Summary: Background: A 4G/5G polymorphism in the promoter region of the plasminogen activator inhibitor type 1 (PAI-1) gene has been reported to enhance the plasma levels of PAI-1, which plays an important role in fibrinolysis disorders and venous thromboembolism, but a large number of studies have reported inconclusive results. Therefore, we performed a meta-analysis to analysis these associations. Materials and methods: We performed a publication search for articles published before April 2019 by using the electronic databases of web of Science, Embase, PubMed, CNKI, CBM and WanFang data with the following terms “PAI-1”, “polymorphism”, “Venous Thromboembolism”. Two investigators independently extracted data and assessed study quality. Statistical analyses were undertaken using Stata 14.0. Results: A total of 27 studies, with 3135 patients and 5346 controls were included. Overall, the variant PAI-1 4G/4G and PAI-1 4G/5G was associated with venous thromboembolism risk, compared with the PAI-1 5G/5G allele in the populations included in the analysis. Stratified analysis revealed that PAI-1 4G/4G and PAI-1 4G/5G genotypes were associated with an increased VTE risk among Asia populations in all five genetic models. Conclusions: The PAI-1 4G/5G polymorphism may be a potential biomarker of VTE risk, particularly in Asia populations. Further larger studies with multi-ethnic populations are required to further assess the association between PAI-1 4G/4G polymorphisms and VTE risk.

To compare the efficacy and toxicity of irinotecan-based chemotherapy (IBC) and non-irinotecan-based chemotherapy (NIBC) as first-line treatment for stage IIIB/IV non-small cell lung cancer (NSCLC). PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), abstracts from the annual meetings of ASCO and the ESMO up to 2014 were searched for randomized controlled trials (RCTs) that compared IBC with NIBC. Data on overall survival (OS) and progression-free survival (PFS) were meta-analyzed to provide hazard ratios (HRs), while data on overall response rate (ORR) and frequencies of toxicity were meta-analyzed to provide relative risk ratios (RR). Seven RCTs (6 RCTs from Asian population and 1 from non-Asian population) involving 1473 patients with previously untreated stage IIIB/IV NSCLC were included in the meta-analysis. IBC and NIBC were associated with similar ORR (RR: 1.08, 95 %CI: 0.94 to 1.23, p = 0.30), OS (HR: 0.97, 95 %CI: 0.88 to 1.07, p = 0.56), and PFS (HR: 1.02, 95 %CI: 0.97 to 1.08, p = 0.38). However, the subgroups between Asian and non-Asian patients differed significantly in OS (HR: 0.94 vs 1.87, p = 0.007). There was no significant difference for hematological toxicity (RR: 0.79, 95 %CI: 0.60 to 1.04, p = 0.09) and significant worse for non-hematological toxicity (RR: 2.28, 95 %CI: 1.60 to3.24, p < 0.001), when IBC compared to NIBC. As the available evidence suggests that IBC and NIBC are equivalent in terms of ORR, PFS, OS, at least in Asian patients, we recommend that IBC be considered as a first-line treatment in Asian patients with stage IIIB/IV NSCLC. However, the non-hematological toxicity of IBC must be considered.

Estimating the prognosis of esophageal squamous cell carcinoma based on The Cancer Genome Atlas (TCGA) of m6A methylation- associated genes Yu Pu, Xianfeng Lu, Xueqin Yang, Yi Yang, Dong Wang, Mengxia Li, Wei Guan, Mingfang Xu

