Main Article Content
Abstract
Purpose: to study the clinical, laboratorial, and therapeutic data of patients with pilocytic astrocytomas, their predictive factors, and to propose a therapeutic strategy. Methods: Retrospective analysis of clinical files of pediatric patients followed between 1984 and 2014 in a single institution. Results: There were 48 patients (22 boys and 26 girls). Age at diagnosis varied from 6 months to 15,2 years (mean: 6,9 years). Mean follow-up was 8,9 years (6 months to 21.5 years). Twenty-five (52%) were cerebellar, 8(17%) hemispheric, 10(21%) hypothalamic-chiasmatic, and 5 (10%) midbrain. Twenty-eight tumors were solid-cystic, 9 solid, 4 cystic, and 7 unknown. Total gross resection was achieved in 17 (35%), partial resection in 27 (56%). Two patients had biopsy only and 2 were not operated on. Adjuvant therapy was performed in 17 patients (9 radiotherapy, 7 chemotherapy and 1 both therapies). Recurrence occurred in 14 patients, 8 of which remained stable after reoperation associated or not to adjuvant therapy. Significant predictor factors were gross total resection and lower age at diagnosis. Conclusions: The epidemiological and clinical data of this cohort of patients do not differ from those from distinct geographical regions. Except the extension of resection and age at diagnosis, all other parameters analyzed failed to show prognostic significance. Albeit biological behavior of residual tumors is unpredictable, most of them remain stable for many years even after a first recurrence. These tumors must be treated cautiously. Chemo and/or radiotherapy should be considered only in those cases with more than one recurrence. Keywords: Pilocytic astrocytoma, pediatric brain tumor, epidemiology, prognostic factors, treatment.
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Copyright (c) 2017 Sergio Vranjac, Sergio Rosemberg
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References
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- Rosemberg S, Fujiwara D. Epidemiology of pediatric tumors of the nervous system according to the WHO 2000 classification: a report of 1195 cases from a single institution. Childs Nerv Syst. 2005, 21:940-944.
- Becker AP, Oliveira RS, Saggioro FP, Neder L, Chimelli LMC, Machado HR: In pursuit of prognostic factors in children with pilocytic astrocytomas. Childs Nerv Syst. 2010, 26:19-28.
- Fernandez C, Figarella-Branger D, Girard N, Bouvier-Labit C, Gouvernet J, Paredes AP, Lena G: Pilocytic astrocytomas in children: Prognostic factors- a retrospective study of 80 cases. Neurosurgery.2003, 53:544-553.
- Tihan T, Ersen A, Qaddoumi I, Sughayer MA, Tolunay A, Al-Hussaini M, Phillips J, Gupta N, Goldhoff P, Baneerjee A: Pathologic Characteristics of Pediatric Intracranial Pilocytic Astrocytomas and Their Impact on Outcome in 3 Countries: A Multi-institutional Study. Am J Surg Pathol. 2012, 36: 43-55.
- Listernick R, Charrow J, Greenwald MJ, Esterly NB: Optic gliomas in children with neurofibromatosis type 1. J Pediatr. 1989, 114:788-792.
- Kleihues PDNL, Wiestler OD, Burguer PC, Scheitauer BW: WHO grading of tumors of the central nervous system. In: WHO Classification of the Central Nervous System, 4th ed. Louis DN, Ohgaki H, Wiestler OD, Cavene WK, eds. International Agency for Research on Cancer; Lyon. 2007:10-11.
- Scheitauer BW, Hawkins C, Tihan T, Vandenberg SR, Burger PC: Pilocytic astrocitoma. In: WHO Classification of the Central Nervous System, 4th ed. Louis DN; Ohgaki H, Wiestler OD, Cavene WK, eds. International Agency for Research on Cancer, Lyon. 2007:14-21.
- Desai KI, Nadkarni TD, Muzumdar DP, Goel A: Prognostic factors for cerebellar astrocytomas in chidren: A study of 102 cases. Pediatr Neurosurg 2001, 35:311-317.
- Dirven CM, Mooij JJA, Molenaar WM: Cerebellar pilocytic astrocytoma: a treatment protocol based upon analysis of 73 cases and review of the literature. Childs Nerv Syst.1997, 13:17-23.
