Applications of diffusion tensor imaging integrated with neuronavigation to prevent visual damage during tumor resection in the optic radiation area.

Background: Intracranial tumors involving the temporo-occipital lobe often compress or destroy the optic radiation (OpR), resulting in decreased visual function. The aim of this study is to explore the value of diffusion tensor imaging (DTI) tractography integrated with neuronavigation to prevent visual damage when resecting tumors involving the OpR and find potential factors affecting patients' visual function and quality of life (QOL). Methods: Our study is a cross-sectional study that included 28 patients with intracranial tumors in close morphological relationship with the OpR recruited between January 2020 and February 2022. The surgical incision and approach were preoperatively designed and adjusted according to the DTI tractography results and visual function scores. All patients underwent examinations of visual acuity (VA) and visual field index (VFI) and completed visual function and QOL scales at admission and 2 months after discharge. Logistic regression and linear regression analysis were conducted to evaluate clinical factors potentially affecting pre/postoperative OpR morphology, VA, VFI, visual function, and QOL. Results: Lesion size was the main factor found to affect visual function (ß = -0.74, 95%CI: -1.12~-0.36, P = 0.05), VA (left: ß = -0.11, 95%CI: -0.14~-0.08, P < 0.001; right: ß = -0.15, 95%CI: -0.17~-0.13, P < 0.001), and VFI (left: ß = -0.11, 95%CI: -0.14~-0.08, P < 0.001; right: ß = -0.14, 95%CI: -0.16~-0.12, P < 0.001). Lesion size, edema, and involvement of the lateral ventricle temporal horn were factors affecting OpR morphology and QOL. The 28 patients showed significantly improved VA, VFI, visual function, and QOL results (P < 0.05) 2 months after discharge. Conclusions: Combining DTI of OpR mapping and microscopic-based neuronavigation aided precise mapping and thus preservation of visual function in patients undergoing tumor resection. Potential clinical factors affecting patients' visual function and QOL scores were identified which are useful for assessing a patient's condition and predicting prognosis.

Identification of Key Biomarkers and Immune Infiltration in Sporadic Vestibular Schwannoma Basing Transcriptome-Wide Profiling.

BACKGROUND: Vestibular schwannoma is a common intracranial tumor, with 95% of the cases being sporadic vestibular schwannoma (SVS). The purpose of this study was identifying genes responsible for inflammation in SVS and clarifying its underlying immune mechanisms. METHODS: Transcriptional sequencing datasets (GSE141801 and GSE108237) from the Gene Expression Omnibus database were used in this study. The candidate modules closely related to SVS and hub genes were screened out by weighted gene coexpression network analysis. Τhe sensitivity and specificity of the hub genes for SVS prediction were evaluated by receiver operating characteristic curve analysis. The CIBERSORT algorithm was subsequently applied to analyze the immune infiltration between SVS and controls. Finally, biological signaling pathways involved in the hub genes were identified via gene set enrichment analysis. RESULTS: A total of 39 significantly enriched in myelination and collagen-containing extracellular matrix DEGs were identified at the screening step. Three hub genes (MAPK8IP1, SLC36A2, and OR2AT4) were identified, which mainly enriched in pathways of melanogenesis, GnRH, and calcium signaling pathways. Compared with normal nerves, SVS tissue contained a higher proportion of T cells, monocytes, and activated dendritic cells, whereas proportions of M2 macrophages were lower. CONCLUSIONS: The integrated analysis revealed the pattern of immune cell infiltration in SVS and provided a crucial molecular foundation to enhance understanding of SVS. Hub genes MAPK8IP1, SLC36A2, and OR2AT4 are potential biomarkers and therapeutic targets to facilitate the accurate diagnosis, prognosis, and therapy of SVS.

Integrated Analysis of Transcriptome and Differential Methylation of Neurofibromatosis Type 2 Vestibular Schwannomas.

BACKGROUND: Vestibular schwannoma is the third most common benign intracranial tumor that can occur sporadically or be associated with neurofibromatosis type 2 (neurofibromatosis type 2 vestibular schwannoma [NF2-VS]). The aim of this study is to provide a comprehensive bioinformatic analysis of methylated-differentially expressed genes (MDEGs) in NF2-VS. METHODS: Transcriptional sequencing datasets (GSE141801 and GSE108524) and gene methylation microarrays (GSE56598) from the Gene Expression Omnibus database were used to identify and analyze MDEGs in NF2-VS. A protein-protein interaction (PPI) network was built, and the hub genes and modules were identified. Finally, potential pharmacotherapy targeting MDEGs were extracted for NF2-VS. RESULTS: A total of 57 hypermethylation-low expression genes and 88 hypomethylation-high expression genes were identified. Pathways associated with aberrantly MDEGs included P13K-AKT, MAPK, and Ras, which were also involved in NF2-VS. Six hub genes (EGFR, CCND1, CD53, CSF1R, PLAU, and FGFR1) were identified from the PPI network. Modification of the aforementioned genes altered cell-to-cell communication, response to stimulus, cellular regulation, and membrane and protein bindings. Thirty drugs targeting these pathways were selected based on the hub genes. CONCLUSIONS: Analysis of MDEGs may enrich the understanding of the molecular mechanisms of NF2-VS pathogenesis and lay the groundwork for potential biomarkers and therapeutic targets for NF2-VS.

