Radiation-induced Brain Necrosis Research Articles

Radiation-induced glymphatic dysfunction in patients with nasopharyngeal carcinoma: a study using diffusion tensor image analysis along the perivascular space.

Radiation encephalopathy (RE) refers to radiation-induced brain necrosis and is a life-threatening complication in patients with nasopharyngeal carcinoma (NPC) after radiotherapy (RT), and radiation-induced pre-symptomatic glymphatic alterations have not yet been investigated. We used diffusion tensor image analysis along the perivascular space (DTI-ALPS) index to examine the pre-symptomatic glymphatic alterations in NPC patients following RT. A total of 109 patients with NPC consisted of Pre-RT (n = 35) and Post-RT (n = 74) cohorts were included. The post-RT NPC patients, with normal-appearing brain structure at the time of MRI, were further divided into Post-RT-RE- (n = 58) and Post-RT-RE+ (n = 16) subgroups based on the detection of RE in follow-up. We observed lower DTI-ALPS left index, DTI-ALPS right index and DTI-ALPS whole brain index in post-RT patients than that in pre-RT patients (p < 0.05). We further found that post-RT-RE+ patients demonstrated significantly lower DTI-ALPS right (p = 0.013), DTI-ALPS whole brain (p = 0.011) and marginally lower DTI-ALPS left (p = 0.07) than Post-RT non-RE patients. Significant negative correlations were observed between the maximum dosage of radiation-treatment (MDRT) and DTI-ALPS left index (p = 0.003) as well as DTI-ALPS whole brain index (p = 0.004). Receiver operating characteristic (ROC) curve analysis showed that DTI-ALPS whole brain index exhibited good performance (AUC = 0.706) in identifying patients more likely developing RE. We concluded that glympathic function was impaired in NPC patients following RT and DTI-ALPS index may serve as a novel imaging biomarker for diagnosis of RE.

Radiation-Induced Brain Necrosis: The Role of The PSMA PET/CT Evaluation - Case Report

This is a case of a 69-year-old patient with Prostate Cancer (PCa) who underwent PSMA PET in three different evaluation scenarios: Biochemical Relapse (BCR), response assessment and differential diagnosis between Radiation-induced Brain Necrosis (RBN), and neoplastic tissue viability. PSMA PET showed superiority compared to conventional imaging exams in all scenarios and impacted on the management of the patient.

Progression of cognitive dysfunction in NPC survivors with radiation-induced brain necrosis: A prospective cohort

Background and purposeThe evidence of longitudinal changes in cognition in nasopharyngeal carcinoma (NPC) survivors with radiation-induced brain necrosis (RIBN) after radiotherapy (RT) remained insufficient. We aimed to estimate the clinical progression rate of cognitive decline and identify patients with differential decline rates. Materials and methodsBased on an ongoing prospective cohort study, NPC patients aged ≥18 years old and diagnosed with RIBN were included in this current analysis if they finished the time frame of 3-year follow-up and had at least twice cognition assessments. The Chinese version of the Montreal Cognitive Assessment (MoCA) was used to assess the cognitive state. Linear mixed-effect models were used to analyze the annual progression rates of MoCA total and seven sub-items scores. ResultsAmong 134 patients in this study, the transition probability from normal to mild/moderate cognitive dysfunction were 14.2 % (19/134) and 1.49 % (2/134) respectively during the median follow-up time of 2.35 years. The total MoCA score declined by −0.569 (SE 0.208) points annually (p = 0.008). Patients with ≤6 years of duration from RT to RIBN have higher annual progression rate of total scores [−0.851 (SE 0.321), p = 0.013; p for interaction = 0.041]. ConclusionOur findings of the annual decline rate of cognition in NPC patients with RIBN from a 3-year longitudinal data, particularly for those who developed RIBN rapidly after RT, have important implications for the upcoming clinical trials designed to prevent or decrease cognitive decline in NPC patients with RIBN, regarding the selection of study patients and the calculation of sample size.

