Skip to main content
SpringerLink
Log in

A multimodal imaging-based classification for pediatric diffuse intrinsic pontine gliomas

  • Research
  • Published:
Neurosurgical Review Aims and scope Submit manuscript

Abstract

Object

Pediatric diffuse intrinsic pontine glioma (DIPG) is a radiologically heterogeneous disease entity, here we aim to establish a multimodal imaging-based radiological classification and evaluate the outcome of different treatment strategies under this classification frame.

Methods

This retrospective study included 103 children diagnosed with DIPGs between January 2015 and August 2018 in Beijing Tiantan Hospital (Beijing, China). Multimodal radiological characteristics, including conventional magnetic resonance imaging (MRI), diffuse tensor imaging/diffuse tensor tractography (DTI/DTT), and positron emission tomography (PET) were reviewed to construct the classification. The outcome of different treatment strategies was compared in each DIPG subgroup using Kaplan–Meier method (log-rank test) to determine the optimal treatment for specific DIPGs.

Results

Four radiological DIPG types were identified: Type A (“homocentric”, n=13), Type B (“ventral”, n=41), Type C (“eccentric”, n=37), and Type D (“dorsal”, n=12). Their treatment modalities were grouped as observation (43.7%), cytoreductive surgery (CRS) plus radiotherapy (RT) (24.3%), RT alone (11.7%), and CRS alone (20.4%). CRS+RT mainly fell into type C (29.7%), followed by type B1 (21.9%) and type D (50%). Overall, CRS+RT exhibited a potential survival advantage compared to RT alone, which was more pronounced in specific type, but this did not reach statistical significance, due to limited sample size and unbalanced distribution.

Conclusion

We proposed a multimodality imaging-based radiological classification for pediatric DIPG, which was useful for selecting optimal treatment strategies, especially for identifying candidates who may benefit from CRS plus RT. This classification opened a window into image-guided integrated treatment for pediatric DIPG.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig.1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

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

References

  1. Johung TB, Monje M (2017) Diffuse Intrinsic Pontine Glioma: New Pathophysiological Insights and Emerging Therapeutic Targets. Curr Neuropharmacol 15:88–97. https://doi.org/10.2174/1570159x14666160509123229

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Epstein F, McCleary EL (1986) Intrinsic brain-stem tumors of childhood: surgical indications. J Neurosurg 64:11–15. https://doi.org/10.3171/jns.1986.64.1.0011

    Article  PubMed  CAS  Google Scholar 

  3. Frazier JL, Lee J, Thomale UW, Noggle JC, Cohen KJ, Jallo GI (2009) Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies. J Neurosurg Pediatr 3:259–269. https://doi.org/10.3171/2008.11.PEDS08281

    Article  PubMed  Google Scholar 

  4. Freeman CR, Suissa S (1986) Brain stem tumors in children: results of a survey of 62 patients treated with radiotherapy. Int J Radiat Oncol Biol Phys 12:1823–1828. https://doi.org/10.1016/0360-3016(86)90325-1

    Article  PubMed  CAS  Google Scholar 

  5. Hargrave D, Bartels U, Bouffet E (2006) Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol 7:241–248. https://doi.org/10.1016/S1470-2045(06)70615-5

    Article  PubMed  Google Scholar 

  6. Mandell LR, Kadota R, Freeman C, Douglass EC, Fontanesi J, Cohen ME et al (1999) There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy. Int J Radiat Oncol Biol Phys 43:959–964. https://doi.org/10.1016/s0360-3016(98)00501-x

    Article  PubMed  CAS  Google Scholar 

  7. Elhammady MS, Teo C (2013) Surgical management of adult intrinsic brainstem tumors. Neurosurgery 60(Suppl 1):131–138. https://doi.org/10.1227/01.neu.0000430770.33467.be

    Article  PubMed  Google Scholar 

  8. Klimo P Jr, Nesvick CL, Broniscer A, Orr BA, Choudhri AF (2016) Malignant brainstem tumors in children, excluding diffuse intrinsic pontine gliomas. J Neurosurg Pediatr 17:57–65. https://doi.org/10.3171/2015.6.PEDS15166

    Article  PubMed  Google Scholar 

  9. Mehta VS, Chandra PS, Singh PK, Garg A, Rath GK (2009) Surgical considerations for 'intrinsic' brainstem gliomas: proposal of a modification in classification. Neurol India 57:274–281. https://doi.org/10.4103/0028-3886.53272

    Article  PubMed  CAS  Google Scholar 

  10. Sinha S, Kale SS, Chandra SP, Suri A, Mehta VS, Sharma BS. Brainstem gliomas: surgical indications and technical considerations in a series of 58 cases. Br J Neurosurg 2014;28:220-5. https://doi.org/10.3109/02688697.2013.829562.

