Immune checkpoint inhibition and single fraction stereotactic radiosurgery in brain metastases from non-small cell lung cancer: an international multicenter study of 395 patients.

PURPOSE: Approximately 80% of brain metastases originate from non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) are frequently utilized in this setting. However, concerns remain regarding the risk of radiation necrosis (RN) when SRS and ICI are administered concurrently. METHODS: A retrospective study was conducted through the International Radiosurgery Research Foundation. Logistic regression models and competing risks analyses were utilized to identify predictors of any grade RN and symptomatic RN (SRN). RESULTS: The study included 395 patients with 2,540 brain metastases treated with single fraction SRS and ICI across 11 institutions in four countries with a median follow-up of 14.2 months. The median age was 67 years. The median margin SRS dose was 19 Gy; 36.5% of patients had a V12 Gy ≥ 10 cm3. On multivariable analysis, V12 Gy ≥ 10 cm3 was a significant predictor of developing any grade RN (OR: 2.18) and SRN (OR: 3.95). At 1-year, the cumulative incidence of any grade and SRN for all patients was 4.8% and 3.8%, respectively. For concurrent and non-concurrent groups, the cumulative incidence of any grade RN was 3.8% versus 5.3%, respectively (p = 0.35); and for SRN was 3.8% vs. 3.6%, respectively (p = 0.95). CONCLUSION: The risk of any grade RN and symptomatic RN following single fraction SRS and ICI for NSCLC brain metastases increases as V12 Gy exceeds 10 cm3. Concurrent ICI and SRS do not appear to increase this risk. Radiosurgical planning techniques should aim to minimize V12 Gy.

Gamma Knife Radiosurgery for SUNCT: A Case Series.

BACKGROUND: The treatment of medically refractory patients with chronic short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is challenging. Stereotactic radiosurgery targeting the trigeminal nerve and sphenopalatine ganglion (SPG) has been used as a less-invasive treatment. The outcomes of this procedure have been described in a few case reports. OBJECTIVES: The objective of the study was to report on the effect of Gamma Knife radiosurgery (GKRS) in 5 patients with chronic SUNCT. METHODS: Retrospective review of our GKRS database identified 5 patients with chronic SUNCT who underwent GKRS targeted to the trigeminal nerve and SPG. A maximum dose of 80-85 Gy and 80 Gy was, respectively, delivered to the trigeminal nerve and SPG. Pain intensity and facial numbness were evaluated using the Barrow Neurological Institute (BNI) scores. RESULTS: These 5 patients were clinically followed for a mean period of 26.2 months. Within a period ranging from 2 days to 9 months, GKRS was successful in reducing pain attacks and autonomic symptoms in all 5 patients. At the last assessments, BNI pain scores of I, II, and IIIa were achieved in 1, 1, and 3 patients, respectively. Two patients developed nonbothersome facial numbness (BNI facial numbness score II). CONCLUSIONS: These 5 cases show that GKRS targeted to both the trigeminal nerve and the SPG is effective in reducing pain and autonomic symptoms of patients with SUNCT, although nonbothersome trigeminal sensory disturbances may occur.

Radiation necrosis in renal cell carcinoma brain metastases treated with checkpoint inhibitors and radiosurgery: An international multicenter study.

BACKGROUND: Patients with renal cell carcinoma (RCC) brain metastases are frequently treated with immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS). However, data reporting on the risk of developing radiation necrosis (RN) are limited. METHODS: RN rates were compared for concurrent therapy (ICI/SRS administration within 4 weeks of one another) and nonconcurrent therapy with the χ2 test. Univariable logistic regression was used to identify factors associated with developing RN. RESULTS: Fifty patients (23 concurrent and 27 nonconcurrent) with 395 brain metastases were analyzed. The median follow-up was 12.1 months; the median age was 65 years. The median margin dose was 20 Gy, and 4% underwent prior whole-brain radiation therapy (WBRT). The median treated tumor volume was 3.32 cm3 (range, 0.06-42.38 cm3 ); the median volume of normal brain tissue receiving a dose of 12 Gy or higher (V12 Gy) was 8.42 cm3 (range, 0.27-111.22 cm3 ). Any-grade RN occurred in 17.4% and 22.2% in the concurrent and nonconcurrent groups, respectively (P = .67). Symptomatic RN occurred in 4.3% and 14.8% in the concurrent and nonconcurrent groups, respectively (P = .23). Increased tumor volume during SRS (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.01-1.19; P = .04) was associated with developing RN, although V12 Gy (OR, 1.03; 95% CI, 0.99-1.06; P = .06), concurrent therapy (OR, 0.74; 95% CI, 0.17-2.30; P = .76), prior WBRT, and ICI agents were not statistically significant. CONCLUSIONS: Symptomatic RN occurs in a minority of patients with RCC brain metastases treated with ICI/SRS. The majority of events were grade 1 to 3 and were managed medically. Concurrent ICI/SRS does not appear to increase this risk. Attempts to improve dose conformality (reduce V12) may be the most successful mitigation strategy in single-fraction SRS.

