The safety of trastuzumab deruxtecan (DS-8201) with a focus on interstitial lung disease and/or pneumonitis: A systematic review and single-arm meta-analysis.

BACKGROUND: Previous studies involving risk-benefit analysis of trastuzumab deruxtecan (DS-8201) have indicated the benefit of this treatment, although it may increase the risk of interstitial lung disease (ILD) and/or pneumonitis in certain patients. This study aimed to assess the safety of DS-8201. METHODS: A search was done for relevant articles in four electronic databases: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. All reports published up until November 2, 2022, were included, and study types were restricted to clinical trials; the last search was then updated to January 10, 2023. We also assessed the quality of the literature with the Cochrane Handbook for Systematic Reviews of Interventions and the Methodological Index for Non-Randomized Studies tool, and then performed a meta-analysis with R version 4.2.1. RESULTS: A total of 1428 patients reported in 13 articles were included in this study. The analysis revealed that the most common all-grade treatment-emergent adverse events (TEAEs) were nausea and fatigue. The most common TEAE of grade 3 or above (grade ≥3) was neutropenia. The incidences of ILD and/or pneumonitis for all-grade and grade ≥3 TEAEs were 12.5% and 2.2%, respectively. CONCLUSIONS: This comprehensive summary of the incidence of TEAEs associated with DS-8201 in clinical trials provides an important guide for clinicians. The most common TEAEs were gastrointestinal reactions and fatigue; meanwhile, the most common grade ≥3 TEAE was hematological toxicity. ILD and/or pneumonitis were specific adverse drug reactions associated with DS-8201, of which physicians should be particularly aware for their higher morbidity and rates of grade ≥3 TEAEs.

Hematologic side effects of immune checkpoint inhibitor with or without chemotherapy in patients with advanced and metastatic gastrointestinal cancer: A systematic review and network meta-analysis of phase 3 trials.

Background: The regimens of immune checkpoint inhibitors (ICIs) alone or with chemotherapy are emerging as systemic therapy for patients with advanced and metastatic gastrointestinal cancers. However, the risk of treatment-related hematologic toxicity stays unclear. Methods: We enrolled in phase 3 randomized clinical trials (RCTs) comparing PD-1, PD-L1, and CTLA-4 inhibitors in advanced and metastatic gastrointestinal cancers. The incidences of overall treatment-related adverse events (TRAEs), discontinuation, leukopenia, neutropenia, thrombocytopenia, and anemia were extracted for the Bayesian network meta-analysis. Analyses with poor convergence or low incidence were reported as incidences with 95% CIs instead. Results: Sixteen phase 3 RCTs with 9732 patients who received systemic therapy were included. A total of 150 (1.54% [95% CI 1.31-1.80]) treatment-related death events were recorded, whereas 13 (0.13% [95% CI 0.08-0.22]) of them were hematologic. 0.24% (95% CI 0.12-0.48) patients received ICI plus chemotherapy were recorded for hematological deaths, 0.09% (95% CI 0.01-0.23) were for chemotherapy alone, and 0.05% were for ICI alone (95% CI 0.01-0.29). Febrile neutropenia was the most frequent cause of death in ICI with chemotherapy. For grade ≥3 TRAEs, we found nivolumab plus chemotherapy (OR 1.63 [95% CI 0.84-3.17]) had a higher risk than other treatments. Overall, ICI monotherapy led to fewer AEs than chemotherapy-based regimens in the analyses of leukopenia, neutropenia, thrombocytopenia, and anemia. Among the 11 treatments, toripalimab plus chemotherapy possessed the highest risk in any-grade leukopenia (OR 1.84 [95% CI 0.48, 6.82]) and neutropenia (OR 1.71 [95% CI 0.17, 17.40]) respectively. For grade ≥3 hematologic AEs, neutropenia (20.08% [95% CI 18.67-21.56]) related to ICI plus chemotherapy was the most dominant. ICI plus chemotherapy was likely to increase the incidence than dosing these drugs alone. Conclusion: Using ICI alone had a low incidence of causing hematologic mortality and AEs, while the combination with chemotherapy might magnify the side effects. Comprehensively, pembrolizumab plus chemotherapy and sintilimab plus chemotherapy were the safest regimens in terms of leukopenia and neutropenia respectively. This study will guide clinical practice for ICI-based chemotherapy. Systematic Review Registration: PROSPERO, identifier CRD42022380150.

miRNAs as therapeutic predictors and prognostic biomarkers of neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis.

