Symptomatic Radiation-induced Changes Research Articles

Stereotactic radiosurgery for arteriovenous malformations in pediatric patients: an updated systematic review and meta-analysis.

Intracranial arteriovenous malformations are the most common cause of intracranial hemorrhages in pediatric patients. Stereotactic radiosurgery (SRS) has been used extensively to treat these lesions. The authors conducted a systematic review and meta-analysis to report treatment outcomes and long-term complications. This study follows the PRISMA and MOOSE guidelines, with the search spanning electronic databases up to February 6, 2024. The outcome measures included obliteration rate, hemorrhage in the latency period, symptomatic radiation-induced changes (RICs), cyst formation, and radiation-induced tumorigenesis. A total of 1493 patients across 24 studies were included. The pooled complete obliteration after single-fraction SRS was 64.7% (95% CI 58%-69%). The pooled post-SRS hemorrhage rate at the final follow-up was 6.2% (95% CI 5%-8%). The overall incidence rate of RIC was 31.3% (267/854 patients), and the incidence of symptomatic RIC was 8.8% (114/1289 patients). For permanent symptomatic RIC, the pooled incidence was 4.8% (62/1283 patients). At final follow-up, 17 cases of radiation-induced necrosis were documented among 654 patients (2.6%). Similarly, cyst formation was reported in 1.3% of cases (17/1265 patients) and radiation-induced tumors occurred in 0.15% of cases (2/1342 patients). SRS can be considered an effective intervention for appropriately selected pediatric patients with arteriovenous malformations. Long-term complication rates appear to be low but additional longitudinal studies are required to better define the long-term outcomes.

Stereotactic Radiosurgery Outcomes in Arteriovenous Malformations: A Pediatric-Adult Comparative Meta-Analysis

Stereotactic radiosurgery (SRS) is an established treatment for brain arteriovenous malformations (AVMs), but outcomes between pediatric and adult populations are not well compared. We conducted a systematic review and meta-analysis comparing SRS outcomes for pediatric versus adult AVMs. PubMed was searched for studies reporting SRS outcomes for pediatric or adult AVMs up to January 2024. Primary outcome was obliteration rate, with secondary outcomes including post-SRS hemorrhage, symptomatic radiation-induced changes (RICs), and permanent RICs. Pooled estimates were calculated using random effects models. Analysis included 22 studies with 3469 patients (1316 pediatric, 2153 adult). Pooled obliteration rate was 63% (95% confidence interval: 56%-70%) overall, with no significant difference between pediatric (61%) and adult (67%) cohorts (P= 0.38). Post-SRS hemorrhage rates were similar (5% pediatric, 6% adult, P= 0.60). Symptomatic RICs occurred in 9% (95% confidence interval: 6%-13%) overall, with 10% in both cohorts (P= 0.91). Permanent RIC rates were 4% in pediatric and 3% in adult cohorts (P= 0.43). Cyst formation (0.6%) and radiation-induced tumors (0.2%) were rare. All-cause mortality was significantly lower in the pediatric cohort (2.6% vs. 9.8%, P= 0.003). Hemorrhagic AVM presentation was inversely correlated with symptomatic RICs across both groups. SRS is a reasonable treatment option for appropriately selected AVM patients in both pediatric and adult populations, offering comparable obliteration rates and adverse event profiles. The lower mortality in pediatric patients underscores the importance of early intervention in this population given their high cumulative lifetime rupture risks.

Comparison of Repeat Versus Initial Stereotactic Radiosurgery for Intracranial Arteriovenous Malformations: A Retrospective Multicenter Matched Cohort Study.

Studies comparing neurological and radiographic outcomes of repeat to initial stereotactic radiosurgery (SRS) intracranial arteriovenous malformations are scarce. Our aim was to perform a retrospective matched comparison of patients initially treated with SRS with those undergoing a second radiosurgical procedure. We collected data from arteriovenous malformations managed in 21 centers that underwent initial and repeated radiosurgery from 1987 to 2022. Based on arteriovenous malformations volume, margin dose, deep venous drainage, deep, and critical location, we matched 1:1 patients who underwent an initial SRS for treatment-naive arteriovenous malformations and a group with repeated SRS treatment. After the selection process, our sample consisted of 328 patients in each group. Obliteration in the initial SRs group was 35.8% at 3 and 56.7% at 5 years post-SRS, while the repeat SRS group showed obliteration rates of 33.9% at 3 years and 58.6% at 5 years, without statistically significant differences (P = .75 and P = .88, respectively). There were no statistically significant differences between the 2 groups for obliteration rates (hazard ratio = 0.93; 95% CI, 0.77-1.13; P = .5), overall radiation-induced changes (RIC) (OR = 1.1; 95% CI, 0.75-1.6; P = .6), symptomatic RIC (OR = 0.78; 95% CI, 0.4-1.5; P = .4), and post-SRS hemorrhage (OR = 0.68; 95% CI; P = .3). In matched cohort analysis, a second SRS provides comparable outcomes in obliteration and RIC compared with the initial SRS. Dose reduction on repeat SRS may not be warranted.

