Clinical significance of prognostic nutritional index in renal cell carcinomas

Prognostic nutritional index (PNI) could reflect the nutrition and inflammation status in cancer patients. This study aims to identify the prognostic significance of PNI in patients with renal cell carcinoma (RCC).A total of 694 RCC patients from our institution were included in this study. The prognostic correlation between PNI and overall survival (OS) and recurrence-free survival (RFS) was analyzed respectively using Kaplan–Meier method and univariate and multivariate Cox model. Studies about the association between pretreatment or preoperative PNI and prognosis of RCC were systemically reviewed and a meta-analysis method was performed to further evaluate the pooled prognostic value of PNI in RCC.267 (38.47%) RCC patients had low PNI according to the cut off value (49.08). Low PNI was associated with poor OS (P < .001) and RFS (P < .001), respectively. In the multivariate Cox analysis, PNI was identified to be an independent prognostic factor for OS (hazard ratio [HR] = 2.13, 95%CI: 1.25–3.62, P = .005). Compared to other nutritional indexes, this risk correlation of PNI is better than that of geriatric nutritional risk index (GNRI; HR = 1.19; P = .531), while is no better than that of neutrophil–lymphocyte ratio (NLR; 1/HR = 2.56; P < .001) and platelet–lymphocyte ratio (PLR; 1/HR = 2.85; P < .001) respectively. Meanwhile, additional 4785 patients from 6 studies were included into pooled analysis. For RCC patients who underwent surgery, low preoperative PNI was significantly associated with worse OS (pooled HR = 1.57, 95%CI: 1.37–1.80, P < .001) and worse RFS (pooled HR = 1.69, 95%CI: 1.45–1.96, P < .001). Furthermore, low PNI (<41–51) was also significantly associated with poor OS (HR = 1.78, 95%CI: 1.26–2.53 P < .05) and poor RFS (HR = 2.03, 95%CI: 1.40–2.95, P < .05) in advanced cases treated with targeted therapies.The present evidences show that PNI is an independent prognostic factor in RCC. Low PNI is significant associated with poor prognosis of RCC patients.     

Thymosin alpha-1 therapy improves postoperative survival after curative resection for solitary hepatitis B virus-related hepatocellular carcinoma: A propensity score matching analysis

Thymosin alpha-1 (Tα1) is an immunomodulatory and antiviral agent with potential effects on chronic hepatitis B and liver cancer. Its impact on solitary hepatocellular carcinoma (HCC) remains controversial, so we aimed to investigate the efficacy of Tα1 in solitary HBV-related HCC patients after curative resection.Between May 2010 and April 2016, 468 patients with solitary HBV-related HCC after curative resection were analyzed. Propensity score matching (PSM) was used to minimize confounding variables. Risk factors were identified by the Cox proportional hazards model. Recurrence-free survival (RFS) rates, overall survival (OS) rates, immunological, and virologic response were compared.The median follow up was 60.0 months. Immunological response improved in the Tα1 group compared with the control group (P < .001) but the virologic response was similar between 2 groups after 24 months. Patients with Tα1 therapy had better RFS and OS before (P = .018 and P < .001) and after (P = .006 and P < .001) propensity matching. Multivariate analysis revealed that Tα1 therapy was an independent prognostic factor for both OS (P < .001, HR = 0.308, 95% CI: 0.175–0.541) and RFS (P < .001, HR = 0.381, 95% CI: 0.229–0.633).Tα1 as an adjuvant therapy improves the prognosis of solitary HBV-related HCC patients after curative liver resection.     

The relationship between NLR/PLR/LMR levels and survival prognosis in patients with non-small cell lung carcinoma treated with immune checkpoint inhibitors

Background:The relationship between neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) and the dire prognosis of non-small cell lung carcinoma patients who received immune checkpoint inhibitors (ICIs) are not known yet.Methods:We screened the articles that meet the criteria from the database. The relationship between NLR/PLR/LMR levels and the survival and prognosis of non-small cell lung cancer patients treated with ICIs was analyzed. Summarize hazard ratio (HR) with 95% confidence interval (CI) to study progression-free survival (PFS) and overall survival (OS).Results:Thirty-four studies involving 3124 patients were enrolled in the final analysis. In short, high pre-treatment NLR was related to poor OS (HR = 2.13, 95% CI:1.74–2.61, P < .001, I² = 83.3%, P < .001) and PFS (HR = 1.77, 95% CI:1.44–2.17, P < .001, I² = 79.5%, P < .001). Simultaneously, high pre-treatment PLR was related to poor OS (HR = 1.49, 95% CI:1.17–1.91, P < .001, I² = 57.6%, P = .003) and PFS (HR = 1.62, 95% CI:1.38–1.89, P < .001, I² = 47.1%, P = .036). In all subgroup analysis, most subgroups showed that low LMR was related to poor OS (HR = 0.45, 95% CI: 0.34–0.59, P < .001) and PFS (HR = 0.60, 95% CI: 0.47–0.77, P < 0.001, I² = 0.0%, P < .001).Conclusion:High pre-treatment NLR and pre-treatment PLR in non-small cell lung carcinoma patients treated with ICIs are associated with low survival rates. Low pre-treatment and post-treatment LMR are also related to unsatisfactory survival outcomes. However, the significance of post-treatment NLR and post-treatment PLR deserve further prospective research to prove.     