- Due-Tonessen BJ, Helseth E, Scheie D, Skullerud K, Aamodt G, Lundar T: Long-term outcome after resection of benign cerebellar astrocytomas in children and young adults (0-19 years): Report of 110 consecutives cases. Pediatr Neurosurg.2002, 37:71-80.
- Fisher PG, Tihan T, Goldthwaite PT, Wharam MD, Carson BS, Weingart JD, Repka MX, Cohen KJ, Burger PC: Outcome analysis of childhood low-grade astrocytomas. Pediatr Blood Cancer.2008, 51(2):245-250.
- Horbinski C, Hamilton RL, Lovell C, Burnham J, Pollack IF: Impact of morphology, MIB-1, p53 and MGMT on outcome pilocytic astrocytomas. Brain Pathology. 2010,20:581-588.
- Malik A, Prabal DEB, Sharma MC, Sarkar C: Neuropathological spectrum of pilocytic astrocitoma- an Indian series of 120 cases. Pathol Oncol Res. 2006, 12:164-171.
- Tibbets KM, Emnett R, Gao F, Perry A, Gutmann DH, Leonard JR: Histopathologic predictors of pylocitic astrocytoma event-free survival. Acta Neuropathol. 2009, 117:657-665.
- Villarejo F, Diego JMB, La Riva AG: Prognosis of cerebellar astrocytomas in children. Childs Nerv Syst. 2008, 24:203-210.
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- Sharma MK, Mansur DB, Reifenberger G, Perry A, Leonard JR, Aldape KD, Albin MG, Emnett RJ, Loeser S, Watson MA, et al: Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin. Cancer Res. 2007, 67:890-900.
- Benesch M, Eder HG, Sovinz P, Raith J, Lackner H, Moser A, Urban C: Residual or recurrent cerebellar low-grade glioma in children after tumor resection: Is re-treatment needed? A single center experience from 1983 to 2003. Pediatr Neurosurg. 2006, 42:159-164.
- Hargrave D: Pediatric high and low grade glioma: the impact of tumor biology on current and future therapy. Br J Neurosurg. 2009, 23:351-363.
- Karajannis M, Allen JC, Newcomb EW: Treatment of pediatric brain tumors. J Cell Physiol. 2008, 217:584-589.
- Mueller S, Chang S: Peditaric brain tumors: Current strategies and future therapeutic approaches. Neurotherapeutics. 2009, 6:570-586.
- Qaddoumi I, Sultan I, Broniscer A: Pediatric low- grade gliomas and the need for new options for Therapy: why and how?. Cancer Biol Ther. 2009, 8:4-10.
- Sievert AJ, Fisher MJ: Pediatric low-grade gliomas. J Child Neurol. 2009, 24:1397-1408.
- Stokland T, Liu JF, Ironside JW, Ellison DW, Taylor R, Robinson KJ, Picton SV, Walker DA: A multivariate analysis of factors determining tumor progression in childhood low-grade glioma: a population-based cohort study (CCLG CNS9702). Neuro-Oncology. 2010, 12:1257-1268.
- Packer RJ, Lange B, Ater J, et al: Carboplastin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol. 1993, 11:850-856.
- Packer RJ, Lange B, Ater J, Nicholson S, Allen J, Walker R, Prados M, Jakacki R, Reaman G, Needles MN, Philips PC, Ryan J, Boyett JM, Geyer R, Finlay J: Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas. J Neurosurg. 1997, 86:747-754.
- Ronghe M, Hargrave D, Bartels U, Tabori U, Vaidya S, Chandler C, Kulkarni A, Bouffet E: Vincristine and Carboplatin Chemotherapy for Unresectable and/or Recurrent Low-Grade Astrocytoma of the Brainstem. Pediatr Blood Cancer. 2010, 55:471–477.
- Skowronka-Gardas A: A literature review of the recent radiotherapy clinical trials in pediatric brain tumors. Reviews on Recent Clinical Trial. 2009, 4:42-55.
- Wisoff JH, Sanford RA, Heier LA, Sposto R, Burger PC, Yates AJ, Holmes EJ, Kun LE : Primary Neurosurgery for Pediatric Low-Grade Gliomas: A Prospective Multi-Institutional Study From the Children’s Oncology Group. Neurosurgery. 2011, 68:1548-1555.
- -Jones DT, Kocialkowski S, Liu L, Pearson DM, Backlund LM, Ichimura K, Collins VP: Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res. 2008, 68:8673-7.
