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Year : 2015  |  Volume : 11  |  Issue : 3  |  Page : 654

Primary spinal glioblastoma treated with adjuvant radiation and temozolomide: Report of two cases

Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication9-Oct-2015

Correspondence Address:
Supriya Mallick
Department of Radiation Oncology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.137998

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 > Abstract 

Primary spinal glioblastoma multiforme (GBM) is a rare entity, which is invariably associated with poor outcome. Standard treatment is surgery followed by post-operative radiotherapy. Due to paucity of cases role of chemotherapy is investigational. We intend to report two cases of primary spinal GBM treated with radiation and adjuvant temozolomide.

Keywords: Chemoradiotherapy, glioblastoma multiforme, spinal cord, surgery

How to cite this article:
Mallick S, Madan R, Julka P K. Primary spinal glioblastoma treated with adjuvant radiation and temozolomide: Report of two cases. J Can Res Ther 2015;11:654

How to cite this URL:
Mallick S, Madan R, Julka P K. Primary spinal glioblastoma treated with adjuvant radiation and temozolomide: Report of two cases. J Can Res Ther [serial online] 2015 [cited 2023 Jan 27];11:654. Available from: https://www.cancerjournal.net/text.asp?2015/11/3/654/137998

 > Introduction Top

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, however, it is rare in the spinal region. Spinal GBM accounts for 1-5% of all GBM and approximately 1.5% of all spinal tumors. [1] It has a predilection of development at the cervical or cervico-thoracic region. [2] Leptomeningeal dissemination with simultaneous intramedullary metastasis from cerebral GBM have been described. This entity poses challenge to treat. [3],[4] Even with aggressive management, these tumors are generally associated with a dismal outcome. Standard treatment for spinal GBM is maximal safe surgical resection followed by adjuvant radiotherapy. Role of chemotherapy (CT) in prolonging survival is still debatable, however a few authors have reported better outcome with addition of CT. [5] Cerebrospinal fluid (CSF) involvement and consecutive intracranial seeding determine the prognosis of patients with spinal GBM. Thus, regular monitoring of CSF-cytology and/or spinal magnetic resonance imaging (MRI) appears to be advisable in spinal GBM. Here we are reporting two cases of spinal GBM, who underwent surgery followed by post-operative radiotherapy (PORT) and concurrent and adjuvant temozolomide (TMZ).

 > Case ReportS Top

Case 1

The first case is about a 40-year-old male patient who presented with a 4 week history of lower back pain and progressing paraparesis. There was no complaint of bowel or bladder incontinence. Physical examination revealed relatively preserved sensory function and joint position sense. Spinal MRI revealed an intramedullary mass at D10-L1 vertebral level. CSF cytology analysis was negative. Patient underwent microsurgical subtotal resection. Histological examination revealed grade 4 asrtocytic tumor. Immunohistochemistry showed increased proliferation rate and accumulation of p53 protein. He was planned for PORT 45 gray/25 fractions/5 weeks with concurrent TMZ 75 mg/m 2 daily during radiation. After completion of concurrent treatment adjuvant treatment was given with TMZ 150-200 mg/m 2 D1-D5 every 4 weekly for six cycles. Patient was alive for 14 months after treatment completion and died due to unknown reason.

Case 2

A 23-year-old female patient presented with low back pain radiating to both legs and progressive weakness in both lower limbs (right > left) since 1 year. MRI revealed intramedullary space occupying lesion extending from D9-L1 vertebrae. She underwent D9-L1 laminoplasty with near total excision of the tumor. Post-operative histopathological examination showed GBM. She received PORT 50.4 gray/28 fractions/5 fractions/week with concurrent (75 mg/m 2 ) TMZ. After completion of concurrent treatment adjuvant treatment was given with TMZ 150-200 mg/m 2 D1-D5 every 4 weekly for six cycles. She survived for 18 months after completion of treatment and died due to progressive disease.