Prognostic and clinicopathological significance of miR-638 in cancer patients: A meta-analysis

Introduction:MiR-638 is believed to be involved in human cancers. However, the prognostic value of miR-638 in human carcinomas is controversial and inconclusive. Therefore, we conducted this meta-analysis to investigate the association between miR-638 expression and clinical outcomes in the patients with various cancers.Methods:We searched Pubmed, Embase, Wanfang, and the China National Knowledge Infrastructure (CNKI) up to September 1, 2020 to identify relevant studies. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were used to correlate expression of miR-638 with prognosis and clinicopathological features.Results:A total of 18 studies involving 1886 patients were included in the meta-analysis. The results revealed that low miR-638 expression was significantly correlated with poor overall survival (OS) (HR = 2.09, 95% CI: 1.46–2.98, P < .001), but not with disease-free survival (DFS) (HR = 1.71, 95% CI: 0.31–9.56, P = .540). Subgroup analysis found that low miR-638 expression was associated with worse OS in patients with digestive system cancer (HR = 2.47, 95% CI: 1.85–3.30, P < .001), the reported directly from articles group (HR = 2.12, 95% CI: 1.34–3.33, P < .001), survival curves group (HR = 2.02, 95% CI: 1.07–3.80, P = .029), in studies with sample size ≥100 (HR = 2.12, 95% CI: 1.34–3.35, P = .001), and in studies with sample size <100 (HR = 2.02, 95%CI: 1.09–3.75, P = .025). Moreover, cancer patients with low miR-638 expression were prone to tumor size (OR = 1.47, 95% CI: 1.03–2.09, P = .035), earlier lymph node metastasis (present vs absent, OR = 2.26, 95% CI: 1.63–3.14, P < .001), earlier distant metastasis (present vs absent, OR = 2.60, 95% CI: 1.45–4.67, P < .001), TNM stage (III-IV vs I-II, OR = 2.01, 95% CI: 1.35–2.99, P = .001), and portal vein invasion (present vs absent, OR = 4.39, 95% CI:2.23–8.64, P < .001), but not associated with age, gender, tumor differentiation, and vascular invasion.Conclusions:MiR-638 may serve as a promising indicator in the prediction of prognosis and clinicopathological features in patients with different kinds of cancers.     

Prognostic value of EGFR and p-EGFR in nasopharyngeal carcinoma: A systematic review and meta-analysis

Purpose:To evaluate the prognostic effect and clinical significance of epidermal growth factor receptor and its phosphorlated form (EGFR/p-EGFR) in nasopharyngeal carcinoma.Methods:A systematic review and meta-analysis was designed. We visited PubMed, Embase, China National Knowledge Infrastructure Database, Database of Chinese sci-tech periodicals, WanFang Database, and China Biology Medicine disc to search for Chinese and English publications of prospective studies and retrospective studies investigating the association of EGFR/p-EGFR and nasopharyngeal carcinoma prognosis from inception to April 2021. The inclusion criteria were that the samples should be pathologically confirmed as nasopharyngeal carcinoma and the expression of EGFR/p-EGFR should be detected via immunohistochemistry; the study should analyze the prognostic significance of EGFR/p-EGFR in nasopharyngeal carcinoma; hazard ratio (HR) and 95% confidence interval (CI) should be reported in the study or could be derived from survival curves; and the outcomes of the study should include overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS).Results:A total of 18 studies evaluating 1451 samples were included. For studies that reported OS as an outcome, EGFR overexpression indicated worse OS of nasopharyngeal carcinoma patients. The heterogeneity between studies was high (I² = 91%, P < .01), and a random-effect model was used to combine the effect size (HR = 1.71, 95% CI [1.21, 2.41], P < .01). Further sensitivity analysis and prespecified subgroup analysis were performed to detect the source of heterogeneity, and the results showed that the heterogeneity could not be eliminated. Publication bias assessed by funnel plots and Begg test and Egger test was low (Begg test: P = .846 and Egger test: P = .074). p-EGFR was not correlated with the OS of nasopharyngeal carcinoma patients (HR = 1.01, 95% CI [0.88, 1.15], P = .92). For studies that reported DFS, EGFR overexpression was associated with worse DFS in patients with nasopharyngeal carcinoma (HR = 2.53, 95% CI [1.84, 3.47], P < .01). For studies that reported PFS, EGFR overexpression was not correlated with the PFS of nasopharyngeal carcinoma patients (HR = 1.86, 95% CI [0.90, 3.82], P = .09). For studies that reported DMFS, EGFR overexpression was not correlated with the DMFS of nasopharyngeal carcinoma patients, and high heterogeneity between studies was detected (I² = 97%, P < .01). A random-effect model was used to combine the effect size (HR = 1.80, 95% CI [0.56, 5.76], P = .32). A sensitivity analysis was conducted. Publication bias was detected to be low (Begg test: P = .817 and Egger test: P = .954). There was no correlation between p-EGFR overexpression and DMFS in patients with nasopharyngeal carcinoma (HR = 1.20, 95% CI [0.95, 1.52], P = .12).Conclusion:In nasopharyngeal carcinoma patients, EGFR overexpression could be used as a biomarker that predicts poor OS and DFS, but not a prognostic biomarker for PFS and DMFS. The overexpression of p-EGFR was not shown to be associated with the prognosis of nasopharyngeal carcinoma patients and could not be used as a prognostic biomarker.Ethics and dissemination:This study was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), and reported as stated by the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Neither ethical approval nor informed consent was required since this study was conducted based on previous publications.INPLASY registration number:INPLASY 202150010     