220 Outcome Evaluation of Repeat Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations

INTRODUCTION: Repeat stereotactic radiosurgery (SRS) for persistent cerebral arteriovenous malformation (AVM) has generally favorable patient outcomes. However, reporting studies are limited by small patient numbers and single-institution biases. METHODS: This multicenter, retrospective cohort study included patients treated with repeat, single-fraction SRS between 1987 and 2022. The primary outcome was a favorable patient outcome, defined as a composite of nidus obliteration in the absence of hemorrhage or radiation-induced neurological deterioration. Secondary outcomes were obliteration, hemorrhage risk, and symptomatic radiation-induced changes. Competing risk analysis was performed to compute yearly rates and identify predictors for each outcome. RESULTS: The cohort comprised 505 patients [254 (50.3%) males; median (IQR) age, 34 (15) years] from 14 centers. The median clinical and MRI follow-up was 52 (61) months and 47 (52) months, respectively. At last follow-up, favorable outcome was achieved by 268 (53.1%) patients (5-year probability = 50%, 95% CI = 45%-55%). Obliteration was achieved by 300 (59.4%) patients (5-year probability = 56%, 95% CI = 51%-61%). Twenty-eight patients (5.6%) experienced post-SRS hemorrhage with an annual incidence rate of 1.38 per 100 patient-years. Symptomatic radiation-induced changes were evident in 28 (5.6%) patients, with most occurring in the first 3 years. Larger nidus volumes (between 2 and 4cm3, subdistribution hazard [SDH] 0.61, 95% CI 0.44-0.86, p = 0.005; >4 cm3, SDH 0.47, 95% CI 0.32-0.7, p < 0.001) and brainstem/basal ganglia involvement (SDH = 0.6, 95% CI = 0.45-0.81, p < 0.001) were associated with reduced probability of favorable outcome. CONCLUSIONS: Repeat stereotactic radiosurgery confers reasonable obliteration rates with a low complication risk. With most complications occurring in the first three years, extending the latency period to 5 years generally increases the rate favorable patient outcomes and reduces the necessity of a third intervention.

1133 Biologically Effective Dose and Prediction of Obliteration of Arteriovenous Malformations in Pediatric Patients Treated by Gamma Knife Radiosurgery

INTRODUCTION: Stereotactic radiosurgery (SRS) represents an effective treatment for pediatric arteriovenous malformations (AVMs). Biologic effective dose (BED) is recognized as a predictive variable for outcomes in the adult population, but its role has never been studied in pediatric outcomes. METHODS: Retrospective data for = 18 years old patients treated with single-session SRS for AVM was collected from 1989 – 2019. BED calculations were performed using an a/b ratio of 2.47. Kaplan-Meier analysis was used to evaluate obliteration, new hemorrhage, and radiation-induced changes (RIC). Cox-regression analysis was used for obliteration prediction using two models (margin dose versus BED). RESULTS: One-hundred-ninety-seven patients [median age = 13.1 years, Interquartile range (IQR) = 5.2] were included; 72.6% presented initially with spontaneous hemorrhage. A median margin dose of 22 Gy (IQ = 4.0) with a median BED of 183.2Gy (IQR = 70.54) was used to treat AVMs with a median volume of 2.8 cm3 (IQR = 2.9). Following SRS, obliteration was confirmed in 115 patients (58.4%) using MRI and angiography at a median follow-up of 2.85 years (IQR = 2.26). The cumulative obliteration probability was 43.6% (95% CI = 36.1-50.3), 60.5% (95% CI+=2.2-67.4), 66.0% (95% CI= 56.0-73.7) at 3, 5 and 10 years respectively. In multivariate analysis, a BED >180 Gy [HR = 2.11, 95% CI=1.30-3.40, p = 0.002] in model 1, and a margin dose >20 Gy [HR = 1.90, 95% CI = 1.15-3.13, p = 0.019] in model 2, were associated with obliteration. An AVM nidus volume >4 cm3 was associated with lower obliteration rates in both models. The probability of symptomatic RIC at 10 years was 8.6% (95% CI = 3.5-13.4). Neither BED nor margin dose were associated with RIC occurrence, with the only predictive factor being deep AVM location [HR = 3, 95% CI = 1-9.1, p = 0.048]. CONCLUSIONS: This study confirms BED as a predictor for pediatric AVM obliteration. Optimization of BED in pediatric AVM SRS planning may improve cumulative obliteration rates.

