group, and in one patient in the chemotherapy alone group (unknown cause).In this interim analysis, sintilimab plus IBI305 plus cisplatin and pemetrexed was generally efficacious and well tolerated in patients with EGFR-mutated NSCLC who progressed after receiving EGFR tyrosine-kinase inhibitor therapy.Innovent Biologics and the National Natural Science Foundation of China.For the Chinese translation of the abstract see Supplementary Materials section.

Extensive-stage small-cell lung cancer (ES-SCLC) is associated with poor prognosis and treatment options are scarce. Immunotherapy has shown robust clinical activity in ES-SCLC in previous phase 3 trials. We aimed to assess the efficacy and safety of adebrelimab (SHR-1316), a novel anti-PD-L1 antibody, with standard chemotherapy as a first-line treatment for ES-SCLC.The CAPSTONE-1 study was a randomised, double-blind, placebo-controlled, phase 3 trial, done in 47 tertiary hospitals in China. Key inclusion criteria were patients aged 18-75 years, with previously untreated histologically or cytologically confirmed ES-SCLC and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Eligible patients were randomly assigned (1:1) to receive four to six cycles of carboplatin (area under the curve of 5 mg/mL per min, day 1 of each cycle) and etoposide (100 mg/mBetween Dec 26, 2018, and Sept 4, 2020, 462 eligible patients were enrolled and randomly assigned: 230 (50%) patients received adebrelimab plus chemotherapy (adebrelimab group) and 232 (50%) patients received placebo plus chemotherapy (placebo group). At data cutoff (Oct 8, 2021), median follow-up was 13·5 months (IQR 8·9-20·1). Median overall survival was significantly improved in the adebrelimab group (median 15·3 months [95% CI 13·2-17·5]) compared with the placebo group (12·8 months [11·3-13·7]; hazard ratio 0·72 [95% CI 0·58-0·90]; one-sided p=0·0017). The most common treatment-related grade 3 or 4 adverse events were decreased neutrophil count (174 [76%] patients in the adebrelimab group and 175 [75%] patients in the placebo group), decreased white blood cell count (106 [46%] and 88 [38%]), decreased platelet count (88 [38%] and 78 [34%]), and anaemia (64 [28%] and 66 [28%]). Treatment-related serious adverse events occurred in 89 (39%) patients in the adebrelimab group and 66 (28%) patients in the placebo group. Four treatment-related deaths were reported: two each in the adebrelimab group (respiratory failure and interstitial lung disease and pneumonia) and placebo group (multiple organ dysfunction and unknown cause of death).Adding adebrelimab to chemotherapy significantly improved overall survival with an acceptable safety profile in patients with ES-SCLC, supporting this combination as a new first-line treatment option for this population.Jiangsu Hengrui Pharmaceuticals.

BACKGROUND: Early diagnosis of non-small cell lung cancer (NSCLC) is crucial for treatment. Circulating cell-free DNA (cfDNA) is an extracellular nucleic acid found in serum, and tumor cfDNA circulating in the blood may be used as a biomarker for early diagnosis. The purpose of this study was to evaluate the application value of cfDNA as a biomarker for the diagnosis of NSCLC through meta-analysis. METHODS: We searched the China National Knowledge Infrastructure (CNKI), Wanfang, VIP, PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science databases using the following search terms: lung cancer, NSCLC, biomarkers, circulating cfDNA, cfDNA, circulating tumor DNA (ctDNA), circulating cell-free tumor DNA, and diagnosis. The retrieval period was set until September 2021. According to PICOS (patients, intervention, comparison, outcomes, and study design) principles the inclusion criteria were: aged ≥18 years; at least 10 NSCLC cases; NSCLC patients diagnosed by histopathology or cytology; circulating cfDNA was detected; outcome data could be completely extracted. Bias risk assessment was conducted according to the QUADAS (Quality Assessment of Diagnostic Accuracy Studies). RevMan 5.3 was used for meta-analysis. RESULTS: Eight studies met the inclusion criteria, including a total of 618 NSCLC patients and 635 healthy subjects. The overall sensitivity and specificity were 0.79 [95% confidence interval (CI): 0.75–0.82] and 0.81 (95% CI: 0.78–0.84), respectively. The area under the curve (AUC) of the summary receiving operating characteristic (SROC) curve was 0.8941. The pooled positive likelihood ratio, pooled negative likelihood ratio, and pooled diagnostic odds ratio were 5.37 (95% CI: 2.67–10.81), 0.24 (95% CI: 0.15–0.38), and 24.68 (95% CI: 8.85–68.84), respectively. The patient selection bias was high in two articles was high, unclear in one article, and low in the remaining five ones. The risk of bias in the research index test was unclear in one article, and low in the remaining seven articles. The reference standard bias, and flow and time bias of all articles was low. CONCLUSIONS: Circulating cfDNA is an efficacy biomarker in diagnosis of NSCLC. Its clinical application technology is worthy of further research.

