Journal of Neuro-Oncology最新文献

Purpose: Here we assess whether the volume of cerebral ischemia induced during glioma surgery may negatively impact survival independently of neurological function. We also evaluate the sensitivity of intraoperative MRI (iMRI) in detecting cerebral ischemia during surgery.

Methods: We retrospectively reviewed 361 cranial surgeries that used a 3 Tesla iMRI. 165 patients met all inclusion criteria and were included in the final analysis. Diffusion weighted imaging (DWI) obtained during iMRI was compared to postoperative DWI obtained within 7 days of the operation in cases where no further resection occurred after the iMRI.

Results: 42 of 165 patients (25%) showed at least some evidence of restricted diffusion on postoperative (poMRI). 37 of these 42 (88%) cases lacked evidence of restricted diffusion on iMRI, meaning iMRI had a false-negative rate of 88% and a sensitivity of 12% in assessing the extent of ischemic brain after surgery. In high-grade gliomas, the volume of restricted diffusion on poMRI was predictive of overall survival, independent of new functional deficits acquired during surgery (p = 0.011).

Conclusion: This study presents the largest case series to date analyzing the sensitivity of iMRI in detecting surgical ischemia. In high-grade gliomas, increased volume of ischemia correlated with worsening median overall survival (OS) irrespective of postoperative neurologic deficits. Future work will focus on improving intraoperative detection of ischemia during the hyperacute phase when interventions such as blood pressure modulation or direct application of vasodilator agents may be effective.

Purpose: Mexico has the second highest incidence of central and peripheral nervous system cancer cases in Latin America, but clinical and research resources to improve oncologic care are biased towards high-income countries. We carried out a retrospective study to identify sociodemographic factors associated with more severe clinical presentation among surgical neuro-oncology who underwent surgery at a major public referral hospital in Mexico City.

Methods: The hospital electronic medical record was reviewed to identify all surgical neuro-oncology patients who underwent surgery between January 1 and December 31, 2022. Descriptive statistics were used to characterize the patient population and outcomes; statistical analysis was performed to determine association between sociodemographic variables and advanced clinical presentation.

Results: A total of 366 neuro-oncology patients underwent surgery during the study period. The median patient age was 48 (IQR 17-83). The majority of patients were female (60.1, n = 220), single (51.4%, n = 188), and 29.2% (n = 107) endorsed being the primary provider for their family. The median number of dependents per patient was 4 (IQR 2-50), while the median monthly income was 10269 Mexican pesos (MXN) (IQR 2000-13500] and the median travel distance to INNN was 49 km (IQR 22-174). On multivariate analyses, having a higher number of dependents was associated with increased odds of presenting with longer symptom duration (p = 0.01). Divorced/separated status was associated with increased odds of presenting with tumors > 35mL in volume (p = 0.04). Primary provider (p = 0.01) and higher average monthly income (p = 0.03) was associated with decreased odds of presenting with tumors > 35mL.

Conclusions: This is the first study to recognize that certain sociodemographic factors are associated with more severe clinical presentation among surgical neuro-oncology patients. Further studies are needed in order to decern specific causes for delayed presentation in this patient population in order to create targeted interventions and decrease delays in care.

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.

Purpose: Angiogenesis is a crucial step in tumorigenesis of glioblastoma (GBM). Bevacizumab, an anti-vascular endothelial growth factor drug, is approved for second-line therapy for GBM. Glioma stem cells, presumably the cell of origin of GBM, take an active role in angiogenesis. The subventricular zone (SVZ) is the brain's largest reservoir of neural stem cells, and GBM near this region (SVZ GBM) is associated with a poor prognosis. This study aims to evaluate the potential impact of second-line bevacizumab treatment on survival in patients with SVZ GBM.

Methods: The electronic medical records of adult patients with newly diagnosed SVZ GDM under treated between 1/2011 and 12/2021 were retrospectively reviewed. Clinical, surgical, radiological, and outcome parameters were compared between patients treated with bevacizumab after first relapse to patients without such treatment.

Results: The cohort included 67 patients. 45 (67.1%) were treated with bevacizumab after the first relapse while 22 (32.9%) were not. The only statistically significant difference between groups was the rate of re-surgery, which was higher in the non-bevacizumab group (40.9% vs. 15.6%; p = 0.023), indicating that the groups were quite homogenous. In general, bevacizumab as a second-line treatment did not affect OS in SVZ GBM cases. However, it significantly prolongs survival time from 1st relapse by an average of more than 4 months, including after adjustment to re-surgery variable (HR = 0.57, 95% CI 0.34-0.94, p = 0.028 and HR = 0.57, 95%CI = 0.34-0.97, PV = 0.038; respectively). Furthermore, when adjusting to time from diagnosis to 1st relapse, bevacizumab treatment was also associated with prolonged OS (HR = 0.58; p = 0.043). In a subgroup analysis, comparing patients treated with both re-surgery and bevacizumab to patients treated in any other way, patients with the combined treatment had the longest mean OS of the entire cohort (22.16 ± 7.81 m vs. 13.60 ± 6.86, p = 0.049; HR = 0.361 95%CI 0.108-1.209, p = 0.085).