Stereotactic radiosurgery for brain arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia

ObjectiveBrain arteriovenous malformations (AVMs) in patients with hereditary hemorrhagic telangiectasia (HHT) present different characteristics from sporadic AVMs, and they have lower initial bleeding rates. Conservative management is usually preferred for the treatment of these lesions. In this case study, we present the largest series of HHT patients treated with stereotactic radiosurgery to date.MethodsWe identified eight patients with HHT and 14 AVMs. We retrospectively collected clinical, radiographic, and treatment characteristics of the patients and each AVM.ResultsMost patients in our sample presented with small AVMs. The median volume of these AVMs was 0.22 cm3 (IQR 0.08–0.59). Three out of eight patients presented with initial intracerebral hemorrhage (ICH). The majority of lesions had low (12/14) Spetzler-Martin grades (I–II). Median maximum and margin doses used for treatment were 36.2 (IQR 35.25–44.4) and 20 (IQR 18–22.5) Gy, respectively. The overall obliteration rate after SRS was 11/14, and the median time to obliteration across all 11 obliterated AVMs was 35.83 months (IQR, 17–39.99). Neurological status was favorable with all patients having a mRS of 0 or 1 at the last follow-up. Symptomatic radiation-induced changes (RIC) after SRS were low (7.1%), and there were no permanent RIC.ConclusionsPatients with HHT who present with multiple brain AVMs are generally well served by SRS. Obliteration can be achieved in the majority of HHT patients and with a low complication rate. In the current study, initial hemorrhage rates prior to SRS were noticeable which supports the decision to treat these AVMs. Future studies are needed to better address the role of SRS for HHT patients harboring ruptured and unruptured AVMs.

Predictors of radiation-induced changes in arteriovenous malformation patients undergoing radiosurgery: Insights from a Malaysian linear accelerator cohort.

Radiation-induced changes (RICs) post-stereotactic radiosurgery (SRS) critically influence outcomes in arteriovenous malformation (AVM) treatments. This study aimed to identify predictors of RICs, described the types and severity of RICs, and assessed their impact on patient's functional outcomes to enhance risk assessment and treatment planning for AVM patients. This retrospective study analyzed 87 AVM patients who underwent SRS at Hospital Kuala Lumpur between January 2015 and December 2020. RICs were identified through detailed magnetic resonance imaging evaluations, and predictive factors were determined using multiple logistic regression. Functional outcomes were assessed with the modified Rankin scale (mRS). Among the cohort, 40.2% developed RICs, with radiological RICs in 33.3%, symptomatic RICs in 5.7%, and permanent RICs in 1.1%. Severity categorization revealed 25.3% as Grade I, 13.8% as Grade II, and 1.1% as Grade III. Notably, higher Pollock-Flickinger scores and eloquence location were significant predictors of RIC occurrence. There was a significant improvement in functional outcomes post-SRS, with a marked decrease in non-favorable mRS scores from 8.0% pre-SRS to 1.1% post-SRS (P = 0.031). The study identified the eloquence location and Pollock-Flickinger scores as predictors of RICs post-SRS. The significant reduction in non-favorable mRS scores post-SRS underscores the efficacy of SRS in improving patient outcomes. Their results highlighted the importance of personalized treatment planning, focusing on precise strategies to optimize patient outcomes in AVM management, reducing adverse effects while improving functional outcomes.

Third Stereotactic Radiosurgery for Residual Arteriovenous Malformations: A Retrospective Multicenter Study

