Percutaneous Disc Biopsy versus Bone Biopsy for the Identification of Infectious Agents in Osteomyelitis/Discitis.

PURPOSE: To determine whether sampling of the disc or bone is more likely to yield positive tissue culture results in patients with vertebral discitis and osteomyelitis (VDO). MATERIALS AND METHODS: Retrospective review was performed of consecutive patients who underwent vertebral disc or vertebral body biopsy at a single institution between February 2019 and May 2023. Inclusion criteria were age ≥18 years, presumed VDO on spinal magnetic resonance (MR) imaging, absence of paraspinal abscess, and technically successful percutaneous biopsy with fluoroscopic guidance. The primary outcome was a positive biopsy culture result, and secondary outcomes included complications such as nerve injury and segmental artery injury. RESULTS: Sixty-six patients met the inclusion criteria; 36 patients (55%) underwent disc biopsy, and 30 patients (45%) underwent bone biopsy. Six patients required a repeat biopsy for an initially negative culture result. No significant demographic, laboratory, antibiotic administration, or pain medication use differences were observed between the 2 groups. Patients who underwent bone biopsy were more likely to have a history of intravenous drug use (26.7%) compared with patients who underwent disc biopsy (5.5%; P = .017). Positive tissue culture results were observed in 41% of patients who underwent disc biopsy and 15% of patients who underwent bone biopsy (P = .016). No vessel or nerve injuries were detected after procedure in either group. CONCLUSIONS: Percutaneous disc biopsy is more likely to yield a positive tissue culture result than vertebral body biopsy in patients with VDO.

Therapeutic approaches for spinal synovial sarcoma: a comprehensive review of the literature.

OBJECTIVE: Synovial sarcoma (SS) is a relatively rare type of soft-tissue sarcoma that is commonly treated with surgery, radiation, chemotherapy, and palliative care. Stereotactic radiosurgery (SRS) is an emerging approach that shows promise in treating CNS conditions, but it has not been studied for SS. The authors present a systematic review that explores the effectiveness of different treatments, with a focus on SRS, for managing spinal SS. METHODS: A systematic PubMed search was conducted that covered studies from 1964 to 2022, yielding 70 relevant studies. Inclusion criteria encompassed primary and metastatic spinal SS, various treatment modalities, patient age 17 years or older, English-language studies, retrospective series, and case reports. Based on these criteria, 26 studies were included in this review and 44 were excluded. RESULTS: Of the included studies, 15 patients from 9 studies were treated with surgical intervention followed by both conventional radiotherapy (RT) and chemotherapy, 10 patients from 10 studies were treated with surgery followed by RT, 5 studies comprising 8 patients were exclusively treated with surgery, 5 cases in 3 studies were treated with surgery plus concomitant chemotherapy, 4 patients in 2 studies were treated with SRS, and only 1 study reported treatment without surgery and with chemotherapy and RT. The median progression-free survival and overall survival periods observed in the SRS-treated patients were 37 months and 60 months, respectively, which were higher than those of any other treatment method or combination used. CONCLUSIONS: The authors' study offers a thorough review of spinal SS treatments. They are hopeful that this will aid clinicians in informed decision-making for better patient outcomes.

Stereotactic Radiosurgery for Cranial and Spinal Hemangioblastomas: A Single-Institution Retrospective Series.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) has been an attractive treatment modality for both cranial and spinal hemangioblastomas, especially for multiple lesions commonly associated with von Hippel-Lindau (VHL) disease. This study aims to provide the largest long-term analysis of treatment efficacy and adverse effects of SRS for cranial and spinal hemangioblastomas at a single institution. METHODS: We evaluated the clinical and radiological outcomes of patients with hemangioblastomas treated with CyberKnife SRS at our institute from 1998 to 2022. The follow-up data were available for 135 hemangioblastomas in 35 patients. Twenty-eight patients had 123 hemangioblastomas associated with VHL, and 7 had 12 sporadic hemangioblastomas. The median age was 36 years, and the median tumor volume accounted for 0.4 cc. The SRS was administered with the median single-fraction equivalent dose of 18 Gy to the 77% median isodose line. RESULTS: At a median follow-up of 57 months (range: 3-260), only 20 (16.2%) of the VHL-associated and 1 (8.3%) sporadic hemangioblastomas progressed. The 5-year local tumor control rate was 91.3% for all hemangioblastomas, 91.7% among the sporadic lesions, and 92.9% in patients with VHL. SRS improved tumor-associated symptoms of 98 (74.8%) of 131 symptomatic hemangioblastomas, including headache, neck pain, dizziness, visual disturbances, dysesthesia, ataxia, motor impairment, seizures, and dysphagia. Two patients developed radiation necrosis (5.7%), and 1 of them required surgical resection. CONCLUSION: SRS is a safe and effective treatment option for patients with hemangioblastomas in critical locations, such as the brainstem, cervicomedullary junction, and spinal cord, and in patients with multiple hemangioblastomas associated with VHL disease.

