Repeat stereotactic radiosurgery for progressive vestibular schwannomas after primary gamma knife radiosurgery.

PURPOSE: Limited data provides guidance on the management of vestibular schwannomas (VSs) that have progressed despite primary Gamma Knife radiosurgery (GKRS). The present article reports our long-term experience after repeat GKRS for VS with sustained progression after solely primary GKRS management. METHODS: A retrospective review of 1997 patients managed between 1987 and 2023 was conducted. Eighteen patients had sustained tumor progression after primary GKRS and underwent repeat GKRS. The median repeat GKRS margin dose was 11 Gy (IQR: 11-12), the median tumor volume was 2.0 cc (IQR: 1.3-6.3), and the median cochlear dose in patients with preserved hearing was 3.9 Gy (IQR: 3-4.1). The median time between initial and repeat GKRS was 65 months (IQR: 38-118). RESULTS: The median follow-up was 70 months (IQR: 23-101). After repeat GKRS, two patients had further tumor progression at 4 and 21 months and required partial resection of their tumors. The 10-year actuarial tumor control rate after repeat GKRS was 88%. Facial nerve function was preserved in 13 patients who had House-Brackmann grade 1 or 2 function at the time of repeat GKRS. Two patients with serviceable hearing preservation (Gardner-Robertson grade 1 or 2) at repeat GKRS retained that function afterwards. In patients with tinnitus, vestibular dysfunction, and trigeminal neuropathy, symptoms remained stable or improved for 16/16 patients, 12/15 patients, and 10/12 patients, respectively. One patient developed facial twitching in the absence of tumor growth 21 months after repeat GKRS. CONCLUSIONS: Repeat GKRS effectively controlled tumor growth and preserved cranial nerve outcomes in most patients whose VS had sustained progression after initial primary radiosurgery.

The role of spine stereotactic radiosurgery for patients with breast cancer metastases.

PURPOSE: Breast cancer that metastasizes to the spine is associated with low quality of life and poor survival. Radiosurgery has an increasing role in this patient population. This single-institution (2003-2023) study analyzes clinical outcomes and prognostic factors for patients who underwent spinal stereotactic radiosurgery (SSRS) for metastatic breast cancer. METHODS: Ninety patients (155 unique breast cancer spinal metastases) were treated with SSRS. The median age was 57 years (range: 35-88), and the median KPS was 80 (range: 40-100). Forty-two (27%) lesions were managed surgically prior to radiosurgery. At SSRS, 75 (48%) lesions impinged or compressed the spinal cord per the epidural spinal cord scale (ESCC). Seventy-nine (51%) lesions were categorized as potentially unstable or unstable by the Spinal Instability Neoplastic Score (SINS). RESULTS: The median follow-up was 15 months (range: 1-183). The median single-session tumor volume was 25.4 cc (range: 2-197), and the median single-fraction prescription dose was 17 Gy (range: 12-25). Seven (5%) lesions locally progressed. The 1-, 2-, and 5-year local control rates were 98%, 97%, and 92%, respectively. The median overall survival (OS) for the cohort was 32 months (range: 2-183). The 1-, 2-, and 5-year OS rates were 72%, 53%, and 30%, respectively. On univariate analysis, KPS ≥ 80 (p = 0.009, HR: 0.51, 95% CI: 0.31-0.84) was associated with improved OS. Patient-reported pain improved (68%), remained stable (29%), or worsened (3%) following radiosurgery. Fifteen (10%) radiation-induced toxicities were reported. CONCLUSIONS: Spinal radiosurgery is a safe and highly effective long-term treatment modality for metastases to the spine that originate from breast cancer.

Stereotactic radiosurgery for patients with spinal metastases from prostate cancer.

