Differences between Survival Rates and Patterns of Failure of Patients with Lung Adenocarcinoma and Squamous Cell Carcinoma Who Received Single-Fraction Stereotactic Body Radiotherapy.

We investigated the survival and patterns of failure in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) in early stage non-small cell lung cancer (NSCLC) treated with single-fraction stereotactic body radiation therapy (SF-SBRT) of 27-34 Gray. A single-institution retrospective review of patients with biopsy-proven early stage ADC or SCC undergoing definitive SF-SBRT between September 2008 and February 2023 was performed. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes included local failure (LF), nodal failure (NF), and distant failure (DF). Of 292 eligible patients 174 had adenocarcinoma and 118 had squamous cell carcinoma. There was no significant change in any outcome except distant failure. Patients with ADC were significantly more likely to experience distant failure than patients with SCC (p = 0.0081). In conclusion, while SF-SBRT produced similar LF, NF, DFS, and OS, the higher rate of distant failure in ADC patients suggests that ongoing trials of SBRT and systemic therapy combinations should report their outcomes by histology.

Impact of metabolic syndrome on morbidity and mortality following transforaminal interbody fusion (TLIF).

Study design: Retrospective Multi-Institutional Database Study. Objective: Investigate the effect of metabolic syndrome (MetS) on the outcomes of Transforaminal Lumbar Interbody Fusion (TLIF). Summary of background data: TLIF procedures in lumbar spine pathology are common. MetS is a combination of conditions, including medication required hypertension, diabetes mellitus (DM), and body mass index (BMI) of 30 kg/m2s or more. The prevalence of MetS has increased drastically over the past two decades. Our study aimed to understand the effect of MetS on morbidity and mortality of TLIF postoperatively. Methods: Our study used American College of Surgeons National Surgical Quality Improvement (ACS-NSQIP) data from 2006 to 2019 to find all patients who underwent TLIF. Patients with MetS were compared to those without MetS. Fisher's test identified univariate relationships between MetS and preoperative/postoperative variables. Multivariable logistic regression models were utilized to analyze the association between MetS and postoperative morbidity and mortality. Results: 54,980 patients were identified who received TLIF. 10.7 % had MetS preoperatively. Patients with and without MetS showed statistically significant univariate differences in most preoperative and postoperative variables. After adjusting for preoperative comorbidities, patients with MetS had greater multivariate-adjusted odds of wound infections (aOR = 1.5889, CI 1.1952-2.112, p = 0.00144), pulmonary events (aOR = 1.5517, CI 1.1207-2.1485, p = 0.00813), renal events (aOR = 2.8685, CI 1.5511-5.3045, p = 0.00078), sepsis (aOR = 1.6773, CI 1.1647-2.4155, p = 5.44E-03), and return to OR (aOR = 1.4764, CI 1.2201-1.7866, p = 6.19E-05). Conclusions: Patients with MetS are at elevated risk for various morbidity and mortality markers after TLIF. Surgeons performing TLIFs on these patients should be aware of the increased potential for postoperative events that may complicate the patient's recovery. Level of evidence: Level III.

Postoperative Morbidity and Mortality in Lumbar Spine Surgery Patients With Chronic Kidney Disease and Chronic Steroid Use.

BACKGROUND: Perioperative steroids have traditionally been administered during lumbar spine surgery in order to decrease local inflammation and prevent scar tissue formation, which can otherwise contribute to significant, long-lasting postoperative pain due to the formation of epidural fibrosis around lumbar nerve roots. However, the use of steroids in lumbar spine patients has raised concerns of postoperative wound complications caused by corticosteroid-induced immunomodulatory effects and changes in collagen synthesis. Patients with chronic kidney disease (CKD) undergoing spine surgery are at a particularly elevated risk of various complications due to chronic CKD-related systemic inflammation and endothelial dysfunction. It is currently uncertain whether chronic steroid use in CKD patients exerts a protective effect postoperatively due to decreased systemic inflammation or instead is correlated with increased rates of wound complications. RESULTS: Using adjusted odds ratios to control for CKD-related comorbidities, our study of lumbar spine fusion patients who were chronic steroid users vs nonusers found no significant differences in rates of postoperative wound infections in later stage CKD patients. However, we also did not observe statistically significant reductions in hospital length of stay or rates of 30-day mortality, sepsis, or cardiac, pulmonary, and renal events. CONCLUSIONS: Our results indicate chronic steroid use neither contributes significantly to rates of wound infections nor exerts a protective effect against postoperative inflammatory complications in lumbar spine patients with CKD. CLINICAL RELEVANCE: Our findings do not support the practice of holding steroids in chronic users prior to lumbar spine surgery. Perioperative steroids do not appear to increase the risk of postoperative complications, but neither do they improve lumbar spine patient outcomes.

