Patient-specific meta-analysis (MA) of two validation studies to predict pathologic outcomes in prostate cancer (PCa) using a 17-gene genomic prostate score (GPS).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 100-100
Author(s):  
Matthew R. Cooperberg ◽  
Timothy C. Brand ◽  
Jeff Simko ◽  
Isabell Sesterhenn ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Predictive Value ◽  
Validation Studies ◽  
Risk Group ◽  
Meta Analysis ◽  
Patient Specific ◽  
Net Benefit ◽  
Clinical Risk ◽  
Risk Estimates ◽  
Number Of Patients ◽  
Wide Range

100 Background: We validated a biopsy-based assay as a predictor of PCa aggressiveness in two independent patient cohorts. Using GPS with NCCN risk group, the test provides an estimate of likelihood of favorable pathology (LFP) in low-intermediate risk PCa based on data from the first validation study. The second study re-confirmed the association between GPS and LFP. We combined information from both studies to provide more precise estimates of LFP, and examined predictive models using GPS with other clinical risk tools. Methods: Patient-specific MA provides precision-weighted predictions for individual patients using data from multiple studies (Crager and Tang, J. Appl. Stat. 2014). MA was performed on the two validation studies (732 patients total) using GPS (scale 0-100) with CAPRA score, NCCN risk group, or AUA/EAU risk group as predictors of LFP (Gleason score 3+3 or 3+4, organ-confined disease). Decision curves were calculated using the MA risk estimates. Results: MA provided more precise estimates of LFP with narrower confidence intervals (CIs) than either study alone (median width 24% narrower than the smaller of the two individual study CIs). GPS added significant predictive value for LFP to each of the 3 clinical classifiers. A model utilizing GPS and CAPRA provided the most risk discrimination. In decision-curve analysis, greater net benefit was shown when combining GPS with each clinical classifier compared with the clinical classifier alone. Over a wide range of threshold probabilities, incorporation of GPS would be expected to lead to fewer treatments of patients with favorable pathology without increasing the number of patients with adverse pathology left untreated. The proportion of men with MA-estimated LFP > 80% was 31% with GPS and CAPRA, and 23% with GPS and NCCN risk group; 11% were identified with LFP > 80% using NCCN risk group alone. Conclusions: Patient-specific MA of two independent studies provided more precise risk estimates reflecting the complete body of evidence. GPS adds predictive value to three clinical risk tools. The MA-estimated LFP identified more patients with an LFP > 80% than identified by clinical classifiers alone.

Successful Abolition of Prophylactic Cranial Irradiation in Children with Non-T Acute Lymphoblastic Leukemia (ALL) in the Japan Association of Childhood Leukemia Study (JACLS) ALL-02 Trial

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1506-1506 ◽  
Author(s):  
Daiichiro Hasegawa ◽  
Junichi Hara ◽  
Souichi Suenobu ◽  
Yoshihiro Takahashi ◽  
Atsushi Sato ◽  
...  
Keyword(s):  
High Risk ◽  
Induction Therapy ◽  
Early Phase ◽  
Systemic Chemotherapy ◽  
Risk Group ◽  
Cranial Irradiation ◽  
Cns Relapse ◽  
Cranial Nerve Palsies ◽  
Number Of Patients ◽  
Wide Range