Sluggish dynamics of polysulfide (LiPS) conversion leads to reduced utilization of active sulfur and rapid capacity decay. Introducing catalysts into lithium-sulfur battery systems is a feasible and imperative strategy to tackle this problem. Previous research studies have mainly been focused on selecting new catalysts and design functional structures to improve performance, and ignoring the interaction between catalysts and their carriers. Herein, by simply fabricating a high-efficiency ZnS quantum dot@graphene nanosheet catalyst (ZnS QD@rGO), we utilized enhanced interfacial electronic interaction to accelerate polysulfide conversion for high energy density Li-S batteries. With the smaller size of ZnS, the interfacial electronic interaction becomes more enhanced, which was evidenced by DFT calculations and XPS experiments. After mixing with sulfur, the electrodes achieved a high capacity of 857.8 mA h g-1 at 1 C and a retention of 91.2% after 300 cycles. Also, a sulfur cathode with a high actual capacity of ∼4.0 mA h cm-2 could be obtained, with no obvious capacity decay within 100 cycles. We believe that this strategy represents a new perspective on designing efficient high-load electrodes for Li-S batteries.

Background This study aimed to explore associations between PDL1 polymorphisms and efficacy of apatinib for patients with previously treated advanced non–small cell lung cancer (NSCLC) in a real-world setting. Methods We retrospectively recruited 148 patients with previously treated advanced NSCLC from January 2015 to December 2019 continuously. Clinical efficacy in patients receiving apatinib treatment was evaluated. Adverse reactions were documented during treatment. Biological specimens of peripheral blood and cancer tissue biopsies were obtained for the genotyping of genetic variations in PDL1 and corresponding gene-mRNA expression, respectively. Univariate association analysis between the status of PDL1 genetic variations and survival was performed with Kaplan–Meier survival analysis. Results The objective response rate of the 148 patients was 17.6% and disease-control rate 68.9%. Prognostic data suggested that median progression-free survival (PFS) was 3.8 (95% CI 3.13–4.47) months and median overall survival (OS) 10.5 (95% CI 9.06–11.95) months. Regarding PDL1 genetic variation, only rs2297136 was of clinical significance. Prognosis analysis revealed that PFS and OS for the rs2297136 genotype were significantly different. Median PFS of patients with TC/CC and TT genotypes was 3 and 4.5 months, respectively (P=0.006). Median OS of the two genotypes was 9 and 11.6 months, respectively (P=0.04). Furthermore, the safety profile suggested that the most common adverse reactions were hypertension, dermal toxicity, fatigue, and oral toxicity. This study failed to find any significant association between adverse reactions and rs2297136. Interestingly, mRNA-expression analysis demonstrated that mRNA expression of PDL1 in biopsy cancer–tissue specimens was significantly different based on rs2297136-genotype status (P