Vertebral Bone Quality Score Independently Predicts Proximal Junctional Kyphosis and/or Failure After Adult Spinal Deformity Surgery.

BACKGROUND: Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) can be catastrophic complications associated with adult spinal deformity (ASD) surgery. These complications are markedly influenced by osteoporosis, leading to additional vertebral fracture and pedicle screw loosening. The MRI-based vertebral bone quality score (VBQ) is a newly developed tool that can be used to assess bone quality. OBJECTIVE: To investigate the utility of the VBQ score in predicting PJK and/or PJF (PJF/PJK) after ASD correction. METHODS: We conducted a retrospective chart review to identify patients age ≥50 years who had received ASD surgery of 5 or more thoracolumbar levels. Demographic, spinopelvic parameters, and procedure-related variables were collected. Each patient's VBQ score was calculated using preoperative T1-weighted MRI. Univariate analysis and multivariate logistic regression were performed to determine potential risk factors of PJK/PJF. Receiver operating characteristic analysis and area-under-the-curve values were generated for prediction of PJK/PJF. RESULTS: A total of 116 patients were included (mean age, 64.1 ± 6.8 years). Among them, 34 patients (29.3%) developed PJK/PJF. Mean VBQ scores were 3.13 ± 0.46 for patients with PJK/PJF and 2.46 ± 0.49 for patients without, which was significantly different between the 2 groups ( P < .001). On multivariate analysis, VBQ score was the only significant predictor of PJK/PJF (odds ratio = 1.745, 95% CI = 1.558-1.953, P < .001), with a predictive accuracy of 94.3%. CONCLUSION: In patients undergoing ASD correction, higher VBQ was independently associated with PJK/PJF occurrence. Measurement of VBQ score on preoperative MRI may be a useful adjunct to ASD surgery planning.

Vertebral bone quality score independently predicts cage subsidence following transforaminal lumbar interbody fusion.

BACKGROUND CONTEXT: Cage subsidence following transforaminal lumbar interbody fusion (TLIF) has been associated with poor bone quality. Current evidence suggests that the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score correlates with poor bone quality. PURPOSE: To our knowledge, this is the first study to assess whether the VBQ score can predict the occurrence of postoperative cage subsidence after TLIF surgery. DESIGN/SETTING: Retrospective single-center cohort. PATIENT SAMPLE: Patients undergoing single-level TLIF for degenerative spine disease between February 2014 and October 2021. OUTCOME MEASURES: Extent of subsidence. METHODS: Demographic, procedure-related, and radiographic data were collected for study patients. VBQ scores were determined from preoperative T1-weighted MRI. Subsidence was defined as ≥2 mm of migration of the cage into the superior or inferior end plate or both. Univariate and multivariate logistic regression were used to determine the correlation between potential risk factors for subsidence and actual subsidence rates. RESULTS: Subsidence was observed among 42 of the 74 study patients. The mean VBQ scores were 2.9±0.5 for patients with subsidence and 2.5±0.5 for patients without subsidence. The difference among groups was significant (p=.003). On multivariate logistic regression, a higher VBQ score was significantly associated with an increased risk of subsidence (OR=1.5, 95% CI=1.160-1.973, p=.004) and was the only significant independent predictor of subsidence after TLIF. CONCLUSION: We found that a higher VBQ score was significantly associated with cage subsidence following TLIF. The MRI-VBQ score may be a valuable tool for assisting in identifying patients at risk of cage subsidence following TLIF.

