Chemotherapy Potentially Facilitates the Occurrence of Radiation Encephalopathy in Patients With Nasopharyngeal Carcinoma Following Radiotherapy: A Multiparametric Magnetic Resonance Imaging Study

Abstract

Radiation encephalopathy (RE) is deemed to be a disease induced only by radiotherapy (RT), with the effects of chemotherapeutic agents on the brains of nasopharyngeal carcinoma (NPC) patients being largely overlooked. In this study, we investigated structural and functional brain alterations in NPC patients following RT with or without chemotherapy. Fifty-six pre-RT, 37 post-RT, and 108 post-CCRT (concomitant chemo-radiotherapy) NPC patients were enrolled in this study. A surface-based local gyrification index (LGI) was obtained from high resolution MRI and was used to evaluate between-group differences in cortical folding. Seed-based functional connectivity (FC) analysis of resting-state fMRI data was also conducted to investigate the functional significance of the cortical folding alterations. Compared with the Pre-RT group, patients in the Post-CCRT group showed LGI reductions in widespread brain regions including the bilateral temporal lobes, insula, frontal lobes, and parietal lobes. Compared with the Post-RT group, patients in the Post-CCRT group showed LGI reductions in the right insula, which extended to the adjacent frontal lobe. Seed-based FC analysis showed that patients in the Post-CCRT group had lower FC between the insula and the left middle frontal gyrus than patients in the Pre-RT group. The follow-up results showed that patients in the Post-CCRT group had a much higher RE incidence rate (20.4%) than patients in the Post-RT group (2.7%; P = 0.01). These findings indicate that chemotherapy potentially facilitated the occurrence of RE in NPC patients who underwent radiotherapy.

Keywords: cerebral cortex; consolidation chemotherapy; nasopharyngeal carcinoma; neuroimaging; radiotherapy.

Figure 1

Flow diagram for the NPC patient selection, grouping, and analysis. NPC, nasopharyngeal carcinoma; RT, radiotherapy; CCRT, concomitant chemo-radiotherapy; LGI, local gyrification index; RE, radiation encephalopathy; ROI, region of interest; FC, functional connectivity.

Figure 2

Between-group differences in LGI. Compared with the pre-RT group, no significant LGI difference was observed in patients in the post-RT group (A). Compared with the pre-RT group, patients in the post-CCRT group showed widespread LGI reductions in the right inferior and superior parietal lobule, bilateral superior temporal gyrus (STG), left middle temporal gyrus (MTG), bilateral insula, and precentral, postcentral, supramarginal, inferior, and middle frontal gyri (B). Compared with the post-RT group, patients in the post-CCRT group showed significant LGI reduction in the right insula, extending to the adjacent frontal lobe and superior temporal gyrus (C). Colored areas denote regions where a significant difference in LGI was observed between the indicated groups. The absolute value or the magnitude of the color bar is corresponding to log10 (1/P), and the sign of the color bar denotes the directions of the changes.

Figure 3

Between-group differences in seed-based FC analysis. Compared with the pre-RT group, patients in the post-CCRT group showed significantly decreased functional connectivity between the left middle frontal gyrus and the brain region of interest from the LGI analysis [(A) left lateral; (B) right lateral; (C) left medial; (D) right medial]. A t-score color bar is shown at the bottom. L, left; R, right.