Treatment burden and long‐term health deficits of patients with low‐grade gliomas or glioneuronal tumors diagnosed during the first year of life

Abstract

BACKGROUND: Low-grade gliomas (LGGs) and low-grade glioneuronal tumors (LGGNTs) diagnosed during the first year of life carry unique clinical characteristics and challenges in management. However, data on the treatment burden, outcomes, and morbidities are lacking. METHODS: A retrospective study of LGGs and LGGNTs diagnosed in patients younger than 12 months at St. Jude Children's Research Hospital (1986 was conducted. RESULTS: For the 51 patients (including 31 males), the mean age at diagnosis was 6.47 months (range, 0.17-11.76 months), and the mean follow-up period was 11.8 years (range, 0.21-29.19 years). Tumor locations were hypothalamic/optic pathway (61%), hemispheric (12%), brainstem (12%), cerebellar (8%), and spinal (8%). There were 41 patients with histological diagnoses: 28 had World Health Organization grade 1 tumors, 6 had grade 2 tumors, and 7 had an LGG/LGGNT not definitively graded. Forty-one patients required an active intervention at diagnosis. Throughout their treatment course, 41 patients eventually underwent tumor-directed surgeries (median, 2 surgeries; range, 1-6), 39 received chemotherapy (median, 2 regimens; range, 1-13), and 21 received radiotherapy. Forty patients experienced disease progression (median, 2 progressions; range, 1-18). Ten patients died of progression (n = 5), malignant transformation (n = 2), a second cancer (n = 2), or a shunt infection (n = 1). The 10-year overall survival, progression-free survival, and radiation-free survival rates were 85% ± 5.3%, 16.9% ± 5.3%, and 51.2% ± 7.5%, respectively. Forty-nine patients experienced health deficits (eg, endocrinopathies, obesity, seizures, visual/hearing impairments, neurocognitive impairments, and cerebrovascular disease). Predictors of progression and toxicities were defined. CONCLUSIONS: Infantile LGG/LGGNT is a chronic, progressive disease universally associated with long-term morbidities and requires multidisciplinary intervention.

Invited Review: DNA methylation‐based classification of paediatric brain tumours

“…This is particularly problematic for malignancy assessment of paediatric glial tumours and can result in an over estimation of malignancy for some patients as exemplified by a subset of paediatric glioblastoma and anaplastic pilocytic astrocytoma . On top of this, the consequences of a misdiagnosis are particularly grave in the paediatric context, for example the application of an unnecessary brain irradiation due to an overestimation of the malignancy of a glioma may lead to lifelong cognitive, endocrine and cerebral vascular dysfunction as well as the risk of radiation induced secondary brain tumours .…”

Glioneuronal Tumors: Insights into a Rare Tumor Entity

“…Generally, the outcome in patients with glioneuronal tumors can be broadly discussed in the context of progression of disease, transformation to higher grade tumors and the long-term complications of treatment or late effects. In a series of patients treated at the St. Jude Children' s Research Hospital (1986 to 2015), progression of disease and transformation to higher grade glioma accounted for 66% of the mortality (24). Other causes included secondary malignancy, shunt infection/sepsis, suicide and motor vehicle accidents (24).…”

“…In a series of patients treated at the St. Jude Children' s Research Hospital (1986 to 2015), progression of disease and transformation to higher grade glioma accounted for 66% of the mortality (24). Other causes included secondary malignancy, shunt infection/sepsis, suicide and motor vehicle accidents (24). In this series, the median age at death for the cohort was 14.26 years (range, 0.58-32 years), and the median time to death from diagnosis was 4.02 years (range, 0.21-24 years).…”

“…They identified postoperative gain in cognitive function in seizurefree patients, but at a relatively low level, and high levels of anxiety and depression (23). In a series of 51 patients with low grade glioma and glioneuronal tumors managed at the St. Jude' s Children' s Research Hospital, USA, (1986 to 2015) with a mean age at diagnosis of 6.47 months (range, 0.17-11.76) and mean duration of follow-up of 11.8 years, 96% of patients experienced at least one long-term deficit, such as endocrinopathy and obesity (51%), neurological deficit and seizure (43%), visual and hearing loss (56%), neurocognitive impairment (49%), cerebrovascular disease and scoliosis (27%) and secondary malignancy (14%) (24). Late effects correlated with tumor location (hypothalamic/optic pathway), administration of radiation therapy and more chemotherapy regimens (24).…”

“…In sub-totally resected disease and recurrent or grade II/III tumors, adjuvant treatment in the form of radiation and or chemotherapy may be administered; however, data on improvements in outcome are lacking (14)(15)(16)(17)(18)(19)(20)(21). Due to the indolent behavior of these tumors, late effects and survival are increasingly being examined (22)(23)(24).…”