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Immune checkpoint inhibitors and immunotherapy have been shown to improve survival rates, especially in non-small cell lung cancer (NSCLC) patients. More recently, several trials have evaluated the clinical roles of immunotherapy as neoadjuvant settings for NSCLC. There trials suggested that neoadjuvant immunotherapy may effectively reduce the risk of the local recurrence and metastasis of cancer, and significantly improved overall survival and cure rates. Here we conducted a review to summarize the possible mechanism, clinical development, and research progress of neoadjuvant immunotherapy in NSCLC.Relevant articles for this review were retrieved from Google Scholar, Clinicaltrials.gov., and PubMed using the terms "non-small-cell lung cancer", "NSCLC", "neoadjuvant", "immunotherapy", "immune checkpoint inhibitors", "mechanisms", and "toxicity". The primary focus was placed on clinical studies and conference abstracts measuring the safety and efficacy of neoadjuvant immunotherapy in NSCLC until May 2022.After reviewing the preclinical and clinical trial, the preclinical study showed that neoadjuvant immune checkpoint inhibitor promotes antitumor immunity through the enhancement of T cell effector function and the induction of long-term memory. The initial results of preliminary early-phase trials suggested that neoadjuvant immunotherapy is a promising therapeutic strategy for resectable NSCLC patients, with long-term response and modest toxicity, many of these regimens are currently being evaluated by randomized phase III trials. In addition, the major pathologic response of neoadjuvant immunotherapy ranged up to 45% in these studies when used alone, and up to around 83-86% when used in combination with chemotherapy, therefore it has been seen as a rather potent tumor debulking agent.Neoadjuvant immunotherapy has been shown to be a novel integral component of NSCLC care. However, there are also several research questions that requires further investigation, such as the side effects, the optimally treated patients, and the time of preoperative immunotherapy.

Even though cytopenia caused by either chemotherapy or radiotherapy is a common complication in cancer patients, chemoradiotherapy remains an essential treatment for the majority of patients. The purpose of this study was to look into the clinical efficacy and cost-effectiveness of recombinant human thrombopoietin (rhTPO) in treating chemo- or chemoradiotherapy-induced grade II, III, and IV thrombocytopenia. From December 2019 to November 2020, 233 lung cancer patients admitted to our hospital with chemotherapy- or chemoradiotherapy-induced thrombocytopenia were enrolled and treated with rhTPO. The study's findings revealed a significant disparity in the use of concurrent chemoradiotherapy in patients with grade II, III, and IV thrombocytopenia. All costs, including rhTPO treatment costs, platelet costs, drug costs, and nondrug costs, tended to rise as the severity of thrombocytopenia increased. In the treatment of chemotherapy or radiotherapy-induced thrombocytopenia, rhTPO has shown good clinical efficacy. In the treatment of grade II thrombocytopenia, rhTPO has a favorable economic evaluation. As a result, early intervention and thrombocytopenia treatment should be provided, which warrants further clinical investigation.

BACKGROUND: Anaplastic lymphoma kinase (ALK) fusion is an important oncogenic driver in non-small cell lung cancer (NSCLC). Reports on the intergenic region (IGR) as an ALK fusion partner are rare. Here, we report the case of a patient with advanced NSCLC harboring a human immunodeficiency virus type I enhancer binding protein 1 (HIVEP1)-ALK fusion that responded effectively to alectinib. CASE DESCRIPTION: A 60-year-old non-smoking male was referred with a 3-month history of productive cough secondary to lung adenocarcinoma metastatic to mediastinal lymph nodes, brain, liver, and bone (T2N3M1c, stage IVB). Next-generation sequencing identified an IGR (upstream HIVEP1-) ALK fusion, and immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) results were consistent with an ALK-positive tumor. The patient was subsequently started on alectinib, with no obvious adverse reaction. After 1 month of therapy, the patient achieved significantly remission of the clinical symptoms and had led to an ongoing partial response (PR) lasting >33 months. CONCLUSIONS: Our experience highlights the efficacy of alectinib in a patient with HIVEP1-ALK fusion positive NSCLC with multiple metastases including brain disease, and the need for multiple genetic testing methods to verify the oncogenicity of ALK fusions prior to treatment. It could provide useful guidance for the treatment of similar cases in the future.