Efficacy and Safety of First-Line Treatment Strategies for Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis.

BACKGROUND: Targeted therapies have led to significant improvement in the management and prognosis of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). We performed a network meta-analysis of frontline treatment options of ALK-positive NSCLC to provide clinical guidance. METHODS: PubMed, Embase, ClinicalTrials.gov, and international conference databases were searched to identify relevant trials from inception to June 30, 2021. Phase III randomized controlled trials (RCTs) comparing treatments for patients with ALK-positive advanced NSCLC in the first-line setting were included in a Bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcomes: progression-free survival (PFS), overall survival (OS), risk of the central nervous system (CNS) progression, adverse events (AEs) of grade (G) 3 or higher (G3 AEs), or serious AEs (SAEs). Hazard ratios (HRs) and CI for primary outcome of PFS and secondary outcome of OS and risk of CNS progression were obtained. A multivariate, consistency model, fixed-effects analysis was used in the network meta-analysis. Data on G3 AEs and SAEs were abstracted and meta-analyzed. Risk of bias (RoB) was assessed using the Cochrane Collaboration's tool. RESULTS: Nine RCTs comprising 2,484 patients were included with seven treatments: alectinib, brigatinib, ceritinib, crizotinib, ensartinib, lorlatinib, and chemotherapy. Compared with chemotherapy, ALK-tyrosine kinase inhibitors (TKIs) significantly prolong PFS and reduced risk of CNS progression except for ceritinib. Lorlatinib appears superior at reducing risk of CNS progression. None of the ALK-TKIs have a significantly prolonged OS as compared with chemotherapy. Lorlatinib increases the risk of G3 AEs as compared with alectinib (odds ratio 4.26 [95% CrI 1.22 to 15.53]), while alectinib caused the fewest G3 AEs. CONCLUSIONS: Lorlatinib is associated with the highest PFS benefit and lowest risk of CNS progression benefits for patients with advanced ALK-positive NSCLC, compared with other first-line treatments, but with higher toxicity. The implementation of a newer generation of ALK-TKIs in the first-line treatment of ALK-positive NSCLC into current clinical practice is evolving rapidly.

Reliability and toxicity of bevacizumab for neurofibromatosis type 2-related vestibular schwannomas: A systematic review and meta-analysis.

BACKGROUND: The anti-angiogenic agent bevacizumab is currently the only drug used clinically for neurofibromatosis type 2-related vestibular schwannomas (NF2-VS). Though benefits have been demonstrated in several cases, the standardized dosage remains unclear. OBJECTIVE: Our meta-analysis was performed to systematically and comprehensively investigate the reliability and toxicity of bevacizumab in the treatment of NF2-VS, with particular emphasis on the impact of dosage. METHODS: The literature search was conducted for studies providing data on patients treated with bevacizumab for NF2-VS across PubMed, Embase, and Cochrane Library until December 31, 2020. Two reviewers extracted the incidence rate of results independently. Then we calculated and pooled unadjusted incidence rate with 95% CIs for each study. The subgroups analyzed were conducted. RESULTS: Fourteen citations (prospective or retrospective observational cohort studies) were eligible based on data from a total of 247 patients with NF2 and 332 related VSs. The pooled results showed that the radiographic response rate (RRR) was 30% [95% CI (20%-42%)], the hearing response rate (HRR) was 32% [95% CI (21%-45%)]. The incidence of major complications was: hypertension 29% [95% CI (23%-35%)], proteinuria 30% [95% CI (18%-44%)], menstrual disorders 44% [95% CI (16%-73%)], hemorrhage 14% [95% CI (4%-26%)], grade3/4 events 12% [95% CI (4%-22%)]. CONCLUSIONS: Nearly one-third of NF2-VS patients may benefit significantly from bevacizumab due to hearing improvement and tumor reduction. Menstrual disorders were the most common adverse events. The high-dose regimen didn't show better efficacy, but results varied considerably according to age.