Genetic and histopathological associations with outcome in pediatric pilocytic astrocytoma

View More View Less
  • 1 Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri;
  • | 2 South Georgia Medical Center, Valdosta, Georgia;
  • | 3 Department of Neuroscience, Washington University School of Medicine, St. Louis;
  • | 4 Department of Pediatrics, Washington University School of Medicine, Division of Hematology and Oncology, St. Louis;
  • | 5 Department of Radiation Oncology, Washington University School of Medicine, St. Louis;
  • | 6 Department of Radiology, Washington University School of Medicine, St. Louis; and
  • | 7 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
Print or Print + Online Sign in

OBJECTIVE

Pilocytic astrocytomas (PAs) have a generally favorable prognosis; however, progression or recurrence after resection is possible. The prognostic value of histopathological qualifiers (defined below) or BRAF alterations is not well understood. The aim of this study was to identify the prognostic value of genetic and histopathological features of pediatric PAs.

METHODS

Patients treated for a WHO grade I PA at a single institution were analyzed for histopathological and genetic features and outcomes. “Histopathological qualifier” refers to designations such as "WHO grade I PA with increased proliferative index." BRAF alterations include gene fusions and point mutations. Patients with neurofibromatosis type 1 were excluded.

RESULTS

A total of 222 patients were analyzed (51% female, mean age 9.6 years). Tumors were located in the cerebellum/fourth ventricle (51%), optic pathway/hypothalamus (15%), brainstem (12%), and cerebral cortex (11%). BRAF alterations were screened for in 77 patients and identified in 56 (73%). Histopathological qualifiers were present in 27 patients (14%). Resection was performed in 197 patients (89%), 41 (21%) of whom displayed tumor progression or recurrence after resection. Tumor progression or recurrence was not associated with histopathologic qualifiers (p = 0.36) or BRAF alterations (p = 0.77). Ki-67 proliferative indices were not predictive of progression or recurrence (p = 0.94). BRAF alterations, specifically KIAA1549 fusions, were associated with cerebellar/fourth ventricular tumor location (p < 0.0001) and younger patient age (p = 0.03). Patients in whom gross-total resection was achieved had lower rates of progression and recurrence (p < 0.0001).

CONCLUSIONS

Histopathological features/qualifiers and BRAF alterations were not associated with tumor recurrence/progression in pediatric PAs. The extent of resection was the only factor analyzed that predicted outcome.

ABBREVIATIONS

EGB = eosinophilic granular body; EOR = extent of resection; GTR = gross-total resection; NTR = near-total resection; PA = pilocytic astrocytoma; PFS = progression-free survival; STR = subtotal resection.

Supplementary Materials

    • Supplemental Table 1 (PDF 449 KB)

Diagram from Behbahani et al. (pp 488–496).

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
  • 1

    Udaka YT, Packer RJ. Pediatric brain tumors. Neurol Clin. 2018;36(3):533556.

  • 2

    Burkhard C, Di Patre PL, Schüler D, Schüler G, Yaşargil MG, Yonekawa Y, et al. A population-based study of the incidence and survival rates in patients with pilocytic astrocytoma. J Neurosurg. 2003;98(6):11701174.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Collins VP, Jones DT, Giannini C. Pilocytic astrocytoma: pathology, molecular mechanisms and markers. Acta Neuropathol. 2015;129(6):775788.

  • 4

    Salles D, Laviola G, Malinverni ACM, Stávale JN. Pilocytic astrocytoma: a review of general, clinical, and molecular characteristics. J Child Neurol. 2020;35(12):852858.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Rodriguez FJ, Lim KS, Bowers D, Eberhart CG. Pathological and molecular advances in pediatric low-grade astrocytoma. Annu Rev Pathol. 2013;8:361379.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Johnson DR, Brown PD, Galanis E, Hammack JE. Pilocytic astrocytoma survival in adults: analysis of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. J Neurooncol. 2012;108(1):187193.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Giannini C, Scheithauer BW, Burger PC, Christensen MR, Wollan PC, Sebo TJ, et al. Cellular proliferation in pilocytic and diffuse astrocytomas. J Neuropathol Exp Neurol. 1999;58(1):4653.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Ohgaki H, Kleihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol. 2005;64(6):479489.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Sievert AJ, Fisher MJ. Pediatric low-grade gliomas. J Child Neurol. 2009;24(11):13971408.

