Long-term follow-up of surgical intervention pattern in pediatric low-grade gliomas: report from the German SIOP-LGG 2004 cohort

View More View Less
  • 1 Pediatric Neurosurgery, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin;
  • | 2 Pediatric and Adolescent Medicine, Swabian Children’s Cancer Research Center, Medical Faculty, University of Augsburg;
  • | 3 Institute of Diagnostic and Interventional Neuroradiology, University Hospital Würzburg;
  • | 4 Institute of Diagnostic and Interventional Neuroradiology, Medical Faculty, University of Augsburg;
  • | 5 Department of Pediatric Oncology/Hematology, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin;
  • | 6 Hopp Children’s Cancer Center Heidelberg (KiTZ), German Cancer Research Center (DKFZ), and Heidelberg University Hospital, Heidelberg;
  • | 7 Department of Neuropathology, DGNN Brain Tumor Reference Centre, University of Bonn Medical Centre, Bonn;
  • | 8 Institute for Neuropathology, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin;
  • | 9 Department of Radiation Oncology, University Hospital Leipzig;
  • | 10 Department of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre Essen (WPE), West German Cancer Centre (WTZ), German Cancer Consortium (DKTK), Essen;
  • | 11 Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg;
  • | 12 Division of Pediatric Neurosurgery, Department of Neurosurgery, Heidelberg University Hospital, Heidelberg;
  • | 13 Department of Pediatric Neurosurgery, University Children’s Hospital, University of Würzburg;
  • | 14 Division of Pediatric Neurosurgery, Department of Neurosurgery, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen; and
  • | 15 Institute of Biometry and Clinical Epidemiology, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany
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
USD  $45.00
USD  $515.00
USD  $612.00
Print or Print + Online Sign in

OBJECTIVE

Neurosurgical treatment is an integral part of the treatment algorithms for pediatric low-grade glioma (LGG), yet patterns of surgical procedures are rarely challenged. The objective of this study was to evaluate surgical treatment patterns in pediatric LGG.

METHODS

The German Societé Internationale d’Oncologie Pédiatrique (SIOP)–LGG 2004 cohort was analyzed to identify relevant patient and tumor characteristics associated with time to death, next surgery, number of resections, and radiological outcome.

RESULTS

A total of 1271 patients underwent 1713 neurosurgical interventions (1 intervention in 947, 2 in 230, 3 in 70, and 4–6 in 24). The median age of the study population was 8.57 years at first surgery, and 46.1% were female. Neurofibromatosis type 1 (NF1) was found in 4.4%, and 5.4% had tumor dissemination. Three hundred fifty-four patients (27.9%) had chemotherapy and/or radiotherapy. The cumulative incidence of second surgery at 10 years was 26%, and was higher for infants, those with spinal and supratentorial midline (SML) tumors, and those with pilomyxoid astrocytomas. The hazard ratio for subsequent surgery was higher given dissemination and noncomplete initial resection, and lower for caudal brainstem and SML tumors. Among 1225 patients with fully documented surgical records and radiological outcome, 613 reached complete remission during the observation period, and 50 patients died. Patients with pilocytic astrocytoma had higher chances for a final complete remission, whereas patients with initial partial or subtotal tumor resection, dissemination, NF1, or primary tumor sites in the spinal cord and SML had lower chances.

CONCLUSIONS

Neurosurgery is a key element of pediatric LGG treatment. In almost 50% of the patients, however, at least some tumor burden will remain during long-term follow-up. This study found that most of these patients reached a stable disease status without further surgeries. Multidisciplinary team decisions must balance the goal of complete resection, risk factors, repeated surgeries, and possible treatment alternatives in a wide range of heterogeneous entities. Procedural details and neurological outcome should be recorded to better assess their impact on long-term outcome.

ABBREVIATIONS

CI = confidence interval; CR = complete remission; DG2 = diffuse glioma grade II; DLGG = disseminated LGG; HR = hazard ratio; IQR = interquartile range; LGG = low-grade glioma; NF1 = neurofibromatosis type 1; OR = odds ratio; PA = pilocytic astrocytoma; PD = progressive disease; PFS = progression-free survival; RR = rate ratio; SD = stable disease; SEGA = subependymal giant cell astrocytoma; SIOP = Societé Internationale d’Oncologie Pédiatrique; SML = supratentorial midline.

Supplementary Materials

    • Supplemental Material (PDF 578 KB)

Illustration from Cinalli et al. (pp 330–341). Printed with permission from © CC Medical Arts.

