Does stereoscopic imaging improve the memorization of medical imaging by neurosurgeons? Experience of a single institution.

Stereoscopic imaging has increasingly been used in anatomical teaching and neurosurgery. The aim of our study was to analyze the potential utility of stereoscopic imaging as a tool for memorizing neurosurgical patient cases compared to conventional monoscopic visualization. A total of 16 residents and 6 consultants from the Department of Neurosurgery at Charité - Universitätsmedizin Berlin were recruited for the study. They were divided into two equally experienced groups. A comparative analysis of both imaging modalities was conducted in which four different cases were assessed by the participants. Following the image assessment, two questionnaires, one analyzing the subjective judgment using the 5-point Likert Scale and the other assessing the memorization and anatomical accuracy, were completed by all participants. Both groups had the same median year of experience (5) and stereoacuity (≤ 75 s of arc). The analysis of the first questionnaire demonstrated significant subjective superiority of the monoscopic imaging in evaluation of the pathology (median: monoscopic: 4; stereoscopic: 3; p = 0.020) and in handling of the system (median: monoscopic: 5; stereoscopic: 2; p < 0.001). The second questionnaire showed that the anatomical characterization of the pathologies was comparable between both visualization methods. Most participants rated the stereoscopic visualization as worse compared to the monoscopic visualization, probably due to a lack of familiarity with the newer technique. Stereoscopic imaging, however, was not objectively inferior to traditional monoscopic imaging for anatomical comprehension. Further methodological developments and incorporation in routine clinical workflows will most likely enhance the usability and acceptance of stereoscopic visualization.

360° 3D virtual reality operative video for the training of residents in neurosurgery.

OBJECTIVE: Training of residents is an essential but time-consuming and costly task in the surgical disciplines. During the coronavirus disease 2019 pandemic, surgical education became even more challenging because of the reduced caseload due to the increased shift to corona care. In this context, augmented 360° 3D virtual reality (VR) videos of surgical procedures enable effective off-site training through virtual participation in the surgery. The goal of this study was to establish and evaluate 360° 3D VR operative videos for neurosurgical training. METHODS: Using a 360° camera, the authors recorded three standard neurosurgical procedures: a lumbar discectomy, brain metastasis resection, and clipping of an aneurysm. Combined with the stereoscopic view of the surgical microscope, 7- to 10-minute 360° 3D VR videos augmented with annotations, overlays, and commentary were created. These videos were then presented to the neurosurgical residents at the authors' institution using a head-mounted display. Before viewing the videos, the residents were asked to fill out a questionnaire indicating their VR experience and self-assessment of surgical skills regarding the specific procedure. After watching the videos, the residents completed another questionnaire to evaluate their quality and usefulness. The parameters were scaled with a 5-point Likert scale. RESULTS: Twenty-two residents participated in this study. The mean years of experience of the participants in neurosurgery was 3.2 years, ranging from the 1st through the 7th year of training. Most participants (86.4%) had no or less than 15 minutes of VR experience. The overall quality of the videos was rated good to very good. Immersion, the feeling of being in the operating room, was high, and almost all participants (91%) stated that 360° VR videos provide a useful addition to the neurosurgical training. VR sickness was negligible in the cohort. CONCLUSIONS: In this study, the authors demonstrated the feasibility and high acceptance of augmented 360° 3D VR videos in neurosurgical training. Augmentation of 360° videos with complementary and interactive content has the potential to effectively support trainees in acquiring conceptual knowledge. Further studies are necessary to investigate the effectiveness of their use in improving surgical skills.

Motor excitability in bilateral moyamoya vasculopathy and the impact of revascularization.