Abstract Abstract 1506 BACKGROUND: A wide range of neuropsychological sequelae, noted in long-term survivors of ALL, have been in part ascribed to cranial irradiation (CRT), especially in children who are more vulnerable than adults. We had attempted to abandon prophylactic CRT by intensifying systemic chemotherapy and protracted triple IT (TIT) in ALL-02 trial; whereas one third of patients received CRT for CNS directed therapy in the former study (ALL-97). We present here the results of JACLS ALL-02 trials especially about the effect of the CNS-directed therapy. PATIENTS AND METHODS: Between 2002 and 2008, 1139 children with newly diagnosed non-T ALL with 1–18 years of age were enrolled to JACLS ALL-02 trial. Patients with Ph+ALL and T-ALL were registered to independent protocol. The criteria for diagnosis of CNS disease of the JACLS ALL-02 trial were defined as a CSF pleocytosis of > 5 cells /microL and the presence of recognizable blast cells on a well-stained cytospin preparation, or the presence of cranial-nerve palsies at a diagnosis of leukemia. Treatment group was divided into 3 groups according to the BFM-style initial prednisolone (PSL) response and the modified National Cancer Institute (NCI) workshop criteria. PSL good responders were divided into standard risk (SR) and high risk (HR) by WBC 10,000 and age 10. BCP-ALL with PSL poor responders and acute mixed lineage leukemia/ acute unclassified leukemias were treated in extremely high risk (ER). The SR patients with unequivocal CNS involvement (CNS3) at diagnosis were treated as an HR group. The patients in M1 marrow at day 33 with M2/M3 at the day 15 bone marrow (BM) were assigned to shift higher risk after induction therapy. Treatment of ALL-02 consists of early phase and maintenance phase. Early phase includes induction, consolidation, sanctuary (2 courses of high-dose MTX at a dose of 3g /m2), and re-induction therapy for 15 to 26 weeks depending on risk group. Prophylactic CRT was replaced by protracted TIT (MTX, CA, HDC) in all except the patients with CNS3 at diagnosis in ALL-02 trial. The patients with CNS3 at diagnosis received CRT at a dose of 12 Gy. Depending on the risk group, protracted TIT was given during induction, intensification and maintenance in ALL-02 (12 doses in SR and 15 in HR/ER). Accumulative doses of DEX were 120 mg/m2 in SR, whereas 170 mg/m2 in HR and 670 mg/m2 in ER. Treatment duration is 24 months for any risk. The patients assigned ER were candidate for allogeneic stem cell transplantation (SCT) by the end of early phase, provided HLA-matched siblings were available. The probability of event-free survival (EFS) and overall survival were constructed using the Kaplan-Meier method. Events in the analysis of EFS included induction failure, death, relapse and secondary malignant neoplasm. All statistical analyses were done according to intent-to treat methods. RESULTS: The numbers of patients at each risk in ALL-02 were 457 (40%) for SR, 543 (48%) for HR, and 139 (12%) for ER. The number of patients with CNS3 at diagnosis was 31 (2.7%). Of 1139 patients, 16 patients (1.4%) had CNS relapses of the leukemia (an isolated CNS relapse: 10 pts, a combined CNS and BM relapse: 6 pts). The 5-year EFS rate ALL-02 was 83.7% (SE=1.1), slightly better than for ALL-97 (79.3%, SE=1.7, p =0.054). The 5-year cumulative risk of an isolated and total CNS relapse was lower in ALL-02 than in ALL-97 (isolated CNS relapse: 0.9% vs 2.7%, p=0.017, total CNS relapse: 4.5% vs 1.4%, p =0.01). The proportion of CRT and SCT were 2%, 8% in ALL-02 respectively, whereas 31%, 11% in ALL-97 respectively. CONCLUSIONS: The ALL-02 trial found that CRT was abolished successfully, in all except those with CNS3 at diagnosis, with substitution of more intensive systemic chemotherapy and protracted TIT. Disclosures: No relevant conflicts of interest to declare.