BACKGROUND AND OBJECTIVES: There are no studies evaluating the efficacy and safety of more than 2 stereotactic radiosurgery (SRS) procedures for cerebral arteriovenous malformations (AVM). The aim of this study was to provide evidence on the role of third single-session SRS for AVM residual. METHODS: This multicenter, retrospective study included patients managed with a third single-session SRS procedure for an AVM residual. The primary study outcome was defined as AVM nidus obliteration without AVM bleeding or symptomatic radiation-induced changes (RIC). Secondary outcomes evaluated were AVM obliteration, AVM hemorrhage, asymptomatic, and symptomatic RIC. RESULTS: Thirty-eight patients (20/38 [52.6%] females, median age at third SRS 34.5 [IQR 20] years) were included. The median clinical follow-up was 46 (IQR 14.8) months, and 17/38 (44.7%) patients achieved favorable outcome. The 3-year and 5-year cumulative probability rates of favorable outcome were 23% (95% CI = 10%-38%) and 53% (95% CI = 29%-73%), respectively. The cumulative probability of AVM obliteration at 3 and 5 years after the third SRS was 23% (95% CI = 10%-37%) and 54% (95% CI = 29%-74%), respectively. AVM bleeding occurred in 2 patients, and 1 of them underwent subsequent resection. The cumulative probability rate of post-SRS AVM hemorrhage remained constant at 5.3% (95% CI = 1%-16%) during the first 5 years of follow-up. Transient symptomatic RIC managed conservatively occurred in 5/38 patients (13.2%) at a median time of 12.5 (IQR 22.5) months from third SRS. Radiation-induced cyst formation was noted in 1 patient (4.2%) 19 months post-SRS. No mortality, radiation-associated malignancy, or permanent symptomatic RIC was noted during follow-up. CONCLUSION: A third single-session SRS to treat a residual intracranial AVM offers obliteration in most patients. The risk of RIC was low, and these effects were transient. While not often required, a third SRS can be performed in patients with persistent residual AVMs.

Biologically Effective Dose and Prediction of Obliteration of Arteriovenous Malformations in Pediatric Patients Treated by Gamma Knife Radiosurgery.

Stereotactic radiosurgery (SRS) represents an effective treatment for pediatric arteriovenous malformations (AVMs). Biological effective dose (BED) has shown promising results in 2 previous studies as a predictive variable for outcomes in adults, but its role has never been studied in pediatric outcomes. Retrospective data for patients 18 years or younger treated with a single-session SRS for AVMs were collected from 1989 to 2019. BED calculations were performed using an α/β ratio of 2.47. Kaplan-Meier analysis was used to evaluate obliteration, new hemorrhage, and radiation-induced changes (RIC). Cox-regression analysis was used for obliteration prediction using 2 models (margin dose vs BED). One hundred ninety-seven patients (median age = 13.1 years, IQR = 5.2) were included; 72.6% (143/197) of them presented initially with spontaneous hemorrhage. A median margin dose of 22 Gy (IQR = 4.0) with a median BED of 183.2 Gy (IQR = 70.54) was used to treat AVM with a median volume of 2.8 cm 3 (IQR = 2.9). After SRS, obliteration was confirmed in 115/197 patients (58.4%) using magnetic resonance imaging and angiography at a median follow-up of 2.85 years (IQR = 2.26). The cumulative obliteration probability was 43.6% (95% CI = 36.1-50.3), 60.5% (95% CI+ = 2.2-67.4), and 66.0% (95% CI = 56.0-73.7) at 3, 5, and 10 years, respectively. In Cox multivariate analysis, a BED >180 Gy (hazard ratio [HR] = 2.11, 95% CI = 1.30-3.40, P = .002) in model 1 and a margin dose >20 Gy (HR = 1.90, 95% CI = 1.15-3.13, P = .019) in model 2 were associated with obliteration. An AVM nidus volume >4 cm 3 was associated with lower obliteration rates in both models. The probability of symptomatic RIC at 10 years was 8.6% (95% CI = 3.5-13.4). Neither BED nor margin dose was associated with RIC occurrence, with the only predictive factor being deep AVM location (HR = 3, 95% CI = 1-9.1, P = .048). This study confirms BED as a predictor for pediatric AVM obliteration. Optimization of BED in pediatric AVM SRS planning may improve cumulative obliteration rates.

Outcome Evaluation of Repeat Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations.

Repeat stereotactic radiosurgery (SRS) for persistent cerebral arteriovenous malformation (AVM) has generally favorable patient outcomes. However, reporting studies are limited by small patient numbers and single-institution biases. The purpose of this study was to provide the combined experience of multiple centers, in an effort to fully define the role of repeat SRS for patients with arteriovenous malformation. This multicenter, retrospective cohort study included patients treated with repeat, single-fraction SRS between 1987 and 2022. Follow-up began at repeat SRS. The primary outcome was a favorable patient outcome, defined as a composite of nidus obliteration in the absence of hemorrhage or radiation-induced neurological deterioration. Secondary outcomes were obliteration, hemorrhage risk, and symptomatic radiation-induced changes. Competing risk analysis was performed to compute yearly rates and identify predictors for each outcome. The cohort comprised 505 patients (254 [50.3%] males; median [interquartile range] age, 34 [15] years) from 14 centers. The median clinical and magnetic resonance imaging follow-up was 52 (interquartile range, 61) and 47 (interquartile range, 52) months, respectively. At last follow-up, favorable outcome was achieved by 268 (53.1%) patients (5-year probability, 50% [95% CI, 45%-55%]) and obliteration by 300 (59.4%) patients (5-year probability, 56% [95% CI, 51%-61%]). Twenty-eight patients (5.6%) experienced post-SRS hemorrhage with an annual incidence rate of 1.38 per 100 patient-years. Symptomatic radiation-induced changes were evident in 28 (5.6%) patients, with most occurring in the first 3 years. Larger nidus volumes (between 2 and 4 cm3, subdistribution hazard, 0.61 [95% CI, 0.44-0.86]; P=0.005; >4 cm3, subdistribution hazard, 0.47 [95% CI, 0.32-0.7]; P<0.001) and brainstem/basal ganglia involvement (subdistribution hazard, 0.6 [95% CI, 0.45-0.81]; P<0.001) were associated with reduced probability of favorable outcome. Repeat SRS confers reasonable obliteration rates with a low complication risk. With most complications occurring in the first 3 years, extending the latency period to 5 years generally increases the rate of favorable patient outcomes and reduces the necessity of a third intervention.