OBJECTIVE: Motor cortical dysfunction has been shown to be reversible in patients with unilateral atherosclerotic disease after cerebral revascularization. Moyamoya vasculopathy (MMV) is a rare bilateral stenoocclusive cerebrovascular disease. The aim of this study was to analyze the corticospinal excitability and the role of bypass surgery in restoring cortical motor function in patients by using navigated transcranial magnetic stimulation (nTMS). METHODS: Patients with bilateral MMV who met the criteria for cerebral revascularization were prospectively included. Corticospinal excitability, cortical representation area, and intracortical inhibition and facilitation were assessed by nTMS for a small hand muscle (first dorsal interosseous) before and after revascularization. The clinically and/or hemodynamically more severely affected hemisphere was operated first as the leading hemisphere. Intra- and interhemispheric differences were analyzed before and after direct or combined revascularization. RESULTS: A total of 30 patients with bilateral MMV were examined by nTMS prior to and after revascularization surgery. The corticospinal excitability was higher in the leading hemisphere compared with the non-leading hemisphere prior to revascularization. This hyperexcitability was normalized after revascularization as demonstrated in the resting motor threshold ratio of the hemispheres (preoperative median 0.97 [IQR 0.89-1.08], postoperative median 1.02 [IQR 0.94-1.22]; relative effect = 0.61, p = 0.03). In paired-pulse paradigms, a tendency for a weaker inhibition of the leading hemisphere was observed compared with the non-leading hemisphere. Importantly, the paired paradigm also demonstrated approximation of excitability patterns between the two hemispheres after surgery. CONCLUSIONS: The study results suggested that, in the case of a bilateral chronic ischemia, a compensation mechanism between both hemispheres seemed to exist that normalized after revascularization surgery. A potential role of nTMS in predicting the efficacy of revascularization must be further assessed.

Tumor-Associated Microglia/Macrophages as a Predictor for Survival in Glioblastoma and Temozolomide-Induced Changes in CXCR2 Signaling with New Resistance Overcoming Strategy by Combination Therapy.

Tumor recurrence is the main challenge in glioblastoma (GBM) treatment. Gold standard therapy temozolomide (TMZ) is known to induce upregulation of IL8/CXCL2/CXCR2 signaling that promotes tumor progression and angiogenesis. Our aim was to verify the alterations on this signaling pathway in human GBM recurrence and to investigate the impact of TMZ in particular. Furthermore, a combi-therapy of TMZ and CXCR2 antagonization was established to assess the efficacy and tolerability. First, we analyzed 76 matched primary and recurrent GBM samples with regard to various histological aspects with a focus on the role of TMZ treatment and the assessment of predictors of overall survival (OS). Second, the combi-therapy with TMZ and CXCR2-antagonization was evaluated in a syngeneic mouse tumor model with in-depth immunohistological investigations and subsequent gene expression analyses. We observed a significantly decreased infiltration of tumor-associated microglia/macrophages (TAM) in recurrent tumors, while a high TAM infiltration in primary tumors was associated with a reduced OS. Additionally, more patients expressed IL8 in recurrent tumors and TMZ therapy maintained CXCL2 expression. In mice, enhanced anti-tumoral effects were observed after combi-therapy. In conclusion, high TAM infiltration predicts a survival disadvantage, supporting findings of the tumor-promoting phenotype of TAMs. Furthermore, the combination therapy seemed to be promising to overcome CXCR2-mediated resistance.

Collateralization and ischemia in hemodynamic cerebrovascular insufficiency.

BACKGROUND: Moyamoya disease and atherosclerotic cerebrovascular occlusive disease lead to hemodynamic impairment of cerebral blood flow. One major differentiation between both disease entities lies in the collateralization pathways. The clinical implications of the collateralization pathways for the development of hemodynamic ischemia remain unknown. The aim was to characterize collateralization and ischemia patterns in patients with chronic hemodynamic compromise. METHODS: Hemodynamic compromise was verified using acetazolamide-stimulated xenon-CT or SPECT in 54 patients [30 moyamoya and 24 atherosclerotic cerebrovascular disease (ACVD)]. All patients received MRI to differentiate hemodynamic ischemia into anterior/posterior cortical border zone infarction (CBI), inferior border zone infarction (IBI) or territorial infarction (TI). Digital subtraction angiography was applied to evaluate collateralization. Collateralization was compared and correlated with the localization of ischemia and number of vascular territories with impaired cerebrovascular reserve capacity (CVRC). RESULTS: MM patients showed collateralization significantly more often via pericallosal anastomosis and the posterior communicating artery (flow in the anterior-posterior direction; MM: 95%/95% vs. ACVD: 23%/12%, p < 0.05). ACVD patients demonstrated collateralization via the anterior and posterior communicating arteries (flow in the posterior-anterior direction, MM: 6%/5% vs. ACVD: 62%/88%, p < 0.05). Patterns of infarction were comparable (aCBI: MM: 36% vs. ACVD: 35%; pCBI: MM: 10% vs. ACVD: 20%; IBI: MM: 35% vs. ACVD: 41%; TI: MM: 13% vs. ACVD: 18%). The number and localization of vascular territories with impaired CVRC were comparable. CONCLUSIONS: Despite significant differences in collateralization, the infarct patterns and severity of CVRC impairment do not differ between MMV and ACVD patients. Cerebral collateralization does not allow reaching conclusions about the localization of cerebral ischemia or severity of impaired CVRC in chronic hemodynamic impairment.