- - Sievert AJ, Jackson EM, Gai X, Hakonarson H, judkins AR, Resnick AC, Sutton LN, Storm PB, Shaikh TH, Biegel JA: Duplication of 7q34 in pediatric low-grade astrocytomas detected by high-density single-nucleotide polymorphism-based genotype arrays results in a novel BRAF fusion gene. Brain Pathol. 2009, 19:449-458.
- - Colin C, Padovani L, Chappé C, Mercurio S, Scavarda D, Loundou A, Frassineti F, Andre N, Bouvier C, Korshunov A, Lena G, Figarella-Branger D: Outcome analysis of childhood pilocytic astrocytomas: a retrospective study of 148 cases at single institution. Neuropathol Appl Neurobiol. 2013, 39:693-705.
References
CBTRUS [ http://www.cbtrus.org/2011-NPCR-SEER/WEB-0407-Report-3-3-2011.pdf ]. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2004-2007. Update February 2011.
Rosemberg S, Fujiwara D. Epidemiology of pediatric tumors of the nervous system according to the WHO 2000 classification: a report of 1195 cases from a single institution. Childs Nerv Syst. 2005, 21:940-944.
Becker AP, Oliveira RS, Saggioro FP, Neder L, Chimelli LMC, Machado HR: In pursuit of prognostic factors in children with pilocytic astrocytomas. Childs Nerv Syst. 2010, 26:19-28.
Fernandez C, Figarella-Branger D, Girard N, Bouvier-Labit C, Gouvernet J, Paredes AP, Lena G: Pilocytic astrocytomas in children: Prognostic factors- a retrospective study of 80 cases. Neurosurgery.2003, 53:544-553.
Tihan T, Ersen A, Qaddoumi I, Sughayer MA, Tolunay A, Al-Hussaini M, Phillips J, Gupta N, Goldhoff P, Baneerjee A: Pathologic Characteristics of Pediatric Intracranial Pilocytic Astrocytomas and Their Impact on Outcome in 3 Countries: A Multi-institutional Study. Am J Surg Pathol. 2012, 36: 43-55.
Listernick R, Charrow J, Greenwald MJ, Esterly NB: Optic gliomas in children with neurofibromatosis type 1. J Pediatr. 1989, 114:788-792.
Kleihues PDNL, Wiestler OD, Burguer PC, Scheitauer BW: WHO grading of tumors of the central nervous system. In: WHO Classification of the Central Nervous System, 4th ed. Louis DN, Ohgaki H, Wiestler OD, Cavene WK, eds. International Agency for Research on Cancer; Lyon. 2007:10-11.
Scheitauer BW, Hawkins C, Tihan T, Vandenberg SR, Burger PC: Pilocytic astrocitoma. In: WHO Classification of the Central Nervous System, 4th ed. Louis DN; Ohgaki H, Wiestler OD, Cavene WK, eds. International Agency for Research on Cancer, Lyon. 2007:14-21.
Desai KI, Nadkarni TD, Muzumdar DP, Goel A: Prognostic factors for cerebellar astrocytomas in chidren: A study of 102 cases. Pediatr Neurosurg 2001, 35:311-317.
Dirven CM, Mooij JJA, Molenaar WM: Cerebellar pilocytic astrocytoma: a treatment protocol based upon analysis of 73 cases and review of the literature. Childs Nerv Syst.1997, 13:17-23.
Due-Tonessen BJ, Helseth E, Scheie D, Skullerud K, Aamodt G, Lundar T: Long-term outcome after resection of benign cerebellar astrocytomas in children and young adults (0-19 years): Report of 110 consecutives cases. Pediatr Neurosurg.2002, 37:71-80.
Fisher PG, Tihan T, Goldthwaite PT, Wharam MD, Carson BS, Weingart JD, Repka MX, Cohen KJ, Burger PC: Outcome analysis of childhood low-grade astrocytomas. Pediatr Blood Cancer.2008, 51(2):245-250.
Horbinski C, Hamilton RL, Lovell C, Burnham J, Pollack IF: Impact of morphology, MIB-1, p53 and MGMT on outcome pilocytic astrocytomas. Brain Pathology. 2010,20:581-588.
Malik A, Prabal DEB, Sharma MC, Sarkar C: Neuropathological spectrum of pilocytic astrocitoma- an Indian series of 120 cases. Pathol Oncol Res. 2006, 12:164-171.