477 Stereotactic Radiosurgery With Versus Without Prior Onyx Embolization for Brain Arteriovenous Malformations

INTRODUCTION: Investigations of the combined effects of neoadjuvant Onyx embolization and stereotactic radiosurgery (SRS) on brain arteriovenous malformations (AVM) have not accounted for initial angioarchitectural features prior to neuroendovascular intervention. METHODS: The International Radiosurgery Research Foundation AVM databases from 1987–2018 were retrospectively reviewed. Patients were categorized, based on AVM treatment approach, into Onyx embolization and SRS (OE+ SRS) or SRS alone (SRS-only) cohorts and then propensity score-matched in a 1:1 ratio. Primary outcome was AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiologic and symptomatic radiation-induced changes (RIC), and cyst formation. Comparisons were analyzed using crude rates and cumulative probabilities adjusted for competing risk of death. RESULTS: The matched OE + SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs. 47.2% for OE + SRS vs. SRS-only cohorts, respectively; OR = 0.679, p = 0.327) and cumulative probabilities at 3, 4, 5, and 6 years (33.7%, 44.1%, 57.5%, and 65.7% for OE + SRS cohort vs. 34.8%, 45.5%, 59.0%, and 67.1% for SRS-only cohort, respectively; SHR = 0.961, p = 0.896) of obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE + SRS cohort were 18.9% and 9.4%, respectively. CONCLUSIONS: Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. Our analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration. However, given the risks incurred by nidal embolization using Onyx, this neoadjuvant intervention should be employed judiciously in multimodal treatment strategies involving SRS for appropriately selected large-volume or angioarchitecturally high-risk AVMs.

Radiation-Induced Changes Associated with Obliteration of Brain AVMs after Repeat Radiosurgery.

Radiation-induced changes can occur after stereotactic radiosurgery for brain AVMs, potentially causing symptomatic complications. We evaluated the incidence of such changes and the efficacy of repeat gamma knife radiosurgery for incompletely obliterated AVMs. We retrospectively evaluated 150 patients who underwent gamma knife radiosurgery for AVMs between 2002 and 2020; twenty-five underwent further radiosurgical procedures for incompletely obliterated AVMs. We recorded the median margin doses at the first (median, 20 Gy; range, 12-23 Gy; AVM volume, 0.026-31.3 mL) and subsequent procedures (median, 18 Gy; range, 12-23 Gy; AVM volume, 0.048-9.2 mL). After the first treatment, radiologic radiation-induced changes developed in 48 (32%) patients, eight of whom had symptomatic changes. After repeat gamma knife radiosurgery, 16 of 25 patients achieved complete AVM obliteration (64%). The development of radiation-induced changes after the first treatment was significantly associated with successful obliteration by subsequent radiosurgery (OR = 24.0, 95% CI 1.20-483, P = .007). Radiation-induced changes occurred in only 5 (20%) patients who underwent a second gamma knife radiosurgery, one of whom experienced transient neurologic deficits. Between the first and repeat gamma knife radiosurgery procedures, there was no significant difference in radiologic and symptomatic radiation-induced changes (P = .35 and P = 1.0, respectively). Radiation-induced changes after the first gamma knife radiosurgery were associated with AVM obliteration after a repeat procedure. The risk of symptomatic radiation-induced changes did not increase with retreatment. When the first procedure fails to achieve complete AVM obliteration, a favorable outcome can be achieved by a repeat gamma knife radiosurgery, even if radiation-induced changes occur after the first treatment.