Augmented 360° Three-Dimensional Virtual Reality for Enhanced Student Training and Education in Neurosurgery.

OBJECTIVE: This prospective study assesses the acceptance and usefulness of augmented 360° virtual reality (VR) videos for early student education and preparation in the field of neurosurgery. METHODS: Thirty-five third-year medical students participated. Augmented 360° VR videos depicting three neurosurgical procedures (lumbar discectomy, brain metastasis resection, clipping of an aneurysm) were presented during elective seminars. Multiple questionnaires were employed to evaluate conceptual and technical aspects of the videos. The analysis utilized ordinal logistic regression to identify crucial factors contributing to the learning experience of the videos. RESULTS: The videos were consistently rated as good to very good in quality, providing detailed demonstrations of intraoperative anatomy and surgical workflow. Students found the videos highly useful for their learning and preparation for surgical placements, and they strongly supported the establishment of a VR lounge for additional self-directed learning. Notably, 81% reported an increased interest in neurosurgery, and 47% acknowledged the potential influence of the videos on their future choice of specialization. Factors associated with a positive impact on students' interest and learning experience included high technical quality and comprehensive explanations of the surgical steps. CONCLUSIONS: This study demonstrated the high acceptance of augmented 360° VR videos as a valuable tool for early student education in neurosurgery. While hands-on training remains indispensable, these videos promote conceptual knowledge, ignite interest in neurosurgery, and provide a much-needed orientation within the operating room. The incorporation of detailed explanations throughout the surgeries with augmentation using superimposed elements, offers distinct advantages over simply observing live surgeries.

Corrigendum: What if: a retrospective reconstruction of resection cavity stereotactic radiosurgery to mimic neoadjuvant stereotactic radiosurgery.

[This corrects the article DOI: 10.3389/fonc.2023.1056330.].

What if: A retrospective reconstruction of resection cavity stereotactic radiosurgery to mimic neoadjuvant stereotactic radiosurgery.

Introduction: Neoadjuvant stereotactic radiosurgery (NaSRS) of brain metastases has gained importance, but it is not routinely performed. While awaiting the results of prospective studies, we aimed to analyze the changes in the volume of brain metastases irradiated pre- and postoperatively and the resulting dosimetric effects on normal brain tissue (NBT). Methods: We identified patients treated with SRS at our institution to compare hypothetical preoperative gross tumor and planning target volumes (pre-GTV and pre-PTV) with original postoperative resection cavity volumes (post-GTV and post-PTV) as well as with a standardized-hypothetical PTV with 2.0 mm margin. We used Pearson correlation to assess the association between the GTV and PTV changes with the pre-GTV. A multiple linear regression analysis was established to predict the GTV change. Hypothetical planning for the selected cases was created to assess the volume effect on the NBT exposure. We performed a literature review on NaSRS and searched for ongoing prospective trials. Results: We included 30 patients in the analysis. The pre-/post-GTV and pre-/post-PTV did not differ significantly. We observed a negative correlation between pre-GTV and GTV-change, which was also a predictor of volume change in the regression analysis, in terms of a larger volume change for a smaller pre-GTV. In total, 62.5% of cases with an enlargement greater than 5.0 cm3 were smaller tumors (pre-GTV < 15.0 cm3), whereas larger tumors greater than 25.0 cm3 showed only a decrease in post-GTV. Hypothetical planning for the selected cases to evaluate the volume effect resulted in a median NBT exposure of only 67.6% (range: 33.2-84.5%) relative to the dose received by the NBT in the postoperative SRS setting. Nine published studies and twenty ongoing studies are listed as an overview. Conclusion: Patients with smaller brain metastases may have a higher risk of volume increase when irradiated postoperatively. Target volume delineation is of great importance because the PTV directly affects the exposure of NBT, but it is a challenge when contouring resection cavities. Further studies should identify patients at risk of relevant volume increase to be preferably treated with NaSRS in routine practice. Ongoing clinical trials will evaluate additional benefits of NaSRS.

