The introduction of immunotherapy has revolutionized the management and prognosis of patients with malignant melanoma. In this study, we explored the role of 2-[18F]-FDG PET/CT in evaluating treatment response and predicting outcomes in melanoma patients undergoing immunotherapy. The results of our study demonstrate the potential of metabolic parameters derived from PET/CT scans as valuable prognostic indicators.
Our study cohort consisted of 92 consecutive patients with malignant melanoma who underwent serial 2-[18F]-FDG PET/CT scans at various time points after starting immunotherapy. The analysis of PET/CT scans provided valuable insights into the metabolic changes in melanoma patients during immunotherapy. We observed a slight increase in bone marrow FDG uptake between PET0 and the 6-month scan (PET1), which could be indicative of treatment-induced inflammation. However, this inflammation appeared to subside or decrease in intensity over time, as evidenced by a less pronounced difference in SLR between PET1 and subsequent scans (PET2, PET3). This suggests that the initial inflammatory response might resolve during the course of immunotherapy, possibly in response to treatment efficacy.
Clinical disease control, defined as complete, partial, or stable disease, was achieved in a significant proportion of patients after 6, 18, and 36 months. Notably, patients without clinical disease control exhibited higher bone marrow FDG uptake and a more widespread metabolic disease pattern. Additionally, the median SLR values were slightly higher in patients without disease control after 6 and 18 months. These findings suggest that the SLR may have predictive value in monitoring treatment response and prognosis, especially in the earlier stages of immunotherapy. Currently, data available in literature did not demonstrate any correlation between SLR and the response to therapy [11–13], differently from the present study. However, in all three papers [11–13], the number of patients was lower than 50 and different PET parameters were used, such as SUVmax or SUVmean.
We further investigated the relationship between SLR and patient prognosis. The median SLR at PET0 was higher in patients who remained alive throughout the follow-up period compared to those who died. This finding suggests that a higher SLR at baseline might be indicative of better disease control and improved survival. Similar data were also reported by other researcher’s group [4, 9]. However, the values of median SLR became more similar between the two groups of patients in the subsequent PET scans conducted after 6, 18, and 36 months. This observation suggests that the initial SLR might lose its predictive value over time and highlights the importance of monitoring SLR changes during of immunotherapy. However, as emerged from the present study, the changes in SLR between the baseline and the 6-month PET/CT scan differed between patients with a good prognosis and those with a poor prognosis. Indeed, the SLR increased during the first 6 months of immunotherapy in patients with a better prognosis compared to those with a worse prognosis. The most plausible hypothesis to explain this phenomenon is the increase in splenic function, given that the spleen is a lymphoid organ. However, the variability in SLR is not observed in subsequent scans, probably because it may be influenced by various factors, including treatment response and disease dynamics. In the study by Prigent et al [7], a change of SLRmean > 25% at 3 months from the start of ICIs compared to the baseline was associated with a poor prognosis. The authors explained this phenomenon by correlating the value of SLR with the immune system activation, although they suggested a validation of the changes in SLR with a large series.
The presence of signs of inflammation on PET1 was associated with higher baseline SLR values, further supporting the link between inflammation and metabolic parameters. However, this association became less evident in the subsequent PET2 scan, possibly indicating the dynamic nature of inflammation during treatment. The changes in SLR between PET1 and PET2 were more pronounced than in later scans, suggesting that early assessment of SLR may have greater prognostic significance.
There are certain limitations that need to be acknowledged. The study cohort was relatively small, and the follow-up period varied among patients. Additionally, as with any observational study, there may be confounding factors that could influence the results.