Surgery and stereotactic radiosurgery for spinal leiomyosarcoma: a single-institution retrospective series and systematic review.

OBJECTIVE: Leiomyosarcoma (LMS) is a rare, aggressive soft-tissue sarcoma that seldom spreads to the bone. The spine can be either the site of LMS osseous metastases or the primary tumor site. The optimal treatment option for spinal LMS is still unclear. The authors present a cohort of patients with spinal LMS treated with either upfront surgery or upfront CyberKnife stereotactic radiosurgery (SRS). METHODS: The authors retrospectively studied the clinical and radiological outcomes of 17 patients with spinal LMS treated at their institution between 2004 and 2020. Either surgery or SRS was used as the upfront treatment. The clinical and radiological outcomes were assessed. A systematic review of the literature was also conducted. RESULTS: Of the 17 patients (20 spinal lesions), 12 (70.6%) were female. The median patient age was 61 years (range 41-80 years). Ten patients had upfront surgery for their spinal lesions, and 7 had upfront CyberKnife radiosurgery. The median follow-up was 11 months (range 0.3-130 months). The median overall survival (OS) for the entire cohort was 13 months (range 0.3-97 months). In subgroup analysis, the median OS was lower for the surgical group (13 months, range 0.3-50 months), while the median OS for the SRS group was 15 months (range 5-97 months) (p = 0.5). Forty percent (n = 4) of those treated with surgery presented with local recurrence at a median of 6.7 months (range 0.3-36 months), while only 14% (n = 1) of those treated with CyberKnife radiosurgery had local recurrence after 5 months. Local tumor control (LTC) rates at the 6-, 12-, and 18-month follow-ups were 72%, 58%, and 43%, respectively, for the SRS group and 40%, 30%, and 20%, respectively, for the surgery group (p < 0.05). The literature review included 35 papers with 70 patients harboring spinal LMS; only 2 patients were treated with SRS. The literature review confirms the clinical and radiological outcomes of the surgical group, while data on SRS are anecdotal. CONCLUSIONS: The authors present the largest series in the literature of spinal LMS and the first on SRS for spinal LMS. This study shows that LTC is statistically significantly better in patients receiving upfront SRS instead of surgery. The OS does not appear different between the two groups.

The outcome of central nervous system hemangioblastomas in Von Hippel-Lindau (VHL) disease treated with belzutifan: a single-institution retrospective experience.

PURPOSE: Belzutifan is a Hypoxia Inducible Factor 2-alpha inhibitor approved in 2021 by the FDA for the treatment of renal cell carcinoma (RCC) in patients with Von-Hippel Landau (VHL) disease. These patients can also present with central nervous system (CNS) hemangioblastomas (HBs). We aim to study the effectiveness and adverse effects of belzutifan for CNS HBs, by reporting our preliminary institutional experience. METHODS: We present a series of VHL patients with CNS HBs undergoing treatment with belzutifan for RCC. All the included patients met the RECIST inclusion criteria. The clinical and radiological outcome measures included: Objective response rate (ORR), time-to-response (TTR), adverse events (AE), and patient response. Patient response was classified as partial response (PR), complete response (CR), progressive disease (PD), or stable disease (SD). RESULTS: Seven patients with 25 HBs were included in our study. A belzutifan dose of 120 mg/day PO was administered for a median of 13 months (range 10-17). Median follow up time was 15 months (range 10-24). An ORR of 71% was observed. The median TTR was 5 months (range: 1-10). None of the patients showed CR, while 5 patients (71.4%) showed PR and 2 (28.5%) showed SD. Among patients with SD the maximum tumor response was 20% [increase/decrease] of the lesion diameter. All the patients experienced decreased hemoglobin concentration, fatigue, and dizziness. None of the patients experienced severe anemia (grade 3-4 CTCAE). CONCLUSION: Belzutifan appears to be an effective and safe treatment for CNS hemangioblastoma in VHL patients. Further clinical trials to assess the long-term effectiveness of the medication are required.