PURPOSE: Accumulating evidence has shown that microRNAs (miRNAs) are promising biomarkers of neoadjuvant chemotherapy (NAC) response in breast cancer (BC). However, their predictive roles remain controversial. Thus, this systematic review and meta-analysis aimed to describe the role of miRNA expression in NAC response and prognosis in BC to increase statistical power and improve translation. METHODS: A systematic review of electronic databases for relevant studies was conducted following PRISMA guidelines. Data were extracted, collated, and combined by odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals (CIs) to estimate the strength of the associations. RESULTS: Of the 560 articles screened, 59 studies were included in our systematic review, and 5 studies were included in the subsequent meta-analysis. Sixty of 123 miRNAs were found to be related with NAC response and an elevated baseline miR-7 level in tissues was associated with a higher pathological complete response rate (OR 5.63; 95% CI 2.15-14.79; P = 0.0004). The prognostic value of 39 miRNAs was also studied. Of them, 26 miRNAs were found to be associated with survival. Pooled HRs indicated that patients with increased levels of serum miR-21 from baseline to the end of the second NAC cycle and from baseline to the end of NAC had a worse disease-free survival than those with decreased levels. CONCLUSION: Our results highlight that a large number of miRNAs have possible associations with NAC response and prognosis in BC patients. Further well-designed studies are needed to elucidate the molecular mechanisms underlying these associations.

Circulating microRNAs as indicators in the prediction of neoadjuvant chemotherapy response in luminal B breast cancer.

PURPOSE: Circulating microRNAs (miRNAs) have been indicated as predictive biomarker for the response to neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer (BC); however, to date the conclusions have been controversial. The biological characteristics of BC were affected by molecular subtypes. Hence, we aimed to investigate the predictive effect of miRNAs on NAC response in luminal B BC patients. METHODS: Thirty-seven luminal B BC patient under NAC were prospectively enrolled in this study. Based on their clinical, pathological, and comprehensive response, the patients were defined as responder or non-responders, respectively. Circulating miRNAs were isolated from blood samples before and at the middle of NAC, and candidate miRNAs (miR-34a-5p, miR-125b-5p, miR-210, miR-222, miR-375, miR-718, miR-4516, and let-7g) were analyzed by quantitative real-time polymerase chain reaction (PCR). In addition, the association between miRNAs and disease-free survival (DFS) was examined. RESULTS: miR-718, miR-4516, miR-210, and miR-125b-5p were found to be specific miRNAs associated with chemo-sensitivity of luminal B HER2 negative patients (n = 24). In the luminal B HER2 positive cohort (n = 13), dynamics of miR-222 and let-7g correlated with pathological response. Treatment-induced increase in miR-34a-5p in the responders except who reached pathologic complete response (pCR) was consistently identified across all luminal B patients and its two subgroups. Finally, after adjustments for Neo-Bioscore, patients with increased levels of miR-125b-5p during NAC had a worse DFS than those with decreased levels (HR = 5.86, 95% CI = 1.39-24.62, p = 0.016). CONCLUSION: Specific circulating miRNAs were identified as predictive markers for NAC response and prognosis in luminal B BC. The underlying mechanism needs further studies.

Co-expression and prognosis analyses of GLUT1-4 and RB1 in breast cancer.

