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Original Article

Outcome of supratentorial intraaxial extra ventricular primary pediatric brain tumors: A prospective study

Mohana Rao Patibandla, Suchanda Bhattacharjee1, Megha S. Uppin2, Aniruddh Kumar Purohit1 Department of , Krishna Institute of Medical Sciences Secunderabad, Departments of 1Neurosurgery and 2Pathology, Nizam’s Institute of Medical Sciences, Hyderabad, Andhra Pradesh, India

Address for correspondence: Dr. Mohana Rao Patibandla, Department of Neurosurgery, University of Colorado Denver, 13123, E 16th Ave, Aurora, CO 80045, USA. Email: [email protected]

ABSTRACT

Introduction: Tumors of the central (CNS) are the second most frequent malignancy of childhood and the most common solid tumor in this age group. CNS tumors represent approximately 17% of all malignancies in the pediatric age range, including adolescents. Glial in children account for up to 60% of supratentorial intraaxial tumors. Their histological distribution and prognostic features differ from that of adults. Aims and Objectives: To study clinical and pathological characteristics, and to analyze the outcome using the Engel’s classification for , Karnofsky’s score during the available follow‑up period of minimum 1 year following the surgical and adjuvant therapy of supratentorial intraaxial extraventricular primary pediatric (SIEPP) brain tumors in children equal or less than 18 years. Materials and Methods: The study design is a prospective study done in NIMS from October 2008 to January 2012. All the patients less than 18 years of age operated for SIEPP brain tumors proven histopathologically were included in the study. All the patients with recurrent or residual primary tumors or secondaries were excluded from the study. Post operative CT or magnetic resonance imaging (MRI) is done following . Results and Analysis: There were 2, 8 and 20 patients in the age range of 0-2 years, >2‑10 years and 10‑18 years, respectively. There were 21 male patients and 9 female patients. Out of 30 patients, 16 had lesion in the temporal lobe, 6 in frontal lobe, 4 in thalamus, 3 in parietal lobe and 1 in occipital lobe. Out of 30 patients, 11 patients had malignant lesions and nineteen patients had benign lesions. Gross total excision could be achieved in 19 patients and subtotal in 11 patients. Seven patients had mortality and four of the remaining 23 patients had increased deficits postoperatively. Remaining 19 patients either improved or remained same. Conclusions: SIEPP brain tumors have male preponderance, occur in 95% of patients in the age range of 7-18 years and have temporal lobe as the most common site of origin. The presentation has good outcome compared to raised features. The seizure control is quite good irrespective of subtotal or gross total excision in temporal lobe low grade tumors. All PNETs have survival of less than 1 year even with adjuvant chemo and radiotherapy.

Key words: Brain tumors, extraventricular, intraaxial, outcome, pediatric, supratentorial

Introduction

Access this article online Tumors of the (CNS) are, as a group, Quick Response Code: the second most frequent malignancy of childhood and the Website: most common solid tumor in this age group. CNS tumors www.pediatricneurosciences.com represent approximately 17% of all malignancies in the pediatric age range, including adolescents.[1] DOI: 10.4103/1817-1745.147571 Glial neoplasms in children account for up to 60% of supratentorial hemispheric tumors. They encompass a

