Page 17 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

components. When interim [18F]FDG PET is performed after 1 or 2 treatment cycles, it evaluates the response of the cells with the highest mitotic index, thereby providing an early evaluation of chemosensitivity. On the other hand, after 3 or 4 cycles of therapy, the [18F]FDG uptake of interim [18F]FDG PET is more dependent upon the tumor regrowth and inflammatory response (e.g. by macrophages). At this time point, interim [18F]FDG PET is also able to identify DLBCL patients with slow responding disease to R-CHOP treatment [37]. In studies that investigated the predictive value of interim [18F]FDG PET, timing of interim [18F]FDG PET varies considerably, both between and within studies, ranging from interim [18F]FDG PET being performed after 1 to 4 treatment cycles [26]. The timing of interim [18F]FDG PET may affect the visual and ∆SUVmax cut‐off that should be used. Studies were consistent with a 66% threshold for interim [18F]FDG PET after 2 cycles [33,35,36], whereas after 4 cycles the optimal cut-off is found at higher ∆SUVmax values, with reported thresholds ranging from 70% to 73% [35,38]. These findings illustrate that results of interim [18F]FDG PET scans performed after different treatment cycles cannot be merged a priori, and that timing is an important factor to consider in the search for the most optimal interim [18F]FDG PET assessment methodology and criteria.
Combination with established/new prognostic factors
Clinical prognostic indices
Estimation of prognosis of DLBCL is currently still based on the international prognostic index (IPI) or age-adjusted IPI (aaIPI), introduced in the early nineties [39]. This clinical risk score has several adaptations since then (e.g. R-IPI, NCCN-IPI) [40,41] and it was proven that is has still prognostic value after the introduction of rituximab [42]. However, almost half of the patients fall into the intermediate risk group [40,41], none of these criteria identify a poor prognosis group with survival clearly below 50% and the current criteria do not result into different treatment decisions outside clinical trials [43]. Therefore, the incremental predictive value of baseline and/or interim [18F]FDG PET in addition to clinical prognostic baseline indices is of high interest.
General introduction
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