Spinal metastases of pineal region glioblastoma with primitive neuroectodermal features highlighting the importance of molecular diagnoses: illustrative case.

BACKGROUND: Glioblastoma (GBM) is the most common primary brain tumor with poor patient prognosis. Spinal leptomeningeal metastasis has been rarely reported, with long intervals between the initial discovery of the primary tumor in the brain and eventual spine metastasis. OBSERVATIONS: Here, the authors present the case of a 51-year-old male presenting with 7 days of severe headache, nausea, and vomiting. Magnetic resonance imaging of the brain and spine demonstrated a contrast-enhancing mass in the pineal region, along with spinal metastases to T8, T12, and L5. Initial frozen-section diagnosis led to the treatment strategy for medulloblastoma, but further molecular analysis revealed characteristics of isocitrate dehydrogenase-wild type, grade 4 GBM. LESSONS: Glioblastoma has the potential to show metastatic spread at the time of diagnosis. Spinal imaging should be considered in patients with clinical suspicion of leptomeningeal spread. Furthermore, molecular analysis should be confirmed following pathological diagnosis to fine-tune treatment strategies.

Stereotactic Radiosurgery for Contrast-Enhancing Satellite Nodules in Recurrent Glioblastoma: A Rare Case Series From a Single Institution.

Introduction Glioblastoma (GBM) is the most common malignant adult brain tumor and is invariably fatal. The standard treatment for GBM involves resection where possible, followed by chemoradiation per Stupp's protocol. We frequently use stereotactic radiosurgery (SRS) as a single-fraction treatment for small (volume ≤ 1cc) nodular recurrent GBM to the contrast-enhancing target on T1 MRI scan. In this paper, we aimed to evaluate the safety and efficacy of SRS for patients with contrast-enhancing satellite nodules in recurrent GBM. Methods This retrospective study analyzed the clinical and radiological outcomes of five patients who underwent CyberKnife (Accuray Inc., Sunnyvale, California) SRS at the institute between 2013 and 2022. Results From 96 patients receiving SRS for GBM, five (four males, one female; median age 53) had nine distinct new satellite lesions on MRI, separate from their primary tumor beds. Those nine lesions were treated with a median margin dose of 20 Gy in a single fraction. The three-, six, and 12-month local tumor control rates were 77.8%, 66.7%, and 26.7%, respectively. Median progression-free survival (PFS) was seven months, median overall survival following SRS was 10 months, and median overall survival (OS) was 35 months. Interestingly, the only lesion that did not show radiological progression was separate from the T2-fluid attenuated inversion recovery (FLAIR) signal of the main tumor. Conclusion Our SRS treatment outcomes for recurrent GBM satellite lesions are consistent with existing findings. However, in a unique case, a satellite nodule distinct from the primary tumor's T2-FLAIR signal and treated with an enlarged target volume showed promising control until the patient's demise. This observation suggests potential research avenues, given the limited strategies for 'multicentric' GBM lesions.

Practical Guideline for Prevention of Patchy Hair Loss following CyberKnife Stereotactic Radiosurgery for Calvarial or Scalp Tumors: Retrospective Analysis of a Single Institution Experience.

INTRODUCTION: Patchy alopecia is a common adverse effect of stereotactic radiosurgery (SRS) on the calvarium and/or scalp, yet no guidelines exist for its prevention. This study aims to investigate the incidence and outcomes of patchy alopecia following SRS for patients with calvarial or scalp lesions and establish preventive guidelines. METHODS: The study included 20 patients who underwent CyberKnife SRS for calvarial or scalp lesions, resulting in a total of 30 treated lesions. SRS was administered as a single fraction for 8 lesions and hypofractionated for 22 lesions. The median SRS target volume was 9.85 cc (range: 0.81-110.7 cc), and the median prescription dose was 27 Gy (range: 16-40 Gy), delivered in 1-5 fractions (median: 3). The median follow-up was 15 months. RESULTS: Among the 30 treated lesions, 11 led to patchy alopecia, while 19 did not. All cases of alopecia resolved within 12 months, and no patients experienced other adverse radiation effects. Lesions resulting in alopecia exhibited significantly higher biologically effective dose (BED) and single-fraction equivalent dose (SFED) on the overlying scalp compared to those without alopecia. Patients with BED and SFED exceeding 60 Gy and 20 Gy, respectively, were 9.3 times more likely to experience patchy alopecia than those with lower doses. The 1-year local tumor control rate for the treated lesions was 93.3%. Chemotherapy was administered for 26 lesions, with 11 lesions receiving radiosensitizing agents. However, no statistically significant difference was found. CONCLUSION: In summary, SRS is a safe and effective treatment for patients with calvarial/scalp masses regarding patchy alopecia near the treated area. Limiting the BED under 60 Gy and SFED under 20 Gy for the overlying scalp can help prevent patchy alopecia during SRS treatment of the calvarial/scalp mass. Clinicians can use this information to inform patients about the risk of alopecia and the contributing factors.