216 / Journal of Pediatric Neurosciences / Volume 9 / Sep-Dec / 2014 Patibandla, et al.: Supratentorial intra axial pediatric brain tumors diverse range of pathology, including pilocytic and fibrillary Results and Analysis , , , and , as well as less common lesions unique to the There were 2, 8 and 20 patients in the age range of 0-2 years, pediatric age group: pleomorphic xanthoastrocytoma (PXA), >2‑10 years and 10‑18 years, respectively. There were 21 male dysembryoplastic neuroepithelial tumor (DNET), and patients and 9 female patients. Five patients presented with desmoplastic infantile (DIG). Their histologic . Twelve of them presented with seizures. Four of distribution and prognostic features differ from that of adults, them had only and 14 patients had raised ICP. Out because the majority of these tumors in children are low of 30 patients, 16 had lesion in the temporal lobe, 6 had in the grade (up to 80% of supratentorial tumors), and a strong frontal lobe, 4 in thalamus, 3 in the parietal lobe and 1 in the association exists between extent of surgical resection and occipital lobe. Out of 30 patients, 11 patients had malignant patient outcome.[2] lesions, among them multiforme (GBM), primitive neuroectodermal tumor (PNET), anaplastic Many supratentorial are also found deep, near midline (AA) and anaplastic (AE) were structures as opposed to a more common lobar location present in 4, 4, 2 and 1, respectively. Nineteen patients had in adults. Radiologically, pediatric low‑grade gliomas also benign lesions, among them 5, 1, 1, 1, 2, 2, 4, and 3 were pilocytic differ in that they often enhance with contrast, and this astrocytoma (PA), pilomyxoid astrocytoma (PMA), fibrillary enhancement does not suggest that these neoplasms are astrocytoma (FA) (OLIGO), pleomorphic malignant.[2] xanthoastrocytoma (PXA), ependymoma (EPEN), dysembryoplastic neuroepithelial tumor (DNET), and In the supratentorial compartment, low‑grade gliomas in ganglioglioma, respectively. Gross total excision could be children can arise not only from the hemisphere but also achieved in 19 patients and subtotal in 11 patients [Figure 1, from optic nerve, chiasm, and visual pathways, as well as Table 1]. Seven patients had mortality and among them deep seated regions like hypothalamus, thalamus, and basal three had PNET, three had GBM and one had pleomorphic ganglia. xanthoastrocytoma. Four of the remaining 23 patients had increased deficits postoperatively. Remaining 19 patients either improved or remained the same. Aims and Objectives To study clinical and pathological characteristics of Discussion supratentorial intraaxial extraventricular primary pediatric (SIEPP) brain tumors in children equal or less than Total number of patients with gliomas in this study was 22. 18 years. To analyze factors that affect outcome following Of the 22 patients, 15 were astrocytomas, 3 ependymomas, management of these tumors. To determine the outcome using 1 oligodendroglioma, 3 gangliogliomas. Seventeen of the the Engel’s classification for seizures, Karnofsky’s score during 22 patients were males and females were 5 only. the available follow‑up period of minimum 1 year following Except one all (n = 22) patients (95%) were in the age range surgery and adjuvant treatment of these tumors. of 7-18 years. This could be multifactorial like the lesion incidence increases with age. Also, the referral pattern to our institute might have affected the age range of the patients Materials and Methods because usually the infant patient population is referred to the pediatric hospitals close to our area e.g. Govt. Pediatrics The study design is a prospective study done in Nizam’s Hospital etc., Seventeen of the 22 glioma patients were males Institute of Medical Sciences from October 2008 to January and only 5 were females. Contrary to the existing western 2012. All the patients with age less than 18 years operated literature,[1] social factors in the Indian population may have for SIEPP brain tumors proven histopathologically were included in the study. All the patients with recurrent or residual primary tumors or secondaries were excluded from  the study.   The patients were evaluated with complete neurological  examination and radiologically with CT and MRI studies.  In the surgery, if greater than 90% of the lesion was  WRWDO excised, it was considered as gross total excision and  VXEWRWDO O $ F 0 $ )$ others were considered subtotal excision. $$ 3; *% 31(7 30 and radiotherapy were given specific to the lesion. In '1(7 the follow up patients were assessed at the end of the JDJQOLR st rd th $(RFFLSLWD 1 month, 3 month, 6 month, and 1 year and then each 3$WKDODPL 3$WHPSRUDO year following surgery. Postoperative CT or MRI was done HSHQG\PRPD« following surgery. Figure 1: Extent of excision vs pathology

2014 / Sep-Dec / Volume 9 / Journal of Pediatric Neurosciences / 217 Patibandla, et al.: Supratentorial intra axial pediatric brain tumors

