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Purpose: Chordomas are rare malignant tumors that occur primarily in the axial skeleton. We seek to analyze trends affecting five-year overall survival (5y OS) among patients with primary spinal chordomas (PSC) of the vertebrae and sacrum/pelvis., Methods: The Surveillance, Epidemiology, and End Results (SEER) Program was used to identify patients with PSC (ICD-O-3 histology codes 9370/3, 9371/3, and 9372/3) of the spine or sacrum/pelvis. Multivariate and univariate survival analyses were conducted to assess demographic, disease, or treatment characteristic trends., Results: Eight-hundred-ninety-six patients diagnosed with PSC were identified. Patients 0-54 years at diagnosis had improved 5y OS compared to those either 55-69 years (HR = 1.78; p = 0.046) or those between 70 and 85 + years (HR = 3.92; p < 0.001). Histology impacted 5y OS: Cox regression demonstrated variance among the three histologies assessed (p < 0.001), while univariate analysis demonstrated patients with dedifferentiated chordoma (1.0% of cohort; 33.3% [1.9,64.7]) and chondroid chordoma (2.0% of cohort; 52.5% [26.1,78.9]) had decreased 5y OS compared to those with general chordoma (72.2% [68.8,75.6]; p < 0.001). Nonmarried patients had decreased 5y OS on univariate analysis (65.2% [59.4,71.0] versus 76.2% [72.0,80.4]), with widowed patients being the primary driver of this on subanalysis. Treatment with gross total resection was associated with increased 5y OS (HR = 0.22, p < 0.001), as was treatment with radiotherapy (HR = 0.69, p = 0.030)., Conclusion: Patient age and marital status were significant demographic factors associated with changes in 5y OS among those with PSC. PSC histology is a potentially important prognostic factor in the management of disease., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Chordomas are rare malignant bone tumors arising in the axial skeleton, with an incidence of 0.3-0.88 per million inhabitants. We studied the annual incidence rate and centralization of treatment for chordoma in the Netherlands., Methods: We retrieved pathology excerpts from the PALGA nationwide Dutch Pathology Registry between 1991 and 2019 for patients with a chordoma to calculate incidence rates. From pathology reports we extracted patient age at diagnosis, sex, year of diagnosis, localization of primary tumor, histologic chordoma subtype (conventional including chondroid, poorly differentiated or dedifferentiated), center of diagnosis (bone tumor referral center (BTC) or other hospital), and partial identification of the BTCs., Results: A total of 420 individual chordoma patients were identified in the given time period. The incidence of chordoma increased from 0.593 per million inhabitants between 1991-1995 to 1.111 from 2015-2019 (P = 0.001). Median age at diagnosis was 63 years (range 1-95), 252 patients (60%) were male. The proportion of samples analyzed in a BTC either primarily or secondary, as a consultation, revision or referral, increased significantly from 29.3% to 84.4% (P < 0.001). Most primary and secondary samples were analyzed at the Leiden University Medical Center (LUMC, 54.4% and 57% respectively)., Conclusions: This study shows an increase in the standardized incidence of pathology proven chordoma in the Netherlands. We observed an increase in samples being analysed in the specialized BTCs as well, which is in line with current guidelines and will hopefully lead to more accurate diagnoses and optimal treatment plans for chordoma patients in specialized treatment centers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/aim: Sacral chordoma is a rare primary bone neoplasm associated with high morbidity. The aim of this study is to identify demographic and clinicopathological characteristics of this tumor and evaluate their impact on survival outcomes., Patients and Methods: The Surveillance, Epidemiology and End Results (SEER) database collecting data between 2000 and 2018 was searched for all cases of sacral chordoma. We analyzed demographic aspects, cancer stage and treatment patterns. Overall survival was calculated using the Kaplan-Meier method and compared between subgroups using the log-rank test. A multivariate Cox hazard regression analysis was conducted to identify independent predictors of overall survival., Results: Four hundred and forty-two patients were identified with a mean age of 62.7 years. Most tumors presented regional invasion at diagnosis (43.2%). Mean overall survival was 124.7 months. No significant difference in terms of overall survival was found between surgery alone and surgery associated with radiotherapy. Both options provided a significantly increased survival than radiotherapy alone. Age of less than 50 years or between 50 and 69 correlated significantly with improved survival., Conclusion: Age and stage at diagnosis impact significantly survival outcomes. Surgery remains the mainstay treatment with the highest overall survival. Its association with radiotherapy is currently questionable and needs further research., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Chordoma is a locally aggressive bone tumor with a high capability of recurrence. Because chordoma often occurs at critical locations next to neurovascular structures, there is an urgent need to introduce validated biomarkers. T-box transcription factor T (TBXT; OMIM: 601397) plays an important role in the pathogenesis and survival of chordoma cells., Methods: Herein, we aimed to show whether rs2305089 polymorphism is correlated with chordoma in the Iranian population. In order to detect rs2305089, tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) was used. In total, 19 chordoma patients and 108 normal healthy individuals were recruited and screened using T-ARMS-PCR. The results were subsequently validated by Sanger sequencing., Results: The genotype distributions and allele frequencies were significantly different among the patient and healthy groups (p-value <0.05). The A allele of rs2305089 showed a significant positive association with chordoma risk (p-value <0.05). DNA sequencing verified the T-ARMS-PCR results as well. This study demonstrated the association between TBXT rs2305089 and chordoma in an Iranian population using a simple, accurate, and cost-effective T-ARMS-PCR assay., Conclusions: Our results were in line with those of previous studies showing that TBXT rs2305089 is associated with chordoma development. We also developed an efficient T-ARMS-PCR assay to determine the genotype of rs2305089., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: We investigated the frequency of postoperative major complications, length of stay (LOS), and associated risk factors for primary C2-involved upper cervical chordoma through the combined anterior retropharyngeal-posterior approach., Methods: Clinical data were collected from 102 patients with primary C2-involved upper cervical chordoma treated at our institute from January 2016 to January 2021. Additionally, the Changzheng Hospital (CZH) surgical classification system was designed to describe the different anatomic types of C2 chordomas. A multivariate logistic regression analysis was performed and a multivariate Cox proportional hazards model was used to identify the risk factors associated with the occurrence of major complications and prolonged length of stay (LOS), respectively., Results: The incidence of major complication was 29.41% (30 of 102) in our cohort. A long surgical duration (P = 0.001), increased age (P = 0.001), more preoperative comorbidities (P = 0.008) and CZH types indicating extensive tumor involvement (P < 0.001) were identified as significant predictors of the occurrence of a major complication postoperatively. The mean LOS for the entire study population was 21.50 ± 0.64 days. The patients who experienced complications required a significant longer LOS (25.50 ± 1.26 days) than those without complications (19.83 ± 0.65; P < 0.001). The independent factors affecting LOS included age (P = 0.001), Frankel grade (P = 0.001), CZH classification (P < 0.001), and surgical duration (P = 0.001)., Conclusions: Patients who are older, experience longer operative duration, or have larger tumor extension have a greater risk of postoperative major complication. The LOS can be predicted by age, preoperative neurological deficit, CZH classification, surgical approach, and surgical duration. Accordingly, patients with these risk factors should be monitored and targeted with preventative measures., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Chordoma is a rare tumor that occurs along the axial spine in pediatrics and adults, with an incidence of approximately 350 cases per year in the United States. While typically described as slow-growing, many patients will eventually develop loco-regional relapse or metastatic disease with few treatment options. Despite numerous efforts over the last 10+ years, effective treatments for patients are lacking. As subtypes of chordoma are identified and described in more detail, further knowledge regarding the natural history of each type, tumor location, age differences, genomic variability, and an overall better understanding of chordoma may be the key to developing meaningful clinical trials and effective therapies for patients with chordoma., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Less than 5% of chordomas occur in pediatric patients. While many studies have explored the treatment and outcomes of skull base chordomas, few have focused on the differences between pediatric and adult populations. The aim of this study is to analyze the epidemiological variables and clinical outcomes between pediatric and adult skull base chordomas using a large-sample, population-based cancer database., Methods: The National Cancer Database was queried between 2004 and 2015 for skull base chordomas. We stratified patients as pediatric (<18 years) and adults (≥18 years). We compared several clinical covariates between the two groups., Results: Our cohort consisted of 658 patients, 61 pediatric (9.3%), and 597 adults (90.7%). Pediatric patients were more likely to have larger tumor size (41.4 ± 15.7 mm versus 34.1 ± 15.8 mm, p < 0.01) and universally treated at academic facilities. There was no significant difference in overall survival., Conclusions: Pediatric skull base chordomas are rare tumors that are managed with aggressive surgical resection, followed by radiation. While there may be difference between tumor presentation, outcomes between pediatric and adult patients are similar.