300 Stereotactic Radiosurgery With Versus Without Embolization for Brain Arteriovenous Malformations

INTRODUCTION: Prior comparisons of brain arteriovenous malformations (AVMs) treated using stereotactic radiosurgery (SRS) with or without embolization were inherently flawed, due to differences in the pre-treatment nidus volumes. METHODS: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987–2018. Patients were categorized into the embolization and SRS (E+SRS) or SRS alone (SRS-only) cohorts. The two cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was defined as AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiologic and symptomatic radiation-induced changes (RIC), and cyst formation. RESULTS: The matched cohorts each comprised 101 patients. Crude AVM obliteration rates were similar between the matched E+SRS versus SRS-only cohorts (48.5% vs. 54.5%; OR = 0.788, p = 0.399). Cumulative probabilities of obliteration at 3, 4, 5, and 6 years were also similar between the E+SRS (33.0%, 46.4%, 56.2%, and 60.8%, respectively) and SRS-only (32.9%, 46.2%, 56.0%, and 60.6%, respectively) cohorts (SHR = 1.005, p = 0.981). Cumulative probabilities of radiologic RIC at 3, 4, 5, and 6 years were lower in the E+SRS (25.0%, 25.7%, 26.7%, and 26.7%, respectively) versus SRS-only (45.3%, 46.2%, 47.8%, and 47.8%, respectively) cohort (SHR = 0.478, p = 0.004). Symptomatic and asymptomatic embolization-related complication rates were 8.3% and 18.6%, respectively. Rates of post-SRS hemorrhage, all-cause mortality, symptomatic RIC, and cyst formation were similar between the matched cohorts. CONCLUSION: This study refutes the prevalent notion that AVM embolization negatively affects the likelihood of obliteration after SRS.

Imaging Markers Associated With Radiation-Induced Changes in Brain Arteriovenous Malformations After Radiosurgery.

Radiation-induced changes (RICs) in brain tissue, seen as increased perinidal T2-weighted hyperintensity on MRI, are commonly observed in patients with brain arteriovenous malformations (BAVMs) within 2 years after Gamma Knife (Elekta) radiosurgery (GKRS). To explore the imaging markers associated with RICs in patients with BAVMs. We retrospectively included 106 treatment-naïve patients with BAVMs who received GKRS alone between 2011 and 2018 and had ≥24 months of clinical and MRI follow-up. Pre-GKRS angiography and MRIs were analyzed for morphological characteristics and quantitative digital subtraction angiography parameters. RIC severity was categorized as mild (grade I), moderate (grade II), or severe (grade III). Firth logistic regression analysis was conducted to determine the associations between the parameters and RICs. Among the 106 patients, 83 (78.3%) developed RICs, with 16 categorized as grade I, 62 as grade II, and 5 as grade III. RICs were symptomatic in 19 patients (17.9%). In multivariable models, BAVMs with a volume of >5 cm3 (odds ratio [OR]: 4.322, P = .024) and neoangiogenesis on angiography before treatment (OR: 3.846, P = .029), and thrombus within nidus or drainage vein on follow-up MRI (OR: 3.679, P = .001) were independently associated with grade II or III RICs. Symptomatic RICs were more likely to develop in basal ganglia or brainstem. Large BAVMs and neoangiogenesis were associated with moderate to severe RICs in treatment-naïve patients with BAVMs. Our findings may assist with the complication risk assessment for these patients.

Effect of Prior Embolization on Outcomes After Stereotactic Radiosurgery for Pediatric Brain Arteriovenous Malformations: An International Multicenter Study.

Pediatric brain arteriovenous malformations (AVMs) are a significant cause of morbidity but the role of multimodal therapy in the treatment of these lesions is not well understood. To compare the outcomes of stereotactic radiosurgery (SRS) with and without prior embolization for pediatric AVMs. We retrospectively evaluated the International Radiosurgery Research Foundation pediatric AVM database. AVMs were categorized, based on use of pre-embolization (E+SRS)or lack thereof (SRS-only). Outcomes were compared in unadjusted and inverse probability weight (IPW)-adjusted models. Favorable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC). The E+SRS and SRS-only cohorts comprised 91 and 448 patients, respectively. In unadjusted models, the SRS-only cohort had higher rates of obliteration (68.5%vs 43.3%, <.001) and favorable outcome (61.2%vs 36.3%, P<.001) but a lower rate of symptomatic RIC (9.0%vs 16.7%, P=.031). The IPW-adjusted rates of every outcome were similar between the 2 cohorts. However, cumulative obliteration rates at 3, 5, 8, and 10 yr remained higher in the absence of prior embolization (46.3%, 64.6%, 72.6%, and 77.4% for SRS-only vs 24.4%, 37.2%, 44.1%, and 48.7% for E+SRS cohorts, respectively; SHR=0.449 [0.238-0.846], P=.013). Embolization appears to decrease cumulative obliteration rates after SRS for pediatric AVMs without affecting the risk of post-treatment hemorrhage or adverse radiation effects arguingagainst the routine use of pre-SRS embolization. While endovascular therapy can be considered for occlusion of high-risk angioarchitectural features prior toSRS, future studies are necessary to clarify its role.

