Cerebral Radiation Necrosis Research Articles

Is Bevacizumab a Cost-Effective Regimen for Treating Cerebral Radiation Necrosis in the United States?

BackgroundBevacizumab 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 to corticosteroids for treating CRN from the US payers’ perspective. MethodsDecision 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 literature. 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 the models. ResultsIn 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 nonrecurrence 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 United States, the probabilities of bevacizumab being cost-effective for CRN short and long-term treatment were 63.9% and 49%, respectively. ConclusionsCompared with corticosteroids, bevacizumab is an economical alternative for CRN short-term treatment from the US payers’ perspective, whereas long-term therapy draws an opposite conclusion.

Bevacizumab reduces cerebral radiation necrosis due to stereotactic radiotherapy in non-small cell lung cancer patients with brain metastases: an inverse probability of treatment weighting analysis.

Cerebral radiation necrosis (RN), a severe complication of stereotactic radiotherapy (SRT), has been shown to significantly decrease patient survival time and quality of life. The purpose of this study was to analyze whether bevacizumab can prevent or reduce the occurrence of SRT-induced cerebral RN in non-small cell lung cancer (NSCLC) patients with brain metastases. We retrospectively reviewed the clinical records of NSCLC patients with brain metastases from March 2013 to June 2023 who were treated with SRT. Patients were divided into two groups: those in the bevacizumab group received SRT with four cycles of bevacizumab, and patients in the control group received SRT only. Inverse probability of treatment weighting (IPTW) was performed based on a multinomial propensity score model to balance the baseline characteristics. The chi-square test was used. A Cox model was used to evaluate overall survival (OS). A total of 80 patients were enrolled, namely, 28 patients in the bevacizumab group and 52 patients in the control group. The possibility of developing cerebral RN and/or symptomatic edema (RN/SE) was significantly decreased in patients treated with bevacizumab compared to those who did not receive bevacizumab before IPTW (p=0.036) and after IPTW (p=0.015) according to chi-square analysis. The IPTW-adjusted median OS was 47.7 months (95% CI 27.4-80.8) for patients in the bevacizumab group and 44.1 months (95% CI 36.7-68.0) (p=0.364) for patients in the control group. The application of bevacizumab concurrent with SRT may prevent or reduce the occurrence of cerebral RN in NSCLC patients with brain metastases.

Cost-effectiveness analysis of bevacizumab for cerebral radiation necrosis treatment based on real-world utility value in China.

Bevacizumab shows superior efficacy in cerebral radiation necrosis (CRN) therapy, but its economic burden remains heavy due to the high drug price. This study aims to evaluate the cost-effectiveness of bevacizumab for CRN treatment from the Chinese payers' perspective. Adecision tree model was developed to compare the costs and health outcomes of bevacizumab and corticosteroids for CRN therapy. Efficacy and safety data were derived from the NCT01621880 trial, which compared the effectiveness and safety of bevacizumab monotherapy with corticosteroids for CRN in nasopharyngeal cancer patients, and demonstrated that bevacizumab invoked asignificantly higher response than corticosteroids (65.5% vs. 31.5%, P < 0.001) with no significant differences in adverse events between two groups. The utility value of the "non-recurrence" status was derived from real-world data. Costs and other utility values were collected from an authoritative Chinese network database and published literature. The primary outcomes were total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). The uncertainty of the model was evaluated via one-way and probabilistic sensitivity analyses. Bevacizumab treatment added 0.12 (0.48 vs. 0.36) QALYs compared to corticosteroid therapy, along with incremental costs of $2010 ($4260 vs. $2160). The resultant ICER was $16,866/QALY, which was lower than the willingness-to-pay threshold of $38,223/QALY in China. The price of bevacizumab, body weight, and the utility value of recurrence status were the key influential parameters for ICER. Probabilistic sensitivity analysis revealed that the probability of bevacizumab being cost-effectiveness was 84.9%. Compared with corticosteroids, bevacizumab is an economical option for CRN treatment in China.

Characterization of cerebral radiation necrosis following the treatment of sinonasal malignancies.

Our study aims to determine the incidence and potential risk factors for cerebral radiation necrosis (CRN) following treatment of sinonasal malignancies. 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. 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. 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. Level 3.

Can low-dose intravenous bevacizumab be as effective as high-dose bevacizumab for cerebral radiation necrosis?

