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

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Stereotactic radiosurgery for brain metastases from human epidermal receptor 2 positive breast Cancer: an international, multi-center study.

PURPOSE: To report patient outcomes and local tumor control rates in a cohort of patients with biopsy-proven HER-2 positive breast cancer treated with stereotactic radiosurgery (SRS) for brain metastases (BM). METHODS: This international, retrospective, multicenter study, included 195 female patients with 1706 SRS-treated BM. Radiologic and clinical outcomes after SRS were determined and prognostic factors identified. RESULTS: At SRS, median patient age was 55 years [interquartile range (IQR) 47.6-62.0], and 156 (80%) patients had KPS ≥ 80. The median tumor volume was 0.1 cm3 (IQR 0.1-0.5) and the median prescription dose was 16 Gy (IQR 16-18). Local tumor control (LTC) rate was 98%, 94%, 93%, 90%, and 88% at six-, 12-, 24-, 36- and 60-months post-SRS, respectively. On multivariate analysis, tumor volume (p = < 0.001) and concurrent pertuzumab (p = 0.02) improved LTC. Overall survival (OS) rates at six-, 12-, 24-, 36-, 48-, and 60-months were 90%, 69%, 46%, 27%, 22%, and 18%, respectively. Concurrent pertuzumab improved OS (p = 0.032). In this patient subgroup, GPA scores ≥ 2.5 (p = 0.038 and p = 0.003) and rare primary tumor histologies (p = 0.01) were associated with increased and decreased OS, respectively. Asymptomatic adverse radiation events (ARE) occurred in 27 (14.0%) and symptomatic ARE in five (2.6%) patients. Invasive lobular carcinoma primary (p = 0.042) and concurrent pertuzumab (p < 0.001) conferred an increased risk for overall but not for symptomatic ARE. CONCLUSION: SRS affords effective LTC for selected patients with BM from HER-2 positive breast cancer. Concurrent pertuzumab improved LTC and OS but at the same time increased the risk for overall, but not symptomatic, ARE.

Effect of Fluid Therapy on Acid-Base Balance in Patients Undergoing Clipping for Ruptured Intracranial Aneurysm: A Prospective Randomized Controlled Trial.

Objectives Neurosurgical patients often receive 0.9% normal saline (NS) during the perioperative period. Theoretically, a balanced salt solution (BSS) is better than 0.9% saline. We compared the effects of two different fluids on acid-base balance, renal function, and neurological outcome in patients who underwent clipping following subarachnoid hemorrhage from a ruptured intracranial aneurysm. Materials and Methods Patients in group NS ( n = 30) received 0.9% saline and group BSS ( N = 30) received BSS (Plasmalyte-A) in the perioperative period for 48 hours. Comparison of arterial pH, bicarbonate, and base deficit measured preoperatively, intraoperatively (first and second hour), and postoperatively (at 24 and 48 hours) was the primary outcome of the study. The secondary outcome compared serum electrolytes, renal function tests, urine neutrophil gelatinase-associated lipocalin (NGAL), serum cystatin C, and the neurological outcome using modified Rankin score (MRS) at discharge, 1, and 3 months. Results In group NS, significantly low pH at 1-hour intraoperative period was seen compared with group BSS (7.37 ± 0.06 vs. 7.40 ± 0.05, p = 0.024). The bicarbonate level in group NS was significantly lower and the base deficit was higher at second intraoperative hour (bicarbonate: 17.49 vs. 21.99 mEq/L, p = 0.001; base deficit: 6.41 mmol/L vs. 1.89 mmol/L, p = 0.003) and at 24 hours post-surgery (bicarbonate: 20.38 vs. 21.96 mEq/L, p = 0.012; base deficit: 3.56 mmol/L vs. 2.12 mmol/L, p = 0.034)). Serum creatinine was higher in group NS at 24 hours (0.66 vs. 0.52 mg/dL, p = 0.013) and 48 hours (0.62 vs. 0.53 mg/dL, p = 0.047). Serum urea, electrolytes, cystatin, urine NGAL, and MRS were comparable. Conclusion In neurosurgical patients undergoing clipping for ruptured intracranial aneurysm, using a BSS during the perioperative period is associated with a better acid-base and renal profile. However, the biomarkers of kidney injury and long-term outcomes were comparable.