IMMU-54. PNEUMOCYSTIS JIROVECII PNEUMONIA INFECTION IN A PATIENT WITH ANAPLASTIC ASTROCYTOMA AND RADIATION NECROSIS IN THE SETTING OF CORTICOSTEROID AND PEMBROLIZUMAB USE

Abstract We present a case with anaplastic astrocytoma and radiation-induced brain necrosis, diagnosed with pneumocystis jirovecii pneumonia(PJP) while receiving corticosteroid and pembrolizumab, an immune checkpoint inhibitor(ICI). ICIs have significantly changed management of many cancer types and are known to be associated with immune related adverse events(irAEs). Recently, concerns have emerged regarding the potential relationship between ICI use and infection risks, and PJP, a rare opportunistic infection, has been reported in patients with ICI treatments with or without corticosteroid use. A 40-year-old man with anaplastic astrocytoma and radiation-induced brain necrosis on corticosteroid and pembrolizumab presented with high fever and tachycardia over three days, and the patient later developed hypoxia and cough. The patient was on dexamethasone for brain radiation necrosis for two months and he received one dose of pembrolizumab two weeks prior to his symptom onset, based on genetic information that showed hypermutated tumor and abnormal DNA mismatch repair protein expression. Chest CT showed abnormal findings from infectious or inflammatory process. Bronchoalveolar lavage sample confirmed positive pneumocystis jiroveci PCR test, confirmed PJP, and he was treated with clindamycin, primaquine, and prednisone. To the best of our knowledge, this is the first reported case of PJP in a patient with primary brain tumor receiving corticosteroid and pembrolizumab. ICIs are being investigated in patients with primary brain tumors and wildly used in patients with malignancies with frequent central nervous system involvements, such as malignant melanomas and non-small cell lung cancers. Awareness of risk for infectious conditions including PJP in patients on ICI treatment, especially with corticosteroid use is crucial for implementing appropriate prophylactic measures and prompt diagnosis and treatment interventions.

Outcomes of 30 Gy/5 Fr Hypofractionated Stereotactic Radiation Therapy for Small Brain Metastases (≤2 cm).

Stereotactic radiosurgery (SRS)-used for brain metastases (BMs) with a tumor diameter of ≤2 cm-has a high local control rate, however, it can cause symptomatic radiation-induced brain necrosis. Hypofractionated stereotactic radiation therapy (HFSRT) is not commonly used for such lesions and its effectiveness remains unknown. Herein, the efficacy of 30 Gy 5-fraction HFSRT for treating BMs of <2 cm was retrospectively evaluated. Patients who received HFSRT and had a gross tumor volume (GTV) of ≤2 cm in maximum diameter were included in the study (49 patients; 179 BMs; median follow-up period, 11.9 months). The mean GTV Peripheral Dose (D95) was 36.2 Gy. The local control (LC) rates at 1 and 2 years were 93.0% and 81.5%, respectively, for all lesions. The 1-year LC rates were 93.6% and 92.0% for ≤1.0-cm and 1.0-2.0-cm lesions, respectively. Multivariate analysis revealed that the only significant difference was in GTV maximal tumor diameter (HR=1.961, p=0.0002). Notably, only one patient had asymptomatic radiation necrosis. Owing to the high toxicity of SRS, 5-fraction HFSRT can be an effective treatment strategy for BMs of <2 cm.

High-dose bevacizumab for radiation-induced brain necrosis: a case report.

Radiation-induced brain necrosis (RIBN) is a common adverse event from radiation therapy. We present a case of a 56-year-old man, diagnosed with non-small-cell lung cancer with brain metastases 2years prior, for which he had received whole brain radiotherapy and brain stereotactic radiosurgery, who presented to the oncology unit with headache, dizziness and abnormal gait. MRI of the brain revealed radiological worsening of a cerebellar mass, including edema and mass effect. After a multidisciplinary tumor board meeting, the patient was diagnosed with RIBN and received 4 cycles of high-dose bevacizumab, with complete symptom resolution and significant radiological response. We report the successful use of a high-dose, shorter-duration treatment protocol of bevacizumab for RIBN.

