scholarly journals Individual Patient-Level Meta-Analysis of the Performance of the Decipher Genomic Classifier in High-Risk Men After Prostatectomy to Predict Development of Metastatic Disease

2017 ◽  
Vol 35 (18) ◽  
pp. 1991-1998 ◽  
Author(s):  
Daniel E. Spratt ◽  
Kasra Yousefi ◽  
Samineh Deheshi ◽  
Ashley E. Ross ◽  
Robert B. Den ◽  
...  

Purpose To perform the first meta-analysis of the performance of the genomic classifier test, Decipher, in men with prostate cancer postprostatectomy. Methods MEDLINE, EMBASE, and the Decipher genomic resource information database were searched for published reports between 2011 and 2016 of men treated by prostatectomy that assessed the benefit of the Decipher test. Multivariable Cox proportional hazards models fit to individual patient data were performed; meta-analyses were conducted by pooling the study-specific hazard ratios (HRs) using random-effects modeling. Extent of heterogeneity between studies was determined with the I2 test. Results Five studies (975 total patients, and 855 patients with individual patient-level data) were eligible for analysis, with a median follow-up of 8 years. Of the total cohort, 60.9%, 22.6%, and 16.5% of patients were classified by Decipher as low, intermediate, and high risk, respectively. The 10-year cumulative incidence metastases rates were 5.5%, 15.0%, and 26.7% ( P < .001), respectively, for the three risk classifications. Pooling the study-specific Decipher HRs across the five studies resulted in an HR of 1.52 (95% CI, 1.39 to 1.67; I2 = 0%) per 0.1 unit. In multivariable analysis of individual patient data, adjusting for clinicopathologic variables, Decipher remained a statistically significant predictor of metastasis (HR, 1.30; 95% CI, 1.14 to 1.47; P < .001) per 0.1 unit. The C-index for 10-year distant metastasis of the clinical model alone was 0.76; this increased to 0.81 with inclusion of Decipher. Conclusion The genomic classifier test, Decipher, can independently improve prognostication of patients postprostatectomy, as well as within nearly all clinicopathologic, demographic, and treatment subgroups. Future study of how to best incorporate genomic testing in clinical decision-making and subsequent treatment recommendations is warranted.

2021 ◽  
Author(s):  
Ashwin Subramaniam ◽  
Christopher Anstey ◽  
J Randall Curtis ◽  
Sushma Ashwin ◽  
Mallikarjuna PONNAPA REDDY ◽  
...  

Abstract Purpose: Frailty is often used in clinical decision-making for patients with COVID-19, yet studies have found variable influence of frailty on outcomes in those admitted to the intensive care unit (ICU). In this individual patient data meta-analysis, we evaluated the characteristics, and outcomes of frail patients admitted to ICU with COVID-19.Methods: We contacted the corresponding authors of sixteen eligible studies published between December 1st 2019 and February 28th 2021 reporting the clinical frailty scale (CFS) in patients with confirmed COVID-19 admitted to ICU. Individual patient data was obtained from 7 studies. We classified patients as non-frail (CFS=1-4) or frail (CFS=5-8). The primary outcome was hospital mortality. We also compared the use of mechanical ventilation (MV) and the proportion of ICU bed-days between frailty categories. Results: Of the 2001 patients admitted to ICU, 388 (19.4%) were frail. Increasing age and sequential organ failure assessment (SOFA) score, CFS ≥4, use of MV, vasopressors, renal replacement therapy and hyperlactatemia were risk factors for death in a multivariable analysis. Hospital mortality was higher in frail patients (65.2% vs. 41.8%; p<0.001), with adjusted mortality increasing with a rising CFS score beyond 3. Younger and non-frail patients were more likely to receive MV. Frail patients spent less time on MV (median days [IQR] 9 [5-16] vs. 11 [6-18]; p=0.012) and accounted for only 12.3% of total ICU bed-days. Conclusion: Frail patients with COVID-19 were commonly admitted to ICU and had greater hospital mortality but spent relatively fewer days in ICU when compared with non-frail patients. Frail patients receiving MV were at greater risk of death than non-frail patients. Systematic review registration: Registration protocol in PROSPERO (CRD42020224255).