Patients treated with immune checkpoint inhibitors (ICIs) often experience unique immune-related adverse events (irAEs), and the previous studies demonstrated an association between irAEs and better outcomes in patients with ICI treatment for advanced non-small cell lung cancer (NSCLC). However, the correlation between the occurrence of mild and severe irAEs and prognosis remains unclear. Additionally, little is known regarding the association between the timing of mild and severe irAEs and clinical outcomes. We retrospectively conducted a multicenter study of advanced NSCLC patients treated with ICI monotherapy. Of the 222 patients, 79 patients (35.6%) experienced at least one irAE, and most were of grade 1 or 2 (mild) (26.6%). The most common irAEs were pneumonitis (n = 21, 9.5%) and skin-related adverse reactions (n = 19, 8.6%). The median progression-free survival of all patients treated with ICIs was 3.2 months. Patients experiencing irAEs had a better prognosis than those without such events (6.5 vs. 2.6 months, p = 0.004), and mild irAEs were associated with the best prognosis. The difference in overall survival between mild and severe irAEs was significant (34.3 vs. 17.3 months, p = 0.021). We further analyzed differences between patients with irAEs occurring at 3 or 6 weeks, and found that the earlier the occurrence of mild irAEs, the better the prognosis; however, the opposite was true for severe irAEs. In summary, patients with early occurring mild irAEs showed better clinical outcomes, whereas those with early severe irAEs tended to show poorer clinical outcomes.

Immunotherapy has demonstrated good efficacy and survival outcomes in solid tumours. However, efficacy data for immune checkpoint inhibitors (ICIs) in advanced thymic carcinoma are lacking. The present study aimed to assess the activity of ICIs in advanced thymic carcinoma.A multicentre retrospective study was conducted to explore the efficacy and safety of ICIs for advanced thymic carcinoma. Objective response rate (ORR), progression-free survival (PFS), overall survival, and immune-related adverse events (irAEs) were analysed. In addition, factors independently associated with treatment efficacy and survival outcomes were evaluated.A total of 77 patients with advanced thymic carcinoma were enrolled between March 2016 and September 2021. The ORR was existing the difference between ICIs monotherapy (n = 23) and ICIs combined with chemotherapy (n = 54) (17.4% versus 44.4%, P = 0.024). The ICIs combination treatments were associated with better median PFS (mPFS) compared to ICIs monotherapy (12.7 months versus 2.1 months, P lt; 0.001). Notably, liver or brain metastasis was a poor prognostic factor of mPFS (1.8 months versus 3.5 months, P = 0.012) in the ICIs monotherapy group. In addition, mPFS for the first-line treatment (n = 27) was longer than that for ICIs as the second- or posterior-line treatment (n = 50) (P lt; 0.001). The incidence of irAEs was 54.5% (42/77) in the 77 enrolled patients. The incidence of grade 3-4 irAE was 15.6% (12/77).Immunotherapy is effective in advanced thymic carcinoma, especially for combination with chemotherapy showed promising antitumour activity, which indicates worthy of combination treatment strategy for further study. IrAEs also require close monitoring and management.

The incidence of primary and acquired BRAF mutations is low in non-small cell lung cancer (NSCLC), with limited demographic and treatment outcome data available for this patient population. We evaluated lung cancer samples with programmed cell death ligand 1 (PD-L1) information extracted from 12 051 cases (cohort A) of lung cancer from OncoPanscan™-based sequencing of tissue (Genetron Health) and conducted retrospective multicenter data analysis using the database of Zhejiang Cancer Hospital and four other centers (cohort B, including 73 primary BRAF mutation and 14 acquired BRAF mutation cases) to compare treatment outcomes of patient groups with primary and acquired BRAF mutations. In cohort A, after propensity score analysis, 165 samples of NSCLC with BRAF mutations were screened along with 165 paired non-BRAF mutation samples. We observed no significant differences in the proportion of samples with ≥1% PD-L1 between BRAF and non-BRAF mutant groups. The median progression-free survival (mPFS) period in 13 patients with primary BRAF mutations receiving BRAF tyrosine kinase inhibitors (BRAF-TKIs) was 7.0 months. The group with primary BRAF mutations receiving immune checkpoint inhibitor (ICI) combination chemotherapy had better PFS than those administered ICI monotherapy (14.77 months vs. 5.0 months, p = 0.025) and similar results were obtained for OS (unreached vs. 20.3 months, p = 0.013). For acquired BRAF mutations, mPFS of BRAF-TKI, ICI-based, and chemotherapy-based regimens were 3.8, 1.5, and 1.9 months, respectively. Therefore, for patients with the primary BRAF V600E mutation, targeted therapy or immunochemotherapy could serve as effective treatment choices, while for those with acquired BRAF V600E, targeted drug therapy may remain the preferred solution in China.

