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Primary Spinal Cord Glioblastoma Multiforme: A Rare but Uniformly Fatal Neoplasm
Letter to the Editor Primary Spinal Cord Glioblastoma Multiforme: A Rare but Uniformly Fatal Neoplasm
LETTER: he article by Behmanesh et al.,1 entitled “Management of Patients with Primary Intramedullary Spinal Cord Glioblastoma,” published in WORLD NEUROSURGERY, was read with great interest. The authors present 4 cases of spinal cord glioblastoma multiforme (GBM) managed at their institution over a 10-year period. All patients were female, and the mean age was 33.5 years (range, 14e50 years). Two tumors each were located in the cervical and thoracic region. Preoperatively, there was 1 patient each with McCormick grade IeIV. A biopsy was performed for all cases, and all patients received adjuvant radiation therapy and temozolomide. In the follow-up period, 3 patients were McCormick grade IV, and 1 patient had neurologic improvement from McCormick grade IV to McCormick grade III. All tumors progressed at a mean interval of 18.2 months (range, 6e32 months). Brain dissemination was observed in 1 case. For disease progression, 1 patient underwent additional therapy with bevacizumab, 1 patient received rapamycin and sunitinib, and the third patient received chlorethyl-cyclohexyl-nitrosourea and etoposide as additional therapy. All patients died of their disease with a median survival after diagnosis of 32.5 months. The cause of death was respiratory paralysis in 2 cases and severe pneumonia in another 2 cases. The authors concluded that although the surgical outcome of spinal cord GBM remains poor, an aggressive multimodal and interdisciplinary treatment for the disease might be associated with longer survival.
T
After a detailed analysis of this article, I have 2 concerns. First, on what basis did the authors provide different types of adjuvant therapies to their patients at the time of tumor progression? Are there any studies to support this, or was the decision based on the opinion of an oncologist on an individual case-by-case basis? Second, a mention of MIB-1 labeling index of all their cases would have been beneficial for reasons mentioned subsequently. GBM is a highly heterogeneous, high-grade central nervous system neoplasm. Surgery with adjuvant temozolomide and radiotherapy is the mainstay of treatment, and complete removal is an independent prognostic factor for survival in cranial GBM. Similarly, the MIB-1 labeling index is one of the many prognostic factors impacting the outcome. However, the prognosis remains dismal with most GBMs recurring within a short span of time and patients dying of their disease. Recent strategies for recurrent cranial GBM have included angiogenesis inhibitors (bevacizumab, sunitinib, irinotecan), stereotactic radiosurgery, and targeted molecular therapies. Furthermore, RESURGE (Surgery for Recurrent Glioblastoma), a randomized phase II trial, is underway to determine the efficacy of repeat surgery in recurrent cranial GBM.2-6 Immunotherapy is thought to be a promising treatment modality, and a synergistic effect could possibly be obtained by combining with other options.6
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In contrast to cranial GBM, spinal GBM often affects younger individuals. Except in the study by Kaley et al.,7 the mean age has always been <40 years. Rapid-onset neurologic deficit is the usual clinical scenario. The thoracic cord is the most frequently affected. Outcome of spinal cord GBM is very poor, similar to cranial GBM. A high incidence of leptomeningeal involvement and cerebrospinal fluid dissemination is noted that forms an important cause of mortality in spinal GBM. In this context, some authors assert that whole-brain radiation with focal spinal radiation therapy needs to be given.8-10 In my opinion, as the extent of resection has not been shown to improve survival in spinal GBM as opposed to its cranial counterparts, aggressive resection is probably not warranted because it is associated with very high risk of producing postoperative neurologic deficits.1,8,11 However, a recent article containing a literature review on pediatric primary spinal cord GBM concluded that gross total resection followed by radiation therapy produced a better outcome than subtotal resection with radiation therapy.12 Further research would shed more light on this controversial topic. The survival rates in the study by Behmanesh et al.1 were better than all the other studies related to spinal GBM. Hence these results should provide further impetus for future high-quality studies of recurrent cranial GBM and spinal GBM in the hope of improving survival and overall outcome of these otherwise uniformly fatal neoplasms. G. Lakshmi Prasad Department of Neurosurgery, Kasturba Medical College, Manipal University, Manipal, India To whom correspondence should be addressed: G. Lakshmi Prasad, M.B.B.S., M.Ch. [E-mail: [email protected]] http://dx.doi.org/10.1016/j.wneu.2017.02.125.
