Journal of Neuro-Oncology最新文献

Purpose: A majority of published series report on stereotactic body radiation therapy (SBRT) for 1-2 contiguous vertebral levels due to concerns regarding setup accuracy and radiation toxicity. This study evaluates patients with metastases spanning ≥ 3 contiguous levels treated with SBRT and augments its findings with a review of other studies investigating multilevel spine SBRT.

Methods: Analysis of a prospectively collected database of 49 patients with 55 metastases spanning ≥ 3 contiguous vertebral levels treated with SBRT at a single institution (2002-2023) was performed. Outcomes identified included local failure (LF), pain response, overall survival, and toxicity. The median single-fraction prescription dose was 15 Gy (range: 8-18); multifractionated treatment utilized prescription doses of 18-30 Gy in 2-5 fractions.

Results: Median follow-up was 7 months (range: 1-103). The 6-month, 1-year, and 2-year cumulative incidence rates of LF were 7%, 11%, and 11%, respectively. No prognostic factors were associated with LF. Pain was reported to improve or remain stable for 49 lesions (89%). Ten adverse radiation events (18%) were identified; pain flare (5%), dermatitis (4%), and vertebral compression fracture (VCF, 9%). The 3-month, 6-month, and 1-year cumulative incidence rates of VCF were 4%, 7%, and 7%, respectively. No instances of esophageal toxicity or myelopathy were observed.

Conclusions: This study of multilevel SBRT is one of the largest to investigate outcomes in this challenging clinical scenario. Spine SBRT confers low rates of LF and toxicity for patients with multilevel disease, which was previously considered a relative contraindication. Spine SBRT may be considered in this patient population instead of low-dose palliative RT.

Background: Glioblastoma (GBM) is an aggressive therapy-resistant brain tumour that may impacts the integrity of the blood-brain barrier (BBB). The BBB is a protective barrier of the central nervous system formed mainly by endothelial cells. This study aimed to investigate the in vitro effect of GBM cells on the BBB.

Methods: Brain endothelial (bEnd.3) cells were used as a model of the BBB. Glioblastoma-conditioned media (CM) was extracted at the 48-h (h) time-point from the U87 GBM cells and diluted to 40% with fresh media. The effect of the U87-CM collected at 48 h on bEnd.3 cell growth was evaluated following 48 and 72 h of treatment using the xCELLigence system. Additionally, bEnd.3 cell growth was also investigated in a U87 and bEnd.3 co-culture model continuously for 48 h using the xCELLigence system. The migration of bEnd.3 cells was assessed following 48 and 72 h using the migration scratch assay. The barrier integrity was evaluated continuously for 1 h using the transwell permeability, and the tight junction (TJ) protein expression was evaluated using Western blot assay following 48 and 72 h.

Results: There was a significant decrease in bEnd.3 cell growth following 32 h (p < 0.05), 40 h (p < 0.01), and 48 h (p < 0.001) of treatment with U87-CM, while co-culturing of bEnd.3 and U87 cells increased cell growth following 16 h (p < 0.05), 24 h (p < 0.001), 32 h (p < 0.01), 40 h (p < 0.001), and 48 h (p < 0.001). The migration of bEnd.3 cells significantly increased following both 24 (p < 0.05) and 48 h (p < 0.01) of treatment with U87-CM. The permeability of bEnd.3 cells co-cultured with U87 for 48 h was significantly increased (p < 0.05) at the 15- and 30-min time points. Furthermore, the expression of ZO-1 and occludin was significantly increased (p < 0.05) in both bEnd.3 cells treated with U87-CM as well as bEnd.3 cells co-cultured with U87 cells.

Conclusion: The current findings suggest that U87 cells alter the integrity of bEnd.3 cells possibly through the secretomes in the CM and through cell-cell interactions in co-culture models. This may assist in the understanding of the mechanisms by which GBM affects the BBB, which may aid in the management thereof.

Purpose: Acromegaly is characterized by an insidious clinical presentation and delayed diagnosis. Longer delays are associated with more comorbidities which can persist after treatment of the growth hormone-secreting pituitary adenoma (GH-PA). Surgery is the primary therapy of GH-secreting PA, which can lead to durable remission. However, approximately 50% of patients require medical treatment postoperatively. Survival normalizes after achieving biochemical control. This mini-review will address ends of the spectrum challenges in acromegaly, including delayed diagnosis and management of the residual tumor and persistent comorbidities.

