Case series review of neuroradiologic changes associated with immune checkpoint inhibitor therapy

Abstract

While immuno-oncotherapy (IO) has significantly improved outcomes in the treatment of systemic cancers, various neurological complications have accompanied these therapies. Treatment with immune checkpoint inhibitors (ICIs) risks multi-organ autoimmune inflammatory responses with gastrointestinal, dermatologic, and endocrine complications being the most common types of complications. Despite some evidence that these therapies are effective to treat central nervous system (CNS) tumors, there are a significant range of related neurological side effects due to ICIs. Neuroradiologic changes associated with ICIs are commonly misdiagnosed as progression and might limit treatment or otherwise impact patient care. Here, we provide a radiologic case series review restricted to neurological complications attributed to ICIs, anti-CTLA-4 and PD-L-1/PD-1 inhibitors. We report the first case series dedicated to the review of CNS/PNS radiologic changes secondary to ICI therapy in cancer patients. We provide a brief case synopsis with neuroimaging followed by an annotated review of the literature relevant to each case. We present a series of neuroradiologic findings including nonspecific parenchymal and encephalitic, hypophyseal, neural (cranial and peripheral), meningeal, cavity associated, and cranial osseous changes seen in association with use of ICIs. Misdiagnosis of radiologic abnormalities secondary to neurological irAEs can impact patient treatment regimens and clinical outcomes. Rapid recognition of various neuroradiologic changes associated with ICI therapy can improve patient tolerance and adherence to cancer therapies.

Advanced MRI Protocols to Discriminate Glioma From Treatment Effects: State of the Art and Future Directions

“…Reports of histologic changes specific to glioma are lacking, but the histology of pseudoprogression seen in the melanoma of brain metastases demonstrated clusters of tumor cells with surrounding reactive astrocytosis, inflammatory cells, and microglial cells (37). Generalized neuroradiologic changes and neurotoxicities, such as aseptic encephalitis or meningitis, have also been documented in the use of immunotherapy for tumors outside of the CNS (38)(39)(40), and these changes could contribute to the posttreatment effects of immunotherapy for HGG.…”

Elderly patient with unresectable advanced‑stage hepatocellular carcinoma who received atezolizumab plus bevacizumab and achieved a complete response: A case report

“…At present, researchers have not yet determined whether immune checkpoint inhibitor (ICI)-containing therapies, such as atezolizumab plus bevacizumab, are effective and safe for use in elderly patients with advanced-stage HCC ( 10 , 11 ). Treatment with ICIs can increase the risk of multi-organ autoimmune inflammatory responses, which are the most common type of complication associated with this type of treatment ( 12 ).…”