Autologous cell immunotherapy (IGV-001) with IGF-1R antisense oligonucleotide in newly diagnosed glioblastoma patients.

Standard-of-care first-line therapy for patients with newly diagnosed glioblastoma (ndGBM) is maximal safe surgical resection, then concurrent radiotherapy and temozolomide, followed by maintenance temozolomide. IGV-001, the first product of the Goldspire™ platform, is a first-in-class autologous immunotherapeutic product that combines personalized whole tumor-derived cells with an antisense oligonucleotide (IMV-001) in implantable biodiffusion chambers, with the intent to induce a tumor-specific immune response in patients with ndGBM. Here, we describe the design and rationale of a randomized, double-blind, phase IIb trial evaluating IGV-001 compared with placebo, both followed by standard-of-care treatment in patients with ndGBM. The primary end point is progression-free survival, and key secondary end points include overall survival and safety.

Glioblastoma (GBM) is a fast-growing brain tumor that happens in about half of all gliomas. Surgery is the first treatment for patients with newly diagnosed GBM, followed by the usual radiation and chemotherapy pills named temozolomide. Temozolomide pills are then given as a long-term treatment. The outcome for the patient with newly diagnosed GBM remains poor. IGV-001 is specially made for each patient. The tumor cells are removed during surgery and mixed in the laboratory with a small DNA, IMV-001. This mix is the IGV-001 therapy that is designed to give antitumor immunity against GBM. IGV-001 is put into small biodiffusion chambers that are irradiated to stop the growth of any tumor cells in the chambers. In the phase IIb study, patients with newly diagnosed GBM are chosen and assigned to either the IGV-001 or the placebo group. A placebo does not contain any active ingredients. The small biodiffusion chambers containing either IGV-001 or placebo are surgically placed into the belly for 48 to 52 h and then removed. Patients then receive the usual radiation and chemotherapy treatment. Patients must be adults aged between 18 and 70 years. Patients also should be able to care for themselves overall, but may be unable to work or have lower ability to function. Patients with tumors on both sides of the brain are not eligible. The main point of this study is to see if IGV-001 helps patients live longer without making the illness worse compared with placebo. Clinical Trial Registration: NCT04485949 (ClinicalTrials.gov).

Association between systemic treatment with immune checkpoint inhibitor therapy in renal cell carcinoma and reduced risk of brain metastasis development.

OBJECTIVE: Immune checkpoint inhibitor (ICI) efficacy in the treatment of metastatic renal cell carcinoma (RCC) without brain metastases (BMs) is well established in several clinical trials; however, patients with BMs were typically excluded from these trials. Therefore, the efficacy of ICI in the treatment or prevention of BM remains unclear. The primary aim of the study was to address the efficacy of ICI in treatment of patients with RCC BMs compared with patients receiving targeted therapies. A secondary aim was to evaluate the risk of RCC BM development among patients who received ICI versus targeted therapies early in their treatment course. METHODS: A retrospective single-center review between 2011 and 2018 identified 425 patients treated for metastatic RCC. The study group included patients who received ICI and/or targeted therapies during their disease. Data analyzed included demographic information, systemic treatments, overall survival from RCC diagnosis (OSRCC) and from BM diagnosis (OSBM), and BM development. Fisher's exact test was used to evaluate the frequency of BM occurrence. Survival was assessed using Kaplan-Meier curves and log-rank tests. RESULTS: Of the 425 patients, 125 received ICI and 300 were treated with molecular targeted agents only during their clinical course. BMs occurred in 113 (9.5%) of the 425 patients. Among patients with BMs, OSRCC was improved with the use of ICI (77.2 vs 25.2 months, p < 0.001), with 1-, 2-, and 5-year survival rates of 93.9%, 81.8%, and 62.6%, respectively. The use of ICI was associated with increased OSBM (21.7 vs 8.9 months, p = 0.001). The rate of BM development was lower when patients were treated with ICI (8/100 [8.0%]) compared with targeted therapy (47/267 [17.6%]) (OR 0.41, 95% CI 0.18-0.89; p = 0.021). CONCLUSIONS: ICI was associated with improved OSRCC and OSBM in patients with BMs and decreased the probability of BM development in patients with metastatic RCC. Prospective trials are needed to further evaluate optimal use of ICI in treatment of RCC BMs.

Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of cytoreductive surgery in the management of progressive glioblastoma in adults.

QUESTION: In patients with previously diagnosed glioblastoma who are suspected of experiencing progression, does repeat cytoreductive surgery improve progression free survival or overall survival compared to alternative interventions? TARGET POPULATION: These recommendations apply to adults with previously diagnosed glioblastoma who are suspected of experiencing progression of the neoplastic process and are amenable to surgical resection. RECOMMENDATION: Level II: Repeat cytoreductive surgery is recommended in progressive glioblastoma patients to improve overall survival.

Genetic analysis of a malignant meningioma and associated metastases.

To identify genes altered in a highly aggressive metastatic meningioma primary as well as its metastases. Exome sequencing of a primary anaplastic meningioma and metastatic lesions in which DNA could be extracted and compared to germline DNA. Genetic analysis of the metastatic sites found 31 common mutations among the primary tumor and two metastatic sites. Additionally, genetic mutations were identified which were either infrequently (MUC3A, ALDH1A3, HOXA1) or not at all previously described in meningiomas (CASS4, CMKLR1). Exome sequencing of a metastatic meningioma and its distant metastases outside the CNS identified mutations that were not previously well described.

Neurosurgical involvement in clinical trials for CNS tumors.

INTRODUCTION: Most clinical trials in neurooncology are led by investigators primarily trained in neurology or medical oncology. While neurosurgeons are trained to be problem-solvers and innovators, research training has historically been focused on laboratory-based discovery approaches and formalized training in prospective clinical trials research is not part of routine graduate training. METHODS: We reviewed literature that demonstrates that innovation and problem-solving are integral to the practice of neurosurgery cite multiple examples of advances in technique and technology that may have had an empirical origin but that led to prospective clinical trials resulting in change in practice. RESULTS: Neurosurgeons have developed and led both traditional (clinical outcome-oriented) and translational prospective clinical trials that have evaluated the best use of currently available therapeutics or tested the ability of novel therapeutics to alter the biology and/or course of disease. CONCLUSIONS: In this review, we focus on a number of the recently developed technologies and therapeutics that were evaluated in clinical trials led or co-led by neurosurgeons. We also highlight some of the barriers that need to be addressed in order to foster neurosurgical participation and leadership in the prospective development of novel therapeutics.

Impact of cerebrospinal fluid flow study in patients undergoing intrathecal chemotherapy via ventricular catheter reservoir.

PURPOSE: Leptomeningeal carcinomatosis (LMC) is a form of CNS cancer metastasis with severe morbidity. Intrathecal chemotherapy (ITC) administration through an implanted ventricular catheter reservoir (IVCR) is often utilized. Additionally, a nuclear imaging flow study can be performed prior to ITC administration to assess cerebrospinal fluid (CSF) flow. The clinical impact of a CSF flow study is unclear. METHODS: A retrospective chart review identified 31 patients with LMC that underwent IVCR placement between 2011 and 2019. Data extracted included patient demographics, nuclear imaging flow study, surgical complications, ITC toxicities and outcomes. RESULTS: Potential drug-induced neurologic toxicities (headache, nausea/vomiting, altered mental status, etc.) were noted in (n = 4/16) 25% of patients who underwent a flow study prior to initiation of ITC, compared to (n = 1/15) 6.6% of patients who did not undergo a flow study. Median overall survival (OS) was 4.0 and 32.8 months for the patients that underwent a flow study versus patients who did not, respectively (p < 0.01). The mean interval from IVCR implantation to initiation of ITC was 15.2 ± 8.5 days and 3.3 ± 3.0 days in patients who underwent CSF flow study and patients that did not, respectively (p < 0.0001). CONCLUSIONS: A flow study can provide information regarding CSF flow dynamics prior to initiation of ITC; however this might delay initiation of ITC which may negatively impact OS. Additionally, in our study patients that underwent a flow study had more ITC induced drug toxicity events compared to those that did not. Further studies are needed to clarify the role of CSF flow study in these patients.