Prognostic significance of the expression of metastasis-associated in colon cancer-1 in gynecologic cancers and breast cancer: A protocol for systematic review and meta-analysis

Background:The prognostic role of the expression of metastasis-associated in colon cancer-1 (MACC1) in gynecologic cancers and breast cancer remains unclear. The aim of this systematic review and meta-analysis was to determine the prognostic significance of MACC1 expression in gynecologic cancers and breast cancer.Materials and methods:PubMed, Web of Science and Embase were comprehensively searched up to February 9, 2020. Studies focusing on the relationship between the expression of MACC1 and prognosis in gynecologic cancers and breast cancer were included into the analysis. Pooled hazard ratio (HR) or odd ratio with 95% confidence interval (CI) was used to estimate the prognostic value of the expression of MACC1.Results:A total of 1,811patients with gynecologic cancers or breast cancer were included into the analysis. Patients with high expression of MACC1 tended to suffer a shorter overall survival (HR = 2.76, 95%CI = 2.12–3.59, P < .01) and recurrence-free survival (HR = 2.37, 95%CI = 1.44–3.90, P < .01) compared to those with low expression of MACC1. High expression of MACC1 was significantly associated with worse tumor differentiation (P = .04), more advanced FIGO stage (P < .01) and earlier lymph node metastasis (P < .01) compared to low expression of MACC1.Conclusion:Compared to low expression of MACC1, high expression of MACC1 predicts a worse prognosis of gynecologic cancers and breast cancer. The expression of MACC1 can serve as a prognostic indicator of gynecologic cancers and breast cancer.     

The prognostic value of lncRNA AGAP2-AS1 in cancer patients: A meta-analysis

Background:ArfGAP with GTPase domain, Ankyrin repeat and PH domain 2 Antisense 1 (AGAP2-AS1) is a promising long noncoding RNA that may possess prognostic value for different types of tumors. The objective of this meta-analysis is to evaluate the prognostic value of long noncoding RNA AGAP2-AS1 in cancer patients.Methods:A systematic literature search of the PubMed, Cochrane Library, EMBASE, Medline, Web of Science, CNKI, Weipu, and Wanfang electronic databases were carried out in this meta-analysis. Synthetic hazard ratios (HRs) or odd ratios (ORs) with 95% confidence intervals (CIs) were obtained to determine the prognostic and clinicopathological significance of AGAP2-AS1 expression in tumors.Results:The final meta-analysis included 10 studies that contained 948 patients. The pooled results provided evidence that AGAP2-AS1 overexpression predicted reduced overall survival (OS) (HR = 1.77, 95% CI: 1.49–2.09, P < .00001), disease-free survival (HR = 1.84, 95% CI: 1.40–2.41, P < .0001), and progression-free survival (HR = 1.84, 95% CI: 1.01–3.33, P = .04) and for various cancers. Additionally, the AGAP2-AS1 overexpression was concerned with lymph node metastasis (positive vs negative, OR = 2.95, 95% CI: 1.96–4.45, P < .00001), advanced tumor node metastasis stage (III/IV vs I/II, OR = 3.73, 95% CI: 2.71–5.13, P < .00001), and tumor size (larger vs smaller, OR = 2.28, 95% CI: 1.24–4.18, P = .008). Besides, data from gene expression profiling interactive analysis dataset verified the results in our meta-analysis. The results showed that the expression level of AGAP2-AS1 was higher in most tumor tissues than in the corresponding normal tissues and was linked to poor OS and disease-free survival.Conclusions:Our results indicated that AGAP2-AS1 overexpression was closely correlated with shorter OS in multiple cancer types, suggesting that AGAP2-AS1 might function as a promising predictor for clinical outcomes in cancer.     