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.

Initial Report of Boswellia Serrata for Management of Cerebral Radiation Necrosis after Stereotactic Radiosurgery for Brain Metastases

Radiation necrosis (RN) is a concerning late toxicity after radiation therapy (RT) for brain metastases. Oral corticosteroids are the mainstay of management; however, they are not optimal for long-term use given multiple side effects and drug interactions, particularly with the emergence of immunotherapy for several cancers. Boswellia serrata (BS) is an over-the-counter supplement used for its anti-inflammatory properties and has been recently shown to reduce cerebral edema after brain RT. We evaluated the response rates with BS in a series of patients with brain metastases treated with stereotactic radiosurgery (SRS) who developed RN. We included patients who developed RN after SRS for brain metastases at our institution from 2020-2022 and were treated with BS. Patients were prescribed over the counter BS 4.2-4.5g daily in divided doses. Follow-up MRI imaging was obtained every 2-3 months after starting BS. Response was assessed using Response Assessment in Neuro-Oncology (RANO) criteria. Primary endpoint was ≥25% decrease in edema volume on T2-FLAIR MRI from baseline. Patients were censored if they had tumor progression or repeat RT to necrotic area, or death. Kaplan-Meier curves were used for survival estimates. A total of 50 patients received BS for Grade 1-3 CTCAE v5.0 RN (G1 = 11, G2 = 36, and G3 = 3). Median age was 62.8 years (range 36.9 - 50) and median RT dose was 24 Gy in 3 fractions. Median time to RN after SRS was 10 months(m). Median follow-up after starting BS was 6m and 40 patients had at least 1 follow up MRI available to evaluate response. The best response was complete response (CR) in 15% patients and partial response (PR) in 40% while 35% had stable disease (SD) and 10% had progressive disease. Median time to CR was 9m (6-12m) and PR was 6m (3-12m). Percentage of patients who had any response (CR or PR) at 3, 6, 9 and 12 months was 25%, 60%, 43% and 50%, respectively. 56% patients had symptomatic RN, of which 35.7% had improvement in symptoms with BS alone, while 64% required steroid use. Overall, median duration of response in patients with CR, PR or SD was 7.5m(range 2-31m). Salvage treatment for RN was steroids (33), surgery (4), Bevacizumab (5) or hyperbaric oxygen therapy (1). No patients had any CTCAE grade 3 or higher toxicities. 3 patients (6%) had any side-effects all of whom had Grade 1-2 gastrointestinal intolerance or diarrhea. 2 patients stopped treatment due to enrolment on an immunotherapy clinical trial. Overall, 39 patients remained on BS at last follow-up or death. We observed >50% response rates with use of BS in our cohort of patients with Grade 1-3 RN after SRS. More than 1/3rd patients with symptomatic RN were able to avoid long-term steroid use. BS is an easily available over-the-counter drug that appears to be a safe and promising treatment option for RN, and can potentially decrease steroid dependence in these patients, reducing the risk of several side-effects. Further prospective studies to compare Boswellia with placebo is warranted.

Stereotactic Radiotherapy (SRT) in Combination with Aumolertinib to Treat Intracranial Oligometastatic Non-Small Cell Lung Cancer (NSCLC): An Update of a Phase II, Prospective Study