Purpose Next generation sequencing (NGS) has been used frequently in advanced non-small cell lung cancer (NSCLC) patients. Here, we investigated the treatment selections and clinical benefits of NGS technologies for patients with advanced lung cancer in a real-world setting.Methods This retrospective study enrolled patients with advanced NSCLC who received genetic testing. Patients received either NGS or routine testing (EGFR and/or ALK and/or ROS1 only). Clinical outcomes were compared between patients received NGS and those undergoing routine testing. Propensity score analysis was used to prevent survival bias associated with patient characteristics. Overall survival (OS) was the primary outcome. Results Of 6,451 patients with advanced NSCLC, 5,666 (87.8%) patients underwent routine testing (RT) and 785 (12.2%) were tested by NGS. The median OS was 22.6 months and the 5-year survival rate was 22.89%. Comparison of OS showed no difference according to propensity score analysis (24.8 months vs 24 months, P=0.533). With uncommon mutations, propensity score analysis showed that 1 and 2-year survival rate was significantly higher in the NGS testing group than in the routine testing group. This could be due to the higher rate of patients receiving targeted therapy (68.0% vs. 53.6%; P=0.042) and off-label drugs (28.10% vs. 11.40%; P=0.002).Conclusion NGS was not independently with a significant benefit comparing with RT in most advanced NSCLC patients. NGS could provide clinical value for rare mutations that were not available in RT, and the future benefits of NGS in immunotherapy need to be further explored.

Background: The rapid development of detection technologies has resulted in an increased use of next generation sequencing (NGS) in advanced non-small cell lung cancer (NSCLC) patients. Here, we investigated the clinical benefits of different detection technologies for patients with advanced lung cancer in a real world setting. Methods: This retrospective study enrolled advanced NSCLC patients diagnosed between January 1, 2013 and June 30, 2019 in Zhejiang Cancer Hospital who received genetic testing. Patients received either NGS or routine testing (EGFR and/or ALK and/or ROS1 only). Although different panels were used for NGS, they all included nine genes mentioned as molecular biomarkers in the NCCN guidelines (EGFR, ALK, ROS1, KRAS, HER2, BRAF, MET, RET, and NTRK). Clinical outcomes were compared between advanced NSCLC patients who received NGS and those undergoing routine testing. Overall survival (OS) and survival rates were analyzed. Propensity score analysis was used to prevent survival bias associated with patient characteristics.Results: Of 6,451 patients with advanced NSCLC included in the analysis, 5,666 (87.8%) patients underwent routine testing and 785 (12.2%) were tested by NGS. The median OS was 22.6 months and the 5-year survival rate was 22.89%. Comparison of OS showed an absolute difference between the two cohorts according to unadjusted survival curves (24.8 months vs. 22.1 months, P=0.0097), whereas no difference in OS was observed using propensity score analysis (P=0.533). The 1-year survival rate was significantly higher in patients tested by NGS than in those undergoing routine testing (82.0% vs. 70.7%, P=0.0004). In patients with uncommon mutations and in those receiving targeted therapies, propensity score analysis showed that the 1- and 2-year mortalities were significantly lower in the NGS group than in the routine testing group without mutations. This could be due to the higher rate of patients receiving targeted therapy (68.0% vs. 53.6%; P=0.042) and off-label drugs (28.10% vs. 11.40%; P=0.002) in the NGS testing cohort.Conclusions: Although propensity score analysis showed NGS had no significant benefit with RT, NGS detected more uncommon mutations and improved off-label drugs treatments. The findings highlight the importance of NGS detection, lead to a clinical benefit in uncommon mutations.

Background It has been reported that Osaka prognostic score (OPS), based on C-reactive protein (CRP), total lymphocyte counts (TLC) and albumin (ALB), was relevant to prognosis in colorectal cancer. However, the role of OPS regarding prognosis in patients with esophageal squamous cell carcinoma (ESCC) has not been reported. The current study aimed to explore the clinical outcome of OPS and establish and validate a nomogram for survival prediction in ESCC after radical resection. Methods This retrospective study included 395 consecutive ESCC patients with radical resection. Then patients were randomly divided into two cohorts: training cohort (276) and validation cohort (119). The OPS, based on TLC, CRP and ALB, was constructed to verify the prognostic value by Kaplan-Meier curves and Cox analyses. A nomogram model for prognosis prediction of cancer-specific survival (CSS) was developed and validated in two cohorts. Results Kaplan-Meier curves regarding the 5-year CSS for the groups of OPS 0, 1, 2 and 3 were 55.3, 30.6, 17.3 and 6.7% (P P Conclusion The OPS serves as a novel, convenient and effective predictor in ESCC after radical resection. The OPS-based nomogram has potential independent prognostic value, which can accurately and effectively predict individual CSS in ESCC after radical resection.

