and G.H.K.; funding acquisition, K.W.K.; investigation, H.J.P., G.H.K., C.W.L., and S.Y.; methodology, H.J.P., G.H.K., and K.W.K.; project administration, K.W.K.; resources, H.J.P. impact of iRECIST on assessing treatment efficacy UNC0646 of immune checkpoint inhibitors (ICIs) over RECIST 1.1. Articles that evaluated the treatment response and outcome based on both RECIST 1.1 and iRECIST were eligible. Data regarding overall response rates (ORR) and disease control rate (DCR) based on RECIST 1.1 and iRECIST, and data required to estimate individual patient data of progression-free survival (PFS) Influenza B virus Nucleoprotein antibody were extracted. Estimates were compared using meta-regression and pooled incidence rate ratios. The pooled difference of restricted mean survival time (RMST) of PFS between two criteria were calculated. Eleven studies with 6210 patients were analyzed. The application of iRECIST had no impact on the response-related endpoint by showing no significantly different ORR and DCR from RECIST 1.1 (pooled ORR, 23.6% and 24.7% [= 0.72]; pooled DCR, 45.3% and 48.7% [= 0.56] for iRECIST and RECIST 1.1, respectively) and had a minor impact on a survival endpoint by showing longer RMST of PFS than RECIST 1.1 (pooled difference, 0.46 months; 95% CI, 0.10C0.82 months; = 0.01). Such a modest benefit of iRECIST should be considered when we design a clinical trial for immune checkpoint inhibitors. = 0.72). The pooled incidence rate ratio between ORR and iORR was 0.97 (95% CI, 0.90C1.03), also indicating no significant difference between ORR and iORR. No heterogeneity was present (I2 = 0.00%; 0.99). Open in a separate window Figure 2 Forest plots showing the pooled estimate of (A) incidence rate ratio of ORR and (B) incidence rate ratio of DCR according to RECIST 1.1 and iRECIST. The pooled incidence rate ratio of ORR per RECIST 1.1 and iORR per iRECIST is 0.97 (95% CI, 0.90C1.03), and the pooled incidence rate ratio of DCR per RECIST 1.1 and iDCR per iRECIST is 0.96 (95% CI, 0.91C1.01), indicating no significant increase in both ORR and DCR using iRECIST compared with RECIST 1.1. i indicates immune responses assigned using iRECIST. Abbreviations: CI, confidence interval; CR, complete response; DCR, discase control rate; IRR, incidence rate ratio; ORR, overall response rate; PR, partial response; SD, stable disease. As presented in Figure 2B, disease control rates per RECIST 1.1 (DCRs) ranged from 21.2% to 64.3%, and the DCRs per iRECIST (iDCRs) ranged from 21.2% to 69.0%. The pooled DCR and iDCR were 45.3% (95% CI, 37.1C53.6%) and 48.7% (95% CI, 40.7C56.8%), respectively (Figure S3). There was no significant difference between DCR and iDCR (meta-regression, = 0.56; pooled incidence rate ratio, 0.96 [95% CI, 0.91C1.01]). Heterogeneity was absent (I2 = 0.00%; 0.99). In these meta-analyses, no significant publication bias was detected on the funnel plots and the rank correlation test (Figure S4). Table 2 lists the pooled incidence of response-related endpoints in the subgroups classified according to the tumor type, drug type, study design, and prior systemic treatment. All sensitivity analyses showed no significant difference in estimates between the pooled ORR and iORR ( 0.63), and between the pooled DCR and iDCR ( 0.23). The pooled rate of PD date discordance between RECIST 1.1 and iRECIST were equal or less than 5.4%. Table 2 Sensitivity analyses according to tumor type, drug type, study design, and prior treatment. ValueValue= 0.10) and no significant publication bias (= 0.73). The discordant cases showed PD on RECIST 1.1 was followed by tumor shrinkage; they were reset as iSD, iPR, or iCR upon subsequent assessment based on iRECIST, with i indicates immune responses assigned using iRECIST. Open in a separate window Figure 3 A forest plot showing the pooled incidence rate of.The survRM2 package was used to derive the RMST estimates according to RECIST 1.1 and iRECIST (i.e., RMSTPFS and RMSTiPFS) from each study. restricted mean progression-free survival time by 0.46 months. Therefore, the application of iRECIST had no impact on the response-related endpoints but had a minor impact on the survival endpoint, compared to RECIST 1.1. Such a modest benefit