BACKGROUND: Current treatment methods for patients with triple-negative breast cancer (TNBC) are very limited, and the prognosis of TNBC is relatively poor. It has been reported that glucose transporter 1 (GLUT1) is overexpressed in breast cancer cells; however, its association with the prognosis is mostly unclear. Moreover, retinoblastoma gene 1 (RB1) might be used as a biomarker for the sensitivity of breast cancer cells to GLUT1 inhibitors, which brought us to the hypothesis that there might be a close correlation between the expression of GLUT1-4 and the expression of RB1. METHODS: In this study, we systematically analyzed the co-expression of GLUT1-4 and the influence of GLUT1-4 gene expression on the prognosis of breast cancer using data mining methods. We also explored possible relationships between GLUT1-4 and RB1 expression in breast cancer tissues. We used public databases such as ONCOMINE, GEPIA, LinkedOmics, and COEXPEDIA. RESULTS: According to the results, the mRNA expression of SLC2A1 was significantly higher in breast cancer, while the expression levels of SLC2A2-4 were downregulated. The results also indicate that GLUT1 expression does not have significant influence on the overall survival of patients with breast cancer. The mRNA expression of SLC2A1 and RB1 is significantly correlated, which means that tissues with high RB1 mRNA expression might have relatively higher mRNA expression of SLC2A1; however, further study analyzing their roles in the expression regulation pathways with human samples is needed to verify the hypothesis. CONCLUSIONS: The mRNA expression of SLC2A1 was significantly higher in breast cancer. The overall survival of breast cancer patients wasn't significantly correlated with GLUT1-4 expression. The mRNA expression of SLC2A1 and RB1 is significantly correlated according to the analysis conducted in LinkedOmics. It provides reference for future possible individualized treatment of TNBC using GLUT1 inhibitors, especially in patients with higher mRNA expression of RB1. Further study analyzing the roles of these two genes in the regulation pathways is needed.

Case report: Secondary sclerosing cholangitis induced by lapatinib and vinorelbine in a metastasis breast cancer patient.

Secondary sclerosing cholangitis (SSC) is a rare cholestatic liver disease that may have a severe clinical course. A 61-year-old woman with a history of metastasis breast cancer was admitted to our hospital for the second cycle of chemotherapy with lapatinib and vinorelbine. The patient had no reports of elevated liver function tests (LFTs) in the previous multiple chemotherapies or history of liver disease. However, the admission laboratory results showed severe cholestatic liver injury with the possibility of SSC by magnetic resonance cholangiopancreatography. Although chemotherapy was discontinued and patient was treated with hepatoprotective drugs, the LFTs did not improve and liver biopsy indicated mild injury of intrahepatic bile duct epithelium and hepatocyte. We added ursodeoxycholic acid and prednisolone to protect the liver, and laboratory data showed a response. To prevent the progression, lapatinib and vinorelbine were reintroduced and transient increases in alanine aminotransferase and γ-glutamyl transpeptidase were observed. With no evidence of viral or autoimmune liver disease, SSC induced by lapatinib and vinorelbine was diagnosed. This is the first case report of tyrosine kinase inhibitors and vinorelbine induced SSC and clinicians should be aware of the possibility of it. More case reports about this adverse drug reaction are needed to delineate optimal management.

Assessment of CPS + EG, Neo-Bioscore and Modified Neo-Bioscore in Breast Cancer Patients Treated With Preoperative Systemic Therapy: A Multicenter Cohort Study.