EGFR-mutant non-small-cell lung cancer (NSCLC) patients inevitably develop drug resistance when treated with EGFR tyrosine kinase inhibitors (TKIs). Systematic genetic analysis is important to understand drug-resistant mechanisms; however, the clinical significance of co-occurring genetic alterations at baseline, co-acquired mutations at progressive disease (PD), and the clonal evolution remain underinvestigated. We performed targeted sequencing of pre-treatment and PD tumor samples from 54 EGFR-mutant NSCLC patients. Ten additional patients were sequenced using whole-exome sequencing to infer the clonal evolution patterns. We observed a domain-dependent effect of PIK3CA mutation at baseline on patient progression-free survival (PFS). In addition, at baseline, 9q34.3/19p13.3 (NOTCH1/STK11/GNA11) showed a co-deletion pattern, which was associated with a significantly worse PFS (p = 0.00079). T790M-postive patients with other concurrent acquired oncogenic mutations had a significantly shorter PFS (p = 0.005). Besides acquired T790M mutation, chromosomal instability (CIN) related genes, including AURKA and TP53 alterations, were the most frequently acquired events. CIN significantly increased during TKI treatment in T790M-negative patients and is a candidate resistance mechanism to the first-generation TKIs. Clonal evolution analyses suggest that the composition and relationship among resistant subclones, particularly relationship with T790M subclone, affect patients’ outcomes. Overall, our findings of novel co-occurring alterations and clonal evolution patterns can be served as predictive biomarkers to stratify patients and help to better understand the drug-resistant mechanism to TKIs.

// Ying Jin 1, 2 , Yang Shao 3 , Xun Shi 1 , Guangyuan Lou 1 , Yiping Zhang 1 , Xue Wu 3 , Xiaoling Tong 3 , Xinmin Yu 1, 4 1 Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China 2 Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, China 3 Geneseeq Technology Inc., Toronto, Ontario, Canada 4 Zhejiang Key Laboratory of Diagnosis and Treatment Technology of Thoracic Oncology, Hangzhou, China Correspondence to: Xinmin Yu, email: yu_xinm@sina.cn Keywords: non-small-cell lung cancer, epithelial growth factor receptor, tyrosine kinase inhibitor, drug resistance, next generation sequencing Received: April 29, 2016 Accepted: July 28, 2016 Published: August 12, 2016 ABSTRACT Patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive epithelial growth factor receptor (EGFR) mutations invariably develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Identification of actionable genetic alterations conferring drug-resistance can be helpful for guiding the subsequent treatment decision. One of the major resistant mechanisms is secondary EGFR-T790M mutation. Other mechanisms, such as HER2 and MET amplifications, and PIK3CA mutations, were also reported. However, the mechanisms in the remaining patients are still unknown. In this study, we performed mutational profiling in a cohort of 83 NSCLC patients with TKI-sensitizing EGFR mutations at diagnosis and acquired resistance to three different first-generation EGFR TKIs using targeted next generation sequencing (NGS) of 416 cancer-related genes. In total, we identified 322 genetic alterations with a median of 3 mutations per patient. 61% of patients still exhibit TKI-sensitizing EGFR mutations, and 36% of patients acquired EGFR-T790M . Besides other known resistance mechanisms, we identified TET2 mutations in 12% of patients. Interestingly, we also observed SOX2 amplification in EGFR-T790M negative patients, which are restricted to Icotinib treatment resistance, a drug widely used in Chinese NSCLC patients. Our study uncovered mutational profiles of NSCLC patients with first-generation EGFR TKIs resistance with potential therapeutic implications.

