Gelsolin knockdown confers radiosensitivity to glioblastoma cells.

OBJECTIVE: Radiotherapy (RT) is a cornerstone of the glioblastoma (GBM) treatment. However, the resistance of tumour cells to radiation results in early recurrence. The mechanisms underlying GBM radioresistance remain unclear. Screening for differentially expressed genes (DEGs) related to radiation might be a potential solution to this problem. METHOD: RT-associated DEGs were screened based on the RNA sequencing of 15 paired primary and recurrent GBMs. The mRNA and protein expression of candidate genes were validated in RNA sequencing of The Chinese Genome Atlas (CGGA) dataset and 18 cases of GBM samples. The relationship between the candidate gene and radiation was confirmed in irradiated GBM cells. The association of candidate gene with clinical characteristics and survival was investigated in the CGGA and TCGA dataset. Biological function and pathway analysis were explored by gene ontology analysis. The association of the candidate gene with radiosensitivity was verified using cell counting Kit-8, comet, and colony formation assays in vitro and subcutaneous tumour xenograft experiments in vivo. RESULTS: Gelsolin (GSN) was selected for further study. GSN expression was significant elevated in recurrent GBM and up-regulated in irradiated GBM cell lines. High expression of GSN was enriched in malignant phenotype of glioma. Moreover, high expression of GSN was associated with poor prognosis. Further investigation demonstrated that GSN-knockdown (GSN-KD) combined with RT significantly inhibited cell proliferation and enhanced radiosensitivity in vivo and in vitro. Mechanistically, GSN-KD could lead to more serious DNA damage and promotes apoptosis after RT. CONCLUSION: Radiation induced up-regulated of GSN. GSN-KD could enhance the radiosensitivity of GBM.

Timing of microsurgical resection for ruptured brain arteriovenous malformations: a propensity score-matched analysis using prospective single-center registry data.

OBJECTIVE: The optimal microsurgical timing in ruptured brain arteriovenous malformations (AVMs) is not well understood and is surrounded by controversy. This study aimed to elucidate the impacts of microsurgical resection timing on clinical outcomes. METHODS: The authors retrieved and reviewed the records on all ruptured AVMs treated at their institution and registered in a nationwide multicenter prospective collaboration registry between August 2011 and August 2021. Patients were dichotomized into an early resection group (≤ 30 days from the last hemorrhagic stroke) and a delayed resection group (> 30 days after the last hemorrhagic stroke). Propensity score-matched analysis was used to compare long-term outcomes. The primary outcome was neurological status as assessed using the modified Rankin Scale (mRS). The secondary outcomes were complete obliteration rate, postoperative seizure, and postoperative hemorrhage. RESULTS: Of the 3649 consecutive AVMs treated at the authors' institution, a total of 558 ruptured AVMs were microsurgically resected and had long-term follow-up. After propensity score matching, 390 ruptured AVMs (195 pairs) were included in the comparison of outcomes. The mean (± standard deviation) clinical follow-up duration was 4.93 ± 2.94 years in the early resection group and 5.61 ± 2.56 years in the delayed resection group. Finally, as regards the distribution of mRS scores, short-term neurological outcomes were better in the delayed resection group (risk difference [RD] 0.3%, 95% CI -0.1% to 0.6%, p = 0.010), whereas long-term neurological outcomes were similar between the two groups (RD 0.0%, 95% CI -0.2% to 0.2%, p = 0.906). Long-term favorable neurological outcomes (early vs delayed: 90.8% vs 90.3%, p > 0.999; RD 0.5%, 95% CI -5.8% to 6.9%; RR 1.01, 95% CI 0.94-1.07) and long-term disability (9.2% vs 9.7%, p > 0.999; RD -0.5%, 95% CI -6.9% to 5.8%; RR 0.95, 95% CI 0.51-1.75) were also similar between these groups. In terms of secondary outcomes, postoperative seizure (early vs delayed: 8.7% vs 5.6%, p = 0.239; RD 3.1%, 95% CI -2.6% to 8.8%; RR 1.55, 95% CI 0.74-3.22), postoperative hemorrhage (1.0% vs 1.0%, p > 0.999; RD 0.0%, 95% CI -3.1% to 3.1%; RR 1.00, 95% CI 0.14-7.04), and hospitalization time (16.4 ± 8.5 vs 19.1 ± 7.9 days, p = 0.793) were similar between the two groups, whereas early resection had a lower complete obliteration rate (91.3% vs 99.0%, p = 0.001; RD -7.7%, 95% CI -12.9% to 3.1%; RR 0.92, 95% CI 0.88-0.97). CONCLUSIONS: Early and delayed resection of ruptured AVMs had similar long-term neurological outcomes. Delayed resection can lead to a higher complete obliteration rate, although the risk of rerupture during the resection waiting period should be vigilantly monitored.

