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Robot-guided convection-enhanced delivery of carboplatin for advanced brainstem glioma

  • Technical Note - Pediatrics
  • Published:
Acta Neurochirurgica Aims and scope Submit manuscript

Abstract

Background

Patients with diffuse intrinsic pontine glioma (DIPG) have a poor prognosis with median survival reported as 9 months. The failure of systemic chemotherapy to improve prognosis may be due to inadequate penetration of the blood–brain barrier (BBB). Convection-enhanced delivery (CED) has the potential to improve outcomes by facilitating bypass of the BBB. We describe the first use of carboplatin for the treatment of advanced DIPG using a robot-guided catheter implantation technique.

Methods

A 5-year-old boy presented with a pontine mass lesion. The tumor continued to progress despite radiotherapy. Using an in-house modification to neuroinspire stereotactic planning software (Renishaw Plc., Gloucestershire, UK), the tumor volume was calculated as 43.6 ml. A transfrontal trajectory for catheter implantation was planned facilitating the in-house manufacture of a recessed-step catheter. The catheter was implanted using a neuromate robot (Renishaw Plc., Gloucestershire, UK). The initial infusion of carboplatin (0.09 mg/ml) was commenced with real-time T2-weighted MRI, facilitating estimation of the volume of infusate distribution. Infusions were repeated on a total of 5 days.

Results

The catheter implantation and infusions were well tolerated. A total volume of 49.8 ml was delivered over 5 days. T2-weighted MRI on completion of the final infusion demonstrated signal change through a total volume of 35.1 ml, representing 95 % of the targeted tumor volume. Follow-up at 4 weeks revealed clinical signs of improvement and increased T2 signal change throughout the volume of distribution. However, there was tumor progression in the regions outside the volume of distribution.

Conclusions

This case demonstrates the feasibility of accurately and safely delivering small-diameter catheters to the brainstem using a robot-guided implantation procedure, and real-time MRI tracking of infusate distribution.

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References

  1. Albright AL, Packer RJ, Zimmerman R, Rorke LB, Boyett J, Hammond GD (1993) Magnetic resonance scans should replace biopsies for the diagnosis of diffuse brain stem gliomas: a report from the Children’s Cancer Group. Neurosurgery 33(6):1026–1029

    Article  PubMed  CAS  Google Scholar 

  2. Bobo RH, Laske DW, Akbasak A, Morrison PF, Dedrick RL, Oldfield EH (1994) Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci USA 91(6):2076–2080

    Article  PubMed  CAS  Google Scholar 

  3. Bouffet E, Raquin M, Doz F, Gentet JC, Rodary C, Demeocq F, Chastagner P, Lutz P, Hartmann O, Kalifa C (2000) Radiotherapy followed by high-dose busulfan and thiotepa: a prospective assessment of high-dose chemotherapy in children with diffuse pontine gliomas. Cancer 88(3):685–692

    Article  PubMed  CAS  Google Scholar 

  4. Chen MY, Lonser RR, Morrison PF, Governale LS, Oldfield EH (1999) Variables affecting convection-enhanced delivery to the striatum: a systematic examination of rate of infusion, cannula size, infusate concentration, and tissue-cannula sealing time. J Neurosurg 90(2):315–320

    Article  PubMed  CAS  Google Scholar 

  5. Degen JW, Walbridge S, Vortmeyer AO, Oldfield EH, Lonser RR (2003) Safety and efficacy of convection-enhanced delivery of gemcitabine or carboplatin in a malignant glioma model in rats. J Neurosurg 99(5):893–898

    Article  PubMed  CAS  Google Scholar 

  6. Epstein F, Wisoff JH (1988) Intrinsic brainstem tumors in childhood: surgical indications. J Neurooncol 6(4):309–317

    Article  PubMed  CAS  Google Scholar 

  7. Grigsby PW, Thomas PR, Schwartz HG, Fineberg B (1987) Irradiation of primary thalamic and brainstem tumors in a pediatric population. A 33-year experience. Cancer 60(12):2901–2906

    Article  PubMed  CAS  Google Scholar 

  8. Iyer RR, Butman JA, Walbridge S, Gai ND, Heiss JD, Lonser RR (2011) Tracking accuracy of T2- and diffusion-weighted magnetic resonance imaging for infusate distribution by convection-enhanced delivery. J Neurosurg 115(3):474–480

    Article  PubMed  Google Scholar 

  9. Kalifa C, Valteau D, Pizer B, Vassal G, Grill J, Hartmann O (1999) High-dose chemotherapy in childhood brain tumours. Childs Nerv Syst 15(10):498–505

    Article  PubMed  CAS  Google Scholar 

  10. Kaplan AM, Albright AL, Zimmerman RA, Rorke LB, Li H, Boyett JM, Finlay JL, Wara WM, Packer RJ (1996) Brainstem gliomas in children. A Children’s Cancer Group review of 119 cases. Pediatr Neurosurg 24(4):185–192

