Age at diagnosis for lung, colon, breast and prostate cancers: An international comparative study.

Differences in the average age at cancer diagnosis are observed across countries. We therefore aimed to assess international variation in the median age at diagnosis of common cancers worldwide, after adjusting for differences in population age structure. We used IARC's Cancer Incidence in Five Continents (CI5) Volume XI database, comprising cancer diagnoses between 2008 and 2012 from population-based cancer registries in 65 countries. We calculated crude median ages at diagnosis for lung, colon, breast and prostate cancers in each country, then adjusted for population age differences using indirect standardization. We showed that median ages at diagnosis changed by up to 10 years after standardization, typically increasing in low- and middle-income countries (LMICs) and decreasing in high-income countries (HICs), given relatively younger and older populations, respectively. After standardization, the range of ages at diagnosis was 12 years for lung cancer (median age 61-Bulgaria vs 73-Bahrain), 12 years for colon cancer (60-the Islamic Republic of Iran vs 72-Peru), 10 years for female breast cancer (49-Algeria, the Islamic Republic of Iran, Republic of Korea vs 59-USA and others) and 10 years for prostate cancer (65-USA, Lithuania vs 75-Philippines). Compared to HICs, populations in LMICs were diagnosed with colon cancer at younger ages but with prostate cancer at older ages (both pLMICS-vs-HICs < 0.001). In countries with higher smoking prevalence, lung cancers were diagnosed at younger ages in both women and men (both pcorr < 0.001). Female breast cancer tended to be diagnosed at younger ages in East Asia, the Middle East and Africa. Our findings suggest that the differences in median ages at cancer diagnosis worldwide likely reflect population-level variation in risk factors and cancer control measures, including screening.

Cancer Stage Compared With Mortality as End Points in Randomized Clinical Trials of Cancer Screening: A Systematic Review and Meta-Analysis.

Importance: Randomized clinical trials of cancer screening typically use cancer-specific mortality as the primary end point. The incidence of stage III-IV cancer is a potential alternative end point that may accelerate completion of randomized clinical trials of cancer screening. Objective: To compare cancer-specific mortality with stage III-IV cancer as end points in randomized clinical trials of cancer screening. Design, Setting, and Participants: This meta-analysis included 41 randomized clinical trials of cancer screening conducted in Europe, North America, and Asia published through February 19, 2024. Data extracted included numbers of participants, cancer diagnoses, and cancer deaths in the intervention and comparison groups. For each clinical trial, the effect of screening was calculated as the percentage reduction between the intervention and comparison groups in the incidence of participants with cancer-specific mortality and stage III-IV cancer. Exposures: Randomization to a cancer screening test or to a comparison group in a clinical trial of cancer screening. Main Outcomes and Measures: End points of cancer-specific mortality and incidence of stage III-IV cancer were compared using Pearson correlation coefficients with 95% CIs, linear regression, and fixed-effects meta-analysis. Results: The included randomized clinical trials tested benefits of screening for breast (n = 6), colorectal (n = 11), lung (n = 12), ovarian (n = 4), prostate (n = 4), and other cancers (n = 4). Correlation between reductions in cancer-specific mortality and stage III-IV cancer varied by cancer type (I2 = 65%; P = .02). Correlation was highest for trials that screened for ovarian (Pearson ρ = 0.99 [95% CI, 0.51-1.00]) and lung (Pearson ρ = 0.92 [95% CI, 0.72-0.98]) cancers, moderate for breast cancer (Pearson ρ = 0.70 [95% CI, -0.26 to 0.96]), and weak for colorectal (Pearson ρ = 0.39 [95% CI, -0.27 to 0.80]) and prostate (Pearson ρ = -0.69 [95% CI, -0.99 to 0.81]) cancers. Slopes from linear regression were estimated as 1.15 for ovarian cancer, 0.75 for lung cancer, 0.40 for colorectal cancer, 0.28 for breast cancer, and -3.58 for prostate cancer, suggesting that a given magnitude of reduction in incidence of stage III-IV cancer produced different magnitudes of change in incidence of cancer-specific mortality (P for heterogeneity = .004). Conclusions and Relevance: In randomized clinical trials of cancer screening, incidence of late-stage cancer may be a suitable alternative end point to cancer-specific mortality for some cancer types, but is not suitable for others. These results have implications for clinical trials of multicancer screening tests.