IDH-mutant grade 4 astrocytoma: a comparison integrating the clinical, pathological, and survival features between primary and secondary patients.

OBJECTIVE: IDH-mutant grade 4 astrocytomas (AIDHmut/G4) are divided into primary de novo (pAIDHmut/G4) and secondary with a history of prior lower-grade gliomas (LGGs; sAIDHmut/G4). The mutational spectrum and DNA methylation patterns are homogeneous within de novo pAIDHmut/G4 and evolved sAIDHmut/G4, but the two groups have different diagnoses, management, and outcomes. This study sought to systematically compare the clinical, pathological, and survival characteristics between them. METHODS: Of the 871 grade 4 astrocytomas with data for IDH mutation, 698 (80.1%) were primary and 173 (19.9%) were secondary. Of the 698 primary tumors, 103 (14.8%) were pAIDHmut/G4, and of the 173 secondary tumors, 108 (62.4%) were sAIDHmut/G4. Clinical, pathological, and survival features were compared between pAIDHmut/G4 and sAIDHmut/G4. Multivariate analyses were performed to identify prognostic factors. RESULTS: Patients with sAIDHmut/G4 had significantly shorter median overall survival (OS; 11.8 vs 34.2 months, hazard ratio [HR] 2.69, 95% confidence interval [CI] 1.367-5.306, p = 0.004) and progression-free survival (PFS; 8.5 vs 24.3 months, HR 2.83, 95% CI 1.532-5.235, p = 0.001) than patients with pAIDHmut/G4. In patients with sAIDHmut/G4, resection status and chemotherapy were independent prognostic factors for OS and PFS; in patients with pAIDHmut/G4, LGG component, resection status, and O6-methylguanine DNA methyltransferase promoter methylation were independent prognostic factors. The therapeutic strategies of LGGs did not influence survival of patients with sAIDHmut/G4, but patients who had not received radiotherapy or chemotherapy when they were diagnosed with LGGs were found to benefit from radiotherapy or chemotherapy when they progressed to sAIDHmut/G4. CONCLUSIONS: The different clinical characteristics, survival, and risk factors between sAIDHmut/G4 and pAIDHmut/G4 provide a reference to guide treatment decisions in AIDHmut/G4.

Re-rupture in ruptured brain arteriovenous malformations: a retrospective cohort study based on a nationwide multicenter prospective registry.