Patient-specific meta-analysis of 3 validation studies of the 12-gene colon cancer recurrence score assay for recurrence risk assessment after surgery with or without 5FU and oxaliplatin.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3599-3599
Author(s):  
Greg Yothers ◽  
Alan P. Venook ◽  
Takeharu Yamanaka ◽  
Yan Lin ◽  
Michael Crager ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Meta Analysis ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Current Medical ◽  
Stage Ii ◽  
Patient Specific ◽  
Risk Estimates ◽  
Oxaliplatin Treatment ◽  
Current Medical Practice

3599 Background: The 12-gene Oncotype DX Colon Recurrence Score assay is a clinically validated genomic assay that evaluates recurrence risks in stage II and stage III colon cancer patients independent of clinical-pathologic features. Improved colon cancer care has reduced recurrence rates since the late 1990’s. Methods: Pre-specified patient-specific meta-analysis methods were used to estimate 1-, 3- and 5-year recurrence risk combining the 12-gene colon recurrence score (RS) validation studies CALGB 9581, NSABP C-07 and SUNRISE. Cox models had effects for RS result, number of nodes examined (<12 or ≥ 12), T-stage, MMR status, and stage (II, IIIAB or IIIC). Baseline cumulative hazard estimates used the latest two studies to reflect current medical practice. Estimates for surgery, surgery+5FU and surgery+5FU+oxaliplatin treatment were provided by integrating stage-specific 5FU hazard ratios from a meta-analysis of the QUASAR study (2007) and a pooled analysis of NSABP studies (Wilkinson 2010), and oxaliplatin treatment effect estimates from NSABP C-07. Recurrence risk with 5FU alone was not estimated for MMR-deficient patients due to expected lack of 5FU efficacy in these patients (Sargent 2010). Results: In the overall population of 2,179 patients, 55%, 32% and 13% were Stage II, IIIA/B and IIIC, 63% had ≥12 nodes examined, 90% were T3, and 88% were MMR proficient. Median RS result was 31 (IQR 23–39). RS result and each clinical-pathologic factor contributed independent prognostic information (meta-analysis Wald tests, all p<.001). Risk estimates are generally lower than previous RS report risk estimates. For patients with pathological stage II, T3, MMR-proficient tumors with ≥12 nodes examined, approximately 40% are expected to have 5-year recurrence risk ≤10% with surgery alone based on the distribution of RS results. The table shows example 5-year recurrence risk estimates for specific RS results and clinical-pathologic characteristics. Conclusions: The new recurrence risk estimates provide more patient-specific information reflecting more current medical practice than previous reports using RS result, allowing better, more individualized treatment decisions.[Table: see text]

scholarly journals A nomogram for predicting postoperative pulmonary infection in esophageal cancer patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shuang Li ◽  
Jingwen Su ◽  
Qiyu Sui ◽  
Gongchao Wang
Keyword(s):  
Esophageal Cancer ◽  
Pulmonary Infection ◽  
Predictive Accuracy ◽  
Patient Specific ◽  
Individual Risk ◽  
Multivariable Logistic Regression Analysis ◽  
Net Benefit ◽  
Curative Surgery ◽  
Individual Probability ◽  
Wide Range

Abstract Background Although postoperative pulmonary infection (POI) commonly occurs in patients with esophageal cancer after curative surgery, a patient-specific predictive model is still lacking. The main aim of this study is to construct and validate a nomogram for estimating the risk of POI by investigating how perioperative features contribute to POI. Methods This cohort study enrolled 637 patients with esophageal cancer. Perioperative information on participants was collected to develop and validate a nomogram for predicting postoperative pulmonary infection in esophageal cancer. Predictive accuracy, discriminatory capability, and clinical usefulness were evaluated by calibration curves, concordance index (C-index), and decision curve analysis (DCA). Results Multivariable logistic regression analysis indicated that length of stay, albumin, intraoperative bleeding, and perioperative blood transfusion were independent predictors of POI. The nomogram for assessing individual risk of POI indicated good predictive accuracy in the primary cohort (C-index, 0.802) and validation cohort (C-index, 0.763). Good consistency between predicted risk and observed actual risk was presented as the calibration curve. The nomogram for estimating POI of esophageal cancer had superior net benefit with a wide range of threshold probabilities (4–81%). Conclusions The present study provided a nomogram developed with perioperative features to assess the individual probability of infection may conducive to strengthen awareness of infection control and provide appropriate resources to manage patients at high risk following esophagectomy.