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

USD  $515.00

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

USD  $612.00
USD  $515.00
USD  $612.00
  • 1

    Ghazwani Y, Patay Z, Sadighi ZS, et al. Handedness switching as a presenting sign for pediatric low-grade gliomas: an insight into brain plasticity from a short case series. J Pediatr Rehabil Med. 2021;14(1):3136.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Gnekow AK, Kandels D, Pietsch T, et al. Doubling recruitment of pediatric low-grade glioma within two decades does not change outcome—report from the German LGG studies. Klin Padiatr. 2021;233(3):107122.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3

    Gnekow AK, Kandels D, Tilburg CV, et al. SIOP-E-BTG and GPOH guidelines for diagnosis and treatment of children and adolescents with low grade glioma. Klin Padiatr. 2019;231(3):107135.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):12311251.

  • 5

    Goodden J, Pizer B, Pettorini B, et al. The role of surgery in optic pathway/hypothalamic gliomas in children. J Neurosurg Pediatr. 2014;13(1):112.

  • 6

    Ater JL, Zhou T, Holmes E, et al. Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children’s Oncology Group. J Clin Oncol. 2012;30(21):26412647.

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

    Gnekow AK, Falkenstein F, von Hornstein S, et al. Long-term follow-up of the multicenter, multidisciplinary treatment study HIT-LGG-1996 for low-grade glioma in children and adolescents of the German Speaking Society of Pediatric Oncology and Hematology. Neuro Oncol. 2012;14(10):12651284.

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

    Gnekow AK, Walker DA, Kandels D, et al. A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma—a final report. Eur J Cancer. 2017;81(206):225.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Kandels D, Pietsch T, Bison B, et al. Loss of efficacy of subsequent nonsurgical therapy after primary treatment failure in pediatric low-grade glioma patients—report from the German SIOP-LGG 2004 cohort. Int J Cancer. 2020;147(12):34713489.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Lassaletta A, Zapotocky M, Bouffet E, Hawkins C, Tabori U. An integrative molecular and genomic analysis of pediatric hemispheric low-grade gliomas: an update. Childs Nerv Syst. 2016;32(10):17891797.

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

    Massimino M, Spreafico F, Riva D, et al. A lower-dose, lower-toxicity cisplatin-etoposide regimen for childhood progressive low-grade glioma. J Neurooncol. 2010;100(1):6571.

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

    Stokland T, Liu JF, Ironside JW, et al. A multivariate analysis of factors determining tumor progression in childhood low-grade glioma: a population-based cohort study (CCLG CNS9702). Neuro Oncol. 2010;12(12):12571268.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Balogun JA, Rutka JT. Surgery of intracranial gliomas in children. Prog Neurol Surg. 2018;30(204):217.

  • 14

    Pollack IF. The role of surgery in pediatric gliomas. J Neurooncol. 1999;42(3):271288.

  • 15

    Foster MT, Harishchandra LS, Mallucci C. Pediatric central nervous system tumors: state-of-the-art and debated aspects. Front Pediatr. 2018;6 309.

  • 16

    Jakola AS, Skjulsvik AJ, Myrmel KS, et al. Surgical resection versus watchful waiting in low-grade gliomas. Ann Oncol. 2017;28(8):19421948.

  • 17

    Walker DA, Liu J, Kieran M, et al. A multi-disciplinary consensus statement concerning surgical approaches to low-grade, high-grade astrocytomas and diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using the Delphi method. Neuro Oncol. 2013;15(4):462468.

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

    Traunwieser T, Kandels D, Pauls F, et al. Long-term cognitive deficits in pediatric low-grade glioma (LGG) survivors reflect pretreatment conditions-report from the German LGG studies. Neurooncol Adv. 2020;2(1):vdaa094.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Fangusaro J, Witt O, Hernáiz Driever P, et al. Response assessment in paediatric low-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. Lancet Oncol. 2020;21(6):e305e316.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20

    Warmuth-Metz M, Bison B, Leykamm S. Neuroradiologic review in pediatric brain tumor studies. Klin Neuroradiol. 2009;19(4):263273.

  • 21

    D’Angelo F, Ceccarelli M, et al. The molecular landscape of glioma in patients with neurofibromatosis 1. Nat Med. 2019;25(1):176187.

  • 22

    Ryall S, Tabori U, Hawkins C. Pediatric low-grade glioma in the era of molecular diagnostics. Acta Neuropathol Commun. 2020;8(1):30.

  • 23

    Wisoff JH, Sanford RA, Heier LA, et al. Primary neurosurgery for pediatric low-grade gliomas: a prospective multi-institutional study from the Children’s Oncology Group. Neurosurgery. 2011;68(6):15481555.

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

    Hill CS, Khan M, Phipps K, Green K, Hargrave D, Aquilina K. Neurosurgical experience of managing optic pathway gliomas. Childs Nerv Syst. 2021;37(6):19171929.

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

    El Beltagy MA, Reda M, Enayet A, et al. Treatment and outcome in 65 children with optic pathway gliomas. World Neurosurg. 2016;89(525):534.