REFERENCES 1. Behmanesh B, Setzer M, Konczalla J, Harter P, Quick-Weller J, Imoehl L, et al. Management of patients with primary intramedullary spinal cord glioblastoma. World Neurosurg. 2017;98:198-202. 2. Wang Y, Xing D, Zhao M, Wang J, Yang Y. The role of a single angiogenesis inhibitor in the treatment of recurrent glioblastoma multiforme: a meta-analysis and systematic review. PLoS One. 2016;11:e0152170. 3. Grisanti S, Ferrari VD, Buglione M, Agazzi GM, Liserre R, Poliani L, et al. Second line treatment of recurrent glioblastoma with sunitinib: results of a phase II study and systematic review of literature [e-pub ahead of print]. J Neurosurg Sci. 2016. 4. Zhang G, Huang S, Wang Z. A meta-analysis of bevacizumab alone and in combination with irinotecan in the treatment of patients with recurrent glioblastoma multiforme. J Clin Neurosci. 2012;19:1636-1640. 5. Holt DE, Bernard ME, Quan K, Clump DA, Engh JA, Burton SA, et al. Salvage stereotactic radiosurgery for recurrent glioblastoma multiforme with prior radiation therapy. J Cancer Res Ther. 2016;12:1243-1248. 6. Cihoric N, Tsikkinis A, Minniti G, Lagerwaard FJ, Herrlinger U, Mathier E, et al. Current status and perspectives of interventional clinical trials for glioblastoma—analysis of Clinical Trials.gov. Radiat Oncol. 2017;12:1. 7. Kaley TJ, Mondesire-Crump I, Gavrilovic IT. Temozolomide or bevacizumab for spinal cord high-grade gliomas. J Neurooncol. 2012;109:385-389. 8. Prasad GL, Borkar SA, Subbarao KC, Suri V, Mahapatra AK. Primary spinal cord glioblastoma multiforme: a report of two cases. Neurol India. 2012;60:333-335.
104: 1020-1021, AUGUST 2017 WORLD NEUROSURGERY
LETTER TO THE EDITOR
9. Raco A, Esposito V, Lenzi J, Piccirilli M, Delfini R, Cantore G. Long-term followup of intramedullary spinal cord tumors: a series of 202 cases. Neurosurgery. 2005; 56:972-981.
11. Liu A, Sankey EW, Bettegowda C, Burger PC, Jallo GI, Groves ML. Poor prognosis despite aggressive treatment in adults with intramedullary spinal cord glioblastoma. J Clin Neurosci. 2015;22:1628-1631.
10. 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;30:489-494.
12. Konar SK, Bir SC, Maiti TK, Nanda A. A systematic review of overall survival in pediatric primary glioblastoma multiforme of the spinal cord. J Neurosurg Pediatr. 2017;19:239-248.
WORLD NEUROSURGERY 104: 1020-1021, AUGUST 2017
www.WORLDNEUROSURGERY.org
1021
LETTER: he article by Behmanesh et al.,1 entitled “Management of Patients with Primary Intramedullary Spinal Cord Glioblastoma,” published in WORLD NEUROSURGERY, was read with great interest. The authors present 4 cases of spinal cord glioblastoma multiforme (GBM) managed at their institution over a 10-year period. All patients were female, and the mean age was 33.5 years (range, 14e50 years). Two tumors each were located in the cervical and thoracic region. Preoperatively, there was 1 patient each with McCormick grade IeIV. A biopsy was performed for all cases, and all patients received adjuvant radiation therapy and temozolomide. In the follow-up period, 3 patients were McCormick grade IV, and 1 patient had neurologic improvement from McCormick grade IV to McCormick grade III. All tumors progressed at a mean interval of 18.2 months (range, 6e32 months). Brain dissemination was observed in 1 case. For disease progression, 1 patient underwent additional therapy with bevacizumab, 1 patient received rapamycin and sunitinib, and the third patient received chlorethyl-cyclohexyl-nitrosourea and etoposide as additional therapy. All patients died of their disease with a median survival after diagnosis of 32.5 months. The cause of death was respiratory paralysis in 2 cases and severe pneumonia in another 2 cases. The authors concluded that although the surgical outcome of spinal cord GBM remains poor, an aggressive multimodal and interdisciplinary treatment for the disease might be associated with longer survival.