Conclusions: The use of bevacizumab as a second-line therapy in SVZ GBM cases may positively affect survival after relapse, even when given as a monotherapy. Additionally, in certain yet-to-be-identified sub-populations, bevacizumab may even extend overall survival. Further research is required to accurately identify SVZ GBM patients who would benefit most from anti-angiogenic therapy.

Background: Survival times of patients with IDH-mutant gliomas are variable and can extend to decades. Many studies provide progression-free rather than overall survival times and prognostic factors remain ill-defined. Here we explored characteristics of short- and long-term survivors within a cohort of patients with extended follow-up.

Methods: This single-center, case-control study included 86 patients diagnosed between 1998 and 2023 who either died within 6 years after diagnosis or survived at least 15 years. Patient characteristics and prognostic factors were stratified by short- (< 6 years) versus long-term (≥ 15 years) survival.

Results: Forty-seven patients (55%) diagnosed with astrocytoma and 39 patients (45%) with oligodendroglioma were included retrospectively. Median follow-up of the survivors was 16.6 years (range 15-28.9). Thirty-four deaths (40%) had been reported at database closure. Long-term survival was associated with CNS WHO grade 2 (p < 0.01), smaller tumor volumes (p = 0.01), lack of contrast enhancement (p < 0.01), wait-and-scan strategies (p < 0.01) and female sex (p = 0.04). In multivariate analyses for oligodendroglioma, larger T2 tumor volumes were associated with shorter survival (HR 1.02; 95% CI 1.01-1.05; p = 0.04). In patients with astrocytoma, lack of contrast enhancement (HR 0.38; 95% CI 0.15-0.94; p = 0.04) and wait-and-scan strategies (HR 5.75; 95% CI 1.66-26.61; p = 0.01) were associated with longer survival.

Conclusion: Large T2 tumor volume and contrast enhancement may be important risk factors for shorter survival, while age might be of lesser importance. Wait-and-scan strategies may yield excellent long-term survival in some patients with astrocytoma.

Purpose: This study systematically reviews and meta-analyses the extent of ethnic minority representation in neuro-oncology Phase III and IV clinical trials, explores the effect of ethnicity on outcomes, and identifies predictors for the inclusion of ethnicity data in publications.

Methods: Adhering to PRISMA guidelines, we conducted a comprehensive literature search across multiple databases, on Phase III and IV trials in neuro-oncology that reported on adult and/or paediatric subjects. Through meta-analysis, we synthesized information on overall survival, event-free survival, and the incidence of adverse outcomes across ethnicities.

Results: From 448 identified articles, a fraction reported ethnicity data, with an even smaller number providing outcome data stratified by ethnicity. Most study participants were identified as White, underscoring a significant underrepresentation of minorities. Our meta-analysis did not reveal significant outcome differences by ethnicity, which may be attributed to the limited and inadequate reporting of data. Predictors for including ethnicity data were identified, including trials in North America(OR2.39, 95%CI 1.18-5.12, p < 0.02),trials of drugs or biologic agents(OR 5.28, 95%CI 1.43-3.42, p < 0.05),and trials funded by charities(OR 2.28, 95% CI 1.04-5.27, p < 0.05) or pharmaceutical companies(OR 3.98, 95% CI 1.60-10.0, p < 0.005).

Conclusion: The underrepresentation of minorities in neuro-oncology clinical trials and the inadequately characterized impact of ethnicity on treatment outcomes highlight a critical need for more inclusive recruitment strategies and improved reporting standards. Change is necessary to ensure trials reflect the diversity of the patient population, which is essential for developing tailored strategies and improving outcomes. Future research should prioritize understanding the role of ethnicity in neuro-oncology to facilitate personalized treatment approaches.

Background: The last decade has seen major international research efforts focus on better understanding disease heterogeneity in meningioma. Multiple molecular platforms have generated significant biological and clinical utility, and there is a need to translate these findings into routine clinical practice. Here we review the role of DNA methylation profiling in meningioma and advocate for its widespread adoption.

Methods: We review modern DNA methylation-based classification and outcome prediction tools in meningioma. Biological classifiers, which were constructed agnostic to outcome using unsupervised approaches, outcome predictors, and liquid biopsy models are discussed in detail.

Results: DNA methylation has been used for biological classification and outcome in meningioma with considerable success. Several groups have proposed novel molecular classification systems which share similar features with one another and outperform WHO grade in their ability to predict outcome and explain subgroup-specific biological processes. In addition, recent studies have suggested a role for methylation-based liquid-biopsy in meningioma, which represents an exciting avenue for further exploration.

Conclusions: DNA methylation profiling has been revolutionary in meningioma. There is a need for widespread adoption of these approaches to personalize care and inform clinical trial design.

