Abstract
Purpose
The benefit of radical resections for glioblastoma patients remains a source of contention in the literature. Few studies have been conducted in pediatric patients, and it is becoming increasingly evident that data regarding adult glioblastoma (GB) patients cannot be generalized to pediatric patients affected by this neoplasm. A comparative effectiveness study is performed for different extent of resection (EOR) groups in the largest cohort of pediatric GB (pGB) patients.
Methods
The Surveillance, Epidemiology, and End Results (SEER) cancer registry was used to identify pGB patients from 1988 through 2009. Multivariate- and multiple propensity score (mPS)-adjusted analyses were used to determine the effect of gross total resection (GTR), partial resection (PR), and biopsy (Bx) on overall survival. Survival prospects were summarized using direct adjusted survival curves.
Results
A total of 342 pGB patients were identified, and 35.4 % of patients received a GTR, 28.8 % PR, 17.3 % Bx, and 17.0 % did not undergo surgery. In our cohort, a median overall survival of 12 months was observed with 1-, 2-, and 5-year survival rates of 51.7, 28.3, and 15.7 %, respectively. EOR was a predictor of survival in both the multivariate- (P < 0.001) and mPS-adjusted model (P < 0.001). Compared to the GTR group, a higher mortality rate was observed in patients who underwent a PR (HR 1.50; 95 % CI, 1.02–2.21) or Bx (HR 1.87; 95 % CI, 1.18–2.98). There were no significant differences in (adjusted) mortality risk between the PR and Bx groups.
Conclusion
Our study suggests that GTR is independently associated with improved survival for pediatric patients with glioblastoma.
Similar content being viewed by others
References
Aalen OO (1989) A linear regression model for the analysis of life times. Stat Med 8:907–925
Aalen OO (1993) Further results on the non-parametric linear regression model in survival analysis. Stat Med 12:1569–1588
Adams H, Avendano J, Raza SM, Gokaslan ZL, Jallo GI, Quinones-Hinojosa A (2012) Prognostic factors and survival in primary malignant astrocytomas of the spinal cord: a population-based analysis from 1973 to 2007. Spine 37:E727–E735. doi:10.1097/BRS.0b013e31824584c0
Ansari M, Nasrolahi H, Kani AA, Mohammadianpanah M, Ahmadloo N, Omidvari S, Mosalaei A (2012) Pediatric glioblastoma multiforme: a single-institution experience. Indian J Med Paediatr Oncol Off J Indian Soc Med Paediatr Oncol 33:155–160. doi:10.4103/0971-5851.103142
Artico M, Cervoni L, Celli P, Salvati M, Palma L (1993) Supratentorial glioblastoma in children: a series of 27 surgically treated cases child’s nervous system: ChNS. Off J Int Soc Pediatr Neurosurg 9:7–9
Bohinski RJ, Kokkino AK, Warnick RE, Gaskill-Shipley MF, Kormos DW, Lukin RR, Tew JM Jr (2001) Glioma resection in a shared-resource magnetic resonance operating room after optimal image-guided frameless stereotactic resection. Neurosurgery 48:731–742 discussion 742-734
Byeon SJ, Myung JK, Kim SH, Kim SK, Phi JH, Park SH (2012) Distinct genetic alterations in pediatric glioblastomas Child’s Nervous System: ChNS. Off J Int Soc Pediatr Neurosurg 28:1025–1032. doi:10.1007/s00381-012-1773-1
Chastagner P, Kalifa C, Doz F, Bouffet E, Gentet JC, Ruchoux MM, Bracard S, Desandes E, Frappaz D (2007) Outcome of children treated with preradiation chemotherapy for a high-grade glioma: results of a French Society of Pediatric Oncology (SFOP) pilot study. Pediatr Blood Cancer 49:803–807. doi:10.1002/pbc.21051
Cohen KJ, Pollack IF, Zhou T, Buxton A, Holmes EJ, Burger PC, Brat DJ, Rosenblum MK, Hamilton RL, Lavey RS, Heideman RL (2011) Temozolomide in the treatment of high-grade gliomas in children: a report from the Children's Oncology Group. Neuro-Oncology 13:317–323. doi:10.1093/neuonc/noq191
Das KK, Mehrotra A, Nair AP, Kumar S, Srivastava AK, Sahu RN, Kumar R (2012) Pediatric glioblastoma: clinico-radiological profile and factors affecting the outcome Child’s Nervous System: ChNS. Off J Int Soc Pediatr Neurosurg 28:2055–2062. doi:10.1007/s00381-012-1890-x
