IKIP downregulates THBS1/FAK signaling to suppress migration and invasion by glioblastoma cells.

Background: Inhibitor of NF-κB kinase-interacting protein (IKIP) is known to promote proliferation of glioblastoma (GBM) cells, but how it affects migration and invasion by those cells is unclear. Methods: We compared levels of IKIP between glioma tissues and normal brain tissue in clinical samples and public databases. We examined the effects of IKIP overexpression and knockdown on the migration and invasion of GBM using transwell and wound healing assays, and we compared the transcriptomes under these different conditions to identify the molecular mechanisms involved. Results: Based on data from our clinical samples and from public databases, IKIP was overexpressed in GBM tumors, and its expression level correlated inversely with survival. IKIP overexpression in GBM cells inhibited migration and invasion in transwell and wound healing assays, whereas IKIP knockdown exerted the opposite effects. IKIP overexpression in GBM cells that were injected into mouse brain promoted tumor growth but inhibited tumor invasion of surrounding tissue. The effects of IKIP were associated with downregulation of THBS1 mRNA and concomitant inhibition of THBS1/FAK signaling. Conclusions: IKIP inhibits THBS1/FAK signaling to suppress migration and invasion of GBM cells.

Management of cavernous sinus meningiomas: Clinical features, treatment strategies, and long-term outcomes.

OBJECTIVES: The purpose of this research was to summarize the clinical and prognostic features of cavernous sinus meningiomas (CSM), evaluate the treatment strategies and long-term prognosis of CSM, and improve the management of CSM and the treatment effect for patients. METHODS: We retrospectively studied the data of 54 patients who received initial surgical resection and 45 patients who received initial gamma knife radiosurgery (GKRS) for CSM at West China Hospital of Sichuan University from 2009 to 2021. Progression-free survival (PFS), Karnofsky Performance Scale (KPS) scores and neurological function recovery were adopted to assess a comprehensive management strategy for CSM. RESULTS: Gross total resection (GTR) was performed in 51.9 % of cases with 3.7 % surgical mortality. The average follow-up time was 48.7 months, with a progression rate of 29.3 %. The overall improvement rate for cranial nerve function deficits was 50.0 %. By survival analysis, the extent of resection and the histological grade were significantly related to the prognosis. The role of postoperative GKRS is uncertain. For patients who received initial GKRS, the progression rate was 17.8 %, and the overall improvement rate for cranial nerve function deficits was 61.1 %. Primary treatment with GKRS showed better long-term tumor control in patients with CSM (P = 0.046). CONCLUSIONS: Maximum safe resection of CSM can improve the neurological function and quality of life of patients, but aggressive resection will cause high perioperative mortality and complication rates. For CSM patients who are suitable for initial gamma knife treatment, choosing GKRS can achieve better long-term tumor control and neurological outcomes.

Comparative dosimetric study of radiotherapy in high-grade gliomas based on the guidelines of EORTC and NRG-2019 target delineation.

Purpose: Radiotherapy is one of the most important treatments for high-grade glioma (HGG), but the best way to delineate the target areas for radiotherapy remains controversial, so our aim was to compare the dosimetric differences in radiation treatment plans generated based on the European Organization for Research and Treatment of Cancer (EORTC) and National Research Group (NRG) consensus to provide evidence for optimal target delineation for HGG. Methods: We prospectively enrolled 13 patients with a confirmed HGG from our hospital and assessed dosimetric differences in radiotherapy treatment plans generated according to the EORTC and NRG-2019 guidelines. For each patient, two treatment plans were generated. Dosimetric parameters were compared by dose-volume histograms for each plan. Results: The median volume for planning target volume (PTV) of EORTC plans, PTV1 of NRG-2019 plans, and PTV2 of NRG-2019 plans were 336.6 cm3 (range, 161.1-511.5 cm3), 365.3 cm3 (range, 123.4-535.0 cm3), and 263.2 cm3 (range, 116.8-497.7 cm3), respectively. Both treatment plans were found to have similar efficiency and evaluated as acceptable for patient treatment. Both treatment plans showed well conformal index and homogeneity index and were not statistically significantly different (P = 0.397 and P = 0.427, respectively). There was no significant difference in the volume percent of brain irradiated to 30, 46, and 60 Gy according to different target delineations (P = 0.397, P = 0.590, and P = 0.739, respectively). These two plans also showed no significant differences in the doses to the brain stem, optic chiasm, left and right optic nerves, left and right lens, left and right eyes, pituitary, and left and right temporal lobes (P = 0.858, P = 0.858, P = 0.701 and P = 0.794, P = 0.701 and P = 0.427, P = 0.489 and P = 0.898, P = 0.626, and P = 0.942 and P = 0.161, respectively). Conclusion: The NRG-2019 project did not increase the dose of organs at risk (OARs) radiation. This is a significant finding that further lays the groundwork for the application of the NRG-2019 consensus in the treatment of patients with HGGs. Clinical trial registration: The effect of radiotherapy target area and glial fibrillary acidic protein (GFAP) on the prognosis of high-grade glioma and its mechanism, number ChiCTR2100046667. Registered 26 May 2021.