Optimizing the synergy between stereotactic radiosurgery and immunotherapy for brain metastases.

Solid tumors metastasizing to the brain are a frequent occurrence with an estimated incidence of approximately 30% of all cases. The longstanding conventional standard of care comprises surgical resection and whole-brain radiotherapy (WBRT); however, this approach is associated with limited long-term survival and local control outcomes. Consequently, stereotactic radiosurgery (SRS) has emerged as a potential alternative approach. The primary aim of SRS has been to improve long-term control rates. Nevertheless, rare observations of abscopal or out-of-field effects have sparked interest in the potential to elicit antitumor immunity via the administration of high-dose radiation. The blood-brain barrier (BBB) has traditionally posed a significant challenge to the efficacy of systemic therapy in managing intracranial metastasis. However, recent insights into the immune-brain interface and the development of immunotherapeutic agents have shown promise in preclinical and early-phase clinical trials. Researchers have investigated combining immunotherapy with SRS to enhance treatment outcomes in patients with brain metastasis. The combination approach aims to optimize long-term control and overall survival (OS) outcomes by leveraging the synergistic effects of both therapies. Initial findings have been encouraging in the management of various intracranial metastases, while further studies are required to determine the optimal order of administration, radiation doses, and fractionation regimens that have the potential for the best tumor response. Currently, several clinical trials are underway to assess the safety and efficacy of administering immunotherapeutic agents concurrently or consecutively with SRS. In this review, we conduct a comprehensive analysis of the advantages and drawbacks of integrating immunotherapy into conventional SRS protocols for the treatment of intracranial metastasis.

Stereotactic Radiosurgery for Medically Refractory Trigeminal Neuralgia Secondary to Stroke: A Systematic Review and Clinical Case Presentation.

BACKGROUND: Trigeminal neuralgia (TN) is a paroxysmal, unilateral, brief, shock-like pain in ≥1 divisions of the trigeminal nerve. It can result from multiple causes; however, TN secondary to stroke is very rare. METHODS: We present the case of TN secondary to pontine infarction treated with incremental doses of neuropathic pain medication for >5 years before conservative management failed. He was then treated with stereotactic radiosurgery (SRS). Additionally, we conducted a systematic review using standard PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines for all the cases of TN with brainstem stroke from 1976 to 2022. RESULTS: Our patient was an 82-year-old man. Magnetic resonance imaging demonstrated a pontine lesion consistent with stroke. The Barrow Neurological Institute (BNI) score at presentation was 5. He received a marginal dose of 60 Gy to the 80% isodose line in a single fraction to a volume of 0.05 cm3. The immediate post-treatment BNI score was 0 and remained at 0 for 3 months, when he experienced recurrence. The recurrence was treated with oxcarbazepine. His pain remained well controlled with a lower dose of oxcarbazepine, and he had no adverse effects at 1 year of follow-up with a BNI score of 3. The systemic review identified 21 case reports with a combined cohort of 25 patients with TN secondary to stroke. Only 3 patients were treated with SRS, 2 of whom reported symptom improvement at 6 months and 8 months of follow-up with no adverse events. CONCLUSIONS: Our case and literature review demonstrate durable and effective treatment with SRS, which can be considered a safe and effective treatment option for patients with stroke-associated TN.

Stereotactic radiosurgery for sarcoma metastases to the brain: a single-institution experience.