 > Discussion Top

In contrast to intracranial GBM primary spinal glioblastoma is an extremely rare tumor with fewer than 200 cases reported in the medical literature until date. This may be attributed to the fact that absolute number of neuroglial cells is relatively rare in spinal cord. [6] In contrast to intracranial GBM, it occurs at relatively younger age(<30 years) with no sex predilection. [7]

Clinical presentation depends upon the site and extent of the spinal cord involvement and may include various features of cord compression, leg weakness and muscle atrophy and bladder-bowel disturbance.

It is invariably associated with dismal outcome, which can be estimated by the fact that the median survival in various studies is only 15 months (range: 6-28). Treatment outcome of recently published cases spinal GBM has been tabulated in [Table 1]. Survival duration over 18 months is seen in approximately 32% patients. Longest reported survival is 64 months. [8] Although this data might indicate a relatively better prognosis in spinal GBM, but it cannot be inferred conclusively owing to the paucity of cases. [9]
Table 1: Recently published reports of spinal GBM

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Radiology and histopathology are sine qua non to establish the diagnosis of spinal GBM. Contrast enhanced MRI is the imaging modality of choice, it shows hypointense signals in T1-weighted images and hyperintense signals on T2-weighted MRI images. The histopathological features of spinal-GBM are identical to intracranial tumors including cellular pleomorphism, high mitotic activity, necrosis and vascular proliferation [7] [Figure 1]. Owing to their glial origin they show at least focal expression of glial fibrillary acidic protein and S-100 protein. Routine CSF cytology is recommended as various authors have reported rate of intracranial metastasis as high as 26% via CSF spread. The high rate of leptomeningeal spread has been attributed to the relatively thin parenchyma in the spinal cord and hence, the short distance to the subarachnoid space. [16]
Figure 1: Photomicrograph showing a high grade glioma with high mitotic activity, nuclear pleomorphism and ares of necrosis. (a) H and E, ×200, tumor cells are positive for epidermal growth factor receptor (b) ×400 and p53 (c) ×200

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Similar to intra cranial GBM surgery remains the primary treatment of choice in spinal glioblatoma and the extent of surgery is one of the most important prognostic factor. Being a rare tumor the optimum adjuvant treatment is yet not defined in spinal glioblastoma. Addition of radiotherapy is associated with better outcome in spinal GBM. Role of CT is not well-established. Different authors have tried a wide spectrum of treatment regimens with variable response. TMZ in concurrent and adjuvant setting has shown favorable outcomes in different studies. [5] The better outcome with addition of TMZ may be explained by two reasons: (1) It is a potent radiosensitizer and (2) as the tolerance of spinal cord for radiation is less than that of brain, addition of TMZ can compensate for the low radiation dose. Because of high risk of intracranial and leptomeningeal spread, whole brain radiation along with focal spinal irradiation has been recommended by few authors. While others have suggested craniospinal irradiation and administration of intrathecal CT. [17]

In our cases, we have followed the NCIC-EORTC protocol for GBM with a modified dose of Radiotherapy of 45-50.4 gray @ 1.8 gray/fraction to avoid the toxicity of spinal cord. Both the patients received post-operative concurrent chemo-radiotherapy and adjuvant CT with TMZ.

 > Conclusion Top

Based on the above cases it can be concluded that the treatment outcome remains guarded for spinal GBM owing to its aggressive nature and difficulty to optimize surgical excision and increasing radiation dose. However, addition of TMZ seems to improve outcome in such cases.

