Late Effects of Conformal Radiation Therapy for Pediatric Patients With Low-Grade Glioma: Prospective Evaluation of Cognitive, Endocrine, and Hearing Deficits

Abstract

A B S T R A C T PurposeWe conducted a prospective trial to evaluate late effects in pediatric patients with low-grade glioma (LGG) treated with conformal radiation therapy (CRT). Patients and MethodsBetween August 1997 and August 2006, 78 pediatric patients with LGG (mean age, 9.7 years; standard deviation, Ϯ4.4 years) received 54 Gy of CRT with a 10-mm clinical target volume margin. Tumor locations were diencephalon (n ϭ 58), cerebral hemisphere (n ϭ 3), and cerebellum (n ϭ 17). Baseline and serial evaluations were performed to identify deficits in cognition, endocrine function, and hearing. Deficits were correlated with clinical factors and radiation dose within specific normal tissue volumes. ResultsCognitive effects of CRT through 5 years after CRT correlated with patient age, neurofibromatosis type 1 status, tumor location and volume, extent of resection, and radiation dose. The effect of age exceeded that of radiation dose; patients younger than 5 years experienced the greatest decline in cognition. Before CRT, growth hormone (GH) secretion abnormality was diagnosed in 24% of tested patients, and 12% had precocious puberty. The 10-year cumulative incidence of GH replacement was 48.9%; of thyroid hormone replacement, 64.0%; of glucocorticoid replacement, 19.2%; and of gonadotropin-releasing hormone analog therapy, 34.2%. The mean Ϯ standard errors of the cumulative incidence of hearing loss at 10 years did not exceed 5.7% Ϯ 3.3% at any frequency. ConclusionTo our knowledge, this is the largest series of prospectively followed children with LGG to undergo irradiation. Adverse effects are limited and predictable for most patients; however, this study provides additional evidence that CRT should be delayed for young patients and identifies the potential benefits of reducing radiation dose to normal brain.

Favorable outcome with conservative treatment for children with low grade brainstem tumors

“…Data regarding long-term toxicity of radiotherapy were reported in multiple studies. However, very few patients with BSLGT were included in these studies [26,29]. Edwards et al reported excellent short-term functional outcome following irradiation in five patients with focal brainstem astrocytomas [30].…”

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

“…However, some studies have reported an increased risk for vascular events and secondary radiation-induced malignancies, 18,43,44 and long-term survival after radiation has not been addressed adequately. Our study raises major concerns regarding the association of radiotherapy with increased overall and tumor-related late deaths.…”

“…[13][14][15][16] However, in the context of a low-grade tumor, potential sequelae associated with radiotherapy are a major concern, especially in young children. 13,17,18 The comparison of previous studies is often inconclusive; newly recognized pathological entities such as pilomyxoid astrocytoma and pleomorphic xanthoastrocytoma were not described in older studies, 10,11,19,20 some studies incorporated patients diagnosed before the widespread use of magnetic resonance imaging, 5 and others used series from referral centers, where patient bias exists. 21,22 The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database 5 and Childhood Cancer Survivor Study [23][24][25][26] have been valuable resources in the study of the long-term outcomes of pediatric cancers.…”

Neuro-cognitive sequelae of the treatment of brain tumors among children and adolescents, and the possibilities for neuro-rehabilitation with a case report

“…Neurokognitivne funkcije koje su osetljive na doze RT su brzina procesiranja, verbalno rezonovanje i pamćenje, vizuelna percepcija, jezik i akademsko postignuće. Levi temporalni režanj je podložan propadanju kada se taj deo zrači većim dozama zračenja kao i kada se zrači ceo mozak i supratentorijalni deo (45Gy) što je povezano sa lošijim intelektualnim funkcionisanjem [47] NEUROKOGNITIVNA PROCENA Američka Akademija za pedijatriju i Grupa za pedijatrijsku onkologiju (COG -Children Oncology Group) pored ostalih standarda, propisali su i standard vezan za obaveznu neuropsihološku procenu i praćenje dece i mladih koji se leče od tumora CNS-a. Neuropsihološka procena prema navedenim preporukama podrazumeva procenu inteligencije, brzinu procesiranja, akademsko postignuće, pamćenje, pažnju i koncentraciju, vizuo-motornu i vizuospacijalnu organizaciju, verbalnu fluentnost, egzekutivne funkcije i planiranje (2).…”