Hippocampus-sparing radiotherapy using volumetric modulated arc therapy (VMAT) to the primary brain tumor: the result of dosimetric study and neurocognitive function assessment

Abstract

BackgroundWe hypothesized that hippocampal-sparing radiotherapy via volumetric modulated arc therapy (VMAT) could preserve the neurocognitive function (NCF) of patients with primary brain tumors treated with radiotherapy.MethodsWe reviewed data from patients with primary brain tumors who underwent hippocampal-sparing brain radiotherapy via VMAT between February 2014 and December 2015. The optimization criteria for the contralateral hippocampus was a maximum dose (Dmax) of less than 17 Gy. For NCF evaluations, the Seoul Verbal Learning Test for total recall, delayed recall, and recognition (SVLT-TR, DR, and Recognition) was performed at baseline and at seven months after radiotherapy.ResultsA total of 26 patients underwent NCF testing seven months after radiotherapy. Their median age was 49.5 years (range 26–77 years), and 14 (53.8%) had grade III/IV tumors. The median Dmax to the contralateral hippocampus was 16.4 Gy (range 3.5-63.4). The median mean dose to the contralateral hippocampus, expressed as equivalent to a 2-Gy dose (EQD2/2), was 7.4 Gy2 (0.7–13.1). The mean relative changes in SVLT-TR, SVLT-DR, and SVLT-Recognition at seven months compared to the baseline were − 7.7% (95% confidence interval [CI], − 19.6% to 4.2%), − 9.2% (95% CI, − 25.4% to 7.0%), and − 3.4% (− 12.7% to 5.8%), respectively. Two patients (7.7%) showed deteriorated NCF in the SVLT-TR and SVLT-DR, and three (11.5%) in the SVLT-Recognition. The mean dose of the left hippocampus and bilateral hippocampi were significantly higher in patients showing deterioration of the SVLT-TR and SVLT-Recognition than in those without deterioration.ConclusionsThe contralateral hippocampus could be effectively spared in patients with primary brain tumor via VMAT to preserve the verbal memory function. Further investigation is needed to identify those patients who will most benefit from hippocampal-sparing radiotherapy of the primary brain tumor.Electronic supplementary materialThe online version of this article (10.1186/s13014-018-0975-4) contains supplementary material, which is available to authorized users.

Optimizing Adjuvant Stereotactic Radiotherapy of Motor-Eloquent Brain Metastases: Sparing the nTMS-Defined Motor Cortex and the Hippocampus

“…For the hippocampus, recent radiotherapy optimization studies have aimed at reducing maximum dose to 16-17 Gy and minimum dose to 9 Gy in hippocampus-sparing whole-brain radiotherapy (14,25). However, while a significant correlation was observed between mean dose to the left hippocampus and cognitive deterioration (25) as well as hippocampal volume reduction (41), no dose cut-off was defined in these studies. Hippocampus volume loss was observed to be significant one year after high-dose radiotherapy (> 40 Gy), but not after low-dose radiotherapy (< 10 Gy) by Seibert et al (42).…”

“…Furthermore, the hippocampus has been identified as an additional critical structure of radiation-induced cognitive deficits, which has not been considered in previous studies on nTMS in radiotherapy. In addition to the observed negative impact of whole-brain radiotherapy on cognitive outcome (14,15), several studies have focussed on the hippocampus itself as one of the most critical structures for radiation injury owing to the ongoing neurogenesis in the subgranular zone of its dentate gyrus (16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Higher dose to the hippocampus has particularly been associated with impaired verbal memory and higher executive functions (20,25).…”

Neurocognitive Decline Following Radiotherapy: Mechanisms and Therapeutic Implications

“…Previous studies have suggested that techniques allowing selective avoidance of the hippocampal neural stem-cell compartment cause a lower degree of cognitive impairment relative to WBRT [13,48]. With the development of IMRT, volumetric-modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT), hippocampal-sparing WBRT has been increasingly used as an adjuvant to surgery in the treatment of primary brain neoplasms and in management of brain metastases [49][50][51]. The results of ongoing randomized clinical trials will help to clarify the role of hippocampal-sparing WBRT in cognitive preservation [45,46,52].…”

Intracranial failure after hippocampal-avoidance prophylactic cranial irradiation in limited-stage small-cell lung cancer patients

“…According to the National Comprehensive Cancer Network guidelines, PCI is the standard treatment for both extensive and limited-stage SCLC, and methods of reducing neurocognitive dysfunction within the scope of PCI need to be determined. According to previous dosimetric studies, neurocognitive dysfunction occurs because the mean dose to the hippocampus exceeds approximately 19–20 Gy 21 . Besides HA-PCI, lowering the WBRT dose could be an alternative method.…”