Background: Chordoma is a rare malignant bone tumor, and the survival prediction for patients with chordoma is difficult. The objective of this study was to construct and validate a nomogram for predicting cancer-specific survival (CSS) in patients with spinal chordoma., Methods: A total of 316 patients with spinal chordoma were identified from the SEER database between 1998 and 2015. The independent prognostic factors for patients with spinal chordoma were determined by univariate and multivariate Cox analyses. The prognostic nomogram was established for patients with spinal chordoma based on independent prognostic factors. Furthermore, we performed internal and external validations for this nomogram., Results: Primary site, disease stage, histological type, surgery, and age were identified as independent prognostic factors for patients with spinal chordoma. A nomogram for predicting CSS in patients with spinal chordoma was constructed based on the above 5 variables. In the training cohort, the area under the curve for predicting 1-, 3-, and 5-year CSS were 0.821, 0.856, and 0.920, respectively. The corresponding area under the curve in the validation cohort were 0.728, 0.804, and 0.839, respectively. The calibration curves of the nomogram showed a high degree of agreement between the predicted and the actual results, and the decision curve analysis further demonstrated the satisfactory clinical utility of the nomogram., Conclusions: The prognostic nomogram provides a considerably more accurate prediction of prognosis for patients with spinal chordoma. Clinicians can use it to categorize patients into different risk groups and make personalized treatment methods.

Background: Sacral tumors and tumor-like lesions are a rare group of lesions that can affect children and adults of all ages. Little is known about clinical characteristics of age, gender, histologic type, and anatomic site in China., Methods: A total of 1385 patients with sacral tumors and tumor-like lesions, which had the clinical record at our bone tumor center from January 2000 to November 2018 were analyzed. The metastatic cancers were not included in the present study., Results: A total of 51.7% (716 cases) were malignant and 48.3% (669 cases) were benign tumors or tumor-like lesions. Of malignant tumors, chordoma was the most common malignant tumor (316 cases, 22.8% of all tumors), followed by chondrosarcoma, myeloma, and other histologic types. The most common histological type of benign tumors was a giant cell tumor accounting for 14.8% (205 cases) of all tumors, followed by neurofibroma, schwannoma, and other types. The most common age group affected by malignant bone tumors was the 51- to 60-year-old group, followed by the 41- to 50-year-old group. The most commonly affected age group for benign tumors and tumor-like lesions was the 31- to 50-year-old group, followed by the 21- to 30-year old group. Furthermore, the following histologic types had gender predilection. Chordoma, chondrosarcoma, myeloma, and osteosarcoma affected more frequently males than females. Malignant peripheral nerve sheath tumor, lymphoma, giant cell tumor, neurofibroma, tuberculosis, teratoma, and epidermoid cyst more frequently affected females than males., Conclusions: The large cohort of sacral tumors and tumor-like lesions in our database may reveal their clinical characteristics of age, gender, histologic type, and anatomic site in China and features of sacral tumors and tumor-like lesions are fairly distinct from the mobile spine and extremities.

Background: No standard treatment exists for advanced chordoma. Apatinib has been found to have promising efficacy and manageable adverse effects for the treatment of solid tumours. We aimed to investigate the safety and antitumour activity of apatinib in patients with advanced chordoma., Methods: We did a single-arm, phase 2 study at one tertiary hospital in Shanghai, China. Eligible patients were aged 18-75 years, with histologically confirmed advanced chordoma that was unresectable or resectable only through demolitive surgery, who had previously received surgical treatment, with at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, evidence of tumour progression on enhanced CT or MRI in the previous 6 months, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients received oral 500 mg apatinib once daily until disease progression or unacceptable toxicity. The co-primary endpoints were progression-free survival and objective response rate according to RECIST 1.1 and Choi criteria by investigator assessment. Progression-free survival was assessed in the intention-to-treat population. Objective response rate was assessed in the per-protocol population, which included all enrolled patients who were compliant with the protocol and had at least one post-baseline assessment. Safety was analysed in all patients with complete safety data. This study is ongoing, but recruitment is complete. This study is registered with Chictr.org.cn, ChiCTR-OIC-17013586., Findings: Between Aug 21, 2017, and May 31, 2019, we screened 32 patients, of whom 30 were enrolled. Median follow-up was 14·2 months (IQR 9·4-19·7). Of the 27 patients included in the per-protocol population, one patient (3·7%; 95% CI 0-11·3) achieved an objective response according to RECIST, and seven patients (25·9%; 8·3-43·6) achieved an objective response according to Choi criteria. Median progression-free survival was 18 months (95% CI 3-34) according to RECIST and 18 months (3-33) according to Choi criteria. The most common treatment-related grade 3 adverse events were hypertension (seven [24%] of 29 patients) and proteinuria (two [7%]). No treatment-related grade 4 adverse events or treatment-related deaths were observed., Interpretation: To our knowledge, this is the first trial of apatinib for the treatment of advanced chordoma. Apatinib shows promising activity and manageable toxicity and thus might be an option for the treatment of advanced chordoma., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To gain insight into the role of germline genetics in the development of chordoma, the authors evaluated data from 2 sets of patients with familial chordoma, those with and without a germline duplication of the T gene (T-dup+ vs T-dup-), which was previously identified as a susceptibility mechanism in some families. The authors then compared the patients with familial tumors to patients with sporadic chordoma in the US general population reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program through 2015., Methods: Evaluation of family members included review of personal and family medical history, physical and neurological examination, and pre- and postcontrast MRI of the skull base and spine. Sixteen patients from 6 white families with chordoma had a chordoma diagnosis at family referral. Screening MR images of 35 relatives revealed clival lesions in 6, 4 of which were excised and confirmed to be chordoma. Thus, data were available for 20 patients with histologically confirmed familial chordoma. There were 1759 patients with histologically confirmed chordoma in SEER whose race was known., Results: The median age at chordoma diagnosis differed across the groups: it was lowest in T-dup+ familial patients (26.8 years, range 5.3-68.4 years); intermediate in T-dup- patients (46.2 years, range 11.8-60.1 years); and highest in SEER patients (57 years, range 0-98 years). There was a marked preponderance of skull base tumors in patients with familial chordoma (93% in T-dup+ and 83% in T-dup-) versus 38% in the SEER program (37% in white, 53% in black, and 48.5% in Asian/Pacific Islander/American Indian/Alaska Native patients). Furthermore, 29% of white and 16%-17% of nonwhite SEER patients had mobile-spine chordoma, versus no patients in the familial group. Several T-dup+ familial chordoma patients had putative second/multiple primary chordomas., Conclusions: The occurrence of young age at diagnosis, skull base presentation, or multiple primary chordomas should encourage careful review of family history for patients diagnosed with chordoma as well as screening of at-risk family members by MRI for early detection of chordoma. Furthermore, given genetic predisposition in some patients with familial chordoma, identification of a specific mutation in a family will permit surveillance to be limited to mutation carriers-and consideration should be given for imaging the entire neuraxis in any chordoma patient presenting at an early age or with a blood relative with chordoma. Finally, future studies should explore racial differences in age at diagnosis and presenting site in chordoma.

Purpose: Chordomas account for 1% to 4% of all bone malignancies and 0.5% of all primary intracranial central nervous system tumors. Prior epidemiologic literature is based on limited population data. The purpose of this study is to provide the largest and most inclusive population based study of the descriptive epidemiology of chordomas., Methods: The Centers for Disease Control and Prevention and National Program of Cancer Registries were queried for chordoma in all locations. Age-adjusted incidence per 100,000 persons was calculated by age, sex, race, and ethnicity. Annual percentage change was calculated using Joinpoint., Results: From 2004 to 2014, a total of 3670 chordomas were diagnosed in the US. The most common location was cranial (38.7%), followed by sacral (34.3%) and spinal (27.0%). The average age-adjusted incidence rate was 0.088 per 100,000 persons per year (95% CI 0.086-0.091), with an annual percentage change of 1.29% (95% CI 0.31-2.28%). For all chordomas, the incidence peaks in the 75-84 year age group. The male-to-female incidence rate ratio is 1.54 (p < 0.001). American Indian/Alaskan Native and Black patients had a statistically lower incidence rate than White and Asian/Pacific Islander patients., Conclusion: Approximately 0.088 chordomas per 100,000 persons are newly diagnosed in the US each year, with cranial location being the most common, followed by sacral and spinal. Incidence increases with age, and men are at a significantly higher risk than women. This investigation represents the largest population-based epidemiologic study of chordomas in the US.

