• bibliometric
• coccygeal chordomas
• coccyx chordomas
• sacral chordomas
• sacrococcygeal chordomas
• spine

• chordoma
• drug repurposing
• functional genomics
• multi-omics
• precision oncology
• rare cancer
• synthetic lethality
• target discovery

• chordoma
• metastasis
• rhinology
• skull base
• systematic review

• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Chordoma/drug therapy
• Chordoma/metabolism
• Chordoma/pathology
• Drug Discovery
• Humans
• Organoids/metabolism
• Treatment Outcome

• P30 CA016042 NCI NIH HHS
• R01 CA244729 NCI NIH HHS
• R01 CA264248 NCI NIH HHS
• NIH
• UCLA DGSOM

• bone sarcoma
• chemotherapy
• chordoma
• cisplatin
• imatinib
• systemic treatment

Retrorectal or presacral tumors are rare lesions located in the presacral area and considered as being derived from multiple embryological remnants. These tumors are classified as congenital, neurogenic, osseous, inflammatory, or miscellaneous. The most common among these are congenital benign lesions that present with non-specific symptoms, such as lower back pain and change in bowel habit. Although congenital and developmental tumors occur in younger patients, the median age of presentation is reported to be 45 years. Magnetic resonance imaging plays a crucial role in treatment management through accurate diagnosis of the lesion, the evaluation of invasion to adjacent structures, and the decision of appropriate surgical approach. The usefulness of preoperative biopsy is still debated; currently, it is only indicated for solid or heterogeneous tumors if it will alter the treatment management. Surgical resection with clear margins is considered the optimal treatment; described approaches are transabdominal, perineal, combined abdominoperineal, and minimally invasive. Benign retrorectal tumors have favorable long-term outcomes with a low incidence of recurrence, whereas malignant tumors have a potential for distant organ metastasis in addition to local recurrence.

• Retrorectal tumors
• Congenital cystic lesions
• Teratomas
• Perineal approach
• Transabdominal approach, Combined abdominoperineal approach

Chordoma is a rare, slow growing and locally aggressive mesenchymal neoplasm with uncommon distant metastases. It is a chemo-resistant disease with surgery and radiotherapy being the mainstay in treatment of localized disease. In advanced disease imatinib has a role. We report a case of metastatic sacral chordoma with symptomatic and radiological response to erlotinib post-progression on imatinib.

A 48-year-old male with a sacral chordoma underwent partial sacrectomy followed by post-operative radiotherapy. Upon recurrence he received palliative radiotherapy to hemipelvis and was offered therapy with imatinib. However, the disease was refractory to imatinib and he was started on treatment with erlotinib—showing a partial response on imaging at two months. He is currently doing well at 13 months since start of erlotinib.

As seen in previously reported cases, erlotinib is a therapeutic option in advanced chordoma, even in imatinib refractory cases and thus warrants exploration of its therapeutic role in prospective clinical trials.

• Chordoma
• EGFR
• Erlotinib

• Brachyury
• Chordoma
• Genomic
• Sacral
• Sequencing
• Skull base
• Targeted therapy

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

• LncRNAs
• biological functions
• clival chordomas
• dural penetration
• microarray analysis

• bone tumor
• chordoma
• erlotinib
• imatinib
• molecular targeted therapy
• systematic review

Chordomas are rare, malignant bone tumors of the skull-base and axial skeleton. Until recently, there was no consensus among experts regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation, the global chordoma patient advocacy group, convened a multi-disciplinary group of chordoma specialists to define by consensus evidence-based best practices for the optimal approach to chordoma. In January 2015, the first recommendations of this group were published, covering the management of primary and metastatic chordomas. Additional evidence and further discussion were needed to develop recommendations about the management of local-regional failures. Thus, ESMO and CF convened a second consensus group meeting in November 2015 to address the treatment of locally relapsed chordoma. This meeting involved over 60 specialists from Europe, the United States and Japan with expertise in treatment of patients with chordoma. The consensus achieved during that meeting is the subject of the present publication and complements the recommendations of the first position paper.

• chemotherapy
• chordoma
• radiotherapy
• relapse
• sarcoma
• surgery

Chordomas are rare tumors that can develop anywhere along the craniospinal axis. These tumors present challenges with respect to diagnosis and treatment due to a high rate of recurrence, even after multiple surgeries, and the propensity to involve any region within the craniospinal axis. New developments in radiation therapy have improved recurrence-free survival in patients with chordomas. Different regimens of chemotherapy and molecularly-targeted therapies, as adjuvants to surgery, have been described in individual case reports and case series. The purpose of this paper is to describe a case of clival chordoma and review recent developments in diagnostic and therapeutic options.

