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Optic nerve thickening on high-spatial-resolution MRI predicts early-stage postlaminar optic nerve invasion in retinoblastoma

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Abstract

Objectives

To assess the diagnostic accuracy of nerve thickening on MRI to predict early-stage postlaminar optic nerve invasion (PLONI) in retinoblastoma. Furthermore, this study aimed to incorporate measurements into a multiparametric model for radiological determination of PLONI.

Methods

In this retrospective multicenter case–control study, high-spatial-resolution 3D T2-weighted MR images were used to measure the distal optic nerve. Histopathology was the reference standard for PLONI. Two neuroradiologists independently measured the optic nerve width, height, and surface at 0, 3, and 5 mm from the most distal part of the optic nerve. Subsequently, PLONI was scored on contrast-enhanced T1-weighted and 3D T2-weighted images, blinded for clinical data. Optic nerve measurements with the highest diagnostic accuracy for PLONI were incorporated into a prediction model for radiological determination of PLONI.

Results

One hundred twenty-four retinoblastoma patients (median age, 22 months [range, 0–113], 58 female) were included, resulting in 25 retinoblastoma eyes with histopathologically proven PLONI and 206 without PLONI. ROC analysis of axial optic nerve width measured at 0 mm yielded the best area under the curve of 0.88 (95% confidence interval: 0.79, 0.96; p < 0.001). The optimal width cutoff was ≥ 2.215 mm, with a sensitivity of 84% (95% CI: 64, 95%) and specificity of 83% (95% CI: 75, 89%) for detecting PLONI. Combining width measurements with the suspicion of PLONI on MRI sequences resulted in a prediction model with an improved sensitivity and specificity of respectively up to 88% and 92%.

Conclusion

Postlaminar optic nerve thickening can predict early-stage postlaminar optic nerve invasion in retinoblastoma.

Clinical relevance statement

This study provides an additional tool for clinicians to help determine postlaminar optic nerve invasion, which is a risk factor for developing metastatic disease in retinoblastoma patients.

Key Points

• The diagnostic accuracy of contrast-enhanced MRI for detecting postlaminar optic nerve invasion is limited in retinoblastoma patients.

• Optic nerve thickening can predict postlaminar optic nerve invasion.

• A prediction model combining MRI features has a high sensitivity and specificity for detecting postlaminar optic nerve invasion.

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Abbreviations

AUC:

Area under the curve

CI:

Confidence interval

CSF:

Cerebrospinal fluid

ICC:

Intraclass correlation coefficient

IQR:

Interquartile ranges

MRI:

Magnetic resonance imaging

PLONI:

Postlaminar optic nerve invasion

ROC:

Receiver operating characteristic

References

  1. Dimaras H, Kimani K, Dimba EA et al (2012) Retinoblastoma Lancet 379:1436–1446

    Article  PubMed  Google Scholar 

  2. Finger PT, Harbour JW, Karcioglu ZA (2002) Risk factors for metastasis in retinoblastoma. Surv Ophthalmol 47:1–16

    Article  PubMed  Google Scholar 

  3. Lu JE, Francis JH, Dunkel IJ et al (2018) Metastases and death rates after primary enucleation of unilateral retinoblastoma in the USA 2007–2017. Br J Ophthalmol. https://doi.org/10.1136/bjophthalmol-2018-312915

    Article  PubMed  Google Scholar 

  4. Kaliki S, Shields CL, Rojanaporn D et al (2013) High-risk retinoblastoma based on international classification of retinoblastoma: analysis of 519 enucleated eyes. Ophthalmology 120:997–1003

    Article  PubMed  Google Scholar 

  5. Bosaleh A, Sampor C, Solernou V et al (2012) Outcome of children with retinoblastoma and isolated choroidal invasion. Arch Ophthalmol 130:724–729

    Article  PubMed  Google Scholar 

  6. Dimaras H, Corson TW, Cobrinik D et al (2015) Retinoblastoma Nat Rev Dis Primers 1:15021

    Article  PubMed  Google Scholar 

  7. Munier FL, Beck-Popovic M, Chantada GL et al (2019) Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. “Alive, with good vision and no comorbidity”. Prog Retin Eye Res 73:100764. https://doi.org/10.1016/j.preteyeres.2019.05.005

  8. Mallipatna ACGB, Chéves-Barrios P (2017) AJCC Cancer Staging Manual. In: Amin MB, Edge SB, Greene FL et al (eds) Springer, New York, pp 819–831