Medial thalamotomy using stereotactic radiosurgery for intractable pain: a systematic review.

Medial thalamotomy using stereotactic radiosurgery (SRS) is a potential treatment for intractable pain. However, the ideal treatment parameters and expected outcomes from this procedure remain unclear. The aim of this systematic review is to provide further insights on medial thalamotomy using SRS, specifically for intractable pain. A systematic review was performed to identify all clinical articles discussing medial thalamotomy using SRS for intractable pain. Only studies in which SRS was used to target the medial thalamus for pain were included. For centers with multiple publications, care was taken to avoid recounting individual patients. The literature review revealed six studies describing outcomes of medial thalamotomy using SRS for a total of 125 patients (118 included in the outcome analysis). Fifty-two patients were treated for cancer pain across three studies, whereas five studies included 73 patients who were treated for nonmalignant pain. The individual studies demonstrated initial meaningful pain reduction in 43.3-100% of patients, with an aggregate initial meaningful pain reduction in 65 patients (55%) following SRS medial thalamotomy. This effect persisted in 45 patients (38%) at the last follow-up. Adverse events were observed in six patients (5%), which were related to radiation in five patients (4%). Medial thalamotomy using SRS is effective for select patients with treatment-resistant pain and is remarkably safe when modern radiation delivery platforms are used. More posteriorly placed lesions within the medial thalamus were associated with better pain relief. More studies are warranted to shed light on differences in patient responses.

Stereotactic radiosurgery for clinoid meningiomas: a multi-institutional study.

PURPOSE: Resection of clinoid meningiomas can be associated with significant morbidity. Experience with stereotactic radiosurgery (SRS) for clinoid meningiomas remains limited. We studied the safety and effectiveness of SRS for clinoid meningiomas. METHODS: From twelve institutions participating in the International Radiosurgery Research Foundation, we pooled patients treated with SRS for radiologically suspected or histologically confirmed WHO grade I clinoid meningiomas. RESULTS: Two hundred seven patients (median age: 56 years) underwent SRS for clinoid meningiomas. Median treatment volume was 8.02 cm3, and 87% of tumors were immediately adjacent to the optic apparatus. The median tumor prescription dose was 12 Gy, and the median maximal dose to the anterior optic apparatus was 8.5 Gy. During a median post-SRS imaging follow-up of 51.1 months, 7% of patients experienced tumor progression. Greater margin SRS dose (HR = 0.700, p = 0.007) and pre-SRS radiotherapy (HR = 0.004, p < 0.001) were independent predictors of better tumor control. During median visual follow-up of 48 months, visual function declined in 8% of patients. Pre-SRS visual deficit (HR = 2.938, p = 0.048) and maximal radiation dose to the optic apparatus of ≥ 10 Gy (HR = 11.297, p = 0.02) independently predicted greater risk of post-SRS visual decline. Four patients experienced new post-SRS cranial nerve V neuropathy. CONCLUSIONS: SRS allows durable control of clinoid meningiomas and visual preservation in the majority of patients. Greater radiosurgical prescription dose is associated with better tumor control. Radiation dose to the optic apparatus of ≥ 10 Gy and visual impairment before the SRS increase risk of visual deterioration.

Clinical and Imaging Outcomes After Trigeminal Schwannoma Radiosurgery: Results From a Multicenter, International Cohort Study.