OBJECTIVE: Brain metastases (BMs) secondary to sarcoma are rare, and their incidence ranges from 1% to 8% of all bone and soft tissue sarcomas. Although stereotactic radiosurgery (SRS) is widely used for BMs, only a few papers have reported on SRS for sarcoma metastasizing to the brain. The purpose of this study was to evaluate the safety and effectiveness of SRS for sarcoma BM. METHODS: The authors retrospectively reviewed the clinical and radiological outcomes of patients with BM secondary to histopathologically confirmed sarcoma treated with SRS, either as primary treatment or as adjuvant therapy after surgery, at their institution between January 2005 and September 2022. They also compared the outcomes of patients with hemorrhagic lesions and of those without. RESULTS: Twenty-three patients (9 females) with 150 BMs secondary to sarcoma were treated with CyberKnife SRS. Median age at the time of treatment was 48.22 years (range 4-76 years). The most common primary tumor sites were the heart, lungs, uterus, upper extremities, chest wall, and head and neck. The median Karnofsky Performance Status on presentation was 73.28 (range 40-100). Eight patients underwent SRS as a primary treatment and 15 as adjuvant therapy to the resection cavity. The median tumor volume was 24.1 cm3 (range 0.1-150.3 cm3), the median marginal dose was 24 Gy (range 18-30 Gy) delivered in a median of 1 fraction (range 1-5) to a median isodose line of 76%. The median follow-up was 8 months (range 2-40 months). Median progression-free survival and overall survival were 5.3 months (range 0.4-32 months) and 8.2 months (range 0.1-40), respectively. The 3-, 6-, and 12-month local tumor control (LTC) rates for all lesions were respectively 78%, 52%, and 30%. There were no radiation-induced adverse effects. LTC at the 3-, 6-, and 12-month follow-ups was better in patients without hemorrhagic lesions (100%, 70%, and 40%, respectively) than in those with hemorrhagic lesions (68%, 38%, and 23%, respectively). CONCLUSIONS: SRS, both as a primary treatment and as adjuvant therapy to the resection cavity after surgery, is a safe and relatively effective treatment modality for sarcoma BMs. Nonhemorrhagic lesions show better LTC than hemorrhagic lesions. Larger studies aiming to validate these results are encouraged.

Stereotactic radiosurgery for distant brain metastases secondary to esthesioneuroblastoma: a single-institution series.

OBJECTIVE: Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare, malignant tumor of neuroectodermal origin that arises from the olfactory neuroepithelium. In this study the authors present the first series in the literature on distant brain metastases (BMs) secondary to ENB that were treated with stereotactic radiosurgery (SRS), to evaluate the safety and effectiveness of SRS for this indication. METHODS: A retrospective analysis of clinical and radiological outcomes of patients with ENB who underwent CyberKnife (CK) SRS at a single center was conducted. The clinical and radiological outcomes of patients, including progression-free survival, overall survival, and local tumor control (LTC) were reported. RESULTS: Between 2003 and 2022, 32 distant BMs in 8 patients were treated with CK SRS at Stanford University. The median patient age at BM diagnosis was 62 years (range 47-75 years). Among 32 lesions, 2 (6%) had previously been treated with surgery, whereas for all other lesions (30 [94%]), CK SRS was used as their primary treatment modality. The median target volume was 1.5 cm3 (range 0.09-21.54 cm3). CK SRS was delivered by a median marginal dose of 23 Gy (range 15-30 Gy) and a median of 3 fractions (range 1-5 fractions) to a median isodose line of 77% (range 70%-88%). The median biologically effective dose was 48 Gy (range 21-99.9 Gy) and the median follow-up was 30 months (range 3-95 months). The LTC at 1-, 2-, and 3-year follow-up was 86%, 65%, and 50%, respectively. The median progression-free survival and overall survival were 29 months (range 11-79 months) and 51 months (range 15-79 months), respectively. None of the patients presented adverse radiation effects. CONCLUSIONS: In the authors' experience, SRS provided excellent LTC without any adverse radiation effects for BMs secondary to ENB.

CyberKnife Radiosurgery for Treatment of Residual or Recurrent Grade 1 Choroid Plexus Papilloma: A Single-Institution Experience.