scholarly journals Patient-specific Meta-analysis of 2 Clinical Validation Studies to Predict Pathologic Outcomes in Prostate Cancer Using the 17-Gene Genomic Prostate Score

Urology ◽  
2016 ◽  
Vol 89 ◽  
pp. 69-75 ◽  
Author(s):  
Timothy C. Brand ◽  
Nan Zhang ◽  
Michael R. Crager ◽  
Tara Maddala ◽  
Anne Dee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Validation Studies ◽  
Meta Analysis ◽  
Patient Specific ◽  
Clinical Validation

scholarly journals A Nomogram Based on a Multiparametric Ultrasound Radiomics Model for Discrimination Between Malignant and Benign Prostate Lesions

2021 ◽  
Vol 11 ◽  
Author(s):  
Lei Liang ◽  
Xin Zhi ◽  
Ya Sun ◽  
Huarong Li ◽  
Jiajun Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Diagnostic Performance ◽  
Clinical Risk Factors ◽  
Net Benefit ◽  
Combined Model ◽  
Clinical Model ◽  
Clinical Risk ◽  
Wide Range ◽  
Multiparametric Ultrasound

ObjectivesTo evaluate the potential of a clinical-based model, a multiparametric ultrasound-based radiomics model, and a clinical-radiomics combined model for predicting prostate cancer (PCa).MethodsA total of 112 patients with prostate lesions were included in this retrospective study. Among them, 58 patients had no prostate cancer detected by biopsy and 54 patients had prostate cancer. Clinical risk factors related to PCa (age, prostate volume, serum PSA, etc.) were collected in all patients. Prior to surgery, patients received transrectal ultrasound (TRUS), shear-wave elastography (SWE) and TRUS-guided prostate biopsy. We used the five-fold cross-validation method to verify the results of training and validation sets of different models. The images were manually delineated and registered. All modes of ultrasound radiomics were retrieved. Machine learning used the pathology of “12+X” biopsy as a reference to draw the benign and malignant regions of interest (ROI) through the application of LASSO regression. Three models were developed to predict the PCa: a clinical model, a multiparametric ultrasound-based radiomics model and a clinical-radiomics combined model. The diagnostic performance and clinical net benefit of each model were compared by receiver operating characteristic curve (ROC) analysis and decision curve.ResultsThe multiparametric ultrasound radiomics reached area under the curve (AUC) of 0.85 for predicting PCa, meanwhile, AUC of B-mode radiomics and SWE radiomics were 0.74 and 0.80, respectively. Additionally, the clinical-radiomics combined model (AUC: 0.90) achieved greater predictive efficacy than the radiomics model (AUC: 0.85) and clinical model (AUC: 0.84). The decision curve analysis also showed that the combined model had higher net benefits in a wide range of high risk threshold than either the radiomics model or the clinical model.ConclusionsClinical-radiomics combined model can improve the accuracy of PCa predictions both in terms of diagnostic performance and clinical net benefit, compared with evaluating only clinical risk factors or radiomics score associated with PCa.

scholarly journals Rates, predictors and mortality of sepsis-induced acute kidney injury: systematic review and meta-analysis

2020 ◽  
Author(s):  
Jie feng Liu ◽  
Hebin Xie ◽  
ziwei ye ◽  
Fen Li ◽  
Lesan Wang
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Septic Shock ◽  
Acute Kidney Injury ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Predisposing Factors ◽  
Cochrane Library ◽  
Patient Specific ◽  
Wide Range

