Integrated Molecular and Histological Insights for Targeted Therapies in Mesenchymal Sinonasal Tract Tumors.

PURPOSE OF REVIEW: This review aims to provide a comprehensive overview of mesenchymal sinonasal tract tumors (STTs), a distinct subset of STTs. Despite their rarity, mesenchymal STTs represent a unique clinical challenge, characterized by their rarity, often slow progression, and frequently subtle or overlooked symptoms. The complex anatomy of the sinonasal area, which includes critical structures such as the orbit, brain, and cranial nerves, further complicates surgical treatment options. This underscores an urgent need for more advanced and specialized therapeutic approaches. RECENT FINDINGS: Advancements in molecular diagnostics, particularly in next-generation sequencing, have significantly enhanced our understanding of STTs. Consequently, the World Health Organization has updated its tumor classification to better reflect the distinct histological and molecular profiles of these tumors, as well as to categorize mesenchymal STTs with greater accuracy. The growing understanding of the molecular characteristics of mesenchymal STTs opens new possibilities for targeted therapeutic interventions, marking a significant shift in treatment paradigms. This review article concentrates on mesenchymal STTs, specifically addressing sinonasal tract angiofibroma, sinonasal glomangiopericytoma, biphenotypic sinonasal sarcoma, and skull base chordoma. These entities are marked by unique histopathological and molecular features, which challenge conventional treatment approaches and simultaneously open avenues for novel targeted therapies. Our discussion is geared towards delineating the molecular underpinnings of mesenchymal STTs, with the objective of enhancing therapeutic strategies and addressing the existing shortcomings in the management of these intricate tumors.

Optimizing radiotherapy strategies for skull base chordoma: a comprehensive meta-analysis and systematic review of treatment modalities and outcomes.

OBJECTIVE: In the treatment of skull base chordoma (SBC) surgery is considered the mainstay approach, and gross-total resection has an established relationship with progression-free survival (PFS) and overall survival (OS). However, the tumor's location often interferes with attempts at complete resection. In this case, surgery for maximal resection followed by high-dose radiotherapy has been demonstrated to be the standard treatment. In this context, various modalities are available, yet no consensus exists on the most effective. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of different radiotherapy modalities for SBC. METHODS: Following PRISMA guidelines, the authors systematically searched for the treatment of SBC with radiation modalities in the PubMed, Cochrane, Web of Science, and EMBASE databases. Outcomes assessed for each modality were as follows: OS, PFS, local control (LC), and complications. The random-effects model was adopted. A single-proportion analysis with 95% CI was used to measure the effects in single-arm analysis. For the comparative analysis, the OR with 95% CI was used to compare outcome treatment effects. Heterogeneity was assessed using I2 statistics, and statistical significance was defined as p < 0.05. RESULTS: A total of 32 studies comprising 3663 patients, with 2322 patients who were treated with radiotherapeutic modalities, were included. Regarding 5-year OS findings in each modality study, the findings were as follows: in photon fractionated radiotherapy, an estimated rate of 77% (69%-84%, 568 patients); in conventional fractionated radiotherapy, 76% (65%-87%, 517 cases); in proton-based + carbon ion-based radiotherapy, 85% (82%-88%, 622 cases); and in a comparative analysis of proton-based and carbon ion-based therapy, there was an OR of 1.2 (95% CI 0.59-2.43, 306 cases). Regarding the 5-year PFS estimate, the rates were as follows: 35% (26%-45%, 95 cases) for photon fractionated therapy; 35% (25%-45%, 85 cases) for stereotactic radiotherapy; 77% (50%-100%, 180 cases) for proton-based and carbon ion-based radiotherapy; and 74% (45%-100%, 102 cases) for proton-based radiotherapy. Regarding LC in periods of 3 and 5 years after proton- and carbon ion-based therapy, the overall estimated rates were 84% (78%-90%, 326 cases) and 75% (65%-85%, 448 cases), respectively. For proton-based radiotherapy and carbon ion-based therapy, the 5-year LC rates were 76% (67%-86%, 259 cases) and 75% (59%-91%, 189 cases), respectively. CONCLUSIONS: The analysis highlights the finding that particle-based modalities like proton beam radiotherapy and carbon ion radiotherapy are the most effective radiation therapies available for the treatment of SBC. Furthermore, it reinforces the idea that surgery followed by radiotherapy constitutes the standard treatment.

