Faculty Bibliography

BACKGROUND:Given the low haemorrhagic risk of intracranial low-grade dural arteriovenous fistulas (dAVFs), the benefits of routine intervention remain controversial. This study compares patient outcomes treated with stereotactic radiosurgery (SRS) versus conservative management. METHOD/METHODS:Multicentre retrospective analysis of the Consortium for Dural Arteriovenous Fistula Outcomes Research and the International Radiosurgery Research Foundation data. Inclusion criteria were (1) intracranial low-grade dAVF diagnosed by catheter-based angiography, (2) no prior dAVF-related haemorrhage and (3) management with upfront SRS (intervention group) or conservative management (observation group). The primary outcome was symptomatic improvement. Secondary outcomes included dAVF obliteration, up-conversion, haemorrhage, improvement and favourable modified Rankin Scale (mRS) at follow-up. RESULTS:304 patients with a mean age of 56 years (SD 13.5) and a follow-up of 46.7 months (SD 45.5) were included. 135 (44.4%) were managed conservatively and 169 (55.6%) had upfront SRS. Compared with the observation group, symptomatic and mRS Score improvement (≥1-point decrease in baseline score) was more likely in the intervention group (95.1% vs 58.5%; OR=13.75 (5.61-33.69) and 37.0% vs 24.0%; OR=1.85 (1.09-3.15), respectively). These findings remained significant after multiple imputation and propensity score matching. Remaining outcomes were similar between groups. The all-cause mortality rate was 5.4% (n=16), unrelated to the dAVF or treatment. Five (3.0%) SRS-related complications were reported and resolved during the follow-up period. CONCLUSIONS:SRS was associated with increased symptomatic and mRS Score improvement for low-grade dAVFs compared with conservative management. SRS had a low complication risk and did not appear to alter dAVF obliteration or haemorrhage. Future prospective trials on SRS as a first-line intervention for symptomatic low-grade dAVFs should be considered.

BACKGROUND:Pituitary metastases (PM) account for 0.4% of all intracranial metastases and typically present with visual and endocrinological deficits. Stereotactic radiosurgery (SRS) has shown excellent tumor control and safety profile in the management of intracranial metastases. However, its role and safety in managing metastases to the pituitary gland are not well-characterized. This study aims to evaluate SRS outcomes and safety profile in the management of PM in a multicenter international cohort. METHODS:The authors retrospectively analyzed data from 63 patients with PM treated with SRS across 12 institutions, assessing clinical and radiological outcomes, including survival rates, tumor control, visual and endocrinological outcomes, and post-treatment complications. RESULTS:Among 63 patients included in the study (median tumor volume: 1.5 cc), SRS demonstrated a local tumor control rate of 93.1% at 12 months. The median survival was 25.4 months and overall survival rates of 77.6%, 65.9%, and 55.1% at 6, 12, and 18 months, respectively. In multivariate analysis, a margin dose for PM > 10 Gy emerged as an independent predictor across progression-free survival (HR: 0.20, p < 0.01), distant metastasis-free survival (HR: 0.30, p = 0.01), and overall survival. (HR: 0.15, p < 0.01). Following SRS, most patients showed stable or improved visual function (n = 17/18). A small percentage of patients experienced complications: developed new visual deficits (n = 1/63), experienced new anterior pituitary hormone deficiency (n = 5/63), and developed arginine vasopressin (AVP)-deficiency post-treatment (n = 2/63). CONCLUSION/CONCLUSIONS:SRS is an important modality in the management of PM, offering excellent local tumor control and survival outcomes with minimal morbidity. These findings support the incorporation of SRS into the multidisciplinary management for treating patients with PM.

