Page 48 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 3
Outcome measures
The primary outcome measure was defined as PFS (preferably) or EFS at 2 years. We included studies with a minimum median follow-up period of 24 months in surviving patients (or for the entire study population), because most patients experience relapse or progression of their disease in the first 2 years after their diagnosis [24,25].
Data extraction and quality assessment
After removing duplicates, two authors independently screened titles and abstracts ofthesearchresultsforeligibility(CNBandNH,AdJ,orHCWdV).Thedecision to include studies in the review was based on the full-text articles (CNB and AdJ or HCWdV). Extensive data extraction forms (available upon request) were developed which included the criteria from the methodological checklists for diagnostic accuracy studies (QUADAS-2) [26] and for prognostic studies (QUIPS) [27]. The forms were tested in a few articles and used independently by two review authors (CNB, AdJ). Consensus meetings (with three experts in nuclear medicine, hematology, and methodology, respectively) were organized to solve disagreements and to decide on eligibility of the final study selection. Besides general information about study design, patients, treatment, interim 18F-FDG PET performance, and outcome measures (used for qualitative study descriptions and determination of eligibility) we extracted outcomes on two types of predictive parameters. For the first predictive meta-analysis we extracted univariate hazard ratios (HRs) and their corresponding 95% confidence intervals. If this data was not reported and not provided after contacting the authors, we used the methods of Tierney et al. [28] to deduce these from reported parameters or from the Kaplan-Meier (KM) curves, using numbers at risk when available. For the second predictive meta-analysis we used a diagnostic approach and constructed 2 × 2 contingency tables to calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of interim 18F-FDG PET for prediction of two-year PFS and - EFS. If no two-year survival percentages were reported we estimated the percentages from the KM curves at this time-point. If information was missing or unclear authors were contacted. A maximum of three reminders were sent. In case of no reply we used the information that was available from the original publication. Individual patient data was not requested for this meta-analysis.
46