  • 26

    Sawamura Y, Kamada K, Kamoshima Y, et al. Role of surgery for optic pathway/hypothalamic astrocytomas in children. Neuro Oncol. 2008;10(5):725733.

  • 27

    Due-Tønnessen BJ, Lundar T, Egge A, Scheie D. Neurosurgical treatment of low-grade cerebellar astrocytoma in children and adolescents: a single consecutive institutional series of 100 patients. J Neurosurg Pediatr. 2013;11(3):245249.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Maharaj A, Manoranjan B, Verhey LH, et al. Predictive measures and outcomes of extent of resection in juvenile pilocytic astrocytoma. J Clin Neurosci. 2019;70(79):84.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Dudley RW, Torok MR, Gallegos DR, et al. Pediatric low-grade ganglioglioma: epidemiology, treatments, and outcome analysis on 348 children from the surveillance, epidemiology, and end results database. Neurosurgery. 2015;76(3):313320.

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

    Lundar T, Due-Tønnessen BJ, Fric R, et al. Neurosurgical treatment of gangliogliomas in children and adolescents: long-term follow-up of a single-institution series of 32 patients. Acta Neurochir (Wien). 2018;160(6):12071214.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31

    Tomita T, Volk JM, Shen W, Pundy T. Glioneuronal tumors of cerebral hemisphere in children: correlation of surgical resection with seizure outcomes and tumor recurrences. Childs Nerv Syst. 2016;32(10):18391848.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Holzapfel J, Kandels D, Schmidt R, et al. Favorable prognosis in pediatric brainstem low-grade glioma: report from the German SIOP-LGG 2004 cohort. Int J Cancer. 2020;146(12):33853396.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Tsang DS, Murphy ES, Ezell SE, Lucas JT Jr, Tinkle C, Merchant TE. Craniospinal irradiation for treatment of metastatic pediatric low-grade glioma. J Neurooncol. 2017;134(2):317324.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Kozyrev DA, Soleman J, Tsering D, et al. Pediatric thalamic incidentalomas: an international retrospective multicenter study. J Neurosurg Pediatr. 2022;29(2):141149.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35

    Stagno V, Mallucci C, Avula S, Pizer B. The use of neo adjuvant single-agent vinblastine for tumour shrinkage in a highly vascular paediatric low-grade glioma. Br J Neurosurg. 2020;34(2):207209.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36

    McAuley E, Brophy H, Hayden J, et al. The benefit of surveillance imaging for paediatric cerebellar pilocytic astrocytoma. Childs Nerv Syst. 2019;35(5):801805.

  • 37

    Stevens SP, Main C, Bailey S, et al. The utility of routine surveillance screening with magnetic resonance imaging to detect tumor recurrence/progression in children with high-grade central nervous system tumors: a systematic review. Pediatr Blood Cancer. 2019;66(2):e27509.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Perwein T, Benesch M, Kandels D, et al. High frequency of disease progression in pediatric spinal cord low-grade glioma (LGG): management strategies and results from the German LGG study group. Neuro Oncol. 2021;23(7):11481162.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39

    Fogarasi A, De Waele L, Bartalini G, et al. EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex. BMC Neurol. 2016;16 126.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Franz DN, Belousova E, Sparagana S, et al. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2013;381(9861):125132.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Mirow C, Pietsch T, Berkefeld S, et al. Children <1 year show an inferior outcome when treated according to the traditional LGG treatment strategy: a report from the German multicenter trial HIT-LGG 1996 for children with low grade glioma (LGG). Pediatr Blood Cancer. 2014;61(3):457463.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42

    Chamdine O, Broniscer A, Wu S, Gajjar A, Qaddoumi I. Metastatic low-grade gliomas in children: 20 years’ experience at St. Jude Children’s Research Hospital. Pediatr Blood Cancer. 2016;63(1):6270.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43

    Gessi M, Engels AC, Lambert S, et al. Molecular characterization of disseminated pilocytic astrocytomas. Neuropathol Appl Neurobiol. 2016;42(3):273278.

  • 44

    Carai A, De Benedictis A, Calloni T, et al. Intraoperative ultrasound-assisted extent of resection assessment in pediatric neurosurgical oncology. Front Oncol. 2021;11 660805.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45

    Wach J, Banat M, Borger V, Vatter H, Haberl H, Sarikaya-Seiwert S. Intraoperative MRI-guided resection in pediatric brain tumor surgery: a meta-analysis of extent of resection and safety outcomes. J Neurol Surg A Cent Eur Neurosurg. 2021;82(1):6474.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 751 751 185
Full Text Views 128 128 43
PDF Downloads 182 182 80
EPUB Downloads 0 0 0