BACKGROUND: This study aimed to investigate the natural history of re-rupture in ruptured brain arteriovenous malformations (AVMs) and to provide comprehensive insights into its associated factors and prevention. METHODS: This study included 1712 eligible ruptured AVMs from a nationwide multicenter prospective collaboration registry between August 2011 and September 2021. The natural rupture risk before intervention and the annual rupture risk after intervention were both assessed. Cox proportional hazard regression models and Kaplan-Meier survival curves were used to explore independent factors associated with AVM re-rupture. The correlation between these factors and AVM re-rupture was verified in multiple independent cohorts, and the prevention effect of intervention timing and intervention strategies on AVM re-rupture was further analyzed. RESULTS: The annual re-rupture risk in ruptured AVMs was 7.6%, and the cumulative re-rupture risk in the first 1, 3, 5, and 10 years following the initial rupture were 10%, 25%, 37.5%, and 50%, respectively. Cox proportional hazard regression analysis confirmed adult patients, ventricular system involvement, and any deep venous drainage as independent factors associated with AVM re-rupture. The intervention was found to significantly reduce the risk of AVM re-rupture (annual rupture risk 11.34% vs 1.70%, p<0.001), especially in those who underwent surgical resection (annual rupture risk 0.13%). CONCLUSIONS: The risk of re-rupture in ruptured AVMs is high. Adult patients, ventricular system involvement, and any deep venous drainage are independent risk factors for re-rupture. Applying the results universally to all ruptured AVM cases may be biased. Intervention could effectively reduce the risk of re-rupture.

Bevacizumab reduces peritumoral brain edema in lung cancer brain metastases after radiotherapy.

BACKGROUND: The aim of this study was to investigate the efficacy of bevacizumab (Bev) in reducing peritumoral brain edema (PTBE) after stereotactic radiotherapy (SRT) for lung cancer brain metastases. METHODS: A retrospective analysis was conducted on 44 patients with lung cancer brain metastases (70 lesions) who were admitted to our oncology and Gamma Knife center from January 2020 to May 2022. All patients received intracranial SRT and had PTBE. Based on treatment with Bev, patients were categorized as SRT + Bev and SRT groups. Follow-up head magnetic resonance imaging was performed to calculate PTBE and tumor volume changes. The edema index (EI) was used to assess the severity of PTBE. Additionally, the extent of tumor reduction and intracranial progression-free survival (PFS) were compared between the two groups. RESULTS: The SRT + Bev group showed a statistically significant difference in EI values before and after radiotherapy (p = 0.0115), with lower values observed after treatment, but there was no difference in the SRT group (p = 0.4008). There was a difference in the distribution of EI grades in the SRT + Bev group (p = 0.0186), with an increased proportion of patients at grades 1-2 after radiotherapy, while there was no difference in the SRT group (p > 0.9999). Both groups demonstrated a significant reduction in tumor volume after radiotherapy (p < 0.05), but there was no difference in tumor volume changes between the two groups (p = 0.4089). There was no difference in intracranial PFS between the two groups (p = 0.1541). CONCLUSION: Bevacizumab significantly reduces the severity of PTBE after radiotherapy for lung cancer. However, its impact on tumor volume reduction and intracranial PFS does not reach statistical significance.

Long-term outcomes of microsurgery and stereotactic radiosurgery as the first-line treatment for arteriovenous malformations: a propensity score-matched analysis using nationwide multicenter prospective registry data.

BACKGROUND: This study aimed to compare the risk and benefit profile of microsurgery (MS) and stereotactic radiosurgery (SRS) as the first-line treatment for unruptured and ruptured arteriovenous malformations (AVMs). MATERIALS AND METHODS: The authors included AVMs underwent MS or SRS as the first-line treatment from a nationwide prospective multicenter registry in mainland China. The authors used propensity score-matched methods to balance baseline characteristics between the MS and SRS groups. The primary outcomes were long-term hemorrhagic stroke or death, and the secondary outcomes were long-term obliteration and neurological outcomes. Subgroup analyses and sensitivity analyses with different study designs were performed to confirm the stability of our findings. RESULTS: Of the 4286 consecutive AVMs in the registry from August 2011 to December 2021; 1604 patients were eligible. After matching, 244 unruptured and 442 ruptured AVMs remained for the final analysis. The mean follow-up duration was 7.0 years in the unruptured group and 6.1 years in the ruptured group. In the comparison of primary outcomes, SRS was associated with a higher risk of hemorrhagic stroke or death both in the unruptured and ruptured AVMs (unruptured: hazard ratio 4.06, 95% CI: 1.15-14.41; ruptured: hazard ratio 4.19, 95% CI: 1.58-11.15). In terms of the secondary outcomes, SRS was also observed to have a significant disadvantage in long-term obliteration [unruptured: odds ratio (OR) 0.01, 95% CI: 0.00-0.04; ruptured: OR 0.09, 95% CI: 0.05-0.15]. However, it should be noted that SRS may have advantages in preventing neurofunctional decline (unruptured: OR 0.56, 95% CI: 0.27-1.14; ruptured: OR 0.41, 95% CI: 0.23-0.76). The results of subgroup analyses and sensitivity analyses were consistent in trend but with slightly varied powers. CONCLUSIONS: This clinical practice-based real-world study comprehensively compared MS and SRS for AVMs with long-term outcomes. MS is more effective in preventing future hemorrhage or death and achieving obliteration, while the risk of neurofunctional decline should not be ignored.

