Metabolic patterns on [18F]FDG PET/CT in patients with unresectable stage III NSCLC undergoing chemoradiotherapy ± durvalumab maintenance treatment

Abstract

Purpose In patients with unresectable stage III non-small-cell lung cancer (NSCLC), durvalumab maintenance treatment after chemoradiotherapy (CRT) significantly improves survival. So far, however, metabolic changes of tumoral lesions and secondary lymphoid organs under durvalumab are unknown. Hence, we assessed changes on [18F]FDG PET/CT in comparison to patients undergoing CRT alone. Methods Forty-three patients with [18F]FDG PET/CT both before and after standard CRT for unresectable stage III NSCLC were included, in 16/43 patients durvalumab maintenance treatment was initiated (CRT-IO) prior to the second PET/CT. Uptake of tumor sites and secondary lymphoid organs was compared between CRT and CRT-IO. Also, readers were blinded for durvalumab administration and reviewed scans for findings suspicious for immunotherapy-related adverse events (irAE). Results Initial uptake characteristics were comparable. However, under durvalumab, diverging metabolic patterns were noted: There was a significantly higher reduction of tumoral uptake intensity in CRT-IO compared to CRT, e.g. median decrease of SUVmax –70.0% vs. –24.8%, p = 0.009. In contrast, the spleen uptake increased in CRT-IO while it dropped in CRT (median + 12.5% vs. –4.4%, p = 0.029). Overall survival was significantly longer in CRT-IO compared to CRT with few events (progression/death) noted in CRT-IO. Findings suggestive of irAE were present on PET/CT more often in CRT-IO (12/16) compared to CRT (8/27 patients), p = 0.005. Conclusion Durvalumab maintenance treatment after CRT leads to diverging tumoral metabolic changes, but also increases splenic metabolism and leads to a higher proportion of findings suggestive of irAE compared to patients without durvalumab. Due to significantly prolonged survival with durvalumab, survival analysis will be substantiated in correlation to metabolic changes as soon as more clinical events are present.

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

“…However, splenic irAEs are relatively rare, and splenic uptake is more often regarded as a surrogate of immune system activation and thus a potential predictor of response to immunotherapy [ 54 ]. In a cohort of 43 patients with stage III NSCLC treated with chemoradiotherapy, of whom 16 had additional durvalumab maintenance treatment, an increase in FDG uptake in the spleen by 12.5% was observed in the ICI group (with significantly longer OS), as opposed to the controls, who had a reduction of splenic activity (−4.4%) [ 73 ]. On the other hand, Prigent et al (2021) noted that a >25% increase in the spleen-to-liver ratio in melanoma patients at 3 months of treatment with ICI indicates a poorer prognosis [ 53 ].…”