Combining TMZ and SB225002 induces changes of CXCR2 and VEGFR signalling in primary human endothelial cells in vitro.

Standard of care therapy for glioblastoma (GBM) consisting of surgical removal, temozolomide (TMZ) and radiotherapy fails to cure the disease and median survival is limited to 15 months. Therapeutic approaches targeting vascular endothelial growth factor (VEGF)­mediated angiogenesis, one of the major drivers of tumour growth, have not prolonged patient survival as reported in clinical studies. Apart from VEGFR signalling, proangiogenic C­X­C motif chemokine receptor 2 (CXCR2) is of special interest as its ligands C­X­C motif chemokine ligand 2 (CXCL2) and interleukin­8 (IL8) are upregulated and associated with reduced survival in GBM patients. As CXCR2 is also expressed by endothelial cells, the aim of the present study was to elucidate the effect of combination therapy on gene and protein expression of primary human endothelial cells (HUVECs). To mimic the GBM specific CXCL2/IL8 oversupply environment [referred to as stimulation (STIM)], HUVECs were treated with a cocktail of CXCL2/IL8 and/or TMZ and/or CXCR2­antagonist SB225002 (SB). In brief, six treatment conditions were utilized: i) Control, ii) STIM (CXCL2/IL8), iii) TMZ + SB, iv) STIM + TMZ, v) STIM + SB, vi) STIM + TMZ + SB followed by either RNA­isolation and RT­qPCR for BAX, BCL2, vascular endothelial growth receptor (VEGFR)1/2, VEGF, CXCR1/2, CXCL2 and IL8 or immunofluorescence staining for VEGFR2 and CXCR2. SB and TMZ led to morphological changes of HUVECs and downregulated antiapoptotic BCL2 in vitro. In addition, gene expression of the alternative proangiogenic CXCL2/IL8/CXCR2 signalling pathway was significantly altered by the combination therapy, while the VEGF/VEGFR1/2 axis was only mildly affected. Furthermore, VEGFR2 and CXCR2 gene and protein expression regulation differed. VEGFR2 was not altered at the gene expression level, while combination therapy with TMZ and SB led to a 74% upregulation of VEGFR2 at the protein level. By contrast, CXCR2 was upregulated 5­fold by the combination therapy at the gene expression level and downregulated by 72.5% at the protein expression level. The present study provided first insights into the molecular changes of two major proangiogenic pathways in primary endothelial cells during treatment with TMZ and SB. Different gene and protein expression levels of the proangiogenic receptors CXCR2 and VEGFR2 in vitro must be taken into consideration in future studies.

Dynamic 18F-FET PET/CT to differentiate recurrent primary brain tumor and brain metastases from radiation necrosis after single-session robotic radiosurgery.

OBJECTIVE: Cyberknife robotic radiosurgery (RRS) provides single-session high-dose radiotherapy of brain tumors with a steep dose gradient and precise real-time image-guided motion correction. Although RRS appears to cause more radiation necrosis (RN), the radiometabolic changes after RRS have not been fully clarified. 18F-FET-PET/CT is used to differentiate recurrent tumor (RT) from RN after radiosurgery when MRI findings are indecisive. We explored the usefulness of dynamic parameters derived from 18F-FET PET in differentiating RT from RN after Cyberknife treatment in a single-center study population. METHODS: We retrospectively identified brain tumor patients with static and dynamic 18F-FET-PET/CT for suspected RN after Cyberknife. Static (tumor-to-background ratio) and dynamic PET parameters (time-activity curve, time-to-peak) were quantified. Analyses were performed for all lesions taken together (TOTAL) and for brain metastases only (METS). Diagnostic accuracy of PET parameters (using mean tumor-to-background ratio >1.95 and time-to-peak of 20 min for RT as cut-offs) and their respective improvement of diagnostic probability were analyzed. RESULTS: Fourteen patients with 28 brain tumors were included in quantitative analysis. Time-activity curves alone provided the highest sensitivities (TOTAL: 95%, METS: 100%) at the cost of specificity (TOTAL: 50%, METS: 57%). Combined mean tumor-to-background ratio and time-activity curve had the highest specificities (TOTAL: 63%, METS: 71%) and led to the highest increase in diagnosis probability of up to 16% p. - versus 5% p. when only static parameters were used. CONCLUSIONS: This preliminary study shows that combined dynamic and static 18F-FET PET/CT parameters can be used in differentiating RT from RN after RRS.

Image-guided robotic radiosurgery for the treatment of arteriovenous malformations.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) are challenging lesions, often requiring multimodal interventions; however, data on the efficacy of stereotactic radiosurgery for cerebral AVMs are limited. This study aimed to evaluate the clinical and radiographic results following robotic radiosurgery, alone or in combination with endovascular treatment, and to investigate factors associated with obliteration and complications in patients with AVM. METHODS: We retrospectively analyzed the clinical and imaging characteristics of 123 patients with AVMs of all Spetzler-Martin grades treated at two institutions by robotic radiosurgery in single-fraction doses (CyberKnife). Embolization was performed before radiosurgery in a subset of patients to attempt to downgrade the lesions. Factors associated with AVM obliteration and complications (toxicity) were identified via univariate and multivariate analyses. RESULTS: The median follow-up time was 48.1 months (range, 3.6-123 months). Five patients were lost to follow-up. The obliteration rate in the 59 patients with a follow-up period exceeding four years was 72.8%. Complete obliteration and partial remission were achieved in 67 (56.8%) and 31 (26.3%) cases, respectively, whereas no change was observed in 20 cases (17.8%). Embolization was performed in 54/123 cases (43.9%). Complete and partial obliteration were achieved in 29 (55.7%) and 14 (26.9%) embolized patients, respectively. In the multivariate analysis, the factors associated with obliteration were age (p = .018) and the Spetzler-Martin grade (p = .041). Treatment-induced toxicity (radiation necrosis and/or edema) was observed in 15 cases (12.7%), rebleeding occurred in three cases (2.5%), and the rate of mortality associated with rebleeding was 1.7%. CONCLUSIONS: CyberKnife radiosurgery is a valid approach for treating AVMs of all Spetzler-Martin-grades, with satisfactory obliteration rates, low toxicity, and a relatively rare incidence of rebleeding.

Risks and Benefits of Fiducial Marker Placement in Tumor Lesions for Robotic Radiosurgery: Technical Outcomes of 357 Implantations.

Fiducial markers (FM) inserted into tumors increase the precision of irradiation during robotic radiosurgery (RRS). This retrospective study evaluated the clinical complications, marker migration, and motion amplitude of FM implantations by analyzing 288 cancer patients (58% men; 63.1 ± 13.0 years) who underwent 357 FM implantations prior to RRS with CyberKnife, between 2011 and 2019. Complications were classified according to the Society of Interventional Radiology (SIR) guidelines. The radial motion amplitude was calculated for tumors that moved with respiration. A total of 725 gold FM was inserted. SIR-rated complications occurred in 17.9% of all procedures. Most complications (32.0%, 62/194 implantations) were observed in Synchrony®-tracked lesions affected by respiratory motion, particularly in pulmonary lesions (46.9% 52/111 implantations). Concurrent biopsy sampling was associated with a higher complication rate (p = 0.001). FM migration occurred in 3.6% after CT-guided and clinical FM implantations. The largest motion amplitudes were observed in hepatic (20.5 ± 11.0 mm) and lower lung lobe (15.4 ± 10.5 mm) lesions. This study increases the awareness of the risks of FM placement, especially in thoracic lesions affected by respiratory motion. Considering the maximum motion amplitude, FM placement remains essential in hepatic and lower lung lobe lesions located >100.0 mm from the spine.

68Ga-DOTATOC-PET/MRI-A Secure One-Stop Shop Imaging Tool for Robotic Radiosurgery Treatment Planning in Patients with Optic Nerve Sheath Meningioma.