BACKGROUND AND OBJECTIVES: An international, multicenter, retrospective study was conducted to evaluate the long-term clinical outcomes and tumor control rates after stereotactic radiosurgery (SRS) for trigeminal schwannoma. METHODS: Patient data (N = 309) were collected from 14 international radiosurgery centers. The median patient age was 50 years (range 11-87 years). Sixty patients (19%) had prior resections. Abnormal facial sensation was the commonest complaint (49%). The anatomic locations were root (N = 40), ganglion (N = 141), or dumbbell type (N = 128). The median tumor volume was 4 cc (range, 0.2-30.1 cc), and median margin dose was 13 Gy (range, 10-20 Gy). Factors associated with tumor control, symptom improvement, and adverse radiation events were assessed. RESULTS: The median and mean time to last follow-up was 49 and 65 months (range 6-242 months). Greater than 5-year follow-up was available for 139 patients (45%), and 50 patients (16%) had longer than 10-year follow-up. The overall tumor control rate was 94.5%. Tumors regressed in 146 patients (47.2%), remained unchanged in 128 patients (41.4%), and stabilized after initial expansion in 20 patients (6.5%). Progression-free survival rates at 3 years, 5 years, and 10 years were 91%, 86%, and 80 %. Smaller tumor volume (less than 8 cc) was associated with significantly better progression-free survival ( P = .02). Seventeen patients with sustained growth underwent further intervention at a median of 27 months (3-144 months). Symptom improvement was noted in 140 patients (45%) at a median of 7 months. In multivariate analysis primary, SRS ( P = .003) and smaller tumor volume ( P = .01) were associated with better symptom improvement. Adverse radiation events were documented in 29 patients (9%). CONCLUSION: SRS was associated with long-term freedom (10 year) from additional management in 80% of patients. SRS proved to be a valuable salvage option after resection. When used as a primary management for smaller volume tumors, both clinical improvement and prevention of new deficits were optimized.

Radiosurgery of limited brain metastases from primary solid tumor: results of the randomized phase III trial (NCT02355613) comparing treatments executed with a specialized or a C-arm linac-based platform.

BACKGROUND: Comparative prospective data regarding different radiosurgery (SRS) modalities for treating brain metastases (BMs) from solid tumors are not available. To investigate with a single institute phase III randomized trial whether SRS executed with linac (Arm-B) is superior to a dedicated multi-source gamma-ray stereotactic platform (Arm-A). METHODS: Adults patients with 1-4 BMs from solid tumors up to 30 mm in maximum diameter were randomly assigned to arms A and B. The primary endpoint was cumulative incidence of symptomatic (grade 2-3) radionecrosis (CIRN). Secondary endpoints were local progression cumulative incidence (CILP), distant brain failure, disease-free survival (DFS), and overall survival (OS). RESULTS: A total of 251 patients were randomly assigned to Arm-A (121) or Arm-B (130). The 1-year RN cumulative incidence was 6.7% in whole cohort, 3.8% (95% CI 1.9-7.4%) in Arm-B, and 9.3% (95% CI 6.2-13.8%) in the Arm-A (p = 0.43). CIRN was influenced by target volume irradiated only for the Arm-A (p << 0.001; HR 1.36 [95% CI 1.25-1.48]). Symptomatic RN occurred in 56 cases at a median time of 10.3 months (range 1.15-54.8 months), 27 in the Arm-B at a median time of 15.9 months (range 4.9-54.8 months), and 29 in the Arm-A at a median time of 6.9 months (1.2-32.3 months), without statistically significant differences between the two arms. No statistically significant differences were recorded between the two arms in CILP, BDF, DFS or OS. The mean beam-on time to deliver SRS was 49.0 ± 36.2 min in Arm-A, and 3.1 ± 1.6 min in Arm-B. CONCLUSIONS: Given the technical differences between the treatment platforms investigated in this single-institution study, linac-based SRS (Arm-B) did not lead to significantly lower grade 2-3 RN rates versus the multi-source gamma-ray system (Arm-A) in a population of patients with limited brain metastases of small volume. No significant difference in local control was observed between both arms. For Arm-B, the treatment delivery time was significantly lower than for Arm-A. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02355613.

The lumbar adjacent-level syndrome: analysis of clinical, radiological, and surgical parameters in a large single-center series.