Introduction: Extensive-stage small cell lung cancer (ES-SCLC) is associated with limited treatment options and poor prognosis. Immunotherapy has recently showed robust clinical activity in ES-SCLC. In this double-blind, phase 3 trial, we evaluated adebrelimab (SHR-1316), a novel anti-PD-L1 antibody, in combination with standard chemotherapy (chemo) as first-line treatment for ES-SCLC. Methods: Patients naïve to systemic treatment for ES-SCLC were randomized 1:1 to receive 4-6 cycles of adebrelimab (20 mg/kg, iv, d1, q3w) or placebo with carboplatin (AUC 5, d1, q3w) plus etoposide (100 mg/m2, d1, d2, d3, q3w), followed by maintenance therapy with adebrelimab or placebo. The primary endpoint was overall survival (OS). Results: 462 patients were randomized and treated (adebrelimab+chemo, n=230; placebo+chemo, n=232). As of Oct 08, 2021, with an median follow-up of 13.5 mo (all patients; 22.5 mo for patients alive), OS was significantly prolonged with adebrelimab+chemo vs placebo+chemo (median, 15.3 mo [95% CI 13.2-17.5] vs 12.8 mo [95% CI 11.3-13.7]; hazard ratio [HR], 0.72 [95% CI 0.58-0.90], 1-sided p=0.0017); OS rate was 62.9% vs 52.0% at 12 mo and 31.3% vs 17.2% at 24 mo. Progression-free survival (PFS) per independent review committee (IRC) was 5.8 mo (95% CI 5.6-6.9) with adebrelimab+chemo vs 5.6 mo (95% CI 5.5-5.7) with placebo+chemo (HR 0.67, 95% CI 0.54-0.83); PFS rate was 49.4% vs 37.3% at 6 mo and 19.7% vs 5.9% at 12 mo. Objective response rate (ORR) and duration of response (DoR) also favored the adebrelimab+chemo group (Table 1). Grade ≥3 treatment-related adverse events occurred in 85.7% vs 84.9% of patients with adebrelimab+chemo vs placebo+chemo, with the most common (frequency ≥5%) being hematological toxicities in both groups. Conclusions: The addition of adebrelimab to chemotherapy significantly improved OS with an acceptable safety profile, supporting this combination as a new first-line treatment option for ES-SCLC. Efficacy outcomes Adebrelimab+Chemo (n=230) Placebo+Chemo (n=232) Median OS (95% CI), mo 15.3 (13.2-17.5) 12.8 (11.3-13.7) HR (95% CI)*, 1-sided log-rank p 0.72 (0.58-0.90); p=0.0017 12-mo OS rate (95% CI), % 62.9 (56.3-68.8) 52.0 (45.4-58.2) 24-mo OS rate (95% CI), % 31.3 (24.9-37.9) 17.2 (12.1-23.0) Median PFS (95% CI), mo 5.8 (5.6-6.9) 5.6 (5.5-5.7) HR (95% CI)*, 1-sided log-rank p 0.67 (0.54-0.83); p Citation Format: Ying Cheng, Jie Wang, Caicun Zhou, Wenxiu Yao, Qiming Wang, Xuhong Min, Gongyan Chen, Xingxiang Xu, Xingya Li, Fei Xu, Yong Fang, Runxiang Yang, Guohua Yu, Youling Gong, Jun Zhao, Yun Fan, Quan Liu, Lejie Cao, Yu Yao, Yunpeng Liu, Xiaoling Li, Jingxun Wu, Zhiyong He, Kaihua Lu, Liyan Jiang, Huiqing Yu, Chengping Hu, Wenhua Zhao, Jian Zhao, Gang Wu, Dingzhi Huang, Chengshui Chen, Cuimin Ding, Baihong Zhang, Xiuwen Wang, Hui Luo, Baolan Li, Ben Zhang, Haowen Li, Ke Ma. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage SCLC: A phase 3 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT038.

Introduction ZL-2306-005 is a randomized, double-blind, multicenter phase 3 study evaluating the efficacy and safety of niraparib, a poly(adenosine diphosphate-ribose) polymerase inhibitor, as first-line maintenance therapy in Chinese patients with platinum-responsive, extensive-stage SCLC (ES-SCLC). Methods Patients with complete response (CR) or partial response (PR) to standardized, platinum-based first-line chemotherapy were randomized 2:1 to receive niraparib or placebo (300 mg [baseline body weight ≥ 77 kg, platelet count ≥ 150,000/μL] or 200 mg) once daily until progression or unacceptable toxicity. Primary end points were progression-free survival (PFS) (blinded independent central review) and overall survival (sample size planned: 591 patients). Secondary end points included investigator-evaluated PFS and safety. Results ZL-2306-005 was terminated early owing to ES-SCLC treatment landscape changes (data cutoff: March 20, 2020). During July 2018–February 2020, a total of 185 of 272 patients screened were randomized (niraparib: n = 125 [CR = 1, PR = 124]; placebo: n = 60 [CR = 1, PR = 59]). Median (95% confidence interval [CI]) PFS (blinded independent central review) was 1.54 months (1.41–2.69, niraparib) and 1.36 months (1.31–1.48, placebo); hazard ratio (HR) = 0.66 (95% CI: 0.46–0.95, p = 0.0242). Median overall survival was 9.92 months (9.33–13.54, niraparib) and 11.43 months (9.53–not estimable, placebo); HR = 1.03 (95% CI: 0.62–1.73, p = 0.9052). Median investigator-evaluated PFS was 1.48 months (1.41–2.56, niraparib) and 1.41 months (1.31–2.00, placebo); HR = 0.88 (95% CI: 0.61–1.26; p = 0.4653). Grade greater than or equal to 3 adverse events occurred in 34.4% (niraparib) and 25.0% (placebo) of patients. Conclusions ZL-2306-005 did not reach primary end points. Nevertheless, niraparib as maintenance therapy modestly improved PFS in patients with platinum-responsive ES-SCLC, with acceptable tolerability profile and no new safety signal.

