Clinical Significance of Signs of Autoimmune Colitis in ¹⁸ F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography of 100 Stage-IV Melanoma Patients

Abstract

Aim: Autoimmune colitis is a typical and possible severe side effect among patients treated with ipilimumab. Patients & methods: We prospectively included 100 patients with metastasized melanoma under ipilimumab treatment in a radiological study of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT). PET evidence of pancolitis (‘PET-colitis’) was correlated with clinical variables. Results: We observed a significant correlation between PET-colitis and clinically significant diarrhoea, although PET-colitis was more frequent (49 vs 29% of patients, respectively). Neither PET-colitis nor diarrhoea was significantly correlated with response to therapy. Other immune-related adverse events, however, such as hypophysitis and hepatitis were associated with response to therapy and overall survival. Conclusion: Increased 18F-FDG uptake in the colon correlated with clinical symptoms but did not predict clinical outcome to ipilimumab.

Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis

“…Regarding the subgroup analyses, the distinct outcomes observed for the anti-PD-1 and anti-CTLA-4 subgroups indicated a possibly different mechanism of irAEs, as CTLA-4 blockade activates T cells at an earlier stage of their development and might thus directly disrupt central tolerance without affecting the tumor immune response. Meanwhile, irAEs induced by PD-1 inhibitors predict a better clinical response by patients with cancer, but the association between irAEs and survival in patients undergoing anti-CTLA-4 therapy remains controversial [8,29,[57][58][59][60], demanding larger size of studies in the future. The ability of irAEs to predict a favorable OS and PFS was consistently significant in patients with NSCLC and other cancers (including RCC and multiple cancer types), but not in patients with melanoma.…”

“…A number of recent studies has supported this hypothesis by showing favorable outcomes for patients with non-small cell lung cancer (NSCLC) and melanoma who developed various irAEs in response to immune checkpoint inhibition [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. However, a definite conclusion has not been drawn based on the findings from each single study, as contradictory results exist [23][24][25][26][27][28][29][30][31][32][33][34][35]. A systemic review included 16 studies and reported that irAEs such as pneumonitis, thyroid disorders, myalgias, and mucosal toxicity did not show a significant correlation with overall survival (OS) [36].…”

Novel Nuclear Medicine Imaging Applications in Immuno-Oncology

“…In the same study, thyroid irAEs were related to good prognosis in patients diagnosed with lung cancer [141]. As regards to enterocolitis, increased FDG uptake correlated with clinical symptoms but did not predict clinical outcome to ipilimumab in 100 advanced melanoma patients [142]. In a study with 41 patients with malignant melanoma treated with ipilimumab, 4 out of 31 patients having disease control were diagnosed sarcoid-like reaction in the follow-up PET/TC, while none of the patients with progressive disease [143].…”

Positron emission tomography as an adjuvant diagnostic test in the evaluation of checkpoint inhibitor-associated acute interstitial nephritis

“…FDG-PET CT has also been investigated in checkpoint inhibitor-associated gastrointestinal toxicities. Lang et al prospectively evaluated 100 patients treated with ipilimumab for melanoma, and had PET-CT performed prior to ipilimumab and after 2 and 4 cycles of ipilimumab [19]. They noted a statistically significant correlation between increased FDG uptake throughout the colon and clinical symptoms of colitis; 29 patients developed clinical signs of colitis, and 21 of these patients had increased colonic uptake on PET-CT.…”