Zhengbo Song,1,2 Xinmin Yu,1,2 Guangyuan Lou,1,2 Xun Shi,1,2 Yiping Zhang1,2 1Department of Chemotherapy, Zhejiang Cancer Hospital, 2Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Zhejiang province, Hangzhou, People’s Republic of China Objective: No definitive chemotherapeutic regimen has been established in patients with non-small-cell lung cancer (NSCLC) who failed second- or third-line treatment. The aim of this study was to evaluate apatinib, a VEGFR-2 inhibitor, in advanced NSCLC as salvage treatment.Methods: We evaluated the efficacy and toxicity of apatinib in patients with previously treated advanced NSCLC from 2014 to 2015 in Zhejiang Cancer Hospital. Survival analysis was performed by the Kaplan–Meier method.Results: Forty-two patients were included in the present study. Four patients achieved partial response, and 22 achieved stable disease, representing a response rate of 9.5% and a disease control rate of 61.9%. Median progression-free survival and overall survival were 4.2 and 6.0months, respectively. The toxicities associated with apatinib were generally acceptable with a total grade 3/4 toxicity of 50%.Conclusion: Apatinib appears to have some activity against advanced NSCLC when utilized as salvage treatment. Keywords: non-small-cell lung cancer, apatinib, VEGF, efficacy

Background Currently, molecular profiles and prognosis of primary pulmonary neuroendocrine carcinoma (PNC) are poorly elucidated. The present study was designed to evaluate genomic abnormalities and survival in patients with primary PNC. Methods Completely resected PNC samples were collected from Zhejiang Cancer Hospital during the period of 2008 to 2015. Nine driver genes, including 6 mutations ( EGFR , KRAS , NRAS , PIK3CA , BRAF , and HER2 ) and 3 fusions ( ALK , ROS1 , and RET ), were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Survival analysis was conducted by the Kaplan-Meier method. Results A total of 108 patients with pathologically confirmed PNC were enrolled. The types were pulmonary large-cell neuroendocrine carcinoma (PLCNC, n = 52), small-cell lung cancer (SCLC, n = 44), and carcinoid (n = 12). Twelve patients (11.1%) harbored genomic aberrations. The most frequent gene abnormalities in decreasing order were PIK3CA (n = 5, 4.6%), EGFR (n = 3, 2.8%), KRAS (n = 2, 1.9%), ALK (n = 1, 0.9%), and RET (n = 1, 0.9%). No ROS1 , BRAF , NRAS , or HER2 mutation was detected. The frequencies of gene aberrations were 15.4%, 6.8%, and 8.3% in PLCNC, SCLC, and carcinoid, respectively. Survival differences existed among PLCNC, SCLC, and carcinoid groups (37.0 vs. 34.0 vs. not reached, P = .035); however, no difference existed between PLCNC and SCLC groups ( P = .606). Conclusions Genomic abnormality is rare in patients with PNC and it is the most frequently observed in PLCNC.

This study aims to evaluate the efficacy and safety of crizotinib for advanced ALK-positive non-small cell lung cancer (NSCLC) patients.Twenty-eight patients with advanced ALK-positive NSCLC were given orally crizotinib 250 mg b. i.d., and were followed up to evaluate the therapeutic efficacy and safety.Among the 28 patients, the objective response rate (ORR) was 71.4% (20/28) and disease control rate (DCR) was 92.9% (26/28). Three patients achieved complete response. Seventeen patients had partial response. The most common drug-related adverse events were mild flickering vision and gastrointestinal reaction. Eleven patients experienced flickering vision. Nine patients had nausea and vomiting. Eight patients had diarrhea. They were all reversible and of grade I or II. Only one patient had grade III myelosuppression. Among the 28 patients, 16 cases were disease-free and 12 cases had progressive disease, with a progression-free survival of 8.2 months.Crizotinib is effective and tolerable in the treatment of advanced ALK-positive NSLCC. However, its long-term treatment efficacy requires to be further studied.

Patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive epithelial growth factor receptor (EGFR) mutations invariably develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Identification of actionable genetic alterations conferring drug-resistance can be helpful for guiding the subsequent treatment decision. One of the major resistant mechanisms is secondary EGFR-T790M mutation. Other mechanisms, such as HER2 and MET amplifications, and PIK3CA mutations, were also reported. However, the mechanisms in the remaining patients are still unknown. In this study, we performed mutational profiling in a cohort of 83 NSCLC patients with TKI-sensitizing EGFR mutations at diagnosis and acquired resistance to three different first-generation EGFR TKIs using targeted next generation sequencing (NGS) of 416 cancer-related genes. In total, we identified 322 genetic alterations with a median of 3 mutations per patient. 61% of patients still exhibit TKI-sensitizing EGFR mutations, and 36% of patients acquired EGFR-T790M. Besides other known resistance mechanisms, we identified TET2 mutations in 12% of patients. Interestingly, we also observed SOX2 amplification in EGFR-T790M negative patients, which are restricted to Icotinib treatment resistance, a drug widely used in Chinese NSCLC patients. Our study uncovered mutational profiles of NSCLC patients with first-generation EGFR TKIs resistance with potential therapeutic implications.