The Performance of Different Machine Learning Algorithm and Regression Models in Predicting High-Grade Intracranial Meningioma.

Meningioma is the most common primary tumor of the central nervous system (CNS). Individualized treatment strategies should be formulated for the patients according to the WHO (World Health Organization) grade. Our aim was to investigate the effectiveness of various machine learning and traditional statistical models in predicting the WHO grade of preoperative patients with meningioma. Patients diagnosed with meningioma after surgery in West China Hospital and Shangjin Hospital of Sichuan University from 2009 to 2016 were included in the study cohort. As the training cohort (n = 1975), independent risk factors associated with high-grade meningioma were used to establish the Nomogram model. which was validated in a subsequent cohort (n = 1048) from 2017 to 2019 in our hospital. Logistic regression (LR), XGboost, Adaboost, Support Vector Machine (SVM), K-Nearest Neighbor (KNN), and Random Forest (RF) models were determined using F1 score, recall, accuracy, the area under the curve (ROC), calibration plot and decision curve analysis (DCA) were used to evaluate the different models. Logistic regression showed better predictive performance and interpretability than machine learning. Gender, recurrence history, T1 signal intensity, enhanced signal degree, peritumoral edema, tumor diameter, cystic, location, and NLR index were identified as independent risk factors and added to the nomogram. The AUC (Area Under Curve) value of RF was 0.812 in the training set, 0.807 in the internal validation set, and 0.842 in the external validation set. The calibration curve and DCA (Decision Curve Analysis) indicated that it had better prediction efficiency of LR than others. The Nomogram preoperative prediction model of meningioma of WHO II and III grades showed effective prediction ability. While machine learning exhibits strong fitting ability, it performs poorly in the validation set.

Clinical features, radiological findings, and prognostic factors for primary intracranial chordoid meningioma.

Objectives: Chordoid meningioma (CM) is an infrequent histologic subtype of meningiomas. Owing to its low occurrence, this subtype has been rarely described. Our subject was to explore the clinical features, radiological characteristics, and prognostic factors of primary intracranial chordoid meningioma. Methods: We reviewed the medical records and collected follow-up information of 34 cases who had been surgically treated and histologically diagnosed with CM at the Department of Neurosurgery, West-China Hospital of Sichuan University, from January 2009 to December 2021. Results: Among all 7,950 meningioma cases, the proportion of primary intracranial CM was 0.43% (34/7,950). The median diagnosis age was 47 (ranging from 12 to 74) and the gender ratio (male to female) was 2.1:1. For radiological features, heterogeneous enhancement, skull base, and ventricular localization, cystic degeneration and dural tail sign were common in CM cases. In treatment, gross total resection (GTR) was achieved in 22/34 cases (64.7%) and subtotal resection (STR) was achieved in 12/34 cases (35.3%). Further, 11/34 patients (32.4%) had received postoperative adjuvant radiotherapy (RT). The follow-up duration ranged from 4 to 157 months after operation. The progression rate was 20.7% (6/29) and the median of PFS was 38 months. By survival analysis, accepting adjuvant radiotherapy and achieving GTR were correlated with longer progression-free survival for prognosis. Conclusion: CM is a rare subtype of meningiomas. In our series, it mainly involved adults and did not show a predilection for women compared with meningiomas in general. For a better prognosis, gross total resection and postoperative adjuvant radiotherapy are recommended. Nevertheless, due to the restriction of the series sample, patients lost for follow-up and inherent biases of a retrospective study, more cases and a shorter follow-up duration are needed for better management of chordoid meningioma.

