Spatial and Temporal Trends in Pancreatic Cancer Burden Attributable to High Body Mass Index at the Global and National Levels.

OBJECTIVES: To examine the spatiotemporal trends in pancreatic cancer (PC) disability-adjusted life years (DALYs) and mortality attributable to high body-mass index (BMI) by age, gender, and countries from 1990 to 2019. METHODS: Data were extracted from the Global Burden of Disease Study 2019 results. We presented the annual number of PC DALYs and mortality, and corresponding age-standardized rates (ASDR and ASMR), which were further stratified by age, gender, and countries. The estimated annual percentage change (EAPC) was computed to assess the longitudinal trends in ASRs. RESULTS: In 2019, 0.7 million DALYs and 31.9 thousand deaths worldwide were caused by PC attributable to high BMI, with the largest amount reported in high-income North America, Western Europe, and East Asia. The corresponding ASDR and ASMR were highest in females and in high SDI regions, while quite varied across countries. The global EAPC in ASDR and ASMR was 1.45 (95% uncertainty interval [UI]: 1.40, 1.50) and 1.44 (95% UI: 1.39, 1.49), respectively. Almost all involved countries demonstrated significant uptrends in ASRs from 1990 to 2019. CONCLUSIONS: More productive efforts to reduce the impact of modifiable risk factors, such as overweight, should be undertaken, and thus effectively curb the rise of PC burden.

Efficacy and safety of anlotinib combined with carboplatin and pemetrexed as first-line induction therapy followed by anlotinib plus pemetrexed as maintenance therapy in EGFR/ALK wild-type advanced non-squamous non-small cell lung cancer in China: a multicenter, single-arm trial.

Background: The efficacy and safety of chemotherapy strategies combining the multi-target receptor tyrosine kinase inhibitor in patients with advanced EGFR/ALK wild-type non-squamous non-small-cell lung cancer (nsq-NSCLC) are undetermined. We aimed to investigate the efficacy and safety of anlotinib combined with carboplatin/pemetrexed-based chemotherapy followed by maintenance therapy (anlotinib plus pemetrexed) in advanced EGFR/ALK wild-type nsq-NSCLC. Methods: Eligible patients with wild-type EGFR/ALK advanced nsq-NSCLC who received first-line therapy in Henan Province from March 2019 to February 2021 were recruited. All patients were treated with anlotinib in combination with carboplatin/pemetrexed-based chemotherapy, followed by maintenance therapy (anlotinib plus pemetrexed). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), disease control rate (DCR), objective response rate (ORR), and adverse events (AEs). Response and AEs were assessed based on the Response Evaluation Criteria in Solid Tumors (1.1) and National Cancer Institute - Common Terminology Criteria for Adverse Events v.4.0.3, respectively. The follow-up interval for survival was 6 weeks and the safety follow-up was performed until the end of treatment. Kaplan-Meier analysis was used to calculate the median PFS and OS. Results: Thirty-eight participants with median age of 62 (range, 33-75) years were evaluated. Five participants were still on maintenance therapy until the end of the study. The majority were non-smokers (68.4%). The median follow-up was 13.6 (range, 12.3-14.9) months. The median PFS (mPFS) was 10.5 (95% CI: 4.1, 17.0) months, and the median OS was 23.4 [95% CI: not evaluable (NE), NE] months. The DCR and ORR were 94.7% and 60.5%, respectively. Grade 3 and above treatment-related adverse events (TRAEs) happened to 12 participants. The most common TRAEs were hypertension (23.7%), neutropenia (19.4%), and bone marrow toxicity (10.5%). Seven patients discontinued treatment, including two patients during induction and five patients during maintenance treatment. No grade 5 TRAE was reported. In the non-smoker participants, the mPFS was 14.5 (95% CI: 4.0-25.0) months. Conclusions: Anlotinib in combination with carboplatin/pemetrexed-based chemotherapy followed by anlotinib plus pemetrexed as maintenance therapy might be an effective choice in treating patients with wild-type EGFR/ALK advanced nsq-NSCLC.