This study was to assess the prognosis stratification of the clinical-pathologic staging system incorporating estrogen receptor (ER)-negative disease, the nuclear grade 3 tumor pathology (CPS + EG), Neo-Bioscore, and a modified Neo-Bioscore system in breast cancer patients after preoperative systemic therapy (PST). A retrospective multicenter cohort study was conducted from 12 participating hospitals' databases from 2006 to 2015. Five-year disease free survival (DFS), disease specific survival (DSS), and overall survival (OS) were calculated using Kaplan-Meier Method. Area under the curve (AUC) of the three staging systems was compared. Wald test and maximum likelihood estimates in Cox proportional hazards model were used for multivariate analysis. A total of 1,077 patients were enrolled. The CPS + EG, Neo-Bioscore, and modified Neo-Bioscore could all stratify the DFS, DSS, and OS (all P < 0.001). While in the same stratum of Neo-Bioscore scores 2 and 3, the HER2-positive patients without trastuzumab therapy had much poorer DSS (P = 0.013 and P values < 0.01, respectively) as compared to HER2-positive patients with trastuzumab therapy and HER2-negative patients. Only the modified Neo-Bioscore had a significantly higher stratification of 5-year DSS than PS (AUC 0.79 vs. 0.65, P = 0.03). So, the modified Neo-Bioscore could circumvent the limitation of CPS + EG or Neo-Bioscore. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03437837.

Identification of SPP1 as an Extracellular Matrix Signature for Metastatic Castration-Resistant Prostate Cancer.

Resistance to androgen deprivation therapy (ADT) is the main challenge for advanced fatal prostate cancer (PCa), which can gradually develop into metastatic castration-resistant prostate cancer (mCRPC). However, the pathologic mechanisms of mCRPC are still far from clear. Given the high incidence and mortality related to mCRPC, understanding the causes and pathogenesis of this condition as well as identifying potential biomarkers are of great importance. In the research reported here, we integrated several gene expression profiles from hormone sensitive prostate cancer (HSPC) and mCRPC datasets to identify differentially expressed genes (DEGs), key biological pathways, and cellular components. We found that extracellular matrix (ECM) genes were significantly enriched, and further filtered them using Pearson correlation analysis and stepwise regression to find ECM signatures to differentiate between the HSPC and mCRPC phenotypes. Six ECM signatures were input into K-nearest neighbor, logistic regression, naive Bayes, and random forest classifiers models. Random forest algorithm with the six-gene prognostic signatures showed best performance, which had high sensitivity and specificity for HSPC and mCRPC classification and further the six ECM signatures were validated in organoid models. Among the six ECM genes, SPP1 was identified as the key hub signature for PCa metastasis and drug resistance development; we found that both protein and mRNA expression levels of SPP1 were remarkably up-regulated in mCRPC compared with HSPC in organoid models and could regulate the androgen receptor signaling pathway. Therefore, SPP1 is a potential novel biomarker and therapeutic target for mCRPC. Further understanding of the role of SPP1 in mCRPC development may help to explore effectively therapeutic approaches for the prevention and intervention of drug resistance and metastasis.

Prognostic value of receptor status conversion following neoadjuvant chemotherapy in breast cancer patients: a systematic review and meta-analysis.

Biomarkers of breast cancer such as hormone receptors (HR) and human epidermal growth factor 2 (HER2) can be altered after neoadjuvant chemotherapy (NAC). However, whether the conversion of these receptors affects the prognosis of patients remains to be determined. We sought to evaluate the prognostic value of HR and HER2 receptors before and after NAC and to analyze their clinical implications. Relevant studies were used to calculate the pooled hazard ratios, 95% confidence interval (95% CI). This meta-analysis included eight studies with 2847 patients. Compared to patients with HR+ → +, patients with HR+ → - have shorter disease free survival (DFS) (hazard ratio = 2.64, 95% CI 1.86-3.75) and overall survival (OS) (hazard ratio = 2.99, 95% CI 1.97-4.54). Furthermore, patients with HR- → + tend to achieve better DFS (hazard ratio = 0.83, 95% CI 0.60-1.17) compared to patients with HR- → -. Patients with HR- → + gain better OS (hazard ratio = 0.67, 95% CI 0.46-0.99) compared to patients exhibiting HR- → -. When comparing patients with HER2+ → - to patients with HER2+ → +, patients with HER2+ → - tended to achieve better DFS (hazard ratio = 1.65, 95% CI 1.08-2.53) though results for OS (hazard ratio = 1.16, 95% CI 0.54-2.49) were not statistically significant. Our data strongly support the need for redetection of HR and HER2 receptor status of surgical sample following neoadjuvant therapy. Changes in HR status induced by NAC can be used as a prognostic factor in breast cancer patients for predicting both OS and DFS. HER2 change may also be valuable for predicting prognosis. Further research should explore therapeutic strategies for those presenting receptor status conversion.