BACKGROUND: Choroid plexus papillomas (CPPs) are rare intraventricular brain tumors derived from the epithelium of the choroid plexus. Gross total resection has traditionally been considered curative, but residual tumor or recurrence remains possible. Stereotactic radiosurgery (SRS) has become a more important strategy for subtotally resected and recurrent tumors. The evidence-based rationale of SRS treatment for residual or recurrent CPP in adult patients is still lacking because of the rarity of the disease. METHODS: We retrospectively reviewed the cases of histopathologically confirmed patients with residual or recurrent CPP treated with SRS at our institute in the adult population between 2005 and 2022. Three patients, with 5 lesions, were identified, with a median age of 63 years. Patients presented initially with hydrocephalus-related symptoms, although ventriculomegaly was noted in only 1 patient radiographically. The tumor location was most commonly in the fourth ventricle or along the foramen of Luschka. Treatment was delivered in a single fraction in 4 lesions and in 3 fractions in 1 patient. The median follow-up was 26 months. RESULTS: The local tumor control rate for the lesions was 80%. One patient developed a new lesion outside the SRS field, and 1 lesion developed progression without the need for subsequent treatment. There was no significant shrinkage of the lesions radiographically. None of the patients showed radiation-related adverse events. No patients required surgical management after SRS treatment at our institution. Based on the literature review, our case series was the second largest retrospective series from a single institution on SRS for recurrent or residual CPP. CONCLUSIONS: SRS for patients with recurrent or residual CPP was a safe and effective treatment modality in this case series. Larger studies are encouraged to validate the role of SRS in the treatment of recurrent or residual CPP.

Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicle Infusion for the Treatment of Respiratory Failure From COVID-19: A Randomized, Placebo-Controlled Dosing Clinical Trial.

BACKGROUND: Bone marrow mesenchymal stem cell (BM-MSC)-derived extracellular vesicles (ExoFlo) convey the immunomodulatory and regenerative properties of intact BM-MSCs. This study aimed to determine the safety and efficacy of ExoFlo as treatment for moderate to severe ARDS in patients with severe COVID-19. RESEARCH QUESTION: Do two doses of ExoFlo safely reduce mortality in COVID-19-associated moderate to severe ARDS compared with placebo? STUDY DESIGN AND METHODS: A prospective phase 2 multicenter double-anonymized randomized placebo-controlled dosing trial was conducted at five sites across the United States with infusions of placebo, 10 mL of ExoFlo, or 15 mL of ExoFlo on days 1 and 4. Patients (N = 102) with COVID-19-associated moderate to severe ARDS were enrolled and randomized to treatment. Adverse events were documented throughout the study. The primary outcome measure was all-cause 60-day mortality rate. Secondary outcomes included time to death (overall mortality); the incidence of treatment-emergent serious adverse events; proportion of discharged patients at 7, 30, and 60 days; time to hospital discharge; and ventilation-free days. RESULTS: No treatment-related adverse events were reported. Mortality (60-day) in the intention-to-treat population was reduced with 15 mL ExoFlo mixed with 85 mL normal saline (ExoFlo-15) compared with placebo (not significant, χ2, P = .1343). For the post hoc subgroup analyses, 60-day mortality was decreased with ExoFlo-15 compared with placebo (relative risk, 0.385; 95% CI, 0.159-0.931; P = .0340; n = 50). With ExoFlo-15, a relative risk of 0.423 (95% CI, 0.173-1.032; P = .0588; n = 24) was determined for participants aged 18 to 65 years with moderate to severe ARDS. Ventilation-free days improved with ExoFlo-15 (P = .0455; n = 50) for all participants aged 18 to 65 years. INTERPRETATION: The 15 mL dose of ExoFlo was found to be safe in patients with severe or critical COVID-19-associated respiratory failure. In participants aged 18 to 65 years, the risk reduction in 60-day mortality was further improved from subjects of all ages in the intention-to-treat population after two doses of 15 mL of ExoFlo compared with placebo. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04493242; URL: www. CLINICALTRIALS: gov.

Cyberknife Radiosurgery for Synovial Sarcoma Metastasizing to the Spine: Illustrative Case Reports.

Synovial sarcoma (SS) is a rare and aggressive type of soft tissue sarcoma that commonly affects young adults. Metastasis in the spine is a rare complication, and the management of these lesions is challenging. Radiosurgery is an increasingly popular treatment option for spinal metastasis due to its ability to deliver high doses of radiation to the target volume with minimal exposure to surrounding healthy tissues. In this paper, we present two cases of SS with spinal metastasis that were treated with CyberKnife radiosurgery (CKRS). The first case was a 52-year-old female with a history of multiple thoracotomies and lobectomies for lung metastases, who was diagnosed with T6-T8 and T4 spinal metastasis. The second case was a 53-year-old female with Down syndrome, who was diagnosed with T12-L1 spinal metastasis. Both patients experienced an improvement in their symptoms following CKRS treatment and showed stable or decreasing lesion sizes on follow-up imaging. The progression-free survival (PFS) in the first case was 37 months and overall survival (OS) was 79 months. In the second case, the PFS was 12 months and OS was 18 months. These cases highlight the potential benefits of CKRS as a treatment option for SS with spinal metastasis and support its use in the management of this challenging condition.

