title: Possible Interaction of Anti-PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases.
abstract: 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.
authors.affiliation: Department of Pathology, Yale University, School of Medicine, New Haven, Connecticut. Akalomari@gmail.com.
authors.forename: Ahmed K
authors.initials: AK
authors.lastname: Alomari
authors.affiliation: Department of Medicine (Medical Oncology), Yale University, School of Medicine, New Haven, Connecticut.
authors.forename: Justine
authors.initials: J
authors.lastname: Cohen
authors.affiliation: Department of Pathology, Yale University, School of Medicine, New Haven, Connecticut.
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Vortmeyer
authors.affiliation: Department of Medicine (Medical Oncology), Yale University, School of Medicine, New Haven, Connecticut.
authors.forename: Anne
authors.initials: A
authors.lastname: Chiang
authors.affiliation: Department of Medicine (Medical Oncology), Yale University, School of Medicine, New Haven, Connecticut.
authors.forename: Scott
authors.initials: S
authors.lastname: Gettinger
authors.affiliation: Department of Medicine (Medical Oncology), Yale University, School of Medicine, New Haven, Connecticut.
authors.forename: Sarah
authors.initials: S
authors.lastname: Goldberg
authors.affiliation: Department of Medicine (Medical Oncology), Yale University, School of Medicine, New Haven, Connecticut.
authors.forename: Harriet M
authors.initials: HM
authors.lastname: Kluger
authors.affiliation: Department of Neurosurgery, Yale University, School of Medicine, New Haven, Connecticut.
authors.forename: Veronica L
authors.initials: VL
authors.lastname: Chiang
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D003131:Combined Modality Therapy / Q000009:adverse effects; D018450:Disease Progression; D005260:Female; D005911:Gliosis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects* / Q000379:methods; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D011832:Radiation Injuries / Q000209:etiology / Q000276:immunology / Q000473:pathology; D016634:Radiosurgery / Q000009:adverse effects* / Q000379:methods
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab