Repeat Gamma Knife radiosurgery for recurrent trigeminal neuralgia in patients with multiple sclerosis: a single-center retrospective study.

PURPOSE: Gamma Knife radiosurgery (GKRS) has emerged as an effective treatment option for trigeminal neuralgia (TN) in patients with multiple sclerosis (MS). To date, the outcomes of repeat GKRS for patients with TN and MS with recurrent pain have been investigated in a few patients. This study aims to report the outcomes and predictive factors of pain reduction for MS patients undergoing repeat GKRS for recurrent TN. METHODS: Eighteen patients with MS underwent repeat GKRS for recurrent TN. A retrospective chart review and telephone interviews were conducted to determine background medical history, dosimetric data, and outcomes of the procedure. Facial pain and sensory function were evaluated using the Barrow Neurological Institute (BNI) scales. RESULTS: Fifteen patients achieved a BNI pain score of IIIa or better, indicating pain reduction, within a median period of 21 days after repeat GKRS. The maximum dose for repeat GKRS ranged from 70 to 85 Gy. Pain recurred in 5 patients after a median period of 12 months after GKRS. Percentages of patients with pain reduction at 1, 2, 3, 5, and 7 years were 60%, 60%, 50%, 50%, and 50%, respectively. Older age at repeat GKRS predicted sustained pain reduction (P = 0.01). Seven patients developed facial sensory disturbances, which were bothersome in two patients. CONCLUSIONS: Repeat GKRS may be used as an effective treatment modality for prolonging the duration of pain reduction time in patients with MS and TN. After repeat GKRS, facial sensory disturbances are common; however, they are often not bothersome.

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.

Staged Gamma Knife radiosurgery for a rosette-forming glioneuronal tumor of the fourth ventricle: a case report.

BACKGROUND: Rosette-forming glioneuronal tumor (RGNT) is a rare slow-growing neoplasm with mixed glial and neurocytic components. Surgical resection is the mainstay of treatment, whereas the role of adjuvant radiation therapies for residual or recurrent tumors has been poorly investigated. CASE PRESENTATION: We describe the case of a patient with a recurrent fourth ventricular RGNT who was treated with two-staged Gamma Knife radiosurgery (GKRS). GKRS was effective in controlling tumor growth and safe up to seven years from treatment. CONCLUSIONS: This case suggests that GKRS may be a safe and effective treatment for patients with recurrent or residual RGNT.

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.

Gamma Knife radiosurgery for the treatment of cluster headache: a systematic review.

Cluster headache (CH) is a severe trigeminal autonomic cephalalgia that, when refractory to medical treatment, can be treated with Gamma Knife radiosurgery (GKRS). The outcomes of studies investigating GKRS for CH in the literature are inconsistent, and the ideal target and treatment parameters remain unclear. The aim of this systematic review is to evaluate the safety and the efficacy, both short and long term, of GKRS for the treatment of drug-resistant CH. A systematic review of the literature was performed to identify all clinical articles discussing GKRS for the treatment of CH. The literature review revealed 5 studies describing outcomes of GKRS for the treatment of CH for a total of 52 patients (48 included in the outcome analysis). The trigeminal nerve, the sphenopalatine ganglion, and a combination of both were treated in 34, 1, and 13 patients. The individual studies demonstrated initial meaningful pain reduction in 60-100% of patients, with an aggregate initial meaningful pain reduction in 37 patients (77%). This effect persisted in 20 patients (42%) at last follow-up. Trigeminal sensory disturbances were observed in 28 patients (58%) and deafferentation pain in 3 patients (6%). Information related to GKRS for CH are limited to few small open-label studies using heterogeneous operative techniques. In this setting, short-term pain reduction rates are high, whereas the long-term results are controversial. GKRS targeted on the trigeminal nerve or sphenopalatine ganglion is associated to a frequent risk of trigeminal disturbances and possibly deafferentation pain.

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.

Neurosurgery during the Greco-Italian War (World War II): the management of war-related head injuries at the Italian field hospital of Sinanaj in Albania.

During the Greco-Italian War (World War II [WWII], 1940-1941), an Italian field hospital was set up in Sinanaj, Albania. The hospital's military surgeons carefully collected information about the characteristics and management of patients with war-related injuries. In 1942, they published a detailed report, with a section dedicated to the management of war-related head injuries. The aim of this report is to analyze that section, to describe the characteristics and neurosurgical management of war-related head injuries, and to depict the status of war neurosurgery in the Royal Italian Army during WWII. The analysis revealed that, during the Greco-Italian War (November 1940-April 1941), 149 patients with war-related head injuries were admitted to the Sinanaj hospital, and 48 patients underwent surgery. Head injuries were caused by bomb fragments in 126 patients, bullets in 5 patients, and other causes (falls from height, vehicle accidents, or rock fragments) in 18 patients. Six patients (12.5%) died after surgery. Before surgery, patients underwent resuscitation with blood transfusions and fluid. Preoperatively, a plain head radiograph was usually acquired to locate metallic and bone fragments. The surgical technique consisted of craniotomy or craniectomy, aggressive debridement of metallic and bone fragments, and watertight dural closure. Surgical drainage, overall aseptic technique, serial spinal taps, and perioperative antibiotics were used to prevent infections. The surgical aims and technique used by the Italian surgeons for the management of head injuries were similar to those of the Allied surgeons during WWII. Operative mortality was also comparable. Although the surgical technique for war-related head injuries has evolved since WWII, many aspects of the technique used by the Italian and Allied surgeons during WWII are still in the standard of care today.

