Mid-term follow-up surgical results in 284 cases of clival chordomas: the risk factors for outcome and tumor recurrence.

OBJECTIVE: Skull base chordoma (SBC) is rare and one of the most challenging diseases to treat. We aimed to assess the optimal timing of adjuvant radiation therapy (RT) and to evaluate the factors that influence resection and long-term outcomes. METHODS: In total, 284 patients with 382 surgeries were enrolled in this retrospective study. Postsurgically, 64 patients underwent RT before recurrence (pre-recurrence RT), and 47 patients underwent RT after recurrence. During the first attempt to achieve gross-total resection (GTR), when the entire tumor was resected, 268 patients were treated with an endoscopic midline approach, and 16 patients were treated with microscopic lateral approaches. Factors associated with the success of GTR were identified using χ2 and logistic regression analyses. Risk factors associated with chordoma-specific survival (CSS) and progression-free survival (PFS) were evaluated with the Cox proportional hazards model. RESULTS: In total, 74.6% of tumors were marginally resected [GTR (40.1%), near-total resection (34.5%)]. History of surgery, large tumor volumes, and tumor locations in the lower clivus were associated with a lower GTR rate. The mean follow-up period was 43.9 months. At the last follow-up, 181 (63.7%) patients were alive. RT history, histologic subtype (dedifferentiated and sarcomatoid), non-GTR, no postsurgical RT, and the presence of metastasis were associated with poorer CSS. Patients with pre-recurrence RT had the longest PFS and CSS, while patients without postsurgical RT had the worst outcome. CONCLUSION: GTR is the goal of initial surgical treatment. Pre-recurrence RT would improve outcome regardless of GTR.

Mean platelet volume and platelet distribution width serve as prognostic biomarkers in skull base chordoma: a retrospective study.

BACKGROUND: Increasing studies have demonstrated that activated platelets play an essential role in tumour progression. However, the level and prognostic role of platelet indices in chordoma patients remain unclear. The aim of the current study was to characterize the prognostic performance of platelet count (PLT), mean platelet volume (MPV) and platelet distribution width (PDW) in skull base chordoma patients. METHODS: 187 primary skull base chordoma patients between January 2008 and September 2014 were enrolled in this retrospective study. The optimal cut-off values were determined by X-tile software, and the correlations between PLT, MPV, PDW and clinicopathological features were further analysed. Kaplan-Meier curve and Cox regression analysis were used for survival analysis. RESULTS: The values of preoperative PTL, MPV and PDW ranged from 104 to 501 × 109/L, 6.7 to 14.2 fl, and 7.8 to 26.2%, respectively. Elevated PLT was associated with larger tumour volume (p = 0.002). Kaplan-Meier survival analysis revealed that increased MPV and PDW were associated with shorter overall survival (p = 0.022 and 0.008, respectively). Importantly, multivariate Cox analysis demonstrated that elevated PDW was an independent unfavourable predictive factor for overall survival (hazard ratio (HR), 2.154, 95% confidence interval (CI), 1.258-3.688, p = 0.005). CONCLUSIONS: Our data show that elevated MPV and PDW are associated with poor outcomes in skull base chordoma and that PDW may be helpful to identify patients with high risk.

Ultrastable Surface-Dominated Pseudocapacitive Potassium Storage Enabled by Edge-Enriched N-Doped Porous Carbon Nanosheets.

The development of ultrastable carbon materials for potassium storage poses key limitations caused by the huge volume variation and sluggish kinetics. Nitrogen-enriched porous carbons have recently emerged as promising candidates for this application; however, rational control over nitrogen doping is needed to further suppress the long-term capacity fading. Here we propose a strategy based on pyrolysis-etching of a pyridine-coordinated polymer for deliberate manipulation of edge-nitrogen doping and specific spatial distribution in amorphous high-surface-area carbons; the obtained material shows an edge-nitrogen content of up to 9.34 at %, richer N distribution inside the material, and high surface area of 616 m2 g-1 under a cost-effective low-temperature carbonization. The optimized carbon delivers unprecedented K-storage stability over 6000 cycles with negligible capacity decay (252 mA h g-1 after 4 months at 1 A g-1 ), rarely reported for potassium storage.

SNF5 as a prognostic factor in skull base chordoma.