INTRODUCTION Prophylactic cranial irradiation (PCI) is recommended for patients with limited-stage small cell lung cancer (LS-SCLC) who achieve good response after chemoradiotherapy. But PCI is neurotoxic. Magnetic resonance imaging (MRI) is the standard tool for evaluating brain metastasis (BM). This study was to retrospectively analyse the necessity of PCI in the era of MRI in LS-SCLC. METHODS From July 2013 to June 2017, 190 patients with LS-SCLC who were treated with definitive chemoradiotherapy were included and analysed in this study. They were divided into the PCI group and non-PCI group. Propensity score matching (PSM) analysis was used to balance the variable differences. The Kaplan-Meier method was applied to estimate survival with log-rank test to ascertain significance between different groups. RESULTS Seventy-seven patients (40.5%) received PCI after chemoradiotherapy. After adjustment for propensity scores, 69 pairs of patients were matched between two groups. After PSM, the 1-year and 3-year OS rates were 96.9% and 48.5% in PCI group versus 89.9% and 25.0% in non-PCI group (HR: 0.419, 95% CI: 0.251-0.701, P = 0.001). The 1-year and 3-year BMFS in PCI group were 96.8% and 67.5% versus 62.3% and 37.9% in non-PCI group (HR: 0.247, 95% CI: 0.132-0.460, P

Yu-Tao Liu,1 Xue-Zhi Hao,1 De-Ruo Liu,2 Gang Cheng,3 Shu-Cai Zhang,4 Wen-Hua Xiao,5 Yi Hu,6 Jun-Feng Liu,7 Ming He,7 Cui-Min Ding,8 Li Zhang,9 Jun Wang,10 Hui Li,11 Gui-Lan Dong,12 Xiu-Yi Zhi,13 Jian Li,14 Yuan-Kai Shi1 1Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of General Thoracic Surgery, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3Department of Medical Oncology, Beijing Hospital, Beijing, People’s Republic of China; 4Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 5Department of Oncology, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, People’s Republic of China; 6Department of Oncology, Chinese PLA General Hospital, Beijing, People’s Republic of China; 7Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 8Department of Respiratory Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 9Department of Respiratory Medicine, Peking Union Medical College Hospital, Affiliated to Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 10Department of Thoracic Surgery, Peking University People’s Hospital, Beijing, People’s Republic of China; 11Department of Thoracic Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, People’s Republic of China; 12Department of Radiotherapy and Chemotherapy, Tangshan People’s Hospital, Tangshan, Hebei, People’s Republic of China; 13Department of Thoracic Surgery, Xuanwu Hospital of Capital Medical University, Beijing, People’s Republic of China; 14Department of Thoracic Surgery, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yuan-Kai ShiDepartment of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, People’s Republic of ChinaTel +86 10 8778 8293Email syuankai@cicams.ac.cnAbstract: The efficacy and possible role of epidermal growth factor receptor tyrosine kinase inhibitors in treating early-stage non-small-cell lung cancer have yet to be established. Therefore, we aimed to explore the efficacy and safety of icotinib in completely resected EGFR-mutant stage II–IIIA lung adenocarcinoma patients who underwent standard chemotherapy. This is a randomised, double-blinded, placebo-controlled, multicentre, Phase III trial. A total of 124 patients aged 18– 75 years who qualified the inclusion criteria were recruited. These patients were randomised (1:1) to receive either icotinib (125 mg 3 times per day) or placebo (the same dosage and frequency) for 36 months, followed by a further 36 months of observational window. The primary endpoint is disease-free survival (DFS), while the secondary endpoints are overall survival, 3-year and 5-year DFS, safety and tolerability of the medication, and health-related quality-of-life. Analyses will be conducted in a full analysis set and a per-protocol set as well. To our knowledge, the present study is the first randomised, double-blinded, placebo-controlled, multicenter trial designed to explore efficacy and safety of icotonib in this population. The results obtained in the near future may provide potential guidance in clinical practice.Trial Registration: This trial was registered on www.ClinicalTrail.gov as NCT02125240.Keywords: EGFR mutation, non-small-cell lung cancer, lung adenocarcinoma, icotinib, adjuvant chemotherapy