Methods: We synthesize relevant literature and present a case of acromegaly that highlights the complexity of clinical decision-making in the diagnosis and treatment of persistent acromegaly.

Results: Despite improved biochemical assays, most patients with acromegaly are diagnosed on average five years after initial symptoms. A high index of suspicion does not rely exclusively on acral enlargement, but also a constellation of manifestations and comorbidities suggestive of acromegaly. Medical therapy is required in patients with persistent biochemical disease. Somatostatin receptor ligands are the cornerstone of medical treatment and can be used alone or in combination with dopamine agonists and growth hormone receptor antagonists. Improved options of medical treatment and careful consideration of comorbidities enables individualized patient management. Reoperation and radiation are considered for tumor progression despite medical therapy. In rare cases of resistant and aggressive tumors, neuro-oncology expertise is required.

Conclusions: Increased awareness through education targeting the multifaceted clinical presentation of acromegaly shortens the time to diagnosis and treatment. Multidisciplinary management by specialists increases the likelihood of biochemical and tumor control.

Purpose: Gliosarcoma is a rare histopathological variant of glioblastoma, but it is unclear whether distinct clinical or molecular features distinguish it from other glioblastomas. The purpose of this study was to characterize common genomic alterations of gliosarcoma, compare them to that of glioblastoma, and correlate them with prognosis.

Methods: This was a single-institution, retrospective cohort study of patients seen between 11/1/2017 to 1/28/2024. Clinical and genomic data were obtained from the medical record. Results were validated using data from AACR Project GENIE (v15.1-public).

Results: We identified 87 gliosarcoma patients in the institutional cohort. Compared to a contemporary cohort of 492 glioblastoma, there was no difference in overall survival, though progression free survival was inferior for patients with gliosarcoma (p = 0.01). Several of the most-commonly altered genes in gliosarcoma were more frequently altered than in glioblastoma (NF1, PTEN, TP53), while others were less frequently altered than in glioblastoma (EGFR). CDKN2A/CDKN2B/MTAP alterations were associated with inferior survival on univariate Cox (HR = 5.4, p = 0.023). When pooled with 93 patients from the GENIE cohort, CDKN2A/B (HR = 1.75, p = 0.039), RB1 (HR = 0.51, p = 0.016), LRP1B (p = 0.050, HR = 2.0), and TSC2 (HR = 0.31, p = 0.048) alterations or loss were significantly associated with survival. These effects remained when controlled for age, sex, and cohort of origin with multivariate Cox.

Conclusion: Gliosarcoma has a similar overall survival but worse response to treatment and different mutational profile than glioblastoma. CDKN2A/B loss and LRP1B alterations were associated with inferior prognosis, while RB1 or TSC2 alterations were associated with improved outcomes. These findings may have implications for clinical management and therapeutic selection in this patient population.

Purpose: Long-term language recovery after left-hemisphere glioma surgery varies substantially across patients. We investigated how well it can be predicted using clinical variables such as the postoperative decline in language processing, tumor grade, resection volume and location, extent of resection, and intraoperative language mapping. Beyond predicting the overall recovery, we examined which domains of language processing are most prone to persistent deficits.

Methods: Fifty-nine patients with left-hemisphere gliomas completed the Russian Aphasia Test (RAT) before surgery, immediately after surgery, and at follow-up three to seventeen months after surgery. We modeled their average language score (Generalized Aphasia Quotient, GAQ) at follow-up using a cross-validated multiple linear regression and calculated the number of patients showing persistent deficits in each subtest of the RAT.

Results: The difference between GAQ scores at follow-up and before surgery was not significant at the group level but varied substantially across patients (mean -1.3%, range -34.2 - 9.2%). Our best-performing model predicted the follow-up GAQ scores with the mean absolute error of 3.5% (cross-validated R² = 0.15). A greater decline in language processing immediately after surgery predicted worse recovery, whereas intraoperative language mapping predicted better recovery. Deficits in sentence repetition, verb production, verb and sentence comprehension, and object naming most often persisted at follow-up.

Conclusion: The postoperative decline in language processing and intraoperative language mapping explain a substantial amount of variability in long-term language recovery. Verbal working memory and lexical retrieval, particularly that of verbs, are most prone to persistent deficits.