Stereotactic radiotherapy (SRT) is highly effective and less toxic for limited intracranial metastases. Aumolertinib is a tolerable third-generation epidermal growth factor receptor tyrosine kinase inhibitor that has CNS efficacy in patients with EGFR-mutant NSCLC. We aim to investigate the efficacy and safety of aumolertinib followed by SRT in patients with intracranial oligometastatic NSCLC. Intracranial oligometastatic Patients with EGFR sensitive mutations (EGFR-TKIs naive) were enrolled and received aumolertinib 110mg daily until intracranial disease progression. Then SRT (32-40 Gy total, 8 Gy/f) was given to intracranial oligo-progression disease if possible. The primary endpoint was intracranial objective response rate (iORR). Secondary endpoints included intracranial progression-free survival (iPFS), intracranial duration of response (iDOR)according to RECIST 1.1, cerebral radiation necrosis rate (CRNR) and overall survival (OS). Safety was evaluated according to Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). This trial is registered with ClinicalTrials.gov, NCT04519983. To February 10, 2023, a total of 38 patients were enrolled and 35 patients were assessable followed for 3 months to 18 months. All patients received 110mg aumolertinib daily and received at least one independent imaging evaluation by a radiologist. After oral administration of aumolertinib, the best response of 94% patients in intracranial and extracranial lesions was partial response (PR). Two patients had stable intracranial disease. At data cut-off, one patient developed intracranial primary lesion progression at 12 months after oral administration of aumolertinib but stable in extracranial lesions. SRT treatment was given to this patient. No grade ≥3 adverse events occurred after continued oral administration of aumolertinib. The most common adverse reactions were rash and abnormal liver enzymes, 1 patient had grade 2 CK elevation. This report showed pronounced intracranial objective response benefit in patients with intracranial oligometastatic disease followed by SRT after intracranial oligo-progression and no new safety signals. Aumolertinib has promising efficacy and good tolerability in intracranial oligometastatic EGFR mutated NSCLC. [Keywords] Non-small cell lung cancer; epidermal growth factor receptor tyrosine kinase inhibitor; Aumolertinib; Stereotactic radiotherapy.

Use of 18F-PSMA PET to Distinguish Cerebral Radiation Necrosis From Tumor Recurrence.

Brain metastasis in prostate adenocarcinoma is extremely rare and usually arises in the setting of widespread osseous and visceral metastases. Surgical resection and radiation therapy, including stereotactic radiosurgery, are the mainstays of treatment for brain metastasis. Radiation necrosis is a common complication of radiotherapy for brain metastasis, and distinguishing it from tumor recurrence by MRI is difficult because of overlapping findings. We present a 73-year-old man with prostate cancer with a solitary brain metastasis where PET with 18F-piflufolostat helped detect disease recurrence in the setting of ambiguous MRI findings.

Effect of Bevacizumab Treatment in Cerebral Radiation Necrosis : Investigation of Response Predictors in a Single-Center Experience.

Bevacizumab is a feasible option for treating cerebral radiation necrosis (RN). We investigated the clinical outcome of RN after treatment with bevacizumab and factors related to the initial response and the sustained effect. Clinical data of 45 patients treated for symptomatic RN between September 2019 and February 2021 were retrospectively collected. Bevacizumab (7.5 mg/kg) was administered at 3-week intervals with a maximum four-cycle schedule. Changes in the lesions magnetic resonance image (MRI) scans were examined for the response evaluation. The subgroup analysis was performed based on the initial response and the long-term maintenance of the effect. Of the 45 patients, 36 patients (80.0%) showed an initial response, and eight patients (17.8%) showed delayed worsening of the corresponding lesion. The non-responders showed a significantly higher incidence of diffusion restriction on MRI than the responders (100.0% vs. 25.0%, p<0.001). The delayed worsening group showed a significantly higher proportion of glioma pathology than the maintenance group (87.5% vs. 28.6%, p=0.005). Cumulative survival rates with sustained effect were significantly higher in the groups with non-glioma pathology (p=0.019) and the absence of diffusion restriction (p<0.001). Pathology of glioma and diffusion restriction in MRI were the independent risk factors for non-response or delayed worsening after initial response. The initial response of RN to bevacizumab was favorable, with improvement in four-fifths of the patients. However, a certain proportion of patients showed non-responsiveness or delayed exacerbations. Bevacizumab may be more effective in treating RN in patients with non-glioma pathology and without diffusion restriction in the MRI.

Https://www.uhms.org/publications/uhm-journal/uhm-journal-ahead-of-print/uhm-journal-ahead-of-print/treatment-of-pediatric-cerebral-radiation-necrosis-using-hyperbaric-oxygenation-a-case-report.html

Introduction: Cerebral radiation necrosis is a rarely encountered in pediatric patients. This case report describes a child with cerebral radiation necrosis who was successfully treated using a corticosteroids, bevacizumab, and hyperbaric oxygenation. Case Report: A 3-year-old boy developed progressive extremity weakness six months after completion of radiation therapy for treatment of a neuroepithelial malignancy. Treatment with corticosteroids and bevacizumab was initiated, but his symptoms did not improve, and he was then referred for hyperbaric oxygen therapy. After completion of 60 hyperbaric treatments, he experienced significant improvements in mobility which remained stable over the next year. Discussion: Cerebral radiation necrosis typically presents in children with symptoms of ataxia or headache. Corticosteroids and bevacizumab are common treatments, but hyperbaric oxygen therapy has also been studied as a therapeutic modality for this condition. When considering the use of hyperbaric oxygenation in pediatric patients, careful attention to treatment planning and patient safety can reduce the risks of adverse events such as middle ear barotrauma and confinement anxiety. Conclusion: Hyperbaric oxygenation, in addition to other available pharmacologic therapies, should be considered for the treatment of pediatric patients with cerebral radiation necrosis.