OBJECTIVE: The development of specific clinical and neurological symptoms and radiological degeneration affecting the segment adjacent to a spinal arthrodesis comprise the framework of adjacent-level syndrome. Through the analysis of a large surgical series, this study aimed to identify possible demographic, clinical, radiological, and surgical risk factors involved in the development of adjacent-level syndrome. METHODS: A single-center retrospective analysis of adult patients undergoing lumbar fusion procedures between January 2014 and December 2018 was performed. Clinical, demographic, radiological, and surgical data were collected. Patients who underwent surgery for adjacent-segment disease (ASD) were classified as the ASD group. All patients were evaluated 1 month after the surgical procedure clinically and radiologically (with lumbar radiographs) and 3 months afterward with CT scans. The last follow-up was performed by telephone interview. The median follow-up for patients included in the analysis was 67.2 months (range 39-98 months). RESULTS: A total of 902 patients were included in this study. Forty-nine (5.4%) patients required reoperation for ASD. A significantly higher BMI value was observed in the ASD group (p < 0.001). Microdiscectomy and microdecompression procedures performed at the upper or lower level of an arthrodesis without fusion extension have a statistically significant impact on the development of ASD (p = 0.001). Postoperative pelvic tilt in the ASD group was higher than in the non-ASD group. Numeric rating scale, Core Outcome Measures Index, and Oswestry Disability Index scores at the last follow-up were significantly higher in patients in the ASD group and in patients younger than 65 years. CONCLUSIONS: Identifying risk factors for the development of adjacent-level syndrome allows the implementation of a prevention strategy in patients undergoing lumbar arthrodesis surgery. Age older than 65 years, high BMI, preexisting disc degeneration at the adjacent level, and high postoperative pelvic tilt are the most relevant factors. In addition, patients older than 65 years achieve higher levels of clinical improvement and postsurgical satisfaction than do younger patients.

Imaging-defined necrosis after treatment with single-fraction stereotactic radiosurgery and immune checkpoint inhibitors and its potential association with improved outcomes in patients with brain metastases: an international multicenter study of 697 patients.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS) are commonly utilized in the management of brain metastases. Treatment-related imaging changes (TRICs) are a frequently observed clinical manifestation and are commonly classified as imaging-defined radiation necrosis. However, these findings are not well characterized and may predict a response to SRS and ICIs. The objective of this study was to investigate predictors of TRICs and their impact on patient survival. METHODS: This retrospective multicenter cohort study was conducted through the International Radiosurgery Research Foundation. Member institutions submitted de-identified clinical and dosimetric data for patients with non-small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC) brain metastases that had been treated with SRS and ICIs. Data were collected from March 2020 to February 2021. Univariable and multivariable Cox and logistic regression analyses were performed. The Kaplan-Meier method was used to evaluate overall survival (OS). The diagnosis-specific graded prognostic assessment was used to guide variable selection. TRICs were determined on the basis of MRI, PET/CT, or MR spectroscopy, and consensus by local clinical providers was required. RESULTS: The analysis included 697 patients with 4536 brain metastases across 11 international institutions in 4 countries. The median follow-up after SRS was 13.6 months. The median age was 66 years (IQR 58-73 years), 54.1% of patients were male, and 57.3%, 36.3%, and 6.4% of tumors were NSCLC, melanoma, and RCC, respectively. All patients had undergone single-fraction radiosurgery to a median margin dose of 20 Gy (IQR 18-20 Gy). TRICs were observed in 9.8% of patients. The median OS for all patients was 24.5 months. On univariable analysis, Karnofsky Performance Status (KPS; HR 0.98, p < 0.001), TRICs (HR 0.67, p = 0.03), female sex (HR 0.67, p < 0.001), and prior resection (HR 0.60, p = 0.03) were associated with improved OS. On multivariable analysis, KPS (HR 0.98, p < 0.001) and TRICs (HR 0.66, p = 0.03) were associated with improved OS. A brain volume receiving ≥ 12 Gy of radiation (V12Gy) ≥ 10 cm3 (OR 2.78, p < 0.001), prior whole-brain radiation therapy (OR 3.46, p = 0.006), and RCC histology (OR 3.10, p = 0.01) were associated with an increased probability of developing TRICs. The median OS rates in patients with and without TRICs were 29.0 and 23.1 months, respectively (p = 0.03, log-rank test). CONCLUSIONS: TRICs following ICI and SRS were associated with a median OS benefit of approximately 6 months in this retrospective multicenter study. Further prospective study and additional stratification are needed to validate these findings and further elucidate the role and etiology of this common clinical scenario.

Concurrent Administration of Immune Checkpoint Inhibitors and Single Fraction Stereotactic Radiosurgery in Patients With Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma Brain Metastases.