Background Context: Malignant primary spinal tumors are rare making it difficult to perform large studies comparing epidemiologic, survival, and treatment trends. We investigated the largest registry of primary bone tumors, the National Cancer Database (NCDB), to compare epidemiologic and survival trends among these tumors., Purpose: To use the NCDB to describe current epidemiologic trends, treatment modalities, and overall survival rates in patients with chordomas, osteosarcomas, chondrosarcomas, and Ewing sarcomas of the mobile spine. The secondary objective was to determine prognostic factors that impact overall survival rates., Study Design: Retrospective study., Patient Sample: A total of 1,011 patients with primary bone tumors of the spine (377 chordomas, 223 chondrosarcomas, 278 Ewing sarcomas, and 133 osteosarcomas)., Outcome Measures: Five-year survival., Methods: We reviewed the records of 1,011 patients in the NCDB from 2004 through 2015 with histologically confirmed primary osteosarcoma, chondrosarcoma, Ewing sarcoma, or chordoma of the spine. Demographic, clinical, and outcomes data were compiled and compared using chi-squared tests and ANOVA. Long-term survival was compared using the Kaplan-Meier method with statistical comparisons based on the log-rank test. Multivariate analysis was performed to determine survival determinants., Results: Surgical resection was the primary mode of treatment for chondrosarcoma (90%), chordoma (84%), and osteosarcoma (80%). The treatment for Ewing sarcoma was multimodal involving chemotherapy, radiation therapy, and surgical resection. Five-year survival rates varied significantly with chordomas and chondrosarcomas having the greatest survival (70% and 69%), osteosarcomas having the worse survival (38%), and Ewing having intermediate 5-year survival at 62% (overall log-rank p<.0001). Multivariate analysis demonstrated significantly improved 5-year survival rates with younger age at diagnosis, private insurance status, lower comorbidity score, lower tumor grade, smaller tumor size, surgical resection, and negative surgical margin. Radiation therapy only improved survival for Ewing sarcoma., Conclusions: This study provides the most comprehensive description of the epidemiologic, treatment, and survival trends of primary bone tumors of the mobile spine. Second, patient and tumor characteristics associated with improved 5-year survival were identified using a multivariate model., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Chordomas are slow-growing but locally invasive tumors. The standard of care consists of surgical resection and radiotherapy (RT) when complete resection is not possible. The reported data has reached equivocal results regarding the effect of adding RT to increase patient survival. We investigated the effect of adjuvant RT on patient survival., Methods: The National Cancer Database was queried for patients with a diagnosis of sacral and vertebral column chordoma from 2004 to 2010. The primary outcome was overall survival, which was assessed using Kaplan-Meier plots. Cox proportional hazards were performed to evaluate the effect of each treatment modality on survival after adjusting for an array of patient demographics, facility type, and tumor characteristics., Results: The data from 282 patients with chordoma were analyzed; 209 patients (74.1%) had undergone gross total resection (GTR) alone. The median follow-up period for the GTR alone and GTR plus RT groups was 63.4 and 67.6 months, respectively. The mean survival was comparable between patients receiving GTR alone and those receiving adjuvant RT, for both sacral (7.7 and 6.9 years, respectively; P = 0.56) and vertebral chordoma (8.8 and 6.2 years, respectively; P = 0.59). Using Cox proportional hazards, we found that compared with GTR alone, GTR plus adjuvant RT did not add any significant survival benefit, for patients with either sacral chordoma (hazard ratio, 0.55; P = 0.43) or vertebral chordoma (hazard ratio, 7.29; P = 0.23)., Conclusion: Using data from a large national cancer registry, we found that the available evidence is not enough to suggest that the addition of RT offers a survival benefit for patients with sacral and spinal chordoma after GTR. Given the non-negligible complications associated with RT, the balance of benefits and risks must be considered during preoperative tailoring of the treatment decisions., (Published by Elsevier Inc.)

Background: Local recurrence rates are high in sacral chordoma patients. Adjuvant radiotherapy may play a role in increasing local control. Patients with locally recurrent tumors continue to comprise a significant proportion of the sacral chordoma population and appear to have worse prognosis than those with primary tumors. High-quality studies comparing presentation and treatments for primary and first local recurrent sacral chordoma tumors are sparse., Purpose: To determine: whether there is a difference in how primary and tumors at first recurrence present; the overall survival, local relapse-free survival, and distant relapse-free survival rates and prognostic factors for patients presenting with a primary tumor; overall survival, local relapse-free survival, and distant relapse-free survival rates and prognostic factors for patients presenting with a first local relapse; if there any differences in overall survival, local relapse-free survival, and distant relapse-free survival rates between patients presenting with a primary tumor and those with a first local relapse., Study Design: Retrospective case series., Patient Sample: One hundred one sacral chordoma cases., Outcome Measure: Overall survival, local relapse-free survival, and distant relapse-free survival rates., Methods: Between 1978 and 2013, 131 patients with sacral chordoma were seen. Of them, 17 patients (13%) presented with a history of more than one local recurrence. One patient (1%) presented with multiple distant metastases. Ten patients (8%) had less than 36 months of follow-up and had no event (eg, death, local recurrence, or distant metastasis). A total of 102 patients met our inclusion criteria: patients with primary or first recurrent tumors, without metastatic disease, who underwent surgery and with at least 36 months of follow-up. One patient (1%) died intraoperatively; therefore, 101 patients were included in the present analysis. Cox proportional hazards regression analysis was performed for primary and local recurrent tumor separately and to compare primary and local recurrent tumors., Results: We analyzed 73 primary and 28 first time recurrent sacral chordomas. Tumor size at presentation was different for primary and recurrent tumors (primary median size: 158 cm 3 , interquartile range [IQR]: 46-634; recurrent median size: 39 cm 3 , IQR: 14-175; p=.001). Overall survival at 5 and 10years for the primary tumors was 79% and 59%, respectively. Local relapse-free survival at 5years was 86%. For primary tumors, not receiving radiation was an independent predictor for worse local relapse-free survival (hazard ratio [HR]: 0.20; 95% confidence interval [CI]: 0.0043-0.90; p=.004) and increased tumor size was an independent predictor for both worse overall survival (HR: 1.68; 95% CI: 1.38-2.42; p=.004) and worse distant relapse-free survival (HR: 2.25; 95% CI: 1.47-3.44; p<.001). For recurrent tumors, the 5- and 10-year overall survival was 65% and 40%, respectively. Local relapse-free survival at 5years was 79% for recurrent tumors. On bivariate analysis, increased tumor size was a significant predictor for worse survival (LR median: 338 mL; IQR: 218-503 mL; no LR median: 26 mL; IQR: 9-71 mL). A trend was seen toward better distant relapse survival for tumors presenting as a primary tumor (HR: 0.51; 95% CI: 0.25-1.06; p=.072)., Conclusion: Using a combination of surgical resection and adjuvant radiotherapy allowed us to obtain a good overall survival, local relapse-free survival, and distant relapse-free survival in patients presenting with either a primary tumor or with a first time local recurrent tumor., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose of Review: Chordoma is an exceedingly rare subtype of bone sarcoma. This review aims to provide a comprehensive insight into chordoma epidemiology, and an update on the recent advances in disease, biology and medical therapies., Recent Findings: The incidence of chordoma is approximately 0.08/100 000 and the 5-year overall age-adjusted relative survival is 72% in the United States and 61% in Europe. Over the last years, significant steps forwards have been done in the comprehension of chordoma complexity, with insights gained into the biology and morphology of this disease. New entities have been described and potentially druggable molecular targets identified. This is becoming all the more relevant today, as new potentially active agents are under development., Summary: Chordoma is a complex disease because of its rarity, biological heterogeneity and peculiar clinical behaviour. Despite the progress done, the outcome in this disease remains unsatisfactory and the identification of active systemic treatments remains an urgent, unmet medical need.

Background and Aims: The aim of this systematic review is to describe the epidemiology of chordoma and to provide a clear overview of clinical prognostic factors predicting progression-free and overall survival., Methods: Four databases of medical literature were searched. Separate searches were performed for each of the two objectives. Reference and citation tracking was performed. Papers were processed by two independent reviewers according to a protocol that included risk of bias analysis. Disagreement was resolved by discussion. Pooled analyses were planned if homogeneity of data would allow., Results: Incidence-incidence rates ranged between 0.18 and 0.84 per million persons per year and varied between countries and presumably between races. On average patients were diagnosed in their late fifties and gender data indicate clear male predominance. Two of the largest studies (n = 400 and n = 544) reported different anatomical distributions: one reporting the skull base and sacrococcygeal area affected in 32% and 29% of cases, whereas the other reporting that they were affected in 26% and 45% of cases, respectively., Prognostic Factors: Statistically significant adverse prognostic factors predicting progression-free and overall survival include female sex, older age, bigger tumour size, increasing extent of tumour invasion, non-total resection, presence of metastasis, local recurrence, and dedifferentiated histological subtype., Conclusions: Incidence rate and anatomical distribution vary between countries and presumably between races. Most chordomas arise in the skull base and sacrococcygeal spine, and the tumour shows clear male predominance. Multiple adverse prognostic factors predicting progression-free and overall survival were identified in subgroups of patients. These slides can be retrieved under Electronic Supplementary Material.