Assessment of the EarlyCDT-Lung test as an early biomarker of lung cancer in ever-smokers: A retrospective nested case-control study in two prospective cohorts.

The EarlyCDT-Lung test is a blood-based autoantibody assay intended to identify high-risk individuals for low-dose computed tomography lung cancer screening. However, there is a paucity of evidence on the performance of the EarlyCDT-Lung test in ever-smokers. We conducted a nested case-control study within two prospective cohorts to evaluate the risk-discriminatory performance of the EarlyCDT-Lung test using prediagnostic blood samples from 154 future lung cancer cases and 154 matched controls. Cases were selected from those who had ever smoked and had a prediagnostic blood sample <3 years prior to diagnosis. Conditional logistic regression was used to estimate the association between EarlyCDT-Lung test results and lung cancer risk. Sensitivity and specificity of the EarlyCDT-Lung test were calculated in all subjects and subgroups based on age, smoking history, lung cancer stage, sample collection time before diagnosis and year of sample collection. The overall lung cancer odds ratios were 0.89 (95% CI: 0.34-2.30) for a moderate risk EarlyCDT-Lung test result and 1.09 (95% CI: 0.48-2.47) for a high-risk test result compared to no significant test result. The overall sensitivity was 8.4% (95% CI: 4.6-14) and overall specificity was 92% (95% CI: 87-96) when considering a high-risk result as positive. Stratified analysis indicated higher sensitivity (17%, 95% CI: 7.2-32.1) in subjects with blood drawn up to 1 year prior to diagnosis. In conclusion, our study does not support a role of the EarlyCDT-Lung test in identifying the high-risk subjects in ever-smokers for lung cancer screening in the EPIC and NSHDS cohorts.

Modifiable risk factors for subsequent lethal prostate cancer among men with an initially negative prostate biopsy.

BACKGROUND: Previously suggested modifiable risk factors for prostate cancer could have resulted from detection bias because diagnosis requires a biopsy. We investigated modifiable risk factors for a subsequent cancer diagnosis among men with an initially negative prostate biopsy. METHODS: In total, 10,396 participants of the Health Professionals Follow-up Study with an initial negative prostate biopsy after 1994 were followed for incident prostate cancer until 2017. Potential risk factors were based on previous studies in the general population. Outcomes included localised, advanced, and lethal prostate cancer. RESULTS: With 1851 prostate cancer cases (168 lethal) diagnosed over 23 years of follow-up, the 20-year risk of any prostate cancer diagnosis was 18.5% (95% CI: 17.7-19.3). Higher BMI and lower alcohol intake tended to be associated with lower rates of localised disease. Coffee, lycopene intake and statin use tended to be associated with lower rates of lethal prostate cancer. Results for other risk factors were less precise but compatible with and of similar direction as for men in the overall cohort. CONCLUSIONS: Risk factors for future prostate cancer among men with a negative biopsy were generally consistent with those for the general population, supporting their validity given reduced detection bias, and could be actionable, if confirmed.

Using Triethylborane to Manipulate Reactivity Ratios in Epoxide-Anhydride Copolymerization: Application to the Synthesis of Polyethers with Degradable Ester Functions.

The anionic ring-opening copolymerization (ROCOP) of epoxides, namely of ethylene oxide (EO), with anhydrides (AH) generally produces strictly alternating copolymers. With triethylborane (TEB)-assisted ROCOP of EO with AH, statistical copolymers of high molar mass including ether and ester units could be obtained. In the presence of TEB, the reactivity ratio of EO (rEO), which is normally equal to 0 in its absence, could be progressively raised to values lower than 1 or higher than 1. Conditions were even found to obtain rEO equal or close to 1. Samples of P(EO-co-ester) with minimal compositional drift could be synthesized; upon basic degradation of their ester linkages, these samples afforded poly(ethylene oxide) (PEO) diol samples of narrow molar mass distribution. In other cases where rEO were lower or higher than 1, the PEO diol samples eventually isolated after degradation exhibited a broader distribution of molar masses because of the compositional drift of initial P(EO-co-ester) samples.