Introduction

Spinal chondrosarcoma exhibits higher invasiveness and a worse prognosis compared to chondrosarcoma in the extremities. The prognosis and therapeutic plan vary greatly among different pathological subtypes of chondrosarcoma. This study aimed to analyze the differences in clinical characteristics, molecular features, therapeutic effects, and prognostic factors among the subtypes of chondrosarcoma in the spine.

Methods

A retrospective review was conducted on 205 patients with spinal chondrosarcoma. The clinical features and immunohistochemical (IHC) markers were compared among the pathological subtypes of chondrosarcoma grade 1, grade 2, grade 3, mesenchymal chondrosarcoma (MCS), dedifferentiated chondrosarcoma (DCS), and clear cell chondrosarcoma (CCCS). Chondrosarcoma grade 1/2/3 are collectively referred to as conventional chondrosarcoma (CCS) for multivariate survival analysis. Univariate and multivariate analyses were performed to investigate independent prognostic factors for overall survival (OS) and recurrence-free survival (RFS) in patients with spinal chondrosarcoma. Furthermore, independent prognostic factors for OS and RFS were identified in CCS and MCS.

Results

MCS patients were younger than the other subtypes. Patients with chondrosarcoma grade 1/2 had better OS than those with chondrosarcoma grade 3, MCS and DCS, while only chondrosarcoma grade 1 patients showed better RFS than chondrosarcoma grade 2/3, MCS and DCS patients. Ki-67 index was higher in chondrosarcoma grade 3, MCS and DCS than chondrosarcoma grade 1/2. The comparison of IHC markers further highlighted the overexpression of P53/MDM2 in MCS and DCS. Gross total resection, including en-bloc and piecemeal resection, significantly improved OS and RFS for CCS patients, while only en-bloc resection significantly improved the prognosis of MCS patients. Chemotherapy appeared to be important for the OS of MCS patients.

Conclusion

P53/MDM2 pathway was upregulated in MCS and DCS compared to chondrosarcoma grade 1/2. Radical tumor resection is crucial for the treatment of spinal chondrosarcoma, while MCS patients require further comprehensive treatments perioperatively.

Glioblastoma remains a fatal diagnosis despite continuous efforts to improve upon the current standard backbone management paradigm of surgery, radiation therapy, systemic therapy and Tumor Treating Fields. Radiation therapy (RT) plays a pivotal role, with progress recently achieved in multiple key areas of research. The evolving landscape of dose and fractionation schedules and dose escalation options for different patient populations is explored, offering opportunities to better tailor treatment to a patient’s overall status and preferences; novel efforts to modify treatment volumes are presented, such as utilizing state-of-the-art MRI-based linear accelerators to deliver adaptive therapy, hoping to reduce normal tissue exposure and treatment-related toxicity; specialized MR techniques and functional imaging using novel PET agents are described, providing improved treatment accuracy and the opportunity to target areas at risk of disease relapse; finally, the role of particle therapy and new altered dose-rate photon and proton therapy techniques in the treatment paradigm of glioblastoma is detailed, aiming to improve tumor control and patient outcome by exploiting novel radiobiological pathways. Improvements in each of these aforementioned areas are needed to make the critical necessary progress and allow for new approaches combining different advanced treatment modalities. This plethora of multiple new treatment options currently under investigation provides hope for a new outlook for patients with glioblastoma in the near future.

Purpose

Improved outcomes have been noted in patients undergoing malignant brain tumor resection at high-volume centers. Studies have arbitrarily chosen high-volume dichotomous cutoffs and have not evaluated volume-outcome associations at specific institutional procedural volumes. We sought to establish the continuous association of volume with patient outcomes and identify cutoffs significantly associated with mortality, major complications, and readmissions. We hypothesized that a linear volume-outcome relationship can estimate likelihood of adverse outcomes when comparing any two volumes.

Methods

The patient cohort was identified with ICD-10 coding in the Nationwide Readmissions Database(NRD). The association of volume and mortality, major complications, and 30-/90-day readmissions were evaluated in multivariate analyses. Volume was used as a continuous variable with two/three-piece splines, with various knot positions to reflect the best model performance, based on the Quasi Information Criterion(QIC).

Results

From 2016 to 2018, 34,486 patients with malignant brain tumors underwent resection. When volume was analyzed as a continuous variable, mortality risk decreased at a steady rate of OR 0.988 per each additional procedure increase for hospitals with 1–65 cases/year(95% CI 0.982–0.993, p < 0.0001). Risk of major complications decreased from 1 to 41 cases/year(OR 0.983, 95% CI 0.979–0.988, p < 0.0001), 30-day readmissions from 1 to 24 cases/year(OR 0.987, 95% CI 0.979–0.995, p = 0.001) and 90-day readmissions from 1 to 23 cases/year(OR 0.989, 95% CI 0.983–0.995, p = 0.0003) and 24–349 cases/year(OR 0.9994, 95% CI 0.999–1, p = 0.01).

Conclusion

In multivariate analyses, institutional procedural volume remains linearly associated with mortality, major complications, and 30-/90-day readmission up to specific cutoffs. The resulting linear association can be used to calculate relative likelihood of adverse outcomes between any two volumes.