Study Design: Retrospective case series., Objective: To report the outcome of a series of patients with sacral chordoma who were surgically treated at a single center., Summary: Chordomas are low-grade malignant tumors that arise from remnants of the notochord. They are most often found in the sacrum, spine and skull-base. These tumors have a slow clinical evolution and may eventually metastasize, even after adequate treatment. Rarely, they can dedifferentiate into high-grade sarcomas. Traditionally, chordomas were considered to be resistant to chemotherapy and standard radiation therapy. However, recently, adrotherapy has been shown to be effective for local and systemic control of the disease. In this study, clinical outcomes and local and systemic recurrence were reviewed to identify prognostic factors for local and systemic control., Methods: Thirty-three patients with sacral chordoma (19 males, 14 females; median age 61 y, range 43-80) who were surgically treated at our institution between 1994 and 2015 were reviewed. In 24 patients, resection was performed above S2. No patients received pre-operative radiotherapy (RT). Three cases received RT (carbon ion therapy) as treatment for local recurrence. Wide (R0) surgical margins were achieved in 17 patients, marginal (R1) margins in 14 patients and intralesional (R2) margins in 2 patients., Results: At a median follow-up of 53 months (range 0-198), 19 patients were continuously disease-free, 6 were disease-free after local recurrence (5) or metastases (1), 3 were alive with disease (2 local recurrence and 1 metastasis), 4 were dead of disease (1 patient died intraoperatively) and 1 was dead of another cause. Local recurrence was observed in 9 cases (27%); all 9 were treated surgically and 3 received carbon ion therapy after surgical intralesional excision. Overall survival at 10 years was 86.6%. Local recurrence-free survival at 10 years was 51%. A statistical analysis confirmed the importance of negative surgical margins (R0) to achieve local control of the disease (p = 0.0007). High resections (above S2) were associated with lower survival and higher risk of local recurrence., Conclusion: Surgical en bloc resection is the primary treatment for sacral chordoma. Carbon ion therapy is used when it is difficult to obtain wide surgical margins. Due to morbidity and the disabling sequelae of surgery, adrotherapy may be considered an alternative to high (above S2-S3) sacral chordoma resections.

Objective: Iatrogenic tumor seeding after open surgery for chordoma has been well described in the literature. The incidence and particularities related to endoscopic endonasal surgery (EES) have not been defined., Methods: The authors retrospectively reviewed their experience with EES for clival chordoma, focusing on cases with iatrogenic seeding. The clinical, radiographic, pathological, and molecular characterization data were reviewed., Results: Among 173 EESs performed for clival chordomas at the authors' institution between April 2003 and May 2016, 2 cases complicated by iatrogenic seeding (incidence 1.15%) were identified. The first case was a 10-year-old boy, who presented 21 months after an EES for a multiply recurrent clival chordoma with a recurrence along the left inferior turbinate, distinct from a right petrous apex recurrence. Both appeared as a T2-hypertintense, T1-isointense, and heterogeneously enhancing lesion on MRI. Resection of the inferior turbinate recurrence and debulking of the petrous recurrence were both performed via a purely endoscopic endonasal approach. Unfortunately, the child died 2 years later due progression of disease at the primary site, but with no sign of progression at the seeded site. The second patient was a 79-year-old man with an MRI-incompatible pacemaker who presented 19 months after EES for his clival chordoma with a mass involving the floor of the left nasal cavity that was causing an oro-antral fistula. On CT imaging, this appeared as a homogeneously contrast-enhancing mass eroding the hard palate inferiorly, the nasal septum superiorly, and the nasal process of the maxilla, with extension into the subcutaneous tissue. This was also treated endoscopically (combined transnasal-transoral approach) with resection of the mass, and repair of the fistula by using a palatal and left lateral wall rotational flap. Adjuvant hypofractionated stereotactic CyberKnife radiotherapy was administered using 35 Gy in 5 fractions. No recurrence was appreciated endoscopically or on imaging at the patient's last follow-up, 12 months after this last procedure. In both cases, pathological investigation of the original tumors revealed a fairly aggressive biology with 1p36 deletions, and high Ki-67 levels (10%-15%, and > 20%, respectively). The procedures were performed by a team of right-handed surgeons (otolaryngology and neurosurgery), using a 4-handed technique (in which the endoscope and suction are typically passed through the right nostril, and other instruments are passed through the left nostril without visualization)., Conclusions: Although uncommon, iatrogenic seeding occurs during EES for clival chordomas, probably because of decreased visualization during tumor removal combined with mucosal trauma and exposure of subepithelial elements (either inadvertently or because of mucosal flaps). In addition, tumors with more aggressive biology (1p36 deletions, elevated Ki-67, or both) are probably at a higher risk and require increased vigilance on surveillance imaging and endoscopy. Further prospective studies are warranted to evaluate the authors' proposed strategies for decreasing the incidence of iatrogenic seeding after EES for chordomas.

Background: Skull base chordomas in children are extremely rare. Their course, management, and outcome have not been defined., Objective: To describe the preeminent clinical and radiological features in a series of pediatric patients with skull base chordomas and analyze the outcome of a cohort who underwent uniform treatment. We emphasize predictors of overall survival and progression-free survival, which aligns with Collins' law for embryonal tumors., Methods: Thirty-one patients with a mean age of 10.7 yr (range 0.8-22) harboring skull base chordomas were evaluated. We retrospectively analyzed the outcomes and prognostic factors for 18 patients treated by the senior author, with uniform management of surgery with the aim of gross total resection and adjuvant proton-beam radiotherapy. Mean follow-up was 119.2 mo (range 8-263)., Results: Abducens nerve palsy was the most common presenting symptom. Imaging disclosed large tumors that often involve multiple anatomical compartments. Patients undergoing gross total resection had significantly increased progression-free survival (P = .02) and overall survival (P = .05) compared with those having subtotal resection. Those who lived through the period of risk for recurrence without disease progression had a higher probability of living entirely free of progression (P = .03; odds ratio = 16.0). Age, sex, and histopathological variant did not yield statistical significance in survival., Conclusion: Long-term overall and progression-free survival in children harboring skull base chordomas can be achieved with gross surgical resection and proton-beam radiotherapy, despite an advanced stage at presentation. Collins' law does apply to pediatric skull base chordomas, and children with this disease have a high hope for cure.

Study Design: Retrospective chart review of patients after surgical resection of chordoma admitted to an inpatient rehabilitation facility., Objective: To evaluate the characteristics associated with improving two or more functional levels and therefore classifying as a substantial responder after an inpatient rehabilitation facility stay in post-resection chordoma patients., Setting: Acute inpatient rehabilitation facility in the United States., Methods: A total of 40 patients were admitted to an inpatient rehabilitation facility from 2010-2015 after chordoma resection. Demographics, tumor management information, lengths of stay and functional independence measures on admission and discharge were collected. Substantial responders were identified as individuals who improved two or more functional levels based on total FIM score change. Logistic regression was used to analyze the available data for association of quantitative and categorical variables with being a substantial responder., Results: The categorical variables analyzed in this study (sex, readmission to an acute hospital, Charlson Comorbidity Index, tumor level, nerve sacrifice, recurrent tumor and metatases) were not associated with being a substantial responder. The quantitative variables age and length of stay at the inpatient rehabilitation facility were individually associated with being a substantial responder, while length of stay at the acute hospital was not., Conclusions: Patients who were younger were more likely to be classified as substantial responders. Patients with longer lengths of stay at the inpatient rehabilitation facility were also more likely to be classified as substantial responders.