  • 10

    Bowers DC, Gargan L, Kapur P, Reisch JS, Mulne AF, Shapiro KN, et al. Study of the MIB-1 labeling index as a predictor of tumor progression in pilocytic astrocytomas in children and adolescents. J Clin Oncol. 2003;21(15):29682973.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Smith JS, Chang EF, Lamborn KR, Chang SM, Prados MD, Cha S, et al. Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol. 2008;26(8):13381345.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Maharaj A, Manoranjan B, Verhey LH, Fleming AJ, Farrokhyar F, Almenawer S, et al. Predictive measures and outcomes of extent of resection in juvenile pilocytic astrocytoma. J Clin Neurosci. 2019;70:7984.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Morreale VM, Ebersold MJ, Quast LM, Parisi JE. Cerebellar astrocytoma: experience with 54 cases surgically treated at the Mayo Clinic, Rochester, Minnesota, from 1978 to 1990.J Neurosurg. 1997;87(2):257261.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Kayama T, Tominaga T, Yoshimoto T. Management of pilocytic astrocytoma. Neurosurg Rev. 1996;19(4):217220.

  • 15

    Horbinski C, Nikiforova MN, Hagenkord JM, Hamilton RL, Pollack IF. Interplay among BRAF, p16, p53, and MIB1 in pediatric low-grade gliomas. Neuro Oncol. 2012;14(6):777789.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Hawkins C, Walker E, Mohamed N, Zhang C, Jacob K, Shirinian M, et al. BRAF-KIAA1549 fusion predicts better clinical outcome in pediatric low-grade astrocytoma. Clin Cancer Res. 2011;17(14):47904798.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Becker AP, Scapulatempo-Neto C, Carloni AC, Paulino A, Sheren J, Aisner DL, et al. KIAA1549: BRAF gene fusion and FGFR1 hotspot mutations are prognostic factors in pilocytic astrocytomas. J Neuropathol Exp Neurol. 2015;74(7):743754.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Jones DT, Gronych J, Lichter P, Witt O, Pfister SM. MAPK pathway activation in pilocytic astrocytoma. Cell Mol Life Sci. 2012;69(11):17991811.

  • 19

    Jacob K, Albrecht S, Sollier C, Faury D, Sader E, Montpetit A, et al. Duplication of 7q34 is specific to juvenile pilocytic astrocytomas and a hallmark of cerebellar and optic pathway tumours. Br J Cancer. 2009;101(4):722733.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20

    Dahiya S, Haydon DH, Alvarado D, Gurnett CA, Gutmann DH, Leonard JR. BRAF(V600E) mutation is a negative prognosticator in pediatric ganglioglioma. Acta Neuropathol. 2013;125(6):901910.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Tibbetts KM, Emnett RJ, Gao F, Perry A, Gutmann DH, Leonard JR. Histopathologic predictors of pilocytic astrocytoma event-free survival. Acta Neuropathol. 2009;117(6):657665.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Bartels U, Hawkins C, Jing M, Ho M, Dirks P, Rutka J, et al. Vascularity and angiogenesis as predictors of growth in optic pathway/hypothalamic gliomas. J Neurosurg. 2006;104(5)(suppl):314320.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Dorward IG, Luo J, Perry A, Gutmann DH, Mansur DB, Rubin JB, Leonard JR. Postoperative imaging surveillance in pediatric pilocytic astrocytomas. J Neurosurg Pediatr. 2010;6(4):346352.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Tu A, Robison A, Melamed E, Buchanan I, Hariri O, Babu H, et al. Proliferative index in pediatric pilocytic astrocytoma by region of origin and prediction of clinical behavior. Pediatr Neurosurg. 2018;53(6):395400.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Krieger MD, Gonzalez-Gomez I, Levy ML, McComb JG. Recurrence patterns and anaplastic change in a long-term study of pilocytic astrocytomas. Pediatr Neurosurg. 1997;27(1):111.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    FoundationOne Liquid CDx: Summary of Safety and Effectiveness Data. Food and Drug Administration; 2020.Accessed October 12, 2021. https://www.accessdata.fda.gov/cdrh_docs/pdf17/P170019S017B.pdf

    • Search Google Scholar
    • Export Citation
  • 27

    Lobbous M, Bernstock JD, Coffee E, Friedman GK, Metrock LK, Chagoya G, et al. An update on neurofibromatosis type 1-associated gliomas. Cancers (Basel). 2020;12(1):E114.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28

    Rodriguez FJ, Scheithauer BW, Burger PC, Jenkins S, Giannini C. Anaplasia in pilocytic astrocytoma predicts aggressive behavior. Am J Surg Pathol. 2010;34(2):147160.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Georgakis MK, Karalexi MA, Kalogirou EI, Ryzhov A, Zborovskaya A, Dimitrova N, et al. Incidence, time trends and survival patterns of childhood pilocytic astrocytomas in Southern-Eastern Europe and SEER, US. J Neurooncol. 2017;131(1):163175.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Hasselblatt M, Riesmeier B, Lechtape B, Brentrup A, Stummer W, Albert FK, et al. BRAF-KIAA1549 fusion transcripts are less frequent in pilocytic astrocytomas diagnosed in adults. Neuropathol Appl Neurobiol. 2011;37(7):803806.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 172 172 172
Full Text Views 32 32 32
PDF Downloads 60 60 60
EPUB Downloads 0 0 0