Preoperative Standardized Uptake Value of Metastatic Lymph Nodes Measured by 18F-FDG PET/CT Improves the Prediction of Prognosis in Gastric Cancer

This study assessed whether preoperative maximum standardized uptake value (SUVmax) of metastatic lymph nodes (LNs) measured by ¹⁸F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) could improve the prediction of prognosis in gastric cancer.One hundred fifty-one patients with gastric cancer and pathologically confirmed LN involvement who had undergone preoperative ¹⁸F-FDG PET/CT prior to curative surgical resection were retrospectively enrolled. To obtain nodal SUVmax, a transaxial image representing the highest ¹⁸F-FDG uptake was carefully selected, and a region of interest was manually drawn on the highest ¹⁸F-FDG accumulating LN. Conventional prognostic parameters and PET findings (primary tumor and nodal SUVmax) were analyzed for prediction of recurrence-free survival (RFS) and overall survival (OS). Furthermore, prognostic accuracy of survival models was assessed using c-statistics.Of the 151 patients, 38 (25%) experienced recurrence and 34 (23%) died during follow-up (median follow-up, 48 months; range, 5–74 months). Twenty-seven patients (18%) showed positive ¹⁸F-FDG nodal uptake (range, 2.0–22.6). In these 27 patients, a receiver-operating characteristic curve demonstrated a nodal SUVmax of 2.8 to be the optimal cutoff for predicting RFS and OS. The univariate and multivariate analyses showed that nodal SUVmax (hazard ratio [HR] = 2.71, P < 0.0001), pathologic N (pN) stage (HR = 2.58, P = 0.0058), and pathologic T (pT) stage (HR = 1.77, P = 0.0191) were independent prognostic factors for RFS. Also, nodal SUVmax (HR = 2.80, P < 0.0001) and pN stage (HR = 2.28, P = 0.0222) were independent prognostic factors for OS. A predictive survival model incorporating conventional risk factors (pT/pN stage) gave a c-statistic of 0.833 for RFS and 0.827 for OS, whereas a model combination of nodal SUVmax with pT/pN stage gave a c-statistic of 0.871 for RFS (P = 0.0355) and 0.877 for OS (P = 0.0313).Nodal SUVmax measured by preoperative ¹⁸F-FDG PET/CT is an independent prognostic factor for RFS and OS. Combining nodal SUVmax with pT/pN staging can improve survival prediction precision in patients with gastric cancer.     

LKB1 expression and the prognosis of lung cancer: A meta-analysis

Background:In the past few decades, many lines of evidence implicate the importance of liver kinase B1 (LKB1) as a tumor suppressor gene in the development and progression of solid tumours. However, the prognostic and clinicopathological value of LKB1 in patients with lung cancer are controversial. This article aimed to investigate the latest evidence on this question.Methods:A systematic literature searched in the PubMed, Web of Science, Embase, Cochrane library, Scopus until September 20, 2020. The association between overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), clinicopathological features and LKB1 were analysed by meta-analysis.Results:Eleven studies including 1507 patients were included in this meta-analysis. The pooled results revealed that low LKB1 expression was significantly associated with poor overall survival (OS) (HR = 1.67, 95% CI: 1.07–2.60, P = .024) in lung cancer. However, no association was found between LKB1 expression and DFS/PFS (HR = 1.29, 95% CI: 0.70–2.39, P = .410). Pooled results showed that low LKB1 expression was associated with histological differentiation (poor vs moderate or well, OR = 4.135, 95% CI:2.524–6.774, P < .001), nodal metastasis (absent vs present, OR = 0.503, 95% CI: 0.303–0.835, P = .008) and smoking (yes vs no, OR = 1.765, 95% CI: 1.120–2.782, P = .014).Conclusion:These results suggest that low expression of LKB1 can be considered as a unfavorable prognostic biomarker for human lung cancer, which should be further researched.     

Association between Alpha B-crystallin expression and prognosis in patients with solid tumors: A protocol for systematic review and meta-analysis

Background:Alpha B-crystallin (CRYAB), as a small heat shock protein, may play critical roles in the tumorigenesis and progression of several kinds of human cancers. However, the prognostic value of CRYAB in solid malignancies remains controversial. The aim of the present study was to investigate the association between CRYAB expression and clinicopathology and prognosis of solid tumor patients.Methods:PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure, and WanFang databases were systematically searched to retrieve studies that investigated the prognostic value of CRYAB expression in various solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to determine the strength of association between CRYAB expression and survival in patients with solid tumors. Odds ratios (ORs) with 95% CIs were pooled to assess the correlation between CRYAB expression and clinicopathological characteristics of patients with solid tumors.Results:A total of 17 studies, including 18 cohorts with 6000 patients, were included in this meta-analysis. Our results showed that increased CRYAB expression could predict poor overall survival (HR = 1.81, 95% CI: 1.50–2.19, P < .001), disease-free survival (HR = 1.47, 95% CI: 1.16–1.86, P = .001), and disease-specific survival (HR = 1.40, 95% CI: 1.19–1.63, P < .001) in patients with cancer. Furthermore, the high expression level of CRYAB was associated with certain phenotypes of tumor aggressiveness, such as lymph node metastasis (OR = 2.46, 95% CI: 1.48–4.11, P = .001), distant metastasis (OR = 3.34, 95% CI: 1.96–5.70, P < .001), advanced clinical stage (OR = 2.24, 95% CI: 1.24–4.08, P = .008), low OS rate (OR = 4.81, 95% CI: 2.82–8.19, P < .001), and high recurrence rate (OR = 1.38, 95% CI: 1.11–1.72, P = .004).Conclusions:CRYAB may serve as a valuable prognostic biomarker and therapeutic target in human solid tumors.     