Radiation necrosis or tumor progression? A review of the radiographic modalities used in the diagnosis of cerebral radiation necrosis

Cerebral radiation necrosis is a complication of radiation therapy that can be seen months to years following radiation treatment. Differentiating radiation necrosis from tumor progression on standard magnetic resonance imaging (MRI) is often difficult and advanced imaging techniques may be needed to make an accurate diagnosis. The purpose of this article is to review the imaging modalities used in differentiating radiation necrosis from tumor progression following radiation therapy for brain metastases. We performed a review of the literature addressing the radiographic modalities used in the diagnosis of radiation necrosis. Differentiating radiation necrosis from tumor progression remains a diagnostic challenge and advanced imaging modalities are often required to make a definitive diagnosis. If diagnostic uncertainty remains following conventional imaging, a multi-modality diagnostic approach with perfusion MRI, magnetic resonance spectroscopy (MRS), positron emission tomography (PET), single photon emission spectroscopy (SPECT), and radiomics may be used to improve diagnosis. Several imaging modalities exist to aid in the diagnosis of radiation necrosis. Future studies developing advanced imaging techniques are needed.

A Comparison of Modalities to Differentiate Radiation Necrosis from Tumor Progression: A Diagnostic Meta-Analysis

<h3>Purpose/Objective(s)</h3> Cerebral radiation necrosis is a complication following radiation treatment to the brain. It is hypothesized that radiation treatment causes vascular injury, leading to tissue ischemia and then radiation necrosis. Radiation necrosis is a delayed phenomenon, occurring several months to years after the completion of radiation therapy. Radiation necrosis can be difficult to diagnose as it appears similar to tumor progression on standard magnetic resonance imaging (MRI). The ability to distinguish the two is important for further treatment strategies, and there is no current guideline on which imaging modality should be used. Various imaging modalities have been studied as an alternative to MRI, including, but not limited to, MR perfusion techniques (MRP), MR spectroscopy (MRS), single photon emission computed tomography (SPECT), and positron emission tomography (PET). We aim to review the existing literature and perform a diagnostic meta-analysis comparing these different imaging modalities to differentiate radiation necrosis from tumor progression. <h3>Materials/Methods</h3> A systematic review adherent to PRISMA guidelines was performed using Scopus and PubMed databases. Sensitivities and specificities were pooled using the inverse-variance method, and 95% confidence intervals were calculated. To compare modalities, Euclidean distances are calculated as the absolute distance from the point (1.0, 1.0) of a theoretical ideal classifier on a graph of sensitivity vs. specificity. For evaluation of Euclidean distance, the lower the value, the closer the test is to optimal, which would be a sensitivity and specificity of 1. <h3>Results</h3> The analysis includes 113 studies with a total of 200 imaging data points, including the following imaging modalities: MRI (n = 13), MRS (n = 21), MRP (n = 12), Dynamic Contrast Enhanced (DCE) MRI (n = 4), Dynamic Susceptibility Contrast MRI (n = 20), MR arterial spin labeling (ASL) (n = 3), Diffusion Weighted Imaging (n = 11), Diffusion Tensor Imaging (DTI) (n = 2), PET (n = 88), and SPECT (n = 26). MRS had the highest pooled sensitivity at 0.92 (95% CI: 0.84 - 0.96), followed by DCE MRI (0.88; 95% CI: 0.70 - 0.96) and then SPECT (0.88; 95% CI: 0.82 - 0.93). The highest pooled specificities were DTI at 0.90 (95% CI: 0.69 - 0.98), SPECT at 0.88 (95% CI: 0.83 - 0.92), and DCE MRI at 0.85 (95% CI: 0.71 - 0.93). For Euclidean distances, SPECT had the lowest at 0.163 (95% CI: 0.106 - 0.248), followed by MRS (0.167; 95% CI: 0.100 - 0.275), and DCE MRI (0.185; 95% CI: 0.077 - 0.414). MRI had the highest Euclidean distance at 0.373 (95% CI: 0.238 - 0.542). <h3>Conclusion</h3> The results from this diagnostic meta-analysis evaluating pooled sensitivities, pooled specificities, and Euclidean distances indicate that SPECT and MRS appear to be promising imaging modalities for the differentiation of radiation necrosis from tumor progression. This study may have implications in the formation of imaging guidelines for this purpose.

