Objective

2-[18F]fluoro-2-deoxy-d-glucose PET/computed tomography ([18F]FDG-PET/CT) is a widely used imaging method in the management of diffuse large B-cell lymphomas (DLBCL). Our aim was to investigate the prognostic performance of different PET biomarkers in a multicenter setting.

Methods

We investigated the baseline and interim PET/CT scans of DLBCL patients included in a prospective, multicentric study coordinated by the International Atomic Energy Agency (IAEA) who received R-CHOP (rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone) immunochemotherapy. The study design was elaborately described before [19], this time a reduced number of patients was included in our sample after the following exclusion criteria: treatment other than R-CHOP; studies performed on a stand-alone PET scanner; studies performed on different PET/CT scanners in baseline and interim setting; missing or compromised imaging data; event-free follow-up lasting less than 24 months. Ten centers in the same number of countries (Brazil, Chile, Hungary, India, Italy, Pakistan, the Philippines, South Korea, Thailand, and Turkey) participated in the IAEA study. The research was approved by the respective ethical review board of each participating center and all subjects signed an informed consent form.

Clinical stage was determined by the baseline PET/CT scans according to the Lugano criteria and R-IPI was calculated for each patient. The volumetric and semiquantitative evaluation of the PET/CT images was performed by central review.

Figure: Transaxial PET images with fused mediastinal lymphoma MTV VOIs. Different MTV segmentation techniques yielding different MTVs: (a) glob4 with 294 cm3, (b) 41pc with 579 cm3, and (c) grad with 798 cm3. bwaMTV, body weight-adjusted metabolic tumor volume; MTV, metabolic tumor volume; VOI, volume of interest.

Lymphoma lesions on baseline PET images were delineated with three different methods: (1) >SUV4 (glob4); 41% isocontour VOI around the local maximum point (41pc); a vendor-specific gradient-based lesion growing algorithm (grad), performed with Mediso InterView™ FUSION processing software (Mediso Medical Imaging Systems, Budapest, Hungary). MTV was calculated as the sum of all lymphoma lesions’ volume on PET images, and TLG was determined as the sum of the product of each lesion’s metabolic volume and SUVmean. Both MTV and TLG values were normalized for patient body weight, thus introducing body weight-adjusted (bwa) MTV and bwaTLG values. Receiver operating characteristics (ROC) analyses were performed to define optimal cutoff points for MTV, TLG, bwaMTV, and bwaTLG for the three different segmentation methods.

Figure: 3D MIP PET images with fused MTV VOIs. (a) 92 kg patient with MTV of 189 cm3 and bwaMTV of 1.76 who showed no progression during 51 months of follow-up. (b) 54 kg patient with MTV of 292 cm3 and bwaMTV of 3.16 who relapsed 7 months after baseline PET (n.b., radiopharmaceutical skin contamination is present in the right cubital area). bwaMTV, body weight-adjusted metabolic tumor volume; MIP, maximum intensity projection; MTV, metabolic tumor volume; VOI, volume of interest.

Interim PET/CT scans were analyzed visually according to the Deauville criteria, resulting in Deauville scores 1–5, and semiquantitatively. Deauville score 5 was defined as lesion SUVmax three times over liver SUVmax. The semiquantitative evaluation methods included the proportional change in SUVmax in percents between the baseline and interim scans (ΔSUVmax) and two semiquantitative ‘Deauville-like’ parameters for which a 3 cm diameter spheric VOI was placed in the unaffected part of the right liver lobe. Modified qPET (mqPET) is the proportion of the hottest lesion’s SUVpeak (the SUVmean of the hottest 1 cm3 in the lesion VOI) and the SUVmean of the liver VOI – the original qPET value, described first by Hasenclever et al. in pediatric Hodgkin’s lymphoma used the mean SUV of the hottest four adjacent voxels in the lesion. Our use of the 1-cm3 SUVpeak was based on the lack of adequate software as well as the hypothesis that in adult patients this volume would not lead to considerable distortion in the results. The rPET, as described before, is the proportion of the SUVmax in the hottest lesion and the SUVmax in the liver reference VOI .

When establishing the diagnostic performance of the above different prognostic biomarkers, 24-month progression-free survival was the clinical endpoint. Statistical calculations were performed in the R environment (The R Foundation, https://www.r-project.org) with R Studio software (RStudio PBC; Boston, Massachusetts, USA).

Results

A total of 107 diffuse large B-cell lymphoma patients were included (54 women; mean age: 53.7 years). MTV and TLG calculations showed good correlation among glob4, 41pc, and grad methods; however, optimal cutoff points were markedly different.

Significantly different PFS was observed between low- and high-risk groups according to baseline MTV, body weight-adjusted (bwa) MTV, TLG, bwaTLG, as well as interim parameters Deauville score, ΔSUVmax, mqPET, and rPET. Univariate Cox regression analyses showed hazard ratios (HRs) lowest for bwaMTVglob4 (HR = 2.3) and highest for rPET (HR = 9.09). In a multivariate Cox-regression model, rPET was shown to be an independent predictor of PFS (P = 0.041; HR = 9.15). Combined analysis showed that ΔSUVmax positive patients with high MTV formed a group with distinctly poor PFS (35.3%).

Conclusion

Baseline MTV and TLG values and optimal cutoff points achieved with different segmentation methods varied markedly and showed a limited prognostic impact. Interim PET/CT parameters provided more accurate prognostic information with semiquantitative ‘Deauville-like’ parameters performing best in the present study.

Full article on Nuclear Medicine Communications.