PURPOSE: Spinal metastases may result in intractable pain, neurological deficit, and vertebral body collapse. There are only a few studies describing outcomes following spine stereotactic radiosurgery (SRS) specifically for prostate cancer metastases. METHODS: A prospectively collected database of patients with prostate cancer spinal metastases treated at the University of Pittsburgh Medical Center from 2003 to 2023 was analyzed. The primary outcome was local control (LC). Secondary outcomes were overall survival (OS), pain resolution, and adverse radiation effects (AREs). RESULTS: Thirty-seven patients and 51 lesions were identified. Fifteen lesions (29%) were previously resected and 34 lesions (67%) were previously irradiated. The median tumor volume was 37.0 cc (range: 2.9-263.3). A majority of lesions (71%) were treated in a single fraction (median 20 Gy, range: 14-22.5); multi-fractionated treatment consisted of 21-30 Gy in 2-5 fractions. Median follow-up was 12 months (range: 1-146). The 6-month, 1-year, and 2-year LC rates were 97%, 91%, and 91%, respectively. No tested prognostic factors were associated with LC, including hormone sensitivity. The 6-month, 1-year, and 2-year OS rates were 71%, 56%, and 32%; age > 70 years (p = 0.048) and tumor volume > 30 cc (p = 0.03) were associated with inferior rates of OS. Complete or partial pain response was observed in 58% of patients. There were 8 instances (16%) of AREs, 2 of which were vertebral compression fractures (4%). CONCLUSION: Radiosurgery as a primary or adjuvant treatment modality for prostate cancer spinal metastases confers durable LC and moderate pain relief with minimal toxicity. Further studies are warranted to optimize management in this patient population.

Stereotactic radiosurgery for patients with brain metastases from gastroesophageal cancers.

BACKGROUND: The prognosis of patients with brain metastases from gastroesophageal (GE) cancers remains unclear despite recent advances in systemic therapies. The authors present a large single-institution experience in the use of stereotactic radiosurgery (SRS). METHODS: A retrospective review of 71 GE cancer patients (64 male, 90.14%) who underwent Gamma Knife SRS was conducted. Overall, 243 brain metastases were treated and the median number of metastases per patient was 2 (range:1-21). The median age at SRS was 66 years (range: 26-85) and the median treatment day KPS was 80 (range: 50-100). The median cumulative tumor volume was 6.7 cc (range: 0.27-104.76) and the median single-session margin dose was 18 Gy (range: 12-20). RESULTS: The median overall survival after SRS was 7 months (range: 1-64). At last follow up, 54 (76.06%) patients were deceased, 8 of whom (14.81%) expired secondary to their intracranial metastases. Four patients (5.63%) experienced local tumor progression at a median time of 8 months (range: 2-13) after SRS. Ten patients (14%) experienced new remote tumor development at a median time of 4 months (range: 0-14) after SRS. Whole-brain radiation therapy (2 patients, 20%) and repeat SRS (8 patients, 80%) were used for newly developed tumors. The incidence of transient adverse radiation effects was 8.45%. CONCLUSIONS: In this study, the 12-month local tumor control rate was 90%. Incidences of adverse radiation effect rates were rare. The median overall survival of 7 months indicates the poor prognosis of patients with brain spread of their GE cancer.

Does Adjuvant Gamma Knife Stereotactic Radiosurgery Have a Role in Treating Optic Nerve Sheath Meningiomas?

BACKGROUND: Meningiomas arising from or adjacent to the optic nerve sheath meningioma (ONSM) are management challenges because of their risk of visual loss. Stereotactic radiosurgery (SRS) is a minimally invasive modality that can be added as adjuvant treatment for patients whose tumor has progressed or recurred after initial resection. METHODS: The authors retrospectively reviewed 2,030 meningioma patients who underwent SRS between 1987 and 2022. In total, 7 patients (4 females; median age = 49) were found with tumors originating from the optic nerve sheath. None of the patients had tumors that engulfed the optic nerve as such tumors typically undergo fractionated radiation therapy (FRT) to preserve vision. The clinical history, visual function, and radiographic and neurological findings were characterized. Outcome measures included visual status, tumor control, and the need for additional management. RESULTS: All patients underwent either initial gross total (n = 1) or partial surgical resection (n = 6) before SRS. Two patients with progressive tumor growth also had SRS after failing additional fractionated radiation after surgery (54 Gy, 30 fractions for both patients). The median time between the date of surgery and the SRS procedure date was 38 months. The Leksell Gamma Knife was used to deliver a margin dose of 12 Gy (range: 8-14 Gy) to a median cumulative tumor volume of 3.3 cc (range: 1.2-18 cc). The median maximal optic nerve radiation dose was 6.5 Gy (range: 1.9-8.1 Gy). After SRS, the median follow-up time was 130 months (range: 26-169 months). Two patients showed local tumor progression at 20 and 55 months after SRS. Four had stable visual function, 2 experienced improved visual acuity, and 1 patient had visual deterioration. CONCLUSIONS: Meningiomas arising from (but not engulfing the optic nerve) represent management quandaries after failed initial surgical removal. In this experience, salvage SRS was associated with tumor control and vision preservation in 5 of 7 patients. Additional experience with this strategy may further define the role of SRS both as a salvage and primary option.

