// Yue-Lun Zhang 1, 2 , Jin-Qiu Yuan 1, 2 , Kai-Feng Wang 3 , Xiao-Hong Fu 1, 2 , Xiao-Ran Han 1, 2 , Diane Threapleton 1 , Zu-Yao Yang 1, 2 , Chen Mao 1, 2 , Jin-Ling Tang 1, 2 1 Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China 2 Shenzhen Municipal Key Laboratory for Health Risk Analysis, Shenzhen Research Institute of The Chinese University of Hong Kong, Shenzhen, Guangdong Province, China 3 Division of Epidemiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong Province, China Correspondence to: Chen Mao, email: maochen@cuhk.edu.hk Jin-Ling Tang, email: jltang@cuhk.edu.hk Keywords: non-small cell lung cancer, epidermal growth factor receptor, prevalence, systematic review, meta-analysis Received: May 17, 2016     Accepted: September 25, 2016     Published: October 12, 2016 ABSTRACT Objectives: Estimate the epidermal growth factor receptor ( EGFR ) mutation prevalence in all non-small cell lung cancer (NSCLC) patients and patient subgroups. Results: A total of 456 studies were included, reporting 30,466 patients with EGFR mutation among 115,815 NSCLC patients. The overall pooled prevalence for EGFR mutations was 32.3% (95% CI 30.9% to 33.7%), ranging from 38.4% (95% CI: 36.5% to 40.3%) in China to 14.1% (95% CI: 12.7% to 15.5%) in Europe. The pooled prevalence of EGFR mutation was higher in females (females vs. males: 43.7% vs. 24.0%; OR: 2.7, 95% CI: 2.5 to 2.9), non-smokers (non-smokers vs. past or current smokers: 49.3% vs. 21.5%; OR: 3.7, 95% CI: 3.4 to 4.0), and patients with adenocarcinoma (adenocarcinoma vs. non-adenocarcinoma: 38.0% vs. 11.7%; OR: 4.1, 95% CI: 3.6 to 4.8). Materials and Methods: PubMed, EMBASE, and the Cochrane Library were searched to June 2013. Eligible studies reported EGFR mutation prevalence and the association with at least one of the following factors: gender, smoking status and histology. Random-effects models were used to pool EGFR mutation prevalence data. Conclusion: This study provides the exact prevalence of EGFR mutations in different countries and NSCLC patient subgroups.

/pdf/the-prevalence-of-egfr-mutation-in-patients-with-non-small-2zch4vyl3c.pdf

The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis

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Pathology And Genetics Of Tumours Of The Lung Pleura Thymus And Heart

Summary Background Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer. Methods In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18–75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. Findings 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67–1·05; median progression-free survival 4·6 months [95% CI 3·5–6·3] vs 3·4 months [2·3–3·8]; p=0·13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 [61%] vs 140 [70%]; p=0·046), especially drug-related diarrhoea (37 [19%] vs 55 [28%]; p=0·033). Interpretation Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer. Funding Zhejiang Beta Pharma (China), the Chinese National Key Special Program for Innovative Drugs, the 863 Project, and Zhejiang Provincial Key Special Program.

/pdf/icotinib-versus-gefitinib-in-previously-treated-advanced-non-n4p4t32r29.pdf

Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases.

Prognostic role of pretreatment blood neutrophil-to-lymphocyte ratio in advanced cancer survivors: A systematic review and meta-analysis of 66 cohort studies

Background

The outcomes of patients with metastatic nasopharyngeal carcinoma (NPC) differ between individuals. The purpose of this study was to examine the impact of neutrophil-to-lymphocyte ratio (NLR) on survival in patients with metastatic NPC.



Methods

A total of 229 patients with disseminated NPC were evaluated. The effects of pretreatment peripheral blood neutrophil, lymphocyte, and NLR on survival were examined using the proportional hazards regression model to estimate hazard ratio (HR). The relationship between short-term treatment efficacy and pretreatment NLR was analyzed using the chi-square test.



Results

The pretreatment elevated neutrophil count (p = .020), percentage of neutrophil (p < .001), and NLR (p = .002) were statistically significantly associated with a poor prognosis. The cutoff value selected for NLR was 3.6. The median survival time was 15.3 months for the high-NLR group and was 23.5 months for the low-NLR group (p < .001).



Conclusion

NLR is a prognosticator in patients with metastatic NPC. © 2014 Wiley Periodicals, Inc. Head Neck 37: 69–75, 2015

Pretreatment neutrophil-to-lymphocyte ratio as predictor of survival for patients with metastatic nasopharyngeal carcinoma.