Intraoperative 3 T MRI is more correlative to residual disease extent than early postoperative MRI.

PURPOSE: Extent of resection of low grade glioma (LGG) is an important prognostic variable, and may influence decisions regarding adjuvant therapy in certain patient populations. Immediate postoperative magnetic resonance image (MRI) is the mainstay for assessing residual tumor. However, previous studies have suggested that early postoperative MRI fluid-attenuated inversion recovery (FLAIR) (within 48 h) may overestimate residual tumor volume in LGG. Intraoperative magnetic resonance imaging (iMRI) without subsequent resection may more accurately assess residual tumor. Consistency in MRI techniques and utilization of higher magnet strengths may further improve both comparisons between MRI studies performed at different time points as well as the specificity of MRI findings to identify residual tumor. To evaluate the utility of 3 T iMRI in the imaging of LGG, we volumetrically analyzed intraoperative, early, and late (~ 3 months after surgery) postoperative MRIs after resection of LGG. METHODS: A total of 32 patients with LGG were assessed retrospectively. Residual tumor was defined as hyperintense T2 signal on FLAIR. Volumetric assessment was performed with intraoperative, early, and late postoperative FLAIR via TeraRecon iNtuition. RESULTS: Perilesional FLAIR parenchymal abnormality volumes were significantly different comparing intraoperative and early postoperative MRI (2.17 ± 0.45 cm3 vs. 5.47 ± 1.07 cm3, respectively (p = 0.0002)). A significant difference of perilesional FLAIR parenchymal abnormality volumes was also found comparing early and late postoperative MRI (5.47 ± 1.07 cm3 vs. 3.22 ± 0.64 cm3, respectively (p = 0.0001)). There was no significant difference between intraoperative and late postoperative Perilesional FLAIR parenchymal abnormality volumes. CONCLUSIONS: Intraoperative 3 T MRI without further resection appears to better reflect the volume of residual tumor in LGG compared with early postoperative 3 T MRI. Early postoperative MRI may overestimate residual tumor. As such, intraoperative MRI performed after completion of tumor resection may be more useful for making decisions regarding adjuvant therapy.

Viral therapies for glioblastoma and high-grade gliomas in adults: a systematic review.

OBJECTIVE: High-grade gliomas (HGGs) inevitably recur and progress despite resection and standard chemotherapies and radiation. Viral therapies have emerged as a theoretically favorable adjuvant modality that might overcome intrinsic factors of HGGs that confer treatment resistance. METHODS: The authors present the results of systematic searches of the MEDLINE and ClinicalTrials.gov databases that were performed for clinical trials published or registered up to July 15, 2020. RESULTS: Fifty-one completed clinical trials were identified that made use of a virus-based therapeutic strategy to treat HGG. The two main types of viral therapies were oncolytic viruses and viral vectors for gene therapy. Among clinical trials that met inclusion criteria, 20 related to oncolytic viruses and 31 to gene therapy trials. No oncolytic viruses have progressed to phase III clinical trial testing, although there have been many promising early-phase results and no reported cases of encephalitis or death due to viral therapy. Three phase III trials in which viral gene therapy was used have been completed but have not resulted in any FDA-approved therapy. Recent efforts in this area have been focused on the delivery of suicide genes such as herpes simplex virus thymidine kinase and cytosine deaminase. CONCLUSIONS: Decades of research efforts and an improving understanding of the immunomodulatory effects of viral therapies for gliomas are informing ongoing clinical efforts aimed at improving outcomes in patients with HGG. The available clinical data reveal varied efficacy among different virus-based treatment strategies.

Advancing gene therapies, methods, and technologies for Parkinson's Disease and other neurological disorders.

