Background: The Treatment Of Brain Arteriovenous malformations Study is a pragmatic study comprising 2 randomized trials and prospective registries of patients with brain arteriovenous malformations (AVMs). We report the results of the stereotactic radiosurgery (SRS) registry. Methods: TOBAS uses an algorithm integrating clinical judgment and randomization. When SRS was selected as the preferred curative modality and randomized allocation of SRS versus observation was judged unreasonable, patients were included in the SRS registry (with/without pre-SRS embolization). The primary outcome was modified Rankin Scale > 2 at last follow-up. Secondary outcomes included serious adverse events, AVM rupture, radiation-induced changes, and magnetic resonance angiographic results at 3 years. Analyses were intent-to-treat. Results: From June 2014 to May 2021, 1010 patients were recruited; 105 (10.4%) were offered participation in the SRS registry. After exclusions, 94 patients were analyzed; most had ruptured (n = 64/94 [68%]), small AVMs (0-3 cm) (84 [89%]), within eloquent brain (57 [61%]). Pre-SRS embolization was performed in 19 (20%); 4 were cured and 3 had endovascular complications, leaving 87/94 (93%) patients who received SRS. The median SRS dose was 22 Gy (interquartile range: 20-24). During a mean follow-up of 51 months, the primary outcome (modified Rankin Scale > 2) occurred in 7/94 (7%; 95% confidence interval [CI]: 4%-15%), with serious adverse events in 16/94 (17%; 95% CI: 11%-26%), including AVM rupture in 5/94 (5%; 95% CI: 2%-12%), and symptomatic radiation-induced changes in 6/87 (7%; 95% CI: 3%-14%). Three-year imaging follow-up, available in 79/94 (84%) confirmed AVM occlusion in 51/79 (65%; 95% CI: 54%-74%) or 54% (95% CI: 44%-64%) of all patients. Conclusions: In this prospective registry, radiosurgery with or without embolization was relatively safe, but of moderate efficacy, with 3-year AVM occlusion in 54%-65% patients.

PURPOSE:The purpose of this study was to determine the capabilities of dynamic susceptibility contrast (DSC)‑derived microvascular and oxygen metabolism metrics to distinguish radiation necrosis (RN) from tumor progression (TP) in irradiated brain metastases. MATERIALS AND METHODS:Fifty‑eight patients who completed cranial irradiation and underwent DSC perfusion MRI between August 2014 and August 2024 were retrospectively included. There were 31 men and 27 women, with a median age of 60.5 years (first quartile [Q1], 52.3; third quartile [Q3], 68.8). Perfusion, microvascular, and metabolic maps were generated with commercially available software. Lesion‑to‑white‑matter ratios were computed for all DSC-derived microvascular and oxygenation metrics including relative cerebral blood volume (rCBV) and oxygen extraction fraction (rOEF). Reference diagnoses were histopathology (n = 11) or multidisciplinary follow‑up (n = 47). Logistic regression analysis was used to identify metrics associated with RN versus TP, and receiver operating characteristic curve analysis was used to estimate diagnostic performance. For prognosis, overall survival was analyzed using Cox proportional hazards models. RESULTS:A total of 58 brain lesions were studied, including 34 TPs and 24 RNs. Patients with RN had longer overall survival than those with TP (median not reached vs. 22 months; P = 0.01). Among all metrics, only rCBV and rOEF differed significantly. TP showed higher median rCBV (1.8; Q1, 1.2; Q3, 2.8) than RN (1.1; Q1, 0.6; Q3, 1.9) (P = 0.02). RN exhibited greater median rOEF (1.9; Q1, 1.4; Q3, 2.1) than TP (1.5; Q1, 1.3; Q3, 1.8, P = 0.03). rCBV achieved an area under the receiver operating characteristic curve (AUC) of 0.69 (95 % confidence interval [CI]: 0.54-0.83), rOEF an AUC of 0.66 (95 % CI: 0.52-0.81), and their combination and AUC of 0.74 (95 % CI: 0.60-0.87) without significant differences (P ≥ 0.19). After adjusting for rCBV in multivariable analysis, rOEF remained significantly associated with RN (odds ratio, 0.23; 95 % CI: 0.06-0.72; P = 0.02). A greater rOEF was also associated with a longer overall survival in Cox analysis (adjusted hazard ratio, 0.72; 95 % CI: 0.55-0.95. P = 0.02). CONCLUSION:Elevated rCBV is in favor of the diagnosis of TP whereas increased rOEF is in favor of the diagnosis of RN in patients with irradiated brain metastases. Although combining metrics did not confer significant diagnostic advantages, rOEF shows an independent association with longer overall survival.