PURPOSE: Stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) are highly effective treatments for brain metastases, particularly when these therapies are administered concurrently. However, there are limited data reporting the risk of radiation necrosis (RN) in this setting. METHODS AND MATERIALS: Patients with brain metastases from primary non-small cell lung cancer, renal cell carcinoma, or melanoma treated with SRS and ICI were considered. Time-to-event analyses were conducted for any grade RN and symptomatic RN (SRN) with death incorporated as a competing risk. As a secondary analysis, recursive partitioning analysis (RPA) was used for model development, and a loop of potential models was analyzed, with the highest-fidelity model selected. Brain V12 Gy thresholds identified on RPA were then incorporated into the competing risks analysis. Concurrent SRS and ICI administration. RESULTS: Six hundred fifty-seven patients with 4182 brain metastases across 11 international institutions were analyzed. The median follow-up for all patients was 13.4 months. The median follow-up was 12.8 months and 14.1 months for the concurrent and nonconcurrent groups, respectively (P = .03). The median patient age was 66 years, and the median Karnofsky Performance Status was 90. In patients with any grade RN, 1- and 2-year rates were 6.4% and 9.9%, respectively. In patients with SRN, 1- and 2-year rates were 4.8% and 7.2%, respectively. On RPA, the highest-fidelity models consistently identified V12 Gy as the dominant variable predictive of RN. Three risk groups were identified by V12 Gy: (1) < 12 cm3; (2) 20 cm3 ≥ V12 Gy ≥ 12 cm3; (3) V12 Gy > 20 cm3. In patients with any grade RN, 1-year rates were 3.7% (V12 Gy < 12 cm3), 10.3% (20 cm3 ≥ V12 Gy ≥ 12 cm3), and 12.6% (V12 Gy > 20 cm3); the 2-year rates were 7.5% (V12 Gy < 12 cm3), 13.8% (20 cm3 ≥ V12 Gy ≥ 12 cm3), and 15.4% (V12 Gy > 20 cm3) (P < 0.001). In patients with any SRN, 1-year rates were 2.4% (V12 Gy < 12 cm3), 8.9% (20 cm3 ≥ V12 Gy ≥ 12 cm3), and 10.3% (V12 Gy > 20 cm3); the 2-year rates were 4.4% (V12 Gy < 12 cm3), 12.4% (20 cm3 ≥ V12 Gy ≥ 12 cm3), and 13.1% (V12 Gy > 20 cm3; P < 0.001). There were no statistically significant differences in rates of any grade RN or SRN when accounting for therapy timing for all patients and by V12 risk group identified on RPA. CONCLUSIONS: The use of SRS and ICI results in a low risk of any grade RN and SRN. This risk is not increased with concurrent administration. Therefore, ICI can safely be administered within 4-weeks of SRS. Three risk groups based on V12 Gy were identified, which clinicians may consider to further reduce rates of RN.

Assessment of prognostic factors in patients with metastatic epidural spinal cord compression (MESCC) from solid tumor after surgery plus radiotherapy: a single institution experience.

PURPOSE: To identify potential prognostic factors predicting functional outcome and survival after surgery followed by radiotherapy for metastatic spinal cord compression due to solid tumors. METHODS: 531 consecutive patients with metastatic epidural spinal cord compression (MESCC) were treated at our institution. Surgery followed by radiation therapy was performed in 151 patients (30%) with various histological diagnoses. Three different surgical procedures were performed: minimal resection with or without instrumented fixation, curettage, and total tumorectomy. Within 1 month after surgery, RT was performed, delivering a total dose of 30-36 Gy (3 Gy per fraction). Ten potential prognostic factors were investigated for relationship with functional outcome and survival. RESULTS: Clinical remission of pain was obtained in 91% of patients and 94 (62.5%) had recovery of neurological deficit. Recurrence in the same site of treatment occurred in nine (6%) patients. Median survival was 14 months (range 0-52 months); OS at 1, 2, and 3 years was 43.6, 37, and 21.5%, respectively. Survival was significantly associated with the histology of primary tumor (P < 0.001) and visceral metastases (P < 0.001) in the whole group; for histology, the prognostic factors statistically significant were other bone metastases in breast cancer, control of primary tumor, and the absence of visceral metastases in NSCLC and kind of surgery in the other. CONCLUSIONS: The key element for successful treatment of MESCC is multidisciplinary care of the patient, which includes all of those prognostic factors that have been, until now, analyzed and compared. In our set of patients treated for vertebral metastases, PS, time to development of symptoms, and the presence of visceral metastases affected functional outcome and survival.

Clinical and radiologic outcomes after stereotactic radiosurgery for meningiomas in direct contact with the optic apparatus: an international multicenter study.