Technical choices significantly alter the adaptive immune response against immunocompetent murine gliomas in a model-dependent manner.

PURPOSE: Due to the recent rise in immunotherapy research to treat glioblastoma (GBM), immunocompetent mouse models have become increasingly crucial. However, the character and kinetics of the immune response against the most prevalent immunocompetent GBM models, GL261 and CT2A, have not been well studied, nor has the impact of commonly-used marker proteins and foreign antigens. METHODS: In this study, we compared the immune response in these models using flow cytometry and immunohistochemistry as well as investigated several factors that influence the immune response, including kinetics, tumor size, and expression of commonly-used marker proteins and foreign antigens. We hypothesize that these factors influence the immune response enough to warrant consideration when studying new immunotherapeutic approaches for GBM. RESULTS: CT2A-Luc, but not GL261-Luc2, drastically increased the number of T cells in the brain compared with wild-type controls, and significantly altered CT2A's responsiveness to anti-PD-1 antibody therapy. Additionally, a larger cell inoculum size in the GL261 model increased the T cell response's magnitude at day 28 post-injection. CT2A and GL261 models both stimulate a peak T cell immune response at day 21 post-injection. CONCLUSIONS: Our results suggest that the impact of foreign proteins like luciferase on the intracranial immune response is dependent upon the model, with CT2A being more sensitive to added markers. In particular, luciferase expression in CT2A could lead to meaningful misinterpretations of results from immune checkpoint inhibitor (ICI) studies.

The Role of Stereotactic Radiosurgery in Patients With Brain Metastases From Colorectal Cancers.

BACKGROUND AND OBJECTIVES: The role of stereotactic radiosurgery (SRS) in patients with brain metastases (BMs) from colorectal cancers (CRCs) has not been established. The authors present a single-institution experience of patients with CRC who underwent SRS with metastatic brain spread. METHODS: We retrospectively analyzed 111 patients with metastatic CRC (64 female, 57.7%), with 449 BMs treated with Gamma Knife SRS between 2000 and 2022. The median age during SRS was 63 years (range: 28-86), and the median Karnofsky Performance Scale was 80 (range: 60-100). The primary sites were colon (85 patients, 76.6%) and rectal (26 patients, 23.4%). Three patients underwent hypofractionated SRS (3 sessions) with a median margin dose of 27 Gy (range: 27-30). All other patients underwent single-session SRS with a median margin dose of 18 Gy (range: 13-20). RESULTS: The median patient survival after SRS was 7 months (range: 1-174). Ninety-eight (88.3%) patients expired at last follow-up and 15 patients (15.3%) died related to progressive intracranial disease. A Karnofsky Performance Scale of <80 at SRS presentation ( P = .02, hazard ratio [HR]: 0.6, 95% CI: 0.4-0.9) and no previous surgical resection ( P < .01, HR: 0.4, 95% CI: 0.3-0.7) were associated with inferior overall survival using multivariate analysis. Seventeen patients (15.3%) had documented local tumor progression after SRS, at a median time of 7 months (range: 3-34) between SRS and progression. Twenty-six patients (23.4%) developed new BMs at a median of 5 months (range: 2-26) between SRS and new tumor detection. Less than three BMs at SRS presentation ( P = .02, HR: 2.6, 95% CI: 1.2-5.6) were associated with better distant tumor control on multivariate analysis. The incidence of adverse radiation effects was 5.4%. CONCLUSION: SRS effectively controls BMs from CRC with low risk of treatment-related toxicity. During follow-up, the development of additional metastases can be safely treated by repeat SRS.

Analysis of injected cement volume and clinical outcomes following balloon-assisted kyphoplasty in a series of 368 patients.