Anti-EGFR monoclonal antibody plus chemotherapy for treating advanced non-small cell lung cancer: A meta-analysis

Background:The use of standard cytotoxic chemotherapy seems to have reached a “treatment plateau”. The application of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) is a new strategy for non-small-cell lung cancer (NSCLC) therapy. We aimed to comprehensively assess the efficacy and safety of anti-EGFR-mAbs plus chemotherapy as first-line therapy for advanced NSCLC.Methods:According to inclusion and exclusion criteria, we conducted a comprehensive literature search of electronic databases. From the included trials, information on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) was extracted.Results:The research showed that compared with chemotherapy alone, anti-EGFR-mAb plus chemotherapy combinations significantly improved OS (HR = 0.88, 95%CI: 0.83-0.94, P < .0001), PFS (HR = 0.89, 95%CI: 0.83-0.95, P = 0.0004) and ORR (OR = 1.39, 95%CI: 1.13-1.69, P = .001). Meta subgroup analyses manifested that the OS of patients with squamous NSCLC treated with anti-EGFR-mAb plus chemotherapy combinations was notably better than that of patients with non-squamous NSCLC treated with the same combinations (HR = 0.82, 95%CI: 0.73-0.92, P = .0005). Compared with the chemotherapy group, combination of chemotherapy and anti-EGFR mAb showed increase in incidences of severe AEs (> = grade 3) that mainly include, leukopenia (OR = 1.53, 95%CI: 1.28-1.82, P < .00001), febrile neutropenia (OR = 1.35, 95%CI: 1.06-1.71, P = .02), hypomagnesemia (OR = 5.68, 95%CI: 3.54-9.10, P < .00001), acneiform rash (OR = 35.88, 95%CI: 17.37-74.10, P < .00001), fatigue (OR = 1.24, 95%CI: 1.02-1.49, P = .03), diarrhea (OR = 1.69, 95%CI: 1.16-2.47, P = .006), and infusion-related reactions (OR = 3.78, 95%CI: 1.93-7.41, P = .0001).Conclusion:Adding an anti-EGFR-mAb to the standard platinum-based chemotherapy regimens used for the first-line treatment of advanced NSCLC resulted in statistically notable improvements in OS, PFS, and ORR. In particular, anti-EGFR-mAb and chemotherapy combinations achieved greater survival benefits in patients with squamous NSCLC than in those with non-squamous NSCLC. In addition, the safety profile of chemotherapy plus anti-EGFR-mAb combinations was acceptable compared to that of chemotherapy alone.     

COL5A2 as a potential clinical biomarker for gastric cancer and renal metastasis

Background:Gastric cancer, characterized by insidious onset and multiple metastasis, is almost incurable and has poor prognosis, and also one of the leading causes of treatment failure and death in patients with gastric cancer (GC). However, the prognosis of collagen type V alpha2 chain (COL5A2) in GC and renal metastasis is unknown.Methods:Recruited 148 patients who underwent GC. The diagnosis of GC was confirmed by ultrasound imaging and pathological examination. Immunohistochemistry and RT-qPCR were performed to exam the expression level of COL5A2. The statistical methods included Pearson chi-square test, Spearman-rho correlation test, univariate and multivariate cox regression analysis. Finally, this research constructed receiver operating characteristic (ROC) curves and applied the area under the curve (AUC).Results:Based on Pearson''s chi-square test, Spearman-rho test, and univariate/multivariate cox regression, pathologic grade (P < .001), renal metastasis (P < .001) and staging (P < .001) were significantly related to COL5A2. And COL5A2 expression (hazard ratio [HR]: 18.834, P < .001) is an independent risk factor of GC. The AUC was used as the degree of confidence in judging each factor: COL5A2 (AUC = 0.878, P < .001), COL1A1 (AUC = 0.636, P = .006), COL1A2 (AUC = 0.545, P = .368), and COL3A1 (AUC = 0.617, P = .019). Through the ROC result, COL5A2 had more advantage as a biomarker for GC than other collagens.Conclusions:COL5A2 gene expression level might be a risk factor for GC. COL5A2 has a strong correlation with the prognosis of the disease.     