Expression of TMEM59L associated with radiosensitive in glioblastoma.

Radiotherapy is one of the cornerstone of the glioblastoma treatment paradigm. However, the resistance of tumor cells to radiation results in poor survival. The mechanism of radioresistance has not been fully elucidated. This study aimed to screen the differential expressed genes related with radiosensitivity. The differentially expressed genes were screened based on RNA sequencing in 15 pairs of primary and recurrent glioblastoma that have undergone radiotherapy. Candidate genes were validated in 226 primary and 134 recurrent glioblastoma (GBM) obtained from the Chinese Glioma Genome Atlas (CGGA) database. RNA and protein expression were verified by Quantitative Real-time PCR (qPCR) and western blot in irradiated GBM cell lines. The candidate gene was investigated to explore the relationship between mRNA levels and clinical characteristics in the CGGA and The Cancer Genome Atlas dataset. Kaplan-Meier survival analysis and Cox regression analysis were used for survival analysis. Gene ontology and KEGG pathway analysis were used for bioinformatics analysis. Four genes (TMEM59L, Gelsolin, ZBTB7A and ATX) were screened. TMEM59L expression was significantly elevated in recurrent glioblastoma and lower in normal brain tissue. We selected TMEM59L as the target gene for further study. The increasing of TMEM59L expression induced by radiation was confirmed by mRNA and western blot in irradiated GBM cell. Further investigation revealed that high expression of TMEM59L was enriched in IDH mutant and MGMT methylated gliomas and associated with a better prognosis. Gene ontology and KEGG pathway analysis revealed that TMEM59L was closely related to the DNA damage repair and oxidative stress respond process. We speculated that the high expression of TMEM59L might enhance radiotherapy sensitivity by increasing ROS-induced DNA damage and inhibiting DNA damage repair process.

Association of the combined stereotactic radiosurgery and embolization strategy and long-term outcomes in brain arteriovenous malformations with a volume ≤10 mL: a nationwide multicenter observational prospective cohort study.

BACKGROUND: To compare the long-term outcomes of stereotactic radiosurgery (SRS) with or without prior embolization in brain arteriovenous malformations (AVMs) (volume ≤10 mL) for which SRS is indicated. METHODS: Patients were recruited from a nationwide multicenter prospective collaboration registry (the MATCH study) between August 2011 and August 2021, and categorized into combined embolization and SRS (E+SRS) and SRS alone cohorts. We performed propensity score-matched survival analysis to compare the long-term risk of non-fatal hemorrhagic stroke and death (primary outcomes). The long-term obliteration rate, favorable neurological outcomes, seizure, worsened mRS score, radiation-induced changes, and embolization complications were also evaluated (secondary outcomes). Hazard ratios (HRs) were calculated using Cox proportional hazards models. RESULTS: After study exclusions and propensity score matching, 486 patients (243 pairs) were included. The median (IQR) follow-up duration for the primary outcomes was 5.7 (3.1-8.2) years. Overall, E+SRS and SRS alone were similar in preventing long-term non-fatal hemorrhagic stroke and death (0.68 vs 0.45 per 100 patient-years; HR=1.46 (95% CI 0.56 to 3.84)), as well as in facilitating AVM obliteration (10.02 vs 9.48 per 100 patient-years; HR=1.10 (95% CI 0.87 to 1.38)). However, the E+SRS strategy was significantly inferior to the SRS alone strategy in terms of neurological deterioration (worsened mRS score: 16.0% vs 9.1%; HR=2.00 (95% CI 1.18 to 3.38)). CONCLUSIONS: In this observational prospective cohort study, the combined strategy of E+SRS does not show substantial advantages over SRS alone. The findings do not support pre-SRS embolization for AVMs with a volume ≤10 mL.