Prognostic Value of Nutritional Assessments on Overall Survival in Head and Neck Cancer Survivors with Radiation-Induced Brain Necrosis.

Malnutrition is related to worsened prognosis, but the association between nutritional risk status and overall survival in radiation-induced brain necrosis (RN) has never been studied. We included consecutive patients who had received radiotherapy for head and neck cancer (HNC) and subsequently developed RN from 8 January 2005 through to 19 January 2020. The primary outcome was overall survival. We utilized three commonly-used nutritional assessments: the Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and the COntrolling NUTritional Status (CONUT) measure, to quantify the baseline nutritional risk. A total of 398 eligible patients were included. During a median follow-up of 2.3 years, 42 (10.6%) patients died of any cause. Malnutrition at admission was associated with an increased risk of future death, as assessed by the GNRI (per 1-point decreased, HR 1.05, 95%CI 1.02-1.09, p = 0.001), the PNI (per 1-point decreased, HR 1.07, 95%CI 1.03-1.12, p = 0.002), and the CONUT (per 1-point increased, HR 1.22, 95%CI 1.08-1.37, p = 0.001). There were no nonlinear correlations between all three indices and post-RN survival. Among HNC survivors with RN, the assessment of nutritional risk by composite indices upon admission could help identify patients who might be at high risk of future death and deliver better nutritional management.

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

BackgroundMethylprednisolone 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.MethodsSixty-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.ResultsThe 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.ConclusionsThe presented radiomics model can be conveniently used to facilitate individualized prediction of the response to methylprednisolone in patients with RN.

Mortality of early treatment for radiation-induced brain necrosis in head and neck cancer survivors: A multicentre, retrospective, registry-based cohort study

SummaryBackgroundThe evidence of early treatment for radiation-induced brain necrosis (RN) in head and neck cancer survivors remains insufficient. This study aimed to determine whether early anti-RN treatment was associated with lower mortality.MethodsIn this cohort study, we utilized data from the Study in Radiotherapy-related Nervous System Complications (NCT03908502) and Hong Kong Cancer Registry. We included consecutive patients who had received radiotherapy (RT) for head and neck cancers and had subsequently developed RN between Jan 8, 2005 and Jan 19, 2020. Patients who had tumor progression before the diagnosis of RN, underwent surgical brain necrosis lesions resection before corticosteroids and/or bevacizumab treatment, had intracranial metastases before the diagnosis of RN, lacked follow-up data, or had a follow-up period of less than three months were excluded. Individual-level data were extracted from electronic medical records of the above-mentioned registries. The primary outcome was all-cause death. The vital status of each patient was confirmed through a standardized telephone interview. We compared patients who received early treatment (initiating bevacizumab or corticosteroids treatment within three months after RN diagnosis) with patients who did not (following a “watch-and-wait” policy).FindingsOf 641 eligible patients, 451 patients (70·4%) received early treatment after RN diagnosis and 190 patients (29·6%) did not. Overall, 112 patients (17·5%) died, of whom 73 (16·2%) in the early treatment group and 39 (20·5%) in the watch-and-wait group, during a median follow-up of 3·87 years. The early treatment group showed a lower risk of all-cause death compared with the watch-and-wait group after adjusting for age, sex, absence or presence of neurological symptoms at baseline, RN lesion features on brain magnetic resonance imaging, history of stroke, prior tumor-related characteristics (TNM stage, RT dose and techniques, and chemotherapy), and the time interval from RT to RN (HR 0·48, 95%CI 0·30 to 0·77; p = 0·0027), and extensive sensitivity analyses yielded similar results. There was no significant difference in the effect of early treatment on post-RN survival among subgroups stratified by presence or absence of neurological symptoms at diagnosis (p for interaction=0·41).InterpretationAmong head and neck cancer survivors with RN, initiating treatment early after RN diagnosis is associated with a lower risk of all-cause mortality as compared with following the watch-and-wait policy, irrespective of whether patients exhibit symptoms or not. Further prospective randomised studies would be needed to validate our findings since the observational study design might lead to some potential confounding. In the absence of data from randomised trials, our study will have an important implication for clinicians regarding the optimal timing of treatment for RN, and provides the foundation and supporting data for future trials on this topic.FundingNational Natural Science Foundation of China (81925031, 81820108026, 81872549, 81801229, 82003389), the Science and Technology Program of Guangzhou (202007030001), Young Teacher Training Program of Sun Yat-sen University (20ykpy106), Key-Area Research and Development Program of Guangdong Province (2018B030340001), the National Medical Research Council Singapore Clinician Scientist Award (NMRC/CSA-INV/0027/2018, CSAINV20nov-0021), the Duke-NUS Oncology Academic Program Goh Foundation Proton Research Programme, NCCS Cancer Fund, the Kua Hong Pak Head and Neck Cancer Research Programme, and the National Research Foundation Clinical Research Programme Grant (NRF-CRP17-2017-05).