INTRODUCTION: Vector-based intracerebral gene therapies are being used to treat specific neurodegenerative conditions such as Parkinson's Disease (PD). This review presents a basis for central nervous system (CNS) gene therapy treatments of neurodegenerative diseases such as PD, as well as the need for novel skill sets and health delivery strategies within the clinical neurosciences (neurology and neurosurgery) to meet future demand for such therapies. STATE OF THE ART: Preclinical vector-based gene therapy approaches have been translated into clinical trials for PD and other neurodegenerative conditions. Unfortunately, such trials, and parallel efforts using other therapeutics, have yet to provide a breakthrough. Image-guided convection enhanced delivery (CED) optimises the parenchymal distribution of gene therapies applied within the CNS, and may ultimately provide such a breakthrough. CLINICAL IMPLICATIONS: Currently, image-guided CED and gene therapy are not part of training programmes for most neurosurgeons and neurologists. As a result, few medical centres and hospitals have sufficiently experienced teams to participate in gene transfer clinical trials for PD or other neurological conditions. If CNS gene therapies prove to be efficacious for PD and/or other conditions, the demand for such treatments will overwhelm the available number of experienced clinical neuroscience teams and treatment centres. FUTURE DIRECTIONS: Expanded indications and demand for CNS gene therapies will require a worldwide educational effort to supplement the training of clinical neuroscience practitioners. Initially, a limited number of Centres of Excellence will need to establish relevant educational training requirements and best practice for such therapeutic approaches. Advanced technologies, including robotics and artificial intelligence, are especially germane in this regard, and will expand the treatment team's capabilities while assisting in the safe and timely care of those afflicted.

Trends in central nervous system tumor incidence relative to other common cancers in adults, adolescents, and children in the United States, 2000 to 2010.

BACKGROUND: Time trends in cancer incidence rates (IR) are important to measure the changing burden of cancer on a population over time. The overall IR of cancer in the United States is declining. Although central nervous system tumors (CNST) are rare, they contribute disproportionately to mortality and morbidity. In this analysis, the authors examined trends in the incidence of the most common cancers and CNST between 2000 and 2010. METHODS: The current analysis used data from the United States Cancer Statistics publication and the Central Brain Tumor Registry of the United States. Age-adjusted IR per 100,000 population with 95% confidence intervals and the annual percent change (APC) with 95% confidence intervals were calculated for selected common cancers and CNST overall and by age, sex, race/ethnicity, selected histologies, and malignancy status. RESULTS: In adults, there were significant decreases in colon (2000-2010: APC, -3.1), breast (2000-2010: APC, -0.8), lung (2000-2010: APC, -1.1), and prostate (2000-2010: APC, -2.4) cancer as well as malignant CNST (2008-2010: APC, -3.1), but a significant increase was noted in nonmalignant CNST (2004-2010: APC, 2.7). In adolescents, there were significant increases in malignant CNST (2000-2008: APC, 1.0) and nonmalignant CNST (2004-2010: APC, 3.9). In children, there were significant increases in acute lymphocytic leukemia (2000-2010: APC, 1.0), non-Hodgkin lymphoma (2000-2010: APC, 0.6), and malignant CNST (2000-2010: APC, 0.6). CONCLUSIONS: Surveillance of IR trends is an important way to measure the changing public health and economic burden of cancer. In the current study, there were significant decreases noted in the incidence of adult cancer, whereas adolescent and childhood cancer IR were either stable or increasing.