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.

Preliminary results of contrast-enhanced sonography in the evaluation of the response of uveal melanoma to gamma-knife radiosurgery.

PURPOSE: Our aim was to prospectively analyze the use of contrast-enhanced ultrasound (CEUS) in the quantitative assessment of the response of uveal melanoma (UM) to gamma-knife radiosurgery (GKR), investigating whether changes in tumor vascularization precede thickness reduction, which on average occurs at 12 months after GKR. METHODS: Ten patients with UM treated with GKR underwent sonography (US) and CEUS at baseline and at 3, 6, and 12 months after GKR. The transverse diameter, thickness, and quantitative parameters of the UM (ie, area under the curve in the wash-in phase, wash-in perfusion index, peak enhancement, and wash-in rate) were calculated by using dedicated software and compared by using Wilcoxon's signed-rank test. RESULTS: The mean tumor thickness on US was significantly less at both 6 (6.6 mm) and 12 months after GKR (5.8 mm) than it was at baseline (8.3 mm; p < 0.05, both comparisons). Compared with baseline data, the median flow quantitative parameters on CEUS were significantly changed as follows: the peak enhancement (in arbitrary units [au]) at baseline was 5 × 10(6) ; 6 months after GKR, it was 2 × 10(1) (p < 0.05), and 12 months after GKR, it was 4 × 10(1) (p < 0.05). The wash-in rate (in au) at baseline was 1 × 10(6) ; 6 months after GKR, it was 2.1 (p < 0.05), and 12 months after GKR, it was 9.3 (p < 0.05). The wash-in perfusion index (in au) at baseline was 2 × 10(7) ; 6 months after GKR, it was 7 × 10(1) (p < 0.05), and 12 months after GKR, it was 1 × 10(2) (p < 0.05). The area under the curve during the wash-in phase (in au) at baseline was 1 × 10(8) ; 12 months after GKR, it was reduced to 6 × 10(2) (p < 0.05). CONCLUSIONS: At 6 months after GKR, a reduction of tumor thickness, as detected on US, occurred in 6 of the 10 patients, whereas a reduction in all the quantitative parameters measured on CEUS occurred in all 10 patients. However, a larger population is needed to investigate whether CEUS could become the first-choice technique for monitoring the response of UM to GKR.

Impact of Multiple Sclerosis Subtypes on Pain Management in Patients With Trigeminal Neuralgia After Stereotactic Radiosurgery: An International Multicenter Analysis.

BACKGROUND AND OBJECTIVES: Trigeminal neuralgia affects approximately 2% of patients with multiple sclerosis (MS) and often shows higher rates of pain recurrence after treatment. Previous studies on the effectiveness of stereotactic radiosurgery (SRS) for trigeminal neuralgia did not consider the different MS subtypes, including remitting relapsing (RRMS), primary progressive (PPMS), and secondary progressive (SPMS). Our objective was to investigate how MS subtypes are related to pain control (PC) rates after SRS. METHODS: We conducted a retrospective multicenter analysis of prospectively collected databases. Pain status was assessed using the Barrow National Institute Pain Intensity Scales. Time to recurrence was estimated through the Kaplan-Meier method and compared groups using log-rank tests. Logistic regression was used to calculate the odds ratio (OR). RESULTS: Two hundred and fifty-eight patients, 135 (52.4%) RRMS, 30 (11.6%) PPMS, and 93 (36%) SPMS, were included from 14 institutions. In total, 84.6% of patients achieved initial pain relief, with a median time of 1 month; 78.7% had some degree of pain recurrence with a median time of 10.2 months for RRMS, 8 months for PPMS, 8.1 months for SPMS ( P = .424). Achieving Barrow National Institute-I after SRS was a predictor for longer periods without recurrence ( P = .028). Analyzing PC at the last available follow-up and comparing with RRMS, PPMS was less likely to have PC (OR = 0.389; 95% CI 0.153-0.986; P = .047) and SPMS was more likely (OR = 2.0; 95% CI 0.967-4.136; P = .062). A subgroup of 149 patients did not have other procedures apart from SRS. The median times to recurrence in this group were 11.1, 9.8, and 19.6 months for RRMS, PPMS, and SPMS, respectively (log-rank, P = .045). CONCLUSION: This study is the first to investigate the relationship between MS subtypes and PC after SRS, and our results provide preliminary evidence that subtypes may influence pain outcomes, with PPMS posing the greatest challenge to pain management.

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.

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.

Evaluation of prognostic factors as predictor of AVMS obliteration after Gamma Knife radiosurgery.