Chordoma: Genetics and Contemporary Management.

Chordomas, arising from notochord remnants, are rare neoplasms with aggressive growth patterns despite their histologically low-grade nature. This review explores their embryological origins, molecular markers like brachyury, and genetic alterations driving pathogenesis. Diagnosis relies on advanced imaging and biopsy confirmation due to overlapping features with chondrosarcoma. The WHO classification distinguishes conventional, dedifferentiated, and poorly differentiated chordomas, each with distinct prognostic implications. Recent genomic analyses uncovered recurrent mutations in PI3K signaling pathways and chromatin remodeling genes, informing prognostic models. Surgery remains the cornerstone of treatment, though adjuvant radiation complements surgical resection. Although chordomas are generally considered refractory to medical therapy, emerging targeted molecular strategies show potential promise in ongoing trials. This review aims to provide a concise yet comprehensive overview of chordomas, guiding clinicians in diagnosis, treatment, and prognostication for improved patient outcomes.

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.

Clinicopathological implications of TIM3+ tumor-infiltrating lymphocytes and the miR-455-5p/Galectin-9 axis in skull base chordoma patients.

Chordoma is difficult to eradicate due to high local recurrence rates. The immune microenvironment is closely associated with tumor prognosis; however, its role in skull base chordoma is unknown. The expression of Galectin-9 (Gal9) and tumor-infiltrating lymphocyte (TIL) markers was assessed by immunohistochemistry. Kaplan-Meier and multivariate Cox analyses were used to assessing local recurrence-free survival (LRFS) and overall survival (OS) of patients. MiR-455-5p was identified as a regulator of Gal9 expression. Immunopositivity for Gal9 was associated with tumor invasion (p = 0.019), Karnofsky performance status (KPS) score (p = 0.017), and total TIL count (p < 0.001); downregulation of miR-455-5p was correlated with tumor invasion (p = 0.017) and poor prognosis; and the T-cell immunoglobulin and mucin-domain 3 (TIM3)+ TIL count was associated with chordoma invasion (p = 0.010) and KPS score (p = 0.037). Furthermore, multivariate analysis indicated that only TIM3+ TIL density was an independent prognostic factor for LRFS (p = 0.010) and OS (p = 0.016). These results can be used to predict clinical outcome and provide a basis for immune therapy in skull base chordoma patients.

Differentiating skull base chordomas and invasive pituitary adenomas with conventional MRI.

Background It is difficult to distinguish between invasive pituitary adenomas (IPAs) and skull base chordomas based on tumor location and clinical manifestations. Purpose To investigate the value of the apparent diffusion coefficient (ADC), T2-weighted (T2W) imaging, and dynamic contrast enhancement (DCE) in differentiating skull base chordomas and IPAs. Material and Methods Data for 21 patients with skull base chordomas and 27 patients with IPAs involving the paranasal sinus were retrospectively reviewed, and all diagnoses were pathologically confirmed. Each patient underwent conventional 3.0 T magnetic resonance imaging (MRI), including, ADC, T2W imaging, and DCE sequences. Regions of interest were drawn in the mass and in normal white matter on ADC maps and T2W imaging. The mean ADC, normal ADC, T2W imaging signal intensity (SI), and relative T2-weighted (rT2W) imaging values were measured. DCE parameters, including types of time signal-intensity curves (TIC), enhancement peak (EP), and maximum contrast enhancement ratio (MCER), were calculated. Differences between skull base chordomas and IPAs were evaluated using the independent samples t-test. Receiver operating characteristic (ROC) curve analyses were also performed. Results When comparing IPAs and chordomas, there were significant differences in mean ADC, normal ADC, rT2W imaging values, TIC, EP, and MCER ( P < 0.01). The areas under curves in the ROC analyses for normal ADC, mean ADC, T2W imaging, rT2W imaging, TIC, EP, and MCER were 1.0, 0.996, 1.0, 0.81, 0.987, and 0.987, respectively. Conclusion ADC, T2W imaging SI, and DCE-related parameters can contribute to the differential diagnosis of skull base chordomas and IPAs.