The current study aimed to characterize SNF5 expression and investigate the relationship between SNF5 and clinicopathological features in skull base chordoma. 48 patients diagnosed with skull base chordoma were enrolled in this study. Tissue microarray and immunohistochemistry were performed to evaluate the expression of SNF5 in skull base chordoma. Kaplan-Meier survival analysis was used to assess survival. Multivariable Cox regression analysis was used to identify risk factors affecting patient survival. The H-scores for cytoplasmic SNF5 ranged from 124.47 to 254.52. Low expression of SNF5 was correlated with shorter overall survival (OS) (p = 0.021). Patients with age > 55 years old had shorter progression free survival (PFS) and OS times than patients whose age ≤ 55 years old (p = 0.005 and 0.003, respectively). The gross total resection group showed longer PFS than the non-gross total resection group (p = 0.024). Females showed shorter PFS times than males (p = 0.033). Multivariable Cox regression analysis showed that age, extent of resection and sex were independent prognostic factors for PFS (p = 0.010, 0.013 and 0.042, respectively). Age was an independent prognostic factor for OS (p = 0.010). Our study indicate that low expression of SNF5 is associated with poor prognosis in skull base chordoma.

Surgical outcome of encapsulated brain abscess in superficial non-eloquent area: A systematic review.

OBJECTIVE: To investigate surgical (aspiration and resection) outcome of encapsulated brain abscess in superficial non-eloquent area. METHODS: We searched Pubmed, Embase and Cochrane Library from the foundation of the database till December 2013. Two researchers screened literatures independently, assessed the quality of the included studies and extracted the data. Revman 5.2.8 was used to do meta-analysis. RESULTS: A total of five studies were included, all retrospective cohort studies. Eighty-four cases were in the abscess aspiration group and 124 cases were in the abscess resection group. Meta-analysis showed that the abscess resection group had lower rate of postoperative residual abscess, lower re-operation rate, higher rate of improvement in neurological status within 1 month after surgery, their OR (95% Confidence Interval (CI)) were 0.12 (0.04, 0.34), 0.07 (0.02, 0.20), 7.9 (3.20, 19.51) respectively; the abscess resection group had shorter duration of post-operative antibiotics and average length of hospital stay; Standard Mean Difference (SMD) (95% CI) were -0.84 (-1.27, -0.41), -1.01 (-1.54, -0.49), respectively. There was no statistically significant difference in the rate of improvement in neurological status at 3 months post-operative and the mortality. CONCLUSIONS: Current evidences suggest that for encapsulated brain abscess in superficial non-eloquent area, abscess resection compared to abscess aspiration had lower post-operative residual abscess rate; lower re-operation rate; higher rate of improvement in neurological status within 1 month after surgery, shorter duration of post-operative antibiotics and average length of hospital stay. There was no statistically significant difference in the rate of improvement in neurological status at 3 months post-operative and the mortality.

A Multiparametric MRI-Based Radiomics Nomogram for Preoperative Prediction of Survival Stratification in Glioblastoma Patients With Standard Treatment.

OBJECTIVE: To construct and validate a radiomics nomogram for preoperative prediction of survival stratification in glioblastoma (GBM) patients with standard treatment according to radiomics features extracted from multiparameter magnetic resonance imaging (MRI), which could facilitate clinical decision-making. METHODS: A total of 125 eligible GBM patients (53 in the short and 72 in the long survival group, separated by an overall survival of 12 months) were randomly divided into a training cohort (n = 87) and a validation cohort (n = 38). Radiomics features were extracted from the MRI of each patient. The T-test and the least absolute shrinkage and selection operator algorithm (LASSO) were used for feature selection. Next, three feature classifier models were established based on the selected features and evaluated by the area under curve (AUC). A radiomics score (Radscore) was then constructed by these features for each patient. Combined with clinical features, a radiomics nomogram was constructed with independent risk factors selected by the logistic regression model. The performance of the nomogram was assessed by AUC, calibration, discrimination, and clinical usefulness. RESULTS: There were 5,216 radiomics features extracted from each patient, and 5,060 of them were stable features judged by the intraclass correlation coefficients (ICCs). 21 features were included in the construction of the radiomics score. Of three feature classifier models, support vector machines (SVM) had the best classification effect. The radiomics nomogram was constructed in the training cohort and exhibited promising calibration and discrimination with AUCs of 0.877 and 0.919 in the training and validation cohorts, respectively. The favorable decision curve analysis (DCA) indicated the clinical usefulness of the radiomics nomogram. CONCLUSIONS: The presented radiomics nomogram, as a non-invasive tool, achieved satisfactory preoperative prediction of the individualized survival stratification of GBM patients.