Maintenance treatment of combination with bevacizumab vs single agent for advanced non-squamous non-small cell lung cancer: A systematic review and meta-analysis

Background:When the patients of advanced non-squamous non-small cell lung cancer (NSCLC) have achieved remission by induction therapy, it is controversial that combination with bevacizumab is used as maintenance therapy. Pemetrexed is a classic drug for maintenance therapy, is bevacizumab the superiority to pemetrexed is also unclear. This meta-analysis aims to evaluate the effectiveness and safety of advanced non-squamous NSCLC in the maintenance treatment.Method:From the establishment as of December 6, 2020, PubMed, Embase, and Cochrane electronic databases were searched and the American Society of Clinical Oncology, European Society of Medical Oncology, and National Comprehensive Cancer Network databases in the past 10 years. The application of combination with bevacizumab, pemetrexed was studied in clinical trials of maintenance treatment for advanced NSCLC. The extracted data include progression-free survival (PFS), overall survival (OS), and grade 3–4 adverse events (AE).Results:Seven clinical trials we screened, 6 were phase III RCTs, and a cohort trial, including 3298 patients. Compared with bevacizumab and pemetrexed, PFS of combination with bevacizumab was significantly improved (hazard ratio [HR] = 0.71, 95% confidence interval [CI] = 0.65–0.77, P < .00001), but OS was not improved (HR = 0.93, 95% CI = 0.85–1.01, P = .10). Compared with bevacizumab and pemetrexed, no significant difference of PFS (HR = 0.87, 95% CI = 0.69–1.09, P = .21), and OS (HR = 0.87, 95% CI = 0.72–1.05, P = .15) was found. A higher incidence of grade 3–4 AE occurred in combination with bevacizumab (odds ratio = 1.63, 95% CI = 1.35–1.97, P < .00001).Conclusions:PFS was significantly improved in patients with advanced non-squamous NSCLC who use bevacizumab combination with single-agent as maintenance treatment, but it does not translate into the advantages of OS; compared with bevacizumab, no PFS and OS benefits were found. A higher incidence of grade 3–4 AE occurred in combination with bevacizumab than pemetrexed and bevacizumab.     

Metastatic site discriminates survival benefit of primary tumor surgery for differentiated thyroid cancer with distant metastases: A real-world observational study

The role of primary tumor surgery in the management of differentiated thyroid cancer (DTC) with distant metastases (DM) remains controversial. We aimed to explore the survival benefit of primary tumor surgery in patients with different metastatic sites.A retrospective cohort study based on the SEER database was conducted to identify DTC patients with DM diagnosed between 2010 and 2016. Patients were divided into following 2 groups: surgery and non-surgery group. Propensity score weighting was employed to balance clinicopathologic factors between the 2 groups.Of 3537 DTC patients with DM, 956 (66.0%) patients underwent primary tumor surgery while 493 (34.0%) patients did not. There were 798 all-cause deaths and 704 DTC-specific deaths over a median follow-up of 22 months. The weighted 3-year overall survival (OS) for the surgery group was 55.2%, compared to 27.8% (P < .001) for the non-surgery group. The magnitude of the survival difference of surgery was significantly correlated with metastatic sites (P_interaction <.001). Significant survival improvements in surgery group compared with non-surgery group were observed in patients with lung-only metastasis (adjusted HR = 0.45, P < .001), bone-only metastasis (adjusted HR = 0.40, P < .001), and liver-only metastasis (adjusted HR = 0.27, P < .001), whereas no survival improvement of surgery was found for patients with brain-only metastasis (adjusted HR = 0.57, P = .059) or multiply organ distant metastases (adjusted HR = 0.81, P = .099).The survival benefit from primary tumor surgery for DTC patients with DM varies by metastatic sites. Decisions for primary tumor surgery of DTC patients with DM should be tailored according to metastatic sites.     

Prognostic markers compared to CD3+TIL in locally advanced nasopharyngeal carcinoma

Locally advanced nasopharyngeal carcinoma (LA-NPC) is more prevalent in some geographic regions, including Saudi Arabia. Typically, Tumor-Node-Metastasis (TNM) staging is used in NPC. However, it is inadequate to assess the prognosis of LA-NPC.Therefore, we analyzed and compared several previously reported prognostic factors in LA-NPC patients, retrospectively, including CD3+tumor-infiltrating lymphocytes (TIL) and peripheral blood hemoglobin, EBV DNA copy number, ratios of albumin-to-alkaline phosphatase ratio (AAPR), neutrophils, or platelets-to-lymphocytes (NLR, PLR). The studied cohort was 83 LA-NPC patients previously recruited for a randomized phase II trial with a different aim.Univariate cox regression analysis showed no significant correlation between any of the tested variables with disease-free survival (DFS) or overall survival (OS) with the exception of low CD3+ TIL infiltration, which correlated significantly with DFS (HR = 6.7, P = <.001) and OS (HR = 9.1, P = .043). Similarly, in a validated multivariate cox regression analysis, only low CD3+ TIL correlated significantly with DFS (HR = 7.0, P < .001 for TIL) and OS (HR = 9.4, P = .040).Among tested parameters, CD3+ TIL was the only independent prognostic marker for DFS and OS in LA-NPC patients treated with CCRT. This study supports the use of CD3+TIL, over other factors, as an independent prognostic factor in LA-NPC.     