Table 1: Extent of excision vs pathology depends upon site of the lesion and age of the patient. Most of the high grade tumors occur in the cerebrum and Pathology Sub total Total Outcome brainstem and in the age group more than 5 years.[1] In DNET 0 4 Engel I KPS‑100 this study, out of the 22 gliomas, high grade lesions were PNET 4 0 3 died and 1 lost for 7 (32%), and low grade lesions were 15 (68%). In our study, follow up six of the seven high grade glioma patients were in the age GBM 3 1 3 died, 1 no recurrence range of 8-17 years. This incidence correlates with other KPS‑100 studies.[1] The percentage of high grade gliomas and age PA thalamic 2 0 No recurrence KPS‑80 representation in the present study correlates with other PA temporal 1 2 No recurrence studies. KPS‑100 PXA 2 1 1 died, 2 no recurrence The extent of surgery and grade of the lesion have the KPS‑90 major impact in survival of pediatric high grade gliomas, Pilomyxoid 1 0 1 recurrence astrocytoma KPS‑80 which is proved in the largest series of Qaddoumi et al. and Ependymoma frontal, 2 0 Engel I the Children’s Cancer Group (CCG) – 43, and CCG – 945 thalamic patients.[1] The better survival of the high grade glioma Anaplastic 0 1 No recurrence, Engel I patients with gross total resection is also confirmed in our ependymoma occipital study as shown in the literature. In the present study, of the Ganglioglioma 1 2 Engel I 2 0 Engel I seven high grade lesions, gross total excision was done in two Fibrillary astrocytoma 0 1 Engel I patients and subtotal excision was done in rest of the five PA: , PMA: Pilomyxoid astrocytoma, FA: Fibrillary astrocytoma, patients. All the patients were administered chemotherapy AA: Anaplastic astrocytoma, GBM: Glioblastoma, OLIGO: Oligodendroglioma, and six of the patients with age more than or equal to 8 years EPEN: Ependymoma, DNET: Dysembryoplastic neuroepithelial tumor, GN: Ganglioglioma, PXA: Pleomorphic xanthoastrocytoma, PNET: Primitive received radiotherapy. Three of the five patients in whom neuroectodermal tumor subtotal excision was done died within 1 year follow up. Mortality in this subset of patients (3/7) is 43%. The other contributed to this finding in our study. Contrary to the two patients with subtotal excision treated with radiotherapy literature where the frontal lobe is the most common site in (RT) and chemotherapy (CT) had recurrence in 1 year. No our study, the temporal lobe is the most common site of the recurrence of the lesion was noticed in the two patients who gliomas origin as seen in 50% of the 22 glioma patients.[1] underwent gross total excision and postoperative RT at the end of 1 year follow up. Of the five pilocytic astrocytomas, three of them were present in the temporal lobe; the other two were in the Of the 15 patients with low grade gliomas (62%), gross total thalamic region. The only patient with PMA originated excision was achieved in six patients and subtotal excision in the thalamus. The two patients with PXA were located was done in the remaining nine patients. One patient died in the temporoparietal region. All the three patients of at 1 year of the follow‑up period (PXA). Mortality in this ganglioglioma originated in the temporal lobe. Temporal lobe subset of patients (1/15) is 7%. One patient got recurrence is the most common site of the glioma origin as seen in the 10 months after the subtotal excision of the PMA in the left 11 of the 22 glioma patients (50%) in our study. thalamus. Remaining 13 patients with low‑grade gliomas, whether total or subtotal excision was performed, are doing In the published medical literature, astrocytomas account well at the end of the follow‑up period of maximum 3 years. for approximately 50% of hemispheric tumors in children, Further follow up of these patients will determine the status occurring at all ages, with a peak incidence between ages 8 of the lesion and outcome of the surgery. and 12. There is no gender predilection.[1] Outcome of low grade gliomas is better than that of high‑grade In this study, the number of patients with astrocytomas was 15 gliomas in this study as already proved in many other studies. constituting 50% of the total study group. There were 12 male The mortality was 7% compared to 43% to latter. The and 3 female patients having astrocytoma. The incidence of recurrence rate is also less in the low‑grade glioma patients. As astrocytoma increases with age as noted in this study. 1, 3 per Qaddoumi et al.,(n = 3419), low grade gliomas represent and 11 patients were with age ranging from 0-2, 2-10 and 55.5% of pediatric gliomas and grade I lesions showed 11-18 years, respectively. Fourteen of the 15 patients were better survival than grade II lesions in all age groups except within 8-18 years age range. There is no preference to side of among infants.[1] Reports of the prognostic value of grade I the cerebrum. As per the location of the lesion, the temporal versus grade II LGG are inconsistent. Some studies have lobe is the most common location of the lesion constituting 7 found no difference in outcome between grades I and II,[2‑4] of the 15 lesions. The other locations are frontal lobe (n = 4) possibly because of the small number of subjects. A larger and thalamus (n = 4). study (n = 278) showed that tumor grade (after pathology review) significantly influenced survival estimates, which were As per Qaddoumi et al., (n = 3419), high grade gliomas 92% for PA, 86% for glioma not otherwise specified, and 48% represent 17% of pediatric gliomas and their frequency for diffuse astrocytoma (P < 0.0001).[5‑8] 218 / Journal of Pediatric Neurosciences / Volume 9 / Sep-Dec / 2014 Patibandla, et al.: Supratentorial intra axial pediatric brain tumors

