2.3. EORTC and PERCIST

The responses to nivolumab were classified as complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), or progressive metabolic disease (PMD).

Tumor responses according to EORTC were as follows.^[15] The CMR was defined as a complete resolution of ¹⁸F-FDG uptake within the measurable target lesion so that it was indistinguishable from the surrounding background with no new ¹⁸F-FDG-avid lesions. In patients with metabolically active lesions on the follow-up scans, the SUVmax values of the lesions (up to a total of 5) of the baseline and follow-up scans were summed (maximum of 2 per organ). If the sum of the SUVmax values decreased by at least 25%, the tumor response was classified as PMR. PMD denoted a 25% increase of the sum of the SUVmax values or the detection of new ¹⁸F-FDG-avid lesions that are characteristic of cancer. The SMD is a disease other than CMR, PMR, or PMD.

PERCIST requires that

the difference between baseline and follow-up normal liver SULmean values must be within 20% (and <0.3 SUL mean units) to be assessed, and

the SULpeak of the tumor had to be greater than the threshold which was defined equal to 1.5 times that of mean liver SUL value + 2 standard deviations (SDs) (mean liver activity).^[16]

This threshold value was also quickly and automatically calculated with the software. If the tumor SULpeak at baseline did not exceed this threefold value, the patient was not eligible for response evaluation with PERCIST.

Tumor responses according to PERCIST were assessed by 2 different approaches.^[19] The first approach was PERCIST5, and this analysis was performed in a manner that was almost the same as that described for EORTC5, but the sum of the SULpeak values was used. Given that the hottest lesions were selected in each scan, target lesions on follow-up scans were not necessarily the same as the target lesions at baseline. CMR completely characterized the ¹⁸F-FDG uptake within the measurable target lesion to less than the mean liver activity, and was indistinguishable from the surrounding background with no new ¹⁸F-FDG-avid lesions. PMR was defined as the decrease of the sum of the SULpeak value by at least 30%. PMD was defined as an increase of the sum of the SULpeak by at least 30% or in the cases of new ¹⁸F-FDG-avid lesions. SMD includes diseases other than CMR, PMR, or PMD. The second approach was the immunotherapy-modified PERCIST5 (imPERCIST5). Although the definition of PMD was different from PERCIST5, the other criterion was the same as PERCIST5. In imPERCIST5, the appearance of new lesions alone did not result in PMD, and PMD was defined only by an increase of the sums of the SULpeak values by 30%. New lesions were included in the sum of the SULpeak if they showed higher uptake than existing target lesions, or if fewer than 5 target lesions were detected on the baseline scan.