Page 65 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Predictive value of interim PET in DLBCL
39,41–43,46] or age-adjusted IPI [44,48,49], some dichotomized the score and others used the individual components. Results were varying widely; in some studies both interim PET and (aa)IPI showed an independent association with PFS or EFS [42,48], others only for interim PET [34,37,39,41,44,53], or (aa) IPI [43,49] or no independent associations were found for both interim PET or (aa)IPI [35,36,38,46]. One could argue that reporting univariate HRs instead of multivariate HRs could result in an overestimation of the predictive value of interimPET.ThreestudiesreportedbothuniandmultivariateHRsanddifferences between univariate and multivariate HRs were −0.99 [41], 0.0 [39],and + 0.2 [42], respectively.
We further decided to choose the DS threshold for the interim response criteria which is most commonly described (DS < = 3 versus DS > = 4), because presenting all thresholds would increase heterogeneity, influence effect sizes, and finally use the same patients data multiple times in the analyses. Four studies presented multiple scores. Mylam et al. [43] published data about positivity for Deauville scores 4 and 5 as well as for Deauville score 5 and for IHP. Kim et al. [35] and Itti et al. [47] presented data about different positivity cutoff values for Deauville scores. Fuertes et al. [45] published a regular Deauville score as well as a 3 point- scale. In this review, we focused on visual response assessment criteria, and the potential added value of quantitative PET metrics is currently being investigated. Recently, a large phase III PET-adapted trial showed in a post-hoc analysis that a SUVmax reduction strategy [56] seems to discriminate better between good and poor outcome compared to the Deauville scoring system [57]. Finally, it should be mentioned that the studies from Safar et al. [50] and Itti et al. [47] had a small overlap in patient inclusion (n = 7); however, this will presumably not bias our results due to the small number.
Conclusion
This systematic review and meta-analysis shows that interim PET in DLBCL patients has predictive value (HR 3.13). However, some diagnostic test characteristics are still too low, especially the positive predictive value should be improved, before a risk stratified treatment approach can be implemented in clinical practice.
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