BACKGROUND AND OBJECTIVES:The American Society for Radiation Oncology guidelines for stereotactic radiosurgery dose suggestions for brain metastases provide excellent local control but at the expense of higher adverse radiation effects (ARE). This study provides evidence that lower single-fraction prescription doses for patients with melanoma metastases who are concurrently receiving immunotherapy or targeted therapy are equally effective and safe. METHODS:This retrospective, multicenter study included 335 patients with melanoma brain metastases who underwent stereotactic radiosurgery between 2009 and 2024. After covariate balancing, 137 patients with 590 metastases were included in the high dose (HD) group and 59 patients with 590 metastases in the reduced dose (RD) group. The RD limits were set at <20 Gy for <2 cm lesions and <18 Gy for ≥2 to <3 cm lesions. RESULTS:After matching, the median diameter (6 vs 5.8 mm, P = .5) and imaging follow-up (6 vs 6 months, P = .13) were comparable. Cumulative incidence of progressing metastases was significantly higher in the HD group compared with the RD group (P < .001) overall, but lower prescription doses resulted in higher progression rates for metastases >2 cm (P = .023). Higher prescription volumes and HD-group prescription doses were linked with local progression in multivariable analysis. Radiographic AREs were significantly more common in the HD group compared with the RD group overall (P < .001) but similar for metastases >2 cm (P = .7). Higher prescription volumes, HD-group prescription doses, and concurrent BRAF or other tyrosine kinase inhibitors were linked with an increased risk of radiographic ARE, whereas concurrent immunotherapy was associated with lower rates of radiographic ARE. CONCLUSION:This study provides evidence that treatment with prescription doses under the currently the American Society for Radiation Oncology-suggested doses for brain melanoma metastases <2 cm is safe, having at least equal local control rate and lower radiographic AREs. Reducing prescription dose for lesions between 2 and 3 cm does not seem to convey reduced ARE rates and could potentially increase local failure.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) represents an effective treatment for nonfunctioning pituitary adenomas (NFPAs). However, no data have yet been published regarding results of SRS on NFPAs after multiple previous resections. METHODS: Retrospective multicentric data of patients diagnosed with NFPA and who underwent multiple resections (>= 2) before SRS were reviewed and analyzed. The treatment interval spanned the period of 1992 to 2022. Cox regression and Kaplan-Meier curves were used to assess predictive factors and the probability of tumor control and hypopituitarism. RESULTS: Among the 311 patients (median age: 50.2 [IQR: 18.0] years), 226 (72.7%) had undergone >= 2 previous resections. The median margin dose was 14 Gy (IQR: 4.0 Gy), and the median tumor volume 3.6 cm3 (IQR: 4.8). Overall, the probability of tumor control after SRS was 93.3% (CI 95%: 89.9-96.9) and 86.7% (CI 95%: 81.1-92.6) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with a decreased risk of tumor progression (hazard ratio = 0.33, CI 95% = 0.15-0.75, P = .008). At a last clinical follow-up of 4.1 (IQR 6.1) years, 10.1% (30/296) developed at least 1 new hormone deficiency after SRS. The cumulative probability of new hormone deficiency was 6.1% (95% CI: 3.0-9.1), 10.3% (95% CI: 5.8-14.6), and 18.9% (95% CI: 11.5-25.8) at 3, 5, and 10 years after SRS, respectively. The average latency between SRS and development of new hormone deficiencies was 3.3 years (IQR 4.1). A maximum point dose to the pituitary stalk >10 Gy was associated with a new deficiency (hazard ratio = 4.06, CI 95% = 1.57-10.5, P-value = .004). CONCLUSION: For patients with NFPA with multiple previous resections, SRS offers effective local tumor control and a low risk of delayed hypopituitarism for managing these challenging adenomas. SRS should be strongly considered in patients with NFPA with 2 previous resections compared with considering a third resection.