A 77-year-old female was referred because of diplopia and progressively worsening headaches. Head imaging revealed a large expansile and erosive mass in the skull base. The patient underwent a successful endoscopic endonasal trans-sphenoidal resection of the mass, with biopsy confirming the diagnosis of chordoma. Postoperatively, the patient experienced an improvement in neurological symptoms.

Chordomas can present a diagnostic challenge due to the rare occurrence and a tendency to involve any region within the craniospinal axis.

• Chemoradiotherapy
• Chondrosarcoma
• Chordoma
• Skull Base
• Skull Base Neoplasms

• ADCC
• ADCC = antibody-dependent cell-mediated cytotoxicity
• E/T ratio = effector cell/target cell ratio
• EGFR
• EGFR = epidermal growth factor receptor
• F = phenylalanine
• FITC = fluorescein isothiocyanate
• MFI = mean fluorescence intensity
• NK = natural killer
• PBMC = peripheral blood mononuclear cell
• PCR = polymerase chain reaction
• V = valine
• antibody-dependent cell-mediated cytotoxicity
• cetuximab
• chordoma
• epidermal growth factor receptor
• haNK = high-affinity natural killer
• immunotherapy
• mAb = monoclonal antibody
• oncology

• Chondrosarcoma
• Chordoma
• Genetics
• Skull base

Chordomas are rare malignant tumours of the axial skeleton and skull base supposed to arise from cellular remnants of the notochord. These tumours have the potential to metastasize (30–40 %), usually in the later course of the disease. However, the greatest morbidity is usually a result of loco-regional recurrence with infiltration and destruction of surrounding bone and soft tissue. Patients with unresectable or metastatic chordoma are faced with a poor prognosis since cytotoxic chemotherapy or other systemic therapies have not proven their efficacy yet. However, several molecularly targeted drugs have been proposed as potentially beneficial, including tyrosine kinase inhibitors (TKIs) directed at vascular endothelial growth factor receptor (VEGFR), like pazopanib and sunitinib.

Five patients with unresectable or metastatic chordoma were treated with VEGFR inhibitors pazopanib or sunitinib in the Leiden University Medical Centre (LUMC) between 2008 and 2015. Two out of four patients treated with pazopanib derived clinical benefit and disease remained stable for respectively 14 and 15 months. The one patient treated with sunitinib achieved a partial response according to RECIST 1.1 which lasted for a total of 27 months. No serious adverse events were observed.

These results on the use of pazopanib and sunitinib in chordoma are promising, with an objective response on sunitinib and a median progression free interval of 8.5 months (range 3–15 months), comparable to that of imatinib, in the pazopanib subgroup. However further research is needed to assess the definite role of VEGFR inhibitors in chordoma.

• Chordoma
• Pazopanib
• Sunitinib
• Tyrosine kinase inhibitor
• Vascular endothelial growth factor

• Children
• Chordoma
• Protontherapy
• Sarcoma

• AZD8931
• EGFR
• ERBB family
• chordoma
• drug screen
• resistance

• Animals
• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Chordoma/drug therapy
• Chordoma/pathology
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Resistance, Neoplasm
• Drug Screening Assays, Antitumor
• ErbB Receptors/antagonists & inhibitors
• Erlotinib Hydrochloride/pharmacology
• Gefitinib
• Humans
• Mice
• Quinazolines/pharmacology
• Signal Transduction
• Xenograft Model Antitumor Assays