Cutaneous metastases in primary advanced non-small cell lung cancer (NSCLC) rarely occur in comparison with other site involvement. The incidence of cutaneous metastases and its prognosis is not well known. Data from a 2,130 patients with advanced NSCLC were analyzed, in order to assess the incidence and survival prognosis of cutaneous metastases in primary advanced NSCLC. The clinical data of 2,130 patients with advanced NSCLC who were admitted to Zhejiang cancer Hospital from January 1998 to December 2007 were retrospectively analyzed. Data pertaining to their presentation, diagnosis treatment, pathology, follow–up, and clinical course were documented. Clinical characteristics were investigated based on the clinical and pathologic records. All of the cutaneous metastases were confirmed by cytology or biopsy. Survival analysis was made by Kaplan–Meier method. The Cox regression model was performed to analyze the relationship between the influential factors and the overall survival. Among the 2,130 advanced NSCLC patients as initial diagnosis, 60 (2.8 %) demonstrated abnormally cutaneous metastases. Fifteen patients with only cutaneous metastases, forty-five subjects combined with other site metastasis. There were 56 patients who received chemotherapy, and the first-line disease control rate was 33.9 %, the median free progression survival time was 1.9 months. There were significant differences in overall survival between cutaneous metastases and non-cutaneous metastases arms (3.9 vs. 10.0 months, P < 0.001). Multivariate analyses revealed that performance status and chemotherapy efficacy statistically associated with overall survival. This retrospective study indicated that 2.8 % of advanced NSCLC patients showed cutaneous metastases as an initial presentation. Cutaneous metastases of lung cancer are of poor prognosis.

Cutaneous metastasis as a initial presentation in advanced non-small cell lung cancer and its poor survival prognosis.

This retrospective study was designed to investigate the clinical characteristics, diagnosis, treatment and prognosis of primary tracheobronchial mucoepidermoid carcinoma (MEC). Clinical data were retrospectively analyzed from 32 patients with pathologically confirmed primary tracheobronchial MEC between January 1990 and December 2010 at Zhejiang Cancer Hospital. The Kaplan-Meier methods were used to estimate and compare survival rates. There were 19 males and 13 females ranging in age from 7 to 73 years, with a median age of 28 years. Twenty-six of the 32 patients were treated with surgery alone. The other six patients were treated with surgery plus postoperative radiotherapy or chemotherapy. Six patients died during the follow-up time. The overall five-year survival rates were 81.25%, whereas the five-year survival rate of seven patients with high-grade tumors was only 28.6%. Stage I and II patients experienced better survival than Stage III and IV patients (the five-year survival rate was 100% and 43.6% respectively, P<0.001). Primary tracheobronchial MEC is a rare disease. Histologic grading and TNM (tumor-node-metastasis)staging are independent prognostic factors. Surgical resection is the primary treatment.

/pdf/primary-tracheobronchial-mucoepidermoid-carcinoma-a-5e7vrfgr8t.pdf

Primary tracheobronchial mucoepidermoid carcinoma--a retrospective study of 32 patients.

Background Adenosquamous carcinoma (ASC) of the lung is a rare subtype of nonsmall-cell lung cancer (NSCLC). To date, the efficacious targeted therapy for advanced ASC remains unclear and the epidermal growth factor receptor (EGFR) mutation rate is not well known. Methods We retrospectively reviewed clinical information of patients with ASC who were treated with gefitinib or erlotinib at Zhejiang Cancer Hospital between January 2007 and December 2011. Survival analysis was evaluated by the Kaplan-Meier method. EGFR mutations were assessed in part using direct sequencing methods. Results In total, 49 patients with a median age of 57 years were used in this study. Thirteen patients achieved a partial response and 19 had disease stabilization. The objective response rate was 26.5%, and the disease control rate was 65.3%. The median progression-free survival and overall survival were 4.3 and 17.6 months, respectively. In 21 patients with adequate specimens for molecular analysis, 7 (33.3%) had EGFR mutations (4 with deletions within exon 19 and 3 with L858R messenger mutation in exon 21). EGFR mutations were significantly more frequent in women (4/9, 44.4%) than men (3/12, 25%), never-smokers (6/15, 40%), and smokers (1/6, 16.7%). Conclusion EGFR-tyrosine kinase inhibitor (TKI) is an effective treatment for ASC. The frequency of EGFR mutation and clinical characteristics of the EGFR mutants in ASC are similar to those of Asian patients with adenocarcinoma.

Therapeutic efficacy of gefitinib and erlotinib in patients with advanced lung adenosquamous carcinoma

Background
Tumor length is an important prognostic factor for many carcinomas, but its role in esophageal cancer remained undetermined. The aim of this study was to investigate the effect of tumor length on survival for patients with confined tumors (grade pT1-2) without lymph-node metastases in esophageal squamous cell carcinoma.

/pdf/analysis-of-the-tumor-length-and-other-prognosis-factors-in-3pivz0ne2b.pdf

Analysis of the tumor length and other prognosis factors in pT1-2 node-negative esophageal squamous cell carcinoma in a Chinese population.

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