Page 16 - Wondergem

Chapter 1
a SUVmax below 10 (29), in another no transformed patient showed a SUVmax below 11.7 (28). This hampers the use of 18F-FDG and SUVmax for detection of transformation in clinical practice. In an attempt to improve on this, the use of alternative tracers can be explored. Conceptually, fluorothymidine (18F-FLT) reflects proliferation more closely than 18F-FDG (30,31). The presumed mechanism of 18F-FLT imaging is uptake in proliferating cells via the pyrimidine salvage pathway, mostly during S-phase (32). After phosphorylation by thymidine kinase 1 (TK-1), a principal enzyme in the DNA- salvage pathway, 18F-FLT is trapped in the cell (Figure 4). There is limited data about 18F-FLT uptake in both aggressive and indolent lymphoma, however hardly any data are available on the value of 18F-FLT-PET in patients with transformed FL (33,34).
In this thesis we compared the diagnostic accuracy of 18F-FDG and 18F-FLT to detect transformation (Chapter 2). As the uptake is known to vary for different indolent lymphoma types (26-29) we only included patients with FL and transformation of FL. We additionally explored the range in uptake defined as the difference between the SUVmax of the lymph node with the highest and the lowest uptake. This might better represent the intra-patient heterogeneity in TFL (lymph nodes with indolent and lymph nodes with aggressive histology co-existing in one patient) than only a SUVmax of the lymph node with the highest uptake. Moreover, it circumvents the problem of comparing values between different patients and scanners. In chapter 3 we further investigated why 18F-FLT uptake in FL does not seem to correlate with proliferation, which we concluded from the experiments described in chapter 2.
Prognosis of transformed FL
Historically,theprognosisoftransformedfollicularlymphomaisverypoor,withamedian OS ranging from 0.7 to 2.7 years only (1,4,6,8,9,20). The adverse effect of transformation on the survival of patients with FL is illustrated by the 10 year overall survival being 75% in FL patients versus 36% in transformed FL patients (4). Patients with limited disease, a complete response to treatment and those being chemotherapy naïve at the time of transformation fared better (4,9,20,35-37). Late transformation (>18 months after FL diagnosis) might also be associated with better survival, although, since it was only reported in one cohort of 60 TFL patients this finding will need to be confirmed (5). The introduction of rituximab in the treatment of TFL has clearly improved survival, with a reported median survival up to 50 months (ref. 5,35,38, describing 60,118 and 172 patients with TFL respectively).
In chapter 4, survival of 161 TFL patients in the Netherlands in the rituximab era is described using data from the Population based Haematological Registry for
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