Development and validation of a preoperative MRI-based radiomics nomogram to predict progression-free survival in patients with clival chordomas.

Objectives: The aim of this study was to establish and validate a MRI-based radiomics nomogram to predict progression-free survival (PFS) of clival chordoma. Methods: A total of 174 patients were enrolled in the study (train cohort: 121 cases, test cohort: 53 cases). Radiomic features were extracted from multiparametric MRIs. Intraclass correlation coefficient analysis and a Lasso and Elastic-Net regularized generalized linear model were used for feature selection. Then, a nomogram was established via univariate and multivariate Cox regression analysis in the train cohort. The performance of this nomogram was assessed by area under curve (AUC) and calibration curve. Results: A total of 3318 radiomic features were extracted from each patient, of which 2563 radiomic features were stable features. After feature selection, seven radiomic features were selected. Cox regression analysis revealed that 2 clinical factors (degree of resection, and presence or absence of primary chordoma) and 4 radiomic features were independent prognostic factors. The AUC of the established nomogram was 0.747, 0.807, and 0.904 for PFS prediction at 1, 3, and 5 years in the train cohort, respectively, compared with 0.582, 0.852, and 0.914 in the test cohort. Calibration and risk score stratified survival curves were satisfactory in the train and test cohort. Conclusions: The presented nomogram demonstrated a favorable predictive accuracy of PFS, which provided a novel tool to predict prognosis and risk stratification. Our results suggest that radiomic analysis can effectively help neurosurgeons perform individualized evaluations of patients with clival chordomas.

Prediction of blood supply in vestibular schwannomas using radiomics machine learning classifiers.

This study attempts to explore the radiomics-based features of multi-parametric magnetic resonance imaging (MRI) and construct a machine-learning model to predict the blood supply in vestibular schwannoma preoperatively. By retrospectively collecting the preoperative MRI data of patients with vestibular schwannoma, patients were divided into poor and rich blood supply groups according to the intraoperative recording. Patients were divided into training and test cohorts (2:1), randomly. Stable features were retained by intra-group correlation coefficients (ICCs). Four feature selection methods and four classification methods were evaluated to construct favorable radiomics classifiers. The mean area under the curve (AUC) obtained in the test set for different combinations of feature selecting methods and classifiers was calculated separately to compare the performance of the models. Obtain and compare the best combination results with the performance of differentiation through visual observation in clinical diagnosis. 191 patients were included in this study. 3918 stable features were extracted from each patient. Least absolute shrinkage and selection operator (LASSO) and logistic regression model was selected as the optimal combinations after comparing the AUC calculated by models, which predicted the blood supply of vestibular schwannoma by K-Fold cross-validation method with a mean AUC = 0.88 and F1-score = 0.83. Radiomics machine-learning classifiers can accurately predict the blood supply of vestibular schwannoma by preoperative MRI data.

Effects of Preoperative Carbamazepine Treatment on Microvascular Decompression for Classical Trigeminal Neuralgia.

BACKGROUND: Carbamazepine (CBZ) is the first-line therapy for trigeminal neuralgia (TN), and microvascular decompression (MVD) is considered to be an effective surgical treatment for TN. However, the effect of preoperative CBZ treatment on MVD outcome is not clear. METHODS: From 2013 to 2019, 63 patients with classical TN underwent MVD at the First Affiliated Hospital of Zhengzhou University, China. Data were collected through telephone follow-up and electronic medical records in April 2020. Short-term surgical outcome and long-term follow-up data were estimated by univariate and multivariate analysis. RESULTS: Multivariate analysis indicated that preoperative CBZ treatment was not a significant predictor for short-term outcomes of MVD (P > 0.05). Multivariate analysis for the long-term outcome of MVD indicated that preoperative CBZ treatment could predict postoperative recurrence of TN (P < 0.05). CONCLUSIONS: For patients with classical TN, a longer preoperative medication history of CBZ treatment had no significant effect on short-term outcome of MVD, but CBZ treatment was associated with a poor long-term outcome following MVD.