of iRECIST should be considered when we design a clinical trial for immune checkpoint inhibitors. Abstract Despite wide recognition of iRECIST, evidence regarding the impact of iRECIST over RECIST 1.1 is lacking. We aimed to evaluate the impact of iRECIST on assessing treatment efficacy of immune checkpoint inhibitors (ICIs) over RECIST 1.1. Articles that evaluated the treatment response and outcome based on both RECIST 1.1 and iRECIST were eligible. Data regarding overall response rates (ORR) and disease control rate (DCR) based on RECIST 1.1 and iRECIST, and data required to estimate individual patient data of progression-free survival (PFS) were extracted. Estimates were compared using meta-regression and pooled incidence rate ratios. The pooled difference of restricted mean survival time (RMST) of PFS between two criteria were calculated. Eleven studies with 6210 patients were analyzed. The application of iRECIST had no impact on the response-related endpoint by showing no significantly different ORR and DCR from RECIST 1.1 (pooled ORR, 23.6% and 24.7% [= 0.72]; pooled DCR, 45.3% and 48.7% [= 0.56] for iRECIST and RECIST 1.1, respectively) and had a minor impact on a survival endpoint by showing longer RMST of PFS than RECIST 1.1 (pooled difference, 0.46 months; 95% CI, 0.10C0.82 months; = 0.01). Such a modest benefit of iRECIST should be considered when we design a clinical trial for immune checkpoint inhibitors. = 0.72). The pooled incidence rate ratio between ORR and iORR was 0.97 (95% CI, 0.90C1.03), also indicating no significant difference between ORR and iORR. No heterogeneity was present (I2 = 0.00%; 0.99). Open in a separate window Figure 2 Forest plots showing the pooled estimate of (A) incidence rate ratio of ORR and (B) incidence rate ratio of DCR according to RECIST 1.1 and iRECIST. The pooled incidence rate ratio of ORR per RECIST 1.1 and iORR per iRECIST is 0.97 (95% CI, 0.90C1.03), and the pooled incidence rate ratio of DCR per RECIST 1.1 and iDCR per iRECIST is 0.96 (95% CI, 0.91C1.01), indicating no significant increase in both ORR and DCR using iRECIST compared with RECIST 1.1. i indicates immune responses assigned using iRECIST. Abbreviations: CI, confidence interval; CR, complete response; DCR, discase control rate; IRR, incidence rate ratio; ORR, overall response rate; PR, partial response; SD, stable disease. As presented in Figure 2B, disease control UNC0646 rates per RECIST 1.1 (DCRs) ranged from 21.2% to 64.3%, and the DCRs per iRECIST (iDCRs) ranged from 21.2% to 69.0%. The pooled DCR and iDCR were 45.3% (95% CI, 37.1C53.6%) and 48.7% (95% CI, 40.7C56.8%), respectively (Figure S3). There was no significant difference between DCR and iDCR (meta-regression, = 0.56; pooled incidence rate ratio, 0.96 [95% CI, 0.91C1.01]). Heterogeneity was absent (I2 = 0.00%; 0.99). In these meta-analyses, no significant publication bias was detected on the funnel plots and the rank correlation test (Figure S4). Table 2 lists the pooled UNC0646 incidence of response-related endpoints in the subgroups classified according to the tumor type, drug type, study design, and prior systemic treatment. All sensitivity analyses showed no significant difference in estimates between the pooled ORR and iORR ( 0.63), and between the pooled DCR and iDCR ( 0.23). The pooled rate of PD date discordance between RECIST 1.1 and iRECIST were equal or less than 5.4%. Table 2 Sensitivity analyses according to tumor type, drug type, study design, and prior treatment. ValueValue= 0.10) and no significant publication bias (= 0.73). The discordant cases showed PD on RECIST 1.1 was followed by tumor shrinkage; they were reset as iSD, iPR, or iCR upon subsequent assessment based on iRECIST, with i indicates immune responses assigned using iRECIST. Open in a separate window Figure 3 A forest plot showing the pooled incidence rate of PD date discordance between RECIST 1.1 and iRECIST. The pooled incidence rate of PD date discordance between RECIST 1.1 and iRECIST was 3.9%; 95% CI, 2.8C5.1%). i indicates immune responses assigned using iRECIST. Abbreviation: CR, complete response; PD, progressive.The pooled incidence rate of PD date discordance between RECIST 1.1 and iRECIST was 3.9%; 95% CI, 