Background: Since chordoma is refractory to chemotherapy and conventional radiotherapy, radical surgical resection is mandatory. However, it is surgically demanding in the craniocervical junction (CCJ) and upper cervical spine., Objective: To analyze long-term surgical results of cervical chordomas., Methods: We retrospectively reviewed 12 consecutive patients who underwent surgical treatment for CCJ or upper cervical chordomas from 2001 to 2009 in 2 academic institutions. We analyzed the progression-free survival and overall survival and compared the results between gross total resection (GTR) cases and partial resection (PR). Complications were analyzed by comparing primary and recurrent tumor. We also delineated the type of radiotherapy., Results: Of the 12 patients, 5 underwent GTR and 7 underwent PR. GTR of the tumor was achieved by intralesional piecemeal removal. No recurrence occurred in the GTR group. PR group had 6 cases of regrowth (85.7%). Ten patients (83.3%) underwent any kind of radiation therapy. There were 3 (60%) patients in the GTR group and 7 (100%) in the PR group. Compared to PR, GTR revealed a better 3-yr progression-free survival rate (100% vs 14.3%) as well as a better 3-yr overall survival rate (100% vs 71.4%). Surgical complication rate (40% for GTR vs 42.9% for PR) was not significantly different between the groups. The surgical complication rates of primary and revision surgery were 25% and 75%, respectively. Complication associated with radiation occurred in 2 patients., Conclusion: Gross total intralesional piecemeal resection with perioperative radiation therapy is an acceptable strategy for CCJ and the upper cervical chordoma management., (Copyright © 2017 by the Congress of Neurological Surgeons)

Study Design: Retrospective study., Objective: The aim of this study was to compare the clinical outcomes between adolescent and young adult (AYA) patients and old adult patients with cervical chordoma who were treated surgically and present the surgical consideration for adolescents and young adults with cervical chordoma., Summary of Background Data: With predominance in senior patients, chordoma is distinctively rare in AYAs. Because of the rarity of AYA chordoma, individual case report represents most of the literature on this disease entity on mobile spine and lack of long-term follow up, which leads to the paucity of clinical evidence for treatment planning and prognosis prediction., Methods: A retrospective study was conducted to investigate the prognosis of AYA patients with cervical chordoma who were treated surgically. We collected the clinical data of these patients and their older counterparts, and further compared the prognosis of the patients in different age groups. To estimate survival curves, Kaplan-Meier method was used, and significance was assessed using a log-rank test., Results: Forty consecutive patients with chordoma of the cervical spine treated in our institution were included in the study. Two groups were identified according to age. Group 1 comprised children and adolescents (age ≤ 25 yrs; n = 9) and Group 2 comprised adults (age > 25 years; n = 31). In comparison, Group 1 was featured by significantly higher rate of recurrence and shorter overall survival, although no difference found in the surgical modality between two groups., Conclusion: There is a dismal prognosis in young patients with chordoma, and thus support the notion that as radical a total en bloc spondylectomy (TES) of the lesions as possible may benefit the overall survival of these young patients. Although the ensuing neurological deficits may be devastating, it will be worth sacrificing if the life expectancy of these young patients is prolonged., Levels of Evidence: 4.

Background: Primary spinal osseous tumors are rare, yet they represent a difficult treatment paradigm because of the complexities of tumor resection and significant resistance to chemotherapy and radiation therapy. The geographic distribution of primary spinal osseous tumors throughout the world appears to be quite variable, with a very low incidence reported in Asian countries., Methods: Data on 1209 cases of primary spinal osseous malignant and benign tumor cases diagnosed during the 20-year period of 1995 through 2015 in eastern China were analyzed., Results: In 780 cases (64.5%), the lesion was benign and in 429 (35.5%) was malignant. The commonest primary malignant tumors were chordoma (9.8% of all cases) followed by plasma cell myeloma (8.5% of all cases). The most common benign tumor was hemangioma (28.1% of all cases) followed by giant cell tumor of bone (15.7% of all cases) and osteoblastoma (4.4% of all cases). The benign tumors affected men in 33.8% of cases and women in 30.7% of cases, the malignant tumors affected men in 23.7% of cases and women in 11.8%. The mean age (mean ± SD) in the benign group was 34.7 ± 19.8 years and in the malignant group was 47.4 ± 16.5 years. Related symptoms were pain (54.4%), radiculopathy (12.9%), cord compression (9.2%), mass (5.7%), pathological fracture (4.7%), deformity (2.1%), and weight loss (1.9%). The anatomical locations included almost every vertebra of the spine. The thoracic spine (38.1%) was the most common location of the tumors, followed by the cervical spine (27.4%) and lumbar spine (18.4%)., Conclusions: Compared with other similar series reported in the literature from the other countries, our results obtained in a developing country were different in some degree. This large series of primary spinal osseous tumors may reflect fairly well their real incidence and provide a sufficiently detailed perspective on epidemiologic studies of primary spinal osseous tumors in eastern China.

Purpose: To establish a chordoma tissue cohort (n = 43) and to correlate localization, size, metastasis, residual disease (R-status), recurrences, histological subtype, matrix content, and Ki-67 proliferation index with patients' overall survival (OS)., Methods and Results: We used routine histopathology supplemented by immunohistochemistry. In our patient cohort (median age 69 years, range 17 to 84 years) the median OS was 8.25 years. 24 chordomas were localized in the sacrum, 6 in lumbar vertebrae, 7 in thoracic and cervical vertebrae, 5 were limited to the clivus, and one was localized in the nasal septum. Ten patients had metastases, with pulmonary, nodal, and hepatic involvement. 23 patients had recurrent disease. 23 chordomas were classified as 'not otherwise specified' (NOS). Besides NOS, we found the following differentiation patterns: renal cell cancer like in six cases, chondroid in four cases, hepatoid differentiation in three cases, and anaplastic morphology in six cases. Ki-67 index of ≥10 %, presence of metastasis, and the low content of extracellular matrix were statistically linked to poor OS (p < 0.05). The matrix-poor phenotype had a higher Ki-67 index (p < 0.05). Furthermore, presence of metastasis was associated with a higher Ki-67 index in the primary lesion, a positive resection margin, and multiple recurrences (p < 0.05 each)., Conclusion: We propose to include these parameters in the final pathologic report of the resected chordoma.

Study Design: Retrospective case series., Objective: To report on the natural history and long-term outcome of a large series of consecutive primary sacral chordoma patients surgically treated at two reference centers., Summary of Background Data: Sacral chordomas are rare tumors with poor long-term prognosis mainly caused by local failure. Till date, a few large series with long follow up are available in literature., Methods: All consecutive patients affected by primary localized sacral chordoma operated on at two Italian reference centers between 1981 and 2012 were included. Overall survival (OS), disease free survival (DFS), crude cumulative incidence (CCI) of local recurrence (LR), and distant metastases (DM) were calculated. Multivariable analyses for OS, DFS, LR, and DM were performed., Results: A total of 99 patients were identified: 65 males and 34 females. Median age was 59 years (range 22-77 yrs), median tumor size was 9 cm (range 4-22). Nineteen patients received pre- or postoperative radiotherapy (RT). Wide (R0) surgical margins were achieved in 46 patients, marginal (R1) margins in 43 patients and intralesional (R2) margins in 10 patients. At a median follow up of 8.7 years (range 1-23.8 yrs) 30 patients died of disease, 31 patients developed local relapse, 16 patients developed distant metastasis, whereas 51 patients are alive without disease. OS and DFS at 5, 10, and 15 year were 92% and 63%, 45% and 62%, 36% and 21%, respectively, without any evidence of a plateau in the curves.CCI of LR and DM were 30% and 9% at 5 years, 46% and 18% at 10 years, 56% and 23% at 15 years. Size of the tumor and quality of surgical margins were the only significant predictors of long-term outcome. DFS for 15 years was, in fact, 49% for R0 and 7% for R1, respectively., Conclusion: In this series, long-term outcome of resected sacral chordoma was poor, with less than 25% patients were disease-free at 15 years. Interestingly, only half of the patients treated with R0 resection had no evidence of recurrence at 15 years. When surgical margins are expected to be positive other treatment modalities should be considered, especially when expected sequelae are substantial as in the case of more cephalad levels of resection., Level of Evidence: 3.

The Perdido Key beach mouse (Peromyscus polionotus trissyllepsis) is a critically endangered subspecies of the oldfield mouse. The captive population, currently maintained by 3 Florida zoos, is entirely derived from just 3 wild-caught ancestor mice. Necropsy and histopathology revealed chordoma of the vertebral column in 38 of 88 (43%) mice. The tumors were locally expansile and invasive masses of large physaliferous (vacuolated) cells with small, round, hyperchromatic nuclei, similar to the "classic" form of chordomas described in humans. Primary tumors rarely contained small amounts of bone and cartilaginous matrix, characteristic of the "chondroid" form. Neoplastic cells contained abundant granules positive by the periodic acid-Schiff reaction. Brachyury and cytokeratin AE1/AE3 were detected in neoplastic cells by immunohistochemistry, but uncoupling protein 1 was not identified. Primary tumors occurred along the entire vertebral column--cervical, 5 of 38 (13%); thoracic, 16 (42%); lumbar, 13 (34%); and sacral, 10 (26%)--and 10 (26%) mice had multiple primary masses. Metastases to the lungs were noted in 13 of the 38 (34%) mice. Mice diagnosed with chordomas postmortem ranged from 424 to 2170 days old, with a mean of 1399 days. The prevalence of chordoma was not significantly different between males (n = 23 of 50; 46%) and females (n = 15 of 38; 39%)., (© The Author(s) 2015.)

