Diagnosis, treatment, and survival in spinal dissemination of primary intracranial glioblastoma: systematic literature review

Abstract

<jats:sec><jats:title>OBJECTIVE</jats:title><jats:p>Spinal metastases from primary intracranial glioblastoma (GBM) are infrequently reported, and the disease has yet to be well characterized. A more accurate description of its clinical presentation and patient survival may improve understanding of this pathology, guide patient care, and advocate for increased inclusion in GBM research. The authors sought to describe the clinical presentation, treatment patterns, and survival in patients with drop metastases secondary to primary intracranial GBM.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>A systematic review was performed using the PRISMA guidelines. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane databases were queried for abstracts that included patients with primary intracranial GBM and metastases to the spinal axis. Descriptive statistics were used to evaluate characteristics of the primary brain lesion, timing of spinal metastases, clinical symptoms, anatomical location of the metastases, and survival and treatment parameters. Kaplan-Meier analysis and log-rank analysis of the survival curves were performed for selected subgroups.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>Of 1225 abstracts that resulted from the search, 51 articles were selected, yielding 86 subjects. The patients’ mean age was 46.78 years and 59.74% were male. The most common symptom was lumbago or cervicalgia (90.24%), and this was followed by paraparesis (86.00%). The actuarial median survival after the detection of spinal metastases was 2.8 months and the mean survival was 2.72 months (95% CI 2.59–4.85), with a 1-year cumulative survival probability of 2.7% (95% CI 0.51%–8.33%). A diagnosis of leptomeningeal disease, present in 53.54% of the patients, was correlated, and significantly worse survival was on log-rank analysis in patients with leptomeningeal disease (p = 0.0046; median survival 2.5 months [95% CI 2–3] vs 4.0 months [95% CI 2–6]).</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>This study established baseline characteristics of GBMs metastatic to the spinal axis. The prognosis is poor, though these results will provide patients and clinicians with more accurate survival estimates. The quality of studies reporting on this disease pathology is still limited. There is significant need for improved reporting methods for spinal metastases, either through enrollment of these patients in clinical trials or through increased granularity of coding for metastatic central nervous system diseases in cancer databases.</jats:p></jats:sec>

Leptomeningeal Metastases of the Spine: A Systematic Review

“…While piecemeal resection and/or targeted radiation of brain metastases may cause the disruption of the blood-brain barrier (BBB) favoring direct trans-meningeal and intrasubarachnoid space spillage of cancers cells, current oncological therapies improve systemic disease control but poorly penetrate the BBB, leading to tumor cell reservoirs within the CNS and higher risk of CSF spreading (68). For these reasons, LMs from CNS and non-CNS tumors are frequently diagnosed at later disease stages, as we found in our pooled spine LMs cases, presenting with a median time interval of 12 months from primary tumor diagnosis (3,8,69). However, as spine LMs may constitute the initial diagnosis of neoplastic diseases in few patients with slow-growing tumors, different leptomeningeal seeding mechanisms should be also considered and identified to guide timely diagnostic and therapeutic strategies (43, 45,47,60).…”

“…Clinical evaluation may support the initial diagnosis of secondary metastases involving the spine, but symptoms of LMs are mostly non-specific (65, 70). Similarly to spine LMs from primary CNS tumors, spine LMs from non-CNS tumors frequently present with sensorimotor deficits, lumbago, and/or radicular pain deriving from spinal cord and nerve root compression (8,13,58). However, as these symptoms may also occur in other benign or malignant conditions, including intervertebral disc herniation or vertebral fracture, patients' history of oncological disease and systemic metastases should be investigated to plan appropriate metastatic diagnostic protocols (71,72).…”

A Retrospective Study on Spinal Dissemination of Supratentorial Glioma

“…Spinal dissemination was first reported and is more common in glioblastoma multiforme (GBM), a grade IV tumor with the most aggressive characteristics ( 18 , 19 ). However, according to our own clinical experience and series of reports, spinal dissemination may also occur in patients with low-grade glioma ( 20 , 21 ).…”

Anaplastic pilocytic astrocytoma of the cerebellum presenting with conus medullaris drop metastasis

“…Glioblastoma is the most frequently reported entity with less than 1% of cases being associated with leptomeningeal dissemination. [21] Spinal drop metastases is more common in the pediatric population, particularly with ependymoma and medulloblastoma. [22] Metastatic tumors to the central nervous system may present with spinal drop metastases as well, sometimes mimicking the radiographic features of high grade primary central nervous system tumors.…”