Comparison of EORTC and PERCIST 1.0 (36)
| Characteristic | EORTC | PERCIST 1.0 |
|---|---|---|
| Measurability of lesions at baseline | 1. Tumor regions defined on pretreatment scan should be drawn on region of high 18F-FDG uptake representing viable tumor. Whole tumor uptake should also be recorded. | 1. Measurable target lesion is hottest single tumor lesion SUL of “maximal 1.2-cm diameter volume ROI in tumor” (SUL peak). SUL peak is at least 1.5-fold greater than liver SUL mean + 2 SDs (in 3-cm spherical ROI in normal right lobe of liver). If liver is abnormal, primary tumor should have uptake > 2.0 × SUL mean of blood pool in 1-cm-diameter ROI in descending thoracic aorta extended over 2-cm z-axis. |
| 2. Same ROI volumes should be sampled on subsequent scans and positioned as close to original tumor volume as possible. Coregistration method should be recorded. | ||
| 3. Uptake measurements should be made for mean and maximal tumor ROI counts per pixel per second calibrated as MBq/L. | 2. Tumor with maximal SUL peak is assessed after treatment. Although typically this is in same region of tumor as that with highest SUL peak at baseline, it need not be. | |
| 4. Alterations in extent of 18F-FDG uptake should be documented, i.e., increase in orthogonal tumor dimensions including longest tumor dimension. | ||
| 5. Partial volume may affect measurement of 18F-FDG uptake. Tumor size from anatomic imaging in relation to PET scanner resolution should be documented where possible. | 3. Uptake measurements should be made for peak and maximal single-voxel tumor SUL. Other SUV metrics, including SUL mean at 50% or 70% of SUV peak, can be collected as exploratory data; TLG can be collected ideally on basis of voxels more intense than 2 SDs above liver mean SUL (see below). | |
| 4. These parameters can be recorded as exploratory data on up to 5 measurable target lesions, typically the 5 hottest lesions, which are typically the largest, and no more than 2 per organ. Tumor size of these lesions can be determined per RECIST 1.1. | ||
| Normalization of uptake | Scanners should provide reproducible data. Reporting would need to be accompanied by adequate and disclosed reproducibility measurements from each center. An empiric 25% was found to be a useful cutoff point, but reproducibility analysis is needed to determine appropriate cutoffs for statistical significance. | Normal liver SUL must be within 20% (and <0.3 SUL mean units) for baseline and follow-up study to be assessable. If liver is abnormal, blood-pool SUL must be within 20% (and <0.3 SUL mean units) for baseline and follow-up study to be assessable. Uptake time of baseline study and follow-up study 2 must be within 15 min of each other to be assessable. Typically, these are at mean of 60 min after injection but no less than 50 min after injection. Same scanner, or same scanner model at same site, injected dose, acquisition protocol (2- vs. 3-dimensional), and software for reconstruction, should be used. Scanners should provide reproducible data and be properly calibrated. |
| Objective response | CMR: complete resolution of 18F-FDG uptake within tumor volume so that it was indistinguishable from surrounding normal tissue. | CMR: complete resolution of 18F-FDG uptake within measurable target lesion so that it is less than mean liver activity and indistinguishable from surrounding background blood-pool levels. Disappearance of all other lesions to background blood-pool levels. Percentage decline in SUL should be recorded from measurable region, as well as (ideally) time in weeks after treatment was begun (i.e., CMR −90, 4). No new 18F-FDG–avid lesions in pattern typical of cancer. If progression by RECIST, must verify with follow-up. |
| PMR: reduction of minimum of 15% ± 25% in tumor 18F-FDG SUV after 1 cycle of chemotherapy, and >25% after more than 1 treatment cycle; reduction in extent of tumor 18F-FDG uptake is not a requirement for PMR. | PMR: reduction of minimum of 30% in target measurable tumor 18F-FDG SUL peak. Absolute drop in SUL must be at least 0.8 SUL units, as well. Measurement is commonly in same lesion as baseline but can be another lesion if that lesion was previously present and is the most active lesion after treatment. ROI does not have to be in precisely same area as baseline scan, though typically it is. No increase, >30% in SUL or size of target or nontarget lesions (i.e., no PD by RECIST or IWC) (if PD anatomically, must verify with follow-up). Reduction in extent of tumor 18F-FDG uptake is not requirement for PMR. Percentage decline in SUL should be recorded, as well as (ideally) time in weeks after treatment was begun (i.e., PMR −40, 3). No new lesions. | |
| SMD: increase in tumor 18F-FDG SUV < 25% or decrease of <15% and no visible increase in extent of 18F-FDG tumor uptake (20% in longest dimension). | SMD: not CMR, PMR, or PMD. SUL peak in metabolic target lesion should be recorded, as well as (ideally) time from start of most recent therapy, in weeks (i.e., SMD −15, 7). | |
