Efficacy of addition immune checkpoint inhibitors to chemotherapy as first-line treatment for small cell lung cancer patients with liver or brain metastases: a systematic review and meta-analysis.

OBJECTIVE: Differential organ-specific tumor response to immune checkpoint inhibitors (ICIs) has been reported in multiple solid tumors. We aim at investigating the efficacy differences of ICIs combined with chemotherapy (CT) vs. CT alone as first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). MATERIALS AND METHODS: We searched PubMed, Embase, Medline, and China National Knowledge Infrastructure databases to identify relevant trials comparing ICIs combined with CT vs. CT alone in ES-SCLC patients with brain or liver metastases. The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS). The pooled hazard ratio (HR) was analyzed using the fixed or random effects model, according to heterogeneity among included trials. RESULTS: We identified 5 randomized controlled trials of 8 studies that involved a total of 1,401 patients, 310 with brain metastases and 1,091 with liver metastases. The quality of included trials was high. The pooled results showed that ICIs combined with CT significantly improved OS of ES-SCLC with liver metastases (HR 0.88, 95%CI: 0.78-1.00, p=0.049), and a tendency to improve PFS (HR 0.86, 95%CI: 0.68-1.07, p=0.17). For patients with brain metastases, no survival benefit could be obtained from combination therapy of ICIs with CT in terms of PFS (HR 0.91, 95%CI: 0.63-1.32, p=0.62) and OS (HR 1.12, 95%CI: 0.88-1.43, p=0.36). No publication bias was detected. CONCLUSIONS: The addition of ICIs to CT significantly improves OS in ES-SCLC patients with liver metastases compared with CT alone. No survival benefit could be obtained from ICIs and CT combination therapy for ES-SCLC with brain metastases.

Correlation of multiple proteins with clinic-pathological features and its prognostic significance in colorectal cancer with signet-ring cell component.

OBJECTIVE: Primary colorectal cancer (CRC) with signet-ring cell (SRC) component is a distinct tumor of colon and rectum, and its prognosis is very poor. Reliable markers to predict the poor clinical outcome of this subgroup cancer remains undetermined. Therefore, we perform this study to investigate the prognosis value of seven proteins in CRC with SRC component . PATIENTS AND METHODS: This study involved 117 patients diagnosed with CRC with SRC component between January 2008 and August 2015 at Fudan University Shanghai Cancer Center. The samples from these patients were analyzed by immunohistochemistry to reveal the expression levels of p53, p21, E-cadherin, COX-2 (Cyclo-oxygenase-2), Bcl-2, CD44 and Ki-67. Kaplan-Meier analysis and log-rank testing were performed to estimate survival. Subsequently, a Cox proportional hazard model was used to calculate hazard ratios for the risk of death. RESULTS: The p21, p53, COX-2, E-cadherin, Bcl-2, CD44 and Ki-67 expression were detected in 60.5%, 61.3%, 69.7%, 68%, 28.6%, 62.2% and 75.6% of the samples, respectively. The positive expression of p53 (p=0.017) and the negative expression of COX-2 (p=0.001) or E-cadherin (p=0.047) in CRC with SRC component were significantly associated with decreased overall survival, but the other expression levels were not. In a multivariate analysis, the negative expression of COX-2 was found to be an independent prognostic factor for poorer overall survival (hazard ratio, 0.37; 95% confidence interval, 0.19 to 0.75, p=0.003) CONCLUSIONS: The COX-2 positive expression in CRC patients with SRC component had a poorer outcome than patients who were COX-2-negative. Therefore, COX-2 could be considered as an indicator for appropriate treatment and intensive follow-up in these subgroup patients.

Does the addition of targeted biological agents to first-line chemotherapy for advanced colorectal cancer increase complete response? A systematic review and meta-analysis.

AIM: The study assessed whether the addition of monoclonal antibodies (MoAbs) to first-line chemotherapy for advanced colorectal cancer (CRC) increases the complete response (CR) compared with controls. METHOD: PubMed was reviewed for randomized clinical trials (RCTs) with approved MoAbs (bevacizumab, cetuximab and panitumumab) vs non-MoAbs as first-line therapy for patients with advanced CRC. The incidence and ratio of CR events were calculated in patients assigned to MoAbs compared with controls. RESULTS: A total of 3790 patients from nine RCTs were included for analysis. The overall incidence of CR in patients treated with MoAbs was 2.4% (95% CI: 1.7-3.3%) compared with 1.3% (95% CI: 0.8-2.2%) in controls. Comparison of the different types of MoAbs showed that the incidence of CR was higher for bevacizumab (3.1%, 95% CI: 2.1-4.3%) than for cetuximab (0.8%, 95% CI: 0.4-1.8%). The addition of MoAbs to chemotherapy significantly increased the OR of obtaining a CR compared with controls (OR = 1.96; 95% CI: 1.12-3.46; P = 0.02). No significant differences in the OR were observed in any of the subgroups. CONCLUSION: The CR is a rare event in advanced CRC; however, the addition of MoAbs to first-line chemotherapy significantly increases the curative rate of metastatic disease compared with controls.

Incidence and risk of hemorrhagic events with vascular endothelial growth factor receptor tyrosine-kinase inhibitors: an up-to-date meta-analysis of 27 randomized controlled trials.

BACKGROUND: We aimed at determining the overall incidence and risk of hemorrhagic events associated with vascular endothelial growth factor receptor-tyrosine-kinase inhibitors (VEGFR-TKIs). METHODS: We searched PubMed, EMBASE and Cochrane library databases for relevant prospective, randomized controlled trials (RCTs). Statistical analyses were conducted to calculate the summary incidence, relative risks (RRs) and 95% confidence intervals (CIs) by using either random-effects or fixed-effects models according to the heterogeneity of included studies. RESULTS: The overall incidence of all-grade and high-grade hemorrhagic events was 9.1% (95% CI: 6.8-12.1%) and 1.3% (95% CI 0.8% to 2.1%), respectively. And the use of VEGFR-TKIs was associated with an increased risk of hemorrhagic events, with a relative risk (RR) of 1.67 (95% CI 1.19-2.33, P = 0.003), but not for high-grade hemorrhagic events (RR 1.23, 95% CI 0.86-1.77, P = 0.25). The risk of developing all-grade hemorrhagic events varied significantly with tumor types (P < 0.001) and different VEGFR-TKIs (P < 0.001). Additionally, the most common causes of all-grade hemorrhagic events were hemoptysis (48.6%) and epistaxis (20.7%), while hemoptysis (41.8%) and CNS hemorrhage (13.4%) was the most common cause of high-grade hemorrhagic events. CONCLUSIONS: While the use of VEGFR-TKIs is associated with a significantly increased risk of developing hemorrhagic events in cancer patients, this is primarily for lower grade events.