However, the optimal surgical treatment for children occur in 95% of patients in the age range of 7-18 years and suffering from associated with temporal‑lobe tumors have temporal lobe as the most common site of origin. The remains controversial.[9‑14] Some authors consider complete seizure presentation has good outcome compared to raised tumor resection alone as an adequate treatment,[11‑14] intracranial pressure features. The seizure control is quite whereas others recommend the additional removal of good irrespective of subtotal or gross total excision in temporal epileptogenic surrounding brain tissue to provide a good lobe low grade tumors. All PNETs with subtotal excision have seizure outcome.[15‑17] While some investigators[17] reported survival of less than 1 year even with adjuvant chemo and significant seizure control following radical tumor removal. radiotherapy. From a surgical point of view, another controversial issue is the resection of mesial temporal structures in addition to the tumor removal. Whether the additional vital brain tissue References resection improves the outcome significantly or not continues to be a matter of debate. In our study, all the temporal 1. Qaddoumi I, Sultan I, Gajjar A. Outcome and prognostic features low‑grade gliomas with seizures as presenting symptom were in pediatric gliomas: A review of 6212 cases from the surveillance, completely seizure free at an average follow‑up of 2.4 years. epidemiology, and end results database. Cancer 2009;115:5761‑70. 2. Rivera‑Luna R, Zapata‑Tarrés M, Medina‑Sansón A, Seizure‑free outcomes were good irrespective of subtotal or López‑Aguilar E, Niembro‑Zúñiga A, Amador Zarco J, et al. Long‑term gross total excision in temporal lobe tumors, correlating with survival in children under 3 years of age with low‑grade astrocytoma. [18] other studies. Childs Nerv Syst 2007;23:543‑7. 3. Prados MD, Edwards MS, Rabbitt J, Lamborn K, Davis RL, Levin VA. Regarding the site of origin of DNET, initial reports Treatment of pediatric low‑grade gliomas with a nitrosourea‑based suggested the location of the tumor to be in temporal lobe multiagent chemotherapy regimen. J Neurooncol 1997;32:235‑41. in 60% of the cases.[19] However, others reported 80-90% 4. Packer RJ, Ater J, Allen J, Phillips P, Geyer R, Nicholson HS, temporal lobe location.[20] All of the four patients of the et al. Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low‑grade gliomas. J Neurosurg present study had the location in the temporal lobe. The 1997;86:747‑54. male and female ratio was 1:1. Age range of this subset of 5. Fisher PG, Tihan T, Goldthwaite PT, Wharam MD, patients was 9 to 17 years. In the literature, surgery is the Carson BS, Weingart JD, et al. Outcome analysis of childhood low‑grade only required therapy and multiple are a better astrocytomas. Pediatr Blood Cancer 2008;51:245‑50. alternative than CT or RT. All the patients in the present 6. Sievert AJ, Fisher MJ. Pediatric low‑grade gliomas. J Child Neurol study were operated by gross total excision. All of them 2009;24:1397‑408. were doing well at the end of one year with good control of 7. Gajjar A, Sanford RA, Heideman R, Jenkins JJ, Walter A, Li Y, et al. seizures (Engel 1). Low‑grade astrocytoma: A decade of experience at St. Jude Children’s Research Hospital. J Clin Oncol 1997;15:2792‑9. 