A radiomics model for predicting the response to methylprednisolone in brain necrosis after radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: Methylprednisolone is recommended as the front-line therapy for radiation-induced brain necrosis (RN) after radiotherapy for nasopharyngeal carcinoma. However, some patients fail to benefit from methylprednisolone or even progress. This study aimed to develop and validate a radiomic model to predict the response to methylprednisolone in RN. METHODS: Sixty-six patients receiving methylprednisolone were enrolled. In total, 961 radiomic features were extracted from the pre-treatment magnetic resonance imagings of the brain. Least absolute shrinkage and selection operator regression was then applied to construct the radiomics signature. Combined with independent clinical predictors, a radiomics model was built with multivariate logistic regression analysis. Discrimination, calibration and clinical usefulness of the model were assessed. The model was internally validated using 10-fold cross-validation. RESULTS: The radiomics signature consisted of 16 selected features and achieved favorable discrimination performance. The radiomics model incorporating the radiomics signature and the duration between radiotherapy and RN diagnosis, yielded an AUC of 0.966 and an optimism-corrected AUC of 0.967 via 10-fold cross-validation, which also revealed good discrimination. Calibration curves showed good agreement. Decision curve analysis confirmed the clinical utility of the model. CONCLUSIONS: The presented radiomics model can be conveniently used to facilitate individualized prediction of the response to methylprednisolone in patients with RN.

A phase 2 study of thalidomide for the treatment of radiation-induced blood-brain barrier injury.

Radiation-induced brain injury (RIBI) is a debilitating sequela after radiotherapy to treat head and neck cancer, and 20 to 30% of patients with RIBI fail to respond to or have contraindications to the first-line treatments of bevacizumab and corticosteroids. Here, we reported a Simon's minmax two-stage, single-arm, phase 2 clinical trial (NCT03208413) to assess the efficacy of thalidomide in patients with RIBI who were unresponsive to or had contraindications to bevacizumab and corticosteroid therapies. The trial met its primary endpoint, with 27 of 58 patients enrolled showing ≥25% reduction in the volume of cerebral edema on fluid-attenuated inversion recovery-magnetic resonance imaging (FLAIR-MRI) after treatment (overall response rate, 46.6%; 95% CI, 33.3 to 60.1%). Twenty-five (43.1%) patients demonstrated a clinical improvement based on the Late Effects Normal Tissues-Subjective, Objective, Management, Analytic (LENT/SOMA) scale, and 36 (62.1%) experienced cognitive improvement based on the Montreal Cognitive Assessment (MoCA) scores. In a mouse model of RIBI, thalidomide restored the blood-brain barrier and cerebral perfusion, which were attributed to the functional rescue of pericytes secondary to elevation of platelet-derived growth factor receptor ß (PDGFRß) expression by thalidomide. Our data thus demonstrate the therapeutic potential of thalidomide for the treatment of radiation-induced cerebral vasculature impairment.

Establishment and Validation of a Predictive Model for Radiation-Associated Aspiration Pneumonia in Patients with Radiation-Induced Dysphagia after Nasopharyngeal Carcinoma.

Introduction: Radiotherapy for patients with head and neck cancers raises their risk of aspiration pneumonia-related death. We aimed to develop and validate a model to predict radiation-associated aspiration pneumonia (RAP) among patients with dysphagia after radiotherapy for nasopharyngeal carcinoma (NPC). Materials and Methods: A total of 453 dysphagic patients with NPC were retrospectively recruited from Sun Yat-Sen Memorial Hospital from January 2012 to January 2018. Patients were randomly divided into training cohort (n = 302) and internal validation cohort (n = 151) at a ratio of 2 : 1. The concordance index (C-index) and calibration curve were used to evaluate the accuracy and discriminative ability of this model. Moreover, decision curve analysis was performed to evaluate the net clinical benefit. The results were externally validated in 203 dysphagic patients from the First People's Hospital of Foshan. Results: Derived from multivariable analysis of the training cohort, four independent factors were introduced to predict RAP, including Kubota water drinking test grades, the maximum radiation dose of lymph node gross tumor volume (Dmax of the GTVnd), neutrophil count, and erythrocyte sedimentation rate (ESR). The nomogram showed favorable calibration and discrimination regarding the training cohort, with a C-index of 0.749 (95% confidence interval (CI), 0.681 to 0.817), which was confirmed by the internal validation cohort (C-index 0.743; 95% CI, 0.669 to 0.818) and the external validation cohort (C-index 0.722; 95% CI, 0.606 to 0.838). Conclusions: Our study established and validated a simple nomogram for RAP among patients with dysphagia after radiotherapy for NPC.