Preoperative Prediction of Meningioma Consistency via Machine Learning-Based Radiomics.

OBJECTIVES: The aim of this study was to establish and validate a radiomics nomogram for predicting meningiomas consistency, which could facilitate individualized operation schemes-making. METHODS: A total of 172 patients was enrolled in the study (train cohort: 120 cases, test cohort: 52 cases). Tumor consistency was classified as soft or firm according to Zada's consistency grading system. Radiomics features were extracted from multiparametric MRI. Variance selection and LASSO regression were used for feature selection. Then, radiomics models were constructed by five classifiers, and the area under curve (AUC) was used to evaluate the performance of each classifiers. A radiomics nomogram was developed using the best classifier. The performance of this nomogram was assessed by AUC, calibration and discrimination. RESULTS: A total of 3840 radiomics features were extracted from each patient, of which 3719 radiomics features were stable features. 28 features were selected to construct the radiomics nomogram. Logistic regression classifier had the highest prediction efficacy. Radiomics nomogram was constructed using logistic regression in the train cohort. The nomogram showed a good sensitivity and specificity with AUCs of 0.861 and 0.960 in train and test cohorts, respectively. Moreover, the calibration graph of the nomogram showed a favorable calibration in both train and test cohorts. CONCLUSIONS: The presented radiomics nomogram, as a non-invasive prediction tool, could predict meningiomas consistency preoperatively with favorable accuracy, and facilitated the determination of individualized operation schemes.

Clinical Implication of Systemic Immune-Inflammation Index and Prognostic Nutritional Index in Skull Base Chordoma Patients.

Inflammation associated markers and nutritional indexes are associated with survival, and act as novel prognostic grading systems in patients with cancer, though the role of these markers in chordoma remains unclear. The current study aimed to characterize systemic immune-inflammation index (SII) and prognostic nutritional index (PNI), and their relationship with clinicopathological data and survival in skull base chordoma. Our retrospective study enrolled 183 patients with primary skull base chordoma who received surgical treatment. Clinicopathological data and preoperative blood tests including neutrophil, lymphocyte, platelet counts and albumin level were collected from medical records. Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), SII, PNI were calculated and the optimal cut-off values of these markers were used for further survival analysis via Kaplan-Meier survival analysis and Cox proportional hazards regression analysis. The value of NLR, PLR, SII, and PNI in skull base chordoma ranged from 0.44-6.48, 45.36-273.94, 113.37-1761.45, and 43.40-70.65, respectively. PNI was significantly correlated with patients' sex (p = 0.005) and age (p = 0.037). SII was positively correlated with NLR and PLR, but negatively correlated with PNI. The median overall survival (OS) time was 74.0 months and Kaplan-Meier survival analysis indicated that all four indexes were associated with OS. Multivariable Cox proportional hazards regression analysis identified that high SII was an independent prognostic factor for poor OS. More importantly, patients with high SII and PNI had the worst outcomes and combined use of SII and PNI increased the predictive ability for patients' survival in skull base chordoma. Our results suggest SII and PNI may be effective prognostic indicators of OS for patients with primary skull base chordoma after surgical resection.

Preoperative Predictors of Early Mortality Risk in Isocitrate Dehydrogenase-Wild-Type Glioblastoma Patients Treated with Standard Therapy.

PURPOSE: Early identification of early mortality for glioblastoma (GBM) patients based on laboratory findings at the time of diagnosis could improve the overall survival. The study aimed to explore preoperative factors associated with higher risk of early death (within 1 year after surgery) for isocitrate dehydrogenase (IDH) -wild-type (wt) GBM patients. PATIENTS AND METHODS: We conducted a retrospective analysis of 194 IDH-wt GBM patients who underwent standard treatment. The probability of dying within 1 year after gross total resection (GTR) was defined as the end point "early mortality". Retrospective collection of predictive factors including clinical characteristics and laboratory data at diagnosis. RESULTS: Median follow-up time after GTR was 16 months (3-41 months). Forty-two patients died within 1 year after surgery (1-year mortality rate: 21.6%). All potential predictive factors were assessed on univariate analyses, which revealed the following factors as associated with higher risk of early death: older age (P = 0.013), occurrence of non-seizures symptoms (P = 0.042), special tumor positions (P = 0.046), higher neutrophil-to-lymphocyte ratio (NLR) (P = 0.015), higher red blood cell distribution width (RDW) (P = 0.019), higher lactate dehydrogenase (LDH) (P = 0.005), and higher fibrinogen (FIB) (P = 0.044). In a multivariate analysis, tumor location (P = 0.012), NLR (P = 0.032) and LDH (P = 0.002) were independent predictors of early mortality. The C-index of the nomogram was 0.795. The calibration curve showed good agreement between prediction by nomogram and actual observation. CONCLUSION: Tumor location, preoperative elevated NLR and serum LDH level were independent predictors for 1-year mortality after GTR. We indicate that increased preoperative NLR or LDH may guide patients to review head magnetic resonance imaging (MRI) more frequently and regularly to monitor tumor progression.

