Extensive Leptomeningeal Intracranial and Spinal Metastases in a Patient with a Supratentorial Glioblastoma Multiforme, IDH-Wildtype

World Neurosurg. 2018 Dec;120:442-447. doi: 10.1016/j.wneu.2018.09.082. Epub 2018 Sep 22.

Abstract

Background: Glioblastoma multiforme (GBM) is usually characterized by diffuse, infiltrative growth and local tumor progression. Extensive leptomeningeal metastases are rarely observed. It is unclear which GBMs are prone to this specific growth pattern and progression, and standardized salvage treatment protocols are unavailable.

Case description: In a 45-year-old man without focal neurologic deficit, a right temporal GBM, IDH-wildtype (biomarkers MGMT promoter methylation negative, Ki-67 proliferation rate 70%) was diagnosed. Gross tumor resection followed by concomitant and adjuvant radiotherapy and chemotherapy with temozolomide was performed. Routine follow-up imaging 8 months later showed a right parietal meningeal tumor. Resection confirmed a distant GBM, and next-generation sequencing revealed high tumor mutational burden, high-frequency microsatellite instability, and a pharmacologically targetable KIT mutation. Complete neuraxis imaging revealed multiple contrast-enhancing tumors in the craniocervical junction and levels C7, Th8-Th11, and S1. The craniocervical tumors and the cervical spine from C1-C2 were irradiated as palliative care, and second-line combined chemotherapy and antiangiogenic therapy with irinotecan and bevacizumab was initiated, which was later changed to an immune-checkpoint blockade with pembrolizumab in combination with bevacizumab owing to tumor progression. Tumor growth was slowed, but the patient eventually developed a progressive paraparesis. Subsequent KIT-targeting tyrosine kinase inhibitor therapy with imatinib was administered for a short time. The patient died 13.8 months after initial diagnosis.

Conclusions: High-risk genetic profiles for GBMs prone to develop extensive leptomeningeal metastases need to be identified. Guidelines on preemptive, complete neuraxis imaging in certain patients with GBM as well as treatment guidelines need to be developed.

Keywords: Biomarker; Extracranial; Genetic profile; Glioblastoma multiforme; Leptomeningeal metastases; Outcome; Salvage treatment.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab / administration & dosage
  • Chemoradiotherapy, Adjuvant
  • DNA Mutational Analysis
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / genetics
  • Glioblastoma / secondary*
  • Glioblastoma / therapy
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Irinotecan / administration & dosage
  • Isocitrate Dehydrogenase / genetics
  • Magnetic Resonance Imaging
  • Male
  • Meningeal Neoplasms / diagnostic imaging
  • Meningeal Neoplasms / genetics
  • Meningeal Neoplasms / secondary*
  • Meningeal Neoplasms / therapy
  • Microsatellite Instability
  • Middle Aged
  • Neurosurgical Procedures
  • Palliative Care
  • Radiotherapy
  • Sequence Analysis, DNA
  • Supratentorial Neoplasms / diagnostic imaging
  • Supratentorial Neoplasms / genetics
  • Supratentorial Neoplasms / pathology*
  • Supratentorial Neoplasms / therapy
  • Temozolomide / therapeutic use

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Alkylating
  • Antineoplastic Agents, Immunological
  • Bevacizumab
  • Irinotecan
  • pembrolizumab
  • Isocitrate Dehydrogenase
  • Temozolomide