Association of embolization with long-term outcomes in brain arteriovenous malformations: a propensity score-matched analysis using nationwide multicenter prospective registry data.

BACKGROUND: Brain arteriovenous malformations (AVMs) account for 25% of hemorrhagic strokes in young adults. Although embolization has been widely performed as a stand-alone procedure to cure brain AVM, it is undermined whether patients benefit from this treatment. This study aimed to compare the long-term outcome of hemorrhagic stroke or death in patients with either conservative management or stand-alone embolization for AVM. METHODS: The study population was derived from a nationwide multicenter prospective collaboration registry (the MATCH registry) between August 2011 and August 2021. The propensity score-matched survival analysis was performed in the overall and stratified AVM cases (unruptured and ruptured), respectively, to compare the long-term outcome of hemorrhagic stroke or death, and neurological status. The efficacy of distinct embolization strategies was also evaluated. Hazard ratios (HRs) with 95% CI were calculated using Fine-Gray competing risk models. RESULTS: Of the 3682 consecutive AVMs, 906 underwent either conservative management or embolization as the stand-alone management strategy. After propensity score matching, a total of 622 (311 pairs) patients constituted an overall cohort. The unruptured and ruptured subgroups were composed of 288 cases (144 pairs) and 252 cases (126 pairs), respectively. In the overall cohort, embolization did not prevent long-term hemorrhagic stroke or death compared with conservative management [2.07 vs. 1.57 per 100 patient-years; HR, 1.28 (95% CI, 0.81-2.04)]. Similar results were maintained in both unruptured AVMs [1.97 vs. 0.93 per 100 patient-years; HR, 2.09 (95% CI, 0.99-4.41)] and ruptured AVMs [2.36 vs. 2.57 per 100 patient-years; HR, 0.76 (95% CI, 0.39-1.48)]. Stratified analysis showed that the target embolization might be beneficial for unruptured AVMs [HR, 0.42 (95% CI, 0.08-2.29)], while the curative embolization improved the outcome of ruptured AVMs [HR, 0.29 (95% CI, 0.10-0.87)]. The long-term neurological status was similar between these two strategies. CONCLUSIONS: This prospective cohort study did not support a substantial superiority of embolization over conservative management for AVMs in preventing long-term hemorrhagic stroke or death.

Assessment of gamma knife radiosurgery for unruptured cerebral arterioveneus malformations based on multi-parameter radiomics of MRI.