Frailty and long-term survival of patients with colorectal cancer: a meta-analysis.

BACKGROUND: Frailty has been related with the risk of postoperative complication in patients with colorectal cancer (CRC). However, the association between frailty and long-term survival in patients with CRC has not been comprehensively evaluated. We performed a meta-analysis to systematically evaluate the relationship between frailty and long-term survival of these patients. METHODS: Relevant cohort studies with follow-up duration ≥ 1 year were identified from Medline, Embase, and Web of Science. A random-effect model after incorporation of the between-study heterogeneity was selected to pool the results. RESULTS: Ten cohort studies with 35,546 patients were included, and 4100 (11.5%) of them had frailty. Pooled results showed that patients with frailty had worse overall survival compared to those without frailty at baseline (relative risk [RR]: 2.21, 95% confidence interval [CI] 1.43-3.41, P < 0.001; I2 = 92%). Results were consistent for studies adjusting age (RR: 2.20, P < 0.001) or including older cancer patients only (RR: 2.28, P = 0.002). Subgroup analyses showed that difference in study design, follow-up duration, or study quality scores may not significantly affect the findings (P for subgroup analyses all > 0.05). Further meta-analyses with two datasets showed that frailty was also associated with worse cancer-specific survival (RR: 4.60, 95% CI 2.75-7.67, P < 0.001; I2 = 38%) and recurrence-free survival (RR: 1.72, 95% CI 1.30-2.28, P < 0.001; I2 = 0%). CONCLUSIONS: Frailty at admission is associated with worse survival of patients with colorectal cancer.

Apatinib in the treatment of gastric cancer in Henan Province: a multicenter prospective real-world observational study (Ahead-HAP01).

Background: Apatinib is approved in China for the treatment of advanced gastric adenocarcinoma that had progressed or relapsed after standard systemic chemotherapy treatments. However, the effectiveness of Apatinib under real-world condition has not been evaluated and the drug performance under ideal and controlled circumstances has not been validated. In fact, genetic factors, poor healthcare access, social economic status, comorbidities compliance and other factors play significant role in drug performance under "real-world" conditions. Real-world experience can help validate the safety and efficacy of apatinib. Methods: In this observational, prospective study we evaluated the safety and efficacy of Apatinib in patient treated in China. Between March 2018 and March 2019, a total of 943 patients with gastric cancer treated with Apatinib were enrolled. Response Evaluation Criteria in Solid Tumors, version 1.1 and Common Terminology Criteria for Adverse Events, version 4.0 were used to evaluate efficacy and adverse effects. Results: The median progression-free survival (PFS) was 5.65 months (5.22-6.05 months), and the median overall survival (OS) was 11.47 months (10.41-12.52 months). Apatinib in combination with more than two agents was superior to single agent apatinib in overall response rate (ORR) [18.18% vs. 9.43%, 95% confidence interval (CI): 1.03-5.90] and disease control rate (DCR) (82.82% vs. 77.87%, 95% CI: 1.21-2.59). Apatinib in combination with single agent chemotherapy was also superior to apatinib alone with DCR (86.29% vs. 77.87%, 95% CI: 1.47-2.99) irrespective of the dose (250 or 500 mg). In the patient cohort who received a starting dose of 250 mg, the DCRs of the combined treatment and monotherapy groups were 86.22% vs. 80.00% (95% CI: 1.18-3.09), respectively. The most common treatment-emergent adverse events were anemia, anorexia and thrombocytopenia (66.28%, 37.75%, 36.06%, respectively). Conclusions: Efficacy of Apatinib in this observational study is promising and toxicities are manageable. Combination of Apatinib with chemotherapy agents has a higher response rate and better disease control at the expense of increased serious adverse events. Better OS can be achieved by receiving apatinib treatment earlier. As a supplement and further validation of explanatory randomized controlled trials, the real-world study reflects the real efficacy of apatinib in practical application.