Background: Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Typically treated with initial surgical resection, and chemoradiotherapy, despite current treatments, patients typically survive only 12-14 months, necessitating new therapeutic approaches. Our meta-analysis evaluates combining antiangiogenic medications with chemoradiotherapy versus using chemoradiotherapy alone in treating newly diagnosed GBM.

Methods: A comprehensive literature search was conducted using PubMed/MEDLINE, Scopus, Cochrane and the Web of Science databases. The search aimed to identify studies reporting overall survival (OS), progression-free survival (PFS), and hazard ratio (HR) with corresponding confidence intervals (CIs) in patients with newly diagnosed GBM. We employed random-effect meta-analysis.

Results: Twelve randomized clinical trials (RCTs) involved 3,309 patients included in the study. The findings showed that angiogenesis inhibitors significantly prolonged PFS [HR 0.85, 95% CI (0.73, 0.99), p-value = 0.04], while there was no significant difference on OS [HR 1.014, 95%CI (0.89, 1.15), p-value = 0.84]. Bevacizumab (BEV) exhibited the highest [HR 0.67, 95% CI (0.56, 0.79), p-value < 0.0001] and thalidomide exhibited the lowest [HR 1.46, 95% CI (1.004, 2.1), p-value = 0.048] improvements of PFS. Meta-regression revealed that age, white race, study sample size, infection, vascular disease complications, KPS > 60, biopsy, gross and subtotal resection can significantly influenced the PFS, while only the year of publication affected OS.

Conclusions: The current study showed that improve the PFS with no significant effect on OS. Our findings may provide some evidence for decision-making regarding the utilization of angiogenesis inhibitors for the treatment of adult patients with newly diagnosed GBM.

Background: Glioblastoma's infiltrative growth and heterogeneity are influenced by neural, molecular, genetic, and immunological factors, with the precise origin of these tumors remaining elusive. Neurogenic zones might serve as the tumor stem cells' nest, with tumors in contact with these zones exhibiting worse outcomes and more aggressive growth patterns. This study aimed to determine if these characteristics are reflected in advanced imaging, specifically diffusion and perfusion data.

Methods: In this monocentric retrospective study, 137 glioblastoma therapy-naive patients (IDH-wildtype, grade 4) with advanced preoperative MRI, including perfusion and diffusion imaging, were analyzed. Tumors and neurogenic zones were automatically segmented. Advanced imaging metrics, including cerebral blood volume (CBV) from perfusion imaging, tissue volume mask (TVM), and free water corrected fractional anisotropy (FA-FWE) from diffusion imaging, were extracted.

Results: SVZ infiltration positively correlated with CBV, indicating higher perfusion in tumors. Significant CBV differences were noted between high and low SVZ infiltration cases at specific percentiles. Negative correlation was observed with TVM and positive correlation with FA-FWE, suggesting more infiltrative tumor growth. Significant differences in TVM and FA-FWE values were found between high and low SVZ infiltration cases.

Discussion: Glioblastomas with SVZ infiltration exhibit distinct imaging characteristics, including higher perfusion and lower cell density per voxel, indicating a more infiltrative growth and higher vascularization. Stem cell-like characteristics in SVZ-infiltrating cells could explain the increased infiltration and aggressive behavior. Understanding these imaging and biological correlations could enhance the understanding of glioblastoma evolution.

Purpose: Vestibular schwannomas (VSs) represent the most common cerebellopontine angle tumors, posing a challenge in preserving facial nerve (FN) function during surgery. We employed the Extreme Gradient Boosting machine learning classifier to predict long-term FN outcomes (classified as House-Brackmann grades 1-2 for good outcomes and 3-6 for bad outcomes) after VS surgery.

Methods: In a retrospective analysis of 256 patients, comprehensive pre-, intra-, and post-operative factors were examined. We applied the machine learning (ML) classifier Extreme Gradient Boosting (XGBoost) for the following binary classification: long-term good and bad FN outcome after VS surgery To enhance the interpretability of our model, we utilized an explainable artificial intelligence approach.

Results: Short-term FN function (tau = 0.6) correlated with long-term FN function. The model exhibited an average accuracy of 0.83, a ROC AUC score of 0.91, and Matthew's correlation coefficient score of 0.62. The most influential feature, identified through SHapley Additive exPlanations (SHAP), was short-term FN function. Conversely, large tumor volume and absence of preoperative auditory brainstem responses were associated with unfavorable outcomes.