The Cost Effectiveness of Polyetheretheketone (PEEK) Cages for Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Cost-effectiveness analysis using a Markov model with inputs from published literature. OBJECTIVE: To learn which graft or hardware option used in a single-level anterior cervical discectomy and fusion (ACDF) is most beneficial in terms of cost, quality of life, and overall cost effectiveness. Options studied were autograft, allograft, and polyetheretherketone (PEEK) cages for cervical fusion. SUMMARY OF BACKGROUND DATA: ACDF is commonly used to treat cervical myelopathy and/or radiculopathy. No study has compared the cost effectiveness of autograft, allograft, and PEEK in 1-level ACDF. MATERIALS AND METHODS: A literature review provided inputs into a Markov decision model to determine the most effective graft or hardware option for 1-level ACDF. Data regarding rate of complications, quality-adjusted life years (QALYs) gained, and cost for each procedure type was collected. The Markov model was first run in a base case, using all currently available data. The model was then tested using 1-way and 2-way sensitivity analyses to determine the validity of the model's conclusions if specific aspects of model were changed. This model was run for 10 years postoperatively. RESULTS: The cost per QALY for each option in the base case analysis was $3328/QALY for PEEK, $2492/QALY for autograft, and $2492/QALY for allograft. All graft/hardware options are cost effective ways to improve outcomes for patients living with chronic neck pain. For graft/hardware options the most cost-effective option was allograft. The incremental cost-effectiveness ratio for PEEK compared with autograft or allograft was >$100,000/QALY. CONCLUSIONS: Allograft is the most cost-effective graft/hardware option for ACDF. Compared with living with cervical myelopathy and/or radiculopathy, ACDF using any graft or hardware option is a cost-effective method of improving the quality of life of patients. PEEK is not a cost-effective option compared with allograft or autograft for use in ACDF.

Preoperative prescription opioid use as an independent predictor of 90-day mortality and adverse events in craniotomy and craniectomy patients.

OBJECTIVE: A growing body of literature suggests that preoperative opioid exposure is an independent predictor of poor outcomes in surgical patients. No outcomes data exist on preoperative opioid use and craniotomies/craniectomies. The objective of this study was to determine the impact of preoperative opioid use on 90-day adverse events after craniotomy or craniectomy. METHODS: A single-center retrospective cohort study of 2445 patients undergoing a craniotomy/craniectomy between January 1, 2013, and October 1, 2018, was conducted. Baseline demographics, pre- and postoperative opioid use (morphine milligram equivalents [MMEs]), and surgical metrics were recorded. Patients were categorized based on whether they took prescription opioids preoperatively, defined as within 1 month of surgery, or were opioid naive. The outcomes were mortality and adverse events 90 days after craniotomy/craniectomy. RESULTS: Overall, 26.6% of patients composed the preoperative opioid group. The median daily MME intake among this group was 34.6 (IQR 14.1-90) MMEs. Lower employment rates (p < 0.001), uninsured status (p = 0.016), and intravenous drug use (p = 0.006) were associated with preoperative opioid use. Preoperative opioid use was associated with increased venous thromboembolism (p = 0.001), acute kidney injury (p = 0.002), acute respiratory failure (p < 0.001), myocardial infarction (p = 0.002), delirium (p < 0.001), and infection (p < 0.001). Preoperative opioid use was an independent predictor of overall 90-day adverse events (OR 1.643, 95% CI 1.289-2.095; p < 0.001) and 90-day mortality (OR 1.690, 95% CI 1.254-2.277; p < 0.001). CONCLUSIONS: Preoperative opioid use was independently associated with 90-day postoperative adverse events and mortality. Opioid use increases vulnerability in craniotomy/craniectomy patients and necessitates close monitoring to improve outcomes.

Vertebral Compression Fracture After Spine Stereotactic Body Radiotherapy: The Role of Vertebral Endplate Disruption.