OBJECTIVE: Balloon-assisted kyphoplasty (BAK) is a modified vertebroplasty technique developed to treat vertebral compression fractures (VCFs) secondary to osteoporosis. This study investigates the association between injected cement volume and the development of subsequent VCFs after BAK. METHODS: A retrospective analysis of 368 patients who underwent BAK at a single institution was performed from 2001 to 2021. Inclusion was defined by at least 2 years of follow-up. Clinical characteristics and outcomes following BAK, including subsequent fractures at adjacent and remote levels, were identified. Patients that underwent a thoracic BAK were stratified by injected cement volume: below or equal to the median (≤ 6.0 mL, 265 vertebrae) or above the median (> 6.0 mL, 144 vertebrae). Patients that underwent a lumbar BAK were similarly stratified: below or equal to the median (≤ 8.0 mL, 233 vertebrae) or above the median (>8.0 mL, 160 vertebrae). RESULTS: A total of 802 vertebrae were treated. The average volume of cement was recorded in the thoracic (6.2 ± 1.9 mL) and lumbar (7.8 ± 1.8 mL) vertebrae. In the thoracic spine, vertebrae that were injected with > 6.0 mL of cement underwent a greater change in local kyphotic angle (P = 0.0001) and were more likely to develop adjacent-level VCFs (P = 0.032) after kyphoplasty. Univariate analysis did not elucidate any additional risk factors. There were no statistical differences in clinical outcomes between the three groups of lumbar vertebrae. CONCLUSIONS: Larger volumes of injected cement were associated with a greater change in local kyphosis and subsequent adjacent-level fractures after BAK in the thoracic spine. This association was not found in the lumbar spine. Close attention to injected cement volumes must be made in the thoracic spine and patients who undergo significant kyphotic correction should be carefully observed postoperatively.

Development of Symptomatic Adjacent and Remote Level Compression Fractures Following Balloon-assisted Kyphoplasty in a Series of 1,318 Patients.

BACKGROUND: Balloon-assisted kyphoplasty (BAK) is a minimally invasive procedure to treat vertebral compression fractures (VCF). BAK not only restores vertebral height and corrects kyphotic deformity by cement augmentation, but it also may alter spinal biomechanics, leading to subsequent adjacent level VCFs. OBJECTIVES: This study aims to investigate the timing, location, and incidence of new VCFs following BAK and identify the risk factors associated with their occurrence. STUDY DESIGN: Single-institution observational study. METHODS: A prospectively collected cohort of 1,318 patients who underwent BAK by a single-surgeon from 2001 through 2022 was analyzed. The patients had pain that was unresponsive to nonsurgical management and a VCF secondary to osteoporosis, trauma, or neoplasm. The time between the index and subsequent fracture, fracture level, number of initial fractures, age, body mass index (BMI), tobacco use, and chronic corticosteroid use were recorded. RESULTS: Of 1,318 patients, 204 (15.5%) patients underwent a second BAK procedure an average of 373 days following BAK (range: 2-3,235 days). Third, fourth, and fifth procedures were less common (45, 12, and 6 patients, respectively). A total of 142 patients (69.6%) developed a subsequent fracture adjacent to the index level; adjacent and remote level fractures developed at different times (mean: 282 vs 581 days, P = 0.001). Patients treated for multiple VCFs in a single surgery were more likely to develop subsequent VCFs (P = 0.024) and at adjacent levels (P = 0.007). Subsequent VCFs were associated with older age (P < 0.001), women (P = 0.045), osteoporosis (P < 0.001), and chronic corticosteroid use (P < 0.001). A subgroup analysis of 812 (61.6%) patients who underwent BAK for degenerative indications revealed that osteoporosis (b = 0.09; 95% CI, 0.03-0.16; P = 0.005) and chronic corticosteroid use (b = 0.06; 95% CI, 0-0.11; P = 0.055) were associated with adjacent level fracture. For the entire cohort, almost every patient treated for both a thoracic and lumbar fracture (92.3%) developed an adjacent level second fracture (P = 0.005). LIMITATIONS: The true incidence of post-BAK fractures may be underestimated as surveillance is not routine in asymptomatic or osteoporotic patients. CONCLUSIONS: Symptomatic post-BAK VCFs are infrequent and may occur long after the initial procedure. Nearly two-thirds of subsequent fractures in our study occurred adjacent to the initially treated level; almost every patient who suffered thoracic and lumbar fractures at the same time developed an adjacent level second fracture. Additionally, osteoporosis and chronic corticosteroid use were associated with adjacent level fractures in patients who underwent surgery for degenerative indications.