Conclusions: We introduce an effective ML model for classifying long-term FN outcomes following VS surgery. Short-term FN function was identified as the key predictor of long-term function. This model's excellent ability to differentiate bad and good outcomes makes it useful for evaluating patients and providing recommendations regarding FN dysfunction management.

Purpose: Mutations in the Isocitrate Dehydrogenase (IDH) genes, IDH1 or IDH2, define a group of adult diffuse gliomas associated with a younger age at diagnosis and better prognosis than IDH wild-type glioblastoma. Within IDH mutant gliomas, a small fraction of astrocytic tumors present with grade 4 histologic features and poor prognosis. In molecular studies, homozygous deletion of CDKN2A/B is independently predictive of poor prognosis and short survival. As a consequence, 2021 WHO classification now also recognizes this molecular feature, CDKN2A/B deletion, as sufficient for classifying an astrocytoma as IDH-mutant, WHO Grade 4, regardless of histological grading. Here, we investigate outcomes of patients with WHO Grade 4 IDH-mutant astrocytoma both with and without CDKN2A/B deletion, to compare these groups and evaluate clinical and radiographic factors that contribute to survival.

Methods: We retrospectively identified 79 patients with IDH-mutant astrocytoma with CDKN2A/B deletion detected at initial diagnosis across five international institutions as well as a comparison group of 51 patients with IDH-mutant, astrocytoma, histologically Grade 4 without detectable CDKN2A/B deletion. We assembled clinical and radiographic features for all patients.

Results: We find that CDKN2A/B deletion was associated with significantly worse overall survival (OS; p = 0.0004) and progression-free survival (PFS; p = 0.0026), with median OS of 5.0 years and PFS of 3.0 years, compared to 10.1 and 5.0 years for tumors with a grade 4 designation based only on histologic criteria. Multivariate analysis confirmed CDKN2A/B deletion as a strong negative prognosticator for both OS (HR = 3.51, p < 0.0001) and PFS (HR = 2.35, p = 0.00095). In addition, in tumors with CDKN2A/B deletion, preoperative contrast enhancement is a significant predictor of worse OS (HR 2.19, 95% CI 1.22-3.93, p = 0.0090) and PFS (HR = 1.74, 95% CI = 1.02-2.97, p = 0.0420).

Conclusions: These findings underscore the severe prognostic impact of CDKN2A/B deletion in IDH-mutant astrocytomas and highlight the need for further refinement of tumor prognostic categorization. Our results provide a key benchmark of baseline patient outcomes for therapeutic trials, underscoring the importance of CDKN2A/B status assessment, in addition to histologic grading, in clinical trial design and therapeutic decision-making for IDH-mutant astrocytoma patients.

Purpose: Toxicities associated with stereotactic radiosurgery (SRS) are important when considering treatment and supportive management for patients with brain metastases. We herein assessed the association between brain metastasis location and risk of toxicity after SRS.

Methods: We conducted a retrospective institutional review of patients treated with SRS for brain metastases between 2008 and 2023. Outcomes included radiation necrosis, seizure, local failure, and overall survival (OS).

Results: We reviewed 215 patients treated to 605 metastases (median diameter 10 mm, IQR 5-17 mm), in the frontal (34%), cerebellar (19%), parietal (16%), temporal (13%), and occipital (13%) regions. Median follow-up was 16 months (IQR 7-36). New-onset seizures developed in 11% (19/174) of patients without prior seizure and was higher in patients with motor or sensory cortex lesions (12/48, 25%) on multivariate analysis (MVA, P = 0.02). SRS-related grade ≥ 2 symptomatic radionecrosis occurred in 6% (33/605) of lesions and correlated with larger metastasis volume (P < 0.001) and renal cell carcinoma histology (P < 0.05), while supratentorial location was nearly significant (MVA, P = 0.06). Median OS across all patients was 16 months (95% CI 12-20). Patients with symptomatic radiation necrosis had a longer median survival compared to those who did not (43 vs. 14 months, P = 0.002), which remained significant alongside Karnofsky performance status and extracranial disease on MVA.

Conclusion: Brain metastasis location in the motor or sensory cortex is associated with increased risk of new-onset seizure following SRS and may warrant consideration of steroid and/or anti-epileptic prophylaxis. Symptomatic radiation necrosis is uncommon in the cerebellum and may be increasing with improvements in survival.