Ethical approval was obtained from the institutional review board for this retrospective analysis. This study comprised an evaluation of the institutional database for medical records between January 2005 and December 2016 to identify patients with brain necrosis after radiotherapy for NPC. A total of 66 NPC patients with RN were enrolled in this study, according to the following inclusion criteria: (a) underwent radiotherapy at least 12 months before the administration of intravenous methylprednisolone; (b) received high-dose or low-dose intravenous methylprednisolone treatment and no bevacizumab has been administrated before (Additional file 1: Appendix A1); and (c) performed pre- and post-treatment magnetic resonance imagings (MRI) of the brain and with measurable lesions in the MRI. The exclusion criteria were as follows: NPC relapse or metastases, surgical brain lesion resection, other tumor diseases, or other diseases of the nervous system. The patient selection process is presented in Fig. 1.

Study flowchart of cohort selection. Abbreviations: NPC = Nasopharyngeal Carcinoma; MRI = Magnetic Resonance Imaging

Demographic and pretreatment clinical characteristics before methylprednisolone administration were derived from medical records, including age, gender, duration between radiotherapy and RN diagnosis (DBRN), duration between radiotherapy and methylprednisolone treatment (DBRM), duration between RN diagnosis and methylprednisolone treatment (DBNM), aspartate transaminase (AST), alanine transaminase (ALT), high-sensitivity C-reaction protein levels (Hs-CRP), the maximum radiation dose of the nasopharynx (Dmax of the GTVnx), the maximum radiation dose of the neck (Dmax of the GTVnd), radiotherapy methods, Montreal Cognitive Assessment score (MoCA), the Late Effects of Normal Tissue (LENT)/Subjective, Objective, Management, Analytic (SOMA) scale score (LENT-SOMA), the volume of brain necrosis, side of the lesions and steroid dose. Tumor staging was performed on the basis of the American Joint Committee on Cancer TNM Staging System Manual, 7th Edition [25 (link)]. The RN volume was detected using T2-weighted fluid-attenuated inversion recovery (FLAIR) images 3 days before methylprednisolone administration (F0) and at 3 months (F1) of follow up. A reduction in RN volume of more than 25% at F1 compared with F0 was defined as effective response [18 (link)].
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