The surgery of skull base epidermoid cysts can be challenging because of intracerebral extensions and the encasement of cranial nerves and internal carotid artery branches.1-3 Advances in magnetic resonance imaging, particularly tractography, may help to visualize the trajectory of displaced cranial nerves,4,5 and thus reduce the surgical risks. We report here the case of a 59-year-old woman who presented with diplopia, left ataxia, and cognitive impairment, which revealed a large right skull base epidermoid cyst with infra-, supra-, and latero-sellar extensions (Video 1). The optic chiasma was pushed superiorly, and the oculomotor nerves were unidentifiable within the tumor. The internal carotid artery termination was stretched by the tumor and the first segment of the middle cerebral artery. Tractography was used to identify the position of the optic, oculomotor, and trigeminal nerves, which were encased within the tumor. A transsylvian approach allowed us to reach the tumor components using interoptic, opticocarotid, and laterocarotid triangles. This multiple window method gave access to most of the tumor's supratentorial component, which was removed using various size suction. Mirrors were useful to enhance the resection. Finally, a near-total removal of the tumor was achieved including the decompression of the brainstem, cranial nerves, and vessels. The capsule was kept in place to preserve critical anatomic structures; however, it should be removed when possible depending on tumor configuration. The patient, who consented to the procedure and to the publication of her images, recovered within a few days.

Stereotactic radiosurgery (SRS) is used to treat residual and recurrent nonfunctioning pituitary adenomas (NFPA). Hypopituitarism is the most common complication with increasing rates over time. We present the largest multicentric cohort evaluating outcomes after radiosurgery for NFPA. Twelve centers contributed retrospective data on 869 patients treated with SRS between 1992 and 2022. Tumor progression was defined as a volumetric increase of =20% from baseline. New-onset hypopituitarism was defined as dysfunction of at least 1 pituitary axis. Kaplan–Meier curves were plotted for the probability of tumor control and new onset hypopituitarism. Cox regression was used to assess predictive factors for tumor control and new pituitary hormone deficiency. A total of 869 patients (median age 52.5 years [Interquartile range (IQR):18.9]) were treated using a median margin dose of 14Gy (IQR:4) for a median tumor volume of 3.4cc (IQR:4.3). With a median radiological follow-up of 3.7 years (IQR:4.8). Volumetric tumor reduction occurred in 451 patients (51.9%), stability in 364 (41.9%) and 54 patients (6.2%) showed tumor progression. The probability of tumor control was 95.5% (95% Confidence Interval [CI]:93.8–97.3) and 88.8% (95%CI:85.2–92.5) at 5 and 10 years. A margin dose >14 Gy was associated with tumor control (Hazard Ratio [HR]:0.33, 95% CI:0.18–0.60, P<0.001). The probability of new hypopituitarism was 9.9% (95%CI:7.3–12.5) and 15.3% (95%CI:11–19.4) at 5 and 10 years. A maximum point dose >10 Gy in the pituitary stalk was associated with new pituitary hormone deficiency (HR:3.47, 95%CI:1.95–6.19). The 10-year cumulative probability of new cortisol, thyroid, gonadotroph, and growth hormone deficiency was 8%, 8.3%, 3.5%, and 4.7%, respectively. SRS for NFPA affords long-term tumor control (10 year:>88%) and low rates of pituitary dysfunction (10-year:15.3%).

