BACKGROUND: Bevacizumab has been demonstrated to have superior efficacy in the treatment of cerebral radiation necrosis (CRN), but its\' high cost may exacerbate the disease burden. This study aimed to assess the cost-effectiveness of bevacizumab in comparison with corticosteroids for treating CRN from the US payers\' perspective.
METHODS: Decision tree models were constructed to simulate the process of bevacizumab and corticosteroids in CRN short-term and long-term therapy. Critical clinical data were derived from the NCT01621880 trial. Costs and utility values were obtained from the US official websites and published literatures. The main outcomes were total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to assess the robustness of models.
RESULTS: In the short-term and long-term models, bevacizumab added 0.11 (0.46 vs 0.35) and 0.16 (0.54 vs 0.38) QALYs compared with corticosteroids therapy, with corresponding incremental costs of $12,351 and $23,253, respectively. The resultant ICERs were $112,987/QALY and $150,245/QALY for short-term and long-term treatment, respectively. The one-way sensitivity analysis indicated that utility value of non-recurrence status, body weight and bevacizumab price per cycle were the most influential factors for ICER of both models. At the willingness-to-pay threshold of $150,000/QALY in the US, the probabilities of bevacizumab being cost-effective for CRN short and long-term treatment were 63.9% and 49%, respectively.
CONCLUSIONS: Compared with corticosteroids, bevacizumab is an economical alternative for CRN short-term treatment from the US payers\' perspective, while long-term therapy draws an opposite conclusion.

UNASSIGNED: Our study aims to determine the incidence and potential risk factors for cerebral radiation necrosis (CRN) following treatment of sinonasal malignancies.
UNASSIGNED: One hundred thirty-two patients diagnosed with sinonasal malignancies over an 18-year period were identified at two institutions. Forty-six patients meeting inclusion criteria and treated with radiation therapy were included for analysis. Demographic and clinical-pathologic characteristics were collected and reviewed. Post-treatment magnetic resonance imaging (MRI) at least 1 year following treatment was reviewed to determine presence or absence of CRN.
UNASSIGNED: CRN was identified on MRI in 8 of 46 patients (17.4%) following radiation treatment. Patients with a history of reirradiation were more likely to develop CRN (50% vs. 10.5%, p < .05). The BEDs of radiation were also higher in CRN patients compared to non-CRN patients, but this difference was not significant (p > .05). CRN patients had a higher proportion of tumors with skull base involvement than non-CRN patients (100% vs. 57.9%, p = .037). Demographics, comorbidities, pathology, primary tumor subsite, chemotherapy use, and stage of disease demonstrated no significant increase in risk of CRN.
UNASSIGNED: Reirradiation and tumor skull base involvement were significant risk factors associated with CRN. Higher average total prescribed and BEDs of radiation were seen in the CRN groups, but these differences were not statistically significant. Gender, comorbidities, tumor subsite, tumor location, and treatment type were not significantly different between groups.
UNASSIGNED: Level 3.

Although intravenous bevacizumab (IVBEV) is the most promising treatment for cerebral radiation necrosis (CRN), there is no conclusion on the optimal dosage. Our retrospective study aimed to compare the efficacy and safety of high-dose with low-dose IVBEV in treating CRN associated with radiotherapy for brain metastases (BMs). This paper describes 75 patients who were diagnosed with CRN secondary to radiotherapy for BMs, treated with low-dose or high-dose IVBEV and followed up for a minimum of 6 months. The clinical data collected for this study include changes in brain MRI, clinical symptoms, and corticosteroid usage before, during, and after IVBEV treatment. At the 3-month mark following administration of IVBEV, a comparison of two groups revealed that the median percentage decreases in CRN volume on T2-weighted fluid-attenuated inversion recovery and T1-weighted gadolinium contrast-enhanced image (T1CE), as well as the signal ratio reduction on T1CE, were 65.8% versus 64.8% (p = 0.860), 41.2% versus 51.9% (p = 0.396), and 37.4% versus 35.1% (p = 0.271), respectively. Similarly, at 6 months post-IVBEV, the median percentage reductions of the aforementioned parameters were 59.5% versus 62.0% (p = 0.757), 39.1% versus 31.3% (p = 0.851), and 35.4% versus 28.2% (p = 0.083), respectively. Notably, the incidence of grade ≥3 adverse events was higher in the high-dose group (n = 4, 9.8%) than in the low-dose group (n = 0). Among patients with CRN secondary to radiotherapy for BMs, the administration of high-dose IVBEV did not demonstrate superiority over low-dose IVBEV. Moreover, the use of high-dose IVBEV was associated with a higher incidence of grade ≥3 adverse events compared with low-dose IVBEV.