OBJECTIVE: Resection of meningiomas in direct contact with the anterior optic apparatus carries risk of injury to the visual pathway. Stereotactic radiosurgery (SRS) offers a minimally invasive alternative. However, its use is limited owing to the risk of radiation-induced optic neuropathy. Few SRS studies have specifically assessed the risks and benefits of treating meningiomas in direct contact with the optic nerve, chiasm, or optic tract. The authors hypothesized that SRS is safe for select patients with meningiomas in direct contact with the anterior optic apparatus. METHODS: The authors performed an international multicenter retrospective analysis of 328 patients across 11 institutions. All patients had meningiomas in direct contract with the optic apparatus. Patients were followed for a median duration of 56 months after SRS. Neurological examinations, including visual function evaluations, were performed at follow-up visits. Clinical and treatment variables were collected at each site according to protocol. Tumor volumes were assessed with serial MR imaging. Variables predictive of visual deficit were identified using univariable and multivariable logistic regression. RESULTS: SRS was the initial treatment modality for 64.6% of patients, and 93% of patients received SRS as a single fraction. Visual information was available for 302 patients. Of these patients, visual decline occurred in 29 patients (9.6%), of whom 12 (41.4%) had evidence of tumor progression. Visual decline in the remaining 17 patients (5.6%) was not associated with tumor progression. Pre-SRS Karnofsky Performance Status predicted visual decline in adjusted analysis (adjusted OR 0.9, 95% CI 0.9-1.0, p < 0.01). Follow-up imaging data were available for 322 patients. Of these patients, 294 patients (91.3%) had radiographic evidence of stability or tumor regression at last follow up. Symptom duration was associated with tumor progression in adjusted analysis (adjusted OR 1.01, adjusted 95% CI 1.0-1.02, adjusted p = 0.02). CONCLUSIONS: In this international multicenter study, the vast majority of patients exhibited tumor control and preservation of visual function when SRS was used to treat meningioma in direct contact with the anterior optic pathways. SRS is a relatively safe treatment modality for select patients with perioptic meningiomas in direct contact with the optic apparatus.

Concurrent Administration of Immune Checkpoint Inhibitors and Stereotactic Radiosurgery Is Well-Tolerated in Patients With Melanoma Brain Metastases: An International Multicenter Study of 203 Patients.

BACKGROUND: Melanoma brain metastases are commonly treated with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs). However, the toxicity of these 2 treatments is largely unknown when administered concurrently. OBJECTIVE: To evaluate the risk of radiation necrosis (RN) with concurrent and nonconcurrent SRS and ICIs. METHODS: The guidelines from the Strengthening the Reporting of Observational Studies in Epidemiology checklist were used. Inverse probability of treatment weighting, univariable and multivariable logistic regression, and the Kaplan-Meier method was utilized. RESULTS: There were 203 patients with 1388 brain metastases across 11 international institutions in 4 countries with a median follow-up of 15.6 months. The rates of symptomatic RN were 9.4% and 8.2% in the concurrent and nonconcurrent groups, respectively ( P =.766). On multivariable logistic regression, V12 ≥ 10 cm 3 (odds ratio [OR]: 2.76; P =.006) and presence of BRAF mutation (OR: 2.20; P =.040) were associated with an increased risk of developing symptomatic RN; the use of concurrent over nonconcurrent therapy was not associated with an increased risk (OR: 1.06; P =.877). There were 20 grade 3 toxic events reported, and no grade 4 events reported. One patient experienced a grade 5 intracranial hemorrhage. The median overall survival was 36.1 and 19.8 months for the concurrent and nonconcurrent groups (log-rank P =.051), respectively. CONCLUSION: Concurrent administration of ICIs and SRS are not associated with an increased risk of RN. Tumors harboring BRAF mutation, or perhaps prior exposure to targeted agents, may increase this risk. Radiosurgical optimization to maintain V12 < 10 cm 3 is a potential strategy to reduce the risk of RN.

Dose to neuroanatomical structures surrounding pituitary adenomas and the effect of stereotactic radiosurgery on neuroendocrine function: an international multicenter study.

OBJECTIVE: Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS: This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes. RESULTS: The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17-2.68, p = 0.006). CONCLUSIONS: SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.

Gamma Knife Radiosurgery for the Treatment of Trigeminal Neuralgia in Patients with Multiple Sclerosis: A Single-Center Retrospective Study and Literature Review.