Using 68 Ga-DOTATATE PET for Postoperative Radiosurgery and Radiotherapy Planning in Patients With Meningioma: A Case Series.

BACKGROUND: For patients with either an incompletely resected meningioma or recurrence after surgery, stereotactic radiosurgery is frequently used. MRI is typically used for stereotactic radiosurgery targeting, but differentiating tumor growth from postoperative change can be challenging. 68 Ga-DOTATATE, a positron emission tomography (PET) radiotracer targeting the somatostatin receptor type 2, has been shown to be a reliable meningioma biomarker. OBJECTIVE: To evaluate the impact of 68 Ga-DOTATATE on treatment planning in patients who had previously undergone meningioma resection. METHODS: We present a consecutive case series of 12 patients with pathology-proven meningioma who received a 68 Ga-DOTATATE PET between April 2019 and April 2021. Treatment planning was performed first using MRI. DOTATATE-PET images were then used to assess accurate tumor identification. RESULTS: Ten patients had WHO Grade 2 meningioma, and 2 patients had Grade 1 tumor. Eight patients had recurrent meningiomas, and 4 patients had newly diagnosed disease. Overall, 68 Ga-DOTATATE PET scans altered previously formulated treatment plans in 5 of 12 patients. In addition, 9 of 12 patients had disease foci not appreciated on MRI. CONCLUSION: In this series, incorporating 68 Ga-DOTATATE PET imaging had clinical utility for most patients in whom it was used. It proved particularly adept in demonstrating intraosseous meningiomas, differentiating recurrence from postoperative changes, and identifying subcentimeter disease foci. It is an imaging modality that our center will continue to use as a means of improving postoperative treatment plans after the surgical resection of meningiomas.

Stereotactic Radiosurgery for Localized Cranial Langerhans Cell Histiocytosis: A Single Institution Experience and Review of Literature.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare idiopathic disease characterized by the clonal proliferation of Langerhans histiocytes in various parts of the body and capable of leading to organ damage and tumor formation. Reports of cranial LCH in the adult population are extremely rare. Although surgery remains the preferred option for localized LCH lesions, the role of stereotactic radiosurgery (SRS) is emerging. OBJECTIVE: To retrospectively review a rare case series to determine the safety and effectiveness of SRS for patients with localized cranial LCH. METHODS: We retrospectively reviewed histopathologically confirmed cases of localized cranial LCH treated with SRS at our institute in the adult population between January 2005 and September 2022. Five patients were identified with a median age of 34 years (19-54 years). The tumor location was in the pituitary stalk in 3 patients, the orbit in one patient, and the parietal skull in one patient. The median target volume was 2.8 cc (range: 0.37-6.11). Treatment was delivered in a single fraction in 4 patients (median margin dose of 8 Gy, range: 7-10 Gy) and in 3 fractions (22.5 Gy) in 1 patient. The median follow-up was 12 years (range: 4-17). None of the patients required craniotomy for tumor debulking before or after SRS. RESULTS: The local tumor control rate for the lesions was 100%. All 3 patients with LCH in the pituitary stalk had diabetes insipidus at the initial presentation and developed panhypopituitarism after SRS. Diabetes insipidus was not improved after SRS. The other 2 patients presented no adverse radiation effects. Based on the literature review, our case series was the largest retrospective series on SRS for localized cranial LCH, with the longest median follow-up. CONCLUSIONS: SRS for patients with localized cranial LCH was a safe and effective treatment modality in this case series. Larger studies are encouraged to validate the role of SRS in the treatment of localized cranial LCH.

CyberKnife Radiosurgery for Extracranial Metastases of Oligodendroglioma: A Clinical Case Report.