  9. Choucair ML, Brisse HJ, Fréneaux P et al (2020) Management of advanced uni- or bilateral retinoblastoma with macroscopic optic nerve invasion. Pediatr Blood Cancer 67:e27998

    Article  PubMed  Google Scholar 

  10. de Jong MC, de Graaf P, Noij DP et al (2014) Diagnostic performance of magnetic resonance imaging and computed tomography for advanced retinoblastoma: a systematic review and meta-analysis. Ophthalmology 121:1109–1118

    Article  PubMed  Google Scholar 

  11. de Graaf P, Barkhof F, Moll AC et al (2005) Retinoblastoma: MR imaging parameters in detection of tumor extent. Radiology 235:197–207

    Article  PubMed  Google Scholar 

  12. Brisse HJ, de Graaf P, Galluzzi P et al (2015) Assessment of early-stage optic nerve invasion in retinoblastoma using high-resolution 1.5 Tesla MRI with surface coils: a multicentre, prospective accuracy study with histopathological correlation. Eur Radiol 25:1443–1452

    Article  PubMed  Google Scholar 

  13. Jansen RW, van der Heide S, Cardoen L et al (2022) MRI can reliably differentiate optic nerve inflammation from tumor invasion in retinoblastoma with orbital cellulitis. Ophthalmology. https://doi.org/10.1016/j.ophtha.2022.06.013

    Article  PubMed  Google Scholar 

  14. De Jong MC, van der Meer FJ, Goricke SL et al (2016) Diagnostic accuracy of intraocular tumor size measured with MR imaging in the prediction of postlaminar optic nerve invasion and massive choroidal invasion of retinoblastoma. Radiology 279:817–826

    Article  PubMed  Google Scholar 

  15. de Jong MC (2017) Epidemiology and imaging of retinoblastoma (Doctoral dissertation, Vrije Universiteit Amsterdam). Retrieved from https://hdl.handle.net/1871/55441

  16. de Jong MC, Van Der Valk P, Jansen RW et al (2020) Full-width postlaminar optic nerve tumor invasion of retinoblastoma as risk-factor for leptomeningeal spread of retinoblastoma. A case report and review of the literature. Ophthalmic Genet 41:69–72

    Article  PubMed  Google Scholar 

  17. Bossuyt PM, Reitsma JB, Bruns DE et al (2003) The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Ann Intern Med 138:W1-12

    Article  PubMed  Google Scholar 

  18. de Graaf P, Goricke S, Rodjan F et al (2012) Guidelines for imaging retinoblastoma: imaging principles and MRI standardization. Pediatr Radiol 42:2–14

    Article  PubMed  Google Scholar 

  19. Koo TK, Li MY (2016) A Guideline of Selecting and Reporting Intraclass Correlation Coefficients for Reliability Research. J Chiropr Med 15:155–163

    Article  PubMed  PubMed Central  Google Scholar 

  20. Bohning D, Holling H, Patilea V (2011) A limitation of the diagnostic-odds ratio in determining an optimal cut-off value for a continuous diagnostic test. Stat Methods Med Res 20:541–550

    Article  PubMed  Google Scholar 

  21. de Jong MC, Kors WA, de Graaf P, Castelijns JA, Kivela T, Moll AC (2014) Trilateral retinoblastoma: a systematic review and meta-analysis. Lancet Oncol 15:1157–1167

    Article  PubMed  Google Scholar 

  22. Sirin S, Schlamann M, Metz KA et al (2015) High-resolution MRI using orbit surface coils for the evaluation of metastatic risk factors in 143 children with retinoblastoma: part 1: MRI vs. histopathology. Neuroradiology 57:805–814

    Article  PubMed  Google Scholar 

  23. Cho SJ, Kim JH, Baik SH, Sunwoo L, Bae YJ, Choi BS (2021) Diagnostic performance of MRI of post-laminar optic nerve invasion detection in retinoblastoma: a systematic review and meta-analysis. Neuroradiology 63:499–509

    Article  PubMed  Google Scholar 

  24. Gizewski ER, Wanke I, Jurklies C, Güngör AR, Forsting M (2005) T1 Gd-enhanced compared with CISS sequences in retinoblastoma: superiority of T1 sequences in evaluation of tumour extension. Neuroradiology 47:56–61