Background/aims: Primary chordomas, rare cancers arising from the notochord remnants, are extremely rare in the pediatric population. This study examined a large cohort of primary chordoma patients to determine factors impacting prognosis and survival., Methods: Demographic and clinical data on 1,358 primary chordoma patients (86 pediatric patients ≤19 years of age and 1,272 adult patients ≥20 years of age) were abstracted from the Surveillance, Epidemiology, and End Result (SEER) database (1973-2011)., Results: Pediatric primary chordomas present most often as small tumors <4 cm in the cranium of male Caucasians. Despite the majority of primary chordomas presenting with locoregional involvement (90.4%), pediatric patients had more distant disease (14.8 vs. 9.2%, p < 0.05). Survival among pediatric patients having surgery only was significantly longer than for adults (22.5 vs. 14.3 years, p < 0.001). Overall survival was longer (17.2 vs. 12.6 years) and overall mortality was lower in pediatric patients (38.4 vs. 49.8%), but cancer-specific mortality was higher (37.2 vs. 28.6%, p < 0.005)., Conclusions: Pediatric primary chordomas present most often as small tumors <4 cm in the cranium of male Caucasians. Despite having a higher rate of metastasis, they have prolonged survival compared to adults. Surgical resection significantly improves survival in pediatric primary chordoma patients, and should be considered as first-line therapy in all eligible children., (© 2016 S. Karger AG, Basel.)

Paediatric chordomas are rare malignant tumours arising from primitive notochordal remnants with a high rate of recurrence. Only 5 % of them occur in the first two decades such less than 300 paediatric cases have been reported so far in the literature. In children, the average age at diagnosis is 10 years with a male-to-female ratio closed to 1. On the opposite to adults, the majority of paediatric chordomas are intracranial, characteristically centered on the sphenooccipital synchondrosis. Metastatic spread seems to be the prerogative of the under 5-year-old children with more frequent sacro-coccygeal locations and undifferentiated histology. The clinical presentation depends entirely on the tumour location. The most common presenting symptoms are diplopia and signs of raised intracranial pressure. Sacrococcygeal forms may present with an ulcerated subcutaneous mass, radicular pain, bladder and bowel dysfunctions. Diagnosis is suspected on computerised tomography showing the bone destruction and with typically lobulated appearance, hyperintense on T2-weighted magnetic resonance imaging. Today, treatment relies on as complete surgical resection as possible (rarely achieved because of frequent invasiveness of functional structures) followed by adjuvant radiotherapy by proton therapy. The role of chemotherapy has not been proven. Prognosis is better than in adults and depends on the extent of surgical resection, age and histology subgroup. Biological markers are still lacking to improve prognosis by developing targeted therapy.

Objective: To determine prevalence, demographic data and clinical presentation of primary vertebral tumors., Material and Method: A retrospective study of the primary spine tumor specimens from Siriraj bone tumor registry from 1996 to 2010., Results: From the study, primary spinal tumors constituted 85 of 1,679 bone tumor cases (5.06%). The common benign spinal tumors were giant cell tumor and hemangioma. The common malignant spinal tumors were chordoma, chondrosarcoma, and osteosarcoma. The mean age ofpresentation was 44.68 years. Fifty-three percent of tumors occurred in females. Pain was the most common presenting symptom, occurring in 73.53% of malignant and 52.94% of benign tumors. Neurological involvement occurred in 25% of malignant tumor Malignant lesions predominated in the sacral region while the most common location ofbenign specimens was thoracic region., Conclusion: The present study was the first demographic study ofprimary spinal tumor in Thai showed variety of prevalence when compared with similar studies based on Western patients. Whether these results reflect differences in the population, race and data collection method.

This study aims to demonstrate survival rates and treatment patterns among patients with chordomas of the skull base using a large population database. Patients with cranial chordomas between 1973 and 2009 were identified from the USA Surveillance, Epidemiology, and End Results (SEER) public use database. Kaplan-Meier analysis was used to examine the effect of surgery and radiation on overall survival. We identified 394 patients with histologically-confirmed cranial chordomas. Median survival was 151 months. Most patients (89.09%) underwent surgery. Less than half (44.92%) received radiation after diagnosis. Patients who underwent surgical resection survived significantly longer than those who did not undergo resection, regardless of other treatments (151 versus 81 months, p<0.001). Ten year survival was lower among patients receiving radiation (44.8% versus 61.4%, p=0.66). Surgery predicted better overall survival by univariate analysis (hazard ratio [HR] 0.603, p=0.0293); younger age at diagnosis (HR 1.028, p<0.001), and later year of diagnosis (HR 0.971, p=0.0027) were prognostic of improved survival in a multivariate model. In subgroup analysis of patients with documented tumor size, smaller tumor size (HR 1.021, p=0.0067), younger age (HR 1.031, p=0.001), and treatment within a higher volume registry (HR 0.490, p=0.0129) predicted improved survival. Surgical intervention offers survival benefit for cranial chordomas. Findings of decreased survival in patients receiving radiation may be associated with selection. Studies examining surgical extent of resection data and radiation details are needed to determine the impact of radiotherapy., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Object: Chordomas of the skull base are rare and locally invasive and have a poor prognosis. The aim of this retrospective multicenter study was to evaluate the current pattern of care and clinical course and to identify prognostic factors., Methods: A total of 47 patients (26 men; mean age 48.5 years) treated in 5 centers were included. Histology was centrally reviewed; additionally, semiquantitative N- and E-cadherin expression analysis was performed. Prognostic factors were obtained from multivariate regression models. For survival analysis the Kaplan-Meier method was used., Results: The median follow-up period was 5.2 years. Complete resection, incomplete resection, and extended biopsy were performed in 14.9%, 80.9%, and 4.3% of patients, respectively. Surgical morbidity was not associated with extent of resection. Adjuvant radiation therapy was performed in 30 (63.8%) of 47 patients. The median progression-free survival (PFS) was 7.3 years. Complete resection prolonged median overall survival (OS) (p = 0.04). Male patients presented with worse PFS (4.8 years vs 9.8 years; p = 0.04) and OS (8.3 years vs not reached; p = 0.03) even though complete resection was exclusively achieved in the male subpopulation. Multivariate analysis confirmed male sex as the most important risk factor for tumor progression (p = 0.04) and death (p = 0.02). Age, duration of symptoms, initial Karnofsky Performance Scale score, brainstem compression, involvement of the petrous bone, infiltration of the dura mater, modality and dose of radiation therapy, and the E- and N-cadherin expression patterns did not gain prognostic relevance., Conclusions: In skull base chordomas, male patients bear a higher risk of progressive disease and death. Male patients might benefit from more aggressive adjuvant therapy and/or from a closer follow-up schedule.

Primary spinal tumors are rare diseases. Primary spinal tumor registry would be useful to help decision making in this complex field of spine surgery. In this article the authors present the latest findings from the Primary Spinal Tumor Registry at the National Centre for Spinal Disorders, Hungary. The registry is based on a novel database management software, the REDCap electronic data capture system. It contains data of 323 patients treated surgically during an 18-year period. Among the 126 malignant tumors, the most frequent was chordoma (61 cases). In the case of benign tumors schwannoma showed the largest prevalence (45 cases). The authors conclude that due to the rarity of the disease and the complexity of the management, multicenter, prospective registries are required to provide high level of evidence. The structure of the Primary Spinal Tumor Registry in the National Centre for Spinal Disorders in Hungary is optimal for user-friendly, fast and secure data collection providing a prospective database for scientific researches and clinical follow-up.