CLRM-06 PROSPECTIVE CLINICAL STUDY OF CONVENTIONALLY FRACTIONATED CONCURRENT CHEMORADIOTHERAPY AND HYPOFRACTIONATED CONCURRENT CHEMORADIOTHERAPY AFTER THE SURGERY OF HIGH-GRADE GLIOMAS

PURPOSETo observe and evaluate the efficacy and safety of conventional fractionated concurrent chemoradiotherapy and hypofractionated concurrent chemoradiotherapy for adjuvant treatment of newly treated high-grade glioma. METHODFor newly treated patients with high-grade gliomas with WHO grade III-IV, all patients started concurrent chemoradiotherapy within 1 month after surgery, and received concurrent temozolomide 75 mg/m2 during radiotherapy until the end of radiotherapy. Sequential temozolomide chemotherapy at 200 mg/m2 for at least 6 cycles. All patients were randomly divided into groups, one group was given conventional fractional irradiation, 60Gy/30f in high-risk areas, 46Gy/23f in low-risk areas, and the other group was given low-fractionated irradiation, 53Gy/15f in high-risk areas, and 53Gy/15f in low-risk areas 43Gy/15f. The overall survival (OS), progression-free survival (PFS), radiation-induced cerebral edema and radiation-induced brain necrosis were evaluated. RESULTAs of December 31, 2022, a total of 60 patients were enrolled, including 30 in the conventional fractionation treatment group and 30 in the hypofractionated treatment group. At present, 58 patients survived and 2 died, 2 in the conventional fractionation group, one due to tumor recurrence and one due to cardiac accident; 7 patients recurred, including 4 in the conventional fractionation group and 3 in the low fractionation group. Radiation cerebral edema occurred in 9 cases, 6 cases in the hypofractionated group and 3 cases in the conventional fractionation group, all of which were completely relieved after dehydration with mannitol, which did not affect the progress of radiotherapy. No radiation necrosis occurred during follow-up. CONCLUSIONCompared with the standard stupp regimen, using 53Gy/15f in the high-risk area and 43Gy/15f in the low-risk area as an adjuvant therapy with concurrent temozolomide and sequential temozolomide, there was no increased risk of disease recurrence, no increased risk of death, and no increased risk of death.

[The safety and efficacy of anlotinib in combination with stereotactic radiotherapy for the treatment of brain metastases from non-small cell lung cancer].