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 133-133
Author(s):  
Daniel Eidelberg Spratt ◽  
Kasra Yousefi ◽  
Samineh Deheshi ◽  
Ashley Ross ◽  
Edward M. Schaeffer ◽  
...  

133 Background: The genomic classifier, Decipher, has been validated to predict risk of metastasis after radical prostatectomy (RP). However, the cohort size and event rate in the previous studies did not allow for a thorough investigation into performance within individual clinicopathologic or treatment subgroups. In this study, we present the first meta-analysis of the performance of the 22-marker genomic classifier in men with prostate cancer (PCa) post-RP. Methods: MEDLINE, EMBASE, and the Decipher genomic resource information database were searched for published reports of men with PCa treated by RP between 2010 and 2016 where the benefit of the Decipher genomic classifier test was assessed. The primary end point was the ability of Decipher to independently improve prognostication of regional or distant metastasis over routine clinicopathologic factors. Meta-analysis was performed with random-effects modeling, and extent of heterogeneity between studies was determined with the I2 test. Results: Five studies (975 total patients, and 855 with individual patient genomic and clinicopathologic data) were eligible for analysis. The median follow-up was 8 years. All patients had clinical high-risk disease, yet 60.9%, 22.6%, and 16.5% of patients were classified as low, intermediate, and high-risk, respectively by Decipher and had 10-year cumulative incidence rates of metastases of 5.5%, 15.0% and 26.7% (p < 0.001), respectively. Adjusting for standard clinicopathologic variables, on multivariable analysis Decipher remained a statistically significant predictor of metastasis (hazard ratio [HR] 1.30 per 0.1 unit, 95% confidence interval [CI] 1.14-1.47, p < 0.001), and the summary HR for metastasis of Decipher across the 5 studies was 1.52 (95% CI 1.39-1.67) per 0.1 unit. Conclusions: The genomic classifier test, Decipher, has the ability to independently improve prognostication of men post-RP, as well as within nearly all clinicopathologic and treatment subgroups. Strong consideration should be given to incorporating the use of genomic testing in clinical decision making and clinical trials to better individualize treatment.


2020 ◽  
Vol 73 ◽  
pp. S723-S724
Author(s):  
Juan Carlos Garcia Pagan ◽  
Oana Nicoara-Farcau ◽  
Debora Angrisani ◽  
Alberto Monescillo ◽  
Guohong Han ◽  
...  

2021 ◽  
Vol 108 (Supplement_4) ◽  
Author(s):  
P Probst ◽  
U Klaiber ◽  
S Seide ◽  
M Kawai ◽  
I Matsumoto ◽  
...  

Abstract Objective Some studies have indicated that resecting the pylorus during partial pancreatoduodenectomy (PD) may lead to reduced delayed gastric emptying (DGE). Randomized controlled trials (RCTs) showed conflicting results regarding superiority of pylorus-resecting PD (prPD) compared to the pylorus-preserving procedure (ppPD). The aim of this individual patient data meta-analysis was to investigate risk factors on an individual patient level which may explain the observed differences between the existing RCTs. Methods RCTs comparing ppPD and prPD were searched systematically in MEDLINE, Web of Science and CENTRAL. Individual patient data (IPD) from existing RCTs were included. The primary endpoint was DGE according to the International Study Group of Pancreatic Surgery (ISGPS) adjusted for age, sex and body-mass-index (BMI). The meta-regression model was applied to the IPD of the RCTs. Mixed effects models were applied to perform meta-analyses. Results IPD from 418 patients (three RCTs) were used for quantitative synthesis. There was no significant statistical difference between ppPD and prPD regarding DGE adjusted for age, sex and BMI (OR 0.72; 95%-CI: 0.41 to 1.22) and DGE grade (RR 1.01; 95%-CI: 0.64 to 1.57). Regarding other relevant perioperative and postoperative outcome parameters, there were also no significant differences among the two techniques. Conclusion This IPD meta-analysis comparing preservation and resection of the pylorus during PD confirmed that the resection of the pylorus is not superior to the pylorus-preserving procedure regarding DGE. The pylorus should therefore be preserved whenever possible. Further RCT are futile, because their results are unlikely to change the pooled estimate for DGE.