    Article  PubMed  CAS  Google Scholar 

  11. Krauze MT, Saito R, Noble C, Bringas J, Forsayeth J, McKnight TR, Park J, Bankiewicz KS (2005) Effects of the perivascular space on convection-enhanced delivery of liposomes in primate putamen. Exp Neurol 196(1):104–111

    Article  PubMed  CAS  Google Scholar 

  12. Lidar Z, Mardor Y, Jonas T, Pfeffer R, Faibel M, Nass D, Hadani M, Ram Z (2004) Convection-enhanced delivery of paclitaxel for the treatment of recurrent malignant glioma: a phase I/II clinical study. J Neurosurg 100(3):472–479

    Article  PubMed  CAS  Google Scholar 

  13. Packer RJ, Boyett JM, Zimmerman RA, Albright AL, Kaplan AM, Rorke LB, Selch MT, Cherlow JM, Finlay JL, Wara WM (1994) Outcome of children with brain stem gliomas after treatment with 7800 cGy of hyperfractionated radiotherapy. A Childrens Cancer Group Phase I/II Trial. Cancer 74(6):1827–1834

    Article  PubMed  CAS  Google Scholar 

  14. Patel NK, Plaha P, Gill SS (2007) Magnetic resonance imaging-directed method for functional neurosurgery using implantable guide tubes. Neurosurgery 61(5 Suppl 2):358–365

    Article  PubMed  Google Scholar 

  15. Salvatore MF, Ai Y, Fischer B, Zhang AM, Grondin RC, Zhang Z, Gerhardt GA, Gash DM (2006) Point source concentration of GDNF may explain failure of phase II clinical trial. Exp Neurol 202(2):497–505

    Article  PubMed  CAS  Google Scholar 

  16. Sampson JH, Archer G, Pedain C, Wembacher-Schroder E, Westphal M, Kunwar S, Vogelbaum MA, Coan A, Herndon JE, Raghavan R, Brady ML, Reardon DA, Friedman AH, Friedman HS, Rodriguez-Ponce MI, Chang SM, Mittermeyer S, Croteau D, Puri RK (2010) Poor drug distribution as a possible explanation for the results of the PRECISE trial. J Neurosurg 113(2):301–309

    Article  PubMed  Google Scholar 

  17. Sampson JH, Raghavan R, Provenzale JM, Croteau D, Reardon DA, Coleman RE, Rodriguez Ponce I, Pastan I, Puri RK, Pedain C (2007) Induction of hyperintense signal on T2-weighted MR images correlates with infusion distribution from intracerebral convection-enhanced delivery of a tumor-targeted cytotoxin. Ajr 188(3):703–709

    Article  PubMed  Google Scholar 

  18. Shuper A, Kornreich L, Loven D, Michowitz S, Schwartz M, Cohen IJ (1998) Diffuse brain stem gliomas. Are we improving outcome? Childs Nerv Syst 14(10):578–581

    Article  PubMed  CAS  Google Scholar 

  19. White E, Bienemann A, Malone J, Megraw L, Bunnun C, Wyatt M, Gill S (2011) An evaluation of the relationships between catheter design and tissue mechanics in achieving high-flow convection-enhanced delivery. J Neurosci Methods 199(1):87–97

    Article  PubMed  Google Scholar 

  20. Whittle IR, Malcolm G, Jodrell DI, Reid M (1999) Platinum distribution in malignant glioma following intraoperative intravenous infusion of carboplatin. Br J Neurosurg 13(2):132–137

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Funding for the 3-T MRI scanner was provided by The Gatsby Foundation. The manufacture of catheters was funded from The Functional Neurosurgery Research Fund. We would like to thank Maureen Wiltshire for her administrative and organizational support. We would also like to thank Ali Bienemann, Marcie Wyatt, Dave Johnson, Owen Lewis, Charlie Irving, Gavin Murray, Catriona Fennelly, Stuart Campbell and Paul Skinner for their assistance in catheter development. We would also like to acknowledge the courage of this child and his family.

Conflicts of interest

N. Barua is a consultant clinical advisor to Renishaw Plc. S. Gill is Renishaw’s clinical director.

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Authors and Affiliations

  1. Department of Neurosurgery, Frenchay Hospital, Bristol, BS16 1LE, UK

    N. U. Barua & S. S. Gill

  2. Department of Paediatric Oncology, Bristol Children’s Hospital, Bristol, UK

    S. P. Lowis

  3. Neuro Applications Division, Renishaw Plc., Wotton-under-Edge, Gloucestershire, UK

    M. Woolley, S. O’Sullivan & R. Harrison

Authors
  1. N. U. Barua
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  2. S. P. Lowis
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  3. M. Woolley
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  4. S. O’Sullivan
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  5. R. Harrison
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  6. S. S. Gill
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Correspondence to S. S. Gill.

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Barua, N.U., Lowis, S.P., Woolley, M. et al. Robot-guided convection-enhanced delivery of carboplatin for advanced brainstem glioma. Acta Neurochir 155, 1459–1465 (2013). https://doi.org/10.1007/s00701-013-1700-6

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  • DOI: https://doi.org/10.1007/s00701-013-1700-6

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