Gamma Knife Radiosurgery for Hypothalamic Hamartoma: A Multi-Institutional Retrospective Study on Safety, Efficacy, and Complication Profile.

BACKGROUND AND OBJECTIVES: Gamma knife radiosurgery (GKRS) is a safe and effective treatment option for hypothalamic hamartomas (HH), but there is no consensus opinion on its timing, dosage, and follow-up. The aim of this study was to define the safety, efficacy, outcome, and complication profile of GKRS in this patient population. METHODS: This retrospective multicentric study involved 39 patients with the mean age of 16 ± 14.84 years. Early seizures resulted in an earlier age of diagnosis in 97% of patients. At baseline, no endocrine abnormalities were seen in 75% of patients while 18.9% showed precocious puberty (PP). The median target volume was 0.55 cc (0.1-10.00 cc), and a median margin dose of 16 Gy (8.1-20.0 Gy) was delivered in a single session. All patients were evaluated for clinical, endocrinological, and radiological outcomes. RESULTS: The median follow-up was 5 (0.1-15) years. The median target volume of the cohort was 0.55 (0.35-1.77) cc. The largest HH was of 10 cc. 24/39 (61.5%) were small HH (Regis I-III). At presentation, 94.8% patients suffered from seizures (87.18% with gelastic seizures). 7/39 patients (17.9%) were presented with both PP and epilepsy. Only one (2.6%) patient presented with PP alone. 29 patients had more than 3-year follow-up. All received ≥16 Gy targeting complete HH. 28% of patients showed regression in HH volume. Patients with Regis grade I-III and longer follow-up (>75 months) showed gradual improvement in seizures. 16/29 patients (55.2%) achieved good seizure control (Engel I/II) while 13 (44.8%) were in Engel III/IV status. Nine patients needed adjuvant treatment because of poor seizure control. Eight patients suffered from transient increase in seizures. One patient developed poikilothermia, and 2 patients developed new onset hormonal deficiency. CONCLUSION: GKRS is a safe and effective modality for treatment of HH with significant improvement in seizure control with minimal disruption of endocrine profile. It provides an excellent safety, efficacy, and complication profile, especially for small HH. Latency of results and its adjuvant nature remain the areas of research and breakthroughs among contemporary treatment options.

Risk of new tumor, carotid stenosis, and stroke after Stereotactic Radiosurgery for Pituitary Tumor: A multicenter study of 2254 patients with imaging follow-up.

BACKGROUND: 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, 2,254 patients with PitNET were studied, 1,377 in the exposed group and 877 in the control group. RESULTS: There were 9,840.1 patient-years at risk for the SRS and 5,266.5 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=0.6), with an incidence rate of 1.32 per 1,000 and 0.95 per 1,000, respectively. SRS was not associated with increased risk of tumorigenesis when stratified by age (HR: 1.59 [95%CI: 0.57, 4.47], p=0.38). 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=0.8). 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<0.001). In cox multivariate analysis stratified by age, SRS (HR 1.85[95%CI:0.64, 5.35], p=0.26) was not associated with risk of new stroke. CONCLUSION: No increased risk of long-term secondary brain tumor, new stenosis or occlusion and stroke was demonstrated in SRS group compared to control in this study with imaging surveillance.

"Now What Do I Do?" - Practical Challenges Faced By Young Neurosurgeons in their Career Management.

Neurosurgical residency is tough. Grueling hours and tough decisions require a mental makeup unlike many other specialties. But the real examination begins after the residency is over. Many young neurosurgeons are faced with a daunting task of deciding their future as soon as they step out of the medical school. Sometimes, such decisions can shape the entire career of the neurosurgeon. However, over the many years of academic teaching and learning what we are not taught is how to "Manage." Management of careers, decision making, and understanding the business end of our profession is lacking. Here, we review the career and decisions needed to be taken by a young neurosurgeon through the glass of a business management mindset. We try to define the opportunities and decisions and how they may reflect on the general population and patients as a whole.

Pleomorphic Xanthoastrocytoma: Multi-Institutional Evaluation of Stereotactic Radiosurgery.

