Page 63 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Predictive value of interim PET in DLBCL
The higher sensitivity values seen in ROC analysis for both IHP and custom criteria vs. the Deauville system may be explained by the lower threshold of test positivity with IHP vs. Deauville (using liver and blood pool activity as the reference tissue, respectively). None of the studies using custom criteria defined a threshold comparable to or higher than hepatic uptake. We found widely ranging positivity rates between studies, which are mainly in agreement with the timing of interim PET between cycles and the criteria used. In an exploratory analysis on five studies [34,37–39,47] that performed interim PET strictly after 2 cycles of therapy and applied the Deauville scoring system we found a pooled estimated HR of 3.48 (95% CI 2.46–4.93) with a corresponding 95% prediction interval of 1.58–7.67 (Supplemental Fig. 3). The positivity rates for these studies ranged between 18 and 46%, PPV from 37 to 74% and NPV from 76 to 91%, comparable to the analysis including all studies.
We chose to present the methodological characteristics along the other characteristics of the study population and treatments (Table 1) and along characteristics (including timing between cycles) of the index test (Table 2).
QUADAS-2 and QUIPS criteria were applied to assess the quality of the studies from the perspective of risk of bias and applicability. In this review, the strict inclusion and exclusion criteria with regard to patient population (>80% DLBCL), index test (interim PET between one and five treatment cycles), and reference standard (PFS and EFS) guaranteed the applicability of the results to the review question. In the subgroup analyses we examined whether bias could have occurred because of methodological shortcomings. It appeared that none of these affected the results. Only characteristics of the population (< 100% DLBCL) and a combination of integrated and standalone systems seemed to have impact on the predictive value of interim PET.
We used a comprehensive search strategy and applied strict inclusion and exclusion criteria. We focused on DLBCL patients, and 2-year PFS. Moreover, we examined the influence of different design characteristics (retrospective and prospective, blinded review or not reported; PFS or EFS), characteristics of patients (100% DLBCL or between 80 and 100%), treatments (ASCT upfront or not, preplanned or consolidative radiotherapy used or unknown), availability of a baseline PET or CT, properties of scans (PET/CT or a combination of PET/CT and PET
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