Optic nerve sheath meningiomas (ONSM) are rare but can lead to irreversible blindness. Hybrid imaging may enhance tumor delineation and diagnostic accuracy via receptor binding. However, relevant clinical data for ONSM are lacking. We evaluated the feasibility of receptor-based hybrid imaging prior to robotic radiosurgery (RRS). We retrospectively analyzed all of our institution's patients with suspected ONSM who underwent combined positron emission tomography and magnetic resonance imaging (PET/MRI) with gallium-68-labeled (DOTA0-Phe1-Tyr3) octreotide (Ga68-DOTATOC) before RRS between 2018 and 2019. Eight patients with ten suspected ONSM (female = 7; median age, 51.2 years; IQR, 43.0-66.0) were included. Nine out of ten ONSM were deemed PET-positive with a median standard uptake value (SUV) max of 5.6 (IQR, 2.6-7.8). For all nine ONSM that presented 68Ga-DOTATOC uptake, hybrid PET/MRI was used for target volume contouring prior to RSS. At a median follow-up of 11.7 months (IQR, 9.4-16.4), tumor control was achieved in all patients. Radiosurgery resulted in the improvement of visual acuity in two of eight patients, whereas six showed stable vision. Ga68-DOTATOC-PET/MRI can be used for target volume contouring prior to RRS for ONSM as it enables safe treatment planning and improves diagnostic accuracy.

Establishment and Validation of CyberKnife Irradiation in a Syngeneic Glioblastoma Mouse Model.

CyberKnife stereotactic radiosurgery (CK-SRS) precisely delivers radiation to intracranial tumors. However, the underlying radiobiological mechanisms at high single doses are not yet fully understood. Here, we established and evaluated the early radiobiological effects of CK-SRS treatment at a single dose of 20 Gy after 15 days of tumor growth in a syngeneic glioblastoma-mouse model. Exact positioning was ensured using a custom-made, non-invasive, and trackable frame. One superimposed target volume for the CK-SRS planning was created from the fused tumor volumes obtained from MRIs prior to irradiation. Dose calculation and delivery were planned using a single-reference CT scan. Six days after irradiation, tumor volumes were measured using MRI scans, and radiobiological effects were assessed using immunofluorescence staining. We found that CK-SRS treatment reduced tumor volume by approximately 75%, impaired cell proliferation, diminished tumor vasculature, and increased immune response. The accuracy of the delivered dose was demonstrated by staining of DNA double-strand breaks in accordance with the planned dose distribution. Overall, we confirmed that our proposed setup enables the precise irradiation of intracranial tumors in mice using only one reference CT and superimposed MRI volumes. Thus, our proposed mouse model for reproducible CK-SRS can be used to investigate radiobiological effects and develop novel therapeutic approaches.

Effectiveness and Safety of Robotic Radiosurgery for Optic Nerve Sheath Meningiomas: A Single Institution Series.

The role of robotic radiosurgery (RRS) in the treatment of optic nerve sheath meningiomas (ONSM) remains controversial and it is only performed in specialized institutions due to tight dose constraints. We evaluated the effectiveness and safety of RRS in the management of ONSM. Twenty-five patients with 27 ONSM lesions who underwent RRS using the Cyberknife (CK) system were retrospectively analyzed (median age, 47.9 years; 84.0% women). Multisession RRS was used with 4-5 fractions with a cumulative dose of 20.0-25.0 Gy in 84.0% of patients and a single fraction at a dose of 14.0-15.0 Gy in 16% of patients. Prior to RRS, seven (28%) patients experienced blindness on the lesion side. In those patients with preserved vision prior to radiosurgery, the visual acuity remained the same in 90.0% and improved in 10.0% of the patients. Overall local tumor control was 96.0% (mean follow-up period; 37.4 ± 27.2 months). Neither patient age, previous surgery, or the period from the initial diagnosis to RRS showed a dependency on visual acuity before or after radiosurgery. RRS is a safe and effective treatment for the management of ONSM. Hypofractionation of radiosurgery in patients with preserved vision before CK treatment results in stable or improved vision.

Efficacy and safety of CyberKnife radiosurgery in elderly patients with brain metastases: a retrospective clinical evaluation.

