# Potential Risk of Cognitive Impairment Due to Irradiation of Neural Structures in Locally Advanced Nasopharyngeal Cancer Treated by Curative Radiotherapy

## TL;DR

This study compares radiotherapy techniques for nasopharyngeal cancer and finds that some increase the risk of cognitive decline due to higher radiation doses to brain structures.

## Contribution

The study evaluates neurocognitive risks across 3D-CRT, IMRT, and VMAT for nasopharyngeal cancer, highlighting hippocampal and temporal lobe dose differences.

## Key findings

- IMRT and VMAT increased mean and minimum doses to the hippocampus and temporal lobes compared to 3D-CRT.
- VMAT plans exceeded hippocampal dose thresholds, risking cognitive toxicity.
- 3D-CRT showed the highest maximum doses to temporal lobes, raising radionecrosis concerns.

## Abstract

Background and Objectives: Brain radionecrosis is an under-recognized but potentially life-altering late complication of radiotherapy in patients with locally advanced nasopharyngeal cancer. Temporal lobe radionecrosis and high-dose exposure to the hippocampus are strongly associated with cognitive decline and radiation-induced dementia, negatively impacting patients’ long-term quality of life (QoL). This study aimed to evaluate and compare radiation dose distributions to critical brain structures across three radiotherapy techniques—3D conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and volumetric-modulated arc therapy (VMAT)—in order to assess potential neurocognitive risks and support hippocampal-sparing protocols. Materials and Methods: Ten patients previously treated with 3D-CRT were retrospectively replanned using IMRT and VMAT techniques on the Eclipse v13.3 (VARIAN) planning system. Bilateral hippocampi and temporal lobes were delineated as organs at risk (OARs) according to the RTOG atlas, and dosimetric parameters including D_max, D_mean, and D_min were recorded. V7.3 values were evaluated for hippocampal avoidance regions. Results: While IMRT and VMAT provided improved target volume coverage and reduced high-dose exposure to many standard OARs, both techniques were associated with increased D_mean and D_min to the hippocampus and temporal lobes compared to 3D-CRT. The highest D_max values to the temporal lobes were observed in 3D-CRT plans, indicating a potential risk of radionecrosis. VMAT plans showed hippocampal mean doses exceeding 10 Gy in some cases, with V7.3 > 40%, breaching established neurocognitive risk thresholds. Conclusions: These findings support the routine delineation of the hippocampus and temporal lobes as OARs in radiotherapy planning for nasopharyngeal cancer. The implementation of hippocampal-sparing strategies, particularly in IMRT and VMAT, is recommended to reduce the risk of radiation-induced cognitive toxicity and preserve long-term QoL in survivors.