OBJECTIVE: The treatment of Gamma knife radiosurgery (GKS) for unruptured Arteriovenous Malformations (AVM) remains controversial. A safe, effective and non-invasive method to predict outcome seems attractive for GKS. The purpose of this study was to develop and validate a MRI based multi-parameter radiomics model predicting the outcome of GKS for unruptured AVM. METHODS: Eighty-eight unruptured AVM patients who initial underwent GKS between January 2011 and December 2016 in our hospital were included in this retrospective study. Patients were divided into two groups named as favourable and unfavourable outcome, according to the clinical outcome. Favourable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC). Multivariate logistic regression analysis was used to select appropriate clinical features and construct a clinical predicting model. In terms of radiomic model, manually segmentation and radiomics extracted were performed on each AVM lesions. Finally, 1684 radiomics features were extracted and Recursive Feature Elimination (RFE) method combined with Random forest classifier were used for feature selection and model construction. The performance of the radiomics model was evaluated by the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In addition, the favourable group was further divided into early and late respond subgroup according to the time of obliteration evaluated by 2 years. The selected features were further compared according the respond time. RESULTS: The median duration of neuroimaging follow-up was 65 months, 56 patients showed favourable outcome and 17 patients were observed obliteration within 2 years. The radiomics model constructed by 12 selected features achieved significant higher AUC of 0.88 (95% confidence interval 0.87-0.90) than traditional scoring system for predicting AVM outcome. Two selected radiomics features named "Dependence Variance" and "firstorder-Skewness" were found significant difference between the patients with early or late-respond. CONCLUSIONS: The results suggest that the radiomics features could be successfully used for the pretreatment prediction of outcome for GKS in unruptured AVMs, which is helpful for decision-making process on unruptured AVM patients.

A Machine Learning Model Predicts the Outcome of SRS for Residual Arteriovenous Malformations after Partial Embolization: A Real-World Clinical Obstacle.

OBJECTIVE: To propose a machine learning (ML) model predicting the favorable outcome of stereotactic radiosurgery (SRS) for residual brain arteriovenous malformation (bAVM) after partial embolization. METHODS: One hundred and thirty bAVM patients who underwent partial embolization followed by SRS were reviewed retrospectively. Patients were split at random split into training datasets (n = 100) and testing datasets (n = 30). Radiomics and dosimetric features were extracted from pre-SRS treatment images. Feature selection was performed to select appropriate radiomics and dosimetric features. Three ML algorithms were applied to construct models using selected features respectively. A total of 9 models were trained to predict favorable outcomes (obliteration without complication) of bAVMs. The efficacy of these models was evaluated on the testing dataset using mean accuracy (ACC) and area under the receiver operating characteristic curve (AUC). RESULTS: The obliteration rate of this cohort was 70.77% (92 of 130) with a mean follow-up of 43.8 months (range, 12-108 months). Favorable outcomes were achieved in 89 patients (68.46%). Four radiomics features and 7 dosimetric features were selected for ML model construction. The dosimetric support vector machines (SVM) model showed the best performance on the training dataset, with an ACC of 0.74 and AUC of 0.78. The dosimetric SVM model also showed the best performance on the testing dataset, with an ACC of 0.83 and AUC of 0.77. CONCLUSIONS: Dosimetric features are good predictors of prognosis for patients with partially embolized bAVM followed by SRS therapy. The use of ML models is an innovative method for predicting favorable outcomes of partially embolized bAVM followed by SRS therapy.

The role of Gamma Knife radiosurgery in the management of skull base chordoma.

Objective: Chordoma is a slow-growing and locally aggressive cancer, which arises from the remnants of the primitive notochord. The first line treatment for the skull base chordoma is neurosurgery. Gamma Knife radiosurgery (GKS) is often be chosen especially in the setting of residual or recurrent chordomas. The purpose of this study is to evaluate the prognosis of patients with skull base chordoma who underwent GKS. Methods: The present study was a retrospective analysis of 53 patients with skull base chordomas who underwent GKS. Univariate Cox and Kaplan-Meier survival analysis were performed to analyze the relationship between the tumor control time and the clinical characteristics. Results: The 1-, 2-, 3-, and 5-year progression free survival (PFS) rates were 87, 71, 51, and 18%, respectively. After performing the univariate analysis, the clinical characteristics were not found to be significantly associated with the time of PFS; however, surgical history, peripheral dose, and tumor volume did have tendencies to predict the prognosis. Conclusion: GKS provided a safe and relatively effective treatment for residual or recurrent chordomas after surgical resection. A higher tumor control rate depends on two approaches, an appropriate dose of radiation for the tumor and the accurate identification of the tumor margins.