Prediction of 30-day and 1-year postoperative complications after balloon-assisted kyphoplasty in the elderly using the Risk Analysis Index.

OBJECTIVE: Vertebral compression fracture (VCF) is the most prevalent fragility fracture. When conservative management fails, patients may undergo balloon-assisted kyphoplasty (BAK). In BAK, an expandable balloon preforms a cavity in the fractured vertebra before injection of bone cement. The aim of this study was to compare outcomes in patients stratified by age and frailty assessed by the Risk Analysis Index (RAI). METHODS: A retrospective analysis of 334 BAK procedures (280 patients) for osteoporotic VCFs at a single institution was performed (2015-2022). Patients with at least 1 year of follow-up were eligible for inclusion. Patient demographics were recorded, including age, sex, BMI, RAI score, tobacco and steroid use, osteoporosis treatments, and bone density. Patients who underwent outpatient surgery were identified, and length of stay (LOS) was obtained for admitted patients. The rates of additional VCFs after kyphoplasty, 30-day and 1-year postoperative complications, and reoperation were identified. RESULTS: The overall rates of additional VCFs, 30-day postoperative complications, 1-year postoperative complications, and reoperation were 16.2%, 5.1%, 12.0%, and 6.3%, respectively. Patients were stratified by age: nonelderly (< 80 years; 220 patients, 263 treated vertebrae) and elderly (≥ 80 years; 60 patients, 71 treated vertebrae). There were no differences in sex (p = 0.593), tobacco use (p = 0.973), chronic steroid use (p = 0.794), treatment for osteoporosis (p = 0.537), bone density (p = 0.056), outpatient procedure (p = 0.273), and inpatient LOS (p = 0.661) between both groups. There were also no differences in the development of additional VCFs (p = 0.862) at an adjacent level (p = 0.739) or remote level (p = 0.814), 30-day and 1-year postoperative complications (p = 0.794 and p = 0.560, respectively), and reoperation rates (p = 0.420). Patients were then analyzed by RAI: nonfrail (RAI score < 30; 203 patients, 243 treated vertebrae) and frail (RAI score ≥ 31; 77 patients, 91 treated vertebrae). There were no differences in tobacco use (p = 0.959), chronic steroid use (p = 0.658), treatment for osteoporosis (p = 0.560), bone density (p = 0.339), outpatient procedure (p = 0.241), inpatient LOS (p = 0.570), and development of additional VCFs (p = 0.773) at an adjacent level (p = 0.390) or remote level (p = 0.689). However, rates of 30-day and 1-year postoperative complications in frail patients more than doubled in comparison with nonfrail patients (p = 0.031 and p = 0.007, respectively), and frail patients trended toward reoperation (p = 0.097). CONCLUSIONS: BAK is a safe treatment in the elderly, and age alone should not be used as an exclusion criterion during patient selection. Frailty, which can be assessed reliably using the RAI, may serve as a better predictor for postoperative complications and reoperation following BAK.

Safety and Efficacy of Balloon-Assisted Kyphoplasty Followed by Stereotactic Body Radiation Therapy for Pathological Fractures.

BACKGROUND AND OBJECTIVES: In patients experiencing pain secondary to pathological compression fractures, balloon-assisted kyphoplasty and subsequent stereotactic body radiation therapy (SBRT) may allow for restoration of vertebral height and irradiation of the underlying malignancy to control local disease progression. The aim of this study was to evaluate the safety and efficacy of kyphoplasty treatment before SBRT in patients with spinal metastases and benign tumors. METHODS: An analysis of a prospectively collected database of 70 patients and 75 metastatic and benign spinal lesions that underwent kyphoplasty before SBRT at a single institution (2002-2023) was conducted. Patient characteristics were recorded, including treatment history, dosimetry and fractionation schedule, pain outcomes, local control (LC), and overall survival. The Bilsky score and Spinal Instability Neoplastic Score were calculated to assess epidural involvement and spinal stability, respectively. RESULTS: The median time from kyphoplasty to SBRT was 29 days (range: 2-159). Seventy-two lesions (96%) were managed with single-fraction SBRT and 3 lesions (4%) with a multifraction regimen. The median single-fraction prescription dose was 20 Gy (range: 12-25) delivered to a median tumor volume of 35.1 cc (range: 2.2-160). After a median follow-up period of 9 months (range: 1-201), 6 lesions (8%) locally progressed. Pain was reported to improve or remain stable for most patients (88%). The LC rate was 88% at 6 months, 1 year, and 2 years. No prognostic factors were significantly associated with LC. The median overall survival was 11 months (range: 1-201) after radiosurgery. There were no reports of cement extravasation or radiation-induced neurological deficit. Two acute pain flares (3%) were reported 1 and 3 months after radiosurgery. CONCLUSION: The combined kyphoplasty and SBRT treatment paradigm can be used to treat patients with painful pathological compression fractures. Long-term LC and patient-reported improvement in pain were observed without the morbidity associated with open surgery.