Olanzapine is an atypical antipsychotic that has shown efficacy for the treatment of nausea, anxiety, and insomnia. This study was conducted to evaluate the efficacy of olanzapine (5 mg) combined with 5-HT3 receptor antagonists and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in lung patients receiving cisplatin-based (25 mg/m2 d1-3) highly emetogenic chemotherapy (HEC). Olanzapine (5 mg) was administered a day prior to cisplatin administration and continued on days 1 to 5. We evaluated complete response (CR) rate and rates of no nausea and no vomiting in 3 periods. In addition, Self-Rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and The Functional Living Index-Emesis (FLIE) questionnaire were also assessed. A total of 40 lung cancer patients were included. CR for acute, delayed, and over all phases were 82.5%, 75.0%, and 70.0%, respectively. The rate of no nausea in the acute phase was 70.0% and 62.5% in delayed phase. The rate of no vomiting in the acute phase was 85.0%, and 77.5% in delayed phase. The rate of no nausea and no vomiting in the overall phase were 57.5% and 75.0%, respectively. The median SAS and SDS score were 37.9 and 41.6 in pre-chemotherapy, respectively. Up to day 6 after chemotherapy treatment, the median SAS and SDS score were 36.9 and 42.0, respectively. The median FLIE score was 111.7. The main side effects were grade 1 somnolence (35.0%) and mild constipation (52.5%). Around 5 mg olanzapine may be used as a potential, safe, and cost-beneficial alternative to prevent nausea and vomiting for HEC, particular for multiday chemotherapy regimen.

Aims. This study aimed to investigate CHRNA3 (rs8040868) and PHACTR2 (rs9390123) single-nucleotide polymorphisms (SNPs) for association with non-small-cell lung cancer (NSCLC) risk in a Chinese population, and whether the environment affects the genetic polymorphisms. Methods. This case and control study included 500 NSCLC patients and 500 age-matched healthy controls. CHRNA3 (rs8040868) and PHACTR2 (rs9390123) SNPs were genotyped and associated for NSCLC risk by computing the odds ratio and 95% confidence interval from multivariate unconditional logistic regression analyses with adjustment of age. Results. The minor allele frequency (MAF) of CHRNA3 (rs8040868) and PHACTR2 (rs9390123) was 0.350 (C) and 0.397 (C), respectively. The frequencies of genotype and allele in CHRNA3 (rs8040868) and PHACTR2 (rs9390123) were not significantly different between the cases and controls, or between either of the subgroups. Conclusion. Although rs8040868 and rs9390123 SNPs are not associated with NSCLC risk in Chinese population, the results strongly suggest that geographical agents interact with human genetic polymorphism independent of ethnic background.

The preclinical experiments and several clinical studies showed icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in Chinese patients with advanced non-small cell lung cancer (NSCLC) who failed previous chemotherapy. We performed a retrospective study of the efficacy and safety of icotinib monotherapy in a different and more recent sample of Chinese patients.The clinical data of 149 patients with advanced NSCLC who were admitted to Zhejiang Cancer Hospital from August 1, 2011 to July 31, 2012 were retrospectively analyzed. All patients were given icotinib treatment after the failure of previous chemotherapy. Univariate and multivariate analyses were conducted based on the Kaplan Meier method and Cox proportional hazards model.The objective response rate was 33/149 and disease control rate was 105/149. No complete response occurred. Median progression free survival (PFS) with icotinib treatment was 5.03 months (95% CI: 3.51 to 6.55). Median overall survival was 12.3 months (95% CI: 10.68 to 13.92). Multivariate analysis showed that the mutation of EGFR and one regimen of prior chemotherapy were significantly associated with longer PFS. At least one drug related adverse event was observed in 65.8% (98/149) of patients, but mostly grade 1 or 2 and reversible and none grade 4 toxicity.Icotinib monotherapy is an effective and well tolerated regimen for Chinese patients with NSCLC after the failure of chemotherapy. It is a promising agent and further study with icotinib in properly conducted trials with larger patient samples and other ethnic groups is warranted.