Clinical and treatment factors determining long‐term outcomes for adult survivors of childhood low‐grade glioma: A population‐based study

Abstract

BACKGROUND:The determinants of outcomes for adult survivors of pediatric low-grade glioma (PLGG) are largely unknown. METH-ODS: This study collected population-based follow-up information for all PLGG patients diagnosed in Ontario, Canada from 1985 to 2012 (n 5 1202) and determined factors affecting survival. The impact of upfront radiation treatment on overall survival (OS) was determined for a cohort of Ontario patients and an independent reference cohort from the Surveillance, Epidemiology, and End Results database. RESULTS: At a median follow-up of 12.73 years (range, 0.02-33 years), only 93 deaths (7.7%) were recorded, and the 20-year OS rate was 90.1% 6 1.1%. Children with neurofibromatosis type 1 had excellent survival and no tumor-related deaths during adulthood. Adverse risk factors included pleomorphic xanthoastrocytoma (P <.001) and a thalamic location (P <.001). For patients with unresectable tumors surviving more than 5 years after the diagnosis, upfront radiotherapy was associated with an approximately 3-fold increased risk of overall late deaths (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.6-6.6; P 5.001) and an approximately 4-fold increased risk of tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P 5.013). In a multivariate analysis, radiotherapy was the most significant factor associated with late all-cause deaths (HR, 3.0; 95% CI, 1.3-7.0; P 5.012) and tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P 5 0.014). A similar association between radiotherapy and late deaths was observed in the independent reference cohort (P <.001). In contrast to early deaths, late mortality was associated not with PLGG progression but rather with tumor transformation and non-oncological causes. CONCLUSIONS: The course of PLGG is associated with excellent long-term survival, but this is hampered by increased delayed mortality in patients receiving upfront radiotherapy. These observations should be considered when treatment options are being weighed for these patients. Cancer 2016;122:1261-9.

Neurologic impairments from pediatric low‐grade glioma by tumor location and timing of diagnosis

“…Our study included a higher proportion of patients with supratentorial LGG, which was similarly reported by other population‐based studies of LGG. A relatively low incidence of spinal cord LGGs has been reported in other studies as well . We found that receiving both chemotherapy and radiation therapy was a risk factor for higher rates of long‐term facial motor and sensory disorder, lower cranial nerve palsies, eye and visual dysfunction, motor weakness, sleep disturbances, and urinary dysfunction.…”

Current Clinical Brain Tumor Imaging

“…Grade I gliomas including pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and subependymal giant cell astrocytoma share a relatively benign biology with an indolent clinical course that is distinct from other diffuse infiltrating glioma grades. 23,24 Grade II–IV gliomas are heterogeneous tumors with variable degrees of infiltration, atypia, and mitotic activity. Microvascular proliferation with endothelial hyperplasia and pseudopallisading necrosis are the defining histological hallmarks of grade IV gliomas, frequently referred to as glioblastomas.…”

Use of bevacizumab as a single agent or in adjunct with traditional chemotherapy regimens in children with unresectable or progressive low‐grade glioma

“…As a result, alternative therapeutic strategies are currently used as firstline treatment, reserving radiation for tumors that have progressed despite the use of multiple lines of chemotherapy. 7,12 A strategy combining close observation with systemic chemotherapy if necessary has become the standard of care. 13 Tumor progression, threat to vision and hypothalamic-pituitary dysfunction in the case of an optic pathway glioma, tumor location, residual disease, age of the patient, and association with neurofibromatosis type 1 (NF1) can influence the decision about particular chemotherapeutic regimens.…”

“…However, due to the tendency of these lesions to be large and to typically affect young children, the potential for radiation‐induced brain injury, with the associated serious cognitive, developmental, and endocrine sequelae in the developing brain, is of major importance. As a result, alternative therapeutic strategies are currently used as first‐line treatment, reserving radiation for tumors that have progressed despite the use of multiple lines of chemotherapy . A strategy combining close observation with systemic chemotherapy if necessary has become the standard of care …”