• History and Examination
    • Neurologically intact
    • No significant PMH
    • Biopsy: anaplastic astrocytoma
    • Patient completed radiation and chemotherapy
    • One year follow- up imaging was obtained
    • Three months after follow-up imaging he presents with urinary retention and leg weakness for seven days
    • MRI findings: enhancing intra/extramedullary mass at T8
    • Physical exam:
      4/5 Hip flexors/Knee extension, 3/5 Plantar flexion/Dorsiflexion
      Decreased light touch in the left lower extremity

    Figure 1

    Figure 2

    Figure 3

    1. What is your diagnosis of the T8 enhancing mass?

    2. What is your treatment recommendation?

    3. What is the maximal single SRS dose that can be safely administered to the spinal cord?

    4. What is the maximal total fractionated dose of radiation that can be safely administered to the spinal cord?

    5. Which of the following describes you?

    6. I practice in one of the following locations.

    7. Comments
     
    • The biopsy first would answer what needs to be done
    • Patient should be biopsied followed by radiotherapy/chemotherapy
    • I correctly diagnosed this as a metastatic GBM but there was no foil for that. Also, I think that surgical intervention in this case is far too aggressive. This patient will lose this battle soon as evidenced by recurrence in just 15 months despite prior surgery and chemo.

     

    Case Explanation:

    • This patient has a history of a Grade III astrocytoma (AA) responsive to radiation and chemotherapy.  AA tend to occur in those 35-55yrs with an incidence of 10-30% of gliomas.
    • Thoracic imaging approximately 15 months after initial diagnosis was consistent with an intradural-intra/extramedullary GBM. 
    • Metastatic gliomas to the spine are rare. The lower cervical and thoracic spine are most commonly affected. In adults, approximately 10-30% of intramedullary astrocytomas are malignant.  Dissemination risks include periventricular location, GFAP+, PTEN mutation, high MIB-1, and biopsy tract involving the ventricles.
      Optimal surgical management remains controversial.  Current interventions are focused on relief of symptoms and quality of life. 
    • Many would agree that a patient with a progressive neurological deficit requires surgical decompression to preserve neurological function.  The extent of resection and survival is unknown. 
    • Some centers might consider biopsy followed by radiotherapy.    
      Numerous studies have focused on the genetic markers of intracranial astrocytomas, but few have investigated spinal gliomas. Glioma genetic/molecular markers are continually evolving.  Common markers to both locations are BRAF, PTEN, and p53.
      In this case, the patient has both a PTEN mutation and methylated MGMT.  PTEN mutation is found in 40% of cases and a correlation with survival is limited.  MGMT promoter methylation in found 50% of GBMs and confers a prognostic benefit and response to alkylating agents.
    • Spinal GBM subtotal resection to preserve neurological function followed by adjuvant radiation therapy is recommended. 
    • The recommended total dose of radiation to the spinal cord established through animal data and published reports is 45-50Gy.  The cervical cord being more tolerant than thoracic, secondary to vascular supply.
    • Other influences include: time between fractionations, volume of tissue treated and chemotherapy
    • Schultheiss et. al. suggested the incidence of radiation induced myelopathy: 45Gy- 0.03% 50Gy- 0.2%, 57-61Gy- 5% and 69Gy- 50%.
    • Ryu S. et al. established the partial volume tolerance of the human spinal cord to be at least 10 Gy to the 10% spinal cord volume (6 mm above and below the target).
    • Others have demonstrated a <1% risk of injury with a maximal cord dose of 13Gy in a single fraction.

    References:

    • Cohen AR, Wisoff JH, Allen JC, Epstein F. Malignant astrocytomas of the spinal cord. J Neurosurg. 1989;70:50-54.

    • Karsy M, Neil JA, Guan J, Mahan MA, Colman H, Jensen RL. A practical review of prognostic correlations of molecular biomarkers in glioblastoma. Neurosurgical Focus. 2015;38(3). E4. Available from: 10.3171/2015.1.FOCUS14755

    • Karsy M, Guan J, Sivakumar W, Neil JA, Schmidt MH, Mahan MA. The genetic basis of intradural spinal tumors and its impact on clinical treatment. Neurosurgical Focus. 2015;39(2). E3.
      Available from: 10.3171/2015.5.FOCUS15143

    • Konar SK, Maiti TK, Bir SC, Kalakoti P, Bollam P, Nanda A. Predictive factors determining the overall outcome of primary spinal glioblastoma multiforme: an integrative survival analysis. World Neurosurg. 2015. Available from: 10.1016/j.wneu.2015.08.078

    • Shahideh M, Fallah A, Munoz DG, Macdonald RL. Systemic review of primary intracranial glioblastoma multiforme with symptomatic spinal metastases, with two illustrative patients. J Clin Neurosci. 2012;19:1080-86.

    • Schultheiss T. The Radiation Dose-Response of the Human Spinal Cord. Int. J. Radiation Oncology Biol. Phys., Vol. 71, No. 5, pp. 1455-59, 2008

    • Schultheeiss T.  Radiation Response of the Central Nervous System. Int. J. Radiation Oncology Biol. Phys. Vol. 31, No. 5. pp. 1093

    • Kirkpatrick et al. RADIATION DOSE–VOLUME EFFECTS IN THE SPINAL CORD. Int. J. Radiation Oncology Biol. Phys., Vol. 76, No. 3, Supplement, pp. S42–S49, 2010

    • Shin, D. Stereotactic spine radiosurgery for intradural and intramedullary metastasis. Neurosurg Focus 27 (6):E10, 2009

    • Ryu S, Yin FF, Rock J, et al. Image-guided intensity-modulated radiosurgery for spinal metastasis. Cancer. 2003;97:2013–2018

     
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