Spine Stereotactic Radiosurgery Provides Long-Term Local Control and Overall Survival for Benign Intradural Tumors.

BACKGROUND AND OBJECTIVES: The role of radiosurgery in the treatment of benign intracranial tumors is well established. However, there are limited long-term follow-up studies on outcomes after stereotactic radiosurgery (SRS) for benign intradural spinal tumors. In this article, we report a large single-institution experience in using SRS to treat patients with benign intradural tumors of the spine. METHODS: Overall, 184 patients (55% female) and 207 benign intradural tumors were treated. The median patient age was 52 years (range: 19-93). Tumor histology included schwannoma (38%), meningioma (15%), neurofibroma (21%), hemangioma (9%), hemangioblastoma (8%), hemangiopericytoma (5%), and paraganglioma (4%). Thirty-four (16%) lesions underwent resection before radiosurgery. Twenty-three (11%) lesions were NF1-mutated. The median single-fraction margin dose was 14 Gy (range: 11-20), and the median multifraction margin dose was 21 Gy (range: 15-30). RESULTS: The median follow-up was 63 months (range: 1-258). At last follow-up, tumors volumetrically regressed (15%), remained stable (77%), or locally progressed (8%, median: 20 months [range: 3-161]) after SRS. The 1-, 5-, and 10-year local control rates were 97%, 92%, and 90%, respectively. On multivariable analysis, the absence of the NF1 mutation (P = .004, hazard ratio: 0.23, 95% CI: 0.08-0.63) and single-fraction SRS (P = .007, hazard ratio: 0.24, 95% CI: 0.08-0.68) correlated with improved local control. The median overall survival was 251 months (range: 1-258), and 1-, 5-, and 10-year overall survival rates were 95%, 85%, and 70%, respectively. For patients with pre-existing symptoms, tumor-associated pain and neurological deficits were noted to improve or remain stable in 85% and 87% of cases, respectively. Adverse radiation effects included delayed myelopathy (1%), acute pain flare (9%), dermatitis (0.5%), dysphagia (0.5%), and dysphonia (0.5%). CONCLUSION: With long-term follow-up, spine radiosurgery is a safe and effective treatment for benign intradural tumors. In carefully selected patients, even with an NF1 mutation, SRS is associated with a high likelihood of local tumor control.

Stereotactic Radiosurgery for Patients with Spinal Metastases from Thyroid Cancer: A 20-Year Experience.

OBJECTIVE: Primary thyroid cancer metastasizing to the spine portends poor survival and low quality of life. Current management strategies continue to evolve. This single-institution retrospective study analyzes outcomes after spinal stereotactic radiosurgery for patients with spinal metastases from thyroid cancer. METHODS: Nineteen patients (median age: 64.5 years) were treated with stereotactic radiosurgery (SRS) for spinal primary thyroid metastases (40 metastases, 47 vertebral levels) between 2003 and 2023. Nineteen (47.5%) lesions had epidural involvement and 20 (50%) lesions were classified as potentially unstable or unstable via the Spinal Instability Neoplastic Score. The median tumor volume per lesion was 33 cc (range: 1.5-153). The median single fraction prescription dose was 20 Gy (range: 12-23.5). RESULTS: The median follow-up period was 15 months (range: 2-40). Five (12.8%) lesions locally progressed at a median of 9 months (range: 4-26) after SRS. The 1-, 2-, and 3-year local tumor control rates per lesion were 90.4%, 83.5%, and 75.9%, respectively. On univariate analysis, age at SRS >70 years (P = 0.05, hazard ratio: 6.86, 95% confidence interval: 1.01-46.7) was significantly correlated with lower rates of local tumor control. The median overall survival was 35 months (range: 2-141). The 1-, 2-, and 3-year overall survival rates were 73.7%, 50.4%, and 43.2%, respectively. For 33 lesions initially associated with pain, patients reported pain improvement (22 lesions, 66.7%), stability (10 lesions, 30.3%), and worsening (1 lesion, 3.0%) after SRS. One patient developed dysphagia 4 months after SRS treatment. CONCLUSIONS: SRS can be utilized as an effective and safe primary and adjuvant treatment option for primary thyroid metastases to the spine.