Objective: To investigate the efficacy and safety of anti-vascular drug anlotinib in combination with stereotactic radiosurgery (SRS) for the treatment of brain metastases from non-small cell lung cancer (NSCLC). Methods: A total of 46 patients diagnosed with NSCLC brain metastases and treated with SRS in Peking University Third Hospital were included from October 2017 to June 2019. Of these, 21 patients (33 lesions) received anlotinib combined with SRS (combined treatment group), while 25 patients (35 lesions) only received SRS (SRS-alone group). The data of combined treatment group and SRS-alone group were compared, including remission rate of intracranial hypertension, response rate (RR) of local control of intracranial lesions, incidence of radiation-induced brain necrosis and intracranial progression-free survival (iPFS). The medication and adverse reactions of anlotinib in the combined treatment group were recorded. Results: The remission rate of intracranial hypertension in the combined treatment group was 71.4% (15/21), which was significantly higher than that in the SRS-alone group [12.0% (3/25), P<0.001). However, the RR of combined treatment group and SRS-alone group was 80.9% (17/21) and 60.0% (15/25), respectively, with no statistically significant difference (P=0.289). The incidence of radiation-induced brain necrosis in the combined treatment group was 3.0% (1/33), which was significantly lower than that in the SRS-alone group [20.0% (7/35), P=0.030]. The iPFS of the combination treatment group was (13.9±2.4) months, which was significantly longer than that in the SRS-alone group [(11.4±1.8) months, P<0.001]. The medication time of anlotinib in the combined treatment group was 6 (6, 18) weeks. One patient developed grade Ⅰ hypertension and one patient developed grade Ⅰ hand-foot syndrome. The incidence of drug-related adverse reactions was 9.5% (2/21). Conclusions: Anlotinib in combination with SRS may relieve brain edema, reduce the rate of radiation-induced brain necrosis, and the rate of drug-related adverse reactions were low.

A novel nomogram to predict overall survival in head and neck cancer survivors with radiation-induced brain necrosis

Background and purposeThe study aimed to develop and validate a novel nomogram to predict overall survival in head and neck cancer survivors following the diagnosis of radiation-induced brain necrosis (RN). Materials and methodsWe included head and neck cancer survivors with RN from a radiation complications registry study. A total of 495 eligible patients were 7:3 randomly allocated to a training cohort and an internal validation cohort. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select significant predictors of post-RN survival in the training cohort, and a multivariable Cox model was used to develop the nomogram. The performance of the nomogram was assessed using the internal validation cohort and externally validated using additional 88 RN patients. ResultsWe identified five predictors of post-RN survival using the training data: age, tumor progression before RN, lower cranial nerves injury, bilateral necrosis, and history of stroke. The nomogram showed favorable performance in the internal validation cohort (C-index 0.761, 95% CI 0.676 to 0.847) and in the external validation cohort (C-index 0.795, 95% CI 0.717 to 0.874). The decision curve analysis indicated that the nomogram was clinically useful when the probabilities of death ranging from 1% to 48% at 1 year, from 3% to 50% at 3 years, and exceeding 2% at 5 years after being diagnosed with RN. ConclusionIn this LASSO-Cox model-based nomogram study, we developed and validated an easily applied model to predict overall survival in head and neck cancer survivors following an RN diagnosis.

Treatment of Radiation-Induced Brain Necrosis.

Radiation-induced brain necrosis (RBN) is a serious complication of intracranial as well as skull base tumors after radiotherapy. In the past, due to the lack of effective treatment, radiation brain necrosis was considered to be progressive and irreversible. With better understanding in histopathology and neuroimaging, the occurrence and development of RBN have been gradually clarified, and new treatment methods are constantly emerging. In recent years, some scholars have tried to treat RBN with bevacizumab, nerve growth factor, and gangliosides and have achieved similar results. Some cases of brain necrosis can be repairable and reversible. We aimed to summarize the incidence, pathogenesis, and treatment of RBN.

Leptomeningeal disease and brain control after postoperative stereotactic radiosurgery with or without immunotherapy for resected brain metastases

PurposeImmunotherapy has shown activity in patients with brain metastases (BM) and leptomeningeal disease (LMD). We have evaluated LMD and intraparenchymal control rates for patients with resected BM receiving postoperative stereotactic...

Blood-Brain Barrier Repair of Bevacizumab and Corticosteroid as Prediction of Clinical Improvement and Relapse Risk in Radiation-Induced Brain Necrosis: A Retrospective Observational Study.