To evaluate single- and multiparametric MRI models to differentiate recurrent glioblastoma (GBM) and treatment-related changes (TRC) in clinical routine imaging. Selective and unselective apparent diffusion coefficient (ADC) and minimum, mean, and maximum cerebral blood volume (CBV) measurements in the lesion were performed. Minimum, mean, and maximum ratiosCBV (CBVlesion to CBVhealthy white matter) were computed. All data were tested for lesion discrimination. A multiparametric model was compiled via multiple logistic regression using data demonstrating significant difference between GBM and TRC and tested for its diagnostic strength in an independent patient cohort. A total of 34 patients (17 patients with recurrent GBM and 17 patients with TRC) were included. ADC measurements showed no significant difference between both entities. All CBV and ratiosCBV measurements were significantly higher in patients with recurrent GBM than TRC. A minimum CBV of 8.5, mean CBV of 116.5, maximum CBV of 327 and ratioCBV minimum of 0.17, ratioCBV mean of 2.26 and ratioCBV maximum of 3.82 were computed as optimal cut-off values. By integrating these parameters in a multiparametric model and testing it in an independent patient cohort, 9 of 10 patients, i.e., 90%, were classified correctly. The multiparametric model further improves radiological discrimination of GBM from TRC in comparison to single-parameter approaches and enables reliable identification of recurrent tumors.

Cerebral radiation necrosis (CRN) is one of the most prominent sequelae following radiation therapy for nasopharyngeal carcinoma (NPC), which might have devastating effects on patients\' quality of life (QOL). Advances in histopathology and neuro-radiology have shed light on the management of CRN more comprehensively, yet effective therapeutic interventions are still lacking. CRN was once regarded as progressive and irreversible, however, in the past 20 years, with the application of intensity-modulated radiation therapy (IMRT), both the incidence and severity of CRN have declined. In addition, newly developed medical agents including bevacizumab-a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), nerve growth factor (NGF), monosialotetrahexosylganglioside (GM1), etc., have shown great potency in successfully reversing radiation-induced CRN. As temporal lobes are most frequently compromised in NPC patients, this review will summarize the state-of-the-art progress regarding the incidence, pathophysiology, prevention, treatment, and prognosis of temporal lobe necrosis (TLN) after IMRT in NPC.

Objective: This study aimed to investigate the relationship between the timing of stereotactic radiosurgery (SRS) intervention and the complications of cerebral radiation necrosis (CRN) in patients with brain metastases of lung adenocarcinoma who received tyrosine kinase inhibitor (TKI) treatment. Methods: A total of 361 targets from 257 patients with brain oligometastases of lung adenocarcinoma who received CyberKnife treatment between 2010 and 2017 were retrospectively collected from three CyberKnife centers. The difference in brain necrosis between patients with or without TKI application was statistically counted. Logistic regression analysis was used to analyze the effect of applying TKI on the occurrence of CRN in patients and the effect of SRS before and after TKI resistance on CRN. Results: The rate of CRN in the TKI group was significantly higher than that in the non-TKI group. The incidence of brain necrosis in patients undergoing SRS after drug resistance was significantly higher than that in patients undergoing SRS before drug resistance. Regression analysis showed that combination of TKI with SRS, and SRS after TKI resistance were important influencing factors for CRN. Conclusion: Performing the SRS for brain metastases after TKI resistance worsened the occurrence of CRN of patients treated with TKI. Clinical Trial Registration: Chinese clinical trial registry, http://www.chictr.org.cn/edit.aspx?pid=38395&htm=4, Registration number: ChiCTR1900022750.

OBJECTIVE: To investigate the treatment efficacy of ultra-low-dose bevacizumab for cerebral radiation necrosis.
METHODS: Patients with cerebral radiation necrosis after stereotactic radiotherapy (SRT) confirmed by imaging were included. Bevacizumab (1 mg/kg, once every three weeks, for at least three continuous treatments) was administered. The primary endpoints included change in cerebral necrosis symptoms, volume of intracranial edema, and changes in MRI signals. The secondary endpoints were adverse reactions of bevacizumab treatment.
RESULTS: In total, 21 patients were included in this study, all of whom received SRT between December 2016 and February 2019, developed cerebral radiation necrosis, and were treated with bevacizumab. Twenty patients were symptomatic from radiation necrosis, and the symptoms were alleviated in 18 patients (90%). Twenty patients had intracranial edema, and the grade of edema index (EI) was improved in 19 patients (95%). The intensity of the intracranial-enhanced MRI signals was significantly reduced in 20 patients (95.24%). The adverse reactions of bevacizumab treatment were mild, and no adverse reactions more severe than grade 2 were found.
CONCLUSIONS: The preliminary results showed that ultra-low-dose bevacizumab had high efficacy for treating cerebral radiation necrosis, and could be a valid alternative to the standard-dose bevacizumab.
UNASSIGNED: Chinese clinical trial registry (ChiCTR-IOD-16009803).