BACKGROUND AND OBJECTIVES: Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade glial tumor primarily affecting young individuals. Surgery is the primary treatment option; however, managing residual/recurrent tumors remains uncertain. This international multi-institutional study retrospectively assessed the use of stereotactic radiosurgery (SRS) for PXA. METHODS: A total of 36 PXA patients (53 tumors) treated at 11 institutions between 1996 and 2023 were analyzed. Data included demographics, clinical variables, SRS parameters, tumor control, and clinical outcomes. Kaplan-Meier estimates summarized the local control (LC), progression-free survival, and overall survival (OS). Secondary end points addressed adverse radiation effects and the risk of malignant transformation. Cox regression analysis was used. RESULTS: A total of 38 tumors were grade 2, and 15 tumors were grade 3. Nine patients underwent initial gross total resection, and 10 received adjuvant therapy. The main reason for SRS was residual tumors (41.5%). The median follow-up was 34 months (range, 2-324 months). LC was achieved in 77.4% of tumors, with 6-month, 1-year, and 2-year LC estimates at 86.7%, 82.3%, and 77.8%, respectively. Younger age at SRS (hazard ratios [HR] 3.164), absence of peritumoral edema (HR 4.685), and higher marginal dose (HR 6.190) were significantly associated with better LC. OS estimates at 1, 2, and 5 years were 86%, 74%, and 49.3%, respectively, with a median OS of 44 months. Four patients died due to disease progression. Radiological adverse radiation effects included edema (n = 8) and hemorrhagic change (n = 1). One grade 3 PXA transformed into glioblastoma 13 months after SRS. CONCLUSION: SRS offers promising outcomes for PXA management, providing effective LC, reasonable progression-free survival, and minimal adverse events.

Psychosurgery in Indian Scenario: Time to Think with Phronesis.

With advances in technology, neurosurgical procedures are being examined for potential use in psychiatric conditions. However, the use of neurosurgical procedures in psychiatry carries the baggage of memories of psychosurgery. Different neurosurgical techniques carry their characteristic safety, efficacy, and complication profile. The introduction of deep brain stimulation has generated a new interest in surgical treatment with a distinct advantage over lesioning procedures used in the past. In such a scenario, it is essential that an informed discussion takes place regarding the use of these neurosurgical procedures in psychiatric disorders such that patient safety, informed consent, regulatory requirements, and research are taken care of.

Institutional Experience of Post-Traumatic Posterior Fossa Extra Dural Hematoma: A Prospective Longitudinal Study.

AIM: To analyze clinical and imaging characteristics of post-traumatic posterior fossa extradural hematoma (PFEDH). MATERIAL AND METHODS: Between 2018 and 2022, 51 patients were admitted to our tertiary care trauma center with a diagnosis of PFEDH. The management decision was tailored by an individual consultant based on clinicoradiological findings. We did a prospective analysis of patient characteristics, radiology, clinical presentation, management, and outcome at discharge and onemonth follow-up. RESULTS: Of the 51 patients diagnosed with a PFEDH, 45 (88.2%) were male, and six (11.8%) were female with a mean age of 31.2 years (range 2-77 years). Twenty-six patients needed surgical evacuation of the EDH, while the rest 25 patients were managed conservatively. There was one crossover patient from the conservative to the surgical arm. Road traffic accidents (RTA) were the most common cause of injury (n=35; 68.6%), followed by falls from height (n=16; 31.4%). Most patients presented with vomiting and loss of consciousness (LOC). At presentation, 30 patients (58.5%) had a GCS 15. Seven patients (13.7%) presented with a GCS of 9-14, and 14 patients (27.5%) with GCS ≤ 8. The mean EDH volume in conservatively and surgically managed patients was 14.1 and 25.1cc, respectively. Five patients (9.8%) had significant midline shift with obliteration of basal cisterns, 15 patients (29.4%) had effacement of the fourth ventricle, and 11 patients (21.5%) had the presence of hydrocephalus. All patients with features suggestive of tight posterior fossa (hydrocephalus, obliterated basal cisterns, and fourth ventricle compression) needed surgical intervention. Of the 25 conservatively managed patients, 24 (96%) had favorable GOS scores at discharge, while one (4%) had an unfavorable score. 16/26 (61.5%) surgically treated patients had a good outcome at discharge (GOS=4-5), while ten patients (38.4%) had adverse outcomes (GOS < 4). Initial EDH volume was inversely correlated with presenting GCS and GOS with a mean volume of 21.5 ± 8.5 cc in patients presenting with a GCS ?8. Patients with a GCS of 15 at presentation had a mean EDH volume of 16.1 ± 8.2 cc. Patients with smaller EDH had much higher GOS scores than patients with higher volume EDH (GOS 1 = 22.0 ± 9.83 cc vs. GOS 5 = 18.9 ± 12.2 cc). Outcomes mainly depended on factors like GCS at arrival and associated supratentorial, thoracic/ abdominal polytrauma. CONCLUSION: In patients with a clot volume of < 15 cm3 and GCS of 15 at presentation with no mass effect and absence of tight posterior fossa, a conservative trial under strict clinicoradiological monitoring in a neuro-critical multidisciplinary setting can be offered with good results. In cases of altered GCS, findings of a TPF, or clinicoradiological deterioration, immediate surgery is warranted.