2.8C5.1%). design a clinical trial for immune checkpoint inhibitors. Abstract Despite wide recognition of iRECIST, evidence regarding the impact of iRECIST over RECIST 1.1 is lacking. We targeted to evaluate the effect of iRECIST on assessing treatment effectiveness of immune checkpoint inhibitors (ICIs) over RECIST 1.1. Content articles that evaluated the treatment response and end result based on both RECIST 1.1 and iRECIST were eligible. Data concerning overall response rates (ORR) and disease control rate (DCR) based on RECIST 1.1 and iRECIST, and data required to estimate individual patient data of progression-free survival (PFS) were extracted. Estimations were compared using meta-regression and pooled incidence rate ratios. The pooled difference of restricted mean survival time (RMST) of PFS between two criteria were calculated. Eleven studies with 6210 individuals were analyzed. The application of iRECIST experienced no impact on the response-related endpoint by showing no significantly different ORR and DCR from RECIST 1.1 (pooled ORR, 23.6% and 24.7% [= 0.72]; pooled DCR, 45.3% and 48.7% [= 0.56] for iRECIST and RECIST 1.1, respectively) and experienced a minor impact on a survival endpoint by showing longer RMST of PFS than RECIST 1.1 (pooled difference, 0.46 months; 95% CI, 0.10C0.82 months; = 0.01). Such a moderate good thing about iRECIST should be considered when we design a medical trial for immune checkpoint inhibitors. = 0.72). The pooled incidence rate percentage between ORR and iORR was 0.97 (95% CI, 0.90C1.03), also indicating no significant difference between ORR and iORR. No heterogeneity was present (I2 = 0.00%; 0.99). Open in a separate window Number 2 Forest plots showing the pooled estimate of (A) incidence rate percentage of ORR and (B) incidence rate percentage of DCR relating to RECIST 1.1 and iRECIST. The pooled incidence rate percentage of ORR per RECIST 1.1 and iORR per iRECIST is 0.97 (95% CI, 0.90C1.03), and the pooled incidence rate percentage of DCR per RECIST 1.1 and iDCR per iRECIST is 0.96 (95% CI, 0.91C1.01), indicating no significant increase in both ORR and DCR using iRECIST compared with RECIST 1.1. i shows immune responses assigned using iRECIST. Abbreviations: CI, confidence interval; CR, total response; DCR, discase control rate; IRR, incidence rate percentage; ORR, overall response rate; PR, partial response; SD, stable disease. As offered in Number 2B, disease control rates per RECIST 1.1 (DCRs) ranged from 21.2% to 64.3%, and the DCRs per iRECIST (iDCRs) ranged from 21.2% to 69.0%. The pooled DCR and iDCR were 45.3% (95% CI, 37.1C53.6%) and 48.7% (95% CI, 40.7C56.8%), respectively (Number S3). There was no significant difference between DCR and iDCR (meta-regression, = 0.56; pooled incidence rate percentage, 0.96 [95% CI, 0.91C1.01]). Heterogeneity was absent (I2 = 0.00%; 0.99). In these meta-analyses, no significant publication bias was recognized within the funnel plots and the rank correlation test (Number S4). Table 2 lists the pooled incidence of response-related endpoints in the subgroups classified according to the tumor type, drug type, study design, and prior systemic treatment. All level of sensitivity analyses showed no significant difference in estimates between the pooled ORR and iORR ( 0.63), and between the pooled DCR and iDCR ( 0.23). The pooled rate of PD day discordance between RECIST 1.1 and iRECIST were equivalent or less than 5.4%. Table 2 Level of sensitivity analyses relating to tumor type, drug type, study design, and prior treatment. ValueValue= 0.10) and no significant publication bias (= 0.73). The discordant instances showed PD on RECIST 1.1 was followed by tumor shrinkage; they were reset as iSD, iPR, or iCR upon subsequent assessment based on iRECIST, with i indicates immune responses assigned using iRECIST. Open in a separate window Number 3 A forest storyline showing the pooled incidence rate of PD day discordance between RECIST 1.1 and iRECIST. The pooled incidence rate of PD day discordance between RECIST 1.1 and iRECIST was 3.9%; 95% CI, 2.8C5.1%). i shows immune responses assigned using iRECIST. Abbreviation: CR, total response; PD, progressive disease; PR, partial response; SD,.