Management of Skull-Base Meningiomas With Extracranial Extensions: Clinical Features, Radiological Findings, Surgical Strategies, and Long-Term Outcomes.

Objectives: The aim of this research was to summarize the clinical and prognostic features of the skull-base meningiomas with extracranial extensions, and enhance the management of skull-base communicative meningiomas. Methods: We retrospectively studied the medical records and analyzed the follow-up information of 53 patients who have done surgery for skull-base meningiomas with extracranial extensions in West China Hospital of Sichuan University from 2009 to 2020. Results: The incidence of skull-base meningiomas with extracranial extensions was 0.74%. The average diagnosis age was 45.9 years, with a 1:3.1 men to women ratio. WHO grade I was seen in 84.9% of patients, and higher grades were found in 15.1%. Heterogeneous enhancement, high bone invasion rate, high incidence of peritumoral edema, and high dural tail sign rate were typical imaging features. Routine craniotomy and endoscopic endonasal approach were adopted, and gross total resection was performed in 62.3% of cases with 20.8% postoperative complication rates. The average follow-up time was 61.5 months, with a recurrence rate of 34.9%. By survival analysis, the extent of resection (p = 0.009) and the histological grade (p = 0.007) were significantly related to the prognosis. Adjuvant radiotherapy proved beneficial in patients with subtotal resection (p = 0.010) and high-grade meningiomas (p = 0.018). Conclusions: Skull-base meningiomas with extracranial extensions were sporadic. According to the tumor location and communication way showed by the preoperative imaging, routine craniotomy or endoscopic endonasal approach with a reasonable skull-base repair strategy could be adopted to achieve the maximum tumor resection. Maximized resection, adjuvant radiotherapy, and low histological grade indicate a better prognosis.

Lateral Ventricular Meningiomas: Clinical Features, Radiological Findings and Long-Term Outcomes.

PURPOSE: Lateral ventricle meningioma (LVM) is a rare type of intracranial meningioma, which has been rarely studied. It has different clinical features, imaging features, and long-term results from other locations. This study investigated the epidemiology, clinical characteristics and prognosis of LVM and comprehensively describes its characteristics. METHODS: This article analyzes the LVMs that were diagnosed pathologically in West China hospital between January 1, 2009 and July 1 2020. Demographic information, imaging characteristics and prognostic factors are discussed. Data analysis was performed using SPSS 23.0 and R version 3.5.3. RESULTS: We collected 7202 meningiomas and 195 LVMs (136 females; median age, 46 years; range, 5-81 years) were included in this study. Gross total resection was completed in 189 patients. The OS rate was 93.8%, and the recurrence rate was 5.2%. Multivariate regression analysis showed that sex (P = 0.01) and tumor size (P = 0.018) were related to WHO grade. Postoperative KPS (P = 0.003) was associated with OS. WHO grade (P = 0.025), extent of tumor resection (P < 0.001), and hospital day (P=0.028) were associated with recurrence. CONCLUSION: LVMs require long-term follow-up, individualized treatment, and follow-up strategies to be formulated according to the relevant risk factors.

Nomograms for Predicting Overall Survival Among Patients with Craniopharyngiomas at Initial Diagnosis: A SEER Population-Based Analysis.