HLA Polymorphisms And TKI-Induced Liver Injury in Patients with Cancer: A Meta-analysis.

Background: Tyrosine kinase inhibitors (TKIs) are widely used for patients with cancer, although liver injury has been observed in a small proportion of these patients. The aim of this study was to investigate the mechanisms underlying TKI-induced liver injury according to HLA polymorphisms. Methods: We systematically searched three electronic databases (PubMed, PMC, EmBase, and the Cochrane library) to identify studies that evaluated the impact of HLA polymorphisms on the incidence of TKI-induced liver injury in cancer patients as of November 2018. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Further, sensitivity analysis and publication bias assessments were also performed. Results: In the final analysis, four studies that involved a total of 12,181 patients were included. Three of the studies included patients who received lapatinib, and the other study included patients who received pazopanib. Overall, carriers of HLA-DQA1*02:01 were associated with an increased risk of liver injury (OR: 6.85; 95%CI: 2.34-20.02; P<0.001). Furthermore, HLA-DQB1*02:02 was correlated with a greater risk of liver injury (OR: 5.61; 95%CI: 2.80-11.25; P<0.001). Finally, HLA-DRB1*07:01 was significantly correlated with a greater risk of liver injury (OR: 4.06; 95%CI: 2.33-7.09; P<0.001). Conclusions: The findings of this meta-analysis confirmed that three polymorphisms of HLA were significantly associated with an increased risk of TKI-induced liver injury. Further work will be required to determine these relationships in patients with specific characteristics.

Extended Adjuvant Therapy With Aromatase Inhibitors for Early Breast Cancer: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Aromatase inhibitors (AIs) are widely used for early breast cancer, whereas the efficacy and safety of extended AI adjuvant therapy compared with shorter AI therapy, observation, or placebo remains controversial. We conducted a quantitative meta-analysis to summarize available randomized controlled trials (RCTs) regarding the efficacy and safety of extended AI therapy for early breast cancer. MATERIALS AND METHODS: We systematically searched PubMed, EmBase, and the Cochrane library to select studies published through March 2018. Studies designed as RCTs and that investigated overall survival (OS) or disease-free survival (DFS) for extended AI and shorter AI therapy, observation, or placebo were included. Hazard ratio (HR) and relative risk (RR) with 95% confidence intervals (CIs) were employed to pool analysis according to data type. RESULTS: We identified 7 RCTs that involved 16,926 patients with early breast cancer. The summary HRs indicated that extended treatment with AIs was not associated with OS (HR, 0.95; 95% CI, 0.82-1.10; P = .488), whereas it could significantly improve DFS as compared with shorter AI therapy, observation, or placebo (HR, 0.75; 95% CI, 0.66-0.86; P < .001). Treatment with extended AIs significantly reduced contralateral breast cancer recurrence (RR, 0.46; 95% CI, 0.34-0.64; P < .001), whereas it has no significant effect on distant metastatic recurrence (RR, 0.80; 95% CI, 0.64-1.00; P = .055), and locoregional recurrence (RR, 0.76; 95% CI, 0.53-1.08; P = .127). There were no significant differences between treatment with extended AIs and control for grade 3 or more adverse events. CONCLUSION: Extended AI therapy could significantly improve DFS, especially for contralateral breast cancer recurrence. There were no significant differences between treatment with AIs and control for OS, distant metastatic and locoregional recurrence, and serious adverse events.

Validation of CPS+EG, Neo-Bioscore, and modified Neo-Bioscore staging systems after preoperative systemic therapy of breast cancer: Protocol of a retrospective multicenter cohort study in China.