Objectives/hypothesis: To determine trends in survival patterns for cranial chordoma in the United States., Study Design: A cross-sectional analysis of a national healthcare database., Methods: All cases of microscopically confirmed cranial chordoma between 1973 and 2009 from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute were examined. Age-adjusted incidence and survival rates were calculated and stratified by treatment. Additionally, in order to assess trends over time, comparisons in survival were conducted for 3 calendar year cohorts: 1975 to 1984, 1985 to 1994, and 1995 to 2004., Results: A total of 594 cases of microscopically confirmed chordoma involving cranial sites were identified, which accounted for 42% of all chordomas. Age-adjusted incidence rate (IR) of all chordomas was 0.089 per 100,000. Overall median survival time with surgery plus radiation was 9.2 years. Age and treatment modality were found to influence patient survival. Specifically, age > 50 years was associated with a significant increase in mortality rate (P < .05). Five-year survival for the 1975 to 1984, 1985 to 1994, and 1995 to 2004 cohort was 48.5%, 73.0%, and 80.7%, respectively, with improved survival in the more recent cohorts (P < 0.01)., Conclusion: This study provides new data regarding survival patterns of cranial chordoma in the United States, with a trend toward improvement in survival in recent decades., (© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Background and Purpose: Distinguishing BNCT from chordoma with imaging is critical because of the profound differences in prognosis and management. Yet few reports define the variable imaging characteristics of BNCT. This study aims to evaluate the prevalence and characteristics of BNCT., Methods: A total of 916 patients with 64-section CT and 1.5T MR imaging through the posterior fossa between 2004 and 2009 were evaluated to catalogue the prevalence, clinical presentation, morphology, and imaging properties associated with BNCT., Results: BNCTs were identified in 7 patients (imaging prevalence of 0.76%). All were midline, T1 hypointense, and T2 hyperintense. When present, the bony stalk often associated with EP measured between 1.65 and 3.72 mm. Five cases demonstrated atypical features such as absence of bony stalk (one case), arterial enhancement (one case), clival erosion (four cases), clinical symptoms (one case), and mass effect (one case)., Conclusion: Many notochordal lesions do not fit neatly into the diagnostic criteria for either EP or chordoma. It may be useful to consider these atypical cases along a spectrum of notochord remnant lesions. Close inspection of imaging reveals BNCTs at a similar frequency to its pathologic prevalence. BNCTs such as EP vary in size and may be easily overlooked., (Copyright © 2013 by the American Society of Neuroimaging.)

Objectives: To propose a new classification for ecchordosis physaliphora (EP) using fast imaging employing steady-state acquisition (FIESTA)., Methods: We evaluated 974 consecutive patients and selected for further study 78 (8.0 %) who manifested an excrescence on the dorsal surface of the clivus (DSC) and/or clivus lesions. Lesions were defined as "classical EP" when they appeared as a hyperintense excrescence (cyst-like component) on DSC. Other lesions were defined as "possible EP"., Results: Of the 78 patients, 17 (22 %) were diagnosed with classical EP, the other 61 with possible EP. The 61 patients with possible EP were further classified into "incomplete EP = EP bud" (n = 55, 90.2 %), characterised by a T2 hypointense protrusion of the clivus, and into "EP variant" (n = 6, 9.8 %), characterised by hyperintense lesions within only clivus. FIESTA findings of incomplete EP were similar to those of classical EP except for lack of the hyperintense excrescence on DSC. Most lesions were located at the level of the Dorello canal at the midline of the craniospinal axis., Conclusion: Our results suggest that the magnetic resonance imaging appearance of EP is diverse. Based on our FIESTA results we propose a new classification for EP, i.e. classical EP, incomplete EP (EP bud) and EP variant., Key Points: • Ecchordosis physaliphora (EP) is a rare benign cystic congenital lesion arising from notochord. • The classical type of EP is frequently associated with a T2 hypointense protrusion. • T2 hypointense protrusions without clivus cysts may represent an incomplete type of EP. • Third type of EP variant only harbours lesions within the clivus.

Chordoma is a primary bone cancer arising on the midline from the skull base to the sacrum. Diagnosis is often delayed because of insidious onset and nonspecific symptoms. Chordomas appear histologically low-grade but are highly invasive and often recur locally. Management centers primarily on radical en bloc surgical resection when possible. Radiation therapy using protons and/or photons is often necessary because complete resection is seldom possible due to critical location and invasion of the cancer cells into surrounding structures. No approved medical therapy exists. The high rate of recurrence is reflected by a median survival of 6 to 7 years. This article reviews the clinical management of chordoma and discusses ongoing research in the field.

Background: Chordomas are rare bone tumors arising from remnants of the embryonic notochord., Methods: Data for this study were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (1973-2009) to calculate the incidence, relative survival (RS), and standardized mortality ratio (SMR) of patients diagnosed with intracranial and extracranial chordomas and to assess the effects of age and sex on this disease., Results: The overall incidence of extracranial and intracranial chordomas was 8.4 per 10 million population. The median overall survival of patients with chordoma patients was 7.7 years. The median survival was 7.7 years for male patients and 7.8 years for female patients. Younger patients (aged <40 years) survived longer compared with older patients (10-year RS, 68% vs 43%). The estimated age-standardized 5-year, 10-year, and 20-year RS rates was 72%, 48%, and 31%, respectively. The SMR in the overall cohort was 4.6 (95% confidence interval, 4.22-5.0) or 21.0 (95% confidence interval, 16.6-27.2) in young adult patients and 3.0 (95% confidence interval, 2.6-3.4) in elderly patients., Conclusions: The elderly had a more aggressive form of this disease; and, other than the incidence, sex did not influence outcome in this disease. The study of chordomas presents a good case for the contribution that the SMR can have on measuring the impact of a disease on a population of patients. Although the younger population has better survival rates, the impact (SMR) in the younger age groups is much higher than in older populations., (Copyright © 2013 American Cancer Society.)

Introduction: Chordoma is a rare malignant bone tumor. The outcome depends on the adequate surgical treatment with complete excision of the tumor with microscopic clear margins., Materials and Methods: We performed a retrospective review of 13 cases of chordomas operated in our center between 1988 and 2009., Results: All cases were treated with wide excision. Inadequate margins were found in seven patients. There were complications in ten patients and long-term sequels in 11 patients. Nine had recurrence within the first 2 years, six of which had inadequate margins. Five had metastatic disease, three of them with inadequate margins. During the follow-up, four patients died. In a posterior review, three patients survive and all of them had clear margins., Conclusions: In our experience, the best treatment is complete excision of the tumor with clear microscopic margins. When this is not possible, local recurrences increase and survival rate decreases.

Aim: To study the clinicopathologic characteristics of chordomas from a single institution., Material and Methods: This study is a retrospective analysis of 18 cases of chordomas diagnosed over a period of 5-years at Sher-i-Kashmir Institute of Medical Sciences, Srinagar, from 2006 to 2010., Results: The overall mean age of the patients was 46.72 years. Males outnumbered females. Sacrum was the commonest site involved. Histopathologically, the majority of cases were conventional chordoma with four cases of chondroid variety. There was a single case of dedifferentiated chordoma that presented with bone metastasis. Most patients did well after surgery and radiotherapy. One patient had a local recurrence and one patient with dedifferentiated variant died on follow-up., Conclusion: Though locally aggressive, chordomas are effectively treated with resection and postoperative radiotherapy.

Chordoma is a rare, but often malignant, bone cancer that preferentially affects the axial skeleton and the skull base. These tumors are both sporadic and hereditary and appear to occur more frequently after the fourth decade of life; however, modern technologies have increased the detection of pediatric chordomas. Chordomas originate from remnants of the notochord, the main embryonic axial structure that precedes the backbone, and share with notochord cells both histological features and the expression of characteristic genes. One such gene is Brachyury, which encodes for a sequence-specific transcription factor. Known for decades as a main regulator of notochord formation, Brachyury has recently gained interest as a biomarker and causative agent of chordoma, and therefore as a promising therapeutic target. Here, we review the main characteristics of chordoma, the molecular markers, and the clinical approaches currently available for the early detection and possible treatment of this cancer. In particular, we report on the current knowledge of the role of Brachyury and of its possible mechanisms of action in both notochord formation and chordoma etiogenesis.

Study Design: Retrospective database review using Surveillance, Epidemiology, and End Results database, National Cancer Institute., Objective: To determine current treatment outcomes and demographic characteristics and to define the prognostic factors and impact of surgery on survival., Summary of the Background Data: Rarity of the disease has limited the number of population-based studies addressing the issues of prognostic factors and the current treatment outcomes., Methods: A total of 962 patients with chordoma, diagnosed between 1973 and 2005, were identified in the Surveillance, Epidemiology, and End Results database. Patient demographics and clinical characteristics, incidence, year of diagnosis, location, size and stage at diagnosis, treatment(s), and survival were extracted. Kaplan-Meier, log-rank, and Cox regression were used to analyze the significance of prognostic factors., Results: Race specific incidence per 100,000 persons in 2005 shows whites to have the highest (0.473) incidence, followed by Asians/Pacific Islanders (0.091), and Afro-Americans (zero), respectively. The incidence difference between whites and Afro-Americans over time is statistically significant (P < 0.001). The age adjusted incidence reveals a peak in eighth decade of life. Survival was not impacted by race. Age category <59, Hispanic ethnicity, size <8 cm, and surgical resection were all independent predictors of better overall survival. Analysis revealed that survival outcomes were very similar in patients with "in-operable disease" and those in which "surgery was recommended but not performed" suggesting that benefits of resection cannot be solely attributed to selection bias., Conclusion: With high local recurrence rates and the significant functional morbidity associated with surgical resections, clinicians are left wondering if surgery constitutes an appropriate treatment option. Our study clearly demonstrates that surgery significantly improves the overall survival for patients with chordoma. We have further identified age <59 and size of primary tumor <8 cm as important prognostic factors determining the outcome with substantial statistical significance.