Comparison of One-day Combined versus Staged Anterior and Posterior Cervical Decompression, Fixation, and Fusion.

AIM: To compare the perioperative outcomes between single-day combined or separate-day staged surgeries for cervical spinal stenosis. MATERIAL AND METHODS: A retrospective cohort analysis was conducted on consecutive patients admitted at a single institution between July 2015 and April 2019, who underwent either single-day combined or separate-day staged surgeries during the same hospitalization period. Demographics, comorbidities, hospital length of stay, and perioperative complications were compared between the patient groups. RESULTS: Eighty patients (combined surgery: n=68, staged surgery: n=12) were included. Dysphagia was the most commonly reported postoperative complication in 44/80 patients (55%). There were no significant differences in the baseline demographics between the two groups. The staged surgery group had significantly longer total time in the operating room (7.2 vs. 8.5 hours, p=0.002), longer duration of general anesthesia (6.7 vs. 7.6 hours, p=0.006), and higher incidence of postoperative delirium (12.1% vs. 50% p=0.005) than the combined surgery group. The mean hospital length of stay was similar in the two groups (combined surgery: 7.5 days vs. staged surgery: 15.1 days, p=0.09). CONCLUSION: Staged anterior and posterior cervical decompressions, stabilizations, and fusions are associated with longer total time in the operating room, longer duration of general anesthesia, and higher incidence of postoperative delirium than combined surgeries.

Ventral Intrameningeal Cyst Treatment and Management: Technical Note.

BACKGROUND: Intrameningeal cysts are rare lesions without definitive etiologies that can involve the dura or arachnoid mater. Spinal arachnoid cysts have been described, and several different etiologies have been hypothesized. This includes one-way valve mechanisms, traumatic herniation of arachnoid through the dura, and abnormal arachnoid membrane proliferation. To the authors' knowledge, no such descriptions exist regarding purely dural-based cystic lesions; however, the authors hypothesize similar mechanisms may be involved. Most notably, a traumatic injury to the dura leading to a one-way valve mechanism may allow for egress of cerebrospinal fluid between the dural layers, splitting them open. This progressive enlargement can lead to displacement of neural elements and subsequent neurological compromise. METHODS: We describe a 17-year-old girl who presented with progressive neck and back pain, left upper-extremity numbness, bilateral lower-extremity weakness, paresthesias, and numbness without obvious etiology despite an extensive neurologic investigation. She had undergone conservative management options including multiple medications, physical and chiropractic therapy, and epidural steroid injections. Computed tomography myelography revealed a cerebrospinal fluid leak into the lumbar epidural space for which surgical exploration was performed. Despite utilizing fluoroscopy and intrathecal fluorescein, no leak source was identified. Fluid collection was found contained within the dural layers rather than the epidural space. RESULTS: An intracystic blood patch was performed with near-complete resolution of the lesion by 6-week follow-up and near-complete return of neurologic function. CONCLUSIONS: Ventral panspinal cysts are an exceedingly rare cause of radiculopathy and myelopathy that can be resolved by an intracystic blood patch.

Racial Disparities Affecting Postoperative Outcomes After Brain Tumor Resection.