Oligodendroglioma is an uncommon glial tumor known for its extremely rare tendency to metastasize to extracranial areas, particularly to the spinal region. We present a rare case of oligodendroglioma that metastasizes to the spinal cord 14 years after resection of the initial tumor. Furthermore, a systematic review of the relevant literature is conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, encompassing oligodendroglioma cases with extracranial metastases. Our PRISMA-guided systematic review fills a critical knowledge gap in neurosurgery by consolidating scattered data on oligodendroglioma metastases, offering pivotal insights for clinical practice and future research. A 50-year-old male patient exhibited severe headaches and dizziness, with MRI findings revealing a significant brain mass suggestive of oligodendroglioma. Consequently, the patient underwent a craniotomy procedure. After 14 years, the patient presented with weakness in both lower extremities and bladder as well as bowel dysfunction. A lumbosacral MRI of the patient revealed two intradural enhancing masses in the lumbosacral spine. Surgical resection was performed, and the characteristics were identical to those of the primary tumor. The systemic review encompassed 52 articles, covering 67 cases of extracranial metastases from oligodendroglioma. Only three cases in the literature review fulfilled the inclusion criteria, demonstrating the required molecular genetic profiles of isocitrate dehydrogenase​​​ (IDH)-mutation and chromosome 1p/19q-codeletion. The inclusion criteria encompassed cases of oligodendroglioma with confirmed extracranial metastases, focusing on those with documented molecular genetic profiles indicating IDH-mutation and 1p/19q-codeletion. Our emphasis was on identifying cases with this specific genetic profile to ensure consistency and relevance in the literature review. Interestingly, our case was the first to exhibit intradural spinal metastases, while the other cases involved metastasis to the spinal bone marrow. Our case and literature review demonstrate that oligodendrogliomas, although exceptionally rare, can metastasize not only to the extracranial area but also to the spinal cord. To improve survival in oligodendroglioma cases, it is recommended to implement regular radiological screening and monitoring to enable early detection and treatment of extracranial metastases.

Inhaled Sargramostim (Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor) for COVID-19-Associated Acute Hypoxemia: Results of the Phase 2, Randomized, Open-Label Trial (iLeukPulm).

INTRODUCTION: Granulocyte-macrophage colony-stimulating factor (GM-CSF), a protein produced in the lung, is essential for pulmonary host defense and alveolar integrity. Prior studies suggest potential benefits in several pulmonary conditions, including acute respiratory distress syndrome and viral infections. This trial evaluated the effect of the addition of inhaled sargramostim (yeast-derived, glycosylated recombinant human GM-CSF) to standard of care (SOC) on oxygenation and clinical outcomes in patients with COVID-19-associated acute hypoxemia. MATERIALS AND METHODS: A randomized, controlled, open-label trial of hospitalized adults with COVID-19-associated hypoxemia (oxygen saturation <93% on ≥2 L/min oxygen supplementation and/or PaO2/FiO2 <350) randomized 2:1 to inhaled sargramostim (125 mcg twice daily for 5 days) plus SOC versus SOC alone. Institutional SOC before and during the study was not limited. Primary outcomes were change in the alveolar-arterial oxygen gradient (P(A-a)O2) by day 6 and the percentage of patients intubated within 14 days. Safety evaluations included treatment-emergent adverse events. Efficacy analyses were based on the modified intent-to-treat population, the subset of the intent-to-treat population that received ≥1 dose of any study treatment (sargramostim and/or SOC). An analysis of covariance approach was used to analyze changes in oxygenation measures. The intubation rate was analyzed using the chi-squared test. All analyses are considered descriptive. The study was institutional review board approved. RESULTS: In total, 122 patients were treated (sargramostim, n = 78; SOC, n = 44). The sargramostim arm experienced greater improvement in P(A-a)O2 by day 6 compared to SOC alone (least squares [LS] mean change from baseline [SE]: -102.3 [19.4] versus -30.5 [26.9] mmHg; LS mean difference: -71.7 [SE 33.2, 95% CI -137.7 to -5.8]; P = .033; n = 96). By day 14, 11.5% (9/78) of sargramostim and 15.9% (7/44) of SOC arms required intubation (P = .49). The 28-day mortality was 11.5% (9/78) and 13.6% (6/44) in the sargramostim and SOC arms, respectively (hazard ratio 0.85; P = .76). Treatment-emergent adverse events occurred in 67.9% (53/78) and 70.5% (31/44) on the sargramostim and SOC arms, respectively. CONCLUSIONS: The addition of inhaled sargramostim to SOC improved P(A-a)O2, a measure of oxygenation, by day 6 in hospitalized patients with COVID-19-associated acute hypoxemia and was well tolerated. Inhaled sargramostim is delivered directly to the lung, minimizing systemic effects, and is simple to administer making it a feasible treatment option in patients in settings where other therapy routes may be difficult. Although proportionally lower rates of intubation and mortality were observed in sargramostim-treated patients, this study was insufficiently powered to demonstrate significant changes in these outcomes. However, the significant improvement in gas exchange with sargramostim shows this inhalational treatment enhances pulmonary efficiency in this severe respiratory illness. These data provide strong support for further evaluation of sargramostim in high-risk patients with COVID-19.