Acute bacterial encephalitis complicated with recurrent nasopharyngeal carcinoma associated with Elizabethkingia miricola infection: A case report.

Elizabethkingia miricola (E. miricola) is an extremely rare pathogenic bacterium, which causes serious infections in patients with primary immunodeficiency or tumors, and it is often misdiagnosed. E. miricola has rarely been known to cause a neurologic infection. We describe the first case of acute bacterial encephalitis associated with E. miricola infection in a man with recurrent nasopharyngeal carcinoma, which was successfully cured by antibiotics. The patient initially presented with recurrent episodes of fever and later showed impaired consciousness but these symptoms were alleviated with antibiotic therapy including cefoperazone/sulbactam. This study highlights that rapid and accurate pathogen detection via metagenomic next-generation sequencing and early use of appropriate antibiotics can improve the prognosis of patients with suspected neurologic E. miricola infection. Early treatment for underlying primary diseases can also significantly improve the outcomes of patients.

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

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.

The correlation between serum apolipoprotein B/apolipoprotein A1 ratio and brain necrosis in patients underwent radiotherapy for nasopharyngeal carcinoma.

INTRODUCTION: The apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio is recognized as a clinical indicator of cardiovascular disease and ischemic cerebral disease. Cerebrovascular dysfunction is also involved in head and neck radiotherapy. The aim of this study was to investigate the correlation between ApoB/ApoA1 ratio and the severity of radiation-induced brain necrosis (RN) in patients who underwent radiotherapy after nasopharyngeal carcinoma (NPC). METHODS: In this retrospective study, 191 NPC patients diagnosed with RN were evaluated. Clinical characteristics, serum lipid, apolipoproteins, and brain magnetic resonance imaging findings were collected. Serum lipid and apolipoproteins were quantified using standard diagnostic assays, and the quality of life (QOL) was assessed by the World Health Organization quality of life abbreviated instrument (WHOQOL-BREF). RESULTS: ApoB/ApoA1 ratio was positively correlated with lesion volume (r = .18, p = .03) and negatively correlated with WHOQOL-BREF scores (r = -.28, p < .01). The ApoB/ApoA1 ratio and intensity-modulated radiation therapy (IMRT) were independent risk factor of RN volume. Moreover, ApoB/ApoA1 ratio was significantly negatively correlated with physical health (r = -.29, p < .01), psychological (r = -.27, p < .01), social relationships (r = -.17, p = .02), and environment (r = -.27, p < .01) domains of WHOQOL-BREF. CONCLUSIONS: Serum ApoB/ApoA1 ratio is positively correlated with RN volume, which indicated serum ApoB/ApoA1 ratio as an independent risk factor for lesion volume in patients with RN after radiotherapy for NPC, suggesting a bright intervention target in RN treatment.

Comparison between high-dose and low-dose intravenous methylprednisolone therapy in patients with brain necrosis after radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: Radiotherapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) and may cause radiation-induced brain necrosis (RN). Intravenous steroids have been considered as an effective treatment for RN. However, evidence concerning the efficacy of different doses of intravenous steroid therapy remains insufficient to establish the optimal regimen for NPC patients with RN. METHODS: We retrospectively reviewed charts of 169 patients who were diagnosed with RN after radiotherapy for NPC, treated with low-dose or high-dose intravenous methylprednisolone (IVMP) and followed up for 12 months. We collected the clinical data, including the Late Effects of Normal Tissue (LENT)/Subjective, Objective, Management, Analytic (SOMA) scales score and Montreal Cognitive Assessment (MoCA) score. Magnetic resonance imaging (MRI) was performed pre- and post-treatment to define the radiographic response. RESULTS: There were no significant differences in the treatment response based on MRI, or changes in clinical symptoms and cognitive function between low and high-dose groups. Thirty of 93 low-dose patients (32.3%) and 21 of 76 high-dose patients (27.6%) presented effective response in MRI, with no significant differences between groups (P = 0.515). Neither group showed a significant difference in the effective rate based on the MoCA total score and LENT/SOMA score. The most commonly reported grade 3 adverse events in the high-dose group (n = 76) were infections and infestations (3 [3.9%] vs. none for low-dose group). CONCLUSIONS: We found low-dose IVMP was not inferior to high-dose IVMP for NPC patients with RN. In addition, treatment-related infections and infestations were likewise more common with high-dose steroid than low-dose steroid.