Introduction The optimal treatment for EGFR-mutant lung adenocarcinoma (LUAD) remains challenging because of intratumor heterogeneity. We aimed to explore a refined stratification model based on the integrated analysis of circulating tumor DNA (ctDNA) tracking. Methods ctDNA was prospectively collected at baseline and at every 8 weeks in patients with advanced treatment-naive EGFR-mutant LUAD under gefitinib treatment enrolled in a phase 2 trial and analyzed using next-generation sequencing of a 168-gene panel. Results Three subgroups categorized by baseline comutations—EGFR-sensitizing mutations (59, 32.8%), EGFR-sensitizing mutations with tumor suppressor mutations (97, 53.9%), and EGFR-sensitizing mutations with other driver mutations (24, 13.3%)—exhibited distinct progression-free survival (13.2 [11.3–15.2] versus 9.3 [7.6–10.5] versus 4.0 [2.4–9.3] months) and overall survival (32.0 [29.2–41.5] versus 21.7 [19.3–27.0] versus 15.5 [10.5–33.7] months, respectively), providing evidence for initial stratification. A total of 63.7% of the patients achieved week 8 ctDNA clearance, with significant difference noted among the three subgroups (74.5% versus 64.0% versus 29.4%, respectively, p = 0.004, Fisher’s exact test). Patients without week 8 ctDNA clearance had worse progression-free survival (clearance versus nonclearance 11.2 [9.9–13.2] versus 7.4 [5.6–9.6] months, p = 0.016, Cox regression], especially in the second subgroup [5.8 (5.6–11.5) months], suggesting the necessity of adaptive stratification during treatment. During follow-up, 56.0% and 20.8% of the patients eventually harbored p.T790M and non-p.T790M mutations, respectively, with a significant difference in non-p.T790M mutations among the three subgroups (7.5% versus 15.7% versus 80.0%, respectively, p Conclusions The patients with baseline comutations and ctDNA nonclearance at first visit might require combined therapy because of the limited survival benefit of EGFR tyrosine kinase inhibitor monotherapy. We proposed a refined stratification mode for the whole-course management of EGFR-mutant LUAD.

The CAPTRA-Lung study (NCT03334864) is a prospective observational study that will capture real-world data of patients with advanced or metastatic non-small cell lung cancer (NSCLC) across China. The study aims to complement the results from current therapeutic regimens to improve the standard of diagnosis and treatment, evaluate the effectiveness and safety of systemic therapy, and determine the factors influencing the outcomes and responses to treatment. From January 2018 to December 2023, eligible patients with advanced or metastatic NSCLC who are receiving treatment and participating in follow-up at 16 institutions in China, will be enrolled. The demographic, clinical, laboratory, and treatment characteristics and responses to treatment will be recorded in a case report form and transcribed into an electronic data capture system. Overall survival, progression-free survival, overall response rate, and incidence of adverse events will be calculated from the time of initial enrolment until progression evaluated by physicians, last contact, date of death, or analysis cutoff date, respectively. Based on the disease characteristics and treatment strategies, four sub-cohorts will also be established. This study cohort could serve as a pool of patients with advanced or metastatic NSCLC to support further research.