An Analysis of Risk Factors for Radiation Necrosis Following Cranial Radiation.

IntroductionRadiation necrosis in the brain is a frequent complication of brain radiation therapy (RT) and is characterized by various neurological symptoms including cognitive dysfunction, headaches, weakness, apraxia, aphasia, and numbness. These symptoms may be progressive and treatment-resistant. Currently, risk factors for radiation necrosis are not well characterized. The goal of this study is to identify risk factors for cerebral radiation necrosis in order to improve clinicians’ ability to appropriately weigh the risks and benefits of brain RT.MethodsA retrospective chart review was performed on patients who were diagnosed with brain tumors and received RT (3D conformal therapy, volumetric modulated arc therapy, stereotactic radiosurgery, or stereotactic radiotherapy) at the University of Arkansas for Medical Sciences from July 1, 2017, to July 1, 2019. Data regarding demographics, characteristics of cancer, chemotherapy status and class, comorbidities, and additional medications of patients were collected via EPIC. Total RT dose, fraction size, volume of brain receiving 12 Gy (V12), and retreatment of locally recurrent tumors were recorded from Eclipse. The diagnosis of radiation necrosis was based on MRI reports that were examined for a time period of 24 months following the completion of radiation treatment and confirmed, when possible, by biopsy. Cases that did not have an MRI available at least two months after the completion of RT were excluded. Statistical association analyses were used to identify candidate risk factors to radiation necrosis. These candidate risk factors were further used to assess their associations to demographics and other characteristics of cancer and treatments. Finally, adjusted and unadjusted logistic regression models were used to predict radiation necrosis using a single risk factor or multiple risk factors. ROC curves were used to evaluate the performance of prediction or discrimination of the logistic regression models.ResultsA total of 139 patients were studied. The mean ± standard deviation (SD) for age was 60.4 ± 13.6 years, female:male ratio was 71:68, and White:African American:other race ratio was 112:24:3. A total of 43 (30.9%) patients were diagnosed with radiation necrosis. Radiation adjuvant to surgery, concurrent systemic therapy status, total dose, and V12 were found to be significantly associated with radiation necrosis and considered candidate risk factors of radiation necrosis in the study. Predictive models showed adjusted odds ratios ([aORs] 95% confidence intervals or CIs) of 3.70 (1.01-13.56) and 8.19 (1.78-37.78) with radiation adjuvant to surgery and concurrent systemic therapy, respectively. For every one unit (log-transformed) increase of total dose and V12, the aORs (95% CI’s) were 27.35 (3.74-200.16) and 1.63 (1.15-2.32), respectively.ConclusionOur study suggested a positive correlation of concurrent systemic therapy status and post-surgical adjuvant RT with the incidence of radiation necrosis. It further demonstrated that greater total RT dose and V12 were related to the risk of developing radiation necrosis following brain RT. Given the findings of this study, the aforementioned factors should be considered when weighing the risk of radiation necrosis with the benefits of treatment.

Hyperbaric Oxygen Therapy for Cerebral Radiation Necrosis Secondary to Stereotactic Radiation: A Case Series

Introduction: Stereotactic radiosurgery (SRS) is an excellent option for the treatment of numerous central nervous system diseases. There exist several forms of SRS, including gamma-knife surgery (GKS) and cyber-knife surgery. The most significant complication of SRS is the delayed effects of therapeutic radiation, also known as radionecrosis. The current treatment options for radionecrosis have a significant side effect profile and posit challenges for medical management. More recently, hyperbaric oxygen therapy (HBO2) has emerged as an option for treatment with minimal side effects. Methods: We present a retrospective case series examining ten patients treated with HBO2 after receiving radiotherapy. Of these cases, six were treated with GKS, two were treated with cyber-knife surgery, and two with Intensity-modulated radiation therapy (IMRT). Results: In all ten cases, the patients reported significant improvement in clinical symptoms. Conclusions: These cases demonstrate the efficacy of HBO2 as a treatment for cerebral radionecrosis.