Whole genome sequencing of skull-base chordoma reveals genomic alterations associated with recurrence and chordoma-specific survival.

Chordoma is a rare bone tumor with an unknown etiology and high recurrence rate. Here we conduct whole genome sequencing of 80 skull-base chordomas and identify PBRM1, a SWI/SNF (SWItch/Sucrose Non-Fermentable) complex subunit gene, as a significantly mutated driver gene. Genomic alterations in PBRM1 (12.5%) and homozygous deletions of the CDKN2A/2B locus are the most prevalent events. The combination of PBRM1 alterations and the chromosome 22q deletion, which involves another SWI/SNF gene (SMARCB1), shows strong associations with poor chordoma-specific survival (Hazard ratio [HR] = 10.55, 95% confidence interval [CI] = 2.81-39.64, p = 0.001) and recurrence-free survival (HR = 4.30, 95% CI = 2.34-7.91, p = 2.77 × 10-6). Despite the low mutation rate, extensive somatic copy number alterations frequently occur, most of which are clonal and showed highly concordant profiles between paired primary and recurrence/metastasis samples, indicating their importance in chordoma initiation. In this work, our findings provide important biological and clinical insights into skull-base chordoma.

A Series of 62 Skull Base Chordomas in Pediatric and Adolescent Patients: Clinical Characteristics, Treatments, and Outcomes.

BACKGROUND: Skull base chordomas in pediatric and adolescent patients are rare and challenging for surgeons. OBJECTIVE: Well-specified diagnosis and treatment are of great value for the long-term control of chordoma. This study summarizes well-followed pediatric and adolescent chordoma (PAC) patients treated in a single Asian center. METHODS: PAC patients were enrolled. Data collected included clinical presentation, tumor volume, texture, surgical approach, pathology, complications, adjuvant radiotherapy (RT), and long-term outcomes. RESULTS: Sixty-two patients were identified from a total of 516 skull base chordoma patients (12%). Diplopia was the most prominent complaint (30%). The craniocervical junction area was the most common location (41.8%) and had the highest proportion of large tumors. The gross total resection (GTR) rate was 20.3%. The GTR rate was lowest for tumors located in the craniocervical junction area. Thirty-eight cases experienced surgical complications. Of note, there was a significant difference in the complication rate between endoscopic approaches (22.7%) and open approaches (57.9%) (P = 0.005). The mean follow-up was 66.5 months. The GTR group showed better survival compared with the non-GTR group (P = 0.043). Metastases were found in two cases. No significant difference in the overall survival (OS) time was found between the group with RT and the group without RT (P = 0.559). CONCLUSIONS: A higher proportion of PAC patients than previously reported exist in the population in Asia, and the metastatic rate is lower. GTR predicts excellent long-term control of the disease. RT should be considered on an individual basis.

Prognostic Value of Cumulative Score Based on Preoperative Fibrinogen and Albumin Level in Skull Base Chordoma.