Polyurethanes from Direct Organocatalytic Copolymerization of p-Tosyl Isocyanate with Epoxides.

The direct copolymerization of p-tosyl isocyanate (TSI) with epoxides, initiated by onium salts in the presence of trialkylborane, to produce polyurethanes is reported. The rate of copolymerization and the (regio)selectivity were investigated in relation to the trialkylborane and the initiator used. Under optimized conditions such copolymerizations have been successfully performed for a wide range of epoxides, including ethylene oxide, propylene oxide, 1-octene oxide, cyclohexene oxide, and allyl glycidyl ether. These copolymerizations afford a new category of polyurethanes, clear of side products such as cyclic oxazolidinone, isocyanurate, and poly(isocyanate) linkages. The experimental conditions used in this work are compatible with those for the organocatalytic (co)polymerization of other oxygenated monomers and CO2 , holding the potential for their terpolymerization with p-tosyl isocyanate and the development of new materials with unprecedented properties.

The association between fasting blood glucose trajectory and cancer risk in Chinese population without diabetes.

To examine the associations between fasting blood glucose (FBG) trajectories, the changes in FBG over time and the risk of cancer, particularly for gastrointestinal cancer, we enrolled 69,742 participants without diabetes from the Kailuan cohort. FBG trajectories (2006-2010) were modeled by group-based trajectory modeling, and five trajectories were identified: low-increasing (n = 6,275), moderate-stable (n = 44,120), moderate-increasing (n = 10,149), elevated-decreasing (n = 5,244) and elevated-stable (n = 3,954). A total of 1,364 cancer cases were accumulated between 2010 and 2015, including 472 gastrointestinal cancer cases. We used Cox proportional hazards regression models to evaluate the associations between FBG trajectory patterns and the risk of cancer. We further assessed the associations while carefully controlling for initial body mass index (BMI) in 2006 and for changes in BMI during 2006-2010. Relative to the moderate-stable group, we found a higher hazard ratio (HR) for overall cancer in the low-increasing group (HR = 1.26, 95% confidence interval (CI) 1.06-1.50); and for gastrointestinal cancer in the elevated-stable group (HR = 1.66, 95% CI 1.22-2.26). Moreover, among participants with an initial BMI ≥25 kg/m2 , a positive association with the low-increasing group was observed for both overall cancer and gastrointestinal cancer (HR = 1.54, 95% CI 1.17-2.04; HR = 1.65, 95% CI 1.02-2.66; respectively); among participants with a stable BMI (4.40% loss-5.15% gain), a positive association with the elevated-stable group was observed both for overall cancer and gastrointestinal cancer (HR = 1.43, 95% CI 1.10-1.87; HR = 1.95, 95% CI 1.33-2.86; respectively). Our study observed that FBG trajectories were associated with cancer risk among participants without diabetes, and BMI may modify the associations.

The association of diabetes with risk of prostate cancer defined by clinical and molecular features.

BACKGROUND: To prospectively examine the association between diabetes and risk of prostate cancer defined by clinical and molecular features. METHODS: A total of 49,392 men from the Health Professionals Follow-up Study (HPFS) were followed from 1986 to 2014. Data on self-reported diabetes were collected at baseline and updated biennially. Clinical features of prostate cancer included localised, advanced, lethal, low-grade, intermediate-grade, and high-grade. Molecular features included TMPRSS2: ERG and PTEN subtypes. Cox proportional hazards regression models were used to evaluate the association between diabetes and incidence of subtype-specific prostate cancer. RESULTS: During 28 years of follow-up, we documented 6733 incident prostate cancer cases. Relative to men free from diabetes, men with diabetes had lower risks of total (HR: 0.82, 95% CI: 0.75-0.90), localised (HR: 0.82, 95% CI: 0.74-0.92), low-and intermediate-grade prostate cancer (HR: 0.77, 95% CI: 0.66-0.90; HR: 0.77, 95% CI: 0.65-0.91, respectively). For molecular subtypes, the HRs for ERG-negative and ERG-positive cases were 0.63 (0.42-0.95) and 0.72 (0.46-1.12); and for PTEN-intact and PTEN-loss cases were 0.69 (0.48-0.98) and 0.52 (0.19-1.41), respectively. CONCLUSION: Besides providing advanced evidence for the inverse association between diabetes and prostate cancer, this study is the first to report associations between diabetes and ERG/PTEN defined prostate cancers.

