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BACKGROUND: Immune checkpoint inhibitors (ICIs) have dramatically altered the treatment landscape for patients with melanoma. However, their use also generates unique immune-related adverse effects (irAEs). We performed a systematic review and network meta-analysis to compare the risk of pneumonitis associated with ICIs for patients with advanced or metastatic melanoma. METHODS: Phase II/III randomized clinical trials (RCTs) with ICIs were identified through comprehensive searches of multiple databases. An NMA was conducted to compare the risk of pneumonitis associated with ICIs and all-grade (grade 1-5) and high-grade (grade 3-5) immune-related pneumonitis (IRP) were estimated by odds ratios (ORs). RESULTS: A total of 10 randomized clinical trials involving 5,335 patients were enrolled in this study. Conventional chemotherapy was associated with a lower risk of grade 1-5 IRP compared with ICIs monotherapy (OR, 0.14, 95% CI, 0.03 to 0.73) and dual ICIs combination (OR, 0.03, 95% CI, 0.00 to 0.19). In addition, dual ICIs combination showed a noticeably higher risk than ICI monotherapy (OR, 4.45, 95% CI, 2.14 to 9.25) of grade 1-5 IRP. No significant difference in grade 1-5 IRP was observed between cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) inhibitors. As to grade 3-5 IRP, no statistically significant difference was found among different ICIs-based regimens. CONCLUSION: These findings revealed that ICIs could increase the risk of all-grade pneumonitis for patients with advanced melanoma, compared with conventional chemotherapy. Dual ICIs combination could further increase the risk of all-grade pneumonitis than ICIs monotherapy. There was no significant difference in the risk of pneumonia between CTLA-4 and PD-1 inhibitors.
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Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape among non-small-cell lung cancer (NSCLC) patients. The efficacy of ICI therapy in older patients (≥65 years) is controversial and not fully clarified. We performed a systematic review and meta-analysis to evaluate the efficacy of ICIs in patients with advanced or metastatic NSCLC based on age (<65 years vs. ≥65 years). Methods: A comprehensive literature search for eligible randomized control phase II/III trials that compared the efficacy of anti-PD-1/PD-L1 agents against chemotherapy in advanced or metastatic NSCLC patients. Pooled overall survival (OS) and progression-free survival (PFS) estimates were calculated based on random/fixed effects models according to the heterogeneity between the studies. Results: A total of 10 studies involving 8 randomized controlled trials (2 updates) were enrolled in this meta-analysis [2,662 young patients (<65 years) and 1,971 older patients (≥65 years)]. The efficacy of anti-PD-1/PD-L1 agents is comparable between young (<65 years) and older (≥65 years) patients for OS [HR 0.75 95% CI (0.64-0.88) vs. 0.76 95% CI (0.66-0.87)]. However, our pooled analysis was not sufficient to show a significant benefit in terms of PFS for anti-PD-1/PD-L1 agents [HR 0.87 95% CI (0.74-1.01), P = 0.06]. In addition, we failed to see a PFS superiority of anti-PD-1/PD-L1 agents against chemotherapy in two age subgroups [<65 years and ≥65 years, HR 0.85 95% CI (0.72-1.01), P = 0.07 and HR 0.87 95% CI (0.68-1.10), P = 0.25]. Conclusion: ICIs therapy presents comparable efficacy in older advanced or metastatic NSCLC patients with young patients.
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BACKGROUND: Enhanced recovery after surgery (ERAS) is a multimodal, multidisciplinary, evidence-based approach to care for surgical patients and aims at optimizing the perioperative management and outcomes. The ERAS approach was first implemented in colorectal surgery patients; however, the reported applications in pancreatoduodenectomy patients are limited. In recent years, studies on ERAS for patients undergoing pancreaticoduodenectomy have been published. The accumulation of new randomized controlled trials and high-quality case-control studies stimulated us to update the analysis. Our study comprehensively collected data to provide the best evidence summary for the clinic. AIM: To evaluate the safety and feasibility of enhanced recovery after surgery in the perioperative management of pancreatoduodenectomy patients. METHODS: A systematic literature search of PubMed, Embase, and the Cochrane Library was performed up to July 2019. All randomized controlled trials and case-control studies that applied ERAS for patients undergoing pancreaticoduodenectomy were considered for inclusion in this study. The patients were divided into two groups: patients who received the ERAS perioperative management approach were defined as the ERAS group and patients who received the traditional perioperative management approach were defined as the control group. All statistical analyses were conducted using the Revman5.3 software, and the outcomes were calculated as odds ratios or weighted mean differences with their corresponding 95% confidence intervals. A funnel plot was created to assess publication bias. Subgroup and sensitivity analyses were performed to explore the sources of heterogeneity. RESULTS: A total of 20 studies involving 3613 patients (1914 patients in the ERAS group vs. 1699 patients in the control group) were included in this study. Among the 20 studies, 4 were randomized controlled trials, and 16 were case-control studies. The overall postoperative complication rate was significantly lower in the ERAS group (OR = 0.62, 95% CI: 0.53-0.74, P < 0.00001) than in the control group. In addition, the minor complication rate (Clavien-Dindo I-II) was also lower in the ERAS group (OR = 0.70, 95% CI: 0.58-0.86, P = 0.0005). The patients in the ERAS group had a lower incidence of delayed gastric emptying (OR = 0.51, 95% CI: 0.42-0.63, P < 0.00001) and shorter length of hospital stay (WMD = -4.27, 95% CI: -4.81~-3.73, P < 0.00001) than in the control group. The rates of pancreatic fistula (regardless of Grade A/B/C), wound infections, abdominal abscesses, readmission, reoperation, and morbidity were not significantly different between the two groups. CONCLUSION: The ERAS approach is safe and effective in the perioperative management of patients undergoing pancreaticoduodenectomy and helps to accelerate the postoperative recovery and improve prognosis.