• 18387 Cancer Research UK
• J 3640 Austrian Science Fund FWF

• FLLL32
• STAT3
• chordoma
• sacrum
• skull base

Chordomas are rare primary malignant bone tumors arising from embryonal notochord remnants of the axial skeleton. Chordomas commonly recur following surgery and radiotherapy, and there is no effective systemic therapy. Previous studies implicated receptor tyrosine kinases, including epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (IGF-1R), in chordoma biology. We report an adult female patient who presented in 2003 with spinal chordoma, treated with surgery and radiotherapy. She underwent further surgery for recurrent chordoma in 2008, with subsequent progression in pelvic deposits. In June 2009, she was recruited onto the Phase I OSI-906-103 trial of EGFR inhibitor erlotinib with linsitinib, a novel inhibitor of IGF-1R/insulin receptor (INSR). Treatment with 100 mg QD erlotinib and 50 mg QD linsitinib was well-tolerated, and after 18 months a partial response was achieved by RECIST criteria. From 43 months, a protocol modification allowed intra-patient linsitinib dose escalation to 50 mg BID. The patient remained stable on trial treatment for a total of 5 years, discontinuing treatment in August 2014. She subsequently experienced further disease progression for which she underwent pelvic surgery in April 2015. Analysis of DNA extracted from 2008 (pre-trial) tissue showed that the tumor harbored wild-type EGFR, and a PIK3CA mutation was detected in plasma, but not tumor DNA. The 2015 (post-trial) tumor harbored a mutation of uncertain significance in ATM, with no detectable mutations in other components of a 50 gene panel, including EGFR, PIK3CA, and TP53. By immunohistochemistry, the tumor was positive for brachyury, the molecular hallmark of chordoma, and showed weak–moderate membrane and cytoplasmic EGFR. IGF-1R was detected in the plasma membrane and cytoplasm and was expressed more strongly in recurrent tumor than the primary. We also noted heterogeneous nuclear IGF-1R, which has been linked with sensitivity to IGF-1R inhibition. Similar variation in IGF-1R expression and subcellular localization was noted in 15 further cases of chordoma. In summary, this exceptionally durable response suggests that there may be merit in evaluating combined IGF-1R/INSR and EGFR inhibition in patients with chordomas that recur following failure of local treatment.

• EGFR
• IGF-1R
• chordoma
• nuclear IGF-1R
• tyrosine kinase inhibitor

• MRI
• Retrorectal tumour
• presacral tumour
• surgery

Chordoma is an extremely rare cancer, with an incidence of about one case per million persons per year in the USA and Europe (about 300 and 450 cases per year, respectively). The estimated median overall survival of patients with chordoma is approximately 6–7 years, yielding a rough estimate of chordoma prevalence at about 2000 in the USA and 3000 in Europe. Primary tumor develops along the axial spine between the clivus and sacrum and develops from the residual embryonic notochord. Brachyury (T), a transcription factor required for normal embryonic development, is expressed in the notochord and overexpressed in almost all cases of chordoma. The primary treatment for chordoma is surgical excision with wide local margins, when possible. Radiotherapy also plays a significant role in the adjuvant setting and when surgery is not possible. Unfortunately, in the advanced and/or metastatic setting, where the role of surgery and/or radiation is less clear, treatment options are very limited. To date, there have been no randomized, controlled trials in chordoma that have resulted in defined agents of clinical benefit for systemic treatment. This review briefly describes the natural history and initial treatment of chordoma and focuses on treatment options for advanced disease and potential avenues of research that may lead to improved treatment options in the future.

• Brachyury
• Chordoma
• Erlotinib
• Imatinib
• Immunotherapy
• Radiotherapy
• Spine tumor
• Surgery
• Vaccine

• Children
• Chordoma
• Protontherapy
• Sarcoma

• paediatric
• chordoma

• Bone Neoplasms/diagnosis
• Bone Neoplasms/epidemiology
• Bone Neoplasms/therapy
• Brain Neoplasms/diagnosis
• Brain Neoplasms/epidemiology
• Brain Neoplasms/therapy
• Child
• Chordoma/diagnosis
• Chordoma/epidemiology
• Chordoma/therapy
• Female
• Humans
• Male

Chordomas are rare, locally aggressive skull base neoplasms known for local recurrence and not-infrequent treatment failure. Current evidence supports the role of maximal safe surgical resection. In addition to open skull-base approaches, the endoscopic endonasal approach to clival chordomas has been reported with favorable albeit early results. Adjuvant radiation is prescribed following complete resection, alternatively for gross residual disease or at the time of recurrence. The modalities of adjuvant radiation therapy reported vary widely and include proton-beam, carbon-ion, fractionated photon radiotherapy, and photon and gamma-knife radiosurgery. As of now, no direct comparison is available, and high-level evidence demonstrating superiority of one modality over another is lacking. While systemic therapies have yet to form part of any first-line therapy for chordomas, a number of targeted agents have been evaluated to date that inhibit specific molecules and their respective pathways known to be implicated in chordomas. These include EGFR (erlotinib, gefitinib, lapatinib), PDGFR (imatinib), mTOR (rapamycin), and VEGF (bevacizumab). This article provides an update of the current multimodality treatment of cranial base chordomas, with an emphasis on how current understanding of molecular pathogenesis provides a framework for the development of novel targeted approaches.

• cell lines
• chordomas
• molecular genetics
• radiation therapy
• skull-base neoplasms
• surgery

Retrorectal (also known as presacral) tumor (RT) is a rare disease of retrorectal space. They can be classified as congenital, inflammatory, neurogenic, osseous, or miscellaneous. The most common presentation is an asymptomatic mass discovered on routine rectal examination, but certain nonspecific symptoms can be elicited by careful history and physical examination. The primary and only satisfactory treatment is surgery for RTs. Three approaches commonly used for resection are abdominal, transsacral, or a combined abdominosacral approach. Prognosis is directly related primary local control, which is often difficult to achieve for malignant lesions.

