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Development of a clinical scale for assessment of patients with diffuse intrinsic pontine glioma (DIPG) receiving experimental therapy: the PONScore

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Abstract

Purpose

Monitoring neurological side-effects in experimental therapy for diffuse intrinsic pontine glioma (DIPG) can be challenging. We aimed to develop a neurological scale that could be used by non-specialists to quantify neurological changes during experimental treatment of DIPG.

Methods

We developed the Pontine Observational Neurological Score (PONScore) to measure signs and symptoms of DIPG by adapting validated assessment scales of neurological signs and symptoms in children. We developed a prototype score, taught it to paediatric intensive care nursing staff, who used the Score to assess children receiving awake pontine infusion of chemotherapy for treatment of DIPG. We used their feedback to develop the PONScore. Points are allocated for headache, ophthalmoplegia, facial and tongue weakness, dysarthria, paraesthesia, limb weakness and dysmetria with increasing scores reflecting increasing disability. The PONScore was administered every hour during awake pontine infusion. Correlation and agreement calculations between nursing staff, as non-specialists, and a specialist rater were performed in 30 infusions in 6 children (aged 8–11). Changes in PONScore versus volume of infusion are described in a further 55 infusions in 8 children (aged 3–11).

Results

The PONScore demonstrated excellent intra-rater reliability with an intra-class co-efficient of 0.98 (95% CI 0.97–0.99; p-value < 0.001) between a specialist and non-specialist raters with strong correlation between scores and a Spearman correlation coefficient of 0.985 (p < 0.001). PONScores increased from 3.3 to 5.7 (p-value < 0.001) during infusion reflecting accumulation of neurological signs and symptoms during infusion.

Conclusions

We describe a novel neurological scale that can be used by non-specialists to describe acute neurological changes in children receiving experimental therapy for DIPG. Prospective validation as part of a clinical trial is required.

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References

  1. Veldhuijzen van Zanten SE, van Meerwijk CL, Jansen MH et al (2016) Palliative and end-of-life care for children with diffuse intrinsic pontine glioma: results from a London cohort study and international survey. Neuro Oncol 18:582–588

    Article  Google Scholar 

  2. Hargrave D, Bartels U, Bouffet E (2016) Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol 7:241–248

    Article  Google Scholar 

  3. Loveson KF, Fillmore HL (2018) Intersection of brain development and paediatric diffuse midline gliomas: potential role of microenvironment in tumour growth. Brain Sci 8:200

    Article  CAS  Google Scholar 

  4. Cohen KJ, Jones A, Raabe E, Pearl M (2014) Highly selective intra-arterial chemotherapy for the treatment of progressive diffuse intrinsic pontine gliomas (DIPG). Neuro Oncol. https://doi.org/10.1093/neuonc/nou208.24

    Article  PubMed  PubMed Central  Google Scholar 

  5. Singleton WGB, Barua NU, Morgan J et al (2016) NS-21: multi-catheter intermittent convection-enhanced delivery of carboplatin as a treatment for diffuse intrinsic pontine glioma (DIPG): pre-clinical rationale and early clinical experience. Neuro Oncol. https://doi.org/10.1093/neuonc/now078.21

    Article  PubMed Central  Google Scholar 

  6. Souweidane MM, Kramer K, Pandit-Taskar N et al (2018) Convection-enhanced delivery for diffuse intrinsic pontine glioma: a single-centre, dose-escalation, phase 1 trial. Lancet Oncol 19(8):1040–1050

    Article  Google Scholar 

  7. Hollingworth M, Hurter C, Wooley M, Lewis O, Gill S, Zacharoulis S (2018) DIPG-65. preliminary experience of chronic intermittent convection enhanced delivery of carboplatin and valproic acid for the treatment of diffuse intrinsic pontine glioma following radiation therapy. Neuro Oncol. https://doi.org/10.1093/neuonc/noy059.158

    Article  PubMed Central  Google Scholar 

  8. Kieran MW (2015) Time to rethink the unthinkable: upfront biopsy of children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). Pediatr Blood Cancer 62:3–4

    Article  Google Scholar 

  9. Hennika T, Becher OJ (2016) Diffuse intrinsic pontine glioma: time for cautious optimism. J Child Neurol 31:1377–1385

    Article  Google Scholar 

  10. Ostrom QT, Gittleman H, Farah P et al (2013) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro Oncol. https://doi.org/10.1093/neuonc/not151

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bobo RH, Laske DW, Akbasak A et al (1994) Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci USA 91:2076–2080

    Article  CAS  Google Scholar 

  12. Miranpuri G, Hinchman A, Wang A et al (2013) Convection enhanced delivery: a comparison of infusion characteristics in ex vivo and in vivo non-human primate brain tissue. Ann Neurosci 20:108–114

    Article  CAS  Google Scholar 

  13. Killick-Cole CL, Singleton WGB, Bienemann AS et al (2017) Repurposing the anti-epileptic drug sodium valproate as an adjuvant treatment for diffuse intrinsic pontine glioma. PLoS ONE 12(5):e0176855

    Article  Google Scholar 

  14. Barua NU, Lowis SP, Woolley M, O'Sullivan S, Harrison R, Gill SS (2013) Robot-guided convection-enhanced delivery of carboplatin for advanced brainstem glioma. Acta Neurochir (Wien) 155:1459–1465