Predictors of the therapeutic effect of corticosteroids on radiation-induced optic neuropathy following nasopharyngeal carcinoma.

Radiation-induced optic neuropathy (RION) is a severe visual complication resulting from radiotherapy of the head and neck, which mostly occurs in patients with nasopharyngeal carcinoma (NPC) in the southern part of China. The mechanism of RION is unclear. Therefore, identifying risk factors for RION is an important step towards enhancing our understanding. In the current study, we retrospectively reviewed patients with NPC who were admitted to Sun Yat-Sen Memorial Hospital for visual loss between 2006 and 2017. The study included 38 participants (68 eyes) in the corticosteroid-effective group and 35 participants (64 eyes) in the corticosteroids-ineffective group. We analyzed potential risk factors for RION and developed a prediction model for the therapeutic effect of corticosteroid effect based on a random forests method. The prediction model showed a high accuracy with an area under the receiver operating characteristic curve of 0.932 (95% confidence interval = 0.889-0.975). Our results revealed that blood urea nitrogen (BUN) was significantly associated with RION and that RION patients with higher BUN levels responded better to corticosteroid treatment. Altogether, these results suggest that a prediction model, based on clinical factors, could be applied to estimate the therapeutic effect of corticosteroids on RION. Further investigation, however, is needed to confirm the study conclusion.

A nomogram for the prediction of cerebrovascular disease among patients with brain necrosis after radiotherapy for nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: This study sought to develop and validate a nomogram to predict cerebrovascular disease (CVD) among patients with brain necrosis after radiotherapy for nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: A total of 346 eligible patients with brain necrosis after radiotherapy for NPC were divided into a training set (n = 231) and a validation set (n = 115). A multivariate Cox proportional hazards regression model was used to select the significant variables for CVD prediction in the training set. Then, a nomogram was developed based on the regression model. The performance of the nomogram was assessed with respect to discrimination and calibration. All patients were classified into high- or low-risk groups based on the risk scores derived from the nomogram. Moreover, a decision curve analysis was performed with the combined training and validation sets to evaluate the clinical usefulness of the nomogram. RESULTS: Four significant predictors were identified: hypertension, statin treatment, serum level of high-density lipoprotein, and interval between radiotherapy and brain necrosis. The nomogram incorporating these four predictors showed favorable calibration and discrimination regarding the training set, with a C-index of 0.763 (95% CI, 0.694 to 0.832), which was confirmed using the validation set (C-index 0.768; 95% CI, 0.675 to 0.861). Furthermore, the nomogram successfully stratified patients into high- and low-risk groups. The decision curve indicated that our nomogram was clinically useful. CONCLUSION: The nomogram showed favorable predictive accuracy for CVD among patients with brain necrosis after radiotherapy for NPC and might aid in clinical decision making.

Radiotherapy-induced dysphagia and its impact on quality of life in patients with nasopharyngeal carcinoma.

PURPOSE: To investigate the swallowing status and its impact on quality of life (QOL) in patients who underwent radiotherapy for nasopharyngeal carcinoma (NPC). METHODS: In this study, 334 patients with NPC who underwent radiotherapy were reviewed. Clinical characteristics, videofluoroscopic swallowing studies (VFSSs), and scores of the World Health Organization quality of life-BREF (WHOQOL-BREF) were retrospectively analyzed for all patients. RESULTS: In this study, 143 of 334 (42.8%) patients showed dysphagia. The nodular stage N3 of NPC, neoadjuvant and concurrent chemotherapy were clinical predictors for dysphagia. VFSS of patients with dysphagia showed a high incidence of vallecular residue (100%), apraxia (99%), premature bolus loss (98%), bolus formation (98%), pyriform sinus residue (95%), and mastication (94%). Moreover, WHOQOL-BREF scores for the physical health, psychological, and environment domains were lower of the dysphagia group than those of the control group (P < 0.01). Videofluoroscopic dysphagia scale scores showed significant negative correlations with scores for the physical health (R = -0.66, P < 0.01), psychological (R = -0.70, P < 0.01), social relationships (R = -0.56, P < 0.01), and environment (R = -0.61, P < 0.01) domains of WHOQOL-BREF. CONCLUSIONS: Radiotherapy-induced dysphagia is common in NPC patients and is correlated with poor quality of life. Patients, caregivers, and clinical physicians should be aware of these adverse effects and provide timely treatment for radiotherapy-induced dysphagia in collaboration with cross-disciplinary colleagues.