 > References Top

Andrews AA, Enriques L, Renaudin J, Tomiyasu U. Spinal intramedullary glioblastoma with intracranial seeding. Report of a case. Arch Neurol 1978;35:244-5.  Back to cited text no. 1
Cohen AR, Wisoff JH, Allen JC, Epstein F. Malignant astrocytomas of the spinal cord. J Neurosurg 1989;70:50-4.  Back to cited text no. 2
Scoccianti S, Detti B, Meattini I, Iannalfi A, Sardaro A, Leonulli BG, et al. Symptomatic leptomeningeal and intramedullary metastases from intracranial glioblastoma multiforme: A case report. Tumori 2008;94:877-81.  Back to cited text no. 3
Fiorentino A, Caivano R, Chiumento C, Cozzolino M, Fusco V. Radiotherapy and bevacizumab for intramedullary and leptomenigeal metastatic glioblastoma: A case report and review of the literature. Int J Neurosci 2012;122:691-4.  Back to cited text no. 4
Kim WH, Yoon SH, Kim CY, Kim KJ, Lee MM, Choe G, et al. Temozolomide for malignant primary spinal cord glioma: An experience of six cases and a literature review. J Neurooncol 2011;101:247-54.  Back to cited text no. 5
Raco A, Esposito V, Lenzi J, Piccirilli M, Delfini R, Cantore G. Long-term follow-up of intramedullary spinal cord tumors: A series of 202 cases. Neurosurgery 2005;56:972-81.  Back to cited text no. 6
Morais N, Mascarenhas L, Soares-Fernandes JP, Silva A, Magalhães Z, Costa JA. Primary spinal glioblastoma: A case report and review of the literature. Oncol Lett 2013;5:992-6.  Back to cited text no. 7
Marchan EM, Sekula RF Jr, Jannetta PJ, Quigley MR. Long-term survival enhanced by cordectomy in a patient with a spinal glioblastoma multiforme and paraplegia. Case report. J Neurosurg Spine 2007;7:656-9.  Back to cited text no. 8
Strik HM, Effenberger O, Schäfer O, Risch U, Wickboldt J, Meyermann R. A case of spinal glioblastoma multiforme: Immunohistochemical study and review of the literature. J Neurooncol 2000;50:239-43.  Back to cited text no. 9
Singh PK, Singh VK, Tomar J, Azam A, Gupta S, Kumar S. Spinal glioblastoma multiforme: Unusual cause of post-traumatic tetraparesis. J Spinal Cord Med 2009;32:583-6.  Back to cited text no. 10
Stecco A, Quirico C, Giampietro A, Sessa G, Boldorini R, Carriero A. Glioblastoma multiforme of the conus medullaris in a child: Description of a case and literature review. AJNR Am J Neuroradiol 2005;26:2157-60.  Back to cited text no. 11
Bonde V, Balasubramaniam S, Goel A. Glioblastoma multiforme of the conus medullaris with holocordal spread. J Clin Neurosci 2008;15:601-3.  Back to cited text no. 12
O′Halloran PJ, Farrell M, Caird J, Capra M, O′Brien D. Paediatric spinal glioblastoma: Case report and review of therapeutic strategies. Childs Nerv Syst 2013;29:367-74.  Back to cited text no. 13
Ononiwu C, Mehta V, Bettegowda C, Jallo G. Pediatric spinal glioblastoma multiforme: Current treatment strategies and possible predictors of survival. Childs Nerv Syst 2012;28:715-20.  Back to cited text no. 14
Mori K, Imai S, Shimizu J, Taga T, Ishida M, Matsusue Y. Spinal glioblastoma multiforme of the conus medullaris with holocordal and intracranial spread in a child: A case report and review of the literature. Spine J 2012;12:e1-6.  Back to cited text no. 15
Yeung YF, Wong GK, Zhu XL, Ma BB, Hk NG, Poon WS. Radiation-induced spinal glioblastoma multiforme. Acta Oncol 2006;45:87-90.  Back to cited text no. 16
Asano N, Kitamura K, Seo Y, Mukai K, Soga T, Hondo H, et al. Spinal cord glioblastoma multiforme with intracranial dissemination - Case report. Neurol Med Chir (Tokyo) 1990;30:489-94.  Back to cited text no. 17


  [Figure 1]

  [Table 1]

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