    Article  PubMed  Google Scholar 

  25. Grimes DA, Schulz KF (2005) Compared to what? Finding controls for case-control studies. Lancet 365:1429–1433

    Article  PubMed  Google Scholar 

  26. Moll AC, Kuik DJ, Bouter LM et al (1997) Incidence and survival of retinoblastoma in The Netherlands: a register based study 1862–1995. Br J Ophthalmol 81:559–562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Brisse HJ, Guesmi M, Aerts I et al (2007) Relevance of CT and MRI in retinoblastoma for the diagnosis of postlaminar invasion with normal-size optic nerve: a retrospective study of 150 patients with histological comparison. Pediatr Radiol 37:649–656

    Article  PubMed  Google Scholar 

  28. Abramson DH, Schefler AC, Almeida D, Folberg R (2003) Optic nerve tissue shrinkage during pathologic processing after enucleation for retinoblastoma. Arch Ophthalmol 121:73–75

    Article  PubMed  Google Scholar 

  29. Yuan W, Beaulieu-Jones BK, Yu KH et al (2021) Temporal bias in case-control design: preventing reliable predictions of the future. Nat Commun 12:1107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

For the European Retinoblastoma Imaging Collaboration

Funding

This research was funded by the Hanarth Foundation, Grant for project titled MRI-based Deep Learning Segmentation and Quantitative Radiomics in Retinoblastoma: A Next Step Towards Personalized Interventions. The funding sources had no influence on data collection, analysis, manuscript preparation or publication.

Author information

Authors and Affiliations

  1. European Retinoblastoma Imaging Collaboration (ERIC), Amsterdam, The Netherlands

    Christiaan M. de Bloeme, Robin W. Jansen, Sophia Göricke, Sabien van Elst, Hervé J. Brisse, Paolo Galluzzi, Liesbeth Cardoen, Selma Sirin, Mériam Koob, Philippe Maeder, Pim de Graaf & Marcus C. de Jong

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

    Christiaan M. de Bloeme, Robin W. Jansen, Sabien van Elst, Annette C. Moll, Pim de Graaf & Marcus C. de Jong

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

    Christiaan M. de Bloeme, Robin W. Jansen, Steven T. L. Grauwels, Sabien van Elst, Pim de Graaf & Marcus C. de Jong

  4. Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany

    Sophia Göricke

  5. Department of Pediatric Oncology, University Hospital Essen, Essen, Germany

    Petra Ketteler

  6. Department of Radiology, Institut Curie, Paris, France and Paris University, Paris, France

    Hervé J. Brisse & Liesbeth Cardoen

  7. Department of Neuroimaging Unit, Siena University Hospital, Siena, Italy

    Paolo Galluzzi

  8. Department of Diagnostic and Interventional Radiology and Neuroradiology, Children’s Hospital Zurich, Zurich, Switzerland

    Selma Sirin

  9. Department of Radiology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland

    Mériam Koob & Philippe Maeder

  10. Department of Pathology, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

    Paul van der Valk

  11. Department of Ophthalmology, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

    Annette C. Moll

Authors
  1. Christiaan M. de Bloeme
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Consortia

on behalf of the European Retinoblastoma Imaging Collaboration

Corresponding author

Correspondence to Christiaan M. de Bloeme.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Marcus C. de Jong.

Conflict of interest

No conflicting relationship exists for any author.

Statistics and biometry

Marcus C. de Jong has significant statistical expertise and oversaw this process.

Informed consent

Written informed consent was waived by the Institutional Review Board (IRB number IRB00002991).

Ethical approval

Institutional Review Board approval was obtained (Institutional review board of the Amsterdam UMC).

Study subjects or cohorts overlap

Some study subjects have been previously reported in “Magnetic Resonance Imaging Can Reliably Differentiate Optic Nerve Inflammation from Tumor Invasion in Retinoblastoma with Orbital Cellulitis” by R.W. Jansen et al (2022) https://doi.org/10.1016/j.ophtha.2022.06.013.

Methodology

• retrospective

• case–control study

• multicenter study

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de Bloeme, C.M., Jansen, R.W., Göricke, S. et al. Optic nerve thickening on high-spatial-resolution MRI predicts early-stage postlaminar optic nerve invasion in retinoblastoma. Eur Radiol (2023). https://doi.org/10.1007/s00330-023-10471-z

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  • DOI: https://doi.org/10.1007/s00330-023-10471-z

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