Purpose: We assessed the predictive potential of positron emission tomography (PET)/CT-based radiomics, lesion volume, and routine blood markers for early differentiation of pseudoprogression from true progression at 3 months.Experimental Design: 112 patients with metastatic melanoma treated with immune checkpoint inhibition were included in our study. Median follow-up duration was 22 months. 716 metastases were segmented individually on CT and 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET imaging at three timepoints: baseline (TP0), 3 months (TP1), and 6 months (TP2). Response was defined on a lesion-individual level (RECIST 1.1) and retrospectively correlated with FDG-PET/CT radiomic features and the blood markers LDH/S100. Seven multivariate prediction model classes were generated.Results: Two-year (median) overall survival, progression-free survival, and immune progression–free survival were 69% (not reached), 24% (6 months), and 42% (16 months), respectively. At 3 months, 106 (16%) lesions had progressed, of which 30 (5%) were identified as pseudoprogression at 6 months. Patients with pseudoprogressive lesions and without true progressive lesions had a similar outcome to responding patients and a significantly better 2-year overall survival of 100% (30 months), compared with 15% (10 months) in patients with true progressions/without pseudoprogression (P = 0.002). Patients with mixed progressive/pseudoprogressive lesions were in between at 53% (25 months). The blood prediction model (LDH+S100) achieved an AUC = 0.71. Higher LDH/S100 values indicated a low chance of pseudoprogression. Volume-based models: AUC = 0.72 (TP1) and AUC = 0.80 (delta-volume between TP0/TP1). Radiomics models (including/excluding volume-related features): AUC = 0.79/0.78. Combined blood/volume model: AUC = 0.79. Combined blood/radiomics model (including volume-related features): AUC = 0.78. The combined blood/radiomics model (excluding volume-related features) performed best: AUC = 0.82.Conclusions: Noninvasive PET/CT-based radiomics, especially in combination with blood parameters, are promising biomarkers for early differentiation of pseudoprogression, potentially avoiding added toxicity or delayed treatment switch.

Rationale: To compare the diagnostic accuracy of whole-body non-contrast-enhanced PET/MR with that of PET/CT in determining the stage of non-small-cell lung cancer. Methods: This study was approved by the institutional review board and by national government authorities. Forty-two consecutive patients referred for the initial staging of non-small-cell lung cancer underwent whole-body imaging with a sequential trimodality PET/CT-MR system. PET/MR and PET/CT datasets were evaluated separately, and a tumor-node-metastasis (TNM) stage was assigned based on the image analysis. Nodal stations in the chest were identified according to the mapping system of the American Thoracic Society. The standard of reference was histopathology for the tumor stage in 20 subjects, for the nodal stage in 22 patients and for extrathoracic metastases in 5 subjects. All other lesions were confirmed by at least one different imaging method. Wilcoxon signed-ranks test was used for comparing PET/MR with PET/CT. Results: PET/MR did not provide additional information compared with PET/CT. The diagnostic accuracy of both imaging modalities was equal (T staging: P = 0.177, N staging: P = 0.114, M staging: P = 0.465), however with advantages for PET/CT by trend. In the subgroup with histopathological confirmation of T stage and N stage, the situation was similar (T staging: P = 0.705, N staging: P = 0.334). Conclusion: This study indicates that PET/MR using a fast MR protocol does not improve the diagnostic accuracy of the staging of non-small-cell lung cancer.

In academic centers, PET/MR has taken the road to clinical nuclear medicine in the past 6 years since the last review on its applications in head and neck cancer patients in this journal. Meanwhile, older sequential PET + MR machines have largely vanished from clinical sites, being replaced by integrated simultaneous PET/MR scanners. Evidence from several studies suggests that PET/MR overall performs equally well as PET/CT in the staging and restaging of head and neck cancer and in radiation therapy planning. PET/MR appears to offer advantages in the characterization and prognostication of head and neck malignancies through multiparametric imaging, which demands an exact preparation and validation of imaging modalities, however. The majority of available clinical PET/MR studies today covers FDG imaging of squamous cell carcinoma arising from a broad spectrum of locations in the upper aerodigestive tract. In the future, specific PET/MR studies are desired that address specific histopathological tumor entities, nonepithelial malignancies, such as major salivary gland tumors, squamous cell carcinomas arising in specific locations, and malignancies imaged with non-FDG radiotracers. With the advent of digital PET/CT scanners, PET/MR is expected to partake in future technical developments, such as novel iterative reconstruction techniques and deviceless motion correction for respiration and gross movement in the head and neck region. Owing to the still comparably high costs of PET/MR scanners and facility requirements on the one hand, and the concentration of multidisciplinary head and neck cancer treatment mainly at academic centers on the other hand, a more widespread use of this imaging modality outside major hospitals is currently limited.