OBJECTIVE: To investigate racial disparities in 30-day postoperative outcomes of craniotomy for glioma resection. METHODS: 2006-2019 American College of Surgeons' National Surgical Quality Improvement Program files were queried for all patients who underwent a craniotomy for a supratentorial glioma resection. Racial disparities in preoperative variables were studied between the demographic cohorts of Asian, African Americans, Hispanics, and Caucasian. Fisher exact tests were used to examine association of preoperative variables with race. Multivariable logistic regression models, adjusted for all preoperative variables associated with race, were used to determine the odds ratios of postoperative outcomes for each demographic cohort in comparison with Caucasian patients. RESULTS: A total of 12,544 patients were identified: 4% Asian, 5% African American, 7% Hispanic, and 85% Caucasian. African American patients had significantly higher adjusted odds than Caucasian patients of major adverse cardiovascular events (adjusted odds ratio [aOR]: 1.827, 95% confidence interval [CI]: 1.155-2.891, P = 0.01), pulmonary events (aOR: 1.683, 95% CI: 1.145-2.473, P = 0.008), and urinary tract infection (aOR: 2.016, 95% CI: 1.221-3.327, P = 0.006). Asian patients had significantly higher odds than Caucasian patients of requiring a transfusion (aOR: 2.094, 95% CI: 1.343-3.266, P = 0.001). All demographic cohorts had higher odds of having an extended length of stay than Caucasian patients. CONCLUSIONS: African American patients who undergo a craniotomy for glioma resection have almost twice the odds of Caucasian patients of having a postoperative major cardiovascular complication, pulmonary complication, or urinary tract infection. All minority groups have higher odds of an extended length of stay as compared with Caucasian patients.

Mass cytometry detects H3.3K27M-specific vaccine responses in diffuse midline glioma.

BACKGROUNDPatients with diffuse midline gliomas (DMGs), including diffuse intrinsic pontine glioma (DIPG), have dismal outcomes. We previously described the H3.3K27M mutation as a shared neoantigen in HLA-A*02.01+, H3.3K27M+ DMGs. Within the Pacific Pediatric Neuro-Oncology Consortium, we assessed the safety and efficacy of an H3.3K27M-targeted peptide vaccine.METHODSNewly diagnosed patients, aged 3-21 years, with HLA-A*02.01+ and H3.3K27M+ status were enrolled in stratum A (DIPG) or stratum B (nonpontine DMG). Vaccine was administered in combination with polyinosinic-polycytidylic acid-poly-I-lysine carboxymethylcellulose (poly-ICLC) every 3 weeks for 8 cycles, followed by once every 6 weeks. Immunomonitoring and imaging were performed every 3 months. Imaging was centrally reviewed. Immunological responses were assessed in PBMCs using mass cytometry.RESULTSA total of 19 patients were enrolled in stratum A (median age,11 years) and 10 in stratum B (median age, 13 years). There were no grade-4 treatment-related adverse events (TRAEs). Injection site reaction was the most commonly reported TRAE. Overall survival (OS) at 12 months was 40% (95% CI, 22%-73%) for patients in stratum A and 39% (95% CI, 16%-93%) for patients in stratum B. The median OS was 16.1 months for patients who had an expansion of H3.3K27M-reactive CD8+ T cells compared with 9.8 months for their counterparts (P = 0.05). Patients with DIPG with below-median baseline levels of myeloid-derived suppressor cells had prolonged OS compared with their counterparts (P < 0.01). Immediate pretreatment dexamethasone administration was inversely associated with H3.3K27M-reactive CD8+ T cell responses.CONCLUSIONAdministration of the H3.3K27M-specific vaccine was well tolerated. Patients with H3.3K27M-specific CD8+ immunological responses demonstrated prolonged OS compared with nonresponders.TRIAL REGISTRATIONClinicalTrials.gov NCT02960230.FUNDINGThe V Foundation, the Pacific Pediatric Neuro-Oncology Consortium Foundation, the Pediatric Brain Tumor Foundation, the Mithil Prasad Foundation, the MCJ Amelior Foundation, the Anne and Jason Farber Foundation, Will Power Research Fund Inc., the Isabella Kerr Molina Foundation, the Parker Institute for Cancer Immunotherapy, and the National Institute of Neurological Disorders and Stroke (NINDS), NIH (R35NS105068).

Tumor antigens in glioma.