OBJECTIVE: Trigeminal neuralgia (TN) in patients with multiple sclerosis (MS) is a challenging condition to manage that is treated with Gamma Knife radiosurgery (GKRS). The aim of this report is to assess the safety, efficacy, and durability of GKRS for the treatment of TN in patients with MS. Our findings are compared with those of the existing literature and discussed. METHODS: We retrospectively reviewed all patients at our institution who underwent GKRS for the treatment of TN secondary to MS and had 1 or more years of follow-up. Preoperative and postoperative pain intensities and facial numbness were evaluated with the Barrow Neurological Institute scores. Durability of successful pain relief was statistically evaluated with Kaplan-Meier analysis. The prognostic role of perioperative factors was investigated and analyzed using Cox proportional hazards regression. RESULTS: There were 29 patients with MS-TN who underwent GKRS at our institution. Two patients underwent bilateral treatment. Four patients underwent repeat GKRS for pain recurrence. The median period of follow-up assessment was 33 months. Rates of reasonable pain reduction at 1, 3, and 5 years were 70%, 57%, and 57% respectively. All patients who underwent repeat GKRS had durable pain reduction. No prognostic factor for successful pain reduction was found. CONCLUSIONS: Our study shows that GKRS for the treatment of TN secondary to MS is a safe and effective procedure in controlling pain in the short term but often fails to provide long-term pain control. GKRS can be safely repeated to prolong the time of pain reduction.

Stereotactic Radiosurgery for Perioptic Meningiomas: An International, Multicenter Study.

BACKGROUND: Stereotactic radiosurgery (SRS) is increasingly used for management of perioptic meningiomas. OBJECTIVE: To study the safety and effectiveness of SRS for perioptic meningiomas. METHODS: From 12 institutions participating in the International Radiosurgery Research Foundation (IRRF), we retrospectively assessed treatment parameters and outcomes following SRS for meningiomas located within 3 mm of the optic apparatus. RESULTS: A total of 438 patients (median age 51 yr) underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) perioptic meningiomas. Median treatment volume was 8.01 cm3. Median prescription dose was 12 Gy, and median dose to the optic apparatus was 8.50 Gy. A total of 405 patients (93%) underwent single-fraction SRS and 33 patients (7%) underwent hypofractionated SRS. During median imaging follow-up of 55.6 mo (range: 3.15-239 mo), 33 (8%) patients experienced tumor progression. Actuarial 5-yr and 10-yr progression-free survival was 96% and 89%, respectively. Prescription dose of ≥12 Gy (HR: 0.310; 95% CI [0.141-0.679], P = .003) and single-fraction SRS (HR: 0.078; 95% CI [0.016-0.395], P = .002) were associated with improved tumor control. A total of 31 (10%) patients experienced visual decline, with actuarial 5-yr and 10-yr post-SRS visual decline rates of 9% and 21%, respectively. Maximum dose to the optic apparatus ≥10 Gy (HR = 2.370; 95% CI [1.086-5.172], P = .03) and tumor progression (HR = 4.340; 95% CI [2.070-9.097], P < .001) were independent predictors of post-SRS visual decline. CONCLUSION: SRS provides durable tumor control and quite acceptable rates of vision preservation in perioptic meningiomas. Margin dose of ≥12 Gy is associated with improved tumor control, while a dose to the optic apparatus of ≥10 Gy and tumor progression are associated with post-SRS visual decline.

Stereotactic Radiosurgery for Olfactory Groove Meningiomas: An International, Multicenter Study.

BACKGROUND: Stereotactic radiosurgery (SRS) is increasingly considered for selected olfactory groove meningiomas (OGMs). OBJECTIVE: To investigate the safety and efficacy of SRS for OGMs. METHODS: From 20 institutions participating in the International Radiosurgery Research Foundation, we pooled patients who underwent SRS for histologically confirmed or radiologically suspected WHO grade I OGMs and were followed for 6 mo or more after the SRS. RESULTS: In total, 278 (median age 57 yr) patients underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) WHO grade I OGMs Median treatment volume was 4.60 cm3 (range: 0.12-27.3 cm3), median prescription dose was 12 Gy, and median dose to the olfactory nerve was 11.20 Gy. During median post-SRS imaging follow-up of 39 mo (range: 6-240 mo), 43% of patients had partial or marginal response, 54% of patients had stable disease, and 3% of patients experienced progression. During median post-SRS clinical follow-up of 51 mo (range: 6-240 mo), 36 (13%) patients experienced clinical and/or radiological adverse radiation events (AREs). Elevated risk of AREs was associated with larger OGM volume (P = .009) and pre-SRS peritumoral T2/fluid-attenuated inversion-recovery signal abnormalities (P < .001). After the SRS, olfaction remained stable, improved, or deteriorated in 90%, 8%, and 2% of patients, respectively. Complete post-SRS anosmia was predicted by partial/complete anosmia before the SRS (odds ratio [OR] = 83.125; 95% CI [24.589-281.01], P < .001) and prior resection of OGM (OR = 3.919; 95% CI [1.713-8.970], P = .001). CONCLUSION: SRS is associated with durable local control of the majority of OGM patients with acceptable safety profile. SRS allows preservation or improvement of olfactory function in the majority of OGM patients.