Tibbets KM, Emnett R, Gao F, Perry A, Gutmann DH, Leonard JR: Histopathologic predictors of pylocitic astrocytoma event-free survival. Acta Neuropathol. 2009, 117:657-665.
Villarejo F, Diego JMB, La Riva AG: Prognosis of cerebellar astrocytomas in children. Childs Nerv Syst. 2008, 24:203-210.
Pfister S, Janzarik WG, Remke M, Ernst A, Werft W, Becker N, Toedt G, Wittmann A, Kratz C, Olbrich H, Ahmadi R, et al: BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas. J Clin Invest. 2008, 118:1739–1749.
Sharma MK, Mansur DB, Reifenberger G, Perry A, Leonard JR, Aldape KD, Albin MG, Emnett RJ, Loeser S, Watson MA, et al: Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin. Cancer Res. 2007, 67:890-900.
Benesch M, Eder HG, Sovinz P, Raith J, Lackner H, Moser A, Urban C: Residual or recurrent cerebellar low-grade glioma in children after tumor resection: Is re-treatment needed? A single center experience from 1983 to 2003. Pediatr Neurosurg. 2006, 42:159-164.
Hargrave D: Pediatric high and low grade glioma: the impact of tumor biology on current and future therapy. Br J Neurosurg. 2009, 23:351-363.
Karajannis M, Allen JC, Newcomb EW: Treatment of pediatric brain tumors. J Cell Physiol. 2008, 217:584-589.
Mueller S, Chang S: Peditaric brain tumors: Current strategies and future therapeutic approaches. Neurotherapeutics. 2009, 6:570-586.
Qaddoumi I, Sultan I, Broniscer A: Pediatric low- grade gliomas and the need for new options for Therapy: why and how?. Cancer Biol Ther. 2009, 8:4-10.
Sievert AJ, Fisher MJ: Pediatric low-grade gliomas. J Child Neurol. 2009, 24:1397-1408.
Stokland T, Liu JF, Ironside JW, Ellison DW, Taylor R, Robinson KJ, Picton SV, Walker DA: A multivariate analysis of factors determining tumor progression in childhood low-grade glioma: a population-based cohort study (CCLG CNS9702). Neuro-Oncology. 2010, 12:1257-1268.
Packer RJ, Lange B, Ater J, et al: Carboplastin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol. 1993, 11:850-856.
Packer RJ, Lange B, Ater J, Nicholson S, Allen J, Walker R, Prados M, Jakacki R, Reaman G, Needles MN, Philips PC, Ryan J, Boyett JM, Geyer R, Finlay J: Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas. J Neurosurg. 1997, 86:747-754.
Ronghe M, Hargrave D, Bartels U, Tabori U, Vaidya S, Chandler C, Kulkarni A, Bouffet E: Vincristine and Carboplatin Chemotherapy for Unresectable and/or Recurrent Low-Grade Astrocytoma of the Brainstem. Pediatr Blood Cancer. 2010, 55:471–477.
Skowronka-Gardas A: A literature review of the recent radiotherapy clinical trials in pediatric brain tumors. Reviews on Recent Clinical Trial. 2009, 4:42-55.
Wisoff JH, Sanford RA, Heier LA, Sposto R, Burger PC, Yates AJ, Holmes EJ, Kun LE : Primary Neurosurgery for Pediatric Low-Grade Gliomas: A Prospective Multi-Institutional Study From the Children’s Oncology Group. Neurosurgery. 2011, 68:1548-1555.
-Jones DT, Kocialkowski S, Liu L, Pearson DM, Backlund LM, Ichimura K, Collins VP: Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res. 2008, 68:8673-7.
- Sievert AJ, Jackson EM, Gai X, Hakonarson H, judkins AR, Resnick AC, Sutton LN, Storm PB, Shaikh TH, Biegel JA: Duplication of 7q34 in pediatric low-grade astrocytomas detected by high-density single-nucleotide polymorphism-based genotype arrays results in a novel BRAF fusion gene. Brain Pathol. 2009, 19:449-458.
- Colin C, Padovani L, Chappé C, Mercurio S, Scavarda D, Loundou A, Frassineti F, Andre N, Bouvier C, Korshunov A, Lena G, Figarella-Branger D: Outcome analysis of childhood pilocytic astrocytomas: a retrospective study of 148 cases at single institution. Neuropathol Appl Neurobiol. 2013, 39:693-705.