Voxel-based radiomics outlines spatial heterogeneity of cerebral radiation necrosis (RN) associated with bevacizumab (Bev) response in head and neck radiotherapy (RT) patients.

e18063 Background: RN is a debilitating toxicity of head and neck RT, with incidences of 4% to 24%. Bev is a promising drug for managing RN, but there is currently no biomarker that could predict a priori if a patient would benefit from Bev. Here, we aimed to use radiomics to predict Bev response. However, current radiomics tools suffer from issues of interrater contouring variability and explanability of the radiomics models. We therefore investigated a voxel-based radiomics approach to characterize the spatial heterogeneity of RN, and define subregions that are associated with Bev response. Methods: 118 consecutive nasopharyngeal carcinoma (NPC) patients who were diagnosed with RN post-RT, and were treated with Bev between Jul 2012 and Mar 2019 at the Sun Yat-Sen Memorial Hospital were enrolled into the study. 77 patients with 101 brain lesions treated between Jul 2012 and Dec 2017 were assigned to the training set, and 41 patients with 51 brain lesions treated between Jan 2018 and Mar 2019 were used for validation. All patients received Bev prescribed at 5 mg/kg every fortnightly for up to 4 courses. We extracted voxel-based radiomics features from each segment drawn on T2 FLAIR MRI images, followed by a 3-step analysis (individual- and population-level clustering, before delta-radiomics) to obtain a clustered heat map of subregions within the RN lesion. Anatomical correlation to areas of edema, necrosis, and their interphase was performed. Delta-radiomics tracked the ∆ of each cluster to Bev. Features were then extracted from each radiomics cluster for model building. Results: 71 (70.3%) and 34 (66.7%) lesions had documented radiological responses to Bev in the training and validation sets, respectively. Responders (N = 105) and non-responders (N = 47) showed a 71.8% (IQR: 54.7-87.5) and 13.2% (IQR: 7.98-21.4) reduction in RN volumes, respectively. Five optimal clusters were determined using the shoulder method with ΔK metric. Spatial analyses revealed that 2 of the 5 clusters were associated with the edema areas, with 92.6% and 74.3% of the voxels located within this anatomic subregion. The two corresponding clusters were significantly associated with a response to Bev (Odds ratio [OR]: 11.12 (95% CI: 2.54-73.47), P = 0.004; OR: 1.63 [1.07-2.78], P = 0.042). Finally, we developed and validated a clinicoradiomics model based on features extracted from the 2 clusters that improved the prediction of Bev response, compared with a clinical-only model for both the training (AUC 0.852 vs 0.755) and validation (AUC 0.816 vs 0.691) cohorts. Conclusions: Our spatial radiomics approach revealed anatomic subregions that contain relevant radiomics features that could predict Bev efficacy in the treatment of RN in NPC patients. This method would improve the interpretability of radiomics, compared with current methods that lack spatial resolution.

Expert Consensus on the Treatment of Antiangiogenic Agents for Radiation Brain Necrosis

血管内皮生长因子（vascular endothelial growth factor, VEGF）的高水平表达是放射性脑坏死（cerebral radiation necrosis, CRN）发生的重要机制。抗血管生成药物（贝伐珠单抗）通过抑制VEGF，作用于脑坏死区域周围的血管组织，减轻CRN引起的脑水肿。许多研究证实贝伐珠单抗可有效缓解脑坏死症状，改善患者的体力状况评分以及减轻影像学上脑水肿范围。抗血管治疗的疗效主要与药物作用时长相关，低剂量抗血管药物即可达到较好的治疗效果。预防是最好的治疗，CRN的发生与肿瘤相关因素和治疗相关因素相关，通过控制两方面因素，可有效预防CRN。

Multiparametric MRI-guided Hypofractionated Intensity-modulated Radiation Therapy With Simultaneous Integrated Boost for Glioblastoma

