Fractal and Multifractal Analysis of PET-CT Images for Therapy Assessment of Metastatic Melanoma Patients under PD-1 Inhibitors: A Feasibility Study

Abstract

Simple Summary The fractal dimension (FD) and the multifractal spectrum (MFS) are nonlinear quantitative measures which express the heterogeneity in the distribution of the tracer, F-18-fluorodeoxyglucose, (18F-FDG), in the body of patients suffering from metastatic melanoma. Given the well-documented, high accumulation of the tracer in tumor/metastatic sites, the measures expressing the tracer distribution also express the extent of metastases in the body. As such, FD and MFS can be employed to detect the presence of melanoma and to monitor the therapeutic outcome using the PET-CT follow-up digitized scans of the patients. In the present study, the FD and MFS measures of patients are evaluated before and during treatment with PD-1 inhibitors and are compared with the corresponding values of healthy controls. The MFS predictions agree with the PET Response Evaluation Criteria for Immunotherapy (PERCIMT) in 81% of the cases, while the FD agrees in 77% of all cases. Therefore, the quantitative MFS is proposed as an additional, alternative biomarker for monitoring the immunotherapy outcome in melanoma patients, after treatment with PD-1 inhibitors. Abstract Longitudinal whole-body PET-CT scans with F-18-fluorodeoxyglucose (18F-FDG) in patients suffering from metastatic melanoma were analyzed and the tracer distribution in patients was compared with that of healthy controls. Nineteen patients with metastatic melanoma were scanned before, after two and after four cycles of treatment with PD-1 inhibitors (pembrolizumab, nivolumab) applied as monotherapy or as combination treatment with ipilimumab. For comparison eight healthy controls were analyzed. As quantitative measures for the comparison between controls and patients, the nonlinear fractal dimension (FD) and multifractal spectrum (MFS) were calculated from the digitized PET-CT scans. The FD and MFS measures, which capture the dispersion of the tracer in the body, decreased with disease progression, since the tracer particles tended to accumulate around metastatic sites in patients, while the measures increased when the patients’ clinical condition ameliorate. The MFS measure gave better predictions and were consistent with the PET Response Evaluation Criteria for Immunotherapy (PERCIMT) in 81% of the cases, while FD agreed in 77% of all cases. These results agree, qualitatively, with a previous study of our group when treatment with ipilimumab monotherapy was considered.