Clinical tolerance of corticospinal tracts in convection-enhanced delivery to the brainstem

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OBJECTIVE

Convection-enhanced delivery (CED) has been explored as a therapeutic strategy for diffuse intrinsic pontine glioma (DIPG). Variables that may affect tolerance include infusate volume, infusion rate, catheter trajectory, and target position. Supratentorial approaches for catheter placement and infusate distribution patterns may conflict with corticospinal tracts (CSTs). The clinical relevance of these anatomical constraints has not been described. The authors report their experience using CED in the brainstem as it relates to anatomical CST conflict and association with clinical tolerance.

METHODS

In a phase I clinical trial of CED for DIPG (clinical trial registration no. NCT01502917, clinicaltrials.gov), a flexible infusion catheter was placed with MRI guidance for infusion of 124I-8H9, a radioimmunotherapeutic agent. Intra- and postprocedural MR images were analyzed to identify catheter trajectories and changes in T2-weighted signal intensity to approximate volume of distribution (Vd). Intersection of CST by the catheter and overlap between Vd and CST were recorded and their correlation with motor deficits was evaluated.

RESULTS

Thirty-one patients with a mean age of 7.6 years (range 3.2–18 years) underwent 39 catheter insertions for CED between 2012 and 2017. Thirty catheter insertions had tractography data available for analysis. The mean trajectory length was 105.5 mm (range 92.7–121.6 mm). The mean number of intersections of CST by catheter was 2.2 (range 0–3) and the mean intersecting length was 18.9 mm (range 0–44.2 mm). The first 9 infusions in the highest dose level (range 3.84–4.54 ml infusate) were analyzed for Vd overlap with CST. In this group, the mean age was 7.6 years (range 5.8–10.3 years), the mean trajectory length was 109.5 mm (range 102.6–122.3 mm), and the mean overlap between Vd and CST was 5.5 cm3. For catheter placement–related adverse events, 1 patient (3%) had worsening of a contralateral facial nerve palsy following the procedure with two CST intersections, an intersecting distance of 31.7 mm, and an overlap between Vd and CST of 3.64 cm3. For infusion-related adverse events, transient postinfusion deficits were noted in 3 patients in the highest dose level, with a mean number of 2 intersections of CST by catheter, mean intersecting length of 12.9 mm, and mean overlap between Vd and CST of 6.3 cm3.

CONCLUSIONS

A supratentorial approach to the brainstem crossing the CST resulted in one worsened neurological deficit. There does not appear to be a significant risk requiring avoidance of dominant motor fiber tracts with catheter trajectory planning. There was no correlation between Vd–CST overlap and neurological adverse events in this cohort.

Clinical trial registration no.: NCT01502917 (clinicaltrials.gov)

ABBREVIATIONS CED = convection-enhanced delivery; CST = corticospinal tract; CTCAE = Common Terminology Criteria for Adverse Events; DIPG = diffuse intrinsic pontine glioma; FA = fractional anisotropy; FOV = field of view; ROI = region of interest; Vd = volume of distribution; XBRT = external beam radiation therapy.
Article Information

Contributor Notes

Correspondence Peter F. Morgenstern: NewYork-Presbyterian Hospital, Weill Cornell Medical Center, New York, NY. pfmorgenstern@gmail.com.INCLUDE WHEN CITING Published online December 21, 2018; DOI: 10.3171/2018.6.JNS18854.Disclosures Dr. Souweidane reports being a consultant to Aesculap.
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References
  • 1

    Anderson RCKennedy BYanes CLGarvin JNeedle MCanoll P: Convection-enhanced delivery of topotecan into diffuse intrinsic brainstem tumors in children. J Neurosurg Pediatr 11:2892952013

    • Search Google Scholar
    • Export Citation
  • 2

    Barua NULowis SPWoolley MO’Sullivan SHarrison RGill SS: Robot-guided convection-enhanced delivery of carboplatin for advanced brainstem glioma. Acta Neurochir (Wien) 155:145914652013

    • Search Google Scholar
    • Export Citation
  • 3

    Chittiboina PHeiss JDLonser RR: Accuracy of direct magnetic resonance imaging-guided placement of drug infusion cannulae. J Neurosurg 122:117311792015