Stereotactic radiosurgery with versus without prior Onyx embolization for brain arteriovenous malformations.

Investigations of the combined effects of neoadjuvant Onyx embolization and stereotactic radiosurgery (SRS) on brain arteriovenous malformations (AVMs) have not accounted for initial angioarchitectural features prior to neuroendovascular intervention. The aim of this retrospective, multicenter matched cohort study is to compare the outcomes of SRS with versus without upfront Onyx embolization for AVMs using de novo characteristics of the preembolized nidus. The International Radiosurgery Research Foundation AVM databases from 1987 to 2018 were retrospectively reviewed. Patients were categorized based on AVM treatment approach into Onyx embolization (OE) and SRS (OE+SRS) or SRS alone (SRS-only) cohorts and then propensity score matched in a 1:1 ratio. The primary outcome was AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiological and symptomatic radiation-induced changes (RICs), and cyst formation. Comparisons were analyzed using crude rates and cumulative probabilities adjusted for competing risk of death. The matched OE+SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs 47.2% for the OE+SRS vs SRS-only cohorts, respectively; OR 0.679, p = 0.327) and cumulative probabilities at 3, 4, 5, and 6 years (33.7%, 44.1%, 57.5%, and 65.7% for the OE+SRS cohort vs 34.8%, 45.5%, 59.0%, and 67.1% for the SRS-only cohort, respectively; subhazard ratio 0.961, p = 0.896) of AVM obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE+SRS cohort were 18.9% and 9.4%, respectively. Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. These analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration. However, given the risks incurred by nidal embolization using Onyx, this neoadjuvant intervention should be used judiciously in multimodal treatment strategies involving SRS for appropriately selected large-volume or angioarchitecturally high-risk AVMs.

Stereotactic Radiosurgery With Versus Without Embolization for Brain Arteriovenous Malformations.

Prior comparisons of brain arteriovenous malformations (AVMs) treated using stereotactic radiosurgery (SRS) with or without embolization were inherently flawed, due to differences in the pretreatment nidus volumes. To compare the outcomes of embolization and SRS, vs SRS alone for AVMs using pre-embolization malformation features. We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Patients were categorized into the embolization and SRS (E+SRS) or SRS alone (SRS-only) cohorts. The 2 cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was defined as AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiologic and symptomatic radiation-induced changes (RIC), and cyst formation. The matched cohorts each comprised 101 patients. Crude AVM obliteration rates were similar between the matched E+SRS vs SRS-only cohorts (48.5%vs 54.5%; odds ratio=0.788, P=.399). Cumulative probabilities of obliteration at 3, 4, 5, and 6 yr were also similar between the E+SRS (33.0%, 46.4%, 56.2%, and 60.8%, respectively) and SRS-only (32.9%, 46.2%, 56.0%, and 60.6%, respectively) cohorts (subhazard ratio (SHR)=1.005, P=.981). Cumulative probabilities of radiologic RIC at 3, 4, 5, and 6 yr were lower in the E+SRS (25.0%, 25.7%, 26.7%, and 26.7%, respectively) vs SRS-only (45.3%, 46.2%, 47.8%, and 47.8%, respectively) cohort (SHR=0.478, P=.004). Symptomatic and asymptomatic embolization-related complication rates were 8.3% and 18.6%, respectively. Rates of post-SRS hemorrhage, all-cause mortality, symptomatic RIC, and cyst formation were similar between the matched cohorts. This study refutes the prevalent notion that AVM embolization negatively affects the likelihood of obliteration after SRS.

Radiosurgery for Unruptured Intervention-Naïve Pediatric Brain Arteriovenous Malformations.