Comparison of the Efficacy of Sterile Silicone Studs Versus Lidocaine for the Attenuation of the Hemodynamic Response to Skull Pin Insertion: A Randomized Controlled Trial.

BACKGROUND: Skull pin insertion causes hypertension and tachycardia that adversely affects cerebral hemodynamics. We compared the efficacy of sterile silicone studs (SS) and pin site infiltration with lidocaine in attenuation of the sympathetic response to skull pin insertion. METHODS: Adult patients (N = 120) undergoing supratentorial craniotomy under general anesthesia were randomized to receive either medical-grade sterile SS or 2 mL of 2% plain lidocaine infiltration at each pin site. Hemodynamic (heart rate and mean arterial pressure) response to skull pin insertion at baseline and at 0, 1, 2, 3, and 5 minutes after skull pin insertion was compared. Requirement of rescue analgesia (fentanyl), complications such as pin-site bleeding, and surgeon satisfaction score were assessed. RESULTS: Heart rate in the lidocaine group was significantly greater at 0, 1, 2, 3, and 5 minutes after pin insertion compared with the SS group (P < 0.05). Mean arterial pressure was also significantly higher in the lidocaine group at 0, 1, 2, and 3 minutes after pin insertion (P = 0.001, P = 0.01, P = 0.034, and P = 0.042) compared with the SS group. The number of patients requiring fentanyl [17/60 (28.3%) vs. 40/60 (66%), P = 0.001] was lower in the SS group. The incidence of pin site bleeding was also lower in the SS group, and surgeon satisfaction score was greater. CONCLUSIONS: Sterile SS appear to be more effective than lidocaine infiltration in attenuating the hemodynamic response to skull pin insertion with minimal adverse effects. Further multicenter studies are necessary to conclusively establish the safety and efficacy of sterile SS.

Vestibular Schwannoma International Study of Active Surveillance Versus Stereotactic Radiosurgery: The VISAS Study.

PURPOSE: The present study assesses the safety and efficacy of stereotactic radiosurgery (SRS) versus observation for Koos grade 1 and 2 vestibular schwannoma (VS), benign tumors affecting hearing and neurological function. METHODS AND MATERIALS: This multicenter study analyzed data from Koos grade 1 and 2 VS patients managed with SRS (SRS group) or observation (observation group). Propensity score matching balanced patient demographics, tumor volume, and audiometry. Outcomes measured were tumor control, serviceable hearing preservation, and neurological outcomes. RESULTS: In 125 matched patients in each group with a 36-month median follow-up (P = .49), SRS yielded superior 5- and 10-year tumor control rates (99% CI, 97.1%-100%, and 91.9% CI, 79.4%-100%) versus observation (45.8% CI, 36.8%-57.2%, and 22% CI, 13.2%-36.7%; P < .001). Serviceable hearing preservation rates at 5 and 9 years were comparable (SRS 60.4% CI, 49.9%-73%, vs observation 51.4% CI, 41.3%-63.9%, and SRS 27% CI, 14.5%-50.5%, vs observation 30% CI, 17.2%-52.2%; P = .53). SRS were associated with lower odds of tinnitus (OR = 0.39, P = .01), vestibular dysfunction (OR = 0.11, P = .004), and any cranial nerve palsy (OR = 0.36, P = .003), with no change in cranial nerves 5 or 7 (P > .05). Composite endpoints of tumor progression and/or any of the previous outcomes showed significant lower odds associated with SRS compared with observation alone (P < .001). CONCLUSIONS: SRS management in matched cohorts of Koos grade 1 and 2 VS patients demonstrated superior tumor control, comparable hearing preservation rates, and significantly lower odds of experiencing neurological deficits. These findings delineate the safety and efficacy of SRS in the management of this patient population.

