Clinical and radiological features of pseudoprogression in brain tumors treated with immune checkpoint inhibitors.

Purpose: Immune checkpoint inhibitors (ICIs) are increasingly used in cancer treatment, resulting in the emergence of various immune-related adverse effects, including pseudoprogression (PsP). We sought to evaluate the characteristics of pseudoprogression in adults treated with ICIs for brain tumors (either primary or secondary), and to compare it with a non- PsP group.

Methods: We retrospectively identified adults with brain tumors treated with ICIs at our institution between 2015 and 2023. Eligibility required one brain magnetic resonance imaging scan prior to treatment and another obtained within 6 months after treatment initiation. PsP was defined as radiological worsening within 6 months of ICI initiation, followed by stabilization or improvement without therapy modification. Demographic, clinical, and radiological characteristics were analyzed and compared between the PsP and the non-PsP groups.

Results: Among 102 eligible patients, 10 (9.8%) developed PsP. Clinical symptoms occurred in 4 (40%) cases, all of which showed favorable outcomes with corticosteroid therapy. The PsP group had higher baseline tumor burden (p = 1.29 × 10⁻¹³) and higher PD-L1 expression (p < 0.001) than the non-PsP group. Median progression-free survival and overall survival were numerically longer in the PsP group with no significant difference.

Conclusions: PsP is a frequent complication of ICIs. We describe 4 symptomatic patients with pseudoprogression, challenging the iRANO criteria that recommend excluding this diagnosis in symptomatic cases. Clinical impairment should not automatically rule out pseudoprogression, and each case requires thorough evaluation. High PD-L1 expression and greater tumor burden may be associated with PsP, but further studies are needed to confirm these findings.