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Treatment evaluation by volumetric segmentation in pediatric optic pathway glioma: evaluation of the effect of bevacizumab on intra-tumor components

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Abstract

Purpose

Progressive pediatric optic pathway gliomas (OPGs) are treated by diverse systemic antitumor modalities. Refined insights on the course of intra-tumoral components are limited.

Methods

We performed an exploratory study on the longitudinal volumetric course of different (intra-)tumor components by manual segmentation of MRI at the start and after 3, 6 and 12 months of bevacizumab (BVZ) treatment.

Results

Thirty-one patients were treated with BVZ (median 12 months, range: 2–39 months). During treatment the total tumor volume decreased with median 19.9% (range: − 62.3 to + 29.7%; n = 30) within the first 3 months, decreased 19.0% (range: − 68.8 to + 96.1%; n = 28) between start and 6 months and 27.2% (range: −73.4 to + 36.0%; n = 21) between start and 12 months. Intra-tumoral cysts were present in 12 OPGs, all showed a decrease of volume during treatment. The relative contrast enhanced volume of NF1 associated OPG (n = 11) showed an significant reduction compared to OPG with a KIAA1549-BRAF fusion (p < 0.01). Three OPGs progressed during treatment, but were not preceded by an increase of relative contrast enhancement.

Conclusion

Treatment with BVZ of progressive pediatric OPGs leads to a decrease of both total tumor volume and cystic volume for the majority of OPGs with emphasis on the first three months. NF1 and KIAA1549-BRAF fusion related OPGs showed a different (early) treatment effect regarding the tumor enhancing component on MRI, which did not correlate with tumor volume changes. Future research is necessary to further evaluate these findings and its relevance to clinical outcome parameters.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

BVZ:

Bevacizumab

IRI:

Irinotecan

KIAA1549-BRAF:

Fusion of the human gene that encodes the KIAA1549 protein and the B-raf: (proto-)oncogene

MDC:

Modified Dodge Classification

NF1:

Neurofibromatosis type 1

nNF1:

No neurofibromatosis type 1

OPG:

Optic pathway glioma

PMA:

Pilomyxoid astrocytoma

PP:

Percent point

SAT:

Systemic anticancer therapy

Segmentation:

Manual volumetric segmentation

TTV:

Total tumor volume

TDM:

Tumor diameter measurements

VBL:

Vinblastin

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Funding

This study was funded by the ODAS foundation: grant number: 2019-01.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1100DD, Amsterdam, The Netherlands

    Carlien A. Bennebroek, Maartje C. Montauban-van Swijndregt & Peerooz Saeed

  2. Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands

    Carlien A. Bennebroek & Peerooz Saeed

  3. Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

    Christiaan R. Schouten, Marcus C. de Jong & Pim de Graaf

  4. Department of Ophthalmology, Utrecht University Medical Center, Utrecht, The Netherlands

    Giorgio L. Porro

  5. Department of Ophthalmology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Jan W. R. Pott

  6. Department of Pediatrics, Radboud University Medical Center, Amalia Children’s Hospital, Nijmegen, The Netherlands

    Anne T. M. Dittrich

  7. ENCORE-NF1 Center, Department of General Pediatrics, Erasmus MC, Rotterdam, The Netherlands

    Rianne Oostenbrink

  8. Department of Neuro-Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

    Antoinette Y. Schouten-van Meeteren

  9. Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands

    Marcus C. de Jong & Pim de Graaf

Authors
  1. Carlien A. Bennebroek
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Contributions

CAB: Conceptualisation, funding acquisition, methodology, project administration, resources, supervision, validation, writing, original draft preparation. CRS: Data curation, formal analysis, investigation, methodology, project administration, visualisation, writing—original draft preparation. MCMS: Resources, writing, original draft preparation. PS: Funding, writing—review and editing. GLP: Resources, writing—review and editing. JWRP: Resources, writing—review and editing. ATD: Resources, writing—review and editing. RO: Resources, writing—review and editing. AYSM: Funding acquisition, methodology, resources, writing—review and editing. MCJ: Methodology, investigation, normal analysis, writing—review and editing. PG: Conceptualization, methodology, investigation, resources, writing—review and editing, supervision, funding acquisition.

Corresponding author

Correspondence to Carlien A. Bennebroek.

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Competing interests

Author R. Oostenbrink provides advisory consultations for Alexion, with incidental honoraria and is a full member of Genturis ERN.

Ethical approval

This is a retrospective study. The Research Ethics Committee of the Amsterdam UMC, Erasmus MC, Radboud UMC and UMC Groningen have confirmed that no ethical approval is required. Approval according to the principles of the Declaration of Helsinki was granted by the Ethics Committee of University of the UMC Utrecht, Princess Máxima Center.

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Written informed consent for the use of patient data was obtained from parents, legal guardian(s) or children depending on the age of the patients.

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Bennebroek, C.A., Schouten, C.R., Montauban-van Swijndregt, M.C. et al. Treatment evaluation by volumetric segmentation in pediatric optic pathway glioma: evaluation of the effect of bevacizumab on intra-tumor components. J Neurooncol 166, 79–87 (2024). https://doi.org/10.1007/s11060-023-04516-y

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