Stereotactic Radiosurgery With vs. Without Prior Embolization for Brain Arteriovenous Malformations: A Propensity Score Matching Analysis.

Objective: Whether partial embolization could facilitate the post-stereotactic radiosurgery (SRS) obliteration for brain arteriovenous malformations (bAVMs) remains controversial. We performed this study to compare the outcomes of SRS with and without prior embolization for bAVMs. Methods: We retrospectively reviewed the Beijing Tiantan AVMs prospective registration research database from September 2011 to October 2014. Patients were categorized into two groups, combined upfront embolization and SRS (Em+SRS group) and SRS alone (SRS group), and we performed a propensity score matching analysis based on pre-embolization baseline characteristics; the matched groups each comprised 76 patients. Results: The obliteration rate was similar between SRS and Em+SRS (44.7 vs. 31.6%; OR, 1.754; 95% CI, 0.905-3.401; p = 0.096). However, the SRS group was superior to the Em+SRS group in terms of cumulative obliteration rate at a follow-up of 5 years (HR,1.778; 95% CI, 1.017-3.110; p = 0.033). The secondary outcomes, including functional state, post-SRS hemorrhage, all-cause mortality, and edema or cyst formation were similar between the matched cohorts. In the ruptured subgroup, the SRS group could achieve higher obliteration rate than Em+SRS group (56.5 vs. 31.9%; OR, 2.773; 95% CI, 1.190-6.464; p = 0.018). The cumulative obliteration rate at 5 years was also higher in the SRS group (64.5 vs. 41.3%; HR, 2.012; 95% CI, 1.037-3.903; p = 0.038), and the secondary outcomes were also similar between the matched cohorts. Conclusion: Although there was no significant difference in the overall obliteration rate between the two strategies, this study suggested that pre-SRS embolization may have a negative effect on post-SRS obliteration. Furthermore, the obliteration rates of the SRS only strategy was significantly higher than that of the Em+SRS strategy in the ruptured cohort, while no such phenomenon was found in the unruptured cohort.

Radiosurgery-Based AVM Scale Is Proposed for Combined Embolization and Gamma Knife Surgery for Brain Arteriovenous Malformations.

Background and purpose: To evaluate whether a radiosurgery-based arteriovenous malformation (AVM) scale (RBAS) could be used to predict obliteration of brain arteriovenous malformations (bAVMs) supposed for combined endovascular embolization (EMB) and gamma knife surgery (GKS) treatment. Methods: bAVM patients who underwent GKS with or without previous EMB from January 2011 to December 2016 at our institution were retrospectively reviewed. The patients were categorized into a combined treatment group and a GKS group. A 1:1 propensity score matching (PSM) was used to match the two groups. Pre-EMB and pre-GKS RBAS were assessed for every patient. Multivariate analysis was performed to find factors associated with complete obliteration in the combined treatment group. Survival analysis based on sub-groups according to RBAS was performed to compare obliteration rate and find cutoffs for appropriate treatment modalities. Results: A total of 96 patients were involved, and each group comprised 48 patients. There was no difference between the two groups in terms of obliteration rate (75.0 vs. 83.3%, p = 0.174). Pre-EMB RBAS (p = 0.010) and the number of feeding arteries (p = 0.014) were independent factors associated with obliteration rate in the combined treatment group. For the combined treatment patients, sub-group analysis according to pre-EMB RBAS (score <1.0, 1.0-1.5, and >1.5) showed statistical difference in obliteration rate (p = 0.002). Sub-group analysis according to RBAS between the two groups showed that the obliteration rate of the GKS group is significantly higher than the combined group when RBAS >1.5 (47.4 vs. 66.7%, p = 0.036). Conclusions: The RBAS is proposed to be efficient in predicting obliteration of bAVMs supposed to receive combined EMB and GKS treatment. Patients with RBAS >1.5 are inclined to be more suitable for GKS instead of the combined treatment.

Long-term outcomes of brainstem arteriovenous malformations after different management modalities: a single-centre experience.