Participation and yield of a population-based colorectal cancer screening programme in China.

OBJECTIVE: Colorectal cancer (CRC) screening has been widely implemented in many countries. However, evidence on participation and diagnostic yield of population-based CRC screening in China is sparse. DESIGN: The analyses were conducted in the context of the Cancer Screening Program in Urban China, which recruited 1 381 561 eligible participants aged 40-69 years from 16 provinces in China from 2012 to 2015. 182 927 participants were evaluated to be high risk for CRC by an established risk score system and were subsequently recommended for colonoscopy. Participation rates and detection of colorectal neoplasms in this programme were reported and their associated factors were explored. RESULTS: 25 593 participants undertook colonoscopy as recommended, with participation rate of 14.0%. High level of education, history of faecal occult blood test, family history of CRC and history of colonic polyp were found to be associated with the participation in colonoscopy screening. Overall, 65 CRC (0.25%), 785 advanced adenomas (3.07%), 2091 non-advanced adenomas (8.17%) and 1107 hyperplastic polyps (4.33%) were detected. Detection rates of colorectal neoplasms increased with age and were higher for men. More advanced neoplasms were diagnosed in the distal colon/rectum (65.2%). Several factors including age, sex, family history of CRC, dietary intake of processed meat and smoking were identified to be associated with the presence of colorectal neoplasms. CONCLUSION: The diagnostic yield was not optimal using colonoscopy screening in high-risk populations given the relatively low participation rate. Our findings will provide important references for designing effective population-based CRC screening strategies in the future.

Independent and joint associations of blood lipids and lipoproteins with lung cancer risk in Chinese males: A prospective cohort study.

To investigate the independent and joint associations of blood lipids and lipoproteins with lung cancer risk in Chinese males, a prospective cohort study was conducted. A total of 109,798 males with baseline information on total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and non-HDL were prospectively observed from 2006 to 2015 for cancer incidence. Cox proportional hazards models and restricted cubic spline (RCS) analysis were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a 9-year follow-up, a total of 986 lung cancer cases were identified. Multivariable analyses showed that both males with low TC (HRQ1vs.Q2 = 1.27, 95%CI: 1.02-1.60) and males with high TC (HRQ5vs.Q2 = 1.30, 95%CI: 1.04-1.63) had an increased lung cancer risk, and the U-shaped association was also revealed in the RCS analysis (poverall = 0.013, pnonlinear = 0.006). Furthermore, both low TG (HRQ1vs.Q2 = 1.24, 95%CI: 0.99-1.54) and high TG (HRQ5vs.Q2 = 1.27, 95%CI: 1.01-1.59) were associated with increased lung cancer risk, while low LDL-C (HRQ1vs.Q2 = 1.38, 95%CI: 1.11-1.72) was associated with increased lung cancer risk. When TC, TG and LDL-C were considered jointly, the number of abnormal indicators was linearly associated with an increased risk of lung cancer (ptrend < 0.001), as subjects with three abnormal indicators had a twofold higher risk of developing lung cancer (HR = 2.02, 95%CI: 1.62-2.54). Notably, these associations were statistically significant among never smokers, never drinkers and overweight/obese males. These findings suggest that dyslipidemia may potentially be a modifiable risk factor that has key scientific and clinical significance for lung cancer prevention.

Risk prediction models for lung cancer: Perspectives and dissemination.