D-0316 in patients with advanced T790M-positive EGFR-mutant non-small cell lung cancer who progressed on prior EGFR-TKI therapy: results from a phase II study (NCT03861156) Background: Despite initial response to EGFR-TKI, most patients (pts) develop resistance with the EGFR T790M mutation detectable in ~50% of patients treated with first-/second-generation EGFR-TKIs. D-0316 is a third-generation EGFR-TKI that is selective for both EGFR-TKI sensitizing and T790M resistance mutations in pts with non-small cell lung cancer (NSCLC). We report the results of a registered, single-arm, phase II study of D-0316 in NSCLC pts with EGFR T790M who progressed on previous treatment with first-line EGFR-TKIs. Methods: In this phase II, open-label, single-arm study, eligible pts were those who had confirmed locally advanced or metastatic NSCLC, and had disease progression after first-line EGFR-TKI and with T790M mutation. Pts were initially orally given D-0316 50 mg. However, considering the benefits and risks of the pts, the dose was modified to 100 mg once daily with a 21-day lead-in at 75 mg once daily. The primary endpoint was objective response rate (ORR) based on independent review committee (IRC) according to RECIST 1.1.Results: As of October 31, 2019, 176 pts were enrolled in the 50 mg phase, in which 90 pts had partial response, achieving an ORR of 51.1% (95%CI: 43.5-58.7). Despite the immature PFS, disease progression or death occurred in 60 pts (34.1%) and the median PFS was 8.4 months (95% CI: 8.0-NE). Between September 12, 2019 and July 29, 2020, 689 pts were screened and 290 pts (median age 62.5) were enrolled in China and received 100mg D-0316 with a 21-day lead-in at 75 mg. At data cutoff (October 18, 2020), the median duration of follow-up was 5.5 months. 188 of the 290 pts achieved confirmed partial responses by IRC. The ORR was 64.8% (95% CI: 59.0-70.3) and the disease control rate (DCR) was 95.2% (95% CI: 92.0-97.3). The ORR was consistent across in most subgroups. Among 34 pts with brain metastases at baseline, 18 pts achieved confirmed partial responses and the intracranial ORR was 52.9% (95% CI: 35.1-70.2). The PFS, DoR, and OS were premature. The most common treatment-related adverse events were thrombocytopenia (57.2%), headache (27.6%), leukopenia (23.4%), anemia (22.1%) and rash (20.7%). The most common grade 3 or higher treatment-related adverse events were thrombocytopenia (11.7%). One death was due to treatment-related adverse events (interstitial lung disease). Six interstitial lung diseases (2.1%) were observed during study treatment. Conclusion: D-0316 has showed strong anti-tumor activities and tolerable toxicity in pts with EGFR T790M-positive NSCLC who have progressed after EGFR-TKI treatment. Citation Format: Shun Lu, Yiping Zhang, Guojun Zhang, Jianying Zhou, Shundong Cang, Ying Cheng, Gang Wu, Peiguo Cao, Dongqing Lv, Xiangming Jin, Hong Jian, Chengshui Chen, Guanming Jiang, Panwen Tian, Kai Wang, Hui Zhao, Gongyan Chen, Qun Chen, Cuimin Ding, Junquan Yang, Renhua Guo, Guoping Sun, Bin Wang, Liyan Jiang, Wu Zhuang, Zhe Liu, Jian Fang, Yunpeng Liu, Jian Zhang, Jun Chen, Yueyin Pan, Qitao Yu, Min Zhao, Jiuwei Cui, Dianming Li, Tienan Yi, Zhuang Yu, Yan Yang, Yan Zhang, Xiuyi Zhi, Yunchao Huang, Rong Wu, Liangan Chen, Aimin Zang, Lejie Cao, Qingshan Li, Xiaoling Li, Yong Song, Donglin Wang, Shucai Zhang. D-0316 in patients with advanced T790M-positive EGFR-mutant non-small cell lung cancer who progressed on prior EGFR-TKI therapy: results from a phase II study (NCT03861156) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT170.

Increasing evidence has shown that microRNA (miRNA) is extensively involved in the pathophysiology of lung cancer. Microarray data demonstrated the increasing levels of miR-19a in the peripheral blood from patients suffering from lung cancer, which is closely associated with poor prognosis of lung cancer. However, the underlying molecular mechanism of miR-19a remains to be determined. The results of the present study showed a higher expression of miR-19a compared with normal bronchial epithelial cells. Furthermore, lentivirus vectors were constructed to establish cell lines that overexpressed and knocked out miR-19a in order to study the role of miR-19a on the metastasis and proliferation of lung cancer cells. Investigation into the underlying mechanism of miR-19a, revealed that MXD1 may be the key gene targeting miR-19a, participating in the process of proliferation and metastasis of lung cancer cells.