PURPOSE/OBJECTIVE:Bladder cancer rarely metastasizes to the brain. This study was performed to evaluate stereotactic radiosurgery (SRS) for the management of bladder cancer brain metastases. METHODS:Cases of bladder cancer brain metastases treated with SRS were collected by members of the International Radiosurgery Research Foundation (IRRF) and outcome data was analyzed for patients with at least one clinical or imaging follow-up. RESULTS:103 patients received SRS for 301 brain metastases. Median age at SRS was 68 and 73.8% of patients were male. Median KPS was 80%. Median time from primary to brain metastases diagnosis was 18 months. At the time of SRS, 50% of patients had other systemic metastases. The median number of metastases treated was 1, and median cumulative SRS volume was 1.16 cc. Most patients had single fraction SRS using a median margin dose of 18 Gy. At the time of analysis, 9.7% of patients were alive. Median survival after SRS was 7 months. Local control was achieved for 89.3% of metastases, 42% of patients developed new remote brain metastases, and 4.9% had leptomeningeal dissemination. Subsequent management included repeat SRS in 21.7%, surgical resection in 8.8% and WBRT in 7.6% of patients. At last follow-up, 32.1% of patients had improvement of their symptoms, whereas 38.5% remained stable. Adverse radiation effects occurred in 4.3% of treated metastases. On multivariate analyses, KPS ≥ 80% and non-urothelial histology predicted improved survival, while absence of corticosteroid intake predicted longer tumor control. CONCLUSION/CONCLUSIONS:Bladder cancer brain metastases can be safely managed with SRS.

BACKGROUND:Cerebral arteriovenous malformations (AVMs) are complex vascular lesions that pose a risk for hemorrhagic stroke. The number of draining veins has recently emerged as a significant predictor of rupture risk. This multicenter study aimed to evaluate the outcomes in adult AVM patients with single versus multiple draining veins. METHODS:We conducted a retrospective analysis of 735 AVM patients from the Multicenter International Study for Treatment of Brain AVMs (MISTA) database. Patients were categorized into single draining vein (n = 430) and multiple draining veins (n = 305) groups. Logistic and linear regression models were used to assess outcomes, adjusting for baseline characteristics, including age, rupture status, Spetzler-Martin grade, and other relevant factors. RESULTS:After adjustment, no significant differences were observed in complete AVM obliteration at last follow-up between the multiple and single draining veins groups (OR: 1.1; 95 % CI: 0.72-1.93, p = 0.49) after any treatment type. Good functional outcomes at last follow-up (mRS 0-2) were similar between the two groups (OR: 1.00; 95 % CI: 0.48-2.09, p = 0.98), as were retreatment rates (OR: 1.68; 95 % CI: 0.74-3.83, p = 0.21). Ruptured AVMs were more common in the single draining vein group (52.0 % vs. 35.4 %, p < 0.001). Patients in the multiple draining vein group had lower odds of hemorrhagic complications compared to the single vein group (OR: 0.38; 95 % CI: 0.14-1.02, p = 0.05). CONCLUSION/CONCLUSIONS:Single draining vein AVMs were more likely to present with rupture, but no significant differences in obliteration rates, functional outcomes, or retreatment rates were found between the groups after adjustment. These findings suggest that while venous drainage patterns may influence initial presentation, they do not appear to affect overall treatment success or patient prognosis after any treatment type. Further studies are needed to confirm.