Dohrmann GJ, Farwell JR, Flannery JT (1976) Glioblastoma multiforme in children. J Neurosurg 44:442–448. doi:10.3171/jns.1976.44.4.0442
Dolecek TA, Propp JM, Stroup NE, Kruchko C (2012) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro-Oncology 14(Suppl 5):v1–49. doi:10.1093/neuonc/nos218
Fouladi M, Hunt DL, Pollack IF, Dueckers G, Burger PC, Becker LE, Yates AJ, Gilles FH, Davis RL, Boyett JM, Finlay JL (2003) Outcome of children with centrally reviewed low-grade gliomas treated with chemotherapy with or without radiotherapy on Children's Cancer Group high-grade glioma study CCG-945. Cancer 98:1243–1252. doi:10.1002/cncr.11637
Gorlia T, van den Bent MJ, Hegi ME, Mirimanoff RO, Weller M, Cairncross JG, Eisenhauer E, Belanger K, Brandes AA, Allgeier A, Lacombe D, Stupp R (2008) Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. Lancet Oncol 9:29–38. doi:10.1016/S1470-2045(07)70384-4
Hammoud MA, Ligon BL, elSouki R, Shi WM, Schomer DF, Sawaya R (1996) Use of intraoperative ultrasound for localizing tumors and determining the extent of resection: a comparative study with magnetic resonance imaging. J Neurosurg 84:737–741. doi:10.3171/jns.1996.84.5.0737
Hardesty DA, Sanai N (2012) The value of glioma extent of resection in the modern neurosurgical era. Front Neurol 3:140. doi:10.3389/fneur.2012.00140
Imbens G (2000) The role of the propensity score in estimating dose-response functions. Biometrika 87:706–710. doi:10.1093/biomet/87.3.706
Kallappagoudar S, Yadav RK, Lowe BR, Partridge JF (2015) Histone H3 mutations—a special role for H3.3 in tumorigenesis? Chromosoma 124:177–189. doi:10.1007/s00412-015-0510-4
Kramm CM, Wagner S, Van Gool S, Schmid H, Strater R, Gnekow A, Rutkowski S, Wolff JE (2006) Improved survival after gross total resection of malignant gliomas in pediatric patients from the HIT-GBM studies. Anticancer Res 26:3773–3779
Lesniak MS, Klem JM, Weingart J, Carson BS Sr (2003) Surgical outcome following resection of contrast-enhanced pediatric brainstem gliomas. Pediatr Neurosurg 39:314–322
MacDonald TJ, Aguilera D, Kramm CM (2011) Treatment of high-grade glioma in children and adolescents. Neuro-Oncology 13:1049–1058. doi:10.1093/neuonc/nor092
Mahvash M, Hugo HH, Maslehaty H, Mehdorn HM, Stark AM (2011) Glioblastoma multiforme in children: report of 13 cases and review of the literature. Pediatr Neurol 45:178–180. doi:10.1016/j.pediatrneurol.2011.05.004
Nikitovic M, Stanic D, Pekmezovic T, Gazibara MS, Bokun J, Paripovic L, Grujicic D, Saric M, Miskovic I (2015) Pediatric glioblastoma: a single institution experience. Child’s Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery doi:10.1007/s00381-015-2945-6
Ononiwu C, Mehta V, Bettegowda C, Jallo G (2012) Pediatric spinal glioblastoma multiforme: current treatment strategies and possible predictors of survival Child’s Nervous System: ChNS. Off J Int Soc Pediatr Neurosurg 28:715–720. doi:10.1007/s00381-012-1705-0
Paugh BS, Qu C, Jones C, Liu Z, Adamowicz-Brice M, Zhang J, Bax DA, Coyle B, Barrow J, Hargrave D, Lowe J, Gajjar A, Zhao W, Broniscer A, Ellison DW, Grundy RG, Baker SJ (2010) Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J Clin Oncol Off J Am Soc Clin Oncol 28:3061–3068. doi:10.1200/JCO.2009.26.7252
Perkins SM, Rubin JB, Leonard JR, Smyth MD, El Naqa I, Michalski JM, Simpson JR, Limbrick DL, Park TS, Mansur DB (2011) Glioblastoma in children: a single-institution experience. Int J Radiat Oncol Biol Phys 80:1117–1121. doi:10.1016/j.ijrobp.2010.03.013
Rickert CH, Strater R, Kaatsch P, Wassmann H, Jurgens H, Dockhorn-Dworniczak B, Paulus W (2001) Pediatric high-grade astrocytomas show chromosomal imbalances distinct from adult cases. Am J Pathol 158:1525–1532. doi:10.1016/S0002-9440(10)64103-X
Rizzo D, Ruggiero A, Martini M, Rizzo V, Maurizi P, Riccardi R (2015) Molecular biology in pediatric high-grade glioma: impact on prognosis and treatment. BioMed Res Int 2015:215135. doi:10.1155/2015/215135
Rosenbaum PR, Rubin DB (1983) The central role of the propensity score in observational studies for causal effects. Biometrika 70:41–55