BACKGROUND: The reported AVMs obliteration rate after Gamma Knife radiosurgery (GKS) ranges from 70 to 94 %. The objective of the present study was to assess prognostic factors predictive for cerebral AVMs obliteration in 127 patients who underwent GKS. METHODS: The AVMs were classified according to the Spetzler-Martin classification. Twenty-one cases (16.5 %) were classified as grade I, 46 cases (36.2 %) as grade II, 51 cases (40.1 %) as grade III, and nine cases (7.1 %) as grade IV-V. The AVMs were deeply located in 16.5 % of patients. The peripheral prescription dose ranged from 16 to 30 Gy (mean 22.3 Gy). The AVMs volume ranged from 0.1 to 13 cc (mean 2.7 cc). RESULTS: In 72 patients out of the 104 (69.2 %) with a radiological follow-up, MRI showed the AVM obliteration; in 54 cases (60 %) out of the 90 that performed a DSA, a complete AVM obliteration was achieved (average closure time 48.5 months). The volume of the nidus (p = 0.001), the prescription dose (p = 0.004), the 2002 Pollock-Flickinger classification (p = 0.031), and their 2008 revised classification (p = 0.025) were found to be statistically significant in predicting the probability of AVM closure. In the multivariate analysis, only the prescription dose was found to be an independent prognostic factor (p = 0.009) for AVM obliteration. CONCLUSIONS: The volume of the nidus and the prescription dose significantly influence the outcome of radiosurgical treatment. The Pollock-Flickinger classification was found to be a reliable scoring system in predicting the AVM closure and an important tool for selection of patients candidate for GKS.

Gamma Knife Radiosurgery Targeting the Trigeminal Nerve for Tumor-Related Trigeminal Neuralgia: A Case Series.

BACKGROUND: Tumor-related trigeminal neuralgia (TN) is a challenging condition to manage that is commonly treated by surgical resection of the tumor. Stereotactic radiosurgery targeting the tumor is used to control pain and tumor growth in patients unsuitable for surgery. Stereotactic radiosurgery targeting the trigeminal nerve has been explored as a viable treatment for patients with tumor-related TN who are unsuitable for surgical removal of the tumor or whose pain is refractory to radiation therapy targeting the tumor. Information regarding the efficacy of this procedure is limited to only a few studies. We report the outcomes of Leskell Gamma Knife radiosurgery (GKRS) targeting the trigeminal nerve for tumor-related TN from a case series. METHODS: A retrospective review of our GKRS database identified 6 patients with unilateral tumor-related TN treated with GKRS targeting the trigeminal nerve between 2014 and 2020. Five patients had undergone previous radiation therapy targeting the tumor. Facial pain and sensory function were evaluated using the Barrow Neurological Institute scales. RESULTS: Three patients achieved a Barrow Neurological Institute score of IIIb or better, indicating pain reduction, within a mean period of 4.3 months after GKRS. The maximum dose for GKRS ranged from 80 to 88 Gy. Pain recurred in 1 patient at 64 months after GKRS. No patient developed permanent facial sensory disturbances. No adverse event was recorded. CONCLUSIONS: GKRS targeting the trigeminal nerve could be a safe and effective treatment for a subset of patients with tumor-related TN who are unsuitable for surgical removal of the tumor or whose pain is refractory to radiation therapy targeting the tumor.

Gamma Knife Central Lateral Thalamotomy for Chronic Neuropathic Pain: A Single-Center, Retrospective Study.

BACKGROUND: Chronic neuropathic pain can be severely disabling and is difficult to treat. The medial thalamus is believed to be involved in the processing of the affective-motivational dimension of pain, and lesioning of the medial thalamus has been used as a potential treatment for neuropathic pain. Within the medial thalamus, the central lateral nucleus has been considered as a target for stereotactic lesioning. OBJECTIVE: To study the safety and efficacy of central lateral thalamotomy using Gamma Knife radiosurgery (GKRS) for the treatment of neuropathic pain. METHODS: We retrospectively reviewed all patients with neuropathic pain who underwent central lateral thalamotomy using GKRS. We report on patient outcomes, including changes in pain scores using the Numeric Pain Rating Scale and Barrow Neurological Institute pain intensity score, and adverse events. RESULTS: Twenty-one patients underwent central lateral thalamotomy using GKRS between 2014 and 2021. Meaningful pain reduction occurred in 12 patients (57%) after a median period of 3 months and persisted in 7 patients (33%) at the last follow-up (the median follow-up was 28 months). Rates of pain reduction at 1, 2, 3, and 5 years were 48%, 48%, 19%, and 19%, respectively. Meaningful pain reduction occurred more frequently in patients with trigeminal deafferentation pain compared with all other patients (P = .009). No patient had treatment-related adverse events. CONCLUSION: Central lateral thalamotomy using GKRS is remarkably safe. Pain reduction after this procedure occurs in a subset of patients and is more frequent in those with trigeminal deafferentation pain; however, pain recurs frequently over time.

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.

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.