Study Design: A retrospective study of 134 consecutive cases in 92 patients who underwent soft tissue reconstruction of the spinal region following tumor removal., Objective: To better understand how to optimize outcomes in soft tissue reconstruction of the spine region., Summary of Background Data: With the increasing use of instrumentation and the fact that many patients with spinal neoplasms have debilitated wound-healing capacity, most of these patients are at high risk for postsurgical wound complications. Unfortunately, the optimal strategy to prevent and to manage complex wound complications involving the spinal region remains unclear., Methods: Factors potentially associated with the outcome of the reconstruction, including previous radiation therapy, chemotherapy, or surgery; medical comorbidities; timing of the reconstructive surgery; location of the defect; reconstructive approach; and presence of instrumentation, were evaluated and compared., Results: Of 92 patients, 29 patients (32%) developed postoperative wound complications. Among 32 patients with instrumentation of the spine, the 10 patients who had prophylactic soft tissue reconstruction had a significantly lower incidence of complications than did the 22 patients who had not (20% vs. 45%, P = 0.018). Furthermore, those who had previous surgery to the spine had a significantly higher risk of developing exposed instrumentation than did those who did not (21% vs. 0%, P = 0.002). Of 9 patients with exposed instrumentation, all but 1 patient had successful coverage of the instrumentation. Ninety (98%) of 92 patients had successful closure of the wound at the time of their last follow-up., Conclusions: In the presence of instrumentation, providing preemptive soft tissue reconstruction at the time of the initial spinal surgery can help minimize potentially serious wound complications. For management of wound complications that have developed, an aggressive debridement and coverage with well-vascularized tissue can allow for expedient wound healing while maintaining stabilized instrumentation.

We conducted a review of the Leeds Regional Bone Tumour Registry for primary bone tumours of the spine since establishment in 1958 until year 2000. To analyse the incidence of primary tumours of the spine and to record the site of occurrence, sex distribution, survival and pathology of these tumours. Primary tumours of the spine are particularly rare, accounting for between 4 and 13% of published series of primary bone tumours. The Leeds Bone Tumour Registry was reviewed and a total of 2,750 cases of bone tumours and tumour-like cases were analysed. Consultants in orthopaedic surgery, neurosurgery, oncology and pathology in North and West Yorkshire and Humberside contribute to the Registry. Primary bone tumours of the osseous spine constitute only 126 of the 2,750 cases (4.6%). Chordoma was the most frequent tumour in the cervical and sacral regions, while the most common diagnosis overall was multiple myeloma and plasmacytoma. Osteosarcoma ranked third. The mean age of presentation was 42 years and pain was the most common presenting symptom, occurring in 95% of malignant and 76% of benign tumours. Neurological involvement occurred in 52% of malignant tumours and usually meant a poor prognosis. The establishment of Bone Tumour Registries is the only way that sufficient data on large numbers of these rare tumours can be accumulated to provide a valuable and otherwise unavailable source of information for research, education and clinical follow-up.

Chordoma is a rare bone tumor, believed to derive from notochordal rests, which generally arises at the two extremities of axial skeleton. We present a literature review on chordomas. Diagnosis has been greatly improved by MRI and immunohistochemistry. Conversely, complementary immunohistochemistry, cytometry and cytogenetic techniques have failed to improve prognosis evaluation. Radical surgery with free surgical margins is the most accurate curative treatment. Progress in radiotherapy should offer new therapeutic perspectives in the future. The recognition of new entities such as giant notochordal rest or hamartoma, and notochordal cells benign tumor, can lead to confusion since there is no consensus regarding their nature and whether or not they correspond to chordoma precursors. Prudence should be the rule in order to avoid overtreatment.

Aims: Intraosseous benign notochordal cell tumour is a recently recognized condition that may undergo malignant transformation to classic chordoma. The aim of this study was to describe its clinicopathological characteristics., Methods and Results: One hundred vertebral columns from atlas to coccyx and 61 pieces of the clival portion of the skull base, which were dissected from 100 autopsy cases, were examined microscopically. Twenty-six intraosseous benign notochordal cell tumours were found in 20 cases. The patient group consisted of 15 males and five females with a mean age of 63 years. The results, according to anatomical segments, showed that 11.5% of the clivus, 5.0% of the cervical vertebrae, 0% of the thoracic vertebrae, 2.0% of the lumbar vertebrae, and 12.0% of the sacro-coccygeal vertebrae were affected. Microscopic examination revealed well demarcated but unencapsulated sheets of bland physaliphorous cells mimicking adipocytes. The lesions lacked any intercellular myxoid matrix. The affected bone trabeculae were characteristically sclerotic., Conclusions: The study indicated a surprisingly high incidence of intraosseous benign notochordal cell tumours. The anatomical distribution of the tumours was identical to that of classic chordomas. The results support other evidence that classic chordomas develop from intraosseous benign notochordal cell tumours.

In order to study the computerized tomographic (CT) appearances and clinical characteristics of intracranial tumoural haemorrhage (ITH), we analyzed retrospectively fifty-eight patients with ITH and reviewed the literature. As a result, 91% patients had acute or subacute onset and 26% manifested haemorrhage as their first symptoms. CT scanning indicated that intratumoural bleeding occurred in 23 cases, bleeding into parenchyma 18 cases, subarachnoid space 6 cases, ventricle 3 cases and subdural space 8 cases. Thirty-eight patients had emergency operations and the others had selective operations. Both tumours and haematomas were removed all together in all patients. Fifty-five patients were cured or improved and three died during the perioperative stage in our series. Among the patients with ITH, there were 21 metastatic tumours, 19 gliomas, 10 meningiomas, 6 pituitary adenomas, 1 melanoma and 1 acoustic neurilemoma. The onset of most ITH resembled that of cerebrovascular diseases. The location of ITH and the CT appearances of ITH varied in different cerebral tumours. Radical removal of brain tumours with haemorrhage is an effective treatment for ITH, which can greatly decrease the perioperative mortality rate and improve the prognoses of patients., (Copyright 2002 Elsevier Science Ltd.)

Background: Chordoma, a rare tumor arising from notochordal remnants, has been described to date only by single-institution case series or small population-based surveys., Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute, 1973-1995, to calculate age-adjusted incidence and survival rates for 400 cases of microscopically confirmed chordoma and to derive information regarding case distribution and risk of second cancer., Results: The age-adjusted chordoma incidence rate (IR) of 0.08 per 100,000 was age-dependent, more common in males (IR 0.10) than females (IR 0.06) and rare among patients aged <40 years and blacks. Within the axial skeleton 32% of cases were cranial, 32.8% spinal and 29.2% sacral. Young age (<26 years; p = 0.0001) and female sex (p = 0.037) were associated with greater likelihood of cranial presentation. There was no overall increased risk for second primary cancers after chordoma. Median survival was 6.29 years; 5- and 10-year relative survival rates were 67.6% and 39.9%, respectively. Comparison with other bone sarcomas revealed racial disparities in incidence for the two developmental tumors, chordoma and Ewing's sarcoma., Conclusions: This study provides new data regarding incidence and survival patterns of chordoma in the US. Additional epidemiologic studies are required to elucidate the genetic and environmental determinants underlying this rare, distinctive neoplasm.

Mainly between 1945 and 1955, several thousand German patients with ankylosing spondylitis, tuberculosis, or--in a few cases--other diseases received multiple injections of the short-lived alpha-particle emitter radium-224. In the early 1950s, the follow-up of 899 patients was initiated, and the study has continued since then. It includes most of the high-dose patients and nearly all of those treated as children or juveniles, i.e. under the age of 21. In the study cohort, 56 malignant bone tumors occurred in a temporal wave that peaked 8 years after exposure, whereas less than one case would have been expected during the follow-up. Most of the malignant bone tumors were osteosarcomas and fibrous-histiocytic sarcomas. A new analysis has now been performed, primarily because an improved dosimetry resulted in modified bone surface doses, especially for those treated at younger ages. A significant increase in bone tumor risk with decreasing age at exposure is now demonstrated. The earlier finding of an inverse protraction factor is confirmed. In the new formulation, the dependence on dose rate or duration applies only at higher doses; i.e., the initial slope of the dose dependence is unrelated to dose rate or exposure duration, which is in contrast to earlier analyses but is in agreement with microdosimetric considerations and general radiobiological experience.