PLoS Medicine ◽  
2020 ◽  
Vol 17 (11) ◽  
pp. e1003393
Author(s):  
Mohammad S. Hossain ◽  
Robert J. Commons ◽  
Nicholas M. Douglas ◽  
Kamala Thriemer ◽  
Bereket H. Alemayehu ◽  
...  

Background There is a high risk of Plasmodium vivax parasitaemia following treatment of falciparum malaria. Our study aimed to quantify this risk and the associated determinants using an individual patient data meta-analysis in order to identify populations in which a policy of universal radical cure, combining artemisinin-based combination therapy (ACT) with a hypnozoitocidal antimalarial drug, would be beneficial. Methods and findings A systematic review of Medline, Embase, Web of Science, and the Cochrane Database of Systematic Reviews identified efficacy studies of uncomplicated falciparum malaria treated with ACT that were undertaken in regions coendemic for P. vivax between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of P. vivax parasitaemia at days 42 and 63 and associated risk factors were investigated by multivariable Cox regression analyses. Study quality was assessed using a tool developed by the Joanna Briggs Institute. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42018097400). In total, 42 studies enrolling 15,341 patients were included in the analysis, including 30 randomised controlled trials and 12 cohort studies. Overall, 14,146 (92.2%) patients had P. falciparum monoinfection and 1,195 (7.8%) mixed infection with P. falciparum and P. vivax. The median age was 17.0 years (interquartile range [IQR] = 9.0–29.0 years; range = 0–80 years), with 1,584 (10.3%) patients younger than 5 years. 2,711 (17.7%) patients were treated with artemether-lumefantrine (AL, 13 studies), 651 (4.2%) with artesunate-amodiaquine (AA, 6 studies), 7,340 (47.8%) with artesunate-mefloquine (AM, 25 studies), and 4,639 (30.2%) with dihydroartemisinin-piperaquine (DP, 16 studies). 14,537 patients (94.8%) were enrolled from the Asia-Pacific region, 684 (4.5%) from the Americas, and 120 (0.8%) from Africa. At day 42, the cumulative risk of vivax parasitaemia following treatment of P. falciparum was 31.1% (95% CI 28.9–33.4) after AL, 14.1% (95% CI 10.8–18.3) after AA, 7.4% (95% CI 6.7–8.1) after AM, and 4.5% (95% CI 3.9–5.3) after DP. By day 63, the risks had risen to 39.9% (95% CI 36.6–43.3), 42.4% (95% CI 34.7–51.2), 22.8% (95% CI 21.2–24.4), and 12.8% (95% CI 11.4–14.5), respectively. In multivariable analyses, the highest rate of P. vivax parasitaemia over 42 days of follow-up was in patients residing in areas of short relapse periodicity (adjusted hazard ratio [AHR] = 6.2, 95% CI 2.0–19.5; p = 0.002); patients treated with AL (AHR = 6.2, 95% CI 4.6–8.5; p < 0.001), AA (AHR = 2.3, 95% CI 1.4–3.7; p = 0.001), or AM (AHR = 1.4, 95% CI 1.0–1.9; p = 0.028) compared with DP; and patients who did not clear their initial parasitaemia within 2 days (AHR = 1.8, 95% CI 1.4–2.3; p < 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high. Conclusions In this meta-analysis, we found a high risk of P. vivax parasitaemia after treatment of P. falciparum malaria that varied significantly between studies. These P. vivax infections are likely attributable to relapses that could be prevented with radical cure including a hypnozoitocidal agent; however, the benefits of such a novel strategy will vary considerably between geographical areas.


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