BACKGROUND:Ruptured middle cerebral artery aneurysm (MCAa) with intraparenchymal hematoma (IPH) can benefit at the same time from evacuation of the hematoma and exclusion of the aneurysm of a decompressive craniectomy (DC). To date, there are no clear recommendations for performing a DC in such cases. METHODS:We retrospectively collected data from nine French neurosurgical units from January 1, 2013 to December 31, 2020. All MCAa patients with IPH requiring evacuation of the IPH were included in this study. Poor outcomes were defined by an mRs score of 3-6 at 6 months. Propensity score matching was used to analyze the potential effects of DC. RESULTS:Between January 2013 and December 2020, 198 MCAa ruptured with IPH were treated, including 162 MCAa requiring evacuation of the IPH. 50 were treated with DC and 112 without DC. After matching 72 patients, poor neurological prognosis was observed in 27/36 patients (75%) in the DC group versus 18/36 (50%) in the non-DC group (p = 0.026). CONCLUSION:Primary decompressive craniectomy in patients with ruptured MCAa and IPH requiring surgical evacuation increases the risk of poor neurological outcome. RCT are needed to confirm this hypothesis.

BACKGROUND AND OBJECTIVES:Upfront stereotactic radiosurgery (SRS) could be an option for nonfunctioning pituitary adenomas (NFPA) unsuitable for surgery. Only small series evaluate the results of upfront SRS; the aim of the study was to report patient outcomes from a large, international patient cohort. METHODS:The study evaluated tumor control and complications after single-session SRS in a multicentric cohort of untreated NFPA. RESULTS:In total, 132 patients (median age 51.2 [IQR: 27.1] years at SRS, median volume 2.1 [IQR: 2.9] cm 3 ) were included. The probability of tumor control was 100% (95% CI: 100-100), 98.1% (95% CI: 94.6-100), and 92.4 (95% CI: 81.6-100) at 3, 5, and 8 years after SRS. The cumulative probability of new pituitary deficit was 11.7% (95% CI: 3.8-18.9), 24.4% (95% CI: 12.1-35.1), and 29.5% (95% CI: 12.1-26.9) at 3, 5, and 8 years, respectively. No new visual field defect occurred. Before SRS, 50 patients (37.9%) presented with a visual field defect with a complete improvement in 17 (34.7%), partial improvement in 12 (24.5%), and stability in 19 (38.8%) at a last follow-up of 2.2 (3.9) years. One patient (2.0%) worsened after SRS. Before SRS, 10 patients (7.6%) presented with an oculomotor nerve palsy. One patient (0.8%) developed a new transient nerve palsy. At a last follow-up of 2.5 (4.4) years, 5 patients (45.4 35.7%) had a stability of their palsy, 1 had a partial improvement (9.1%), and 5 (45.4%) had a complete improvement. CONCLUSION:Upfront SRS represents an option for appropriately selected patients with NFPA, and it exhibits a favorable efficacy and safety profile, but a longer follow-up is required. Visual improvement is low, and careful selection of patient is required.

OBJECTIVE:There are few reports of outcomes following stereotactic radiosurgery (SRS) for the management of cerebral cavernous malformations (CCMs) of the basal ganglia or thalamus. Therefore, the authors aimed to clarify these outcomes. METHODS:Centers participating in the International Radiosurgery Research Foundation were queried for CCM cases managed with SRS from October 2001 to February 2021. The primary outcome of interest was hemorrhage-free survival (HFS) with a secondary outcome of symptomatic adverse radiation events (AREs). Assessment of the association of prognostic factors with HFS was conducted via Kaplan-Meier analysis and log-rank test. Chi-square tests were conducted to assess potential factors associated with the incidence of AREs. RESULTS:Seventy-three patients were identified. The median patient age was 43.5 years (range 4.4-79.5 years). Fifty-nine (80.8%) patients had hemorrhage prior to SRS. The median treatment volume was 0.9 cm3 (range 0.07-10.1 cm3) with a median margin prescription dose (MPD) of 12 Gy (range 10-20 Gy). One-, 3-, 5-, and 10-year HFS were 93.0%, 89.9%, 89.9%, and 83.0%, respectively, with one hemorrhage-related death approximately 1 year after SRS and nearly 60% and 30% of patients having improvement or stability of symptoms, respectively. There was no correlation between lesion size or MPD and HFS. Seven (9.6%) patients experienced AREs (MPDs > 12 Gy in all cases). Lesion size > 1.0 cm3 was correlated with the incidence of an ARE (p = 0.019). Forty-two (93.3%) of 45 patients treated with an MPD ≤ 12 Gy experienced neither hemorrhage nor AREs following SRS versus 17 (60.7%) of 28 patients treated with an MPD > 12 Gy (p = 0.0006). CONCLUSIONS:SRS is a reasonable treatment strategy and confers clinical stability or improvement and hemorrhage avoidance in patients harboring CCMs of the basal ganglia or thalamus. An MPD of approximately 12 Gy is recommended for the management of CCM.