BACKGROUND: Stereotactic radiosurgery (SRS) has been increasingly applied for up to 10 brain metastases instead of whole brain radiation therapy (WBRT) to achieve local tumor control while reducing neurotoxicity. Furthermore, brain-metastasis incidence is rising due to the increasing survival of patients with cancer. Our aim was to analyze the efficacy and safety of CyberKnife (CK) radiosurgery for elderly patients. METHODS: We retrospectively identified all patients with brain metastases ≥ 65 years old treated with CK-SRS at our institution since 2011 and analyzed data of primary diseases, multimodality treatments, and local therapy effect based on imaging follow-up and treatment safety. Kaplan-Meier analysis for local progression-free interval and overall survival were performed. RESULTS: We identified 97 patients (233 lesions) fulfilling the criteria at the first CK-SRS. The mean age was 73.2 ± 5.8 (range: 65.0-87.0) years. Overall, 13.4% of the patients were > 80 years old. The three most frequent primary cancers were lung (40.2%), kidney (22.7%), and malignant melanoma (15.5%). In 38.5% (47/122 treatments) multiple brain metastases were treated with the CK-SRS, with up to eight lesions in one session. The median planning target volume (PTV) was 1.05 (range: 0.01-19.80) cm3. A single fraction was applied in 92.3% of the lesions with a median prescription dose of 19 (range: 12-21) Gy. The estimated overall survivals at 3-, 6-, and 12 months after SRS were 79, 55, and 23%, respectively. The estimated local tumor progression-free intervals at 6-, 12-, 24-, 36-, and 72 months after SRS were 99.2, 89.0, 67.2, 64.6, and 64.6%, respectively. Older age and female sex were predictive factors of local progression. The Karnofsky performance score remained stable in 97.9% of the patients; only one patient developed a neurological deficit after SRS of a cerebellar lesion (ataxia, CTCAE Grade 2). CONCLUSIONS: SRS is a safe and efficient option for the treatment of elderly patients with brain metastases with good local control rates without the side effects of WBRT. Older age and female sex seem to be predictive factors of local progression. Prospective studies are warranted to clarify the role of SRS treatment for elderly patients.

Factors affecting outcome in frameless non-isocentric stereotactic radiosurgery for trigeminal neuralgia: a multicentric cohort study.

BACKGROUND: Stereotactic radiosurgery (SRS) is an effective treatment for trigeminal neuralgia (TN). Nevertheless, a proportion of patients will experience recurrence and treatment-related sensory disturbances. In order to evaluate the predictors of efficacy and safety of image-guided non-isocentric radiosurgery, we analyzed the impact of trigeminal nerve volume and the nerve dose/volume relationship, together with relevant clinical characteristics. METHODS: Two-hundred and ninety-six procedures were performed on 262 patients at three centers. In 17 patients the TN was secondary to multiple sclerosis (MS). Trigeminal pain and sensory disturbances were classified according to the Barrow Neurological Institute (BNI) scale. Pain-free-intervals were investigated using Kaplan Meier analyses. Univariate and multivariate Cox regression analyses were performed to identify predictors. RESULTS: The median follow-up period was 38 months, median maximal dose 72.4 Gy, median target nerve volume 25 mm3, and median prescription dose 60 Gy. Pain control rate (BNI I-III) at 6, 12, 24, 36, 48, and 60 months were 96.8, 90.9, 84.2, 81.4, 74.2, and 71.2%, respectively. Overall, 18% of patients developed sensory disturbances. Patients with volume ≥ 30 mm3 were more likely to maintain pain relief (p = 0.031), and low integral dose (< 1.4 mJ) tended to be associated with more pain recurrence than intermediate (1.4-2.7 mJ) or high integral dose (> 2.7 mJ; low vs. intermediate: log-rank test, χ2 = 5.02, p = 0.019; low vs. high: log-rank test, χ2 = 6.026, p = 0.014). MS, integral dose, and mean dose were the factors associated with pain recurrence, while re-irradiation and MS were predictors for sensory disturbance in the multivariate analysis. CONCLUSIONS: The dose to nerve volume ratio is predictive of pain recurrence in TN, and re-irradiation has a major impact on the development of sensory disturbances after non-isocentric SRS. Interestingly, the integral dose may differ significantly in treatments using apparently similar dose and volume constraints.