This study aimed to evaluate the efficacy of anaplastic lymphoma kinase (ALK)-inhibitors in the treatment of ALK-positive non-small cell lung cancer (NSCLC) by using a meta-analysis of clinical trials. We searched PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov by using keywords related to the topic in August 2018. The pooled effect sizes were calculated based on a random-effects model. We also performed subgroup meta-analysis by types of ALK inhibitors (crizotinib, ceritinib, and alectinib). A total of 20 clinical trials with 10 single-arm trials and 10 double-arm trials were included in the final meta-analysis. The median overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), 1 year survival rate, and 2 year survival rate were 19.14 months, 8.47 months, 62%, 78%, 74%, and 62%, respectively. ALK inhibitors showed a significantly superior efficacy compared with chemotherapy (hazard ratio (HR) for OS, 0.83; HR for PFS, 0.43; rate difference (RD) for ORR, 0.23; and RD for DCR, 0.10). The current meta-analysis of clinical trials showed the significant efficacy of ALK inhibitors in the treatment of ALK-positive NSCLC. Further head-to-head trials are needed to compare their efficacy with other types of NSCLC treatment regimens. PROSPERO registration: CRD42018085987.

This study aims to investigate the efficacy of targeted therapies in the treatment of non-small cell lung cancer (NSCLC) by using a network meta-analysis of clinical trials. PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov were searched by using keywords related to the topic on 19 September 2018. Two investigators independently selected relevant trials by pre-determined criteria. A pooled response ratio (RR) for overall response rate (ORR) and a hazard ratio (HR) for progression-free survival (PFS) were calculated based on both the Bayesian and frequentist approaches. A total of 128 clinical trials with 39,501 participants were included in the final analysis of 14 therapeutic groups. Compared with chemotherapy, both ORR and PFS were significantly improved for afatinib, alectinib, and crizotinib, while only PFS was significantly improved for cabozantinib, ceritinib, gefitinib, and osimertinib. Consistency was observed between the direct and indirect comparisons based on the Bayesian approach statistically and the frequentist approach visually. Cabozantinib and alectinib showed the highest probability for the first-line treatment ranking in ORR (62.5%) and PFS (87.5%), respectively. The current network meta-analysis showed the comprehensive evidence-based comparative efficacy of different types of targeted therapies, which would help clinicians use targeted therapies in clinical practice.

Purpose: This study evaluated the association between night-shift work (NSW) and breast cancer risk as well as subtypes of breast cancer in Korean women. Patients and methods: The study population included 1721 female breast cancer cases and 1721 female controls matched by age. The subtypes of breast cancer were determined based on estrogen, progesterone, and human epidermal growth factor receptor 2 statuses by reviewing pathology reports. Odds ratios (ORs) for NSW experience, age at commencement of NSW, frequency, and duration were estimated using conditional logistic regression and were adjusted for confounders such as parity and socioeconomic status–related factors. Results: Among 1721 pairs, 10.58% of cases and 9.59% of controls had ever engaged in NSW. NSW was not associated with breast cancer risk in terms of ever having night-shift exposure (adjusted OR was 1.11, 95% confidence interval [CI] =0.89–1.40), duration, frequency, or cumulative working time. The OR for >10 years of lifetime duration of NSW was 1.55 (95% CI 0.89–2.69, P=0.124). In addition, the OR for >35,000 hrs for cumulative frequency of night work was OR=1.42 (95% CI=0.73–2.74, P=0.304). There was no heterogeneity in ORs of ever having NSW and cumulative duration of NSW between four subtypes of breast cancer. Conclusion: NSW including long-term and heavy working exposure was not associated with breast cancer risk.

Resistin is a polypeptide implicated in inflammatory processes, and as such could be linked to colorectal carcinogenesis. In case-control studies, higher resistin levels have been found in colorectal cancer (CRC) patients compared to healthy individuals. However, evidence for the association between pre-diagnostic resistin and CRC risk is scarce. We investigated pre-diagnostic resistin concentrations and CRC risk within the European Prospective Investigation into Cancer and Nutrition using a nested case-control study among 1293 incident CRC-diagnosed cases and 1293 incidence density-matched controls. Conditional logistic regression models controlled for matching factors (age, sex, study center, fasting status, and women-related factors in women) and potential confounders (education, dietary and lifestyle factors, body mass index (BMI), BMI-adjusted waist circumference residuals) were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for CRC. Higher circulating resistin concentrations were not associated with CRC (RR per doubling resistin, 1.11; 95% CI 0.94–1.30; p = 0.22). There were also no associations with CRC subgroups defined by tumor subsite or sex. However, resistin was marginally associated with a higher CRC risk among participants followed-up maximally two years, but not among those followed-up after more than two years. We observed no substantial correlation between baseline circulating resistin concentrations and adiposity measures (BMI, waist circumference), adipokines (adiponectin, leptin), or metabolic and inflammatory biomarkers (C-reactive protein, C-peptide, high-density lipoprotein cholesterol, reactive oxygen metabolites) among controls. In this large-scale prospective cohort, there was little evidence of an association between baseline circulating resistin concentrations and CRC risk in European men and women.

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre‐diagnostic serum resistin concentrations in relation to CRC‐specific and all‐cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC‐specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause‐specific Cox proportional hazards models and further in sensitivity analyses using Fine–Gray proportional subdistribution hazards models. For all‐cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow‐up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC‐specific mortality (HR_Q4vsQ1 = 0.95, 95% CI: 0.73–1.23; P_trend = .97; and HR_{per doubling of resistin concentration} = 1.00; 95% CI: 0.84–1.19; P = .98) or all‐cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre‐diagnostic circulating resistin concentrations and CRC‐specific or all‐cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.

Human fatty acid binding protein‐4 (FABP‐4), a protein elevated in obesity that promotes colon cancer cell invasiveness and metastasis, may be associated with higher mortality in individuals with colorectal cancer (CRC) and may serve as a mediator of the obesity–mortality association in these individuals. We used a causal diagram to inform covariate selection and applied Cox proportional hazards models to estimate hazard ratios (HRs) for CRC‐specific, non‐CRC‐specific, and all‐cause mortality by FABP‐4 levels measured in baseline blood samples from 1371 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. Competing risk analyses were adapted for CRC and non‐CRC deaths. Mediation analyses were conducted to estimate total effects (TEs), direct effects (DEs), and mediation proportions (MPs) by FABP‐4 of pre‐diagnostic body mass index (BMI) on mortality. In the fully adjusted model including BMI, higher circulating FABP‐4 concentrations were associated with higher CRC mortality (HR _Q4vsQ1 = 1.49; 95% CI: 1.11–2.00) and all‐cause mortality (HR _Q4vsQ1 = 1.49; 95% CI: 1.15–1.93), but not statistically associated with non‐CRC mortality (HR _Q4vsQ1 = 1.51; 95% CI: 0.82–2.76). The TE and DE per 5 kg/m ² of BMI on all‐cause mortality were 1.21; 95% CI: 1.10–1.34, and 1.13; 95% CI: 1.02–1.26, respectively, with a MP of 34.5% ( p = .002) by FABP‐4. For CRC‐specific and non‐CRC‐specific mortality, MPs by FABP‐4 were 33.7% ( p = .03) and 36.1% ( p = .02), respectively. In conclusion, higher concentrations of FABP‐4 were associated with higher CRC‐specific and all‐cause mortality in individuals with CRC. FABP‐4 was a significant partial mediator of the adiposity‐mortality relationship in individuals with CRC.