Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors: a European survey

Abstract

Background: Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we conducted a survey among certified European Gliolan users to collect data on their experiences with children.

Methods: Information on patient characteristics, MRI characteristics of tumors, histology, fluorescence qualities, and outcomes were requested. Surgeons were further asked to indicate whether fluorescence was "useful", i.e., leading to changes in surgical strategy or identification of residual tumor. Recursive partitioning analysis (RPA) was used for defining cohorts with high or low likelihoods for useful fluorescence.

Results: Data on 78 patients <18 years of age were submitted by 20 centers. Fluorescence was found useful in 12 of 14 glioblastomas (85 %), four of five anaplastic astrocytomas (60 %), and eight of ten ependymomas grades II and III (80 %). Fluorescence was found inconsistently useful in PNETs (three of seven; 43 %), gangliogliomas (two of five; 40 %), medulloblastomas (two of eight, 25 %) and pilocytic astrocytomas (two of 13; 15 %). RPA of pre-operative factors showed tumors with supratentorial location, strong contrast enhancement and first operation to have a likelihood of useful fluorescence of 64.3 %, as opposed to infratentorial tumors with first surgery (23.1 %).

Conclusions: Our survey demonstrates 5-ALA as being used in pediatric brain tumors. 5-ALA may be especially useful for contrast-enhancing supratentorial tumors. These data indicate controlled studies to be necessary and also provide a basis for planning such a study.

Fig. 1

Distribution of ages for the complete cohort and stratified by recurrence status

Fig. 2

Distribution of administration time of complete cohort, stratified by recurrence status

Fig. 3

Example of fluorescence in ependymoma grade II (female, 12 years of age). Top left: blue light image of typical red fluorescence characterized as strong and related to ependymoma tissue (Zeiss Pentero); top right: Corresponding white light image. Bottom left: preoperative MRI showing tumor of 4th ventricle with patchy contrast-enhancement; middle: blue light image of tissue specimen; right: corresponding white light image

Fig. 4

Decision tree generated from recursive partitioning analysis for ex ante determination of the likelihood for “usefulness”. Factors: Location; contrast enhancement on MRI, recurrence status (“useful” = provoking a change in surgical strategy or helping detect residual tumor; two children with spinal tumors excluded). There are five terminal nodes based on the likelihood of “usefulness” of fluorescence after three splits