A nomogram to predict symptomatic epilepsy in patients with radiation-induced brain necrosis

Xiaolong Huang; Xiaoni Zhang; Xicheng Wang; Xiaoming Rong; Yi Li; Honghong Li; Jingru Jiang; Jinhua Cai; Xiaohuang Zhuo; Yaxuan Pi; Jinpeng Lin; Melvin L K Chua; Andreas A Argyriou; Simona Lattanzi; Charles B Simone 2nd; Jon Glass; Joshua D Palmer; Edward Chow; Paul D Brown; Zongwei Yue; Yamei Tang; AME Radiation Oncology Collaborative Group

doi:10.1212/WNL.0000000000010190

A nomogram to predict symptomatic epilepsy in patients with radiation-induced brain necrosis

Neurology. 2020 Sep 8;95(10):e1392-e1403. doi: 10.1212/WNL.0000000000010190. Epub 2020 Jul 6.

Authors

Xiaolong Huang¹, Xiaoni Zhang¹, Xicheng Wang¹, Xiaoming Rong¹, Yi Li¹, Honghong Li¹, Jingru Jiang¹, Jinhua Cai¹, Xiaohuang Zhuo¹, Yaxuan Pi¹, Jinpeng Lin¹, Melvin L K Chua¹, Andreas A Argyriou¹, Simona Lattanzi¹, Charles B Simone 2nd¹, Jon Glass¹, Joshua D Palmer¹, Edward Chow¹, Paul D Brown¹, Zongwei Yue¹, Yamei Tang²; AME Radiation Oncology Collaborative Group

Affiliations

¹ From the Department of Neurology Bioland Laboratory (X.H., X. Zhang, X.R., Y.L., H.L., J.J., J.C., X. Zhuo, X.P., J.L., Z.Y., Y.T.) and Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center (Y.T.), Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University; Guangdong Province Key Laboratory of Brain Function and Disease (Y.T.), Zhongshan School of Medicine, Sun Yat-Sen University; Department of Oncology (X.W.), The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China; Division of Radiation Oncology and Medical Sciences (M.L.K.C.), National Cancer Centre Singapore; Oncology Academic Programme (M.L.K.C.), Duke-NUS Medical School, Singapore; Department of Neurology (A.A.A.), Saint Andrew's State General Hospital of Patras, Greece; Neurological Clinic, Department of Experimental and Clinical Medicine (S.L.), Marche Polytechnic University, Italy; New York Proton Center (C.B.S.), New York; Thomas Jefferson University (J.G.), Philadelphia, PA; Departments of Radiation Oncology (J.D.P.) and Neurosurgery (J.D.P.), The James Cancer Hospital at The Ohio State University Comprehensive Cancer Center, Columbus; Sunnybrook Health Sciences Centre (E.C.), University of Toronto, Canada; and Radiation Oncology (P.D.B.), Mayo Clinic, Rochester, MN.
² From the Department of Neurology Bioland Laboratory (X.H., X. Zhang, X.R., Y.L., H.L., J.J., J.C., X. Zhuo, X.P., J.L., Z.Y., Y.T.) and Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center (Y.T.), Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University; Guangdong Province Key Laboratory of Brain Function and Disease (Y.T.), Zhongshan School of Medicine, Sun Yat-Sen University; Department of Oncology (X.W.), The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China; Division of Radiation Oncology and Medical Sciences (M.L.K.C.), National Cancer Centre Singapore; Oncology Academic Programme (M.L.K.C.), Duke-NUS Medical School, Singapore; Department of Neurology (A.A.A.), Saint Andrew's State General Hospital of Patras, Greece; Neurological Clinic, Department of Experimental and Clinical Medicine (S.L.), Marche Polytechnic University, Italy; New York Proton Center (C.B.S.), New York; Thomas Jefferson University (J.G.), Philadelphia, PA; Departments of Radiation Oncology (J.D.P.) and Neurosurgery (J.D.P.), The James Cancer Hospital at The Ohio State University Comprehensive Cancer Center, Columbus; Sunnybrook Health Sciences Centre (E.C.), University of Toronto, Canada; and Radiation Oncology (P.D.B.), Mayo Clinic, Rochester, MN. tangym@mail.sysu.edu.cn.

PMID: 32631922
DOI: 10.1212/WNL.0000000000010190

Abstract

Objective: To develop and validate a nomogram to predict epilepsy in patients with radiation-induced brain necrosis (RN).

Methods: The nomogram was based on a retrospective analysis of 302 patients who were diagnosed with symptomatic RN from January 2005 to January 2016 in Sun Yat-sen Memorial Hospital using the Cox proportional hazards model. Discrimination of the nomogram was assessed by the concordance index (C index) and the calibration curve. The results were internally validated using bootstrap resampling and externally validated using 128 patients with RN from 2 additional hospitals.

Results: A total of 302 patients with RN with a median follow-up of 3.43 years (interquartile range 2.54-5.45) were included in the training cohort; 65 (21.5%) developed symptomatic epilepsy during follow-up. Seven variables remained significant predictors of epilepsy after multivariable analyses: MRI lesion volume, creatine phosphokinase, the maximum radiation dose to the temporal lobe, RN treatment, history of hypertension and/or diabetes, sex, and total cholesterol level. In the validation cohort, 28 out of 128 (21.9%) patients had epilepsy after RN within a median follow-up of 3.2 years. The nomogram showed comparable discrimination between the training and validation cohort (corrected C index 0.76 [training] vs 0.72 [95% confidence interval 0.62-0.81; validation]).

Conclusion: Our study developed an easily applied nomogram for the prediction of RN-related epilepsy in a large RN cohort.

Classification of evidence: This study provides Class III evidence that a nomogram predicts post-RN epilepsy.

Publication types

Research Support, Non-U.S. Gov't
Validation Study

MeSH terms

Brain / pathology
Brain / radiation effects
Cranial Irradiation / adverse effects*
Epilepsy / diagnosis*
Epilepsy / etiology*
Female
Head and Neck Neoplasms / radiotherapy
Humans
Male
Middle Aged
Necrosis / etiology
Necrosis / pathology
Nomograms*
Radiation Injuries / complications*
Radiation Injuries / diagnosis
Radiation Injuries / pathology
Retrospective Studies
Risk Factors