Prognostic assessment after preoperative systemic therapy (PST) is critical to develop a therapeutic strategy for breast cancer management. Currently, a clinical-pathologic staging system that incorporates ER status and nuclear grading (CPS + EG), and the Neo-Bioscore system that includes HER2 status into CPS + EG, are used to predict outcomes in patients with breast cancer after PST. While HER2-positive is recognized as a favorable factor in the Neo-Bioscore system based on results in patients administered one year of trastuzumab as anti-HER2 therapy, most HER2-positive cases have difficulty accessing anti-HER2 treatment in China. Therefore, it is crucial that a modified Neo-Bioscore staging system is developed that incorporates an additional factor of poor prognosis, HER2-positive status without trastuzumab treatment, to determine accurate prognosis. We propose a retrospective multicenter cohort study in China to validate CPS + EG, Neo-Bioscore, and the modified Neo-Bioscore system and determine the accuracy of prediction. Primary breast cancer patients without metastasis treated with PST and surgery in academic institutions or hospitals of provincial level in China will be included. Disease-free, disease specific, and overall survival will be calculated using the Kaplan-Meier Method, stratified by CPS + EG, Neo-Bioscore, and the modified Neo-Bioscore staging system. Areas under the curve of each staging system will be calculated. Multivariate analysis using Wald testing and maximum likelihood estimates in a Cox proportional hazards model will be conducted.

Prognostic value of baseline serum HER2 extracellular domain level with a cut-off value of 15 ng/mL in patients with breast cancer: a systematic review and meta-analysis.

PURPOSE: The extracellular domain (ECD) of human epidermal growth factor receptor-2 (HER2) in the blood is a promising biomarker of cancer prognosis and response to therapy, whereas the clinical prognostic role of serum HER2 ECD (sHER2 ECD) level in patients with BC remains controversial. Moreover, its cut-off value significantly varies. Thus, this meta-analysis aimed to quantify the prognostic impact of this biomarker with a specific cut-off value in patients with BC. METHODS: A systematic review of electronic databases was conducted to identify studies that assessed the association between baseline sHER2 ECD level with a cut-off value of 15 ng/mL and clinical outcomes in patients with BC. Overall survival (OS) was the primary endpoint, and disease-free survival (DFS), progression-free survival (PFS), and time to progression (TTP) were the secondary endpoints. An inverse variance random effects meta-analysis was conducted. RESULTS: Twenty-three studies that included 8231 patients with BC who met the inclusion criteria were included. An elevated baseline sHER2 ECD level was associated with a hazard ratio (HR) of 2.28 (95% confidence interval [CI] 2.00-2.61; P < 0.001) for OS, and this effect was observed in all subgroups. The HRs for an elevated sHER2 ECD level for DFS, PFS, and TTP were 2.52 (95% CI 1.90-3.35; P < 0.001), 1.63 (95% CI 1.37-1.95; P < 0.001), and 1.98 (95% CI 1.66-2.36; P < 0.001), respectively. CONCLUSIONS: An elevated sHER2 ECD level with a cut-off value of 15 ng/mL was associated with poor clinical prognosis in patients with BC. Future studies should be conducted to reduce confounding and explore the mechanism.

PIK3CA mutations and their response to neoadjuvant treatment in early breast cancer: A systematic review and meta-analysis.