OBJECTIVE: The objective was to systematically assess lung cancer risk prediction models by critical evaluation of methodology, transparency and validation in order to provide a direction for future model development. METHODS: Electronic searches (including PubMed, EMbase, the Cochrane Library, Web of Science, the China National Knowledge Infrastructure, Wanfang, the Chinese BioMedical Literature Database, and other official cancer websites) were completed with English and Chinese databases until April 30th, 2018. Main reported sources were input data, assumptions and sensitivity analysis. Model validation was based on statements in the publications regarding internal validation, external validation and/or cross-validation. RESULTS: Twenty-two studies (containing 11 multiple-use and 11 single-use models) were included. Original models were developed between 2003 and 2016. Most of these were from the United States. Multivariate logistic regression was widely used to identify a model. The minimum area under the curve for each model was 0.57 and the largest was 0.87. The smallest C statistic was 0.59 and the largest 0.85. Six studies were validated by external validation and three were cross-validated. In total, 2 models had a high risk of bias, 6 models reported the most used variables were age and smoking duration, and 5 models included family history of lung cancer. CONCLUSIONS: The prediction accuracy of the models was high overall, indicating that it is feasible to use models for high-risk population prediction. However, the process of model development and reporting is not optimal with a high risk of bias. This risk affects prediction accuracy, influencing the promotion and further development of the model. In view of this, model developers need to be more attentive to bias risk control and validity verification in the development of models.

Sleep duration and the risk of cancer: a systematic review and meta-analysis including dose-response relationship.

BACKGROUND: The effect of sleep duration on cancer risk remains controversial. We aimed to quantify the available evidence on this relationship using categorical and dose-response meta-analyses. METHODS: Population-based cohort studies and case-control studies with at least three categories of sleep duration were identified by searching PubMed, EMBASE, and the Cochrane Library database up to July 2017. RESULTS: Sixty-five studies from 25 articles were included, involving 1,550,524 participants and 86,201 cancer cases. The categorical meta-analysis revealed that neither short nor long sleep duration was associated with increased cancer risk (short: odds ratio [OR] = 1.01, 95% confidence intervals [CI] = 0.97-1.05; long: OR = 1.02, 95% CI = 0.97-1.07). Subgroup analysis revealed that short sleep duration was associated with cancer risk among Asians (OR = 1.36; 95% CI: 1.02-1.80) and long sleep duration significantly increased the risk of colorectal cancer (OR = 1.21; 95% CI: 1.08-1.34). The dose-response meta-analysis showed no significant relationship between sleep duration and cancer risk. When treated as two linear piecewise functions with a cut point of 7 h, similar nonsignificant associations were found (per 1-h reduction: OR = 1.02, 95% CI = 0.98-1.07; per 1-h increment: OR = 1.003, 95% CI = 0.97-1.03). CONCLUSION: Categorical meta-analysis indicated that short sleep duration increased cancer risk in Asians and long sleep duration increased the risk of colorectal cancer, but these findings were not consistent in the dose-response meta-analysis. Long-term randomized controlled trials and well-designed prospective studies are needed to establish causality and to elucidate the mechanism underlying the association between sleep duration and cancer risk.

The association between fasting blood glucose and the risk of primary liver cancer in Chinese males: a population-based prospective study.

BACKGROUND: To investigate the association between fasting blood glucose (FBG) levels and the risk of incident primary liver cancer (PLC) in Chinese males, a large prospective cohort was performed in the current study. METHODS: A total of 109 169 males participating in the routine checkups every two years were recruited in the Kailuan male cohort study since May 2006. Cox proportional hazards regression models and restricted cubic spline (RCS) were used to evaluate the association between levels of baseline FBG and the risk of incident PLC. RESULTS: Compared to the males with normal FBG (3.9⩽FBG<6.1 mmol l-1), the males with impaired fasting glucose (IFG: 6.1⩽FBG<7.0 mmol l-1) and diabetes mellitus (DM: FBG ⩾7.0 mmol l-1) had a 60% (95% CI: 1.09-2.35) and a 58% (95% CI: 1.07-2.34) higher risk of incident PLC, respectively. Subgroup analysis found that IFG increased the risk of PLC among the non-smoker (HR=1.73, 95% CI: 1.01-2.98) and current alcohol drinker (HR=1.80, 95% CI: 1.03-3.16). While DM increased the risk of PLC especially among the males with normal BMI (<25 kg m-2) (HR=1.76, 95% CI: 1.05-2.94) and the HBV negativity (HR=1.89, 95% CI: 1.16-3.09), RCS analysis showed a positive non-linearly association between the FBG levels and the risk of PLC (p-overall=0.041, p-non-linear=0.049). CONCLUSIONS: Increased FBG may be an important and potentially modifiable exposure that could have key scientific and clinical importance for preventing PLC development.

