PET/CT radiomics for prediction of hyperprogression in metastatic melanoma patients treated with immune checkpoint inhibitors

Abstract

PurposeThis study evaluated pretreatment 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET/CT-based radiomic signatures for prediction of hyperprogression in metastatic melanoma patients treated with immune checkpoint inhibition (ICI).Material and methodFifty-six consecutive metastatic melanoma patients treated with ICI and available imaging were included in the study and 330 metastatic lesions were individually, fully segmented on pre-treatment CT and FDG-PET imaging. Lesion hyperprogression (HPL) was defined as lesion progression according to RECIST 1.1 and doubling of tumor growth rate. Patient hyperprogression (PD-HPD) was defined as progressive disease (PD) according to RECIST 1.1 and presence of at least one HPL. Patient survival was evaluated with Kaplan-Meier curves. Mortality risk of PD-HPD status was assessed by estimation of hazard ratio (HR). Furthermore, we assessed with Fisher test and Mann-Whitney U test if demographic or treatment parameters were different between PD-HPD and the remaining patients. Pre-treatment PET/CT-based radiomic signatures were used to build models predicting HPL at three months after start of treatment. The models were internally validated with nested cross-validation. The performance metric was the area under receiver operating characteristic curve (AUC).ResultsPD-HPD patients constituted 57.1% of all PD patients. PD-HPD was negatively related to patient overall survival with HR=8.52 (95%CI 3.47-20.94). Sixty-nine lesions (20.9%) were identified as progressing at 3 months. Twenty-nine of these lesions were classified as hyperprogressive, thereby showing a HPL rate of 8.8%. CT-based, PET-based, and PET/CT-based models predicting HPL at three months after the start of treatment achieved testing AUC of 0.703 +/- 0.054, 0.516 +/- 0.061, and 0.704 +/- 0.070, respectively. The best performing models relied mostly on CT-based histogram features.ConclusionsFDG-PET/CT-based radiomic signatures yield potential for pretreatment prediction of lesion hyperprogression, which may contribute to reducing the risk of delayed treatment adaptation in metastatic melanoma patients treated with ICI.

Radiomics-guided checkpoint inhibitor immunotherapy for precision medicine in cancer: A review for clinicians

“…(C) Pseudoprogression is defined as an initial radiographic increase in tumor size or the appearance of new lesions, followed by a response. CT-based radiological features were shown to be better predictors of hyperprogression than PET-based features (85).…”

Is 18F-FDG-PET/CT an Optimal Imaging Modality for Detecting Immune-Related Adverse Events after Immune-Checkpoint Inhibitor Therapy? Pros and Cons

“…Some radiological models predicting HPD risk, incorporating FDG PET scans, could potentially enable the prediction of HPD, decreasing the risk of delayed treatment adaptation. Notable is that HPD is associated with a higher metabolic tumor burden at baseline PET/CT [ 114 , 116 , 120 ].…”

Predictive Factors in Metastatic Melanoma Treated with Immune Checkpoint Inhibitors: From Clinical Practice to Future Perspective

“…Future studies should define if a locoregional approach direct to a lesion at a higher risk of progression could improve a patient’s prognosis [ 99 , 100 ]. Radiomic signatures could also help to identify lesions with a high risk of hyperprogression as well as to predict overall survival in patients with brain metastases [ 101 , 102 ]. Even if the potential advantage of radiomic is clear, several limitations to the daily application remain.…”