Table 2.
Proposed criteria for therapeutic evaluation by 18F-FDG PET/CT of solid tumors treated by immune checkpoint inhibitor. RECIST: Response Evaluation Criteria in Solid Tumors, PERCIST: PET Response Criteria in Solid Tumors, PECRIT: PET/CT Criteria for the early prediction of Response to Immune checkpoint inhibitor Therapy, PERCIMT: PET Response Evaluation Criteria for Immunotherapy; imPERCIST5: immunotherapy-modified PERCIST up to five lesions, iPERCIST: immune PERCIST, SUL: standardized uptake value normalized by lean body mass.
| Criteria for therapeutic evaluation | RECIST 1.1 | PERCIST 1.0 | PECRIT | PERCIMT | imPERCIST5 | iPERCIST |
|---|---|---|---|---|---|---|
| Year | 2009 | 2009 | 2017 | 2018 | 2019 | 2019 |
| References | [52] | [54] | [63] | [64] | [65] | [66] |
| Population study | Not defined | Literature review | Retrospective analysis of 20 advanced melanoma patients treated with anti-CTLA-4 (n = 16) or anti-PD-1/PDL-1 (n = 4) | Retrospective analysis of 41 metastatic melanoma patients treated with ipilimumab | Retrospective analysis of 60 metastatic melanoma patients treated with ipilimumab | Retrospective analysis of 28 NSCLC patients treated with nivolumab |
| Objective | Assessment of treatment outcomes | Starting point for clinical trials and structured reporting | Predict clinical benefit | Predict clinical benefit | Determine prognosis of patients | Identify patients who can benefit most from treatment |
| Modality | CT, MRI (18F-FDG PET complementary modality) | Functional imaging (18F-FDG PET) | Combination of anatomic (CT) and functional imaging (18F-FDG PET) | Functional imaging combined with CT (18F-FDG PET/CT) |
Functional imaging (18F-FDG PET) |
Functional imaging (18F-FDG PET) |
| Time | Undetermined | Undetermined | Early: 3–4 weeks after beginning immunotherapy | 3 months after beginning immunotherapy | 3 months after beginning immunotherapy | 2 months after beginning immunotherapy |
| Measurable lesions | ≥ 10 mm, 5 lesions in total, maximum 2 per organ | Minimum tumor SUL 1.5 times the mean SUL of the liver, up to five target lesions per patient | RECIST 1.1 PERCIST 1.0 | Functional size (measured on fused PET/CT) > 1.0 or 1.5 cm Up to 5 target lesions per patient |
PERCIST 1.0 (up to five lesions) |
PERCIST 1.0 |
| New lesion | As progressive disease | As progressive disease | RECIST 1.1 (As progressive disease) |
As progressive disease based on number and functional size (see PMD below) | Do not define PMD but are included in the sum of SULpeak. PMD if summed SULpeak variation is >30% | As progressive disease (but must be confirmed if still unconfirmed PMD) |
| Complete Metabolic Response (CMR) | Disappearence of all lesions | Disappearance of all metabolically active tumors | RECIST 1.1 (Disappearence of all lesions) | Complete resolution of all preexisting 18F-FDG-avid lesions; no new 18F-FDG-avid lesions | Disappearance of all metabolically active tumors | Complete resolution of 18F-FDG uptake within the target lesion |
| Partial Metabolic Response (PMR) | ≥30% decrease from baseline | Reduction in SULpeak in target lesions by a at least 30%, and absolute drop in SUL by at least 0.8 SUL units. |
RECIST 1.1 (decrease in target lesion diameter sum ≥ 30%) | Complete resolution of some preexisting 18F-FDG-avid lesions, no new 18F-FDG-avid lesions | Reduction in SULpeak in target lesions by ≥30% and absolute drop in SUL by ≥0.8 SUL units | ≥30% decrease in the target 18F-FDG SULpeak |
| Stable Metabolic Disease (SMD) | Neither progressive disease (PD), partial response (PR) PR, nor complete response (CR) | Neither PMD, PMR, nor CMR | 1) RECIST 1.1 (Neither PD, PR or CR) 2) Evaluation of change in SULpeak of the hottest lesion of: - >15.5% (clinical benefit predicted) - ≤15.5% (no clinical benefit predicted) |
Neither PMD, PMR, nor CMR | Neither PMD, PMR, nor CMR | Neither PMD, PMR, nor CMR |
| Progressive Metabolic Disease (PMD) | ≥20% increase in the nadir of the sum of target lesions, with a minimum of 5 mm | Increase in SULpeak of > 30% or the appearance of a new metabolically active lesion | RECIST 1.1 (≥20% increase in the nadir of the sum of target lesions, with a minimum of 5 mm) | Four or more new lesions of < 1 cm in functional diameter or Three or more new lesions of > 1 cm in functional diameter or Two or more new lesions of more than 1.5 cm in functional diameter |
>30% increase in SUL peak, with >0.8 SUL unit increase in tumor SULpeak, from baseline scan in a pattern typical of tumor and not of infection/treatment effect. |
≥30% increase in SULpeak or advent of new 18F-FDG-avid lesions: unconfirmed PMD (UPMD) |
| Confirmation PMD | Not applicable | Not applicable | Not applicable | Not applicable | Not applicable | Need to be confirmed by a second PET at 4–8 weeks later: confirmed PMD (CPMD) |