Clinicopathological and prognostic significance of NM23 expression in patients with non-small cell lung cancer: A systematic review and meta-analysis

Background:There is a heated debate on the clinicopathological features and prognostic significance with non-metastasis 23 (NM23) expression in patients with non-small cell lung cancer (NSCLC). Thus, we conducted this meta-analysis to evaluate the clinicopathological features and prognostic significance of NM23 for NSCLC patients.Methods:Pubmed, Embase, and Web of Science were exhaustively searched to identify relevant studies published prior to March, 2020. Odds radios (ORs) and hazard radios with 95% confidence intervals (CIs) were calculated to summarize the statistics of clinicopathological and prognostic assessments. Q-test and I²-statistic were utilized to assess heterogeneity across the included studies. We also performed subgroup analyses and meta-regression analyses to identify the source of heterogeneity. Publication bias was detected by Begg and Egger tests. Sensitivity analysis was used to value the stability of our results. All the data were analyzed using statistical packages implemented in R version 4.0.5.Results:Data from a total of 3170 patients from 36 studies were extracted. The meta-analysis revealed that low expression of NM23 was correlated with higher risk of NSCLC (OR = 4.35; 95% CI: 2.76–6.85; P < .01), poorer tumor node metastasis (TNM) staging (OR = 1.39; 95% CI: 1.01–1.90; P = .04), poorer differentiation degree (OR = 1.37; 95% CI: 1.01–1.86; P = .04), positive lymph node metastasis (OR = 1.83; 95% CI: 1.22–2.74; P < .01), lung adenocarcinoma (OR = 1.45; 95% CI: 1.20–1.75; P < .01), and poorer 5-year overall survival (OS) rate (hazard radio = 2.33; 95%CI: 1.32–4.11; P < .01). The subgroup analyses and meta-regression analyses suggested that the “Publication year”, “Country”, “Sample size”, and “Cutoff value” might be the source of heterogeneity in TNM staging, differentiation degree, and lymph node metastasis. Both Begg test and Egger test verified that there were publication bias in 5-year OS rate. Sensitivity analysis supported the credibility of the results.Conclusion:The reduced NM23 expression is strongly associated with higher risk of NSCLC, higher TNM staging, poorer differentiation degree, positive lymph node metastasis, lung adenocarcinoma, and poorer 5-year OS rate in NSCLC patients, which indicated that NM23 could serve as a biomarker predicating the clinicopathological and prognostic significance of NSCLC.     

Efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitor versus chemotherapy for advanced lung cancer: A meta-analysis

Background:This meta-analysis was performed to compare efficacy and tolerability between antiprogrammed cell death (PD-1)/programmed cell death-ligand-1 (PD-L1) + anticytotoxic T-lymphocyte-associated protein-4 (CTLA-4) treatment and chemotherapy in advanced lung cancer.Methods:Cochrane Library, Embase, and PubMed databases were searched for potential articles. The fixed-effect model or random-effect model was adopted for pooled analysis based on the I² and P-value.Results:Six articles with 1338 patients were identified and subjected to meta-analysis. Compared with chemotherapy, anti-PD-1/PD-L1 + anti-CTLA-4 treatment could significantly improve the overall survival (hazard ratio [HR] = 0.78, 95%confidence interval [CI]: 0.71–0.84, P = .21) and progression-free survival (HR = 0.77, 95%CI: 0.71–0.83, P = .30) of advanced lung cancer patients. Moreover, there was no obvious difference in the incidence of 3 to 4 adverse events (AEs) serious adverse reactions (HR = 1.35, 95%CI: 0.66–2.74, P < .00001) between the 2 treatment groups, but the incidence rates of AEs leading to discontinuation (HR = 2.56, 95%CI: 1.53–4.30, P < .00001) and AEs leading to death (HR = 2.10, 95%CI: 1.21–3.63, P = .20) were higher. Furthermore, no remarkable differences in objective response rate (HR = 1.31, 95%CI: 0.97–1.77, P = .02) were observed between the 2 groups.Conclusion:Our meta-analysis revealed that PD-1/PD-L1 inhibitors plus CTLA-4 inhibitor could markedly improve the endpoint outcomes of patients compared with chemotherapy alone, and did not significantly increase the serious adverse reactions. Thus, it can serve as a new treatment strategy for advanced lung cancer.     