Brainstem cerebral cavernous malformations (CCM) are clinically more aggressive compared to superficial CCMs. Due to their location, resection can be challenging, making stereotactic radiosurgery (SRS) an attractive alternative for symptomatic patient. Brainstem CCM patients (n = 170) were treated with Gamma Knife SRS at 11 radiosurgical centers. Hemorrhagic risk reduction, risk factors of post-SRS hemorrhage, and clinical outcomes were retrospectively analyzed. Most patients had a single (165/170 patients) brainstem CCMs treated; the majority of CCMs (165/181) presented with bleeding. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM (HR: 0.17, p < 0.001) using recurrent multivariate analysis. The annual hemorrhage rate decreased from 14.8 per 100 CCM-years before SRS to 2.3 after treatment. Using univariate Cox-analysis, the probability of a new hemorrhages after SRS was reduced for patient older than 35 years (HR = 0.21, p = 0.002) and increased with a margin dose > 13 Gy (HR = 2.57, p = 0.044). Adverse radiation effect (ARE) occurred in 9 patients (5.3%) and was symptomatic in four (2.4%). At a median follow-up of 3.4 years (Inter-quartile range: 5.4), 13 patients (8.0%) had a worsened clinical status, with the treated CCM being the cause in 5.6% (10) of the patients. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM and conveyed this benefit with a low risk of advrse radiation effects (ARE) and worsening clinical status.

Background Cerebral cavernous malformations (CCMs) frequently manifest with haemorrhages. Stereotactic radiosurgery (SRS) has been employed for CCM not suitable for resection. Its effect on reducing haemorrhage risk is still controversial. The aim of this study was to expand on the safety and efficacy of SRS for haemorrhagic CCM. Methods This retrospective multicentric study included CCM with at least one haemorrhage treated with single-session SRS. The annual haemorrhagic rate (AHR) was calculated before and after SRS. Recurrent event analysis and Cox regression were used to evaluate factors associated with haemorrhage. Adverse radiation effects (AREs) and occurrence of new neurological deficits were recorded. Results The study included 381 patients (median age: 37.5 years (Q1–Q3: 25.8–51.9) with 414 CCMs. The AHR from diagnosis to SRS excluding the first haemorrhage was 11.08 per 100 CCM-years and was reduced to 2.7 per 100 CCM-years after treatment. In recurrent event analysis, SRS, HR 0.27 (95% CI 0.17 to 0.44), p<0.0001 was associated with a decreased risk of haemorrhage, and the presence of developmental venous anomaly (DVA) with an increased risk, HR 1.60 (95% CI 1.07 to 2.40), p=0.022. The cumulative risk of first haemorrhage after SRS was 9.4% (95% CI 6% to 12.6%) at 5 years and 15.6% (95% CI% 9 to 21.8%) at 10 years. Margin doses> 13 Gy, HR 2.27 (95% CI 1.20 to 4.32), p=0.012 and the presence of DVA, HR 2.08 (95% CI 1.00 to 4.31), p=0.049 were factors associated with higher probability of post-SRS haemorrhage. Post-SRS haemorrhage was symptomatic in 22 out of 381 (5.8%) patients, presenting with transient (15/381) or permanent (7/381) neurological deficit. ARE occurred in 11.1% (46/414) CCM and was responsible for transient neurological deficit in 3.9% (15/381) of the patients and permanent deficit in 1.1% (4/381) of the patients. Margin doses >13 Gy and CCM volume >0.7 cc were associated with increased risk of ARE. Conclusion Single-session SRS for haemorrhagic CCM is associated with a decrease in haemorrhage rate. Margin doses ≤13 Gy seem advisable.

