Natural Course and Prognosis of Primary Spinal Glioblastoma: A Nationwide Study

Abstract

Background and objectives: Primary spinal glioblastoma (PsGBM) is extremely rare. The dramatic neurologic deterioration and unresectability of PsGBM makes it a particularly disabling malignant neoplasm. Because it is a rare and heterogeneous disease, the assessment of prognostic factors remains limited.

Methods: PsGBMs were identified from the French Brain Tumor Database and the Club de Neuro-Oncologie of the Société Française de Neurochirurgie retrospectively. Inclusion criteria were age 18 years or older at diagnosis, spinal location, histopathologic diagnosis of newly glioblastoma according to the 2016 World Health Organization classification, and surgical management between 2004 and 2016. Diagnosis was confirmed by a centralized neuropathologic review. The primary outcome was overall survival (OS). Therapeutic interventions and neurologic outcomes were also collected.

Results: Thirty-three patients with a histopathologically confirmed PsGBM (median age 50.9 years) were included (27 centers). The median OS was 13.1 months (range 2.5-23.7), and the median progression-free survival was 5.9 months (range 1.6-10.2). In multivariable analyses using Cox model, Eastern Cooperative Oncology Group (ECOG) performance status at 0-1 was the only independent predictor of longer OS (hazard ratio [HR] 0.13, 95% CI 0.02-0.801; p = 0.02), whereas a Karnofsky performance status (KPS) score <60 (HR 2.89, 95% CI 1.05-7.92; p = 0.03) and a cervical anatomical location (HR 4.14, 95% CI 1.32-12.98; p = 0.01) were independent predictors of shorter OS. The ambulatory status (Frankel D-E) (HR 0.38, 95% CI 0.07-1.985; p = 0.250) was not an independent prognostic factor, while the concomitant standard radiochemotherapy with temozolomide (Stupp protocol) (HR 0.35, 95% CI 0.118-1.05; p = 0.06) was at the limit of significance.

Discussion: Preoperative ECOG performance status, KPS score, and the location are independent predictors of OS of PsGBMs in adults. Further analyses are required to capture the survival benefit of concomitant standard radiochemotherapy with temozolomide.

Figure 1. MRI of Cervical PsGBM

(A) Sagittal T1-weighted MRI showing a thickening of the cervical spinal cord (white star). (B) Sagittal and (C) axial T1-weighted MRI with gadolinium injection demonstrating an enhancement of the anterior cervical spinal cord (white arrow). (D) Sagittal T2-weighted MRI of the same tumor showing peripheral edema in hypersignal. PsGBM = primary spinal glioblastoma

Figure 2. Evolution of Frankel Scores (Neurologic Function) of Patients With PsGBM During the Follow-up

(A) At presentation, 67% of patients were ambulatory (Frankel D and E), before early presentation (B) at the 3-month follow-up, a degradation was noted and only 19% of patients remained ambulatory (Frankel D). At lesion progression, 83% of patients developed plegia (Frankel A and B) and only 7% were ambulatory. PsGBM = primary spinal glioblastoma.

Figure 3. OS Analysis

Kaplan-Meier survival analysis. (A) PFS in months, defined by clinical and MRI progression: table demonstrated the progression rates at 6, 12, and 24 months of follow-up. (B) Overall survival (OS) in months for the 33 patients after PsGBM diagnosis: table demonstrated the survival rates at 6, 12, 36, and 60 months of follow-up. OS = overall survival; PFS = progression-free survival; PsGBM = primary spinal glioblastoma.

Figure 4. OS in Univariate Analyses

(A) The median OS for good prognosis ECOG (0–1) was 31.8 months (SD 3.6) vs 5.4 months (SD 1.5) for poor ECOG (2–4) (p < 0.0001). (B) The median OS for ambulatory patients (Frankel D and E) was 24.4 months (SD 9.3) vs 5.4 months (SD 1.2) for nonambulatory (Frankel A–C) (p = 0.002). (C) The median OS for patients with a KPS <50 was 3.6 months (SD 2.0) vs 18.2 months (SD 5.3) for KPS (50–80), vs 41.2 months (SD 7.2) for KPS >80 (p < 0.0001). (D) The median OS for patients with a cervical PsGBM was 5.9 months (SD 2.7) vs 13.1 months (SD 5.8) for thoracic lesions, vs 37.2 months (SD 6.2) for lumbar PsGBM (p = 0.029). (E) The median OS for patients with concomitant radiochemotherapy with temozolomide according to the Stupp protocol was 31.8 months (SD 8.1) vs 7.6 months (SD 4.07) for other oncological treatment (p = 0.055). ECOG = Eastern Cooperative Oncology Group; KPS = Karnofsky performance status; OS = overall survival; PsGBM = primary spinal glioblastoma.