Immunotherapy applications to glioblastoma represent a new treatment frontier. Antigen-targeted immunotherapy approaches hold enormous potential to elicit antigen-specific anti-tumor effects in central nervous system tumors. Still, the paucity of effective antigen targets remains a significant obstacle in safely and effectively treating glioblastoma and other malignant gliomas with relatively low mutation loads. In this review, we highlight the current understanding of and development of immunotherapy to target 1) shared non-mutant antigens 2) shared mutant antigens (neoantigens) derived from cancer-specific mutations 3) personalized neoantigens derived from tumor-specific genetic alterations containing de novo peptide sequences and 4) virus-derived antigens. We also discuss strategies to enhance tumor immunogenicity and neoantigen prediction. Spatial heterogeneity remains a formidable challenge for immunotherapy of glioma; recent advances in targeting multiple antigens and refining the antigen selection pipeline hold great promise to turn the tide against glioma.

Perioperative Complications Associated with Severity of Anemia in Geriatric Patients Undergoing Spinal Procedures.

OBJECTIVE: To investigate preoperative baseline anemia, stratified by severity as a function of hematocrit level, as a risk factor for perioperative complications in geriatric patients undergoing spinal procedures. BACKGROUND: Previous literature has examined the impact of anemia on risk for complications and adverse outcomes in patients undergoing elective spinal procedures. However, there is a paucity of literature analyzing the impact of anemia in the geriatric population, specifically. METHODS: The American College of Surgeons-National Surgical Quality Improvement Database was used to identify patients older than 65 years who had undergone elective spinal procedures and were subsequently stratified into 3 separate cohorts based on hematocrit levels: severe/moderate (hematocrit level <30%), mild (30%-37%), and no anemia (>38%). These patient samples were then analyzed using multivariate analyses to assess severity of anemia as a risk factor for complications in elderly patients undergoing spinal procedures. RESULTS: When anemia classes were analyzed as separate independent risk factors for complications, mild anemia (class II) was a significant risk factor for the same complications as moderate/severe anemia (class III/IV), with the exception of 2 complications, compared with nonanemic patients. Mild anemia was independently associated with wound dehiscence (odds ratio, 1.521; 95% confidence interval, 1.126-2.054; P = 0.006), whereas moderate/severe anemia did not show an increased risk for wound dehiscence. However, moderate/severe anemia independently increased the risk for deep venous thromboembolism (odds ratio, 1.437; 95% confidence interval, 1.028-2.011; P = 0.034), compared with mild anemia. Both categories of anemia independently increased the risk for additional complications such as deep incisional surgical site infection, organ/space surgical site infection, pneumonia, unplanned intubation, ventilator dependence, progressive renal insufficiency, acute renal failure, urinary tract infections, cardiac arrest, myocardial infarctions, blood transfusions, systemic sepsis, reoperation, extended length of stay of ≥5 days, unplanned readmission, and mortality. CONCLUSIONS: This study indicated that patients with preoperative baseline anemia were at risk for requiring transfusions, renal failure, and infectious complications. Physicians should be cognizant of anemia as a risk factor affecting numerous perioperative complications and adverse outcomes to work toward improving health-related quality of life.

Cold Atmospheric Plasma as an Adjunct to Immunotherapy for Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common and aggressive form of brain cancer in adults. GBM carries a dismal prognosis because of its proliferative, invasive, and angiogenic capabilities and because of its ability to downregulate the immune system. Immune-based therapies under investigation for GBM have been unsuccessful in vivo because of this downregulation. Cold atmospheric plasma (CAP) is a high-energy state of matter that can be applied directly or indirectly to tumor tissue to serve as an adjunct to immunotherapy in the treatment of GBM because it upregulates the immune system by the induction of reactive oxygen species. CAP has the potential to improve the efficacy of existing and investigative immunotherapies for GBM.

A comparison of endoscopic strip craniectomy and pi craniectomy for treatment of sagittal craniosynostosis.

