Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

Abstract

EQD(2) to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients should be enrolled in ongoing prospective trials of hippocampal sparing during cranial irradiation to confirm these preliminary results.

Hippocampal-sparing and target volume coverage in treating 3 to 10 brain metastases: A comparison of Gamma Knife, single-isocenter VMAT, CyberKnife, and TomoTherapy stereotactic radiosurgery

“…8 The hippocampal D40 was constrained to ≤4.5 Gy, equal to an EQD2 of 7.3 Gy, and was chosen based on data demonstrating higher doses being associated with impaired recall after fractionated SRS. 7 Although patients from this series were treated with up to 4 Gy per fraction, a limitation in using an EQD2 to calculate constraints is the uncertainty of linear-quadratic models in the doses used in single-fraction SRS. However, our purpose was to assess the feasibility of meeting hippocampal constraints rather than validating these constraints; a separate trial to evaluate the dose-effect response of the hippocampi to doses used in SRS should be performed.…”

“…The maximum point dose (Dmax) and dose to 40% of the hippocampi (D40) were then calculated, and if Dmax was greater than or equal to 6.60 Gy or the D40 of either hippocampus was greater than 4.50 Gy, replanning with hippocampal constraints was performed. These doses were chosen based on the 2 Gy equivalent doses (EQD2) of a 16 Gy Dmax and 7.60 Gy D40, as published by Gondi et al 7,8 When PTV coverage and hippocampal constraints could not both be met, PTV coverage was prioritized.…”

Evaluating the impact of hippocampal sparing during whole brain radiotherapy on neurocognitive functions: A preliminary report of a prospective phase II study

“…[9] Also, not little evidence supports that impaired hippocampal neurogenesis caused by radiation-induced damage [10][11][12][13] should be strongly associated with NCF impairment. [9,14] Furthermore, several studies showed that isodose distribution in the hippocampus is closely related to NCFs in patients with primary brain tumors [15][16][17] or in those with nasopharyngeal carcinoma. [14] Consequently, it is hypothesized that conformal hippocampal avoidance during the course of WBRT (HA-WBRT) might lead to significant preservation in terms of cognitive function.…”

“…Since the delivery of HA-WBRT instead of conventional WBRT aims to diminish the extent of neurotoxic impact on the hippocampus, which is significantly associated with memory functions, [9,15,18,21,26] three main aspects of NCF, including memory functions, executive functions, and psychomotor speed, were evaluated. First, the selected subtests of the Wechsler Memory Scale -3 rd edition (WMS-III) were used to evaluate patients' verbal and non-verbal episodic memory.…”

Potential for reduced radiation‐induced toxicity using intensity‐modulated arc therapy for whole‐brain radiotherapy with hippocampal sparing

“…Sixty‐seven percent of craniospinal pediatric patients have shown five‐year disease‐free survival rates after craniospinal irradiation (CSI) (5) and 55% of adult craniospinal patients survive more than three years after CSI (6) . However, clinical and preclinical evidence suggest that irradiating a neural stem cell compartment in the hippocampus introduces radiation‐induced neurocognitive toxicity/deficits (short‐ and long‐term memory loss) after conventional nonconformal WBRT within the first one to four months, leading to compromise in QoL 7 , 8 , 9 …”