Bevacizumab biosimilar LY01008 compared with bevacizumab (Avastin) as first-line treatment for Chinese patients with unresectable, metastatic, or recurrent non-squamous non-small-cell lung cancer: A multicenter, randomized, double-blinded, phase III trial.

BACKGROUND: Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC). METHODS: Stage IIIB-IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4-6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127). RESULTS: Between December 15th , 2017, and May 15th , 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25th , 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1-6) and median duration of treatment of 3.0 (range 0.0-5.1) months. ORR of response-evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80-1.04, within the prespecified equivalence margin of 0.75-1.33). Up to May 15th , 2020, with a median follow-up of 13.6 (range 0.8-28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1-year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups. CONCLUSIONS: LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non-squamous NSCLC patients in the first-line setting.

FOXO3A Expression in Upper Tract Urothelial Carcinoma.

BACKGROUND: Epidemiological studies have reported various results regarding whether FOXO3A is related to various carcinomas. However, the prognostic significance of FOXO3A in upper tract urothelial carcinoma (UTUC) remains unclear. The purpose of this study was to validate the correlation between FOXO3A expression and oncological outcomes in UTUC. METHODS: The expression levels of FOXO3A in 107 UTUC patients were examined by immunohistochemistry (IHC). We examined the prognostic role of FOXO3A by using the Cox proportional hazard model. RESULTS: The results indicated that FOXO3A expression was notably decreased in UTUC tissue compared with control tissue. Decreased expression of FOXO3A was also related to advanced pathologic stage (P = 0.026), lymph node metastasis (P = 0.040), lymphovascular invasion (P < 0.001), and adjuvant therapy (P = 0.048). In addition, UTUC patients with low FOXO3A expression had a significantly shorter survival time, including both overall survival (OS) [hazard ratio (HR) 2.382, P = 0.004] and recurrence-free survival (RFS) (HR 2.385, P = 0.004), than those with high expression. Multivariate analyses showed that FOXO3A was a significant predictor for OS (HR 2.145, P = 0.014) and RFS (HR 2.227, P = 0.010) in UTUC patients. CONCLUSION: Our results indicate that FOXO3A may be involved in the recurrence of UTUC and that it has certain clinical value in the therapeutic targeting and prognostic evaluation of UTUC.

Apatinib with etoposide capsules as a third- or further-line therapy for extensive-stage small cell lung cancer: an open-label, multicenter, single-arm phase II trial.

BACKGROUND: Patients with extensive-stage small-cell lung cancer (ES-SCLC) have a particularly poor prognosis. And the treatment options for patients with relapsed or refractory ES-SCLC are limited. Thus, we conducted an open-label, multicenter, single-arm phase II clinical trial to assess the efficacy and safety of apatinib plus etoposide capsules as the third- or further-line treatment in ES-SCLC patients. METHODS: Patients with ES-SCLC who experienced disease progression following 2 to 3 previous therapies from 11 medical centers in China were enrolled to receive apatinib (250 mg/d, continuously) and etoposide capsules (50 mg/d, on day 1-21, per 28 days). The treatment continued until disease progression, treatment intolerance, or death. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and safety. RESULTS: Fifty-six patients with relapsed or refractory ES-SCLC were enrolled from January 2018 to February 2020 and 53 of them were eventually included in the evaluation population. The median follow-up was 9.8 months. At the data cut-off time (March 5, 2020), 39 patients (74%) had died and 44 (83%) had progressed. The median PFS was 3.0 months (95% CI, 2.1-3.9) and the median OS was 5.0 months (95% CI, 3.6-6.4). No complete responses were seen. Eleven patients (21%) showed a best response of partial response and 37 (70%) patients achieved stable disease. The ORR was 20.8% (11/53), and the disease control rate (DCR) was 90.6% (48/53). The 6-month OS rate was 40.1% (95% CI, 26.2-54). After 12 months, the OS rate was 18.4% (95% CI, 4.7-32.1). Possible treatment-related grade III/IV adverse events included leukopenia [8 (15.1%)], neutropenia [7 (13.2%)], anemia [4 (7.4%)], and hand-foot syndrome [2 (3.8%)]. During the study, no mortality occurred as a consequence of treatment. CONCLUSIONS: Apatinib combined with etoposide capsules exhibits efficacy and has an acceptable safety profile. It could be used as a later-line treatment for ES-SCLC patients who have been heavily pretreated with standard therapies. Further exploration of apatinib combined with etoposide capsules in phase III trials is warranted.

