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BACKGROUND: Total neoadjuvant therapy (TNT) is a new strategy combining neoadjuvant therapy and chemotherapy to enhance tumor shrinkage and systemic control. Its effectiveness remains debated. OBJECTIVES: This study conducts a meta-analysis of randomized controlled trials (RCTs) to assess TNT's impact and provide high-quality evidence for rectal cancer treatment decisions. METHOD: We searched China National Knowledge Infrastructure, VIP Database, Wanfang Database, China biomedical literature database, PubMed database, Embase database, and The Cochrane Library for RCTs comparing TNT with neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. The included trials were screened and assessed for quality based on inclusion and exclusion criteria, and meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of 11 RCTs reported in 14 articles, with 1624 cases in the TNT group and 1541 cases in the CRT group. The results of the meta-analysis showed that compared with the CRT group, the TNT group had a higher pathological complete response rate (RR=1.65, 95% CI [1.40, 1.94], P<0.00001), higher T0 downstaging rate (RR=1.51, 95% CI [1.29, 1.77], P<0.00001), higher 3-year overall survival (HR=0.81, 95% CI [0.67, 0.98], P=0.03), and higher 3-year disease-free survival (HR=0.82, 95% CI [0.70, 0.95], P=0.008). However, there was no statistically significant difference between the two groups in terms of R0 resection rate (RR=1.02, 95% CI [0.99, 1.05], P=0.14), sphincter preservation rate (RR=0.94, 95% CI [0.88, 1.01], P=0.12), anastomotic leakage rate (RR=1.42, 95% CI [0.85, 2.38], P=0.18), and grade 3 or higher adverse events (RR=1.21, 95% CI [0.95, 1.54], P=0.13). CONCLUSIONS: In the treatment of locally advanced rectal cancer, TNT offers greater survival benefits compared to neoadjuvant CRT and does not significantly increase the incidence of adverse events. However, further data and studies with long-term outcomes are still required.
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Background: This network meta-analysis aimed at comparing anti-programmed death 1 (anti-PD-1) with anti-programmed death ligand 1(anti-PD-L1) immunotherapy in patients with metastatic, previously treated non-small cell lung cancer (NSCLC) who failed first-line treatment. Methods: We searched electronic databases to identify all eligible clinical trials. End-points included overall survival (OS), progression-free survival (PFS) and objective response. Hazard ratios (HRs) or odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were extracted. Network meta-analysis was performed using the frequentist approach for multiple treatment comparisons. Results: In total, 3024 patients were randomly assigned: 1117 received anti-PD-1 therapy (nivolumab + pembrolizumab), 569 received anti-PD-L1 (atezolizumab) and 1338 received docetaxel. Anti-PD-1 (HR, 0.56; 95% CI, 0.48-0.66) and anti-PD-L1 (HR, 0.64; 95% CI, 0.51-0.79) achieved better OS than docetaxel, and anti-PD-1 was superior to docetaxel in terms of PFS (HR, 0.75; 95% CI, 0.62-0.89). Moreover, anti-PD-1 achieved the highest effect on OS and PFS, with a P-score of 91.2% and 95.5%, respectively. With regard to tumor response, anti-PD-1 group had a higher rate of responders than that in anti-PD-L1 (HR, 0.35; 95% CI, 0.19-0.65) and docetaxel (HR, 0.36; 95% CI, 0.25-0.52) groups. Undoubtedly, anti-PD-1 and anti-PD-L1 obtained less toxicity profile than docetaxel, and no significant difference was observed between anti-PD-1 and anti-PD-L1 groups. Conclusions: Anti-PD-1 may be a better choice for patients with metastatic and previously treated NSCLC who failed first-line treatment in terms of the treatment ranking.
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Background and Objective: Both induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT; IC+CCRT) and CCRT plus adjuvant chemotherapy (AC; CCRT+AC) are standard treatments for advanced nasopharyngeal carcinoma (NPC). However, no prospective randomized trials comparing these two approaches have been published yet. We conducted this network meta-analysis to address this clinical question. Method: We recruited randomized clinical trials involving patients with advanced NPC randomly allocated to IC+CCRT, CCRT+AC, CCRT, or radiotherapy (RT) alone. Pairwise meta-analysis was first conducted, then network meta-analysis was performed using the frequentist approach. Effect size was expressed as hazard ratio (HR) and 95% confidence interval (CI). Results: Overall, 12 trials involving 3,248 patients were recruited for this study, with 555 receiving IC+CCRT, 840 receiving CCRT+AC, 1,039 receiving CCRT, and 814 receiving radiotherapy (RT) alone. IC+CCRT achieved significantly better overall survival ([HR], 0.69; 95% [CI], 0.51-0.92), distant metastasis-free survival (HR, 0.58; 95% CI, 0.44-0.78), and locoregional recurrence-free survival (HR, 0.67; 95% CI, 0.47-0.98) than CCRT. However, survival outcomes did not significantly differ between IC+CCRT and CCRT+AC, or between CCRT+AC and CCRT arms for all the endpoints. As expected, RT alone is the poorest treatment. In terms of P-score, IC+CCRT ranked best for overall survival (96.1%), distant metastasis-free survival (99.0%) and locoregional recurrence-free survival (87.1%). Conclusions: IC+CCRT may be a better and more promising treatment strategy for advanced NPC; however, head-to-head randomized trials comparing IC-CCRT with CCRT-AC are warranted.
