A multivariate analysis of factors determining tumor progression in childhood low-grade glioma: a population-based cohort study (CCLG CNS9702)

Abstract

The purpose of this study was to identify risk factors for the progression of low-grade glioma in children from a large population-based cohort. Patient and tumor details of a national cohort of children with low-grade glioma, recruited into an international multidisciplinary clinical strategy, were subjected to univariate and multivariate analyses of progression-free survival and overall survival. From the cohort of 798 patients, 639 patients were eligible, with a median age 6.71 years (0.26-16.75 years); 49% were males; 15.9% had neurofibromatosis type 1, 63.7% pilocytic astrocytoma, 5.9% fibrillary astrocytoma, 4.2% mixed neuronal-glial tumors, and 3.6% others; 21.1% were diagnosed clinically. Anatomically implicated were 31.6% cerebellum, 24.6% chiasma/hypothalamus, 16.0% cerebral hemispheres, 9.9% brain stem, 6.1% other supratentorial midline structures, 5.9% optic nerve only, 4.5% spinal cord, and 1.4% others. The 5-year overall survival and progression-free survival in the whole cohort were 94.6% and 69.4%, respectively. There was a significant association between age and site (P < .001) and extent of tumor resection and site (P < .001). Multivariate analysis identified young age, fibrillary astrocytoma, and extent of surgical resection as significant independent risk factors for progression. Hypothalamic/chiasmatic tumors demonstrated the most sustained tendency to progress. In conclusion, the influence of age and anatomical site upon the risk of tumor progression suggests that these factors strongly influence tumor behavior for the majority of pilocytic tumors. Age <1 year and 1-5 years, fibrillary histology, completeness of resection, and chiasmatic location are candidates for stratification in future studies.

Functional changes after treatment of optic pathway paediatric low-grade gliomas

“…Although chemotherapy is nowadays the mainstay of treatment when indicated, 18 our study was started in 2004 and surgery was the most used treatment for OPG in our clinic until 2009. Previous studies report 16.9% of relapse after surgical removal and 11% of relapse after nonsurgical treatment, 18,19 According to our results, surgical and nonsurgical treatment modalities of LGG in paediatric patients do not seem sufficient to limit disease progression.…”

The role of surgery in optic pathway/hypothalamic gliomas in children

“…This is particularly noticeable in patients who have NF1, although it is not exclusively the case. 7,14,17,18,23,29,41 A significant number of tumors will, however, grow and require therapeutic interventions. 23,26,27,29 These interventions should be carefully planned and timed with the aim of controlling the tumor itself, with the potential for treatment-related morbidity taken into account.…”

“…21,26 Although it is accepted that radiotherapy can often be effective in controlling growth in these tumors, the late side effects of radiotherapy have led to a reduction in its use, particularly as most of these patients should be expected to survive into adulthood. There remains controversy over the precise role of neurosurgery, 16,18,19,24,35,[39][40][41][42]47 with many teams regarding this as an intervention of last resort with potentially unacceptable morbidity.…”

“…6,8,12,17,23,25,35 A significant proportion (10%-70%) occur in patients with neurofibromatosis Type 1 (NF1). 7,14,17,18,23,26,29,31,41 Up to half of OPHGs are reported to remain stable and not require intervention; hence an initial watch-andwait policy is often employed. This is particularly the case if there is no imminent threat to vital functions and also in patients with NF1.…”

The role of early intra-operative MRI in partial resection of optic pathway/hypothalamic gliomas in children

“…Histologically, OPHGs are nearly always low-grade tumours, with pilocystic astrocytomas (WHO grade I) accounting for the majority, along with a proportion of pilomyxoid astrocytomas (WHO grade II) [5,7,9,11,17,22,30]. A strong association with Neurofibromatosis Type 1 (NF1) is observed, which tends to correlate with a more benign course [6,10,11,13,17,[24][25]28,34].…”