8. Fisher BJ, Leighton CC, Vujovic O, Macdonald DR, Stitt L. Results of In the present study, the gender ratio was 1:1. Age range a policy of surveillance alone after surgical management of pediatric was 1-14 years. Two patients were within 0-2 years range. low grade gliomas. Int J Radiat Oncol Biol Phys 2001;51:704‑10. Other two were 9 years and 14 years of age. Subtotal excision 9. Kim SK, Wang KC, Hwang YS, Kim KJ, Cho BK. Intractable epilepsy could be achieved in all the patients. Postoperatively, the two associated with brain tumors in children: Surgical modality and patients within 0-2 years range were given CT. The other two outcome. Childs Nerv Syst 2001;17:445‑52. patients were given both CT and RT. All four patients died 10. Blümcke I, Wiestler OD. Gangliogliomas: An intriguing tumor within one year follow up. These study findings are correlating entity associated with focal . J Neuropathol Exp Neurol with the existing studies in the literature.[21] 2002;61:575‑84. 11. Clusman H, Kral T, Gleissner U, Sassen R, Urbach H, Blümcke I, et al. Analysis of different types of resection for pediatric patients with Future suggestions to improve study . Neurosurgery 2004;54:847‑60. More number of patients to be involved in each subset of 12. Hammond RR, Duggal N, Woulfe JM, Girvin JP. Malignant transformation of a dysembryoplastic neuroepithelial tumor: Case patients including those below 7 years of age. Volumetric report. J Neurosurg 2000;92:722‑5. analysis depicting objective evidence of extent of tumor 13. Johnson JH Jr, Hariharan S, Berman J, Sutton LN, Rorke LB, Molloy P, excision is more scientific than the personal opinion of et al. Clinical outcome of pediatric gangliogliomas: Ninety‑nine cases operating surgeon and may be included in future studies. over 20 years. Pediatr Neurosurg 1997;27:203‑7. Low grade gliomas require long‑term follow up for better 14. Montes JL, Rosenblatt B, Farmer JP O’Gorman AM, Andermann F, insight into the natural and intervened progression/regression. Walters GV, et al. Lesionectomy of MRI detected lesions in children Pediatric CNS tumor registry has to be formulated for better with epilepsy. Pediatr Neurosurg 1995;22:167‑73. analysis of natural history. 15. Aronica E, Leenstra S, van Veelen CW, van Rijen PC, Hulsebos TJ, Tersmette AC, et al. Glioneuronal tumors and medically intractable epilepsy: A clinical study with long‑term follow‑up of seizure outcome after surgery. Epilepsy Res 2001;43:179‑91. Conclusions 16. Sutten LN, Packer RJ, Rorke LB, Bruce DA, Schut L. Cerebral gangliogliomas during childhood. Neurosurgery 1983;13:124‑8. Supratentorial intraaxial extraventricular primary 17. Morris HH, Matkovic Z, Estes ML, Prayson RA, Comair YG, pediatric (SIEPP) brain tumors have male preponderance, Turnbull J, et al. Ganglioglioma and intractable epilepsy: Clinical and

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neurophysiologic features and predictors of outcome after surgery. 21. Dai AI, Backstrom JW, Bruger PC, Duffner PK. Supratentorial primitive Epilepsia 1998;39:307‑13. neuroectodermal tumors of infancy: Clinical and radiologic findings. 18. Sankhla S, Khan GM. Surgical management of epilepsy associated with Pediatr Neurol 2003;29:430‑4. temporal lobe tumors. J Pediatr Neurosci 2008;3:121‑5. 19. Raymond AA, Halpin SF, Alsanjari N, Cook MJ, Kitchen ND, Fish DR, Cite this article as: Patibandla MR, Bhattacharjee S, Uppin MS, Purohit et al. Dysembryosplastic neuroepithelial tumor. Features in 16 patients. AK. Outcome of supratentorial intraaxial extra ventricular primary pediatric Brain 1994;117:461‑75. brain tumors: A prospective study. J Pediatr Neurosci 2014;9:216-20. 20. Daumas‑Duport C. Dysembryoplastic neuroepithelial tumours. Brain Source of Support: Nil. Conflict of Interest: None declared. Pathol 1993;3:283‑95.

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