OBJECTIVE:Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS. METHODS:This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology. RESULTS:There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9-61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43-61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7-10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%-95%), 87% (95% CI 83%-91%), 86% (95% CI 82%-90%), and 69% (95% CI 59%-81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9-10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%-87%), 81% (95% CI 77%-85%), 78% (95% CI 74%-83%), and 71% (95% CI 63%-79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7-0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7-0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09-1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group. CONCLUSIONS:SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.

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 cm 3 , 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.

OBJECTIVE:The purpose of this study was to describe the long-term outcomes and associated risks related to repeat stereotactic radiosurgery (SRS) for persistent arteriovenous malformations (AVMs) in pediatric patients. METHODS:Under the auspices of the International Radiosurgery Research Foundation, this retrospective multicenter study analyzed pediatric patients who underwent repeat, single-session SRS between 1987 and 2022. The primary outcome variable was a favorable outcome, defined as nidus obliteration without hemorrhage or neurological deterioration. Secondary outcomes included rates and probabilities of hemorrhage, radiation-induced changes (RICs), and cyst or tumor formation. RESULTS:The cohort included 83 pediatric patients. The median patient age was 11 years at initial SRS and 15 years at repeat SRS. Fifty-seven children (68.7%) were managed exclusively using SRS, and 42 (50.6%) experienced hemorrhage prior to SRS. Median AVM diameter and volume were substantially different between the first (25 mm and 4.5 cm3, respectively) and second (16.5 mm and 1.6 cm3, respectively) SRS, while prescription dose and isodose line remained similar. At the 5-year follow-up evaluation from the second SRS, nidus obliteration was achieved in 42 patients (50.6%), with favorable outcome in 37 (44.6%). The median time to nidus obliteration and hemorrhage was 35.5 and 38.5 months, respectively. The yearly cumulative probability of favorable outcome increased from 2.5% (95% CI 0.5%-7.8%) at 1 year to 44% (95% CI 32%-55%) at 5 years. The probability of achieving obliteration followed a similar pattern and reached 51% (95% CI 38%-62%) at 5 years. The 5-year risk of hemorrhage during the latency period after the second SRS reached 8% (95% CI 3.2%-16%). Radiographically, 25 children (30.1%) had RICs, but only 5 (6%) were symptomatic. Delayed cyst formation occurred in 7.2% of patients, with a median onset of 47 months. No radiation-induced neoplasia was observed. CONCLUSIONS:The study results showed nidus obliteration in most pediatric patients who underwent repeat SRS for persistent AVMs. The risks of symptomatic RICs and latency period hemorrhage were quite low. These findings suggest that repeat radiosurgery should be considered when treating pediatric patients with residual AVM after prior SRS. Further study is needed to define the role of repeat SRS more fully in this population.

BACKGROUND:Stereotactic radiosurgery (SRS) is used to treat recurrent or residual nonfunctioning pituitary neuroendocrine tumors (NFPA). The objective of the study was to assess imaging and development of new pituitary hormone deficiency. METHODS:Patients treated with single-session SRS for a NFPA were included in this retrospective, multicenter study. Tumor control and new pituitary dysfunction were evaluated using Cox analysis and Kaplan-Meier curves. RESULTS:A total of 869 patients (male 476 [54.8%], median age at SRS 52.5 years [Interquartile range (IQR): 18.9]) were treated using a median margin dose of 14Gy (IQR: 4) for a median tumor volume of 3.4 cc (IQR: 4.3). With a median radiological follow-up of 3.7 years (IQR: 4.8), volumetric tumor reduction occurred in 451 patients (51.9%), stability in 364 (41.9%) and 54 patients (6.2%) showed tumor progression.The probability of tumor control was 95.5% (95% Confidence Interval [CI]: 93.8-97.3) and 88.8% (95%CI: 85.2-92.5) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with tumor control (Hazard Ratio [HR]:0.33, 95% CI: 0.18-0.60, P < 0.001). The probability of new hypopituitarism was 9.9% (95% CI: 7.3-12.5) and 15.3% (95% CI: 11-19.4) at 5 and 10 years, respectively. A maximum point dose >10 Gy in the pituitary stalk was associated with new pituitary hormone deficiency (HR: 3.47, 95% CI: 1.95-6.19). The cumulative probability of new cortisol, thyroid, gonadotroph, and growth hormone deficiency was 8% (95% CI: 3.9-11.9), 8.3% (95% CI: 3.9-12.5), 3.5% (95% CI: 1.7-5.2), and 4.7% (95% CI: 1.9-7.4), respectively at 10 years. CONCLUSIONS:SRS provides long-term tumor control with a 15.3% risk of hypopituitarism at 10 years.