| PMD: increase in 18F-FDG tumor SUV of >25% within tumor region defined on baseline scan; visible increase in extent of 18F-FDG tumor uptake (20% in longest dimension) or appearance of new 18F-FDG uptake in metastatic lesions. | PMD: >30% increase in 18F-FDG SUL peak, with >0.8 SUL unit increase in tumor SUV peak from baseline scan in pattern typical of tumor and not of infection/treatment effect. OR: Visible increase in extent of 18F-FDG tumor uptake (75% in TLG volume with no decline in SUL. OR: New 18F-FDG–avid lesions that are typical of cancer and not related to treatment effect or infection. PMD other than new visceral lesions should be confirmed on follow-up study within 1 mo unless PMD also is clearly associated with progressive disease by RECIST 1.1. PMD should be reported to include percentage change in SUV peak, (ideally, time after treatment, in weeks) and whether new lesions are present/absent and their number (i.e., PMD, +35, 4, new: 5). Because SUL is continuous variable, dividing response criteria into limited number of somewhat arbitrary response categories loses much data. For this reason, PERCIST preserves percentage declines in SUV peak in each reported category. Because rapidity with which scan normalizes is important (faster appears better), PERCIST asks for time from start of treatment as part of reporting. For example, CMR 90, 1, is probably superior to CMR 90, 10, especially if latter patient were SMD 20, 1. More than one measurement of PET response may be needed at differing times, and it may be treatment type–dependent. PERCIST 1.0 evaluates SUL peak of only hottest tumor. This is possible limitation of approach, but lesions and their responses are highly correlated in general. Additional data are required to determine how many lesions should be assessed over 1. A suggested option is to include the 5 hottest lesions, or the 5 observed on RECIST 1.1 that are most measurable. Percentage change in SUL can be reported for single lesion with largest increase in uptake or smallest decline in uptake. Additional studies will be needed to define how many lesions are optimal for assessment. | |
| Nonmeasurable disease: CR, disappearance of all known disease, confirmed at ≥4 wk; PR, estimated decrease of ≥50%, confirmed at 4 wk; PD, estimated increase of ≥25% in existent lesions; NC, neither PR nor PD criteria met. | Nontarget lesions: CMR, disappearance of all 18F-FDG–avid lesions: PMD, unequivocal progression of 18F-FDG–avid nontarget lesions or appearance of new 18F-FDG–avid lesions typical of cancer; non-PMD: persistence of one or more nontarget lesions or tumor markers above normal limits. | |
| Overall response | 1. Best response recorded in measurable disease from treatment start to disease progression or recurrence. | |
| 2. Non-PMD in measurable or nonmeasurable nontarget lesions will reduce CR in target lesion to overall PMR. | ||
| 3. Non-PMD in nontarget lesions will not reduce PR in target lesions. | ||
| Duration of response | 1. Overall CMR: from date CMR criteria are first met; to date recurrent disease is first noted. | |
| 2. Overall response: from date CMR or PMR criteria are first met (whichever status came first); to date recurrent disease is first noted. | ||
| 3. SMD: from date of treatment start to date PMD is first noted. |
TLG = total lesion glycolysis; CMR = complete metabolic response; PMR = partial metabolic response; PD = progressive disease; SMD = stable metabolic disease; PMD = progressive metabolic disease; CR = complete remission; PR = partial remission; NC = no change.
For PERCIST: Single-voxel SUL is commonly used but has been reported to be less reproducible than SUL peak, especially with very small single-voxel values. It is suggested, but not required, that lesions assessed on PERCIST be larger than the 1.5-cm-diameter volume ROI used to minimize partial-volume effects. Percentage changes are proposed to deal with SUL peak changes. Use of maximal SUL could be explored. If 5 lesions are used as exploratory approach, it is suggested that sum of SULs of baseline 5 lesions serve as baseline for study. After treatment, sum of same 5 lesions should be used. Percentage change in SUL is based on change in these sums from study 1 to study 2. Exploratory analysis can include calculating percentage change in SUL in individual lesions and averaging them. This may produce different result. We believe summed SUL approach will be less prone to minor errors in measurements.
For total lesion glycolysis: Exploratory analysis can include either all foci of tumor with maximal SUL > 2 SDs above normal liver, 5 lesions with highest SUL, or lesion with highest SUL. It is suggested that threshold approach, typically at 2 SDs above normal liver SUL, be used to generate lower bounds of ROI (3 SDs could be used for very active tumors). We believe this approach will be less variable than methods based on maximal SUL with percentage of maximal cutoff. Criteria for progression include 75% growth in TLG for SUL and are conservatively placed at 75% increase. Because 20% increase in EORTC linear size scales to 73% volume increase, the figures are comparable. Progression is judged from best response if being assessed after first scan was performed. For response by TLG, we propose 45% reduction as useful starting point, but more data are needed to make firm recommendations. If TLG is determined, explicit methodologic details should be provided. It should not be a primary metric, but a secondary endpoint at this time.