Long-term data regarding stereotactic radiosurgery (SRS) as a standalone therapy for unruptured pediatric brain arteriovenous malformations (AVMs) are incompletely defined. To evaluate, in a multicenter, retrospective cohort study, the outcomes after SRS for unruptured, intervention-naïve pediatric AVMs. To retrospectively analyze the International Radiosurgery Research Foundation pediatric AVM database from 1987 to 2018. Pediatric patients with unruptured, previously untreated AVMs who underwent SRS were included. The primary endpoint was a composite of hemorrhagic stroke, death, or permanently symptomatic radiation-induced changes. The study cohort comprised 101 patients (mean follow-up 80.8 mo). The primary endpoint occurred in 14%, comprising hemorrhagic stroke, death, and permanent radiation-induced changes in 6%, 3%, and 8%, respectively. Estimated probabilities of the primary endpoint were 5.2%, 10.8%, and 23.0% at 2, 5, and 10 yr, respectively. Estimated probabilities of AVM obliteration at 5 and 10 yr were 64% and 82%, respectively. Single SRS treatment (P=.007) and higher margin dose (P=.005) were predictors of obliteration. Subgroup analysis of Spetzler-Martin grade I-III AVMs estimated primary endpoint probabilities of 3.7%, 8.4%, and 18.7% at 2, 5, and 10 yr, respectively. Treatment of unruptured, intervention-naïve AVMs in the pediatric population with SRS carries an approximately 2% annual risk of morbidity and mortality, which appears to plateau after 10 yr. The poorly described natural history of pediatric AVMs renders any comparison of SRS vs conservative management imperfect.

Early obliteration of pediatric brain arteriovenous malformations after stereotactic radiosurgery: an international multicenter study.

Stereotactic radiosurgery (SRS) is a treatment option for pediatric brain arteriovenous malformations (AVMs), and early obliteration could encourage SRS utilization for a subset of particularly radiosensitive lesions. The objective of this study was to determine predictors of early obliteration after SRS for pediatric AVMs. The authors performed a retrospective review of the International Radiosurgery Research Foundation AVM database. Obliterated pediatric AVMs were sorted into early (obliteration ≤ 24 months after SRS) and late (obliteration > 24 months after SRS) responders. Predictors of early obliteration were identified, and the outcomes of each group were compared. The overall study cohort was composed of 345 pediatric patients with obliterated AVMs. The early and late obliteration cohorts were made up of 95 (28%) and 250 (72%) patients, respectively. Independent predictors of early obliteration were female sex, a single SRS treatment, a higher margin dose, a higher isodose line, a deep AVM location, and a smaller AVM volume. The crude rate of post-SRS hemorrhage was 50% lower in the early (3.2%) than in the late (6.4%) obliteration cohorts, but this difference was not statistically significant (p = 0.248). The other outcomes of the early versus late obliteration cohorts were similar, with respect to symptomatic radiation-induced changes (RICs), cyst formation, and tumor formation. Approximately one-quarter of pediatric AVMs that become obliterated after SRS will achieve this radiological endpoint within 24 months of initial SRS. The authors identified multiple factors associated with early obliteration, which may aid in prognostication and management. The overall risks of delayed hemorrhage, RICs, cyst formation, and tumor formation were not statistically different in patients with early versus late obliteration.

Abstract 127: Radiosurgery for Unruptured Intervention-Naïve Pediatric Brain Arteriovenous Malformations

Background and Purpose: To evaluate, in a multicenter, retrospective cohort study, the outcomes after stereotactic radiosurgery (SRS) for unruptured, intervention-naïve pediatric brain arteriovenous malformations (AVM). Methods: We retrospectively analyzed the International Radiosurgery Research Foundation pediatric AVM database from 1987-2018. Pediatric patients with unruptured, previously untreated AVMs who underwent SRS were included. The primary endpoint was a composite of hemorrhagic stroke, death, or permanently symptomatic radiation-induced changes (RIC). Results: The study cohort comprised 101 patients (mean follow-up 80.8 months). The primary endpoint occurred in 14%, comprising hemorrhage stroke, death, and permanent RIC in 6%, 3%, and 8%, respectively. Estimated probabilities of the primary endpoint were 5.2%, 10.8%, and 23.0% at 2, 5, and 10 years, respectively (Figure 1). Estimated probabilities of AVM obliteration at 5 and 10 years were 64% and 82%, respectively (Figure 2). Single SRS treatment (p=0.007) and higher margin dose (p=0.005) were predictors of obliteration. Subgroup analysis of Spetzler-Martin grade I-III AVMs estimated primary endpoint probabilities of 3.7%, 8.4%, and 18.7% at 2, 5 and 10 years, respectively. Conclusion: Treatment of unruptured, intervention-naïve AVMs in the pediatric population with SRS carries an approximately 2% annual risk of morbidity and mortality, which appears to plateau after 10 years. The poorly described natural history of pediatric AVMs makes any comparison of SRS versus conservative management imperfect. However, due to the young age at diagnosis and excessive cumulative life hemorrhage risk of an untreated AVM in a child, SRS is likely to have a favorable long-term risk-benefit profile for appropriately selected unruptured pediatric AVMs.