T
After a detailed analysis of this article, I have 2 concerns. First, on what basis did the authors provide different types of adjuvant therapies to their patients at the time of tumor progression? Are there any studies to support this, or was the decision based on the opinion of an oncologist on an individual case-by-case basis? Second, a mention of MIB-1 labeling index of all their cases would have been beneficial for reasons mentioned subsequently. GBM is a highly heterogeneous, high-grade central nervous system neoplasm. Surgery with adjuvant temozolomide and radiotherapy is the mainstay of treatment, and complete removal is an independent prognostic factor for survival in cranial GBM. Similarly, the MIB-1 labeling index is one of the many prognostic factors impacting the outcome. However, the prognosis remains dismal with most GBMs recurring within a short span of time and patients dying of their disease. Recent strategies for recurrent cranial GBM have included angiogenesis inhibitors (bevacizumab, sunitinib, irinotecan), stereotactic radiosurgery, and targeted molecular therapies. Furthermore, RESURGE (Surgery for Recurrent Glioblastoma), a randomized phase II trial, is underway to determine the efficacy of repeat surgery in recurrent cranial GBM.2-6 Immunotherapy is thought to be a promising treatment modality, and a synergistic effect could possibly be obtained by combining with other options.6
1020
www.SCIENCEDIRECT.com
In contrast to cranial GBM, spinal GBM often affects younger individuals. Except in the study by Kaley et al.,7 the mean age has always been <40 years. Rapid-onset neurologic deficit is the usual clinical scenario. The thoracic cord is the most frequently affected. Outcome of spinal cord GBM is very poor, similar to cranial GBM. A high incidence of leptomeningeal involvement and cerebrospinal fluid dissemination is noted that forms an important cause of mortality in spinal GBM. In this context, some authors assert that whole-brain radiation with focal spinal radiation therapy needs to be given.8-10 In my opinion, as the extent of resection has not been shown to improve survival in spinal GBM as opposed to its cranial counterparts, aggressive resection is probably not warranted because it is associated with very high risk of producing postoperative neurologic deficits.1,8,11 However, a recent article containing a literature review on pediatric primary spinal cord GBM concluded that gross total resection followed by radiation therapy produced a better outcome than subtotal resection with radiation therapy.12 Further research would shed more light on this controversial topic. The survival rates in the study by Behmanesh et al.1 were better than all the other studies related to spinal GBM. Hence these results should provide further impetus for future high-quality studies of recurrent cranial GBM and spinal GBM in the hope of improving survival and overall outcome of these otherwise uniformly fatal neoplasms. G. Lakshmi Prasad Department of Neurosurgery, Kasturba Medical College, Manipal University, Manipal, India To whom correspondence should be addressed: G. Lakshmi Prasad, M.B.B.S., M.Ch. [E-mail: [email protected]] http://dx.doi.org/10.1016/j.wneu.2017.02.125.
REFERENCES 1. Behmanesh B, Setzer M, Konczalla J, Harter P, Quick-Weller J, Imoehl L, et al. Management of patients with primary intramedullary spinal cord glioblastoma. World Neurosurg. 2017;98:198-202. 2. Wang Y, Xing D, Zhao M, Wang J, Yang Y. The role of a single angiogenesis inhibitor in the treatment of recurrent glioblastoma multiforme: a meta-analysis and systematic review. PLoS One. 2016;11:e0152170. 3. Grisanti S, Ferrari VD, Buglione M, Agazzi GM, Liserre R, Poliani L, et al. Second line treatment of recurrent glioblastoma with sunitinib: results of a phase II study and systematic review of literature [e-pub ahead of print]. J Neurosurg Sci. 2016. 4. Zhang G, Huang S, Wang Z. A meta-analysis of bevacizumab alone and in combination with irinotecan in the treatment of patients with recurrent glioblastoma multiforme. J Clin Neurosci. 2012;19:1636-1640. 5. Holt DE, Bernard ME, Quan K, Clump DA, Engh JA, Burton SA, et al. Salvage stereotactic radiosurgery for recurrent glioblastoma multiforme with prior radiation therapy. J Cancer Res Ther. 2016;12:1243-1248. 6. Cihoric N, Tsikkinis A, Minniti G, Lagerwaard FJ, Herrlinger U, Mathier E, et al. Current status and perspectives of interventional clinical trials for glioblastoma—analysis of Clinical Trials.gov. Radiat Oncol. 2017;12:1. 7. Kaley TJ, Mondesire-Crump I, Gavrilovic IT. Temozolomide or bevacizumab for spinal cord high-grade gliomas. J Neurooncol. 2012;109:385-389. 8. Prasad GL, Borkar SA, Subbarao KC, Suri V, Mahapatra AK. Primary spinal cord glioblastoma multiforme: a report of two cases. Neurol India. 2012;60:333-335.
104: 1020-1021, AUGUST 2017 WORLD NEUROSURGERY
LETTER TO THE EDITOR
9. Raco A, Esposito V, Lenzi J, Piccirilli M, Delfini R, Cantore G. Long-term followup of intramedullary spinal cord tumors: a series of 202 cases. Neurosurgery. 2005; 56:972-981.
11. Liu A, Sankey EW, Bettegowda C, Burger PC, Jallo GI, Groves ML. Poor prognosis despite aggressive treatment in adults with intramedullary spinal cord glioblastoma. J Clin Neurosci. 2015;22:1628-1631.
10. 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;30:489-494.
12. Konar SK, Bir SC, Maiti TK, Nanda A. A systematic review of overall survival in pediatric primary glioblastoma multiforme of the spinal cord. J Neurosurg Pediatr. 2017;19:239-248.
WORLD NEUROSURGERY 104: 1020-1021, AUGUST 2017
www.WORLDNEUROSURGERY.org
1021