OBJECTIVE: Sagittal craniosynostosis is managed with a wide variety of operative strategies. The current investigation compares the clinical outcomes of two widely performed techniques: pi craniectomy and minimally invasive endoscopic strip craniectomy (ESC) followed by helmet therapy. METHODS: This IRB-approved retrospective study examined patients diagnosed with nonsyndromic, single-suture sagittal craniosynostosis treated with either pi craniectomy or ESC. Included patients had a minimum postoperative follow-up of 5 months. RESULTS: Fifty-one patients met the inclusion criteria (pi 21 patients, ESC 30 patients). Compared to patients who underwent ESC, the pi patients were older at the time of surgery (mean age 5.06 vs 3.11 months). The mean follow-up time was 23.2 months for ESC patients and 31.4 months for pi patients. Initial cranial index (CI) was similar between the groups, but postoperatively the ESC patients experienced a 12.3% mean increase in CI (from 0.685 to 0.767) compared to a 5.34% increase for the pi patients (from 0.684 to 0.719), and this difference was statistically significant (p < 0.001). Median hospital length of stay (1 vs 2 days) and operative duration (69.5 vs 93.3 minutes) were significantly less for ESC (p < 0.001 for both). The ESC patients showed a trend toward better results when surgery was done at younger ages. Craniectomy width in ESC cases was positively associated with CI improvement (slope of linear regression = 0.69, p = 0.026). CONCLUSIONS: While both techniques effectively treated sagittal craniosynostosis, ESC showed superior results compared to pi craniectomy. ESC showed a trend for better outcomes when done at younger ages, although the trend did not reach statistical significance. A wider craniectomy width (up to 2 cm) was associated with better outcomes than smaller craniectomy widths among the ESC patients.

Effectiveness of Positron Emission Tomography/Computed Tomography as a Guide for Palliative Radiation Therapy for Spinal Metastases.

OBJECTIVE: As back pain is the presenting symptom in 95% of patients with epidural spinal metastases, appropriately identifying and treating the most symptomatic levels can provide significant palliation. The purpose of this study was to analyze the ability of combined positron emission tomography (PET)/computed tomography (CT) to identify spinal metastases with high metabolic activity and guide radiotherapy. We sought to correlate improvement in back pain with reduction in standard uptake value (SUV) after treatment. METHODS: Retrospective review was performed of 72 patients with spinal metastases treated with stereotactic ablative radiation therapy at a single center between 2002 and 2014. PET/CT was used to calculate SUVs for spinal metastases, and treatment planning was based on PET/CT results. Preoperative and postoperative pain levels were assessed in all patients. RESULTS: Reduction in pain scores was found in 78% of treated patients. A significant reduction in pain was identified in patients with >5 metastases compared with fewer lesions (P < 0.05). Degree of change in SUV did not correlate significantly with pain relief. However, comparing pretreatment and posttreatment PET/CT, patients with improved pain consistently displayed decreased SUV. CONCLUSIONS: PET/CT was shown to be a useful adjunct in radiation treatment planning with change in SUV correlating with symptomatic improvement. This study paves the way for future prospective studies to further assess utility and cost-effectiveness of this imaging modality in radiation treatment planning for spinal metastases.

Genetically Engineered T-Cells for Malignant Glioma: Overcoming the Barriers to Effective Immunotherapy.

Malignant gliomas carry a dismal prognosis. Conventional treatment using chemo- and radiotherapy has limited efficacy with adverse events. Therapy with genetically engineered T-cells, such as chimeric antigen receptor (CAR) T-cells, may represent a promising approach to improve patient outcomes owing to their potential ability to attack highly infiltrative tumors in a tumor-specific manner and possible persistence of the adaptive immune response. However, the unique anatomical features of the brain and susceptibility of this organ to irreversible tissue damage have made immunotherapy especially challenging in the setting of glioma. With safety concerns in mind, multiple teams have initiated clinical trials using CAR T-cells in glioma patients. The valuable lessons learnt from those trials highlight critical areas for further improvement: tackling the issues of the antigen presentation and T-cell homing in the brain, immunosuppression in the glioma microenvironment, antigen heterogeneity and off-tumor toxicity, and the adaptation of existing clinical therapies to reflect the intricacies of immune response in the brain. This review summarizes the up-to-date clinical outcomes of CAR T-cell clinical trials in glioma patients and examines the most pressing hurdles limiting the efficacy of these therapies. Furthermore, this review uses these hurdles as a framework upon which to evaluate cutting-edge pre-clinical strategies aiming to overcome those barriers.