BACKGROUND AND OBJECTIVES: Vertebral compression fracture (VCF) is a common, but serious toxicity of spinal stereotactic body radiotherapy (SBRT). Several variables that place patients at high risk of VCF have previously been identified, including advanced Spinal Instability Neoplastic Score (SINS), a widely adopted clinical decision criterion to assess spinal instability. We examine the role of tumoral endplate (EP) disruption in the risk of VCF and attempt to incorporate it into a simple risk stratification system. METHODS: This study was a retrospective cohort study from a single institution. Demographic and treatment information was collected for patients who received spinal SBRT between 2013 and 2019. EP disruption was noted on pre-SBRT computed tomography scan. The primary end point of 1-year cumulative incidence of VCF was assessed on follow-up MRI and computed tomography scans at 3-month intervals after treatment. RESULTS: A total of 111 patients were included. The median follow-up was 18 months. Approximately 48 patients (43%) had at least one EP disruption. Twenty patients (18%) experienced a VCF at a median of 5.2 months from SBRT. Patients with at least one EP disruption were more likely to experience VCF than those with no EP disruption (29% vs 6%, P < .001). A nomogram was created using the variables of EP disruption, a SINS of ≥7, and adverse histology. Patients were stratified into groups at low and high risk of VCF, which were associated with 2% and 38% risk of VCF ( P < .001). CONCLUSION: EP disruption is a novel risk factor for VCF in patients who will undergo spinal SBRT. A simple nomogram incorporating EP disruption, adverse histology, and SINS score is effective for quickly assessing risk of VCF. These data require validation in prospective studies and could be helpful in counseling patients regarding VCF risk and referring for prophylactic interventions in high-risk populations.

Pretreatment findings on magnetic resonance imaging in primary central nervous system lymphoma may predict overall survival duration.

BACKGROUND: and purpose: Primary central nervous system lymphoma (PCNSL) lesions often show avid contrast enhancement on T1-weighted contrast-enhanced MRI sequences. However, several case reports and a clinical study have described PCNSL in patients with no contrast enhancement on MRI. We assessed whether overall survival (OS) time was related to any tumor characteristics (lesion location, volume, and number; contrast enhancement; necrosis; proximity to the subarachnoid space; and edema) on MRI in patients with PCNSL. MATERIALS AND METHODS: We retrospectively reviewed records (MRI features, pathology, and survival data) of all patients at our institution with PCNSL who had been seen from, 2007 through 2017, and had undergone pretreatment MRI. RESULTS: We identified 79 patients (42 men, 37 women) with a mean age at diagnosis of 61.7 ± 10.4 years. The mean OS duration was 44.6 ± 41.7 months. The most common pathological diagnosis (74 patients) was diffuse large B-cell lymphoma. No associations were found between OS time and lesion location, volume, and number; contrast enhancement; necrosis; proximity to the subarachnoid space; or edema. However, a sole patient with non-enhancing PCNSL on MRI was found to have low-grade disease, with prolonged survival (>83 months). Several other patients with leptomeningeal disease had a mean OS time of 80 months. Patients with hemorrhagic lesions had a mean OS of 25.5 months. CONCLUSIONS: The survival time for patients with PCNSL may be longer than previously thought, especially for patients with leptomeningeal seeding and lesions with hemorrhagic components Also, non-enhancing tumors may be less aggressive than enhancing tumors.

Surgical Characteristics of Intracranial Biopsy Using a Frameless Stereotactic Robotic Platform: A Single-Center Experience.

BACKGROUND AND OBJECTIVES: Cranial robotics are a burgeoning field of neurosurgery. To date, all cranial robotic systems described have been computerized, arm-based instruments that take up significant space in the operating room. The Medtronic Stealth Autoguide robot has a smaller operating room footprint and offers multiaxial, frame-based surgical targeting. The authors set out to define the surgical characteristics of a novel robotic platform for brain biopsy in a large patient cohort. METHODS: Patients who underwent stereotactic biopsy using the Stealth Autoguide cranial robotic platform from July 2020 to March 2023 were included in this study. Clinical, surgical, and histological data were collected and analyzed. RESULTS: Ninety-six consecutive patients (50 female, 46 male) were included. The mean age at biopsy was 53.7 ± 18.0 years. The mean target depth was 68.2 ± 15.3 mm. The biopsy diagnostic tissue acquisition rate was 100%. The mean time from incision to biopsy tissue acquisition was 15.4 ± 9.9 minutes. Target lesions were located throughout the brain: in the frontal lobe (n = 32, 33.3%), parietal lobe (n = 21, 21.9%), temporal lobe (n = 22, 22.9%), deep brain nuclei/thalamus (n = 13, 13.5%), cerebellum (n = 7, 7.3%), and brainstem (n = 1, 1.0%). Most cases were gliomas (n = 75, 78.2%). Patients were discharged home on postoperative day 0 or 1 in 62.5% of cases. A total of 7 patients developed postoperative complications (7.2%). CONCLUSION: This cranial robotic platform can be used for efficient, safe, and accurate cranial biopsies that allow for reliable diagnosis of intracranial pathology in a minimally invasive setting.