Tumour seeding in the surgical pathway after resection of skull base chordoma.

AIM: The aim of this study is to review the clinical series in which tumour seeding was reported after skull base surgery for chordomas. BACKGROUND: The occurrence of implantation of cancer cells during surgical procedures for the removal of chordoma is a rare event described by a number of authors in a few patient series and case reports. MATERIALS AND METHODS: Literature search was performed by PubMed and Scopus by using the words "surgical tumour seeding, tumour implantation, surgical pathway recurrence, skull base chordoma, and clivus chordoma". RESULTS: Six retrospective series and 7 case reports were included in the analysis. In total, 34 patients are described with pathway recurrence, 30 at a single site and 4 at multiple sites. In the 5 largest chordoma series, the rate of occurrence of surgical seeding ranged from 1.3% to 7.3% (3.9%). In the 34 patients diagnosed with tumour seeding, the most frequent surgical approach was trans-nasal/trans-sphenoidal, that was used in 12 cases. The median time from primary treatment to surgical pathway tumour seeding ranged from 7 to 78 months. Data of the treatment of seeding are available in 26/34 patients. All of them underwent a new surgery, 6 received additional external beam radiotherapy, and 2 intraoperative radiotherapy. CONCLUSIONS: The risk of surgical seeding should be taken into consideration when deciding on the surgical approach and the planning treatment volume for postoperative radiation therapy. The surgical pathway should be included in follow-up studies to diagnose this peculiar type of treatment failure possibly at an early phase.

Skull Base Chordoma in a Young Lady - A Tale of Mismanagement and Redemption: A Case Report and Review of Literature.

Skull base chordomas are a rare entity that requires multidisciplinary decision-making for management. We report a case wherein the patient was initially mismanaged at a peripheral centre, and was then redeemed by a multidisciplinary tumor board decision-making and specialized surgical procedures. We also present a brief review of the therapeutic options.

Intrasellar chordoma masquerading as a pituitary neuroendocrine tumor: Illustrative case.

Background: Chordomas are rare, locally aggressive neoplasms recognized as derivatives of the notochord vestiges. These tumors typically involve the midline axial skeleton, and intracranial chordomas exhibit proclivity for the spheno-occipital region. However, purely intrasellar occurrences are extremely rare. We report a case of intrasellar chordoma, which masqueraded as a pituitary neuroendocrine tumor. Case Description: An 87-year-old female presented with an acutely altered mental state after a few-week course of headaches and decreased left vision. Adrenal insufficiency was evident, and magnetic resonance imaging revealed an intrasellar lesion with heterogeneous contrast enhancement and marked T2 hyperintensity. Central adrenal insufficiency due to an intrasellar lesion was suspected. Cortisol replacement was initiated, and transsphenoidal surgery was performed. Anterosuperior displacement of the normal pituitary gland and the absence of the bony dorsum sellae were notable during the procedure. Histological examination led to a diagnosis of conventional chordoma, and upfront adjuvant stereotactic radiosurgery was executed. She has been free from tumor progression for 12 months. Conclusion: This case and literature review suggested that the pathognomonic features of intrasellar chordoma were heterogeneous contrast enhancement, marked T2 hyperintensity, osteolytic destruction of the dorsum sellae, and anterosuperior displacement of the pituitary gland. Clinical outcomes seemed slightly worse than those of all skull base chordomas, which were the rationale for upfront radiosurgery in our case. Neurosurgeons should include intrasellar chordomas in the differential diagnosis of intrasellar lesions, carefully dissect them from the adjacent critical anatomical structures, and consider upfront radiosurgery to achieve optimal patient outcomes.