Myeloid cells as potential targets for immunotherapy in pediatric gliomas.

Pediatric high-grade glioma (pHGG) including pediatric glioblastoma (pGBM) are highly aggressive pediatric central nervous system (CNS) malignancies. pGBM comprises approximately 3% of all pediatric CNS malignancies and has a 5-year survival rate of approximately 20%. Surgical resection and chemoradiation are often the standard of care for pGBM and pHGG, however, even with these interventions, survival for children diagnosed with pGBM and pHGG remains poor. Due to shortcomings associated with the standard of care, many efforts have been made to create novel immunotherapeutic approaches targeted to these malignancies. These efforts include the use of vaccines, cell-based therapies, and immune-checkpoint inhibitors. However, it is believed that in many pediatric glioma patients an immunosuppressive tumor microenvironment (TME) possess barriers that limit the efficacy of immune-based therapies. One of these barriers includes the presence of immunosuppressive myeloid cells. In this review we will discuss the various types of myeloid cells present in the glioma TME, including macrophages and microglia, myeloid-derived suppressor cells, and dendritic cells, as well as the specific mechanisms these cells can employ to enable immunosuppression. Finally, we will highlight therapeutic strategies targeted to these cells that are aimed at impeding myeloid-cell derived immunosuppression.

Immunotherapy in the Management of Sinonasal Mucosal Melanoma: A Systematic Review.

OBJECTIVE: The aim of this work is to comprehensively review and synthesize the literature related to sinonasal mucosal melanoma (SNMM) treatment with immunotherapy, including potentially targetable genetic mutations, survival outcomes, and adverse events. DATA SOURCES: Embase, Cochrane, Scopus, and Web of Science. REVIEW METHODS: The study protocol was designed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Databases were searched from inception through May 23, 2023. RESULTS: A total of 42 studies met inclusion criteria. Twenty-four of the included studies reported genetic mutations for a combined 787 patients with SNMM. 8.1% (95% confidence interval, CI: 7.6-8.6), 18.9% (95% CI: 18.1-19.8), and 8.5% (95% CI: 8.1-9.0) of reported patients were positive for BRAF, NRAS, and KIT mutations, respectively. The presence of brisk tumor-infiltrating lymphocytes was associated with improved recurrence-free survival and overall survival (OS). Six studies reported a combined 5-year OS after adjuvant immunotherapy treatment of 42.6% (95% CI: 39.4-45.8). Thirteen studies encompassing 117 patients reported adjuvant or salvage immune checkpoint inhibitor (ICI) immunotherapy response rates: 40.2% (95% CI: 36.8-43.6) had a positive response (tumor volume reduction or resolution). Eleven studies reported direct comparisons between SNMM patients treated with or without immunotherapy; the majority (7/11) reported survival benefit for their entire cohort or select subgroups of SNMM patients. With the transition to modern ICIs, there is a stronger trend toward survival improvement with adjuvant ICI. Tumors with Ki67 <40% may respond better to ICI's. CONCLUSION: ICI therapy can be an effective in select SNMM patients, especially those with advanced/metastatic disease.

Machine Learning in Spine Surgery: A Narrative Review.

Artificial intelligence and machine learning (ML) can offer revolutionary advances in their application to the field of spine surgery. Within the past 5 years, novel applications of ML have assisted in surgical decision-making, intraoperative imaging and navigation, and optimization of clinical outcomes. ML has the capacity to address many different clinical needs and improve diagnostic and surgical techniques. This review will discuss current applications of ML in the context of spine surgery by breaking down its implementation preoperatively, intraoperatively, and postoperatively. Ethical considerations to ML and challenges in ML implementation must be addressed to maximally benefit patients, spine surgeons, and the healthcare system. Areas for future research in augmented reality and mixed reality, along with limitations in generalizability and bias, will also be highlighted.

Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming.

Cancers commonly reprogram translation and metabolism, but little is known about how these two features coordinate in cancer stem cells. Here we show that glioblastoma stem cells (GSCs) display elevated protein translation. To dissect underlying mechanisms, we performed a CRISPR screen and identified YRDC as the top essential transfer RNA (tRNA) modification enzyme in GSCs. YRDC catalyzes the formation of N6-threonylcarbamoyladenosine (t6A) on ANN-decoding tRNA species (A denotes adenosine, and N denotes any nucleotide). Targeting YRDC reduced t6A formation, suppressed global translation and inhibited tumor growth both in vitro and in vivo. Threonine is an essential substrate of YRDC. Threonine accumulated in GSCs, which facilitated t6A formation through YRDC and shifted the proteome to support mitosis-related genes with ANN codon bias. Dietary threonine restriction (TR) reduced tumor t6A formation, slowed xenograft growth and augmented anti-tumor efficacy of chemotherapy and anti-mitotic therapy, providing a molecular basis for a dietary intervention in cancer treatment.

Sorting nexin 10 sustains PDGF receptor signaling in glioblastoma stem cells via endosomal protein sorting.

Glioblastoma is the most malignant primary brain tumor, the prognosis of which remains dismal even with aggressive surgical, medical, and radiation therapies. Glioblastoma stem cells (GSCs) promote therapeutic resistance and cellular heterogeneity due to their self-renewal properties and capacity for plasticity. To understand the molecular processes essential for maintaining GSCs, we performed an integrative analysis comparing active enhancer landscapes, transcriptional profiles, and functional genomics profiles of GSCs and non-neoplastic neural stem cells (NSCs). We identified sorting nexin 10 (SNX10), an endosomal protein sorting factor, as selectively expressed in GSCs compared with NSCs and essential for GSC survival. Targeting SNX10 impaired GSC viability and proliferation, induced apoptosis, and reduced self-renewal capacity. Mechanistically, GSCs utilized endosomal protein sorting to promote platelet-derived growth factor receptor ß (PDGFRß) proliferative and stem cell signaling pathways through posttranscriptional regulation of the PDGFR tyrosine kinase. Targeting SNX10 expression extended survival of orthotopic xenograft-bearing mice, and high SNX10 expression correlated with poor glioblastoma patient prognosis, suggesting its potential clinical importance. Thus, our study reveals an essential connection between endosomal protein sorting and oncogenic receptor tyrosine kinase signaling and suggests that targeting endosomal sorting may represent a promising therapeutic approach for glioblastoma treatment.

Loss of Diacylglycerol Kinase α Enhances Macrophage Responsiveness.

The diacylglycerol kinases (DGKs) are a family of enzymes responsible for the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). In addition to their primary function in lipid metabolism, DGKs have recently been identified as potential therapeutic targets in multiple cancers, including glioblastoma (GBM) and melanoma. Aside from its tumorigenic properties, DGKα is also a known promoter of T-cell anergy, supporting a role as a recently-recognized T cell checkpoint. In fact, the only significant phenotype previously observed in Dgka knockout (KO) mice is the enhancement of T-cell activity. Herein we reveal a novel, macrophage-specific, immune-regulatory function of DGKα. In bone marrow-derived macrophages (BMDMs) cultured from wild-type (WT) and KO mice, we observed increased responsiveness of KO macrophages to diverse stimuli that yield different phenotypes, including LPS, IL-4, and the chemoattractant MCP-1. Knockdown (KD) of Dgka in a murine macrophage cell line resulted in similar increased responsiveness. Demonstrating in vivo relevance, we observed significantly smaller wounds in Dgka-/- mice with full-thickness cutaneous burns, a complex wound healing process in which macrophages play a key role. The burned area also demonstrated increased numbers of macrophages. In a cortical stab wound model, Dgka-/- brains show increased Iba1+ cell numbers at the needle track versus that in WT brains. Taken together, these findings identify a novel immune-regulatory checkpoint function of DGKα in macrophages with potential implications for wound healing, cancer therapy, and other settings.