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 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 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.

Abstract Brain death, characterized by the permanent cessation of all brain functions including the brainstem, is subject to varying diagnostic criteria internationally. In France, the confirmation of the clinical criteria requires ancillary tests such as CT angiogram or EEG. The timing of these tests presents challenges, especially in the intensive care setting. This study outlines a novel approach for the assessment of brainstem and cortical functions, improving the precision of brain death diagnosis in high-workload intensive care environments. We detail the implementation of a continuous multimodal neuromonitoring system, utilizing electrocorticography to monitor cortical spreading depolarizations (SD) and employing advanced analytics to track variability in heart and respiratory rates as indicators of brainstem functions. The SD-ICU single-center trial assessed the feasibility and safety of SD monitoring in patients with acute brain injuries, using cortical electrodes. In conjunction with the Moberg CNS monitor, this setup allowed for the collection and analysis of multimodal neuromonitoring data. We highlight the case of a patient who, exhibited an SD-initiated negative ultraslow potential, indicating cortical death. Subsequent fluctuations in heart and respiratory rates’ variability provided a real-time evaluation of the functionality of the brainstem's cardiovascular and respiratory centers. The integration of SD monitoring and variability analyses offers a continuous bedside evaluation, presenting clinicians with real-time biomarkers of brainstem and cortical death. This method could be incorporated into neuromonitoring software, enabling more timely and precise brain death determinations, a paramount improvement given the complexities and demands of ICU care.

Background. A higher risk of secondary brain tumor, carotid stenosis, and stroke has been reported after conventional sella irradiation for pituitary neuroendocrine tumors (PitNET). Stereotactic radiosurgery (SRS), which is a more focused approach, is now increasingly used instead. The aim was to assess the risk of secondary brain tumor, carotid stenosis/occlusion, and stroke after SRS. Methods. In this multicentric retrospective study, 2254 patients with PitNET were studied, 1377 in the exposed group, and 877 in the control group. Results. There were 9840.1 patient-years at risk for the SRS and 5266.5 for the control group. The 15-year cumulative probability of secondary intracranial tumor was 2.3% (95% CI: 0.5%, 4.1%) for SRS and 3.7% (95% CI: 0%, 8.7%) for the control group (P = .6), with an incidence rate of 1.32 per 1000 and 0.95 per 1000, respectively. SRS was not associated with an increased risk of tumorigenesis when stratified by age (HR: 1.59 [95% CI: 0.57, 4.47], Pp = .38). The 15-year probability of new carotid stenosis/occlusion was 0.9% (95% CI: 0.2, 1.6) in the SRS and 2% (95% CI: 0, 4.4) in the control group (P = .8). The 15-year probability of stroke was 2.6% (95% CI: 0.6%, 4.6%) in the SRS and 11.1% (95% CI: 6%, 15.9%) in the control group (P < .001). In Cox multivariate analysis stratified by age, SRS (HR 1.85 [95% CI:0.64, 5.35], P = .26) was not associated with risk of new stroke. Conclusions. No increased risk of long-term secondary brain tumor, new stenosis or occlusion, and stroke was demonstrated in the SRS group compared to the control in this study with imaging surveillance.

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.