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.

Surface-Based Falff: A Potential Novel Biomarker for Prediction of Radiation Encephalopathy in Patients With Nasopharyngeal Carcinoma

“…Although volume-based functional metrics have been commonly adopted to investigate functional alterations in a variety of diseases, they neglect the intersubject variability in cortical folding patterns (Li et al, 2014 ). In contrast, in the surface-based space, anatomical regions can be accurately matched with the same locations in the standard template, which decreases intersubject variability and increases statistical power (Fischl et al, 1999 ; Argall et al, 2006 ; Li et al, 2014 ; Zhang Y. et al, 2019 ). Therefore, compared with volume-based functional metrics, surface-based ones are more specific to the intrinsic functional organization of the cortical mantle and have moderate to high test–retest reliability (Jiang and Zuo, 2016 ).…”

“…Therefore, compared with volume-based functional metrics, surface-based ones are more specific to the intrinsic functional organization of the cortical mantle and have moderate to high test–retest reliability (Jiang and Zuo, 2016 ). Two recent studies showed that surface-based ReHo, instead of volume-based ReHo, could be a useful index to investigate the pathogenesis of major depressive disorder and bipolar disorder (Li et al, 2014 ; Zhang Y. et al, 2019 ). Similar phenomena could also be observed in the structural domain.…”

Interaction of chemotherapy and radiotherapy in altering the shape of subcortical structures in patients with nasopharyngeal carcinoma

“…This retrospective cross-sectional study included 201 patients with pathologically diagnosed NPC from March 2011 to July 2015. They were divided into three groups according to the difference in treatment methods: the Pre-RT group (56 NPC patients who had not received treatment), the Post-RT group (37 NPC patients who had received RT) and the Post-CCRT group (108 NPC patients who had received CCRT) ( 21 ). To measure the effect of RT or CCRT on the structure of subcortical nuclei, other possible confounding factors (such as age, sex, time intervals between RT and sMRI examinations, RT technology, and maximum RT dosage to the temporal lobes) had to be evenly distributed among the groups.…”

“…For each NPC patient, the following clinical data were available: the Karnofsky Performance Status (KPS) score, the main side of NPC, clinical stage, RT techniques, maximum dosage of RT to the temporal lobes, time intervals between RT and MRI examination, detailed information on the chemotherapy agents. All patients receiving RT were given Intensity-modulated radiation therapy (IMRT) or conventional two-dimensional radiotherapy (2D-CRT), as shown in Table 1 [see our previous work ( 21 )]. All patients who presented with stage II-IV NPC according to the 7th edition of the UICC/AJCC (2009) TNM classification (T = Tumor, N = Nodes, and M = Metastasis) ( 23 ) received CCRT, either with or without neoadjuvant/adjuvant chemotherapy.…”

“…In contrast, less attention has been paid to the effect of CT on the brain. Using multimodal MRI data, our recent study investigated the effects of RT and CT on the cortical morphology and functional connectivity in patients with NPC, and found that chemotherapy potentially facilitated the occurrence of radiation encephalopathy in treated NPC patients ( 21 ). One question remains, however, as to whether RT and CT could affect the morphology of subcortical structures in patients with NPC.…”