Comparison of the effects of opioid-free anesthesia (OFA) and opioid-based anesthesia (OBA) on postoperative analgesia and intraoperative hemodynamics in patients undergoing spine surgery: A prospective randomized double-blind controlled trial.

Background: Opioids form the basis of perioperative pain management but are associated with multiple side effects. In opioid-free anesthesia (OFA), several non-opioid drugs or neuraxial/regional blocks are used as substitutes for opioids. Ketamine, a N-methyl-d-aspartate antagonist, provides intense analgesia. However, there is a shortage of literature on the effects of ketamine-based OFA on hemodynamics (HD) and postoperative analgesia in patients undergoing thoracolumbar spine surgery. Materials and Methods: This prospective randomized controlled trial included 60 adult patients. The patients in Group OFA (n = 30) received OFA with ketamine and ketofol (1:5) infusion, and those in Group OBA (n = 30) received opioid-based anesthesia (OBA) with fentanyl and propofol infusion. The postoperative pain-free period, pain scores, rescue analgesia, intraoperative HDs, and postoperative complications were assessed. Results: The mean pain-free period in Group OFA (9.86 ± 1.43 hr) was significantly higher than that in Group OBA (6.93 ± 1.93 hr) (P = 0.002). During the postoperative 48 hours, the total requirement of fentanyl was considerably lower in Group OFA (P < 0.05). There was a significantly higher incidence of hypertension in Group OFA (46%) and hypotension (43%) in Group OBA (43%), respectively. Postoperative nausea vomiting (PONV) was more common in Group OBA at the 2nd and 6th hr (P = 0.046 and P = 0.038). Conclusion: OFA with ketamine and ketofol provided adequate postoperative analgesia with a lower incidence of PONV after spine surgery. However, hypertension in the ketamine group and hypotension in the propofol group required fine titration of the infusion rate of drugs during the intraoperative period.

Comparative analysis of the spatial distribution of brain metastases across several primary cancers using machine learning and deep learning models.

OBJECTIVE: Brain metastases (BM) are associated with poor prognosis and increased mortality rates, making them a significant clinical challenge. Studying BMs can aid in improving early detection and monitoring. Systematic comparisons of anatomical distributions of BM from different primary cancers, however, remain largely unavailable. METHODS: To test the hypothesis that anatomical BM distributions differ based on primary cancer type, we analyze the spatial coordinates of BMs for five different primary cancer types along principal component (PC) axes. The dataset includes 3949 intracranial metastases, labeled by primary cancer types and with six features. We employ PC coordinates to highlight the distinctions between various cancer types. We utilized different Machine Learning (ML) algorithms (RF, SVM, TabNet DL) models to establish the relationship between primary cancer diagnosis, spatial coordinates of BMs, age, and target volume. RESULTS: Our findings revealed that PC1 aligns most with the Y axis, followed by the Z axis, and has minimal correlation with the X axis. Based on PC1 versus PC2 plots, we identified notable differences in anatomical spreading patterns between Breast and Lung cancer, as well as Breast and Renal cancer. In contrast, Renal and Lung cancer, as well as Lung and Melanoma, showed similar patterns. Our ML and DL results demonstrated high accuracy in distinguishing BM distribution for different primary cancers, with the SVM algorithm achieving 97% accuracy using a polynomial kernel and TabNet achieving 96%. The RF algorithm ranked PC1 as the most important discriminating feature. CONCLUSIONS: In summary, our results support accurate multiclass ML classification regarding brain metastases distribution.

Sexual Dysfunction after Clipping of Ruptured Intracranial Aneurysms.