• Retrorectal
• Presacral
• Tumor

• Bone and soft tissue sarcomas
• ErbB receptors
• Prognostic relevance
• Targeted therapy

• Adult
• Antibodies, Monoclonal, Humanized/therapeutic use
• Bevacizumab
• Bone Neoplasms/drug therapy
• Bone Neoplasms/surgery
• Chordoma/drug therapy
• Chordoma/surgery
• Erlotinib Hydrochloride
• Female
• Humans
• Male
• Middle Aged
• Quinazolines/therapeutic use
• Sacrum/surgery
• Skull Neoplasms/drug therapy
• Treatment Outcome

• Base du crâne
• Chordoma
• Chordome
• Diagnosis
• Diagnostic
• Mobile spine
• Prognosis
• Pronostic
• Rachis
• Skull base

• Chordoma
• Metastasis
• Prognostic factors
• Recurrence
• Surgical management
• Survival

Chordomas are rare primary bone tumors that occur along the neuraxis. Primary treatment is surgery, often followed by radiotherapy. Treatment options for patients with recurrence are limited and, notably, there are no FDA approved therapeutic agents. Development of therapeutic options has been limited by the paucity of preclinical model systems. We have established and previously reported the initial characterization of the first patient-derived chordoma xenograft model. In this study, we further characterize this model and demonstrate that it continues to resemble the original patient tumor histologically and immunohistochemically, maintains nuclear expression of brachyury, and is highly concordant with the original patient tumor by whole genome genotyping. Pathway analysis of this xenograft demonstrates activation of epidermal growth factor receptor (EGFR). In vitro studies demonstrate that two small molecule inhibitors of EGFR, erlotinib and gefitinib, inhibit proliferation of the chordoma cell line U-CH 1. We further demonstrate that erlotinib significantly inhibits chordoma growth in vivo. Evaluation of tumors post-treatment reveals that erlotinib reduces phosphorylation of EGFR. This is the first demonstration of antitumor activity in a patient-derived chordoma xenograft model and these findings support further evaluation of EGFR inhibitors in this disease.

• Animals
• Cell Line, Transformed
• Cell Proliferation/drug effects
• Chordoma/drug therapy
• Chordoma/genetics
• Chordoma/metabolism
• Chordoma/pathology
• ErbB Receptors/genetics
• ErbB Receptors/metabolism
• Erlotinib Hydrochloride
• Genome-Wide Association Study
• Heterografts
• Humans
• Mice
• Neoplasm Transplantation
• Protein Kinase Inhibitors/pharmacokinetics
• Quinazolines/pharmacology
• Xenograft Model Antitumor Assays

A 74-year-old man presented with a progressively worsening pain in sacrum and was diagnosed to have a sacral chordoma by biopsy in May, 2004. Percutaneous intratumoral injection with lipiodol-pingyangmycin suspension (LPS) was carried out under image guidance and repeated when the pain in sacrum recurred and the tumor increased. During a 6-year follow-up period, three sessions of this treatment were executed. CT imaging and Karnofsky Performance Score were used to evaluate the size of tumor and quality of life, respectively. The patient was free of pain after each procedure and had a high quality of life with a Karnofsky Performance Score above 80 points. The tumor lesion in sacral area was effectively controlled. No complications were observed. Percutaneous intratumoral injection with LPS under image guidance may be an effective and safe alternative for the patients with sacral chordoma.

• Lipiodol-pingyangmycin suspension
• Percutaneous intratumoral injection
• Sacral chordoma

• Chordomas
• cell lines
• radiation therapy
• review
• skull base neoplasms
• surgery

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.

A ten-year-old male standard dachshund was presented with a history of neck pain and progressive gait disturbances. Following a neurological examination and diagnostic imaging, including CT, a neoplastic lesion involving the third and fourth cervical vertebrae was suspected. The lesion included an extradural mass on the right side of the spinal canal causing a local compression of the cervical cord. Surgery, using a modified dorsal laminectomy procedure, was performed in order to decompress the cervical spinal cord. Histopathological examination of the extradural mass indicated that the tumour was a chondroid chordoma. Following discharge, the quality of life for the dog was very good for a sustained period, but clinical signs recurred at 22 months. The dog was euthanased 25 months post-surgery. On post-mortem examination, a regrowth of neoplastic tissue was found to have infiltrated the bone and spinal cord at C3-C4. This is the first report to show that palliative surgery can offer successful long-lasting treatment of chondroid chordoma of the cervical spine in the dog.