OBJECTIVE: The aims of this study are to clarify the long-term outcomes of brainstem arteriovenous malformations (AVMs) after different management modalities. METHODS: The authors retrospectively reviewed 61 brainstem AVMs in their institution between 2011 and 2017. The rupture risk was represented by annualised haemorrhagic rate. Patients were divided into five groups: conservation, microsurgery, embolisation, stereotactic radiosurgery (SRS) and embolisation+SRS. Neurofunctional outcomes were evaluated by the modified Rankin Scale (mRS). Subgroup analysis was conducted between different management modalities to compare the long-term outcomes in rupture or unruptured cohorts. RESULTS: All of 61 brainstem AVMs (12 unruptured and 49 ruptured) were followed up for an average of 4.5 years. The natural annualised rupture risk was 7.3%, and the natural annualised reruptured risk in the ruptured cohort was 8.9%. 13 cases were conservative managed and 48 cases underwent intervention (including 6 microsurgery, 12 embolisation, 21 SRS and 9 embolisation+SRS). In the selection of interventional indication, diffuse nidus were often suggested conservative management (p=0.004) and nidus involving the midbrain were more likely to be recommended for intervention (p=0.034). The risk of subsequent haemorrhage was significantly increased in partial occlusion compared with complete occlusion and conservative management (p<0.001, p=0.036, respectively). In the subgroup analysis, the follow-up mRS scores of different management modalities were similar whether in the rupture cohort (p=0.064) or the unruptured cohort (p=0.391), as well as the haemorrhage-free survival (p=0.145). In the adjusted Bonferroni correction analysis of the ruptured cohort, microsurgery and SRS could significantly improve the obliteration rate compared with conservation (p<0.001, p=0.001, respectively) and SRS may have positive effect on avoiding new-onset neurofunctional deficit compared with microsurgery and embolisation (p=0.003, p=0.003, respectively). CONCLUSIONS: Intervention has similar neurofunctional outcomes as conservation in these brainstem AVM cohorts. If intervention is adopted, partial obliteration should be avoided because of the high subsequent rupture risk. TRIAL REGISTRATION NUMBER: NCT04136860.

Factors Affecting Volume Reduction Velocity for Arteriovenous Malformations After Treatment With Dose-Stage Stereotactic Radiosurgery.

BACKGROUND AND PURPOSE: The purpose of this study was to identify morphologic and dosimetric features associated with volume reduction velocity for arteriovenous malformation (AVM) after dose-stage stereotactic radiosurgery (DS-SRS). METHODS: Thirty patients with intracranial AVM were treated with DS fractionated SRS at Beijing Tiantan Hospital from 2011 to 2019. The AVM nidus was automatically segmented from DICOMRT files using the 3D Slicer software. The change in lesion volume was obtained from the decrease in the planning target volume (PTV) between the two treatment sessions. The volume reduction velocity was measured by the change in volume divided by the time interval between treatments. Fourteen morphologic features of AVM prior to treatment were extracted from the PTV using 'Pyradiomics' implemented in Python. Along with other dosimetric features, univariate and multivariate analyses were performed to explore predictors of the volume reduction velocity. RESULTS: Among the 15 male (50.0%) and 15 female (50.0%) patients enrolled in this study, 17 patients (56.7%) initially presented with hemorrhage. The mean treatment interval between the initial and second SRS was 35.73 months. In multivariate analysis, the SurfaceVolumeRatio was the only independent factor associated with the volume reduction velocity (p=0.010, odds ratio=0.720, 95% confidence interval: 0.560-0.925). The area under the curve of this feature for predicting the volume reduction velocity after the initial treatment of DS-SRS was 0.83. (p=0.0018). CONCLUSIONS: The morphologic features correlated well with the volume reduction velocity in patients with intracranial AVM who underwent DS-SRS treatment. The SurfaceVolumeRatio could predict the rate of volume reduction of AVMs after DS-SRS.