  11. Teo C, Siu TL (2008) Radical resection of focal brainstem gliomas: is it worth doing? Childs Nerv Syst 24:1307–1314. https://doi.org/10.1007/s00381-008-0647-z

    Article  PubMed  Google Scholar 

  12. Bartels U, Hawkins C, Vezina G, Kun L, Souweidane M, Bouffet E (2011) Proceedings of the diffuse intrinsic pontine glioma (DIPG) Toronto Think Tank: advancing basic and translational research and cooperation in DIPG. J Neurooncol 105:119–125. https://doi.org/10.1007/s11060-011-0704-4

    Article  PubMed  Google Scholar 

  13. Hankinson TC, Campagna EJ, Foreman NK, Handler MH (2011) Interpretation of magnetic resonance images in diffuse intrinsic pontine glioma: a survey of pediatric neurosurgeons. J Neurosurg Pediatr 8:97–102. https://doi.org/10.3171/2011.4.PEDS1180

    Article  PubMed  Google Scholar 

  14. Chiang J, Diaz AK, Makepeace L, Li X, Han Y, Li Y et al (2020) Clinical, imaging, and molecular analysis of pediatric pontine tumors lacking characteristic imaging features of DIPG. Acta Neuropathol Commun 8:57. https://doi.org/10.1186/s40478-020-00930-9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Albert NL, Weller M, Suchorska B, Galldiks N, Soffietti R, Kim MM et al (2016) Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas. Neuro Oncol 18:1199–1208. https://doi.org/10.1093/neuonc/now058

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Flores BC, Whittemore AR, Samson DS, Barnett SL (2015) The utility of preoperative diffusion tensor imaging in the surgical management of brainstem cavernous malformations. J Neurosurg 122:653–662. https://doi.org/10.3171/2014.11.JNS13680

    Article  PubMed  Google Scholar 

  17. Glaudemans AW, Enting RH, Heesters MA, Dierckx RA, van Rheenen RW, Walenkamp AM et al (2013) Value of 11C-methionine PET in imaging brain tumours and metastases. Eur J Nucl Med Mol Imaging 40:615–635. https://doi.org/10.1007/s00259-012-2295-5

    Article  PubMed  CAS  Google Scholar 

  18. Kovanlikaya I, Firat Z, Kovanlikaya A, Ulug AM, Cihangiroglu MM, John M et al (2011) Assessment of the corticospinal tract alterations before and after resection of brainstem lesions using Diffusion Tensor Imaging (DTI) and tractography at 3T. Eur J Radiol 77:383–391. https://doi.org/10.1016/j.ejrad.2009.08.012

    Article  PubMed  Google Scholar 

  19. Lerner A, Mogensen MA, Kim PE, Shiroishi MS, Hwang DH, Law M (2014) Clinical applications of diffusion tensor imaging. World Neurosurg 82:96–109. https://doi.org/10.1016/j.wneu.2013.07.083

    Article  PubMed  Google Scholar 

  20. Lopci E, Franzese C, Grimaldi M, Zucali PA, Navarria P, Simonelli M et al (2015) Imaging biomarkers in primary brain tumours. Eur J Nucl Med Mol Imaging 42:597–612. https://doi.org/10.1007/s00259-014-2971-8

    Article  PubMed  CAS  Google Scholar 

  21. Tinkle CL, Duncan EC, Doubrovin M, Han Y, Li Y, Kim H et al (2019) Evaluation of (11)C-Methionine PET and Anatomic MRI Associations in Diffuse Intrinsic Pontine Glioma. J Nucl Med 60:312–319. https://doi.org/10.2967/jnumed.118.212514

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Zhang L, Jia W, Ji N, Li D, Xiao D, Shan GL et al (2021) Construction of the National Brain Tumor Registry of China for better management and more efficient use of data: a protocol. BMJ Open 11:e040055. https://doi.org/10.1136/bmjopen-2020-040055.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lazar M, Alexander AL, Thottakara PJ, Badie B, Field AS (2006) White matter reorganization after surgical resection of brain tumors and vascular malformations. AJNR Am J Neuroradiol 27:1258–1271

    PubMed  PubMed Central  CAS  Google Scholar 

  24. Rachinger W, Grau S, Holtmannspotter M, Herms J, Tonn JC, Kreth FW (2009) Serial stereotactic biopsy of brainstem lesions in adults improves diagnostic accuracy compared with MRI only. J Neurol Neurosurg Psychiatry 80:1134–1139. https://doi.org/10.1136/jnnp.2009.174250

    Article  PubMed  CAS  Google Scholar 

  25. Cohen KJ, Pollack IF, Zhou T, Buxton A, Holmes EJ, Burger PC et al (2011) Temozolomide in the treatment of high-grade gliomas in children: a report from the Children's Oncology Group. Neuro Oncol 13:317–323. https://doi.org/10.1093/neuonc/noq191