BACKGROUND: Sexual dysfunction significantly affects interpersonal relationships and overall quality of life. It remains a matter of concern for risk assessment and counseling in patients with ruptured intracranial aneurysms. OBJECTIVE: To assess the sexual dysfunctions in patients undergoing clipping for ruptured intracranial aneurysms and comparative evaluation among different anterior circulation aneurysms. METHOD: We prospectively included 40 male patients of ruptured intracranial aneurysms of anterior circulation (age range: 20-60 years; sexually active preoperatively), managed with craniotomy and clipping. We evaluated the sexual outcome in patients with excellent Glasgow outcome score (GOS) five at a minimum one year of follow-up. Patients with GOS-5 status at follow-up were broadly classified into two groups: Anterior communicating artery aneurysm (Acom), and non-Acom) aneurysms. We valued sexual outcome with Subjective Sexual Arousal Scale for Men at follow-up, and compared in the two groups. RESULTS: Mean age of patients was 44.78 ± 9.51 years. Besides 20 Acom aneurysms, other groups included 11 middle cerebral artery aneurysms, five internal carotid artery aneurysms, three posterior communicating artery aneurysms, and one distal anterior cerebral artery aneurysm. The mean follow-up was 24.45 ± 13.58 months. Patients with non-Acom aneurysms had an overall better outcome in the sexual performance domain "P = 0.015," mental satisfaction domain "P = 0.009," and sexual assertiveness domain "P = 0.007." However, there was no statistical difference in partner communication domain "P = 0.593," and partner relationship domain "P = 0.378." Overall, the sexual outcome was inferior in patients treated for Acom aneurysms compared to other anterior circulation aneurysms. CONCLUSIONS: In cases of aneurysmal subarachnoid hemorrhage, sexual dysfunctions are common even after good clinical outcomes. The study revealed prominent differences in outcomes on the sexual quality of life in patients harboring Acom aneurysms as compared to anterior circulation aneurysms located off-midline.

Long-term radiographic and endocrinological outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas.

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.

The relevance of biologically effective dose for pain relief and sensory dysfunction after Gamma Knife radiosurgery for trigeminal neuralgia: an 871-patient multicenter study.

OBJECTIVE: Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure. METHODS: This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value. RESULTS: The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5-95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6-156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I-IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness. CONCLUSIONS: BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

Pediatric cerebral cavernous malformations and stereotactic radiosurgery: an analysis of 50 cases from a multicentric study.

OBJECTIVE: Cerebral cavernous malformations (CCMs) are the second most common vascular anomaly affecting the CNS in children. Although stereotactic radiosurgery (SRS) has been proposed as an alternative to microsurgery in the management of selected cases in adults, there is a paucity of studies focusing on pediatric patients. The aim of this study was to present the outcomes and associated risks of SRS in this subgroup of patients. METHODS: This retrospective multicenter study included pediatric patients treated with single-session SRS for CCMs. The annual hemorrhage rate (AHR) was calculated before and after SRS in hemorrhagic lesions. The Engel classification was used to describe post-SRS epileptic control. Adverse radiation effects (AREs) and the occurrence of new neurological deficits were recorded. RESULTS: The study included 50 patients (median age 15.1 [IQR 5.6] years) harboring 62 CCMs. Forty-two (84%) and 22 (44%) patients had a history of hemorrhage or epilepsy prior to SRS, respectively. The AHR from diagnosis to SRS excluding the first hemorrhage was 7.19 per 100 CCM-years, dropping to 3.15 per 100 CCM-years after treatment. The cumulative risk of first hemorrhage after SRS was 7.4% (95% CI 0%-14.3%) at 5 years and 23.6% (95% CI 0%-42.2%) at 10 years. Eight hemorrhagic events involving 6 CCMs in 6 patients were recorded in the post-SRS follow-up period; 4 patients presented with transient symptoms and 4 with permanent symptoms. Of the 22 patients with pre-SRS seizures, 11 were seizure free at the last follow-up (Engel class I), 6 experienced improvement (Engel class II or III), 5 had no improvement (Engel class IVA or IVB), and 1 experienced worsening (Engel class IVC). Radiographic AREs were documented in 14.5% (9/62) of CCMs, with 4 being symptomatic. CONCLUSIONS: Single-session SRS reduces the CCM hemorrhage rate in the pediatric population and provides adequate seizure control.

Repeat stereotactic radiosurgery for persistent cerebral arteriovenous malformations in pediatric patients.

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.