Sanai N, Berger MS (2008) Glioma extent of resection and its impact on patient outcome. Neurosurgery 62:753–764 discussion 264-756. doi:10.1227/01.neu.0000318159.21731.cf
Sanchez-Herrera F, Castro-Sierra E, Gordillo-Dominguez LF, Vaca-Ruiz MA, Santana-Montero B, Perezpena-Diazconti M, Gonzalez-Carranza V, Torres-Garcia S, Chico-Ponce de Leon F (2009) Glioblastoma multiforme in children: experience at Hospital Infantil de Mexico Federico Gomez Child’s Nervous System: ChNS. Off J Int Soc Pediatr Neurosurg 25:551–557. doi:10.1007/s00381-008-0780-8
Song KS, Phi JH, Cho BK, Wang KC, Lee JY, Kim DG, Kim IH, Ahn HS, Park SH, Kim SK (2010) Long-term outcomes in children with glioblastoma. J Neurosurg Pediatr 6:145–149. doi:10.3171/2010.5.PEDS09558
Spreeuwenberg MD, Bartak A, Croon MA, Hagenaars JA, Busschbach JJ, Andrea H, Twisk J, Stijnen T (2010) The multiple propensity score as control for bias in the comparison of more than two treatment arms: an introduction from a case study in mental health. Med Care 48:166–174. doi:10.1097/MLR.0b013e3181c1328f
Suri V, Das P, Pathak P, Jain A, Sharma MC, Borkar SA, Suri A, Gupta D, Sarkar C (2009) Pediatric glioblastomas: a histopathological and molecular genetic study. Neuro-Oncology 11:274–280. doi:10.1215/15228517-2008-092
Vanan MI, Eisenstat DD (2014) Management of high-grade gliomas in the pediatric patient: past, present, and future. Neuro-Oncol Practice 1:145–157. doi:10.1093/nop/npu022
Walston S, Hamstra DA, Oh K, Woods G, Guiou M, Olshefski RS, Chakravarti A, Williams TM (2015) A multi-institutional experience in pediatric high-grade glioma. Front Oncol 5:28. doi:10.3389/fonc.2015.00028
Wisoff JH, Boyett JM, Berger MS, Brant C, Li H, Yates AJ, McGuire-Cullen P, Turski PA, Sutton LN, Allen JC, Packer RJ, Finlay JL (1998) Current neurosurgical management and the impact of the extent of resection in the treatment of malignant gliomas of childhood: a report of the Children’s Cancer Group trial no. CCG-945. J Neurosurg 89:52–59. doi:10.3171/jns.1998.89.1.0052
Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J, Qu C, Ding L, Huether R, Parker M, Zhang J, Gajjar A, Dyer MA, Mullighan CG, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Ellison DW, Baker SJ (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44:251–253. doi:10.1038/ng.1102
Yang T, Temkin N, Barber J, Geyer JR, Leary S, Browd S, Ojemann JG, Ellenbogen RG (2012) Gross total resection correlates with long-term survival in pediatric patients with glioblastoma. World Neurosurgery doi:10.1016/j.wneu.2012.09.015
Yang T, Temkin N, Barber J, Geyer JR, Leary S, Browd S, Ojemann JG, Ellenbogen RG (2013) Gross total resection correlates with long-term survival in pediatric patients with glioblastoma. World Neurosurg 79:537–544. doi:10.1016/j.wneu.2012.09.015
Zhang X, Akcin H (2012) A SAS macro for direct adjusted survival curves based on Aalen’s additive model. Comput Methods Prog Biomed 108:310–317. doi:10.1016/j.cmpb.2012.01.003
Author contributions
HA and AQH had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. HA is supported by The Prins Bernhard Fonds. AQH is supported by the Howard Hughes Medical Institute (HHMI). The author Jordina Rincon-Torroella is a grant holder for Fundacio “La Caixa” fellowship.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript.
Funding
HA supported by The Prins Bernhard Fonds. AQH supported by the Howard Hughes Medical Institute (HHMI).
Electronic supplementary material
Online Resource 1
(DOC 45 kb)
ESM 2
(GIF 20 kb)
Online Resource 2
– Figure legend (DOC 27 kb)
Online Resource 2
- Results (DOC 41 kb)
ESM 5
(PDF 775 kb)
Rights and permissions
About this article
Cite this article
Adams, H., Adams, H.H.H., Jackson, C. et al. Evaluating extent of resection in pediatric glioblastoma: a multiple propensity score-adjusted population-based analysis. Childs Nerv Syst 32, 493–503 (2016). https://doi.org/10.1007/s00381-015-3006-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00381-015-3006-x