This study investigated the feasibility and efficacy of multiparametric magnetic resonance imaging (MRI)-guided dose-escalated hypofractionated intensity-modulated radiation therapy with simultaneous integrated boost (IMRT-SIB) for glioblastoma. Eighteen patients underwent postoperative IMRT-SIB for glioblastoma using three MRI sequences: double inversion recovery (DIR), diffusion tensor imaging (DTI), and post-gadolinium T1-weighted imaging. Prescribed doses were 60 Gy and 40 Gy in 15 fractions for residual enhancing lesions and surrounding tumor-infiltrating areas, respectively. For surrounding tumor-infiltrating areas, asymmetric margins were set with reference to DTI imaging. The 1-year overall survival rate was 58.0%, and the 1-year local control rate for the residual enhancing lesions was 76.2%, while that for surrounding tumor-infiltrating areas was 39.4%. One patient (6%) developed grade 2 cerebral radiation necrosis 10 months after IMRT-SIB, but there was no grade 3 or higher adverse event. Multiparametric MRI-guided dose-escalated IMRT-SIB with DIR and DTI imaging has the potential to improve local control rates without increasing adverse events.

Low-Dosage Bevacizumab Treatment: Effect on Radiation Necrosis After Gamma Knife Radiosurgery for Brain Metastases.

Cerebral radiation necrosis (RN), a complication of Gamma Knife radiosurgery, is difficult to treat, although bevacizumab seems to be effective. However, clinical data pertaining to bevacizumab treatment for RN are scarce, and its high price is problematic. This study explored the effectiveness of low-dose bevacizumab for RN caused by Gamma Knife. We retrospectively analyzed 22 patients who suffered cerebral RN post-Gamma Knife, and received bevacizumab treatment because of the poor efficacy of glucocorticoids. Low-dose bevacizumab (3 mg/kg) was administered for two cycles at 2-week intervals. T1- and T2-enhanced magnetic resonance imaging (MRI) images were examined for changes in RN status. We also monitored the dose of glucocorticoid, Karnofsky Performance Status (KPS) score, and adverse drug reactions. The mean volume of RN lesions decreased by 45% on T1-weighted images with contrast enhancement, and by 74% on T2-weighted images. All patients discontinued the use of glucocorticoids. According to the KPS scores, all patients showed an improvement in their symptoms and neurological function. No side effects were observed. Low-dosage bevacizumab at a dose of 3 mg/kg every 2 weeks is effective for treating cerebral RN after Gamma knife for brain metastases.

Bevacizumab vs laser interstitial thermal therapy in cerebral radiation necrosis from brain metastases: a systematic review and meta-analysis.

Radiation necrosis (RN) represents a serious post-radiotherapy complication in patients with brain metastases. Bevacizumab and laser interstitial thermal therapy (LITT) are viable treatment options, but direct comparative data is scarce. We reviewed the literature to compare the two treatment strategies. PubMed, EMBASE, Scopus, and Cochrane databases were searched. All studies of patients with RN from brain metastases treated with bevacizumab or LITT were included. Treatment outcomes were analyzed using indirect meta-analysis with random-effect modeling. Among the 18 studies included, 143 patients received bevacizumab and 148 underwent LITT. Both strategies were equally effective in providing post-treatment symptomatic improvement (P = 0.187, I2 = 54.8%), weaning off steroids (P = 0.614, I2 = 25.5%), and local lesion control (P = 0.5, I2 = 0%). Mean number of lesions per patient was not statistically significant among groups (P = 0.624). Similarly, mean T1-contrast-enhancing pre-treatment volumes were not statistically different (P = 0.582). Patterns of radiological responses differed at 6-month follow-ups, with rates of partial regression significantly higher in the bevacizumab group (P = 0.001, I2 = 88.9%), and stable disease significantly higher in the LITT group (P = 0.002, I2 = 81.9%). Survival rates were superior in the LITT cohort, and statistical significance was reached at 18months (P = 0.038, I2 = 73.7%). Low rates of adverse events were reported in both groups (14.7% for bevacizumab and 12.2% for LITT). Bevacizumab and LITT can be safe and effective treatments for RN from brain metastases. Clinical and radiological outcomes are mostly comparable, but LITT may relate with superior survival benefits in select patients. Further studies are required to identify the best patient candidates for each treatment group.

Iatrogenic cerebral radiation necrosis

Cerebral radiation necrosis is the most serious late reaction to high doses of ionising radiation to the brain, and its treatment is generally unsatisfactory. We present a patient who developed...