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. 2024 Feb 27;16(5):964.
doi: 10.3390/cancers16050964.

Prospective Assessment of Fluorine-18-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) for Early Identification of Checkpoint-Inhibitor-Induced Pseudoprogression

Sif Homburg  1 , Charlotte Birk Christensen  2 , Magnus Pedersen  3 , Simon Grund Sørensen  4 , Marco Donia  3 , Inge Marie Svane  3 , Helle Westergren Hendel  2 , Eva Ellebaek  3
Affiliations

Prospective Assessment of Fluorine-18-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) for Early Identification of Checkpoint-Inhibitor-Induced Pseudoprogression

Sif Homburg et al. Cancers (Basel). .

Abstract

The activity of immune checkpoint inhibitors (ICIs) in patients with metastatic melanoma is often monitored using fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scans. However, distinguishing disease progression (PD) from pseudoprogression (PsPD), where increased FDG uptake might reflect immune cell activity rather than tumor growth, remains a challenge. This prospective study compared the efficacy of dual-time point (DTP) FDG-PET/CT with modified response criteria (PERCIMT) in differentiating PsPD from PD. From July 2017-January 2021, 41 patients suspected to have PsPD on an evaluation scan were prospectively included (29 evaluable). A subsequent DTP FDG-PET/CT scan was conducted within 14 days, followed by a confirmatory FDG-PET/CT scan. Additionally, PERCIMT were applied. DTP FDG-PET/CT identified 24% with PsPD and 76% with PD. Applying PERCIMT criteria, 69% showed PsPD, while 31% had PD. On follow-up, 10 patients (34%) demonstrated confirmed PsPD, while 19 (66%) exhibited PD. The sensitivity and specificity of DTP FDG-PET/CT were 20% and 74%, respectively, and for PERCIMT this was 80% and 37%, respectively. Our findings suggest limited efficacy of DTP FDG-PET/CT in distinguishing PsPD from PD in ICI-treated patients with metastatic melanoma. The use of PERCIMT could complement clinical assessment and be incorporated in multidisciplinary team conferences for enhanced decision-making.

Keywords: FDG-PET/CT; PERCIMT; dual-time point FDG-PET/CT; immune checkpoint inhibitors; metastatic melanoma; pseudoprogression.

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Conflict of interest statement

EE received honoraria for consultancies and lectures from Novartis, Merck, Bristol-Myers Squibb, and Pierre Fabre, and conference and travel support from Pierre Fabre and Merck. MD received access to proprietary data from Bristol Myers Squibb, and Genentech and is advisor of Achilles Therapeutics. IMS has received honoraria for consultancies and lectures from Novartis, Roche, Merck, and Bristol Myers Squibb; a restricted research grant from Novartis; and financial support for attending symposia from Bristol Myers Squibb, Merck, Novartis, Pfizer, and Roche. The other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Definition of PERCIMT [12]; PD = progressive disease, SD = stable disease, PR = partial regression, CR = complete regression.
Figure 2
Figure 2
Flowchart; ICI = immune checkpoint inhibitors. PsPD = pseudoprogression. DTP FDG-PET/CT = Dual-time-point fluorodeoxyglucose positron emission tomography/computed tomography. FU FDG-PET/CT = follow-up FDG-PET/CT. CMR = complete metabolic response.
Figure 3
Figure 3
Boxplot of retention index based on early acquisition scan in the true PsPD group versus true PD group. Retention index (RI; y-axis) separated between the PsPD group and the PD group (x-axis). Students t-tests were used to evaluate the significance of the difference for (A) MAX, (B) MEAN, and (C) PEAK. Boxplots indicate the median (central horizontal line) and the lower (25% quantile), and upper (75% quantile) of the data. PsPD = pseudoprogression. PD = progressive disease.
Figure 4
Figure 4
Boxplot of retention index based on delayed acquisition scan in the true PsPD group versus the true PD group. Retention index (RI; y-axis) separated between the PsPD group and the PD group (x-axis). Students t-tests were used to evaluate the significance of the difference for (A) MAX, (B) MEAN, and (C) PEAK. Boxplots indicate the median (central horizontal line) and the lower (25% quantile), and upper (75% quantile) of the data. PsPD = pseudoprogression. PD = progressive disease.
Figure 5
Figure 5
Diagram with an overview of the scans and methods applied and the outcome; FDG-PET = fluorine-18-fluorodeoxyglucose-positron emission tomography. CT = computed tomography. PsPD = pseudoprogression. PD = progressive disease. DTP = Dual-time point. PERCIMT = PET Response Evaluation Criteria for Immunotherapy. FU FDG-PET/CT = follow-up FDG-PET/CT. PsPD FDG-PET/CT = The inclusion FDG-PET/CT with suspected PsPD.
Figure 6
Figure 6
Overall survival (OS) of patients with true PsPD versus patients with true PD; statistical significance (p value) has been evaluated using a COX regression. PsPD = pseudoprogression. PD = progressive disease. OS = overall survival. HR = hazard ratio.
Figure 7
Figure 7
Progression-free survival (PFS) of patients with true PsPD versus patients with true PD. Statistical significance (p value) has been evaluated using a COX regression. PsPD = pseudoprogression. PD = progressive disease. PFS = progression-free survival. HR = hazard ratio.
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