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Chiang KL, Chang KP, Lee YY, Huang PI, Hsu TR, Chen YW et al (2010) Role of temozolomide in the treatment of newly diagnosed diffuse brainstem glioma in children: experience at a single institution. Childs Nerv Syst 26:1035–1041. https://doi.org/10.1007/s00381-010-1106-1

    Article  PubMed  Google Scholar 

  27. Gwak HS, Park HJ (2017) Developing chemotherapy for diffuse pontine intrinsic gliomas (DIPG). Crit Rev Oncol Hematol 120:111–119. https://doi.org/10.1016/j.critrevonc.2017.10.013

    Article  PubMed  Google Scholar 

  28. Osorio DS, Patel N, Ji L, Sposto R, Stanek J, Gardner SL et al (2018) Pre-irradiation intensive induction and marrow-ablative consolidation chemotherapy in young children with newly diagnosed high-grade brainstem gliomas: report of the "head-start" I and II clinical trials. J Neurooncol 140:717–725. https://doi.org/10.1007/s11060-018-03003-z

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Janssens GO, Jansen MH, Lauwers SJ, Nowak PJ, Oldenburger FR, Bouffet E et al (2013) Hypofractionation vs conventional radiation therapy for newly diagnosed diffuse intrinsic pontine glioma: a matched-cohort analysis. Int J Radiat Oncol Biol Phys 85:315–320. https://doi.org/10.1016/j.ijrobp.2012.04.006

    Article  PubMed  Google Scholar 

  30. Hoffman LM, Veldhuijzen van Zanten SEM, Colditz N, Baugh J, Chaney B, Hoffmann M et al (2018) Clinical, Radiologic, Pathologic, and Molecular Characteristics of Long-Term Survivors of Diffuse Intrinsic Pontine Glioma (DIPG): A Collaborative Report From the International and European Society for Pediatric Oncology DIPG Registries. J Clin Oncol 36:1963–1972. https://doi.org/10.1200/JCO.2017.75.9308

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Jansen MH, Veldhuijzen van Zanten SE, Sanchez Aliaga E, Heymans MW, Warmuth-Metz M, Hargrave D et al (2015) Survival prediction model of children with diffuse intrinsic pontine glioma based on clinical and radiological criteria. Neuro Oncol 17:160–166. https://doi.org/10.1093/neuonc/nou104

    Article  PubMed  Google Scholar 

  32. Laigle-Donadey F, Doz F, Delattre JY (2008) Brainstem gliomas in children and adults. Curr Opin Oncol 20:662–667. https://doi.org/10.1097/CCO.0b013e32831186e0.

    Article  PubMed  Google Scholar 

  33. Yoshida K, Sulaiman NS, Miyawaki D, Ejima Y, Nishimura H, Ishihara T et al (2017) Radiotherapy for brainstem gliomas in children and adults: A single-institution experience and literature review. Asia Pac. J Clin Oncol 13:e153–ee60. https://doi.org/10.1111/ajco.12451

    Article  Google Scholar 

  34. Pan CC, Chen X, Xu C, Wu WH, Zhang P, Wang Y et al (2016) Brainstem gangliogliomas: prognostic factors, surgical indications and functional outcomes. J Neurooncol 128:445–453. https://doi.org/10.1007/s11060-016-2131-z

    Article  PubMed  CAS  Google Scholar 

  35. Zhang YS, Pan CC, Zhang P, Dai B, Tang J, Wu Z et al (2017) Prognostic indicators of adult medullary gliomas after microsurgical treatment - A retrospective analysis of 54 patients. J Clin Neurosci 44:122–127. https://doi.org/10.1016/j.jocn.2017.05.041

    Article  PubMed  Google Scholar 

  36. Li D, Jiao YM, Wang L, Lin FX, Wu J, Tong XZ et al (2018) Surgical outcome of motor deficits and neurological status in brainstem cavernous malformations based on preoperative diffusion tensor imaging: a prospective randomized clinical trial. J Neurosurg 130:286–301. https://doi.org/10.3171/2017.8.JNS17854

    Article  PubMed  Google Scholar 

  37. Xiao X, Kong L, Pan C, Zhang P, Chen X, Sun T et al (2021) The role of diffusion tensor imaging and tractography in the surgical management of brainstem gliomas. Neurosurg Focus 50:E10. https://doi.org/10.3171/2020.10.FOCUS20166

    Article  PubMed  Google Scholar 

  38. Xue Z, Kong L, Hao S, Wang Y, Jia G, Wu Z et al (2021) Combined Application of Sodium Fluorescein and Neuronavigation Techniques in the Resection of Brain Gliomas. Front Neurol 12:747072. https://doi.org/10.3389/fneur.2021.747072

