*2.2. Imaging Protocols*

All PET/CT examinations were performed on a state-of-the art clinical scanner (Biograph mCT®, Siemens Healthineers, Erlangen, Germany). All patients fasted overnight before examination. Approximately 300 MBq 18F-FDG were injected intravenously 60 min prior to image acquisition. Standardized CT examination protocols included weightadapted 90–120 mL intravenous CT contrast agent (Ultravist 370®, Bayer Vital, Leverkusen, Germany). Portal-venous phase acquisitions were obtained with 70 s delay time using a tube voltage of 120 kV and a reference dose of 200 mAs. Image reconstruction was performed using iterative CT reconstruction (Siemens SAFIRE®, Forchheim, Germany). PET was acquired from the skull to the mid-thigh level over six to eight bed positions and reconstructed using a 3D ordered subset expectation maximization algorithm (two iterations, 21 subsets, Gaussian filter 2.0 mm, matrix size 400 × 400, and slice thickness 2.0 mm). PET acquisition time was 2–3 min per bed position.

CT was performed with patients in the supine position using a 128-slice MDCT scanner (SOMATOM Definition Flash, Siemens Healthcare, Erlangen, Germany). Contrastenhanced portal-venous phases were obtained using 120-kV photon energy, 200-mAs tube current, a soft tissue image reconstruction kernel, and 1-mm slice thickness for image reconstruction. A weight-adapted iodine contrast agent (Ultravist [Iopromide] 370, Bayer Vital, Leverkusen, Germany) was given intravenously at a rate of 2 mL/s followed by a 30-mL saline chaser. Image acquisition began 70 s after the start of contrast agent injection. Image reconstruction was performed in all patients using filtered back projection.

#### *2.3. Quantitative Image Analysis*

The segmentation of lymphoma manifestations was performed by one reader using approved software for quantification of PET parameters on Syngo.via VB 30A (Siemens Healthineers, Erlangen, Germany). Evaluation included all lesions which were characterized by increased 18F-FDG uptake above liver background activity (Deauville score 4). Segmentation of each lesion was performed manually using 50%-isocontour volumes of interests (VOIs) for quantification. Whole-body MTV and whole-body TLG were calculated as the sum of all quantified lymphoma manifestations per patient.

CT-texture analysis (CTTA) was performed in contrast-enhanced CT images derived from whole-body CT or whole-body 18F-FDG-PET/CT obtained in the portal-venous enhancement phase using a standardized protocol and dedicated radiomics software (Siemens Healthcare, Erlangen, Germany) that is based on the pyradiomics package, a python package for the extraction of radiomics features from medical imaging [13]. A slice thickness of 1 mm was used. Regions of interests (ROIs) were drawn manually in lymphatic tissue carefully excluding neighboring tissues like blood vessels. This standardized procedure of ROI setting was performed by a radiologist with five years of experience in CTTA. Standardized measurements were performed to provide comparability for all data sets. All set ROIs were used to generate specific VOIs. The first step consisted of image filtration for selectively extracting features of different sizes and intensity variation. In the 2nd step, quantification of tissue texture followed. The computation of each texture type for an input VOI involved assigning a new value ("texture value") to all voxel of that VOI and thus creating a "texture image". This involved the creation of a three-dimensional VOI within the largest lymph node, the features of which were used to calculate texture values on a fine spatial scale. Computation was performed on the current voxel and its neighborhood, and the results of that were stored as the current voxel's texture value. To ensure reliable statistics for this patient cohort, we limited analysis of textural parameters to the following 1st order features which describe the distribution of voxel intensities within the mask through commonly used and basic metrics: mean, uniformity, entropy, skewness. The definitions of these textural parameters are provided in Table 2.


**Table 2.** Definitions of measured 1st order textural features \*.

\* Describe the distribution of voxel intensities within the image region defined by the mask through commonly used and basic metrics.

#### *2.4. Laboratory Parameters*

Laboratory parameters were extracted from the clinical data base on the same day as imaging. The upper limits of the reference ranges were: 250 U/L for serum LDH, 0.5 μg/dL for CRP, 130 U/L for AP, 4100–11,800 1/μL for leucocyte count, 158–613 U/mL for soluble IL-2R and 0–4 ng/L for IL-6.