PURPOSE/OBJECTIVE:Immune checkpoint inhibition (ICI) has revolutionized the treatment of melanoma care. Stereotactic radiosurgery combined with ICI has shown promise to improve clinical outcomes in prior studies in patients who have metastatic melanoma with brain metastases. However, others have suggested that concurrent ICI with stereotactic radiosurgery can increase the risk of complications. METHODS:We present a retrospective, single-institution analysis of 98 patients with a median follow up of 17.1 months managed with immune checkpoint inhibition and stereotactic radiosurgery concurrently and non-concurrently. A total of 55 patients were included in the concurrent group and 43 patients in the non-concurrent treatment group. Cox proportional hazards models were used to assess the relation between concurrent or non-concurrent treatment and overall survival or local progression-free survival. The Wald test was used to assess significance. Significant differences between patients in both groups experiencing adverse events including adverse radiation effects, perilesional edema, and neurological deficits were tested for using the Chi-square or Fisher's exact test. RESULTS:Patients receiving concurrent versus non-concurrent ICI showed a significant increase in overall survival (median 37.1 months, 95% CI: 18.9 months - NA versus median 11.4 months, 95% CI: 6.4-33.2 months, p = 0.0056) but not local progression-free survival. There were no significant differences between groups with regards to adverse radiation effects (2% versus 3%), perilesional edema (20% versus 9%), neurological deficits (3% versus 20%). CONCLUSION/CONCLUSIONS:These results suggest that the timing of ICI does not increase risk of neurological complications when delivered within 4 weeks of SRS.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Stereotactic radiosurgery (SRS) with neoadjuvant embolization is a treatment strategy for brain arteriovenous malformations (AVMs), especially for those with large nidal volume or concomitant aneurysms. The aim of this study was to assess the effects of pre-SRS embolization in AVMs with an associated intracranial aneurysm (IA). METHODS:The International Radiosurgery Research Foundation AVM database from 1987 to 2018 was retrospectively reviewed. SRS-treated AVMs with IAs were included. Patients were categorized into those treated with upfront embolization (E + SRS) vs stand-alone SRS (SRS). Primary end point was a favorable outcome (AVM obliteration + no permanent radiation-induced changes or post-SRS hemorrhage). Secondary outcomes included AVM obliteration, mortality, follow-up modified Rankin Scale, post-SRS hemorrhage, and radiation-induced changes. RESULTS:Forty four AVM patients with associated IAs were included, of which 23 (52.3%) underwent pre-SRS embolization and 21 (47.7%) SRS only. Significant differences between the E + SRS vs SRS groups were found for AVM maximum diameter (1.5 ± 0.5 vs 1.1 ± 0.4 cm3, P = .019) and SRS treatment volume (9.3 ± 8.3 vs 4.3 ± 3.3 cm3, P = .025). A favorable outcome was achieved in 45.4% of patients in the E + SRS group and 38.1% in the SRS group (P = .625). Obliteration rates were comparable (56.5% for E + SRS vs 47.6% for SRS, P = .555), whereas a higher mortality rate was found in the SRS group (19.1% vs 0%, P = .048). After adjusting for AVM maximum diameter, SRS treatment volume, and maximum radiation dose, the likelihood of achieving favorable outcome and AVM obliteration did not differ between groups (P = .475 and P = .820, respectively). CONCLUSION/CONCLUSIONS:The likelihood of a favorable outcome and AVM obliteration after SRS with neoadjuvant embolization in AVMs with concomitant IA seems to be comparable with stand-alone SRS, even after adjusting for AVM volume and SRS maximum dose. However, the increased mortality among the stand-alone SRS group and relatively low risk of embolization-related complications suggest that these patients may benefit from a combined treatment approach.

Spetzler-Martin Grade IV arteriovenous malformations (AVMs) are challenging due to high risks associated with both treatment and natural progression. This study compares the outcomes of microsurgical resection and stereotactic radiosurgery (SRS) in high-grade AVMs, analyzing obliteration rates, complications, and functional outcomes. A retrospective cohort of 96 patients treated with either microsurgical resection (33 patients) or SRS (63 patients) was analyzed. Propensity-score matching was employed to account for baseline variables such as AVM size (cm), preoperative embolization and rupture status. Primary endpoints included AVM obliteration, complication rates, and modified Rankin Scale (mRS) scores. After matching, 31 patients per group were analyzed. Microsurgical resection achieved significantly higher obliteration rates (87.1%) compared to SRS (32.3%, p < 0.001). In the matched SRS cohort (n = 31), the actuarial obliteration rates were 11% (95% CI: 0-22%) at 1 year, 17% (95% CI: 0-31%) at 3 years, and 43% (95% CI: 13-63%) at 5 years post-treatment. Complication rates were similar (32.3% resection, 38.7% SRS, p = 0.6). Functional outcomes in terms of improvement in modified Rankin Scale (mRS) scores were observed in 50.0% of microsurgery patients and 41.4% of SRS patients. However, the absolute number of patients improving was similar (13 vs. 12), and the microsurgery group had more cases of worsening mRS scores compared to the SRS group (4 vs. 2). The difference was not statistically significant (p = 0.4). Microsurgical resection offers superior obliteration rates for high-grade AVMs with comparable complication risks to SRS. SRS remains a valuable alternative for select patients, particularly those ineligible for resection. Future research should focus on optimizing multimodal treatment approaches. Clinical trial number Not applicable.

