Cancer therapy-associated CNS neuropathology: an update and review of the literature

Standard therapeutic options for brain tumors include surgery, radiation, and chemotherapy. Unfortunately, these same therapies pose risks of neurotoxicity, the most common long-term complications being radiation necrosis, chemotherapy-associated leukoencephalopathy, and secondary neoplasms. These side effects remain difficult to predict, but are associated with risk factors that include patient age, therapeutic modality and dosage, genetic background, and idiosyncratic predispositions. Experimental treatments designed to enhance efficacy and to minimize neurotoxicity include molecularly targeted, genetic, stem cell, and immune therapies. Newer modifications in radiation and drug delivery include stereotactic radiosurgery, interstitial therapy such as intracavitary brachytherapy and gliadel wafer placement, 3D conformal radiation, boron neutron capture therapy, radiosensitizers, blood-brain barrier disrupting agents, and convection enhanced delivery. Toxicities associated with these newer modalities have yet to be fully investigated and documented. Additionally, a number of recently implemented radiographic techniques such as PET and SPECT imaging have enhanced the ability to distinguish recurrent tumor from radiation necrosis. Nevertheless, post-therapeutic brain biopsies and autopsies remain the gold standard for assessing neurotoxicity, therapeutic efficacy, tumor progression, and the development of secondary neoplasms. At the same time, treatment-associated changes such as tumor necrosis, vasculopathy, inflammation, and cytologic atypia can pose significant diagnostic pitfalls, particularly if the pathologist is not provided a detailed therapeutic history. Therefore, it is critical to recognize the full spectrum of cancer therapy-associated neuropathology, the topic of the current review.