scholarly journals A meta-analytic evaluation of the correlation between event-free survival and overall survival in randomized controlled trials of newly diagnosed Ewing sarcoma.

2020 ◽  
Author(s):  
Kazuhiro Tanaka ◽  
Masanori Kawano ◽  
Tatsuya Iwasaki ◽  
Ichiro Itonaga ◽  
Hiroshi Tsumura
Keyword(s):  
Overall Survival ◽  
Randomized Controlled Trials ◽  
Ewing Sarcoma ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
Randomized Controlled ◽  
Hazard Ratios

Abstract BackgroundIn randomized controlled trials (RCTs) of adjuvant treatment for malignant tumors, event-free survival (EFS) is considered the most acceptable surrogate for overall survival (OS). However, even though EFS has repeatedly been selected as a primary endpoint in RCTs of Ewing sarcoma (ES), the surrogacy of EFS for OS has not been investigated. This study aimed to evaluate the correlation between EFS and OS in RCTs of chemotherapy for newly diagnosed ES using a meta-analytic approach.MethodsWe identified seven RCTs of newly diagnosed ES through a systematic review, and a meta-analysis was performed to evaluate the efficacy and adverse events associated with chemotherapy for previously untreated ES. The correlation between EFS and OS was investigated using weighted linear regression analysis and Spearman rank correlation coefficients (ρ). The strength of the correlation was evaluated using the coefficient of determination (R2). ResultsA total of 3,612 patients were randomly assigned to 17 treatment arms in the eligible RCTs. The meta-analysis revealed that the hazard ratios for OS and EFS showed significantly better results in the experimental treatment groups with increasing toxicities. The correlation between the hazard ratios for EFS and OS was good (R2 = 0.747, ρ = 0.683), and the correlation tended to be more favorable in cases of localized ES (R2 = 0.818, ρ = 0.929). ConclusionsOverall, the trial-level correlation between EFS and OS was good for newly diagnosed ES and was very good in cases of localized disease. EFS may be a useful endpoint in RCTs of ES chemotherapy, and it is worth verifying using individual patient data.

scholarly journals Meta-analytic evaluation of the correlation between event-free survival and overall survival in randomized controlled trials of newly diagnosed Ewing sarcoma.

2020 ◽  
Author(s):  
Kazuhiro Tanaka ◽  
Masanori Kawano ◽  
Tatsuya Iwasaki ◽  
Ichiro Itonaga ◽  
Hiroshi Tsumura
Keyword(s):  
Overall Survival ◽  
Randomized Controlled Trials ◽  
Ewing Sarcoma ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
Randomized Controlled ◽  
Hazard Ratios

Abstract Background In randomized controlled trials (RCTs) of adjuvant treatment for malignant tumors, event-free survival (EFS) is considered the most acceptable surrogate for overall survival (OS). However, even though EFS has repeatedly been selected as a primary endpoint in RCTs of Ewing sarcoma (ES), the surrogacy of EFS for OS has not been investigated. This study aimed to evaluate the surrogacy of EFS for OS in RCTs of chemotherapy for newly diagnosed ES using a meta-analytic approach. Methods We identified seven RCTs of newly diagnosed ES through a systematic review, and a meta-analysis was performed to evaluate the efficacy and adverse events associated with chemotherapy for previously untreated ES. The correlation between EFS and OS was investigated using weighted linear regression analysis and Spearman rank correlation coefficients (ρ). The strength of the correlation was evaluated using the coefficient of determination (R2). Results A total of 3,612 patients were randomly assigned to 17 treatment arms in the eligible RCTs. The meta-analysis revealed that the hazard ratios for OS and EFS showed significantly better results in the experimental treatment groups with increasing toxicities. The correlation between the hazard ratios for EFS and OS was good (R2 = 0.747, ρ = 0.683), and the correlation tended to be more favorable in cases of localized ES (R2 = 0.818, ρ = 0.929). Conclusions Overall, the trial-level correlation between EFS and OS was good for newly diagnosed ES and was very good in cases of localized disease. EFS may be useful as a surrogate endpoint in RCTs of ES, and the surrogacy of EFS is worth verifying using individual data.

scholarly journals Meta-analytic evaluation of the correlation between event-free survival and overall survival in randomized controlled trials of newly diagnosed Ewing sarcoma.