BACKGROUND: Craniopharyngiomas (CPs) are relatively rare benign tumor located in the central nervous system (CNS). This study investigates the related risk factors of survival of craniopharyngiomas and develops a simple but detailed method predicting prognosis based on the Surveillance, Epidemiology, and End Results (SEER) database in order to improve the clinic management of CPs. METHODS: Between 2004 and 2017, 1213 patients diagnosed with craniopharyngiomas registered at the program and were included in the SEER-21 registry database. Overall survival (OS) curves were plotted with the Kaplan-Meier method and significance was determined by Log rank test. Single- and multiple-factor regression analyses were made using Cox proportional hazards model to identify independent predictors related to OS. Subsequently, we developed a nomogram with those factors to predict 3-, 5- and 10-year OS of craniopharyngiomas patients. RESULTS: We identified 1213 patients with craniopharyngioma. The OS rates at 3, 5, and 10 years after diagnosis were 89.1%, 86.2%, and 83%. Age, ethnicity, tumor size and radiation therapy were confirmed to be predictors correlating with OS at initial diagnosis. In multivariate analysis, we found that younger age (P<0.001), smaller tumor size (P<0.001), white ethnicity (P<0.001) and radiation therapy (P=0.004) were the factors that remained significantly associated with better survival. A nomogram was successfully constructed and validated by ROC, calibration plots and C-index of 0.773 (95% CI, 0.708-0.838). CONCLUSION: The well-calibrated nomogram is the first clinical prediction model for predicting the prognosis for patients with craniopharyngiomas at initial diagnosis. Our study indicates that the surgical effect is not clear. Younger white patients with radiotherapy have a better prognosis, and the gross total resection (GTR) was not effective in prolonging the OS of a patient compared to no surgery and subtotal resection (STR).

Nomograms Forecasting Long-Term Overall and Cancer Specific Survival of Patients With Head and Neck Neuroendocrine Carcinoma.

BACKGROUND: The purpose of this retrospective analysis was to build and validate nomograms to predict the cancer-specific survival (CSS) and overall survival (OS) of head and neck neuroendocrine carcinoma (HNNEC) patients. METHODS: A total of 493 HNNEC patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015, and 74 HNNEC patients were collected from the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital (HCH) between 2008 and 2020. Patients from SEER were randomly assigned into training (N=345) and internal validation (N=148) groups, and the independent data group (N=74) from HCH was used for external validation. Independent prognostic factors were collected using an input method in a Cox regression model, and they were then included in nomograms to predict 3-, 5-, and 10-year CSS and OS rates of HNNEC patients. Finally, we evaluated the internal and external validity of the nomograms using the consistency index, while assessing their prediction accuracy using calibration curves. A receiver operating curve (ROC) was also used to measure the performance of the survival models. RESULTS: The 3-, 5-, and 10-year nomograms of this analysis demonstrated that M classification had the largest influence on CSS and OS of HNNEC, followed by the AJCC stage, N stage, age at diagnosis, sex/gender, radiation therapy, and marital status. The training validation C-indexes for the CSS and OS models were 0.739 and 0.713, respectively. Those for the internal validation group were 0.726 and 0.703, respectively, and for the external validation group were 0.765 and 0.709, respectively. The area under the ROC curve (AUC) of 3-, 5-, and 10-year CSS and OS models were 0.81, 0.82, 0.82, and 0.78, 0.81, and 0.82, respectively. The C-indexes were all higher than 0.7, indicating the high accuracy ability of our model's survival prediction. CONCLUSIONS: In this study, prognosis nomograms in HNNEC patients were constructed to predict CSS and OS for the first time. Clinicians can identify patients' survival risk better and help patients understand their survival prognosis for the next 3, 5, and 10 years more clearly by using these nomograms.

Pediatric meningiomas: 10-year experience with 39 patients.

OBJECTIVE: The purpose of this article was to study the characteristics of pediatric meningiomas, including the clinical symptom, anatomic location, radiological finding, treatment approaches, and long-term surgical outcome as well as the possible influence factors of the prognosis. METHODS: We retrospectively reviewed the medical records and follow-up data of 39 pediatric patients who were treated by operation for intracranial meningiomas in West-China Hospital between 2009-2019. RESULTS: The incidence of pediatric meningioma was 0.74%. The mean age at surgery was 12.2 years and the ratio of male to female was 1.3. Three cases (7.7%) were related to neurofibromas. WHO grade I was found in 26 patients (66.7%) and higher grades was seen in 13 (33.3%). The most common location sites were convexity (35.9%). Gross total excision was achieved in 28 patients (71.8%). The mean follow-up period was 54.4 months. The recurrence rate was 41.9%. By survival analysis, only gross total resection (p = 0.028) was associated with favorable outcome. CONCLUSION: Meningiomas in children are very rare and have a slight male predominance. Pediatric meningiomas are more commonly located in intraventricular and have higher incidence rate of high-grade than that in adults. Although being challenging, the gross total excision should be underdone to achieve a better prognosis.