BACKGROUND: PIK3CA mutations frequently occur in breast cancer patients. This study was conducted to evaluate the relationship between PIK3CA mutations and neoadjuvant treatment response and to analyze the clinical implications. METHODS: PubMed, Embase, and the Cochrane database were searched for relevant studies in September 2017. The pooled risk ratio (RR) was estimated using fixed effects or random effects models according to heterogeneity among studies. RESULTS: This meta-analysis included 20 studies with 4392 patients. The pooled RR showed that PIK3CA mutation is correlated to lower pathological complete response (pCR) in unselected HER2+ patients (RR = 0.73; 95% confidence interval [CI] 0.66-0.81), thus the predictive value of PIK3CA status may be stronger in HER2+/HR+ patients (RR = 0.50; 95% CI 0.27-0.93) and those administered dual-targeting treatment (RR = 0.55; 95% CI 0.39-0.78). In contrast with wild type, either exon 9 (RR = 0.55; 95% CI 0.39-0.78) or exon 20 (RR = 0.71; 95% CI 0.58-0.89) mutations were significantly associated with lower pCR. The predictive value of exon 9 mutations was not significantly greater than exon 20 mutations (RR = 0.76; 95% CI 0.51-1.13). CONCLUSION: In early breast cancer, PIK3CA mutations seem to identify HER2+ patients who are less likely to reach pCR. The clinical implications of PIK3CA mutations tend to vary between exon 9 and exon 20. This mechanism should be explored in further studies.

Efficacy of olanzapine for the prophylaxis of chemotherapy-induced nausea and vomiting: a meta-analysis.

AIM: The aim of the present study was to evaluate the efficacy of olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV). METHODS: The literature was searched for randomized controlled trials (RCTs) evaluating the efficacy of olanzapine for the prophylaxis of CINV using PubMed, Embase, Central, as well as clinicaltrials.gov for unpublished studies. The endpoints of the study were the number of patients who achieved a complete response (CR; no emesis and no rescue) and no nausea in the acute, delayed and overall phases. Two authors independently selected studies, assessed the risk of bias and extracted data. The included RCTs were analysed using RevMan 5.3 provided by the Cochrane Collaboration. RESULTS: Ten RCTs were identified for the meta-analysis. Compared with other antiemetic agents, olanzapine significantly improved the CR in the delayed and overall phases, but did not enhance the CR in the acute phase. For the control of CINV, olanzapine was better than and comparable with aprepitant in the acute phase and delayed phase, respectively. Compared with placebo, treatment with 5 mg and 10 mg olanzapine exhibited similar efficacy in terms of the CR in the delayed and overall phases. CONCLUSIONS: Olanzapine is an excellent alternative for the prophylaxis of CINV. Olanzapine 5 mg per day should be recommended as the initial dose because of equivalent efficacy to a 10 mg dose but a lower potential risk of side effects. Further studies are needed to explore the optimal combination of medicines.

Prognostic role of microRNA-21 expression in gliomas: a meta-analysis.

MicroRNA-21 (miRNA-21) has recently been shown to be a promising prognostic tumor biomarker. However, few studies have not supported this idea and have shown inconsistent data. Thus, we conducted a meta-analysis to elucidate the predictive value of miRNA-21 in gliomas. The relevant studies were identified by performing online search in PubMed, EMBASE and Web of Science databases up to Apr 2016. This meta-analysis study included seven eligible studies, consisting of 1121 gliomas and 533 glioblastoma multiforme (GBM) patients. Heterogeneity between studies was assessed using Egger's and Begg's test. Hazard ratios (HRs) with 95 % confidence intervals (CIs) for overall survival (OS), which compared the expression levels of miRNA-21 in patients with gliomas, were extracted and estimated. Our analysis revealed that the high expression of miRNA-21 is associated with the worse OS in gliomas. Further subgroup analysis indicated that increased expression of miRNA-21 was also associated with OS in GBM patients. Moreover, we observed a correlation between miRNA-21 expression and the World Health Organization defined gliomas grading system (WHO grade). Besides, high miRNA-21 expression was significantly correlated with lowered OS both in the Asian group and non-Asian group. In the cut-off subgroup analysis, both mean cut off value and median cut off value were significantly associated with OS. The expression level of miRNA-21 was not high in low KPS (Karnofsky score) group. miRNA-21 appears to be a promising biomarker for predicting the progression of patients with gliomas or GBM. However, due to the limited sample size, further prospective or retrospective multi-center well designed studies with adequate sample size should be conducted to verify its definite prognostic value.