Page 64 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 3
standalone systems), and scoring issues (DS -, IHP -, or custom criteria, central review or local review). Only the patient characteristics and properties of scans affected the results. It appeared that the HR estimates of the included studies were quite homogeneous (I2 = 35%).
By contacting the authors we were able to include most of the eligible studies in our meta-analysis and deducting data that was not presented by the authors directly. Some data though were hard to obtain from the studies.
First of all, the definition of the start of the progression-free survival and event- free survival differed amongst studies. Some studies started their follow-up period at the time from diagnosis and others from initiation of first-line treatment. Recently some data has shown that patients who have a more aggressive disease tend to be treated earlier, so there could be selection bias between studies that have a shorter period between time of diagnosis and initiation of treatment versus studies with a longer period [54]. For future studies it seems important to have a comparable start of the follow-up period and authors should report the interval between diagnosis and start of the treatment to prevent or adjust for this risk of bias.
Another issue is that timing of the interim PET scans between cycles was different between studies; not only did the timing after which cycle the scan is performed differ, but also the number of days between the previous treatment course and interim PET. Unfortunately, not all authors report on this, although it is recommended to perform the scan at least 10 days after the previous course of chemotherapy, because of possible effects on tumor metabolism and systemic effects by, for example, growth factors [55].
In systematic reviews, investigators need to make choices. We chose to use the univariate data. This choice was made because univariate data were available in most studies and because of the large heterogeneity in factors for which the HR was adjusted in the primary articles. The adjusted factors were limited by the low number of events in most studies and partially based on available information such as quantitative PET analyses, immunohistochemistry and collection of specific clinical data (e.g. bone marrow involvement). Fourteen of the 20 studies performed a multivariate analysis. Most articles adjusted for the IPI score [34–
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