BackgroundBlood–brain barrier (BBB) disruption after endothelial damage is a crucial part of radiation-induced brain necrosis (RN), but little is known of BBB disruption quantification and its role in the evaluation of therapeutic effect and prognosis for drug treatment. In this retrospective study, BBB repair by bevacizumab and corticosteroid and the correlation between BBB permeability and treatment response and relapse were evaluated by dynamic contrast-enhanced MRI (DCE-MRI).MethodsForty-one patients with RN after radiotherapy for nasopharyngeal carcinoma (NPC) (28 treated with bevacizumab and 13 with corticosteroid), 12 patients with no RN after NPC radiotherapy, and 12 patients with no radiotherapy history were included as RN, non-RN, and normal groups, respectively. DCE-MRI assessed BBB permeability in white matter of bilateral temporal lobe. DCE parameters were compared at baseline among the three groups. DCE parameters after treatment were compared and correlated with RN volume decrease, neurological improvement, and relapse.ResultsThe extent of BBB leakage at baseline increased from the normal group and non-RN group and to RN necrosis lesions, especially K trans (Kruskal–Wallis test, P < 0.001). In the RN group, bevacizumab-induced K trans and v e decrease in radiation necrosis lesions (both P < 0.001), while corticosteroid showed no obvious effect on BBB. The treatment response rate of bevacizumab was significantly higher than that of corticosteroid [30/34 (88.2%) vs. 10/22 (45.4%), P < 0.001]. Spearman analysis showed baseline K trans, K ep, and v p positively correlated with RN volume decrease and improvement of cognition and quality of life in bevacizumab treatment. After a 6-month follow-up for treatment response cases, the relapse rate of bevacizumab and corticosteroid was 10/30 (33.3%) and 2/9 (22.2%), respectively, with no statistical difference. Post-bevacizumab K trans level predicted relapse in 6 months with AUC 0.745 (P < 0.05, 95% CI 0.546–0.943, sensitivity = 0.800, specificity = 0.631).ConclusionsBevacizumab improved BBB leakage in RN necrosis. DCE parameters may be useful to predict therapeutic effect and relapse after bevacizumab.

Bevacizumab Combined with Corticosteroids Does Not Improve the Clinical Outcome of Nasopharyngeal Carcinoma Patients With Radiation-Induced Brain Necrosis.

ObjectiveOur aim was to compare the clinical outcomes of patients treated with bevacizumab combined with corticosteroids and those with bevacizumab monotherapy from a radiation-induced brain necrosis (RN) registry cohort (NCT03908502).MethodsWe utilized clinical data from a prospective RN registry cohort (NCT03908502) from July 2017 to June 2020. Patients were considered eligible if they had symptomatic RN after radiotherapy for nasopharyngeal carcinoma (NPC) and received bevacizumab (5 mg/kg, two to four cycles) with a minimum follow-up time of 3 months. The primary outcome was a 2-month response rate determined by MRI and clinical symptoms. Secondary outcomes included quality of life [evaluated by the abbreviated World Health Organization Quality of Life (WHOQOL-BREF) questionnaire] and cognitive function (evaluated by the Montreal Cognitive Assessment scale) at 2 months, RN recurrence during follow-up, and adverse events.ResultsA total of 123 patients (34 in the combined therapy group and 89 in the monotherapy group) were enrolled in our study with a median follow-up time of 0.97 year [interquartile range (IQR) = 0.35–2.60 years]. The clinical efficacy of RN did not differ significantly between patients in these two groups [odds ratio (OR) = 1.642, 95%CI = 0.584–4.614, p = 0.347]. Furthermore, bevacizumab combined with corticosteroids did not reduce recurrence compared with bevacizumab monotherapy [hazard ratio (HR) = 1.329, 95%CI = 0.849–2.079, p = 0.213]. The most common adverse events of bevacizumab were hypertension (17.89%), followed by nosebleed (8.13%) and fatigue (8.13%). There was no difference in grade 2 or more severe adverse events between the two groups (p = 0.811).InterpretationOur results showed that the treatment strategy of combining bevacizumab with corticosteroids did not lead to better clinical outcomes for RN patients with a background of radiotherapy for nasopharyngeal carcinoma.