Osmotic Heat Engine Using Thermally Responsive Ionic Liquids.

The osmotic heat engine (OHE) is a promising technology for converting low grade heat to electricity. Most of the existing studies have focused on thermolytic salt systems. Herein, for the first time, we proposed to use thermally responsive ionic liquids (TRIL) that have either an upper critical solution temperature (UCST) or lower critical solution temperature (LCST) type of phase behavior as novel thermolytic osmotic agents. Closed-loop TRIL-OHEs were designed based on these unique phase behaviors to convert low grade heat to work or electricity. Experimental studies using two UCST-type TRILs, protonated betaine bis(trifluoromethyl sulfonyl)imide ([Hbet][Tf2N]) and choline bis(trifluoromethylsulfonyl)imide ([choline][Tf2N]) showed that (1) the specific energy of the TRIL-OHE system could reach as high as 4.0 times that of the seawater and river water system, (2) the power density measured from a commercial FO membrane reached up to 2.3 W/m2, and (3) the overall energy efficiency reached up to 2.6% or 18% of the Carnot efficiency at no heat recovery and up to 10.5% or 71% of the Carnet efficiency at 70% heat recovery. All of these results clearly demonstrated the great potential of using TRILs as novel osmotic agents to design high efficient OHEs for recovery of low grade thermal energy to work or electricity.

Human papillomavirus in semen and the risk for male infertility: a systematic review and meta-analysis.

BACKGROUND: Human papillomavirus (HPV) is one of the most prevalent sexually transmitted viruses. Despite the increasing evidence of HPV prevalence in semen, the worldwide distribution of HPV types in semen and risk for male infertility remain inconclusive. METHODS: Four electronic databases were searched for English language studies conducted between January 1990 and December 2016 that reported HPV DNA prevalence in semen. Based on the PRISMA guidelines, HPV prevalence was estimated among general population and fertility clinic attendees, respectively, and heterogeneity testing was performed using Cochran's Q and I 2 statistics. The association between HPV positivity and male infertility was evaluated by a meta-analysis of case-control studies. RESULTS: A total of 31 eligible studies comprising 5194 males were included. The overall prevalence of HPV DNA in semen was 11.4% (95% CI = 7.8-15.0%) in general population (n = 2122) and 20.4% (95% CI = 16.2-24.6%) in fertility clinic attendees (n = 3072). High-risk type prevalence was 10.0% (95% CI = 5.9-14.0%) and 15.5% (95% CI = 11.4-19.7%), respectively. HPV16 was the most common type, with a prevalence of 4.8% (95% CI = 1.7-7.8%) in general population and 6.0% (95% CI = 3.8-8.2%) in fertility clinic attendees. A significantly increased risk of infertility was found for males with HPV positivity in semen (OR = 2.93, 95% CI = 2.03-4.24). CONCLUSIONS: Seminal HPV infection is common worldwide, which may contribute to the risk of male infertility.

Independent prognostic role of human papillomavirus genotype in cervical cancer.

BACKGROUND: Although the correlation of HPV genotype with cervical precursor lesions and invasive cancer has been confirmed, the role of HPV genotype in cervical cancer prognosis is less conclusive. This study aims to systematically investigate the independent prognostic role of HPV genotype in cervical cancer. METHODS: A total of 306 eligible patients provided cervical cell specimens for HPV genotyping before therapy and had a median follow-up time of 54 months after diagnosis. Survival times were measured from the date of diagnosis to the date of cervical cancer-related death (overall survival, OS) and from the date of diagnosis to the date of recurrence or metastasis (disease free survival, DFS). Log-rank tests and Cox proportional hazard models were performed to evaluate the association between HPV genotype and survival times. RESULTS: A total of 12 types of high-risk HPV were detected and the leading ten types belong to two species: alpha-9 and alpha-7. HPV16 and 18 were the two most common types, with the prevalence of 60.8% and 8.8%, respectively. In the univariate analysis, HPV16-positive cases were associated with better OS (P = 0.037) and HPV16-related species alpha-9 predicted better OS and DFS (both P < 0.01). After adjusting for age, FIGO stage, and therapy, HPV16 showed a hazard ratio (HR) of 0.36 (95% CI: 0.18, 0.74; P = 0.005) for OS, and alpha-9 resulted in a HR of 0.17 (95% CI: 0.08, 0.37; P < 0.001) for OS and 0.32 (95% CI: 0.17, 0.59; P < 0.001) for DFS. CONCLUSIONS: HPV genotype poses differential prognoses for cervical cancer patients. The presence of HPV16 and its related species alpha-9 indicates an improved survival.