2019 ◽  
Author(s):  
Kazuhiro Tanaka ◽  
Masanori Kawano ◽  
Tatsuya Iwasaki ◽  
Ichiro Itonaga ◽  
Hiroshi Tsumura
Keyword(s):  
Overall Survival ◽  
Randomized Controlled Trials ◽  
Ewing Sarcoma ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
Randomized Controlled ◽  
Hazard Ratios

Abstract Background In randomized controlled trials (RCTs) of adjuvant treatment for malignant tumors, event-free survival (EFS) is considered the most acceptable surrogate for overall survival (OS). However, even though EFS has repeatedly been selected as a primary endpoint in RCTs of Ewing sarcoma (ES), the surrogacy of EFS for OS has not been investigated. This study aimed to evaluate the surrogacy of EFS for OS in RCTs of chemotherapy for newly diagnosed ES using a meta-analytic approach. Methods We identified seven RCTs of newly diagnosed ES through a systematic review, and a meta-analysis was performed to evaluate the efficacy and adverse events associated with chemotherapy for previously untreated ES. The correlation between EFS and OS was investigated by weighted linear regression analysis and Spearman rank correlation coefficients (ρ). The strength of the correlation was evaluated using the coefficient of determination (R2). Results A total of 3,612 patients were randomly assigned to 17 treatment arms in the eligible RCTs. The meta-analysis demonstrated that the hazard ratios for OS and EFS showed significantly better results in the experimental treatment groups with increasing toxicities. The correlation between the hazard ratios for EFS and OS was good (R2 = 0.747, ρ = 0.683), and the correlation tended to be more favorable in cases of localized ES (R2 = 0.818, ρ = 0.929). Conclusions Overall, the trial-level correlation between EFS and OS was good for newly diagnosed ES and was very good in cases of localized disease. Given the rare occurrence of ES and difficulty in conducting large-scale RCTs, EFS may be useful as a surrogate endpoint in RCTs of ES. The surrogacy of EFS is worth verifying using individual data.

Overall survival after perioperative chemotherapy in the management of pulmonary metastasis in osteosarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23508-e23508
Author(s):  
Zeba Siddiqui ◽  
Megan E Delisle ◽  
Amirrtha Srikanthan ◽  
Ying Wang
Keyword(s):  
Overall Survival ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Pulmonary Metastasectomy ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Perioperative Chemotherapy ◽  
Extrinsic Factors ◽  
Term Survival ◽  
Randomized Controlled

e23508 Background: Pulmonary metastasectomy is performed on a select cohort of patients with advanced osteosarcoma with the potential for long term survival. However, evidence on peri-operative chemotherapy at time of metastasectomy is not completely understood and difficult to summarize without a systematic examination of existing literature. The purpose of this project is to perform a meta-analysis of existing studies to determine overall survival (OS) and prognostic factors in adults and children with advanced and recurrent osteosarcoma receiving chemotherapy around time of metastasectomy. Methods: We reviewed survival studies conducted in children and adults with advanced and recurrent osteosarcoma who undergo pulmonary metastasectomy published in English with more than 5 patients. The primary outcome was overall survival. Literature searches were performed in multiple electronic databases including Ovid MEDLINE (1946 to present), Ovid EMBASE (1974 to present), Web of Science, and Cochrane Library. Two investigators independently screened all citations, abstracts, and full-text articles. Results: 24 out of 80 observational studies between 1977 to 2018 were included. 2146 patients were studied of which 987 underwent pulmonary metastasectomy for osteosarcoma. 822 patients received perioperative chemotherapy in this setting. No randomized controlled trials were identified. Studies included patients from Asia, Africa, Europe, and North America. The median OS ranged between 20 to 90 months. 5-year OS ranged between 15 to 63%. Factors associated with survival included: age, number of lesions, disease free interval, time of development of metastases, number of lesions and laterality of pulmonary disease. Conclusions: Overall survival in study has a significant range. Factors influencing survival included intrinsic factors such as patient age and disease characteristics, as well as extrinsic factors such as evolution of chemotherapy regimen over the past four decades. The main limitations are related to the inherently low-quality evidence as a result of lack of randomized controlled trials. More comprehensive data is needed to guide shared decision making in this area.