DNA methylation, combined with RNA sequencing, provide novel insight into molecular classification of chordomas and their microenvironment.

Chordomas are rare tumors of notochord remnants, occurring mainly in the sacrum and skull base. Despite of their unusually slow growth, chordomas are highly invasive and the involvement of adjacent critical structures causes treatment challenges. Due to the low incidence, the molecular pathogenesis of this entity remains largely unknown. This study aimed to investigate DNA methylation abnormalities and their impact on gene expression profiles in skull base chordomas. 32 tumor and 4 normal nucleus pulposus samples were subjected to DNA methylation and gene expression profiling with methylation microarrays and RNA sequencing. Genome-wide DNA methylation analysis revealed two distinct clusters for chordoma (termed subtypes C and I) with different patterns of aberrant DNA methylation. C Chordomas were characterized by general hypomethylation with hypermethylation of CpG islands, while I chordomas were generally hypermethylated. These differences were reflected by distinct distribution of differentially methylated probes (DMPs). Differentially methylated regions (DMRs) were identified, indicating aberrant methylation in known tumor-related genes in booth chordoma subtypes and regions encoding small RNAs in subtype C chordomas. Correlation between methylation and expression was observed in a minority of genes. Upregulation of TBXT in chordomas appeared to be related to lower methylation of tumor-specific DMR in gene promoter. Gene expression-based clusters of tumor samples did not overlap with DNA methylation-based subtypes. Nevertheless, they differ in transcriptomic profile that shows immune infiltration in I chordomas and up-regulation of cell cycle in C chordomas. Immune enrichment in chordomas I was confirmed with 3 independent deconvolution methods and immunohistochemistry. Copy number analysis showed higher chromosomal instability in C chordomas. Nine out of eight had deletion of CDKN2A/B loci and downregulation of genes encoded in related chromosomal band. No significant difference in patients' survival was observed between tumor subtypes, however, shorter survival was observed in patients with higher number of copy number alterations.

Radiotherapy After Gross Total Resection of Skull Base Chordoma: A Surveillance, Epidemiology, and End Results Database Analysis of Survival Outcomes.

OBJECTIVE: Skull base chordoma is a rare and locally destructive malignancy which presents unique therapeutic challenges. While achieving gross total resection (GTR) confers the greatest survival advantage, the role of adjuvant radiotherapy (RT) for patients who receive GTR remains unclear in the absence of prospective trials. Here, we aim to assess the effect of RT on survival outcomes in skull base chordoma patients who receive GTR by utilizing the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Patients with diagnostic, primary site, and resection codes specific for chordoma, skull base, and GTR, respectively, were queried in the SEER database (2000-2018). Kaplan-Meier curves (log-rank test) were constructed and Cox proportional hazards models were used to assess survival outcomes. RESULTS: A total of 115 skull base chordomas undergoing GTR were identified, of which 37 (32%) received no RT and 78 (68%) received RT. Median follow-up was 55.00 months (range: 0.00-227.00). Overall survival (OS) of patients with GTR was 85% and 70% at 5 and 10 years, respectively. Multivariate Cox proportional hazard analysis among chordoma patients undergoing GTR found age ≥65 (P < 0.01) was associated with poorer OS outcomes. RT appeared to trend toward offering benefit in terms of OS in patients after GTR, however this did not achieve statistical significance in the adjusted model (HR = 0.51, CI = 0.23-1.16, P = 0.09). When comparing, disease-specific survival was also not improved in patients undergoing RT (HR = 0.58, CI = 0.23-1.46, P = 0.25). CONCLUSIONS: It remains unclear whether RT after GTR of chordoma improved survival outcomes among SEER database patients.