Contribution of spectroscopic magnetic resonance imaging to target volume delineation in Gamma Knife Radiosurgery: Myth or reality?

Brain malignancies are still associated with poor prognosis despite multimodal radiosurgical therapeutic approach using Gamma Knife (GK), CyberKnife (CK), and linear accelerator-based technologies [1]. These advances have significantly improved the treatment outcome. However, the surgical and radiosurgical concept is still “image-guided”, and the success is closely related to precise tumor volume definition. The gross tumor volume (GTV) is defined as the visible contrast- enhancing lesion on magnetic resonance (MR) images with high three-dimensional spatial accuracy. Target delineation requires always both T2-weighted and volumetric T1-weighted sequences. T2-weighted fluid attenuated inversion recovery (FLAIR) sequences analyze the lesions surrounding brain tissues [2,3]. Objective assessment of apparently healthy tissue surrounding brain tumors seems to be a considerable factor interfering not only with the radiosurgical procedure, but also with the recurrence rate and overall survival. Several studies identified infiltrative spectroscopic pattern of the perilesional edema in more than 96% of high-grade gliomas cases and in 11,5% of patients with brain metastasis [4]. Moreover, some autopsy series of brain metastases confirmed infiltrative growth in radiologically healthy surrounding tissues in more than 60% of cases. This unseen malignant component is responsible of 80 % of “early recurrence” which should be considered as natural evolution of the main tumor [5]. In the management of high grade gliomas, the radiosurgeons are faced either to carcinologic incomplete procedures or to overestimated target irradiation with unbalanced benefit/risk action mostly related to radiation-induced brain necrosis [6]. The delineation of clinical target volume (CTV) which is defined as the volume of tissue that contains the GTV and any microscopic tumor or paths of spread, became a standard for any radio-surgical planning. Since a decade, the magnetic resonance spectroscopy (MRS) was standardized in the target volume assessment. The aim is to establish a metabolic lesional cartography. It had been reported that choline/ N- acetylaspartate (NAA) multivoxel MR spectroscopy index higher that 2,5 is in favor of malignancy in glioma with sensitivity of 90 % and specificity of 85 % [7]. However, NAA/Creatine (Cr) and Choline/Cr ratios are more relevant in the analysis of perilesional edema in brain metastasis cases. The introduction of MRS metabolic cartography concept, the use of relevant metabolite and adapted metabolites ratio estimation contributed to precision in radiosurgery. However, MRS is not used for target delineation for Gamma Knife radiosurgical treatment because of its incompatibility with the Leksell Gamma Knife planning software. Recently, we described the development of the first software allowing the integration of metabolic cartography based on multivoxel spectroscopic MRI in the radiosurgical planning for Leksell Gamma Knife Radiosurgery. The few existing meta-analysis could not lead to gold standard volume delineation techniques despite objective advance in imaging assessment [8,9]. Prospective studies using multimodal imaging data will help to overcome this insufficiency for target delineation in radiosurgery