The management of brain metastases is challenging and should ideally be coordinated through a multidisciplinary approach. Stereotactic radiosurgery (SRS) has been the cornerstone of management for most patients with oligometastatic central nervous system involvement (one to four brain metastases), and several technological and therapeutic advances over the past decade have broadened the indications for SRS to include polymetastatic central nervous system involvement (>4 brain metastases), preoperative application and fractionated SRS, as well as combinatorial approaches with targeted therapy and immune-checkpoint inhibitors. For example, improved imaging and frameless head-immobilization technologies have facilitated fractionated SRS for large brain metastases or postsurgical cavities, or lesions in proximity to organs at risk. However, these opportunities come with new challenges and questions, including the implications of tumour histology as well as the role and sequencing of concurrent systemic treatments. In this Review, we discuss these advances and associated challenges in the context of ongoing clinical trials, with insights from a global group of experts, including recommendations for current clinical practice and future investigations. The updates provided herein are meaningful for all practitioners in clinical oncology.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Stereotactic radiosurgery (SRS) is effective for patients with medically refractory trigeminal neuralgia with a 75%-90% response rate. Consideration of the integral dose (ID) to the target nerve within the 50% isodose line was reported to help select prescription doses to maximize effectiveness and minimize bothersome numbness. The objective of this study was to externally validate the ID as a predictor of outcomes after SRS. METHODS:We reviewed the outcomes and parameters of 94 consecutive patients of type 1 trigeminal neuralgia who had SRS for the first time where nerve ID was calculated. 70% of the prescription doses were 80 Gy, with 28% at 85 Gy, and 2% at 70 Gy. RESULTS:The median follow-up time was 14.4 months. A total of 85 (90%) patients reported significant pain relief (Barrow Neurological Institute I-III) after initial SRS. The median pain recurrence-free survival was 82 months (95% CI 41.1-NA), and estimates at 1, 3, and 5 years were 80.5%, 65.5%, and 55.9%, respectively. The ID was not significantly associated with initial pain relief, or affect the risk of pain recurrence or sensory dysfunction after SRS using the Cox proportional hazards model. A nerve mean dose ≥65 Gy was associated with a reduced risk of pain recurrence on multivariate analysis (hazard ratio 0.408, P = .039). Twenty (21%) patients experienced sensory dysfunction after SRS with 3 (3%) requiring further medications, which was not correlated with the prescription dose or brainstem maximum dose. CONCLUSION/CONCLUSIONS:The ID did not predict recurrence-free survival or sensory dysfunction. Our observations suggest improved nerve coverage by the most powerful area of the isocenter, for instance, by targeting a narrower segment if feasible, could result in more durable pain relief. Further studies to validate these findings are needed.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Stereotactic procedures are used to manage a diverse set of patients across a variety of clinical contexts. The stereotactic devices and software used in these procedures vary between surgeons, but the fundamental principles that constitute safe and accurate execution do not. The aim of this work is to describe these principles to equip readers with a generalizable knowledge base to execute and understand stereotactic procedures. METHODS:A combination of a review of the literature and empirical experience from several experienced surgeons led to the creation of this work. Thus, this work is descriptive and qualitative by nature, and the literature is used to support instead of generate the ideas of this framework. RESULTS:The principles detailed in this work are categorized based on 5 clinical domains: imaging, registration, mechanical accuracy, target planning and adjustment, and trajectory planning and adjustment. Illustrations and tables are used throughout to convey the concepts in an efficient manner. CONCLUSION/CONCLUSIONS:Stereotactic procedures are complex, requiring a thorough understanding of each step of the workflow. The concepts described in this work enable functional neurosurgeons with the fundamental knowledge necessary to provide optimal patient care.