Lighting the Way for Children with Aggressive Brain Tumors

Brain cancer has been increasing worldwide over the past two decades and is now the most common solid tumor diagnosed in childhood.  Thankfully, brain tumors in children behave much less aggressively than those occurring in adulthood. As you might expect, childhood brain tumors also tend to be much easier to treat, though the diagnosis understandably causes a great deal of stress for the entire family.

There are great differences among brain tumors in children, and the most aggressive types are the high-grade gliomas, malignant tumors that arise from the brain’s supportive tissue (glial cells). A classic example is glioblastoma multiforme (GBM), which is less common in children than in adults.  GBMs seem to occur with greater frequency in families with certain genetic diseases, such as hereditary nonpolyposis colon cancer and tuberous sclerosis.

Relatively little is known about the clinical outcome of GBM and other high-grade gliomas diagnosed in children.  Most children diagnosed with these aggressive brain tumors receive surgery and radiation, and in some cases chemotherapy.  In a recent study of children with GBM, the overall survival rate was 67% at 1 year, 52% at 2 years, and 40% at 5 years.

Fluorescence-guided surgery is a surgical approach that utilizes the fluorescing potential of compounds known as photosensitizers.  These compounds become preferentially concentrated in tumor tissues.  Upon being exposed to specific light frequencies, the malignant tissues begin to glow, and this helps the surgeon better distinguish the malignant tissue from normal tissue during surgery.

One such compound is 5-aminolevulinic acid (5-ALA), which has been well studied as an adjunct for the surgery of adult malignant glioma.  In that population, it has been shown to improve the rate of total tumor removal as well as patient survival.  So far, only a few reports of fluorescence-guided surgery in children have been published.

Researchers from the Department of Neurosurgery at Heinrich-Heine-Universität in Düsseldorf, Germany, recently reported on a pilot study of 16 pediatric brain tumors, all treated with 5-ALA-guided surgery.  The average age was nine years old, and the range was from one to 16 years of age.

In this group, various types of brain tumors were found, including pilocytic astrocytoma, classical medulloblastoma, anaplastic astrocytoma, anaplastic ependymoma, and glioblastoma.   Positive fluorescence was observed in cases of glioblastoma, anaplastic astrocytoma, and medulloblastoma, respectively.

Thus, definite fluorescence occurred in high-grade gliomas as well as one medulloblastoma after oral administration of 5-ALA.  The investigators further noted that adverse reactions observed in children were similar to those reported for adults, although they caution that very young children could be at increased risk. Further studies are needed to clarify the various properties of 5-ALA in children and to assess its prognostic role in the treatment of pediatric brain tumors.
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Beez T1, Sarikaya-Seiwert S, Steiger HJ, Hänggi D. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of brain tumors in children-a technical report. Acta Neurochir (Wien). 2014 Mar;156(3):597-604.

Sturm D, Bender S, Jones DT, Lichter P, Grill J, Becher O, Hawkins C, Majewski J, Jones C, Costello JF, Iavarone A, Aldape K, Brennan CW, Jabado N, Pfister SM. Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge. Nat Rev Cancer. 2014 Jan 24;14(2):92-107.

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