Change in Neurocognitive Functioning After Treatment with Cranial Radiation in Childhood

Authors: BJ Spiegler, E Bouffet, ML Greenberg, et al.
Source:Journal of Clinical Oncology 22 (2004) 706–713.

Background

Treatment of pediatric posterior fossa tumors has evolved in the multimodality setting to the point that emphasis is no longer just on improving survival but in minimizing toxicities. Neurocognitive decline in patients with a primary brain malignancy treated with a multimodality approach including surgery, radiation and in the majority of cases chemotherapy has been documented by a number of studies. Patients are now living longer, long enough to demonstrate significant neurocognitve deficits in some cases. Confounding our ability to refine treatment strategies is the relative rarity in absolute numbers of study subjects. The prospect of a defining randomized study remains elusive. To that end, Spiegler and colleagues have conducted a retrospective study of change in neurocognitive functioning in patients with posterior fossa tumors after treatment with surgery, cranial radiation, and in most cases chemotherapy in childhood.

Methods

• Population characteristics included 34 children treated for malignant posterior fossa (PF) tumors in the past 20 years. 25 were males. 30 had medulloblastoma and four had empendymoma. Gross total resection was achieved in 50% of patients.
• Radiation exposure: 33 patients were treated with cranial radiation. 12 were treated to 23.4-30.2 Gy while 21 treated to 34-36 Gy. All received a PF boost with total dose to the PF from 45-55.8 Gy. One patient was treated to the PF only and received 54 Gy.
• 11 patients had a ventriculo-peritoneal shunt for hydrocephalus and 24 patients received Chemo. The type and dose were not specified, presumably because it was thought not to be relevant.
• All patients were seen for neuropsychologic evaluation after a single course of cranial radiation. Each patient had a neuropsychological evaluation at a minimum of two separate times so that change in neuropsycologic function could be measured.
• Mean age of diagnosis was six years which was similar to that of a larger population of 180 patients with medulloblastoma over the same period at the same institution.
• The investigators used a battery of tests to measure intelligence, receptive language, visual-motor functioning, verbal memory, visual memory, problem-solving and fluency, and fine motor skills.
• Half of the patients had their first assessment within 6 months of diagnosis. Median time to first assessment was 0.71 years (range 0 to 9.33 years): median time to last assessment was 4.71 years (range 1.33 to 15.25).
• Used mixed model regression to measure the change in scores over time and fit their data. Accuracy of fit to data was not discussed.

Results and Conclusions

• Intellectual functioning decrease on average by 2 I.Q points per year for the total population. A subset of patients whose initial evaluation occurred within six months of diagnosis showed an average of 3 I.Q. points decline per year.
• Visual motor function and visual memory also decreased in both populations but more rapidly in the subpopulation.
• Receptive vocabulary and verbal memory demonstrated a slight downward trend with less than 1 I.Q. point change per year.
• Executive function & fine motor skills were also relatively unchanged.

Discussion

This study reports on a retrospective trial of change in neurocognitive functioning in patients with posterior fossa tumors after treatment with surgery, cranial radiation, and in most cases chemotherapy in childhood. Since most pediatric patients with posterior fossa tumors are treated with a similar multimodality approach, this study forms an observational basis regarding outcomes patients, families, and practitioners can expect to encounter. The study further makes inroads by examining specific changes in neurocognitive function not previously studied in this population.

The failure of this study to examine and separate contributions of a neoplastic primary in brain, surgery, chemotherapy, or radiation to neurocognitive decline in this population lend a somewhat hollow ring to its title. It is likely that radiation to the whole brain or posterior fossa has a detrimental effect on neurocognitive function. Its relative contribution to the decline seen in this population remains uncharacterized.