    Article  PubMed  PubMed Central  Google Scholar 

  39. Jackson S, Patay Z, Howarth R, Pai Panandiker AS, Onar-Thomas A, Gajjar A et al (2013) Clinico-radiologic characteristics of long-term survivors of diffuse intrinsic pontine glioma. J Neurooncol 114:339–344. https://doi.org/10.1007/s11060-013-1189-0

    Article  PubMed  PubMed Central  Google Scholar 

  40. Kaye EC, Baker JN, Broniscer A (2014) Management of diffuse intrinsic pontine glioma in children: current and future strategies for improving prognosis. CNS Oncol. 3:421–431. https://doi.org/10.2217/cns.14.47

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Pedersen H, Schmiegelow K, Hamerlik P (2020) Radio-Resistance and DNA Repair in Pediatric Diffuse Midline Gliomas. Cancers (Basel):12. https://doi.org/10.3390/cancers12102813

  42. Mursch K, Halatsch ME, Markakis E, Behnke-Mursch J (2005) Intrinsic brainstem tumours in adults: results of microneurosurgical treatment of 16 consecutive patients. Br J Neurosurg 19:128–136. https://doi.org/10.1080/02688690500145530

    Article  PubMed  CAS  Google Scholar 

  43. Pierre-Kahn A, Hirsch JF, Vinchon M, Payan C, Sainte-Rose C, Renier D et al (1993) Surgical management of brain-stem tumors in children: results and statistical analysis of 75 cases. J Neurosurg 79:845–852. https://doi.org/10.3171/jns.1993.79.6.0845

    Article  PubMed  CAS  Google Scholar 

  44. Wei J, Gabrusiewicz K, Heimberger A (2013) The controversial role of microglia in malignant gliomas. Clin Dev Immunol 2013:285246. https://doi.org/10.1155/2013/285246

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Roesch S, Rapp C, Dettling S, Herold-Mende C (2018) When Immune Cells Turn Bad-Tumor-Associated Microglia/Macrophages in Glioma. Int J Mol Sci 19. https://doi.org/10.3390/ijms19020436

Download references

Acknowledgements

We gratefully acknowledge the valuable contribution of Qianqian Liu (Peking Union Medical College) for her assistance in statistical analysis.

Funding

Beijing Municipal Special Funds for Medical Research, grant no. Jing Yi Yan 2018-7;

Capital’s Funds for Health Improvement and Research, grant no. 2020-4-20410;

National Natural Science Foundation of China, grant no. 81872048, 8200112572.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, 100070, China

    Changcun Pan, Mingxin Zhang, Xiong Xiao, Lu Kong, Yuliang Wu, Tao Sun, Peng Zhang, Yibo Geng, Pengcheng Zuo, Yi Wang, Xiaoou Li, Guocan Gu, Tian Li, Zhen Wu, Junting Zhang & Liwei Zhang

  2. Department of Nuclear Medicine, Beijing Tian Tan Hospital, Capital Medical University, Beijing, 100070, China

    Xiaobin Zhao

  3. China National Clinical Research Center for Neurological Diseases, Beijing Tian Tan Hospital, Beijing, 100070, China

    Liwei Zhang

Authors
  1. Changcun Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mingxin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiong Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lu Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuliang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaobin Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tao Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Peng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yibo Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Pengcheng Zuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Xiaoou Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Guocan Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Tian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Zhen Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Junting Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Liwei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design: Changcun Pan, Mingxin Zhang, Xiong Xiao, Lu Kong, Yuliang Wu, Liwei Zhang.

Collection and assembly of data: Xiaobin Zhao, Tao Sun, Peng Zhang, Yibo Geng, Mingxin Zhang, Pengcheng Zuo, Yi Wang, Guocan Gu and Tian Li.

Data analysis and interpretation: Dan Xiao, Mingxin Zhang, Lu Kong, Changcun Pan, Xiong Xiao

Figure preparing: Mingxin Zhang, Yuliang Wu

Manuscript writing: All authors.

Final approval of manuscript: All authors.

Study supervision: All authors.

Corresponding author

Correspondence to Liwei Zhang.

Ethics declarations

Ethics approval

Institutional Review Board approval was obtained.

Consent to participate

Written informed consent was obtained from the parents.

Consent to publish

The authors affirm that human research participants provided informed consent for publication of the images in Supplementary Figure S1, S2 and S3.

Competing Interests

The authors have no relevant financial or non-financial interests to disclose.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Changcun Pan and Mingxin Zhang contributed to this work equally.

Supplementary information

ESM 1

(DOCX 48 kb)

ESM 2

(DOCX 1841 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pan, C., Zhang, M., Xiao, X. et al. A multimodal imaging-based classification for pediatric diffuse intrinsic pontine gliomas. Neurosurg Rev 46, 151 (2023). https://doi.org/10.1007/s10143-023-02068-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10143-023-02068-3

Keywords

Search

Navigation