Summary Background Detection of EGFR mutations in tumour tissue is the gold-standard approach to ascertain if a patient will benefit from treatment with an EGFR tyrosine kinase inhibitor. However, if tissue is scant, another strategy is to use circulating tumour DNA (ctDNA), but this method needs validation in clinical trials. We did a prospective clinical trial to assess ctDNA-based EGFR mutation detection as a selection criterion for patients with lung adenocarcinoma receiving gefitinib as first-line treatment. Methods BENEFIT is a multicentre, single-arm, phase 2 clinical trial at 15 centres in China. Patients aged 18–75 years with stage IV metastatic lung adenocarcinoma and EGFR mutations detected in ctDNA were given oral gefitinib 250 mg once daily as first-line treatment. The primary endpoint was the proportion achieving an objective response. Secondary endpoints included median progression-free survival and safety. Next-generation sequencing (NGS) of a 168-gene panel was used for genetic analysis of baseline blood samples. The primary efficacy analysis was done by intention to treat in patients who had at least one post-baseline tumour assessment. The safety analysis was done in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT02282267. Findings Between Dec 25, 2014, and Jan 16, 2016, 426 patients were screened for the trial, of whom 188 with EGFR mutations in ctDNA were enrolled and received gefitinib. 183 patients had one or more post-baseline tumour assessment and were included in the primary efficacy analysis. Median follow-up was 14·5 months (IQR 12·2–16·5). At the time of data cutoff (Jan 31, 2017), 152 patients had progressive disease or had died. The proportion achieving an objective response was 72·1% (95% CI 65·0–78·5). Median progression-free survival was 9·5 months (95% CI 9·07–11·04). Of 167 patients with available blood samples, 147 (88%) showed clearance of EGFR mutations in ctDNA at week 8, and median progression-free survival was longer for these patients than for the 20 patients whose EGFR mutations persisted at week 8 (11·0 months [95% CI 9·43–12·85] vs 2·1 months [1·81–3·65]; hazard ratio [HR] 0·14, 95% CI 0·08–0·23; p EGFR mutations only (n=58), those with mutations in EGFR and tumour-suppressor genes (n=97), and those with mutations in EGFR and oncogenes (n=24). Corresponding median progression-free survival in these subgroups was 13·2 months (95% CI 11·5–15·0), 9·3 months (7·6–11·0), and 4·7 months (1·9–9·3), respectively ( EGFR mutations only vs mutations in EGFR and tumour-suppressor genes, HR 1·78, 95% CI 1·23–2·58; p=0·002; EGFR mutations only vs mutations in EGFR and oncogenes, 2·66, 1·58–4·49; p=0·0003). The most common grade 3 or 4 adverse events were hepatic function abnormalities (n=24). Serious adverse events were reported in 17 (9%) patients. No unexpected safety events for gefitinib were recorded. Interpretation Detection of EGFR mutations in ctDNA is an effective method to identify patients who might benefit from first-line gefitinib treatment. Further analyses of dynamic alterations of EGFR mutations and accompanying gene aberrances could predict resistance to gefitinib. Funding Guangdong Association of Clinical Trials, AstraZeneca, National Natural Sciences Foundation Key Programme, and National Key Research and Development Programme of China.

Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation.Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety.Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P 0.001) and treatment-related AEs (54.1% versus 90.5%; P 0.001) were significantly fewer in the icotinib group than in the chemotherapy group.First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.

MicroRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs) in miRNA processing machinery genes affect cancer risk, treatment efficacy and patient prognosis. A miR-SNP of rs11077 located in the 3′UTR of miRNA processing machinery gene XPO5 was examined in small cell lung cancer (SCLC) patients to evaluate its association with cancer survival. A total of 42 patients were enrolled in the present study and genotyped for rs11077 and survival was assessed using the Kaplan-Meier method, as well as univariate and multivariate analyses. The AA genotype of rs11077 was identified for its significant association with better survival time (P=0.023). In addition, rs11077 was found to associate independently with overall survival in SCLC patients by multivariate analysis (relative risk 2.469; 95% CI, 1.088–5.603; P=0.031). The findings of this study suggest that although miR-SNP studies for miRNA processing machinery genes are still at an early age, miR-SNPs have an impact on cancer survival. In conclusion, a miR-SNP in the 3′UTR region of the XPO5 gene was identified as an independent prognostic marker for survival of advanced SCLC patients.

Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) may be associated with an increased cancer risk. We investigated the lung cancer risk profile of D-loop SNPs in a case-controlled study. The minor alleles of nucleotides 235A/G and 324A/G were associated with an increased risk for lung cancer patients. The minor alleles of the nucleotides 151C/T, 200A/G, 524C/CA, and 16274G/A were specifically associated with the cancer risk of squamous cell carcinoma, whereas the minor allele of nucleotide 16298T/C was specifically associated with the risk of small cell lung cancer. In conclusion, SNPs in mtDNA are potential modifiers of lung cancer risk. The analysis of genetic polymorphisms in the mitochondrial D-loop can help identify subgroups of patients who are at a high risk of developing lung cancer.

The CAPTRA-Lung study (NCT03334864) is a prospective observational study that will capture real-world data of patients with advanced or metastatic non-small cell lung cancer (NSCLC) across China. The study aims to complement the results from current therapeutic regimens to improve the standard of diagnosis and treatment, evaluate the effectiveness and safety of systemic therapy, and determine the factors influencing the outcomes and responses to treatment. From January 2018 to December 2023, eligible patients with advanced or metastatic NSCLC who are receiving treatment and participating in follow-up at 16 institutions in China, will be enrolled. The demographic, clinical, laboratory, and treatment characteristics and responses to treatment will be recorded in a case report form and transcribed into an electronic data capture system. Overall survival, progression-free survival, overall response rate, and incidence of adverse events will be calculated from the time of initial enrolment until progression evaluated by physicians, last contact, date of death, or analysis cutoff date, respectively. Based on the disease characteristics and treatment strategies, four sub-cohorts will also be established. This study cohort could serve as a pool of patients with advanced or metastatic NSCLC to support further research.

The associations between single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) and cancer risk and disease outcome have been extensively analyzed. We investigated the association between age-at-onset and SNPs in the mitochondrial D-loop using a population-based series of non-small cell lung cancer (NSCLC) patients. The D-loop region of mtDNA from NSCLC patients was amplified and sequenced. The age-at-onset curve of NSCLC patients was calculated using the Kaplan-Meier method at each SNP site and values were compared using the log-rank test. The SNP sites of nucleotides 200G/A and 16362T/C were identified to determine their association with age-at-onset of NSCLC using the log-rank test. The nucleotide 207G/A was identified for its association with age-at-onset at a borderline significance level (P = 0.060). We found that genetic polymorphisms in the D-loop were predictive markers for age-at-onset in NSCLC patients. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop can be used to identify NSCLC patient subgroups at high risk of early onset.

Cuimin Ding,1 Cuiqiao Li,1 Hongjing Wang,1 Bin Li,1 Zhanjun Guo2 1Department of Respiratory Medicine, 2Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China Objectives: MicroRNA (miRNA)-related single-nucleotide polymorphisms (SNPs) in miRNA processing machinery genes can affect cancer risk, treatment efficacy, and patient prognosis. A miR-SNP of rs11077 located in the 3' untranslated region (3' UTR) of the miRNA processing machinery gene XPO5 was examined in 112 advanced non-small-cell lung cancer (NSCLC) patients to evaluate its association with cancer outcome. Materials and methods: The miR-SNP was genotyped with ligase detection reaction method. Survival curves were calculated using the Kaplan–Meier method, and multivariate survival analysis was performed using a Cox proportional hazards model. Results: The AC genotype of rs11077, which carries C or A allele, was significantly associated with a better chemotherapy response (P = 0.001). In addition, rs11077 was independently associated with overall survival in advanced NSCLC patients through multivariate analysis (relative risk 0.457; 95% confidence interval: 0.251–0.831; P = 0.010). Conclusion: rs11077 was associated with chemotherapy response and survival of advanced NSCLC patients. The analysis of miR-SNPs in miRNA processing machinery genes can help identify patient subgroups that are at high risk for poor disease outcomes. Keywords: NSCLC, miR-SNP, survival, XPO5, rs11077, chemotherapy response

9041Background: Icotinib is an oral, selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), which is non-inferior to gefitinib in treating unselected or EGFR-mutated advan...

Accumulation of single-nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) may be associated with disease outcome. Our team investigated the prediction power of D-loop SNPs in non-small cell lung cancer (NSCLC) outcome. In an overall multivariate analysis, allele 16390 was identified as an independent predictor for NSCLC outcome. The length of survival of patients with allele 16390A was significantly shorter than that of patients with allele 16390G (relative risk, 0.323; 95% CI, 0.109-0.951; p=0.040). The analysis of genetic polymorphisms in the mitochondrial D-loop can help identify NSCLC patient subgroups at a high risk for a poor disease outcome.