Surrogate End Points for Median Overall Survival in Metastatic Colorectal Cancer: Literature-Based Analysis From 39 Randomized Controlled Trials of First-Line Chemotherapy

2007 ◽  
Vol 25 (29) ◽  
pp. 4562-4568 ◽  
Author(s):  
Patricia A. Tang ◽  
Søren M. Bentzen ◽  
Eric X. Chen ◽  
Lillian L. Siu
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Randomized Controlled Trials ◽  
Metastatic Colorectal Cancer ◽  
Controlled Trials ◽  
First Line ◽  
End Points ◽  
Randomized Controlled ◽  
Hazard Ratios ◽  
Line Chemotherapy

Purpose Our aims were to determine the correlations between progression-free survival (PFS), time to progression (TTP), and response rate (RR) with overall survival (OS) in the first-line treatment of metastatic colorectal cancer (MCRC), and to identify a potential surrogate for OS. Methods Randomized trials of first-line chemotherapy in MCRC were identified, and statistical analyses were undertaken to evaluate the correlations between the end points. Results Thirty-nine randomized controlled trials were identified containing a total of 87 treatment arms. Among trials, the nonparametric Spearman rank correlation coefficient (rs) between differences (Δ) in surrogate end points (ΔPFS, ΔTTP, and ΔRR) and ΔOS were 0.74 (95% CI, 0.47 to 0.88), 0.52 (95% CI, 0.004 to 0.81), 0.39 (95% CI, 0.08 to 0.63), respectively. The rs for ΔPFS was not significantly different from the rs ΔTTP (P = .28). Linear regression analysis was performed using hazard ratios for PFS and OS. There was a strong relationship between hazard ratios for PFS and OS; the slope of the regression line was 0.54 ± 0.10, indicating that a novel therapy producing a 10% risk reduction for PFS will yield an estimated 5.4% ± 1% risk reduction for OS. Conclusion In first-line chemotherapy trials for MCRC, improvements in PFS are strongly associated with improvements in OS. In this patient population, PFS may be an appropriate surrogate for OS. As a clinical end point, PFS offers increased statistical power at a given time of analysis and a significant lead time advantage compared with OS.

Thromboprophylaxis In Multiple Myeloma Patients Undergoing Immunomodulatory Therapy with Thalidomide and Lenalidomide: A Systematic Review and Meta-Analysis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1090-1090
Author(s):  
Marc Carrier ◽  
Gregoire Le Gal ◽  
Jason Tay ◽  
Cynthia M. Wu ◽  
Agnes Y. Lee
Keyword(s):  
Multiple Myeloma ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Newly Diagnosed ◽  
Bleeding Events ◽  
Randomized Controlled ◽  
Literature Search Strategy ◽  
Previously Treated ◽  
Data Source

Abstract Abstract 1090 Background: The incidence of venous thromboembolism (VTE) in patients with multiple myeloma (MM) is high in patients treated with thalidomide (T)- and lenalidomide (L)-based regimens containing dexamethasone (D) and/or cytotoxic chemotherapy (C). Consensus guidelines recommend routine thromboprophylaxis but reliable data from randomized controlled trials are lacking. Recent observational studies have suggested that thromboprophylaxis might be efficacious in decreasing the risk of VTE in this population. Purpose: To determine the absolute rates of VTE with and without different thromboprophylactic agents (ASA, warfarin, low-molecular-weight-heparin [LMWH]) in patients with newly diagnosed or previously treated MM receiving T- or L-based regimens. Data Source: A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews of published studies up to Jan 2010. Results: A total of 66 studies were included in the analyses. Of these, 61 (4264 patients) and 5 (1119 patients) assessed T- and L-based regimens, respectively. Thalidomide-based regimens The rates of VTE (per 100 patient-cycles) in patients with newly diagnosed MM treated with T-based regimens: The rates of VTE (per 100 patient-months) in patients with previously treated MM managed with T-based regimens: Lenalidomide-based regimens The rates of VTE (per 100 patient-cycles) in patients with newly diagnosed MM treated with L-based regimens: The rate VTE (per 100 patient-months) in patients with previously treated MM managed with L-based regimens: None of the studies reported major bleeding events. Limitations: The definition for VTE varied across studies. Most studies did not outline the diagnostic criteria for VTE. Data are not available (NA) for all prophylaxis regimens. Conclusion: Patients with newly diagnosed or previously treated MM receiving T- or L-based regimens are at high risk of VTE. It is uncertain whether thromboprophylaxis provides a clear benefit, especially in those receiving L-based therapy or have previously treated disease. Randomized controlled trials are needed to address this important clinical need. Disclosures: Lee: Eisai: Research Funding; Sanofi Aventis: Consultancy, Honoraria; Leo Pharma: Consultancy; Pfizer: Consultancy, Honoraria; Bayer: Honoraria; Boehringer Ingelheim: Consultancy, Honoraria, Speakers Bureau.

Sign in / Sign up

Export Citation Format

Share Document