Abstract Background: Due to the high incidence and mortality of sepsis-associated acute kidney injury, a significant number of studies have explored the causes of sepsis-associated acute kidney injury (AKI). However, the opinions on relevant predictive risk factors remain inconclusive. This study aimed to provide a systematic review and a meta-analysis to determine the predisposing factors for sepsis-associated AKI.Method: A systematic literature search was performed in the Medline, Embase, Cochrane Library, PubMed, and Web of Science, databases, with an end-date of 25th May 2019. Valid data were retrieved in compliance with specific inclusion and exclusion criteria.Result: Forty-seven observational studies were included for analysis, achieving a cumulative patient number of 55,911. The highest incidence of AKI was caused by septic shock. Thirty-one potential risk factors were included in the meta-analysis. Analysis showed that 20 factors were statistically significant. The odds ratio (OR) and 95% confidence interval (CI), as well as the prevalence of the most frequently-seen predisposing factors for sepsis-associated AKI, were as follows: septic shock [2.88 (2.36-3.52), 60.47%], hypertension [1.43 (1.20-1.70), 38.39%], diabetes mellitus [1.59 (1.47-1.71), 27.57%], abdominal infection [1.44 (1.32-1.58), 30.87%], the administration of vasopressors [2.95 (1.67-5.22), 64.61%], the administration of vasoactive drugs [3.85 (1.89-7.87), 63.22%], mechanical ventilation [1.64 (1.24-2.16), 68.00%], positive results from blood culture [1.60 (1.35-1.89), 41.19%], and a history of smoking [1.60 (1.09-2.36), 43.09%]. Other risk factors included cardiovascular diseases, coronary artery diseases, liver diseases, unknown infections, the administration of diuretics and ACEI/ARB, infection caused by gram-negative bacteria, and organ transplantation.Conclusion: Risk factors of S-AKI arise from a wide range of sources, making it difficult to predict and prevent this condition. Comorbidities, and certain drugs, are the main risk factors for S-AKI. Our review can provide guidance on the application of interventions to reduce the risks associated with sepsis-associated acute kidney injury and can also be used to tailor patient-specific treatment plans and management strategies in clinical practice.

scholarly journals The Predictive Value of Right Ventricular Longitudinal Strain in Pulmonary Hypertension, Heart Failure, and Valvular Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Marijana Tadic ◽  
Nicoleta Nita ◽  
Leonhard Schneider ◽  
Johannes Kersten ◽  
Dominik Buckert ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Right Ventricular ◽  
Predictive Value ◽  
Longitudinal Strain ◽  
Systolic Function ◽  
Number Of Patients ◽  
Valvular Heart Diseases ◽  
Wide Range

Right ventricular (RV) systolic function has an important role in the prediction of adverse outcomes, including mortality, in a wide range of cardiovascular (CV) conditions. Because of complex RV geometry and load dependency of the RV functional parameters, conventional echocardiographic parameters such as RV fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE), have limited prognostic power in a large number of patients. RV longitudinal strain overcame the majority of these limitations, as it is angle-independent, less load-dependent, highly reproducible, and measure regional myocardial deformation. It has a high predictive value in patients with pulmonary hypertension, heart failure, congenital heart disease, ischemic heart disease, pulmonary embolism, cardiomyopathies, and valvular disease. It enables detection of subclinical RV damage even when conventional parameters of RV systolic function are in the normal range. Even though cardiac magnetic resonance-derived RV longitudinal strain showed excellent predictive value, echocardiography-derived RV strain remains the method of choice for evaluation of RV mechanics primarily due to high availability. Despite a constantly growing body of evidence that support RV longitudinal strain evaluation in the majority of CV patients, its assessment has not become the part of the routine echocardiographic examination in the majority of echocardiographic laboratories. The aim of this clinical review was to summarize the current data about the predictive value of RV longitudinal strain in patients with pulmonary hypertension, heart failure and valvular heart diseases.

scholarly journals The benefit–risk balance for biological agents in juvenile idiopathic arthritis: a meta-analysis of randomized clinical trials