Microstructural parameters from DW-MRI for tumour characterization and local recurrence prediction in particle therapy of skull-base chordoma.

BACKGROUND: Quantitative imaging such as Diffusion-Weighted MRI (DW-MRI) can be exploited to non-invasively derive patient-specific tumor microstructure information for tumor characterization and local recurrence risk prediction in radiotherapy. PURPOSE: To characterize tumor microstructure according to proliferative capacity and predict local recurrence through microstructural markers derived from pre-treatment conventional DW-MRI, in skull-base chordoma (SBC) patients treated with proton (PT) and carbon ion (CIRT) radiotherapy. METHODS: Forty-eight patients affected by SBC, who underwent conventional DW-MRI before treatment and were enrolled for CIRT (n = 25) or PT (n = 23), were retrospectively selected. Clinically verified local recurrence information (LR) and histological information (Ki-67, proliferation index) were collected. Apparent diffusion coefficient (ADC) maps were calculated from pre-treatment DW-MRI and, from these, a set of microstructural parameters (cellular radius R, volume fraction vf, diffusion D) were derived by applying a fine-tuning procedure to a framework employing Monte Carlo simulations on synthetic cell substrates. In addition, apparent cellularity (ρapp ) was estimated from vf and R for an easier clinical interpretation. Histogram-based metrics (mean, median, variance, entropy) from estimated parameters were considered to investigate differences (Mann-Whitney U-test, α = 0.05) in estimated tumor microstructure in SBCs characterized by low or high cell proliferation (Ki-67). Recurrence-free survival analyses were also performed to assess the ability of the microstructural parameters to stratify patients according to the risk of local recurrence (Kaplan-Meier curves, log-rank test α = 0.05). RESULTS: Refined microstructural markers revealed optimal capabilities in discriminating patients according to cell proliferation, achieving best results with mean values (p-values were 0.0383, 0.0284, 0.0284, 0.0468, and 0.0088 for ADC, R, vf, D, and ρapp, respectively). Recurrence-free survival analyses showed significant differences between populations at high and low risk of local recurrence as stratified by entropy values of estimated microstructural parameters (p = 0.0110). CONCLUSION: Patient-specific microstructural information was non-invasively derived providing potentially useful tools for SBC treatment personalization and optimization in particle therapy.

Comparative analysis of histopathological parameters, genome-wide copy number alterations, and variants in genes involved in cell cycle regulation in chordomas of the skull base and sacrum.

Chordomas are rare tumors of the axial skeleton that are refractory to conventional therapy. Few studies have compared the morphological and molecular characteristics of chordomas according to the skull base and sacral locations. Histopathological data and changes revealed by array comparative genomic hybridization (CGH) and next-generation sequencing (NGS) of cell cycle regulation genes were analyzed for 28 skull base (SBCs) and 15 sacral (SC) chordomas. All cases were conventional chordomas. SBCs were significantly more frequent in patients aged <40 years and SCs predominated in patients aged >60 years. Mitotic indices ≥2 mitoses/10 high-power fields were correlated with high degrees of nuclear atypia and Ki67 labeling indices ≥6%. We identified 321 genomic positions, and copy number variation losses were more frequent than gain. Moreover, we report a panel of 85 genetic variants of cell cycle genes and the presence of molecular clusters for chordoma as well in CGH as in NGS. These new data strengthen the view that the chordoma should not be considered as a single molecular entity.

Primary Skull Base Chordomas: A Clinicopathological Analysis of 94 Patients.