Implementation of triggered kilovoltage imaging for stereotactic radiotherapy of the spine for patients with spinal fixation hardware.

Background and purpose: Mitigation of intrafraction motion (IM) is valuable in stereotactic radiotherapy (SRT) radiotherapy where submillimeter accuracy is desired. The purpose of this study was to investigate the application of triggered kilovoltage (kV) imaging for spine SRT patients with hardware by correlating kV imaging with patient motion and summarizing implications of tolerance for IM based on calculated dose. Materials and methods: Ten plans (33 fractions) were studied, correlating kV imaging during treatment with pre- and post-treatment cone beam computed tomography (CBCT). Images were taken at 20-degree gantry angle intervals during the arc-based treatment. The contour of the hardware with a 1 mm expansion was displayed at the treatment console to manually pause treatment delivery if the hardware was visually detected outside the contour. The treatment CBCTs were compared using retrospective image registration to assess the validity of contour-based method for pausing treatment. Finally, plans were generated to estimate dose volume objective differences in case of 1 mm deviation. Results: When kV imaging during treatment was used with the 1 mm contour, 100 % of the post-treatment CBCTs reported consistent results. One patient in the cohort exhibited motion greater than 1 mm during treatment which allowed intervention and re-setup during treatment. The average translational motion was 0.35 mm. Treatment plan comparison at 1 mm deviation showed little differences in calculated dose for the target and cord. Conclusions: Utilizing kV imaging during treatment is an effective method of assessing IM for SRT spine patients with hardware without increasing treatment time.

Neoadjuvant Arterial Embolization of Spine Metastases Associated With Improved Local Control in Patients Receiving Surgical Decompression and Stereotactic Body Radiotherapy.

BACKGROUND: Spine metastases often cause significant pain, instability, and/or neurological morbidity. Local control (LC) of spine metastases has been augmented with advances in systemic therapies, radiation, and surgical technique. Prior reports suggest an association between preoperative arterial embolization and improved LC and palliative pain control. OBJECTIVE: To further elucidate the role of neoadjuvant embolization on LC of spine metastases and the potential for improved pain control in patients receiving surgery and stereotactic body radiotherapy (SBRT). METHOD: A retrospective single-center review between 2012 and 2020 identified 117 patients with spinal metastases from various solid tumor malignancies managed with surgery and adjuvant SBRT with or without preoperative spinal arterial embolization. Demographic information, radiographic studies, treatment characteristics, Karnofsky Performance Score, Defensive Veterans Pain Rating Scale, and mean daily doses of analgesic medications were reviewed. LC was assessed using magnetic resonance imaging obtained at a median 3-month interval and defined as progression at the surgically treated vertebral level. RESULTS: Of 117 patients, 47 (40.2%) underwent preoperative embolization, followed by surgery and SBRT and 70 (59.8%) underwent surgery and SBRT alone. Within the embolization cohort, the median LC was 14.2 months compared with 6.3 months among the nonembolization cohort ( P = .0434). Receiver operating characteristic analysis suggests ≥82.5% embolization predicted significantly improved LC (area under the curve = 0.808; P < .0001). Defensive Veterans Pain Rating Scale mean and maximum scores significantly decreased immediately after embolization ( P < .001). CONCLUSION: Preoperative embolization was associated with improved LC and pain control suggesting a novel role for its use. Additional prospective study is warranted.

Surgical Management of Recurrent Brain Metastasis: A Systematic Review of Laser Interstitial Thermal Therapy.