Contribution of high body mass index and alcohol use to liver cancer-related mortality: A study based on 195 countries or territories.

BACKGROUND: High body mass index (BMI) and alcohol use are well-defined risk factors for liver cancer. AIMS: We aim to describe the contribution of high BMI and alcohol use to liver-cancer-related death at the global and national levels. METHODS: The data of liver cancer-related mortality attributable to all known risk factors, high BMI, and alcohol use were collected from the Global Burden of Disease database. The estimated average percentage change was used to quantify the liver cancer age-standardized mortality rate (ASMR) trends. RESULTS: Globally, approximately 819,435 liver cancer-related deaths occurred in 2017, among which 415,867, 98,552, and 129,287 deaths could be ascribed to all 9 known risk factors, high BMI, and alcohol use, respectively. The overall ASMR increased from 4.42 per 100,000 to 5.17 per 100,000 in the study period. The liver cancer ASMR attributable to high BMI consistently increased at the global level and in most countries. The alcohol use-related liver cancer mortality decreased by 0.17% per year during the study period. However, a significant increase was found after 2008. CONCLUSION: The increase in high BMI-related liver cancer mortality suggests scarce attention to overweight and highlights its priority in future prevention schedules for liver cancer. Effective prevention measures are still needed to mitigate the adverse impact of alcohol consumption.

Mortality trends of colorectal cancer among overweight patients at the global and national levels.

PURPOSE: Colorectal cancer (CRC) is a commonly diagnosed malignancy with highly heterogeneous incidence and mortality rates worldwide. High body mass index (BMI) is a well-defined risk factor for CRC. The mortality trends of CRC among patients who are overweight contributions at the global and national levels are largely unknown. METHOD: We collected data on CRC-related mortality attributable to high BMI from 1990 to 2017 from the Global Burden of Disease Study 2017 database. The annual average percentage change (AAPC) was used to quantify the CRC age-standardized mortality rate (ASMR) trends. RESULTS: Globally, approximately 896,040 CRC-related deaths occurred in 2017, among which 73,222 (8.2%; 54,193 in men and 19,029 in women) deaths were attributable to high BMI. The high-BMI-related CRC ASMR increased from 0.81 per 100,000 in 1990 to 0.93 per 100,000 in 2017, with an AAPC of 0.42 (95% CI 0.36, 0.49). The increasing trend was consistent among populations of different sexes and ages. A more pronounced increase was found in men and in regions with middle or low socio-demographic indexes. CONCLUSION: The increase in high-BMI-related CRC mortality suggests scarce attention to overweight in the current prevention strategies and highlights its priority in future prevention strategies for CRC.

Effect of shenyan xiaobai granule on nephrin and podocin of adriamycin-induced renal injury: A randomised controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: ShenYanXiaoBai granules is a traditional Chinese herbal medicine, It is used widely for the treatment of proteinuria caused by various kidney diseases. AIM OF THE STUDY: This study investigated the mechanism of Shenyan Xiaobai Granule in the treatment of nephritis proteinuria. MATERIALS AND METHODS: 100 male wistar rats were divided into a blank group (n = 20) and a nephropathy group (n = 80) using random number table after 1 week adaptive feeded. Rats were injected with adriamycin (6.5 mg/kg) via the tail vein to induce nephropathy except for blank group. Every rat's urine protein was checked with urine protein dipstick test after three days that showed all rats in nephropathy group were successful modelled. Nephropathy group was divided into model group, benazepril group, ShenYanXiaoBai low dose group, ShenYanXiaoBai high dose group equally. Blank and model group were given distilled water 2 ml as control, then benazepril group received benazepril 0.90 mg/kg, ShenYanXiaoBai low dose group received ShenYanXiaoBai granules 1.80 g/kg as high dose group was given 3.60 g/kg, gavage for 6 days a week last for seven weeks. Urinary albumin/urinary creatinine were measured in seventh day every week. Three rats were randomly selected from each group to be executed in 3th and 5th weekend to detect the mRNA and protein expression level in kidney. The rest rats were as well. CONCLUSIONS: The therapeutic effect of ShenYanXiaoBai high dose group was better than the two other treated groups from the 5th week to the 7th week, the comparison had a significant difference. The therapeutic effect of benazepril group was better than the ShenYanXiaoBai low dose group in the 7 weeks and the comparison had a significant difference.