OBJECTIVE: Inflammation and malnutrition have been shown to be correlated with tumor progression and a poor prognosis in various cancers. However, the clinical implications of biomarkers of inflammation and malnutrition in chordoma have not been elucidated. We attempted to characterize the fibrinogen and albumin levels in skull base chordoma and investigate their correlations with clinicopathological data and survival. METHODS: The preoperative levels of fibrinogen and albumin were assessed in 183 primary skull base chordoma patients. The cutoff values were determined by X-tile software, and their correlations with patient prognosis were further explored using the Kaplan-Meier curve and Cox proportional hazards regression analysis. In addition, the predictive performances of these markers in survival were evaluated by receiver operating characteristic curves. RESULTS: The values of fibrinogen and albumin in skull base chordoma patients ranged from 1.73 to 7.40 and 37.6 to 53.0 g/L, respectively. The optimal cutoff values for fibrinogen and albumin were 3.29 and 44.60 g/L, respectively. Fibrinogen and albumin were correlated with the patient age and tumor pathology types. Albumin, but not fibrinogen, was associated with the patients' progression-free survival and overall survival. Importantly, the FA score, which combines fibrinogen and albumin, could independently predict both progression-free survival and overall survival, and enhanced the performance of fibrinogen or albumin in survival prediction in skull base chordoma. CONCLUSION: Our data reveal the clinical prognostic role of albumin and suggest that the FA score may be a valuable prognostic grading system in skull base chordoma.

Porous Functionalized Covalent-Triazine Frameworks for Enhanced Adsorption Toward Polysulfides in Li-S Batteries and Organic Dyes.

The incorporation of functional building blocks to construct functionalized and highly porous covalent triazine frameworks (CTFs) is essential to the emerging adsorptive-involved field. Herein, a series of amide functionalized CTFs (CTF-PO71) have been synthesized using a bottom-up strategy in which pigment PO71 with an amide group is employed as a monomer under ionothermal conditions with ZnCl2 as the solvent and catalyst. The pore structure can be controlled by the amount of ZnCl2 to monomer ratio. Benefitting from the highly porous structure and amide functionalities, CTF-PO71, as a sulfur cathode host, simultaneously demonstrates physical confinement and chemical anchoring of sulfur species, thus leading to superior capacity, cycling stability, and rate capability in comparison to unfunctionalized CTF. Meanwhile, as an adsorbent of organic dye molecules, CTF-PO71 was demonstrated to exhibit strong chemical interactions with dye molecules, facilitating adsorption kinetics and thereby promoting the adsorption rate and capacity. Furthermore, the dynamic adsorption experiments of organic dyes from solutions showed selectivity/priority of CTF-PO71s for specific dye molecules.

LncRNA and mRNA expression profiles reveal the potential roles of lncRNA contributing to regulating dural penetration in clival chordoma.

Chordoma is a rare bone cancer originating from embryologic notochordal remnants. Clival chordomas show different dural penetration ability, with serious dural penetration exhibiting poorer prognosis. The molecular mechanism of dural penetration is not clear. We analyzed lncRNA and mRNA profiles in 12 chordoma patients with different degrees of dural penetration using expression microarrays. The differentially expressed lncRNAs and mRNAs were used to construct a lncRNA-mRNA co-expression network. LncRNAs were classified into lincRNA, enhancer-like lncRNA, or antisense lncRNA. Biological functions for lncRNAs were predicted according to the lncRNA-mRNA network and adjacent coding genes by pathway analysis. The 2760 lncRNAs and 3988 mRNAs were differentially expressed in chordomas between two groups of patients with and without dural penetration. Possible pathway involvement of the significance among the 55 lncRNAs located in the lncRNA-mRNA network, 24 lincRNAs, 7 enhancer-like lncRNAs, and 14 antisense lncRNAs include cell adhesion, metastasis, invasion, proliferation, and apoptosis. Expression of 10 lncRNAs and mRNAs, and epidermal growth factor mRNA with two identified lncRNAs were subsequently verified by qRT-PCR in chordoma tissues. Our report predicts the biological functions of many lncRNAs which may be used as diagnostic and prognostic biomarkers as well as therapeutic targets during the process of dural penetration in chordoma.

A nomogram to predict the progression-free survival of clival chordoma.

