Interim PET in lymphoma: from Deauville to Peking criteria. On the road, again…

The first set of criteria for PET response assessment in lymphoma proposed by an international committee (International Harmonized Project, IHP criteria) was published in 2007 [1]. The tumor residual uptake observed after treatment was compared visually to a reference background, which was according to the size of the residual lesion, the mediastinal blood pool or the surrounding background. However, these criteria were set only for end-of-treatment PET despite that interim PET (iPET) performed after the first cycles of chemotherapy began to be proposed by several groups as a good tool for early-adapted treatment strategy. In addition, some studies pointed out that several patients classified as PET-positive had a favorable outcome, especially in DLBCL. Moreover, interpretation discrepancies were observed among readers. Consequently, new criteria were proposed to report both interim and end-of-treatment PET, and first published in Leukemia & Lymphoma in 2009 [2]: Deauville criteria was a five-point scale system scoring visually the tumor residual uptake according to different level of regional background taken as a reference. A positive iPET was defined as tumor residual uptake moderately or markedly higher than the liver i.e. Score 4 or 5. Setting a comparison of the tumor residual uptake with a well-defined, recognizable organ i.e. the liver, instead of the mediastinal blood pool, especially when the residual uptake is in a bulky mediastinal mass, improved the inter-observer agreement and also reduced the number of instances of false-positive scans. This five-PS scale became the new standard for PET/CT response assessment in the updated recommendations presented at the 12th International Conference on Malignant Lymphoma and published in 2014 [3]. These criteria were expanded to apply to all FDG-avid histologies, applicable for both interim and end-of-treatment PET. They specified reading the PET on a SUV scale and defined the Score 5 as two to three times the liver SUVmax [3] instead of ‘markedly’. This was needed to improve consistency of PET interpretation but introduced a quantitative analysis of SUV differences, only specified for Score 5. No SUVmax cutoff has to be chosen to discriminate Score 4 and Score 3, and additionally there remain some borderline cases not easily and reproducibly gradable with a SUV scale. This raises some difficulties in interpreting potential PET positivity and opens the road to quantitative assessment. Quantification of the response at interim after two and four cycles of chemotherapy with a DSUVmax approach based of the reduction of SUVmax from baseline, first proposed in 2007 in DLBCL, was shown more reproducible between readers and more robust than Deauville criteria by further decreasing the number of false-positive studies [4]. However, two prospective trials applying this criterion have reported conflicting results. The PETAL study including 600 patients with DLBCL demonstrated that PET after two cycles of immunochemotherapy reported with the DSUVmax approach with a cutoff of 66% of reduction was highly predictive of outcome [5]. By contrast, the SAKK study which included 138 patients treated by R-CHOP on a 14-day cycle could not demonstrate at 2 years any impact of DSUV on EFS [6]. This result could potentially be explained by the presence in the SAKK study of a large percentage of low-risk patients as well as to the chemotherapy regimen used. Indeed, in a retrospective study comparing the study in 114 patients with DLBCL, Deauville criteria with the DSUVmax approach has been shown that the prognostic impact of DSUVmax was lower in low-risk patients or in patients treated by dose-dense– dose-intense immunochemotherapy which could induce an inflammatory reaction