Cerebral radiation necrosis is a common complication of the radiotherapy of brain tumours that can cause significant mortality. Corticosteroids are the standard of care, but their efficacy is limited and the consequences of long-term steroid therapy are problematic, including the risk of adrenal insufficiency (AI). Off-label treatment with the vascular endothelial growth factor A antibody bevacizumab is highly effective in steroid-resistant radiation necrosis. Both the preservation of neural tissue integrity and the cessation of steroid therapy are key goals of bevacizumab treatment. However, the withdrawal of steroids may be impossible in patients who develop AI. In order to elucidate the frequency of AI in patients with cerebral radiation necrosis after treatment with corticosteroids and bevacizumab, we performed a retrospective study at our institution\'s brain tumour centre. We obtained data on the tumour histology, age, duration and maximum dose of dexamethasone, radiologic response to bevacizumab, serum cortisol, and the need for hydrocortisone substitution for AI. We identified 17 patients with cerebral radiation necrosis who had received treatment with bevacizumab and had at least one available cortisol analysis. Fifteen patients (88%) had a radiologic response to bevacizumab. Five of the 17 patients (29%) fulfilled criteria for AI and required hormone substitution. Age, duration of dexamethasone treatment, and time since radiation were not statistically associated with the development of AI. In summary, despite the highly effective treatment of cerebral radiation necrosis with bevacizumab, steroids could yet not be discontinued due to the development of AI in roughly one-third of patients. Vigilance to spot the clinical and laboratory signs of AI and appropriate testing and management are, therefore, mandated.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) has been utilized as adjunctive treatment of CNS tumors and for radiation necrosis (RN) with reported success. The safety and efficacy in pediatric patients is less understood.
METHODS: Seven patients (ages 10-23 years, six females) were treated with HBOT (3-60 sessions) for either RN (n = 5) or tumor-associated edema (n = 2). Tumor diagnosis included low-grade glioma (n = 4, two with neurofibromatosis type 1), meningioma (n = 1), medulloblastoma (n = 1) and secondary high grade glioma (n = 1). Prior therapies included: surgery (n = 4), chemotherapy (n = 4) and radiation (N = 5: four focal, one craniospinal). Three underwent biopsy: one confirming RN, one high-grade glioma, and one low-grade glioma. Patients were assessed for clinical and radiographic changes post HBOT.
RESULTS: Median time to clinical and radiographic presentation was 8.5 months (range 6 months-11 years) in those who had prior radiation. Clinical improvement after HBOT (median: 40 sessions) was observed in four of seven patients. Symptoms were stable in two and worsened in one patient. Radiographic improvement was seen in four patients; three had radiographic disease progression. In the subgroup treated for presumed and biopsy-confirmed RN (n = 5), four of five (80%) had clinical and radiographic improvement. There were no long-term adverse events due to HBOT.
CONCLUSIONS: HBOT is safe and well-tolerated in pediatric and young adult patients with CNS tumors. Clinical and radiographic improvements were observed in over half of patients. Clinical trials are needed to establish safety and efficacy of HBOT as adjunct therapy in pediatric CNS tumors.

Cerebral radiation necrosis (CRN) is a known complication of radiation therapy. Treatment options are limited and include steroids, bevacizumab, and surgery. This study seeks to determine the safety of laser interstitial thermal therapy (LITT) for CRN and identify the pattern of post-ablation volume change over time. Patients undergoing LITT for tumor treatment at Henry Ford Hospital between November 2013 and January 2016 with biopsy-confirmed CRN were prospectively collected and retrospectively reviewed with attention to ablation volume, survival, demographic data, steroid dose, and complications. Imaging occurred at set intervals beginning pre-ablation. Ten patients with 11 ablations were evaluated. Four patients had a primary diagnosis of high-grade glioma, while six had metastatic lesions. An average of 86% of CRN volume was ablated. Ablation volume increased to 430% of initial CRN volume at 1-2 weeks before decreasing to 69% after 6 months. No patient had a decline in baseline neurological examination while in the hospital. Four patients developed delayed neurological deficits likely due to post-operative edema, of which three improved back to baseline. The 6-month survival was 77.8% and the 1-year survival was 64.8% based on Kaplan-Meier curve estimates. In this study, LITT was a relatively safe treatment for CRN, providing both a diagnostic and therapeutic solution for refractory patients. Significant increase in ablation volume was noted at 1-2 months, gradually decreasing in size to less than the original volume by 6 months. Further studies are needed to better define the role of LITT in the treatment of CRN.