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Surrogate End Points for Overall Survival in Loco-Regionally Advanced Nasopharyngeal Carcinoma: An Individual Patient Data Meta-analysis

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机构: [1]Gustave Roussy, Serv Biostat & Epidemiol, Canc Campus, Villejuif, France; [2]Univ Paris Sud, Univ Paris Saclay, INSERM, CESP,U1018, Villejuif, France; [3]Gustave Roussy, Ligue Natl Canc Meta Anal Platform, Canc Campus, Villejuif, France; [4]CHU Vaudois, Lausanne, Switzerland; [5]Pamela Youde Nethersole Eastern Hosp, Hong Kong, Hong Kong, Peoples R China; [6]Sun Yat Sen Univ, State Key Lab Oncol South China, Canc Ctr, Guangzhou, Guangdong, Peoples R China; [7]Chinese Univ Hong Kong, Sir YK Pao Ctr Canc, Hong Kong, Hong Kong, Peoples R China; [8]Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Shanghai, Peoples R China; [9]Hong Kong Sanat & Hosp, Hong Kong, Hong Kong, Peoples R China; [10]Sun Yat Sen Univ, Canc Ctr, Guangzhou, Guangdong, Peoples R China; [11]Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China; [12]Natl Canc Ctr, Singapore, Singapore; [13]SWOG Stat Ctr, Seattle, WA USA; [14]Tuen Mun Hosp Hong Kong, Hong Kong, Hong Kong, Peoples R China; [15]Shin Kong Wu Ho Su Mem Hosp, Taipei, Taiwan; [16]Aristotle Univ Thessaloniki, Sch Med, Thessaloniki, Greece; [17]Gustave Roussy, Dept Radiat Therapy, Villejuif, France; [18]Gustave Roussy, Serv Biostat & Epidemiol, B2M RDC,114 Rue Edouard Vaillant, F-94805 Villejuif, France
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Background: Our objective was to evaluate progression-free survival (PFS) and distant metastasis-free survival (DMFS) as surrogate end points for overall survival (OS) in randomized trials of chemotherapy in loco-regionally advanced nasopharyngeal carcinomas (NPCs). Methods: Individual patient data were obtained from 19 trials of the updated Meta-Analysis of Chemotherapy in Nasopharyngeal Carcinoma (MAC-NPC) plus one additional trial (total = 5144 patients). Surrogacy was evaluated at the individual level using a rank correlation coefficient rho and at the trial level using a correlation coefficient R-2 between treatment effects on the surrogate end point and OS. A sensitivity analysis was performed with two-year PFS/DMFS and five-year OS. Results: PFS was strongly correlated with OS at the individual level (rho = 0.93, 95% confidence interval [CI] = 0.93 to 0.94) and at the trial level (R-2 = 0.95, 95% CI = 0.47 to 1.00). For DMFS, too, the individual-level correlation with OS was strong (rho = 0.98, 95% CI = 0.98 to 0.98); at trial level, the correlation was high but the regression adjusted for measurement error could not be computed (unadjusted R-2 = 0.96, 95% CI = 0.94 to 0.99). In the sensitivity analysis, two-year PFS was highly correlated with five-year OS at the individual level (rho = 0.89, 95% CI = 0.88 to 0.90) and at the trial level (R-2 = 0.85, 95% CI = 0.46 to 1.00); two-year DMFS was highly correlated with five-year OS at the individual level (rho = 0.95, 95% CI = 0.94 to 0.95) and at the trial level (R-2 = 0.78, 95% CI = 0.33 to 1.00). Conclusions: PFS and DMFS are valid surrogate end points for OS to assess treatment effect of chemotherapy in loco-regionally advanced NPC, while PFS can be measured earlier.

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出版当年[2017]版:
大类 | 1 区 医学
小类 | 1 区 肿瘤学
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 肿瘤学
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第一作者机构: [1]Gustave Roussy, Serv Biostat & Epidemiol, Canc Campus, Villejuif, France; [2]Univ Paris Sud, Univ Paris Saclay, INSERM, CESP,U1018, Villejuif, France; [3]Gustave Roussy, Ligue Natl Canc Meta Anal Platform, Canc Campus, Villejuif, France;
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通讯机构: [1]Gustave Roussy, Serv Biostat & Epidemiol, Canc Campus, Villejuif, France; [2]Univ Paris Sud, Univ Paris Saclay, INSERM, CESP,U1018, Villejuif, France; [3]Gustave Roussy, Ligue Natl Canc Meta Anal Platform, Canc Campus, Villejuif, France; [18]Gustave Roussy, Serv Biostat & Epidemiol, B2M RDC,114 Rue Edouard Vaillant, F-94805 Villejuif, France
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