OBJECTIVE: To investigate prognostic factors in patients with primary skull base chordoma (PSBC) to guide future therapeutic advances. METHODS: This retrospective cohort study of 94 PSBC patients was conducted in 2 institutions from January 2006 to December 2013. Independent predictors for progression-free survival (PFS) and overall survival were established with multivariate Cox regression analysis. RESULTS: Age (P = 0.006), extent of resection (P = 0.037), and radiotherapy (RT) (P = 0.027) were established as independent predictors for PFS in PSBC patients. Similarly, age (P = 0.002), extent of resection (P = 0.048), and RT (P = 0.015) were established as independent predictors for overall survival. Meta-analysis manifested that lower MIB-1 correlated with longer PFS in skull base chordoma patients (P < 0.001). RT doubled the 5-year PFS rate from 28.6 ± 12.1% to 61.6 ± 10.7% (P = 0.031) and increased the 5-year overall survival rate from 54.5 ± 13.8% to 84.2 ± 8.4% (P = 0.020) in the subtotal resection/partial resection and MIB-1 labeling index (STR/PR+MIB-1 LI) <2% subgroup. In contrast, in the STR/PR+MIB-1 LI ≥2% subgroup, the survival benefit of RT remained uncertain. Further analysis revealed no survival difference between different RT modalities in STR/PR PSBC patients. CONCLUSIONS: In PSBC patients, age, extent of resection, and adjuvant RT all are independent predictors for PFS. Lower MIB-1 LI is associated with longer PFS in PSBC patients. Adjuvant RT is necessary for PSBC patients who undergo STR/PR with MIB-1 LI <2%. Patients who undergo GTR or STR/PR with MIB-1 LI ≥2% seem nonresponsive to RT.

Impact of Treatment Modalities upon Survival Outcomes in Skull Base and Clival Chordoma: An NCDB Analysis.

Objectives Skull base chordomas are locally aggressive malignant tumors derived from the notochord remnant. There are limited large-scale studies examining the role and extent of surgery and radiation therapy. Design Analysis of the National Cancer Database (NCDB) was performed to evaluate the survival outcomes of various treatments, and to assess for predictors of overall survival (OS). Participants This is a retrospective, population-based cohort study of patients diagnosed with a clival/skull base chordoma between 2004 and 2015 in the NCDB. Main Outcome Measures The primary outcome was overall survival (OS). Results In all, 468 cases were identified. Forty-nine percent of patients received surgery and 20.7% had positive margins. Mean age at diagnosis was 48.4 years in the surgical cohort, and 55% were males. Of the surgical cohort, 33.8% had negative margins, 20.7% had positive margins, and 45.5% had unknown margin status. Age ≥ 65 (hazard ratio [HR]: 3.07; 95% confidence interval [CI]: 1.63-5.76; p < 0.001), diagnosis between 2010 and 2015 (HR: 0.49; 95% CI: 0.26-0.90; p = 0.022), tumor size >5 cm (HR: 2.29; 95% CI: 1.26-4.15; p = 0.007), and government insurance (HR: 2.28; 95% CI: 1.24-4.2; p = 0.008) were independent predictors of OS. When comparing surgery with or without adjuvant radiation, no survival differences were found, regardless of margin status ( p = 0.66). Conclusion Surgery remains the mainstay of therapy. Advanced age (>65 years), large tumor size, and government insurance were predictors of worse OS. Whereas negative margins and the use of adjuvant radiation did not appear to impact OS, these may very well reduce local recurrences. A multidisciplinary approach is critical in achieving optimal outcomes in this challenging disease.

High systemic inflammation score is associated with adverse survival in skull base chordoma.