    • Search Google Scholar
    • Export Citation
  • 4

    Dellaretti MReyns NTouzet GDubois FGusmão SPereira JL: Stereotactic biopsy for brainstem tumors: comparison of transcerebellar with transfrontal approach. Stereotact Funct Neurosurg 90:79832012

    • Search Google Scholar
    • Export Citation
  • 5

    Hamisch CKickingereder PFischer MSimon TRuge MI: Update on the diagnostic value and safety of stereotactic biopsy for pediatric brainstem tumors: a systematic review and meta-analysis of 735 cases. J Neurosurg Pediatr 20:2612682017

    • Search Google Scholar
    • Export Citation
  • 6

    Helton KJWeeks JKPhillips NSZou PKun LEKhan RB: Diffusion tensor imaging of brainstem tumors: axonal degeneration of motor and sensory tracts. J Neurosurg Pediatr 1:2702762008

    • Search Google Scholar
    • Export Citation
  • 7

    Kunwar SChang SWestphal MVogelbaum MSampson JBarnett G: Phase III randomized trial of CED of IL13-PE38QQR vs Gliadel wafers for recurrent glioblastoma. Neuro Oncol 12:8718812010

    • Search Google Scholar
    • Export Citation
  • 8

    Kunwar SPrados MDChang SMBerger MSLang FFPiepmeier JM: Direct intracerebral delivery of cintredekin besudotox (IL13-PE38QQR) in recurrent malignant glioma: a report by the Cintredekin Besudotox Intraparenchymal Study Group. J Clin Oncol 25:8378442007

    • Search Google Scholar
    • Export Citation
  • 9

    Lonser RRWarren KEButman JAQuezado ZRobison RAWalbridge S: Real-time image-guided direct convective perfusion of intrinsic brainstem lesions. Technical note. J Neurosurg 107:1901972007

    • Search Google Scholar
    • Export Citation
  • 10

    Pincus DWRichter EOYachnis ATBennett JBhatti MTSmith A: Brainstem stereotactic biopsy sampling in children. J Neurosurg 104 (2 Suppl):1081142006

    • Search Google Scholar
    • Export Citation
  • 11

    Quick-Weller JLescher SBruder MDinc NBehmanesh BSeifert V: Stereotactic biopsy of brainstem lesions: 21 years experiences of a single center. J Neurooncol 129:2432502016

    • Search Google Scholar
    • Export Citation
  • 12

    Roujeau TMachado GGarnett MRMiquel CPuget SGeoerger B: Stereotactic biopsy of diffuse pontine lesions in children. J Neurosurg 107 (1 Suppl):142007

    • Search Google Scholar
    • Export Citation
  • 13

    Sampson JHAkabani GArcher GEBerger MSColeman REFriedman AH: Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors. Neuro Oncol 10:3203292008

    • Search Google Scholar
    • Export Citation
  • 14

    Sampson JHArcher GPedain CWembacher-Schröder EWestphal MKunwar S: Poor drug distribution as a possible explanation for the results of the PRECISE trial. J Neurosurg 113:3013092010

    • Search Google Scholar
    • Export Citation
  • 15

    Sun XChen ZYang SZhang JYue SWang Z: Role of high-field intraoperative magnetic resonance imaging on a multi-image fusion-guided stereotactic biopsy of the basal ganglia: a case report. Oncol Lett 9:2232262015

    • Search Google Scholar
    • Export Citation
  • 16

    Valles FFiandaca MSBringas JDickinson PLeCouteur RHiggins R: Anatomic compression caused by high-volume convection-enhanced delivery to the brain. Neurosurgery 65:5795862009

    • Search Google Scholar
    • Export Citation
  • 17

    Vogelbaum MASampson JHKunwar SChang SMShaffrey MAsher AL: Convection-enhanced delivery of cintredekin besudotox (interleukin-13-PE38QQR) followed by radiation therapy with and without temozolomide in newly diagnosed malignant gliomas: phase 1 study of final safety results. Neurosurgery 61:103110382007

    • Search Google Scholar
    • Export Citation
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