Rheumatology ◽  
2020 ◽  
Vol 59 (9) ◽  
pp. 2226-2236 ◽  
Author(s):  
Natalia Cabrera ◽  
Gabriela Avila-Pedretti ◽  
Alexandre Belot ◽  
Jean-Paul Larbre ◽  
Sabine Mainbourg ◽  
...  
Keyword(s):  
Adverse Events ◽  
Meta Analysis ◽  
Risk Difference ◽  
Biological Agents ◽  
Baseline Risk ◽  
Control Group ◽  
Net Benefit ◽  
Serious Adverse Events ◽  
Systemic Jia ◽  
Number Of Patients

Abstract Objective To assess the net benefit of biological agents (BA) used in JIA. Methods We systematically searched databases up to March 2019 for randomized controlled trials (RCT) performed in JIA disease. Separate random-effects meta-analyses were conducted for efficacy (ACR paediatric score 30%, ACRpedi30) and serious adverse events for safety. In order to standardize the baseline risk, we performed a meta-analysis of baseline risk in the control group (for both efficacy and safety meta-analysis). The net benefit was determined as the risk difference of efficacy subtracted by the risk difference of safety. Results We included 19 trials: 11 parallel RCTs (754 patients) and 8 withdrawal RCTs (704 patients). The net benefit ranged from 2.4% (adalimumab) to 17.6% (etanercept), and from 2.4% (etanercept) to 36.7%, (abatacept) in parallel and withdrawal trials assessing non-systemic JIA, respectively. In the systemic JIA category, the net benefit ranged from 22.8% (rilonacept) to 70.3% (canakinumab), and from 32.3% (canakinumab) to 58.2% (tocilizumab) in parallel and withdrawal trials, respectively. Conclusion The results suggest that a greater number of patients experienced therapeutic success without serious adverse events in the systemic onset JIA category compared with the BAs for non-systemic JIA categories. Baseline risk, design of trial and JIA categories impact the measure of net benefit of BAs in JIA patients.

Age- and sex-related bone uptake of Tc-99m-HDP measured by whole-body bone scanning

2000 ◽  
Vol 39 (05) ◽  
pp. 127-132 ◽  
Author(s):  
Nicole Sieweke ◽  
K. H. Bohuslavizki ◽  
W. U. Kampen ◽  
M. Zuhayra ◽  
M. Clausen ◽  
...  
Keyword(s):  
Whole Body ◽  
Bone Lesions ◽  
Men And Women ◽  
Bone Uptake ◽  
Normal Bone ◽  
Age Related ◽  
Number Of Patients ◽  
Wide Range ◽  
Bone Scans ◽  
Body Bone

Summary Aim of this study was to validate a recently introduced new and easy-to-perform method for quantifying bone uptake of Tc-99m-labelled diphosphonate in a routine clinical setting and to establish a normal data base for bone uptake depending on age and gender. Methods: In 49 women (14-79 years) and 47 men (6-89 years) with normal bone scans as well as in 49 women (33-81 years) and 37 men (27-88 years) with metastatic bone disease whole-body bone scans were acquired at 3 min and 3-4 hours p.i. to calculate bone uptake after correction for both urinary excretion and soft tissue retention. Results: Bone uptake values of various age-related subgroups showed no significant differences between men and women (p >0.05 ). Furthermore, no differences could be proven between age-matched subgroups of normals and patients with less than 10 metastatic bone lesions, while patients with wide-spread bone metastases revealed significantly increased uptake values. In both men and women highest bone uptake was obtained (p <0.05 ) in subjects younger than 20 years with active epiphyseal growth plates. In men, bone uptake slowly decreased with age up to 60 years and then showed a tendency towards increasing uptake values. In women, the mean uptake reached a minimun in the decade 20-29 years and then slowly increased with a positive linear correlation of age and uptake in subjects older than 55 years (r = 0.57). Conclusion: Since the results proposed in this study are in good agreement with data from literature, the new method used for quantification could be validated in a large number of patients. Furthermore, age- and sexrelated normal bone uptake values of Tc-99m-HDP covering a wide range of age could be presented for this method as a basis for further studies on bone uptake.

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