Multiparametric MRI for early identification of therapeutic response in recurrent glioblastoma treated with immune checkpoint inhibitors.

BACKGROUND: Physiologic changes quantified by diffusion and perfusion MRI have shown utility in predicting treatment response in glioblastoma (GBM) patients treated with cytotoxic therapies. We aimed to investigate whether quantitative changes in diffusion and perfusion after immune checkpoint inhibitors (ICIs) would determine 6-month progression free survival (PFS6) in patients with recurrent GBM. METHODS: Inclusion criteria for this retrospective study were: 1) diagnosis of recurrent GBM treated with ICIs; 2) availability of diffusion and perfusion in pre and post ICIs MRI 3) at least 6 months follow-up from treatment. After co-registration, mean values of the relative-apparent diffusion coefficient (rADC), Ktrans (volume transfer constant), Ve (extravascular extracellular space volume) and Vp (plasma volume) and relative cerebral blood volume (rCBV) were calculated from a volume-of-interest of the enhancing tumor. Final assignment of stable/improved vs. progressive disease was determined on 6-month follow-up using modified RANO criteria. RESULTS: Out of 19 patients who met inclusion criteria, follow-up (Mean +/- SD: 7.8 +/- 1.4 months), 12 were determined to have tumor progression while 7 with treatment response after 6 months following ICIs treatment. Only interval change of rADC was suggestive of treatment response. Patients with treatment response (6/7: 86%) had interval increased rADC while 11/12 (92%) with tumor progression had decreased rADC (p=0.001). Interval change in rCBV, Ktrans, Vp, and Ve were not indicative of treatment response within 6 months. CONCLUSIONS: In patients with recurrent GBM, interval change in rADC is promising in assessing treatment response vs. progression within the first 6 months following ICIs.