Association between hippocampal dose and memory in survivors of childhood or adolescent low-grade glioma: a 10-year neurocognitive longitudinal study

Abstract

Background Hippocampal avoidance has been suggested as a strategy to reduce short-term memory decline in adults receiving whole-brain radiation therapy (RT). The purpose of this study was to determine whether the hippocampal dose in children and adolescents undergoing RT for low-grade glioma was associated with memory, as measured by verbal recall. Methods Eighty patients aged at least 6 years but less than 21 years with low-grade glioma were treated with RT to 54 Gy on a phase II protocol. Patients underwent age-appropriate cognitive testing at baseline, 6 months posttreatment, yearly through 5 years posttreatment, year 7 or 8, and year 10 posttreatment. Random coefficient models were used to estimate the longitudinal trends in cognitive assessment scores. Results Median neurocognitive follow-up was 9.8 years. There was a significant decline in short-delay recall (slope = −0.01 standard deviation [SD]/year, P < 0.001), total recall (slope = −0.09 SD/y, P = 0.005), and long-delay recall (slope = −0.01 SD/y, P = 0.002). On multivariate regression, after accounting for hydrocephalus, decline in short-delay recall was associated with the volume of right (slope = −0.001 SD/y, P = 0.019) or left hippocampus (slope = −0.001 SD/y, P = 0.025) receiving 40 Gy (V40 Gy). On univariate regression, decline in total recall was only associated with right hippocampal dosimetry (V40 Gy slope = −0.002, P = 0.025). In children <12 years, on univariate regression, decline in long-delay recall was only associated with right (V40 Gy slope = −0.002, P = 0.013) and left (V40 Gy slope = −0.002, P = 0.014) hippocampal dosimetry. Conclusion In this 10-year longitudinal study, greater hippocampal dose was associated with a greater decline in delayed recall. Such findings might be informative for radiation therapy planning, warranting prospective evaluation.

Cognitive Decline After Cranial Irradiation: Hoping for a Systematic Application of the Reliable Change Index

“…The aim of this contribution was to unsystematically highlight some methodological issues observed within the literature about the cognitive consequences of cranial irradiation for oncological management (Gondi et al, 2010 , 2012 , 2014 ; Kim et al, 2018 ; Acharya et al, 2019 ; Tringale et al, 2019 ). We advocate that much of the debate and many of the controversial results found within and across these studies are mainly based on such issues; the patients with disease of different clinical stages, the timing of neuropsychological assessment, and the absence of guidelines about the neuropsychological battery to employ for assessing the outcomes make it difficult to compare studies.…”

“…For example, neurocognitive dysfunction was alternatively defined as a z -score drop of 1.5 (Gondi et al, 2012 ; Kim et al, 2018 ) or a decline of more than two standard deviations from the patient's own baseline value (Li et al, 2007 ). In other cases, the longitudinal trends of neurocognitive outcomes have been estimated by means of a regression analysis (Acharya et al, 2019 ).…”

“…Although the RCI is fairly widespread in neuropsychological literature (Chelune et al, 1993 ; Sawrie et al, 1996 ; Maassen, 2004 ; Hensel et al, 2007 ), in some subfields, this index is still employed in an unsystematic way. Here we will focus on the cognitive consequences of cranial irradiation for oncological management (Gondi et al, 2010 , 2012 , 2014 ; Kim et al, 2018 ; Acharya et al, 2019 ; Tringale et al, 2019 ). Converging literature indicates that the link between cranial irradiation and an increased risk of a posttreatment neurocognitive decline occurring months or years after radiation therapy can be taken for granted.…”

In Reply to Byun et al

“…recent phase 2 study of young patients with low-grade glioma found a significant association between shortdelay recall and hippocampal volume receiving radiation. 6 Further prospective study of TVH avoidance in germinoma is warranted, with comprehensive review of all imaging at recurrence to permit correlation to irradiated volumes and longitudinal assessment of neurocognitive function.…”

Could upfront temozolomide chemotherapy postpone the intervene of radiotherapy in young patients with high-risk low-grade gliomas?

“…Worse still, Radiotherapy brings signi cant treatment-related side effects as cognitive dysfunction in the meantime of its controlling tumor recurrence according to a 12-year follow-up for patients below 40 years old [4]. A 10-year follow-up suggested that greater dose of radiotherapy was associated with a greater cognitive decline [5].…”