Lung cancer is increasingly common as a second primary malignancy. However, the clinical characteristics of second primary non-small cell lung cancer after cervical cancer (CC-NSCLC) compared with first primary non-small cell lung cancer (NSCLC1) is unknown. The Surveillance, Epidemiology, and End Results (SEER) cancer registry between 1998 and 2010 was used to conduct a large population-based cohort analysis. The demographic and clinical characteristics, as well as prognostic data, were systematically analyzed. The overall survival (OS) in the two cohorts was further compared. The risk factors of second primary lung cancer in patients with cervical cancer were also analyzed. A total of 557 patients (3.52%) developed second primary lung cancer after cervical cancer, and 451 were eligible for inclusion in the final analyses. Compared with NSCLC1, patients with CC-NSCLC had a higher rate of squamous cell carcinoma (SCC) (36.59% vs 19.07%, P < 0.01). The median OS was longer for CC-NSCLC than for NSCLC1 before propensity score matching (PSM) (16 months vs. 13 months) but with no significant difference after PSM (16 months vs. 17 months). The high-risk factors for the development of cervical cancer to CC-NSCLC include age 50–79 years, black race [odds ratio (OR) 1.417; 95% confidence interval (CI) 1.095–1.834; P < 0.05], and history of radiotherapy (OR 1.392; 95% CI 1.053–1.841; P < 0.05). Age 50–79 years, black race, and history of radiotherapy were independent risk factors for second primary lung cancer in patients with cervical cancer. Patients with CC-NSCLC had distinctive clinical characteristics and better prognosis compared with patients with NSCLC1.

Lung signet ring cell carcinoma (LSRCC) is a very rare type of lung cancer, the clinical characteristics, and prognosis of which remain to be clarified. In order to explore the clinicopathological and survival-related factors associated with LSRCC, we performed a large population-based cohort analysis of data included in the Surveillance, Epidemiology, and End Results (SEER) registry from 2001- 2015. A total of 752 LSRCC and 7518 lung mucinous adenocarcinoma (LMAC) patients were incorporated into our analysis, with respective mean ages of 63.8 and 67.5 years at the time of diagnosis. LSRCC patients were significantly more likely than LMAC patients to have distant-stage disease (72.1% vs. 45.8%, p<0.0001), tumors of a high pathological grade (40.6% vs. 10.8%, p<0.0001), have undergone chemotherapy (62.1% vs. 39.9%, p<0.0001), be male (52.7% vs. 48.5%, p=0.03), and be < 40 years old (3.3% vs. 1.3%, p=0.022), whereas they were less likely to have undergone surgical treatment (52.4% vs. 77.0%, p<0.0001). LSRCC and LMAC patients exhibited median overall survival (OS) duration of 8 and 18 months (p<0.0001), respectively, although these differences were not significant after adjusting for confounding variables. Independent factors associated with a favorable patient prognosis included a primary site in the middle or lower lung lobe, underwent surgery and underwent chemotherapy. However, age ≥ 80 years, higher grade, distant summary stage disease, and T4 stage disease were linked to poor prognosis. Patient age, tumor grade, primary tumor site, summary stage, T stage, surgery, and chemotherapy were all significantly associated with LSRCC patient prognosis.

Rationale: Non-small cell lung cancer (NSCLC) patients with brain metastases (BMs) have been found as subjects of poor prognosis. Whole-brain radiotherapy (WBRT), surgery, and stereotactic radiosurgery, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), or some combinations are the most commonly employed strategies for the treatment of treatments BMs. However, some patients are resistant to all these treatments. Patient Concerns: We present an NSCLC patient with progression of BMs after treatment with WBRT and EGFR-TKIs. The patient was diagnosed with multiple metastases on July 9, 2014, and treated with docetaxel plus cisplatin chemotherapy followed with gefitinib as the maintenance therapy. The patient showed recurrence of BMs after 8-months of chemotherapy. WBRT with 30 Gy was administrated in 10 fractions. Tumor progression of the brain was diagnosed with an magnetic resonance imaging scan after 2-months of WBRT. Diagnoses: The patient was diagnosed as pulmonary adenocarcinoma with diffuse metastases in both lungs and multiple metastases in bone and brain. Progression of BMs was confirmed through magnetic resonance imaging. Interventions: This patient was administered temozolomide (150 mg/m²/d for 5 days every 28-day cycle). As a whole, 6 cycles were performed after the progression of BMs from August 2015. Outcomes: The patient got complete brain remission and lived without discomfort. The intracranial lesion did not progress until the progression of the lung lesion and led to death on February 20, 2019. The intracranial progression-free survival was 42 months, whereas the overall survival was 55 months. Lessons: For patients with NSCLC and BMs, temozolomide can be used as a treatment option, especially in patients with EGFR-TKIs resistance or without driver mutations.