Zumab.Therapies for NSCLC brain metastases3.4 ORREleven radiotherapy-related trials about eight types of treatments reported ORR (Figure 4a). Radiotherapy + nitroglycerin showed a important advantage over radiotherapy alone on ORR (RR: 1.8, 95 CrI: 1.1.0). Adding chemotherapy or other innovative medicines (TMZ, Endo, Veli, or Enza) to radiotherapy didn’t show substantial advantage more than radiotherapy alone (all P 0.05). Sufferers treated with chemotherapy alone had the lowest ORR (versus radiotherapy RR: 0.71, 95 CrI: 0.43.two) (Figure 4b). Only two trials about ICIs for previously treated BMs reported ORR (Figure 4c). Pembrolizumab + chemotherapy showed drastically much better ORR than chemotherapy (RR: 2.0, 95 CrI: 1.2.7), though pembrolizumab monotherapy did not (RR: 1.5, 95 CrI: 0.92.five) (Figure 4d). 3 trials about surgery reported ORR (Figure 4e). Surgery showed a favorable trend of ORR for BMs fromNSCLC but did not attain a statistical distinction (RR: 1.04, 95 CrI: 0.89.21, common effect model).3.five Heterogeneity, consistency, and sensitivity analysisThere was low global heterogeneity for the comparison of radiotherapy-associated regiments (I2 = 0 for OS, I2 = 0 for CNS-PFS, and I2 = 8 for ORR) and low to moderate heterogeneity for the comparison of ICIs (I2 = 22 for OS, I2 = 33 for CNS-PFS, and I2 = 25 for ORR). In addition, nearby heterogeneities were also acceptable among paired treatments (Table S3). With regards to inconsistency, there was no substantial difference among direct and indirect comparisons from the OS, CNS-PFS, and ORR (Figure S3). In the course of the sensitivity analysis, 1 study with unclear random sequence generation(a)RT+Chem RT+TMZ 1 2 RT 2 two 1 RT+Veli 1 RT+Nitro 1 RT+Enza Chem RT+Endo(b)Risk Ratio (95 CrI) Compared with RT RT+Endo RT+Chem RT+TMZ RT+Veli RT+Nitro RT+Enza Chem 0.three 1 8 1.two (0.98, 1.4) 1.1 (0.90, 1.four) 1.0 (0.88, 1.two) 1.0 (0.74, 1.4) 1.eight (1.1, three.0) 1.four (0.31, 7.three) 0.71 (0.43, 1.two)(c)Chem 1 1 Pemb Pemb+Chemo(d)Threat Ratio (95 CrI) Compared with Chem Pemb Pemb+Chemo 0.91RR Weight Weight 95 -CrI (widespread) (random) six.9 37.7 55.four one hundred.0 — ten.two 44.7 45.1 — one hundred.01.five (0.92, two.5) 2.0 (1.2, 3.7)(e)Study Kim,2015 Mandell,1986 Bougie,2015 Common effect model Random effects model2No surgery Surgery Events Total Events Total six 30 31 eight 35 43 86 6 34 57 ten 47 72Risk Ratio1.RU 58841 site 25 (0.Tetrahydrocurcumin MedChemExpress 66, 2.PMID:23847952 38) 1.18 (0.95, 1.48) 0.91 (0.73, 1.14) 1.04 (0.89, 1.21) 1.06 (0.85, 1.32) 0.75 1 1.Heterogeneity: I = 34 , = 0.0154, p = 0.0.No surgery betterSurgery betterFigure four: Pooled result of ORR for distinct treatments for BMs from EGFR/ALK-negative/unselected NSCLC. (a) Network diagram and (b) forest plot of ORR for various treatments compared with radiotherapy alone in newly diagnosed BMs. (c) Network diagrams and (d) forest plot of ORR for distinct treatment options compared with chemotherapy alone in previously treated BMs. (e) Forest plot of ORR comparing surgery with radiotherapy alone. Each and every node in the network diagram represents one therapy, along with the numbers represent direct head-to-head comparisons. Abbreviations: RT, radiotherapy; TMZ, temozolomide; Chem, chemotherapy; Endo, endostatin; Enza, enzastaurin; Nitro, nitroglycerin; Veli, veliparib; and Pemb, pembrolizumab.Chengkai Zhang et al.[27] and an additional study with imbalanced patients’ initial baseline [26] had been excluded. The outcomes showed the identical ranks compared with those from the original NMA (Figure S4). The sensitivity analyses showed that the general outcomes remained robu.