Postoperative survival of EGFR-TKI-targeted therapy in non-small cell lung cancer patients with EGFR 19 or 21 mutations: a retrospective study.

BACKGROUND: The aim of this retrospective study is to identify epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer patients and to compare the long-term postoperative outcomes in different EGFR-TKI-targeted therapy effects between the different EGFR mutation groups. METHODS: A total of 2094 postoperative non-small cell lung cancer (NSCLC) patients with EGFR gene detection were collected in the Department of Pathology in the Cancer Hospital Chinese Academy of Medical Sciences from January 2003 to January 2014. Three hundred sixty-three patients were treated with EGFR tyrosine kinase inhibitor (TKI) after surgery: 184 harbored the exon 19 deletion mutation and 179 cases carried the exon 21 L858R point mutation. The end points included progression-free survival (PFS), overall survival (OS), and the response rate. RESULTS: OS was increased in the EGFR exon 19 deletion group compared with the exon 21 L858R point mutation group (92 vs. 65 months; P < 0.001). But the median PFS did not differ between two groups (12 vs 14 months). The objective response rate (ORR) in 19 deletion group was increased compared with L858R mutation patients (28.35 vs. 22.73%). The disease control rate (DCR) of patients with 19 deletion benefited more from targeted therapy, compared with L858R group (93.71 vs. 84.31%, P = 0.014). In 19 deletion group, a high ORR and DCR were noted in patients treated with icotinib, 16 out of 18 achieved stable disease (SD), and the DCR in this population was 100%. CONCLUSIONS: EGFR subtypes could influence the postoperative survival of NSCLC patients with TKI-targeted therapy.

Metal-Free Alternating Copolymerization of CO2 with Epoxides: Fulfilling "Green" Synthesis and Activity.

Polycarbonates were successfully synthesized for the first time through the anionic copolymerization of epoxides with CO2, under metal-free conditions. Using an approach based on the activation of epoxides by Lewis acids and of CO2 by appropriate cations, well-defined alternating copolymers made of CO2 and propylene oxide (PO) or cyclohexene oxide (CHO) were indeed obtained. Triethyl borane was the Lewis acid chosen to activate the epoxides, and onium halides or onium alkoxides involving either ammonium, phosphonium, or phosphazenium cations were selected to initiate the copolymerization. In the case of PO, the carbonate content of the poly(propylene carbonate) formed was in the range of 92-99% and turnover numbers (TON) were close to 500; in the case of CHO perfectly alternating poly(cyclohexene carbonate) were obtained and TON values were close to 4000. The advantages of such a copolymerization system are manifold: (i) no need for multistep catalyst/ligand synthesis as in previous works; (ii) no transition metal involved in the copolymer synthesis and therefore no coloration of the samples isolated; and (iii) no necessity for postsynthesis purification.

Using UCST Ionic Liquid as a Draw Solute in Forward Osmosis to Treat High-Salinity Water.

The concept of using a thermoresponsive ionic liquid (IL) with an upper critical solution temperature (UCST) as a draw solute in forward osmosis (FO) was successfully demonstrated here experimentally. A 3.2 M solution of protonated betaine bis(trifluoromethylsulfonyl)imide ([Hbet][Tf2N]) was obtained by heating and maintaining the temperature above 56 °C. This solution successfully drew water from high-salinity water up to 3.0 M through FO. When the IL solution cooled to room temperature, it spontaneously separated into a water-rich phase and an IL-rich phase: the water-rich phase was the produced water that contained a low IL concentration, and the IL-rich phase could be used directly as the draw solution in the next cycle of the FO process. The thermal stability, thermal-responsive solubility, and UV-vis absorption spectra of the IL were also studied in detail.