Gamma Knife central lateral thalamotomy for the treatment of neuropathic pain.

OBJECTIVE: The goal of this study was to assess the safety and efficacy of stereotactic central lateral thalamotomy with Gamma Knife radiosurgery in patients with neuropathic pain. METHODS: Clinical and radiosurgical data were prospectively collected and analyzed in patients with neuropathic pain who underwent Gamma Knife central lateral thalamotomy. The safety and efficacy of the lesioning procedure were evaluated by neurological examination and standardized scales for pain intensity and health-related quality of life. Visual analog scale (VAS) for pain, McGill Pain Questionnaire (MPQ), EuroQol-5 dimensions (EQ-5D), and the 36-Item Short Form Health Survey, version 2 (SF-36v2) were measured during baseline and postoperative follow-up evaluations at 3, 6, 12, 24, and 36 months. RESULTS: Eight patients with neuropathic pain underwent Gamma Knife central lateral thalamotomy. Four patients suffered from trigeminal deafferentation pain, 2 from brachial plexus injury, 1 from central poststroke facial neuropathic pain, and 1 from postherpetic neuralgia. No lesioning-related adverse effect was recorded during the follow-up periods. All patients had pain reduction following thalamotomy. The mean follow-up time was 24 months. At the last follow-up visits, 5 patients reported ≥ 50% VAS pain reduction. The overall mean VAS pain score was 9.4 (range 8-10) before radiosurgery. After 1 year, the mean VAS pain score decreased significantly, from 9.4 (range 8-10) to 5.5 (mean -41.33%, p = 0.01). MPQ scores significantly decreased (mean -22.18%, p = 0.014). Statistically significant improvements of the SF-36v2 quality of life survey (mean +48.16%, p = 0.012) and EQ-5D (+45.16%, p = 0.012) were observed. At 2 years after radiosurgery, the VAS pain score remained significantly reduced to a mean value of 5.5 (p = 0.027). Statistically significant improvements were also observed for the MPQ (mean -16.05%, p = 0.034); the EQ-5D (mean +35.48%, p = 0.028); and the SF-36v2 (mean +35.84%, p = 0.043). At the last follow-up visits, pain had recurred in 2 patients, who were suffering from central poststroke neuropathic pain and brachial plexus injury, respectively. CONCLUSIONS: Safe, nonpharmacological therapies are imperative for the management of refectory chronic pain conditions. The present series demonstrates that Gamma Knife central lateral thalamotomy is safe and potentially effective in the long term for relieving chronic neuropathic pain refractory to pharmacotherapy and for restoring quality of life.

Gamma Knife Radiosurgery for Short Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing (SUNCT) Syndrome: Targeting the Trigeminal Nerve and the Sphenopalatine Ganglion. Case Report and Literature Review.

BACKGROUND: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a primary headache syndrome with an unclear pathogenesis, and only in very few cases, SUNCT is secondary to known lesions (secondary SUNCT). Several pharmacological as well as interventional and invasive treatments have been used to treat SUNT cases, with no definitive results. We describe a patient with idiopathic SUNCT syndrome, successfully treated with gamma knife radiosurgery and we report a review of the cases of the literature treated with radiosurgery. CASE REPORT: A 63-year-old woman complained of episodes of intense and regular paroxysmal facial pain in the territory of the maxillary branch of the trigeminal nerve accompanied by inflammation of conjunctiva and involuntary lacrimation from 2006. During the following years, she received several treatments: combination of drugs, acupuncture, and endonasal infiltration of the sphenopalatine ganglion. The frequency of the painful attacks increased progressively and it was impossible for her to have a normal active life. Combined gamma knife radiosurgery treatment, targeting the trigeminal nerve (80 Gy maximum dose) and the sphenopalatine ganglion (80 Gy maximum dose) was performed in April 2016 (visual analog score before treatment = 6). Pain gradually reduced in the following months, as well as frequency and severity of the attacks. No sensory deficit developed. The follow-up length of our patient is 37 months: she is nearly pain free (visual analog score = 2) and has resumed a normal life. CONCLUSIONS: Patients with idiopathic SUNCT have few therapeutic options. Our case demonstrates that gamma knife radiosurgery is a feasible and effective noninvasive option to treat patients with medically refractory idiopathic SUNCT.