Bevacizumab Treatment of Radiation-Induced Brain Necrosis: A Systematic Review

BackgroundRadiation brain necrosis (RBN) is a serious complication in patients receiving radiotherapy for intracranial disease. Many studies have investigated the efficacy and safety of bevacizumab in patients with RBN. In the present study, we systematically reviewed the medical literature for studies reporting the efficacy and safety of bevacizumab, as well as for studies comparing bevacizumab with corticosteroids.Materials and MethodsWe searched PubMed, Cochrane library, EMBASE, and ClinicalTrials.gov from their inception through 1 March, 2020 for studies that evaluated the efficacy and safety of bevacizumab in patients with RBN. Two investigators independently performed the study selection, data extraction, and data synthesis.ResultsOverall, the present systematic review included 12 studies (eight retrospective, two prospective, and two randomized control trials [RCTs]) involving 236 patients with RBN treated who were treated with bevacizumab. The two RCTs also had control arms comprising patients with RBN who were treated with corticosteroids/placebo (n=57). Radiographic responses were recorded in 84.7% (200/236) of patients, and radiographic progression was observed in 15.3% (36/236). Clinical improvement was observed in 91% (n=127) of responding patients among seven studies (n=113). All 12 studies reported volume reduction on T1 gadolinium enhancement MRI (median: 50%, range: 26%–80%) and/or T2 FLAIR MRI images (median: 59%, range: 48%–74%). In total, 46 responding patients (34%) had recurrence. The two RCTs revealed significantly improved radiographic response in patients treated with bevacizumab (Levin et al.: p = 0.0013; Xu et al.: p < 0.001). Both also showed clinical improvement (Levin et al.: NA; Xu et al.: p = 0.039) and significant reduction in edema volume on both T1 gadolinium enhancement MRI (Levin et al.: p=0.0058; Xu et al.: p=0.027) and T2 FLAIR MRI (Levin et al.: p=0.0149; Xu et al.: p < 0.001). Neurocognitive improvement was significantly better after 2 months of treatment in patients receiving bevacizumab than in those given corticosteroids, as assessed by the MoCA scale (p = 0.028). The recurrence rate and side effects of the treatments showed no significant differences.ConclusionsPatients with RBN respond to bevacizumab, which can improve clinical outcomes and cognitive function. Bevacizumab appears to be more efficacious than corticosteroid-based treatment. The safety profile was comparable to that of the corticosteroids.

Role of MRI in Differentiation between Postoperative Tumoral Recurrence and Radiation-Induced Brain Necrosis in Patients of Glioblastoma Multiform

The distinction of radiation-induced brain necrosis (RBN) and recurrent glioblastoma multiform (rGBM) remains a diagnostic challenge due to their similarly on routine follow-up imaging studies and also their clinical manifestations. Our purpose of this review article is to evaluate the role of advanced MR imaging techniques such as Perfusion-weighted imaging (PWI), Diffusion-weighted imaging (DWI) and Magnetic resonance spectroscopy (MRS) in the differentiation of RBN and rGBM and their complications together with our experience and knowledge gained during our neuroimaging practice.

Gamma ray-induced glial activation and neuronal loss occur before the delayed onset of brain necrosis.

Radiotherapy is one of the most effective treatments for head and neck tumors. However, delayed radiation-induced brain necrosis (RN) remains a serious issue due to the lack of satisfying prevention and effective treatment. The pathological role of radiation in the delayed onset of brain necrosis is still largely unknown, and the traditional animal model of whole brain irradiation, although being widely used, does not produce reliable and localized brain necrosis mimicking clinical features of RN. In this study, we demonstrated a successful RN mouse model using optimized gamma knife irradiation in male C57BL/6 mice. On the premise that brain necrosis started to appear at 6weeks postirradiation in our RN model, as confirmed by both MRI and histopathological examinations, we systematically examined different time points before the onset of RN for the histopathological changes and biochemical indicators. Our initial results demonstrated that in the ipsilateral hemisphere of the irradiated brains, a significant decrease in neuronal numbers that occurred at 4weeks and a sustained increase in TNF-α, iNOS, and other inflammatory cytokines beginning at 1-week postirradiation. Changes of cell morphology and cell numbers of both microglia and astrocytes occurred as early as 1-week postirradiation, and intervention by bevacizumab administration resulted in reduced microglia activation and reduction of radiation-induced lesion volume, indicating that chronic glial activation may result in subsequent elevation of inflammatory factors, which led to the delayed onset of neuronal loss and brain necrosis. Since C57BL/6 is the most widely used strain of genetic engineered mouse model, our data provide an invaluable platform for the mechanistic study of RN pathogenesis, identification of potential imaging and biological biomarkers, and the development of therapeutic treatment for the disease.