Trends in and Predictions of Colorectal Cancer Incidence and Mortality in China From 1990 to 2025.

Colorectal cancer (CRC) has emerged as a major public health concern in China during the last decade. In this study, we investigated the disease burden posed by CRC and analyzed temporal trends in CRC incidence and mortality rates in this country. We collected CRC incidence data from the Cancer Incidence in Five Continents, Volume XI dataset and the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of CRC by sex and age, from the 2016 Global Burden of Diseases Study. We used the average annual percentage change (AAPC) to quantify temporal trends in CRC incidence and mortality from 1990 to 2016 and found the ASIR of CRC increased from 14.25 per 100,000 in 1990 to 25.27 per 100,000 in 2016 (AAPC = 2.34, 95% confidence interval [CI] 2.29, 2.39). Cancer cases increased from 104.3 thousand to 392.8 thousand during the same period. The ASIR increased by 2.76% (95% CI 2.66%, 2.85%) and 1.70% (95% CI 1.64%, 1.76%) per year in males and females, respectively. The highest AAPC was found in people aged 15-49 years (2.76, 95% CI 2.59, 2.94). Cancer deaths increased from 81.1 thousand in 1990 to 167.1 thousand in 2016, while the ASMR remained stable (-0.04, 95% CI -0.13, 0.05), A mild increase (AAPC = 0.42, 95% CI 0.34, 0.51) was found among males and a significant decrease (AAPC = -0.75, 95% CI -0.90, -0.60) was found among females. Between 2016 and 2025, cancer cases and deaths are expected to increase from 392.8 and 167.1 thousand in 2016 to 642.3 (95% CI 498.4, 732.1) and 221.1 thousand (95% CI 122.5, 314.8) in 2025, respectively. Our study showed a steady increase in the CRC incidence in China over the past three decades and predicted a further increase in the near future. To combat this health concern, the prevention and management of known risk factors should be promoted through national polices. Greater priority should be given to CRC prevention in younger adults, and CRC screening should be widely adopted for this population.

Association between cyclooxygenase-2 (COX-2) 8473 T > C polymorphism and cancer risk: a meta-analysis and trial sequential analysis.

BACKGROUND: Numerous studies have investigated the relationship between COX-2 8473 T > C polymorphism and cancer susceptibility, however, the results remain controversial. Therefore, we carried out the present meta-analysis to obtain a more accurate assessment of this potential association. METHODS: In this meta-analysis, 79 case-control studies were included with a total of 38,634 cases and 55,206 controls. We searched all relevant articles published in PubMed, EMBASE, OVID, Web of Science, CNKI and Wanfang Data, till September 29, 2017. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the association. We performed subgroup analysis according to ethnicity, source of controls, genotyping method and cancer type. Moreover, Trial sequential analysis (TSA) was implemented to decrease the risk of type I error and estimate whether the current evidence of the results was sufficient and conclusive. RESULTS: Overall, our results indicated that 8473 T > C polymorphism was not associated with cancer susceptibility. However, stratified analysis showed that the polymorphism was associated with a statistically significant decreased risk for nasopharyngeal cancer and bladder cancer, but an increased risk for esophageal cancer and skin cancer. Interestingly, TSA demonstrated that the evidence of the result was sufficient in this study. CONCLUSION: No significant association between COX-2 8473 T > C polymorphism and cancer risk was detected.