The role of immunotherapy in treatment of brain metastases is unknown because most trials exclude patients with active brain lesions. As new immunomodulating agents gain approval for many malignancies, it is important to know if they have unique effects in the central nervous system (CNS). Here, we present a case of a patient with progressing brain metastases treated with a single cycle of pembrolizumab, who presented with mental status changes 11 days thereafter. MRI of the brain showed enlargement of CNS lesions with intense central enhancement and diffuse perilesional edema. Histologic evaluation of a resected lesion revealed isolated clusters of tumor cells surrounded by reactive astrocytosis, scattered inflammatory cells, and an abundance of microglial cells. Given the increasing use of immune checkpoint inhibitors in patients with brain metastases from melanoma and other diseases, recognition of pseudoprogression and management with immune suppression are essential. Cancer Immunol Res; 4(3); 179–82. ©2015 AACR.

Aim: Anorectal fistulas have been a common surgical problem since ancient times. Age-old seton techniques are still practicedsuccessfully in the treatment of complex anal fistulas. Many

Delayed radiation-induced vasculitic leukoencephalopathy related to stereotactic radiosurgery (SRS) of brain metastases has been reported to manifest clinically 9 to 18 months after treatment. Immune-modulating therapies have been introduced to treatment regimens for malignancies with metastatic predilection to the brain. The interaction of these systemic therapies with other modalities of treatment for brain metastases, namely, SRS, has not been fully characterized. We report two patients with metastatic malignancies to the brain who received SRS followed by immunotherapy with monoclonal antibodies (mAb) to programmed death 1 (PD-1). Both patients appeared to have early clinical and radiologic progression of their treated lesions, which was highly suspicious for tumor progression. Both patients underwent surgical resection of their lesions and the material was submitted for histopathologic examination. Pathologic examination in both cases showed predominantly radiation-induced changes characterized by reactive astrocytosis and vascular wall infiltration by T lymphocytes. The accelerated response to SRS in these two patients was temporally related to the initiation of immunotherapy. We propose a possible biologic interaction between SRS and the PD-1 mAbs. Additionally, awareness of this potential occurrence is critical for accurate interpretation and proper management of clinical and radiologic findings in these patients. Cancer Immunol Res; 4(6); 481–7. ©2016 AACR.