The incidence and prognostic effect of Fms-like tyrosine kinase 3 gene internal tandem and nucleolar phosphoprotein 1 genes in acute myeloid leukaemia: A PRISMA-compliant systematic review and meta-analysis

Background:Molecular genotyping is an important prognostic role in acute myeloid leukemia (AML) patients. We aimed to design this meta-analysis to discuss the incidence and prognostic effect of nucleolar phosphoprotein 1 (NPM1) and Fms-like tyrosine kinase 3 gene internal tandem (FLT3-ITD) gene in AML patients.Methods:PubMed, Embase, Medline, and Cochrane library were systematically searched due to May 15, 2020. Four combinations of genotypes (FLT3-ITD^neg/NPM1^mut, FLT3-ITD^pos/NPM1^mut, FLT3-ITD^neg/NPM1^wt, FLT3-ITD^pos/NPM1^wt) were compared in association with the overall survival (OS) and leukemia-free survival (LFS) outcome, which expressed as pooled hazard ratio (HR) and 95% confidence intervals (CIs).Results:Twenty-eight studies were included in our study. The incidence of FLT3-ITD^neg/NPM1^mut, FLT3-ITD^pos/NPM1^mut, FLT3-ITD^neg/NPM1^wt, and FLT3-ITD^pos/NPM1^wt was 16%, 13%, 50%, and 10%, respectively. The patients with FLT3-ITD^neg/NPM1^mut gene may have the best OS and LFS when comparing with FLT3-ITD^pos/NPM1^mut (HR = 1.94 and 1.70, P < .01), FLT3-ITD^neg/NPM1^wt (HR = 1.57 and 2.09, P < .01), and FLT3-ITD^pos/NPM1^wt (HR = 2.25 and 2.84, P < .001).Conclusion:AML patients with FLT3-ITD^neg/NPM1^mut gene type have the best survival outcome than the other 3 gene types, which should be an independent genotyping in AML classification.     

High pretreatment D-dimer level is an independent unfavorable prognostic factor of small cell lung cancer: A systematic review and meta-analysis

Background:High pretreatment level of D-dimer in small cell lung cancer (SCLC) is commonly encountered, but the impact of high pretreatment D-dimer level on the prognosis of SCLC patients remains undetermined. Therefore, we conducted this meta-analysis focusing specifically on the prognostic value of high pretreatment D-dimer level in SCLC patients comprehensively.Methods:We searched systematically in PubMed, Embase, and Web of Science for relevant studies published before January 28, 2019. Outcomes including 1-year overall survival (OS), progression-free survival (PFS) rates, and hazard ratios (HRs) of OS and PFS from multivariate analysis were extracted and analyzed.Results:A total of 5 cohort studies consisting of 813 SCLC patients (473 patients with high pretreatment level of D-dimer and 340 with normal level of D-dimer) were finally included for meta-analysis. We found that patients with high pretreatment level of D-dimer had significantly shorter 1-year OS (47.6% vs 79.9%; fixed effects: risk ratio [RR] = 2.506; 95% confidence interval [CI] = [1.948, 3.224]; P < .001) and PFS (15.8% vs 34.0%; random effects: RR = 1.294; 95% CI = [1.060, 1.579]; P = .011) rates than those with normal level of D-dimer. Moreover, high pretreatment D-dimer level was further proved to remain as an unfavorable predictor of OS (fixed effects: HR = 1.865; 95% CI = [1.469, 2.367]; P < .001; I² = 7.6%) and PFS (fixed effects: HR = 1.513; 95% CI = [1.183, 1.936]; P = .001; I² = 0.0%) in patients with SCLC.Conclusion:High pretreatment level of D-dimer was found to be an independent unfavorable prognostic factor in SCLC patients. However, more studies with sufficient adjustment for confounding factors are encouraged to confirm our conclusions.     

Prognostic factors of patients after liver cancer surgery: Based on Surveillance,Epidemiology, and End Results database

This study aimed to investigate the prognostic factors of patients after liver cancer surgery and evaluate the predictive power of nomogram. Liver cancer patients with the history of surgery in the Surveillance, Epidemiology, and End Results database between 2000 and 2016 were preliminary retrieved. Patients were divided into the survival group (n = 2120, survival ≥5 years) and the death group (n = 2615, survival < 5 years). Single-factor and multi-factor Cox regression were used for analyzing the risk factors of death in patients with liver cancer after surgery. Compared with single patients, married status was the protective factor for death in patients undergoing liver cancer surgery (HR = 0.757, 95%CI: 0.685–0.837, P < .001); the risk of death in Afro-Americans (HR = 1.300, 95%CI: 1.166–1.449, P < .001) was higher than that in Caucasians, while the occurrence of death in Asians (HR = 0.821, 95%CI: 0.1754–0.895, P < .0012) was lower; female patients had a lower incidence of death (HR = 0.875, 95%CI: 0.809–0.947, P < .001); grade II (HR = 1.167, 95%CI: 1.080–1.262, P < .001), III (HR = 1.580, 95%CI: 1.433–1.744, P < .001), and IV (HR = 1.419, 95%CI: 1.145–1.758, P = 0.001) were the risk factors for death in patients with liver cancer. The prognostic factors of liver cancer patients after surgery include the marital status, race, gender, age, grade of cancer and tumor size. The nomogram with good predictive ability can provide the prediction of 5-year survival for clinical development.