The incidence of recurrent metastatic brain tumors is increasing due to advances in local therapy, including surgical and radiosurgical management, as well as improved systemic disease control. The management of recurrent brain metastases was previously limited to open resection and/or irradiation. In recent years, laser interstitial thermal therapy (LITT) has become a promising treatment modality. As systemic and intracranial disease burden increases in a patient, patients may no longer be candidates for surgical resection. LITT offers a relatively minimally invasive option for patients that cannot tolerate or do not want open surgery, as well as an option for accessing deep-seated tumors that may be difficult to access via craniotomy. This manuscript aims to critically review the available data regarding the use of LITT for recurrent intracranial brain metastasis. Ten of seventy-two studies met the criteria for review. Generally, the available literature suggests that LITT is a safe and feasible option for the treatment of recurrent brain metastases involving supratentorial and cortical brain, as well as posterior fossa and deep-seated locations. Among all studies, only one directly compared craniotomy to LITT in the setting of recurrent brain metastasis. Prospective studies are needed to better elucidate the role of LITT in the management of recurrent brain metastases.

Survival benefit with resection of brain metastases from renal cell carcinoma in the setting of molecular targeted therapy and/or immune therapy.

Patient survival with renal cell carcinoma (RCC) has improved with the use of molecular targeted agents and immunotherapy. Given the potential activity of these agents in treating brain metastases, the role of aggressive local management with surgery and/or radiation may diminish. The aim of this study was to evaluate the role of aggressive local therapy for RCC brain metastasis in the setting of molecular targeted agents and/or checkpoint inhibitor therapy. A retrospective single-center review between 2011-2018 identified patients that developed brain metastasis from RCC. Data analyzed included demographic information, systemic treatments, intracranial interventions, progression free survival and overall survival (OS). Of 1194 patients, 108(9.0%) were diagnosed with brain metastasis from RCC. OS from diagnosis of brain metastasis (OSBM) was 12.3 months. OSBM was analyzed based on three treatment groups: systemic therapy (ST) only (2.0 months, n = 23), systemic and radiotherapy (RT + ST) (12.3 months, n = 52), and systemic and radiotherapy plus resection (Surg + RT + ST) (21.7 months, n = 33). Survival benefit was seen with Surg + RT + ST compared to ST (P = 0.001), but not RT + ST (P = 0.081). Progression free survival was significantly prolonged with Surg + RT + ST compared to RT + ST (10.9 vs 5.9 months, respectively, P = 0.04). Variables such as performance status and number of brain metastases at the time of brain metastasis diagnosis did not differ significantly. In the setting of molecular targeted agents and immunotherapy, resection may benefit the appropriate surgical candidate. Prospective clinical trials are necessary to better understand the role of aggressive RCC brain metastasis treatment. Micro Abstract • Renal cell brain metastasis is often excluded from studies and brain metastases effect a large portion of RCC patients. • Retrospective study of 1194 RCC patients, 108 patients had brain metastasis, determination of the role of surgical resection in the setting of recent advances in checkpoint inhibitors. • A benefit was seen in overall survival in patients that had surgical while undergoing radiation therapy and systemic therapies. • In the setting of molecular targeted agents and immunotherapy, resection may benefit the appropriate surgical candidate(s).

Cervical juxtafacet cyst after anterior cervical discectomy and fusion.

Anterior cervical discectomy and fusion (ACDF) is a common neurosurgical procedure, and the benefits, long-term outcomes, and complications are well described in the literature. The development of a juxtafacet joint cyst resulting in radiculopathy is a rare outcome after ACDF and merits further description. The authors describe a patient in whom a juxtafacet joint cyst developed after ACDF procedures, resulting in surgical intervention. When a juxtafacet joint cyst develops after ACDF, symptoms can include radiculopathy, neck pain, and neurological symptoms such as paresthesias and motor weakness. The presence of a juxtafacet joint cyst implies instability in that region of the spine. Patients with this pathological entity may require decompression of neural elements and fusion across the segment involved with the cyst.