Background: The systemic inflammation score (SIS), based on preoperative lymphocyte to monocyte ratio (LMR) and albumin (ALB), was recently developed and is demonstrated to be a novel prognostic indicator in several cancers. However, data discussing the utility of SIS in chordoma are lacking. We aimed to investigate the distribution and the prognostic role of SIS in primary skull base chordoma patients undergoing surgery. Material and methods: Preoperative SIS was retrospectively collected from 183 skull base chordoma patients between 2008 and 2014 in a single center. Its associations with clinical features and overall survival (OS) were further analyzed. The SIS-based nomogram was developed and evaluated by the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: The numbers of patients in the SIS 2, 1, and 0 group were 29 (15.8%), 60 (32.8%), 94 (51.4%), respectively. High SIS was associated with older age (p = 0.008), brainstem involvement of tumors (p = 0.039), and adverse OS (p < 0.001). Importantly, multivariate Cox analysis showed that high SIS independently predicts adverse OS. Furthermore, the nomogram based on SIS and clinical variables showed eligible performance for OS prediction in both training and validation cohorts. Conclusions: The SIS is a promising, simple prognostic biomarker, and the SIS-based nomogram serves as a potential risk stratification tool for outcome in skull base chordoma patients.

The Influence of Facility Volume and Type on Skull Base Chordoma Treatment and Outcomes.

OBJECTIVE: To evaluate the influence of facility case volume and type on skull base chordoma treatment and overall survival (OS). METHODS: The 2004-2016 National Cancer Database was queried for skull base chordoma patients receiving definitive treatment. Facilities were categorized into 2 cohorts by calculating the mean number of patients treated per facility and using cutoff numbers that were 0.5 SD above and below the computed mean to separate the groups. As, by definition of the inclusion criteria, all included facilities treated at least 1 patient, low-volume facilities were defined as treating 1 patient, and high-volume facilities were defined as treating ≥7 patients; mid-volume facilities (facilities treating ≥2 but ≤6 patients) were excluded. Differences in treatment course, outcomes, and OS by facility type were assessed. RESULTS: The study included 658 patients (44.8% female, 79.5% White). The 187 unique facilities were categorized into 95 low-volume facilities (treating 1 patient during timeline) and 26 high-volume facilities (treating ≥7 patients during timeline). Kaplan-Meier log-rank analysis demonstrated a significant positive association between facility volume and OS (P < 0.001) and an improvement in OS in patients at academic facilities (P = 0.018). On Cox proportional hazards multivariate regression after adjusting for sex, age, Charlson-Deyo comorbidity index, and insurance type, high-volume facilities and academic facilities were associated with a lower mortality risk than low-volume facilities and nonacademic facilities (P < 0.001 and P = 0.03, respectively). CONCLUSIONS: Higher facility case volume and academic facility type appear to be associated with improved survival outcomes in treatment of skull base chordomas.

Proteomics Analysis Identified ASNS as a Novel Biomarker for Predicting Recurrence of Skull Base Chordoma.

BACKGROUND: The prognostic factors of skull base chordoma associated with outcomes of patients after surgery remain inadequately identified. This study was designed to identify a novel prognostic factor for patients with skull base chordoma. METHOD: Using a proteomic technique, the tumor biomarkers that were upregulated in the rapid-recurrence group of chordoma were screened and then narrowed down by bioinformatic analysis. Finally one potential biomarker was chosen for validation by immunohistochemistry using tissue microarray (TMA). A total of 187 patients included in TMA were randomly divided into two cohorts, the training cohort included 93 patients and the validation cohort included 94 patients. Kaplan-Meier survival analysis was used to assess the patients' survival. Univariable and multivariable Cox regression analysis were used to identify prognostic factors predicting recurrence-free survival (RFS). CCK-8 assay, clonal formation assay and transwell assay were used to test the effect of asparagine synthetase (ASNS) on the proliferation, migration and invasion in chordoma cell lines. RESULTS: Among 146 upregulated proteins, ASNS was chosen as a potential prognostic biomarker after bioinformatics analysis. The H-scores of ASNS ranged from 106.27 to 239.58 in TMA. High expression of ASNS was correlated with shorter RFS in both the training cohort (p = 0.0093) and validation cohort (p < 0.001). Knockdown of ASNS by small interfering RNA (siRNA) inhibited the growth, colony formation, migration and invasion of chordoma cells in vitro. CONCLUSION: This study indicates that high expression of ASNS is correlated with poor prognosis of patients with skull base chordoma. ASNS may be a useful prognostic factor for patients with skull base chordoma.