OBJECTIVE: Chordoma shows poor patient prognosis because of its high recurrence rate. Even though many clinical factors and biomarkers are reported to be associated with prognosis, no prediction model has been applied clinically. Thus, the authors aim to derive and validate a prognostic nomogram to predict progression-free survival (PFS) of chordoma. METHODS: A total of 201 patients were randomly divided into a derivation group (151 cases) and a validation group (50 cases). The expression levels of biomarkers were quantified using tissue microarray analysis. A nomogram was established via univariate and multivariate Cox regression analysis in the derivation group. The predictive performance of the nomogram was then tested in the validation group. RESULTS: The mean follow-up interval was 57 months (range 26-107 months). One clinical factor and 3 biomarkers were confirmed to be associated with PFS, including degree of resection, E-cadherin, Ki-67, and VEGFA. The nomogram with these prognostic factors had areas under the receiver operating characteristic curve of 0.87 and 0.95 in the derivation group at 3 years and 5 years, respectively, compared with 0.87 and 0.84 in the validation group. Calibration and score-stratified survival curve were good in the derivation group and validation group, respectively. CONCLUSIONS: The established nomogram performs well for predicting the PFS of chordoma and for risk stratification, which could facilitate prognostic evaluation and follow-up.

Predictive Value of Transforming Growth Factor-α and Ki-67 for the Prognosis of Skull Base Chordoma.

OBJECTIVE: We aimed to characterize the expression of transforming growth factor-α (TGF-α) and Ki-67 and to assess the relationship between TGF-α and Ki-67 expression and prognostic factors in skull base chordoma. METHODS: We retrospectively analyzed the data from 46 patients with skull base chordoma. The follow-up duration ranged from 1 to 168 months (mean, 74.1). The survival data were statistically analyzed using the Kaplan-Meier method and multivariate Cox regression analysis. The expression of TGF-α and Ki-67 were detected by immunohistochemical staining of paraffin-embedded patient tissue specimens. RESULTS: The total resection (TR) group had longer overall survival compared with the non-TR group (P = 0.042). The TR group also had longer progression-free survival (PFS) than did the non-TR group (P = 0.046). The group with a high Ki-67 labeling index (Ki-67LI) had shorter overall survival than did the group with a low Ki-67LI (P = 0.039). Also, the group with a high Ki-67LI had significantly shorter PFS than did the group with a low Ki-67LI (P = 0.016). Moreover, the group with high TGF-α expression had significantly shorter PFS compared with the group with low TGF-α expression (P = 0.005). CONCLUSIONS: Our results have shown that high levels of TGF-α and Ki-67 are associated with shorter PFS in patients with chordoma. We have confirmed the role of Ki-67 as a functional molecular marker of poor prognosis. We also identified TGF-α as a potential novel biomarker for predicting prognosis for patients with skull base chordoma.

Analysis of clinical factors and PDGFR-ß in predicting prognosis of patients with clival chordoma.

OBJECTIVEIn this study, the authors' aim was to research clinical features and prognostic factors in patients harboring clival chordomas and explore the relationship between platelet-derived growth factor receptor-ß (PDGFR-ß) expression and tumor invasion and prognosis of clival chordoma.METHODSA total of 242 patients were retrospectively analyzed. Clinical information, including extent of resection, Al-Mefty classification, postoperative complications, and postoperative radiotherapy, was reviewed. Kaplan-Meier analysis was used to estimate survival time. Immunohistochemical analysis, quantitative reverse transcription polymerase chain reaction, and Western blotting were used to measure the expression level of proteins or mRNA. Transwell assaying was performed to measure the invasive ability of the tumor cells.RESULTSAccording to the Al-Mefty classification, there were 37, 112, and 93 type I, II, and III tumors, respectively. Gross-total resection (GTR) was achieved in 86 cases (35.5%), subtotal resection (STR) in 63 cases (26.0%), and partial resection (PR) in 93 cases (38.4%). The 5-year progression-free survival (PFS) and overall survival (OS) rates in the GTR group were significantly higher than those in the non-total resection (NTR; i.e., STR and PR) group (p < 0.001). The 5-year PFS and OS rates for patients with type I tumors were significantly higher than those for patients harboring types II and III tumors (p < 0.001). In the NTR group, the median PFS and OS of patients with lower PDGFR-ß expression were significantly longer than those of patients with higher PDGFR-ß expression. Reduction of PDGFR-ß suppressed the invasion ability of cells in vitro. In addition, reduction of PDGFR-ß can obviously downregulate the expression levels of mammalian target of rapamycin (mTOR) or phospho-mTOR.CONCLUSIONSExtent of resection, Al-Mefty classification, primary tumor, postoperative radiotherapy, and PDGFR-ß expression level are valuable prognostic factors in patients with clival chordomas. PDGFR-ß could regulate invasion through the mTOR pathway in clival chordoma cells.