title: Severe cerebral edema following nivolumab treatment for pediatric glioblastoma: case report.
abstract: Nivolumab is an immune checkpoint inhibitor (ICI) currently undergoing Phase III clinical trials for the treatment of glioblastoma. The authors present the case of a 10-year-old girl with glioblastoma treated with nivolumab under compassionate-use guidelines. After the first dose of nivolumab the patient developed hemiparesis, cerebral edema, and significant midline shift due to severe tumor necrosis. She was managed using intravenous dexamethasone and discharged on a dexamethasone taper. The patient's condition rapidly deteriorated after the second dose of nivolumab, demonstrating hemiplegia, seizures, and eventually unresponsiveness with a fixed and dilated left pupil. Computed tomography of her brain revealed malignant cerebral edema requiring emergency decompressive hemicraniectomy. Repeat imaging demonstrated increased size of the lesion, reflecting immune-mediated inflammation and tumor necrosis. The patient remained densely hemiplegic, but became progressively more interactive and was ultimately extubated. She resumed nivolumab several weeks later, but again her condition deteriorated with headache, vomiting, swelling at the craniectomy site, and limited right-sided facial movement following the sixth dose. MRI demonstrated severe midline shift and uncal herniation despite her craniectomy. Her condition gradually declined, and she died several days later under "do not resuscitate/do not intubate" orders. To the authors' knowledge, this represents the first case of malignant cerebral edema requiring operative intervention following nivolumab treatment for glioblastoma in a pediatric patient.
authors.affiliation: Department of Neurological Surgery, and.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Neurological Surgery, and.
authors.forename: Michael M
authors.initials: MM
authors.lastname: McDowell
authors.affiliation: Department of Neurological Surgery, and.
authors.forename: William C
authors.initials: WC
authors.lastname: Newman
authors.affiliation: Division of Pediatric Hematology/Oncology, Children's Hospital of Pittsburgh, University of Pittsburgh, Pennsylvania.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Mason
authors.affiliation: Department of Neurological Surgery, and.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Greene
authors.affiliation: Department of Neurological Surgery, and.
authors.forename: Mandeep S
authors.initials: MS
authors.lastname: Tamber
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D001929:Brain Edema / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology / Q000601:surgery; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D017809:Fatal Outcome; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000077594:Nivolumab
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000077594:Nivolumab
keywords: ED = emergency department; ICI = immune checkpoint inhibitor; NSCLC = non small cell lung cancer; PCA = posterior cerebral artery; PD1 = programmed cell death protein 1; RCC = renal cell carcinoma; SRS = stereotactic radiosurgery; adverse event; glioblastoma; hemicraniectomy; nivolumab; oncology