Introduction
Peripheral T-cell lymphoma (PTCL) is a rare disease in Europe and North America, with a yearly incidence of less than 1 in 100,000. It encompasses several entities, which are mainly of aggressive behavior. Response to chemotherapy is generally poor, with long-term survival rates of 30% [
1]. Early identification of impending treatment failure may improve outcome.
In a subgroup analysis of the ‘Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas’ (PETAL) trial [
2] we showed that interim [
18F]fluoro-deoxyglucose-positron emission tomography/computed tomography ([
18F]-FDG-PET/CT) predicts outcome in all major PTCL subtypes except anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) which has a much better prognosis than the other entities [
3]. The ∆SUV
max method, comparing the maximum standardized uptake values (SUV
max) at baseline and interim scanning, appeared better suited than the interim PET-based Deauville 5-point scale with a threshold at score 4 (residual lymphoma-related activity above liver) to predict treatment failure. Score 5 (residual activity markedly above liver) performed better, but its imprecise definition hampers clinical use [
4].
To overcome the limitations of visual assessment, we employed qPET (q, quantitative) that relates the SUV of the most intense residual lymphoma-related lesion to the mean SUV of the liver. This procedure, pioneered in pediatric [
5] and adult Hodgkin’s lymphoma [
6] and confirmed in DLBCL [
7], transforms the ordinal Deauville scale into a continuous scale with clearly defined borders between response categories. In this report, we apply qPET to the PTCL population of the PETAL trial and compare it with ∆SUV
max.
Discussion
In the present study, interim [18F]-FDG-PET evaluation by qPET and ∆SUVmax yielded closely related measurements. Outcome prediction was similar, suggesting that the two methods convey comparable information. Importantly and in contrast to the visual Deauville scale, qPET clearly defines DS5, which is crucial for the identification of PTCL patients at high risk of treatment failure.
The correlation between qPET and ∆SUV
max was similar to the findings in DLBCL [
7]. qPET was correlated with baseline SUV
max in PTCL, but not in DLBCL, reflecting differences in the responsiveness to chemotherapy. In most DLBCL patients, response is rapid and accompanied by a marked reduction in [
18F]-FDG uptake. In PTCL, chemotherapy is much less effective. Persistently high [
18F]-FDG uptake translates into high qPET values.
The large sample size (449–898 patients) of our previous qPET studies allowed us to define precise borders between the five Deauville categories [
5‐
7]. Irrespective of disease, the borders identified were identical. Because the relationship between the uptake in a residual lesion and the reference region, as perceived by the reader, should not be disease-specific, we adopted the previously defined quantitative Deauville scale also for PTCL. The small size of our PTCL study precluded a formal confirmation of the thresholds.
Interim assessment in ALK-negative PTCL was characterized by higher positive and lower negative predictive values than in DLBCL [
7], reflecting differences in the frequency of treatment failure [
2]. qDS5 identified 18 of 43 patients (41.9%) to be at risk of treatment failure, all but one of whom progressed or died within 30 months. An SUV
max reduction < 50% allocated 17 patients (39.5%) to the high-risk group, with similarly poor outcome. Both quantitative methods appear suitable to select patients for an early treatment change. qPET may be preferable, because it does not require a baseline [
18F]-FDG-PET/CT, thus minimizing the influence of factors interfering with the evaluation [
7]. However, it is important to mention that the qPET method as described here was developed 10 years ago, based on scanner systems available at that time. With the new PET scanner generations voxel size became markedly smaller so that an adapted qPET calculation is recommendable which is independent of voxel size. In the EuroNet-PHL-C2 and the GPOH-HD2020 registry trials, the SUV
peak is calculated as the SUV
mean of the hottest connected voxels forming a volume of 0.2 ml (instead of the SUV
mean of the 4 hottest voxels) [
9].
For patients failing conventional chemotherapy, the most promising treatment is allogeneic transplantation. In a recent first-line trial, transplantation after five treatment cycles proved impossible in almost a third of patients, mainly because of progression beyond cycle 2 [
10]. The window for allogeneic transplantation may be narrow in high-risk PTCL. Interim [
18F]-FDG-PET could help detect impending progression before it is too late.
The major limitation of our study is its small size, inherent in all investigations in rare diseases. The results should be confirmed in an independent cohort, preferably of larger size.
In conclusion, qPET requiring a single [18F]-FDG-PET scan identifies similarly large fractions of PTCL patients at risk of treatment failure as does ∆SUVmax relying on a comparison of two scans. qPET stringently defines DS5 which is crucial for risk allocation.
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