    Article  CAS  Google Scholar 

  15. Barua NU, Hopkins K, Woolley M et al (2016) A novel implantable catheter system with transcutaneous port for intermittent convection-enhanced delivery of carboplatin for recurrent glioblastoma. Drug Deliv 23:167–173

    Article  CAS  Google Scholar 

  16. Ichord RN, Bastian R, Abraham L et al (2011) Interrater reliability of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) in a multicenter study. Stroke 42:613–617

    Article  Google Scholar 

  17. Schmitz-Hubsch T, de Montcel ST, Baliko L et al (2006) Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology 66:1717–1720

    Article  CAS  Google Scholar 

  18. Brandsma R, Spits AH, Kuiper MJ et al (2014) Ataxia rating scales are age-dependent in healthy children. Dev Med Child Neurol 56:556–563

    Article  Google Scholar 

  19. Wong DL, Baker CM (1998) Pain in children: comparison of assessment scales. Pediatr Nurs 14:9–17

    Google Scholar 

  20. House JW, Brackmann DE (1985) Facial nerve grading system. Otolaryngol Head Neck Surg 93:146–147

    Article  CAS  Google Scholar 

  21. Lazarus CL, Husaini H, Jacobson AS et al (2014) Development of a new lingual range-of-motion assessment scale: normative data in surgically treated oral cancer patients. Dysphagia 29:489–499

    Article  CAS  Google Scholar 

  22. Campbell W, DeJong RN (2005) Cranial nerves. In: Campbell W (ed) DeJong’s the neurologic examination, 7th edn. Lipincott Williams and Wilkins, Philidelphia, pp 146–161

    Google Scholar 

  23. Bland JM, Altman DG (1999) Measuring agreement in method comparison studies. Stat Methods Med Res 8:135–160

    Article  CAS  Google Scholar 

  24. Boateng GO, Neilands TB, Frongillo EA, Melgar-Quiñonez HR, Young SL (2018) Best practices for developing and validating scales for health, social, and behavioral research: a primer. Front Public Health 6:149

    Article  Google Scholar 

  25. Royal College of Nursing (2017) Standards for assessing measuring and monitoring vital signs in infants, children and young people. https://www.rcn.org.uk/-/media/royal-college-of-nursing/documents/publications/2017/may/pub-005942.pdf. Accessed 30 June 2020

  26. Nayak L, DeAngelis LM, Brandes AA, Peereboom DM, Galanis E, Nancy U, Lin NU et al (2017) The Neurologic Assessment in Neuro-Oncology (NANO) scale: a tool to assess neurologic function for integration into the Response Assessment in Neuro-Oncology (RANO) criteria. Neuro Oncol 19:625–635

    Article  Google Scholar 

  27. Helfer JL, Wen PY, Blakeley J, Gilbert MR, Armstrong TS (2016) Report of the Jumpstarting Brain Tumor Drug Development Coalition and FDA clinical trials clinical outcome assessment endpoints workshop (October 15, 2014, Bethesda MD). Neuro Oncol. https://doi.org/10.1093/neuonc/nov270

    Article  PubMed  PubMed Central  Google Scholar 

  28. Armstrong TS, Bishof AM, Brown PD, Klein M, Taphoorn MJ, Theodore-Oklota C (2016) Determining priority signs and symptoms for use as clinical outcomes assessments in trials including patients with malignant gliomas: panel 1 report. Neuro Oncol. https://doi.org/10.1093/neuonc/nov267

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We pay tribute to the bravery of the children and families involved in this treatment. We are grateful to Professor Steven Gill, North Bristol NHS Trust and Harley Street Clinic Children’s Hospital, for his pioneering work regarding multi-catheter awake pontine infusion. Thank you to Professor David Walker, Dr Steve Lowis, Mr Peter Collins, Dr Ali Bienemann, Mr Will Singleton, Mr Neil Barua, Dr David Cronin, Dr James Morgan and Miss Marina Pitsika for their important role in developing this clinical treatment. We are thankful to Dr Kim Bull for her thoughtful insights that helped in the score’s development.

Funding

Milo Hollingworth was supported with funds from the Gatsby Foundation.

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Authors and Affiliations

  1. Department of Neurosurgery, Queens Medical Centre, Nottingham University Hospital NHS Trust, Nottingham, NG7 2UH, UK

    Milo Alexander Hollingworth

  2. Paediatric Haemato-Oncology, CUMC/Herbert Irving Pavilion, New York, NY, 10032, USA

    Stergios Zacharoulis

Authors
  1. Milo Alexander Hollingworth
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Contributions

MH conducted the work, collected and analysed the data and wrote the manuscript. SZ supervised the work and developed the manuscript.

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Correspondence to Milo Alexander Hollingworth.

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Ethics approval for treatment on compassionate grounds was granted by the institutional ethics committee.

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Hollingworth, M., Zacharoulis, S. Development of a clinical scale for assessment of patients with diffuse intrinsic pontine glioma (DIPG) receiving experimental therapy: the PONScore. J Neurooncol 149, 263–272 (2020). https://doi.org/10.1007/s11060-020-03594-6

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  • DOI: https://doi.org/10.1007/s11060-020-03594-6

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