Skull Base Chordoma: Long-Term Observation and Evaluation of Prognostic Factors after Surgical Resection.

BACKGROUND: Skull base chordoma (SBC) is relatively rare and data on its clinical outcome after surgical resection and adjuvant radiotherapy are still limited. OBJECTIVE: Analyzing the clinical postoperative outcome of SBC patients and defining prognostic factors regarding current treatment modalities. METHODS AND MATERIAL: In this study, 41 SBC patients from 2001 to 2017 were retrospectively analyzed in this single-center study. RESULTS: The most common clinical symptoms were headache (63%) and problems concerning vision (54%) like diplopia. The follow-up controls took place from 1 to 192 months. The mean survival time for the patients was 123.37 months (95% CI 90.89-155.86). The 5- and 10-year survival rates were 73.3 and 49%, respectively. Regarding the Karnofsky-Performance Scale (KPS), Cox regression showed a significant relationship between the survival rates in the overall study population and pre-surgery KPS (P = 0.004). This was further supported with a positive significant correlation between the pre-surgery KPS and the KPS at the last follow-up (P = 0.039). CONCLUSION: Statistical analysis showed that repeat surgical resection and radiotherapy could be prognostic factors. Furthermore, we were able to show that mortality decreased by 4.5% with each 10 points increase of pre-surgery KPS. This could be a major prognostic factor when deciding treatment modalities. Nevertheless, further standardized clinical studies with a larger patient population should be carried out to extrapolate prognostic factors and improve treatment modalities.

Multivariate Analysis and Validation of the Prognostic Factors for Skull Base Chordoma.

Background: Skull base chordoma is a rare tumor with low-grade malignancy and a high recurrence rate, the factors affecting the prognosis of patients need to be further studied. For that, we investigated prognostic factors of skull base chordoma through the database of the Surveillance, Epidemiology, and End Results (SEER) program, and validated in an independent data set from the Xiangya Hospital. Methods: Six hundred and forty-three patients diagnosed with skull base chordoma were obtained from the SEER database (606 patients) and the Xiangya Hospital (37 patients). Categorical variables were selected by Chi-square test with a statistical difference. Survival curves were constructed by Kaplan-Meier analysis and compared by log-rank test. Univariate and multivariate Cox regression analyses were used to explore the prognostic factors. Propensity score matching (PSM) analysis was undertaken to reduce the substantial bias between gross total resection (GTR) and subtotal resection (STR) groups. Furthermore, clinical data of 37 patients from the Xiangya Hospital were used as validation cohorts to check the survival impacts of the extent of resection and adjuvant radiotherapy on prognosis. Results: We found that age at diagnosis, primary site, disease stage, surgical treatment, and tumor size was significantly associated with the prognosis of skull base chordoma. PSM analysis revealed that there was no significant difference in the OS between GTR and STR (p = 0.157). Independent data set from the Xiangya Hospital proved no statistical difference in OS between GTR and STR groups (p = 0.16), but the GTR group was superior to the STR group for progression-free survival (PFS) (p = 0.048). Postoperative radiotherapy does not improve OS (p = 0.28), but it can prolong PFS (p = 0.0037). Nomograms predicting 5- and 10-year OS and DSS were constructed based on statistically significant factors identified by multivariate Cox analysis. Age, primary site, tumor size, surgical treatment, and disease stage were included as prognostic predictors in the nomograms with good performance. Conclusions: We identified age, tumor size, surgery, primary site, and tumor stage as main factors affecting the prognosis of the skull base chordoma. Resection of the tumor as much as possible while ensuring safety, combined with postoperative radiotherapy may be the optimum treatment for skull base chordoma.