Management Of Chordomas Research Articles

Chordoma Management: A Review of the Literature

Chordoma is an uncommon bone neoplasm. Despite being considered a low-grade or benign bone tumor because of its histology, it is aggressive and locally invasive. It has a poor prognosis because it has a high rate of recurrence and is likely to be malignant. Chordoma is usually recurrent. Although its histology is considered a low-grade tumor or benign tumor, its behaviour of recurrence leads to a poor prognosis and higher likelihood of malignant tumors occurring. Chordoma is believed to emerge from transformed remnants of notochord and appears to favor the axial bone. The most commonly affected parts of chordoma are at the sacrum, vertebra, and skull base. The present gold standard for management of chordoma is a wide surgical resection. This article highlights recent practices and future directions for treatment. Keywords : chordoma, recurrent chordoma, treatment of chordoma DOI: 10.31524/bkkmedj.2019.02.019

Extended endoscopic endonasal surgery for clival chordoma and chondrosarcoma: Our experience in 14 cases

ObjectiveTo report our experience in the management of chordoma and chondrosarcoma with extended endoscopic endonasal surgery. MethodWe performed a retrospective analysis of a series of 14 patients with clival chordoma or chondrosarcoma who had extended endoscopic endonasal surgery from 2008 to 2016 performed by the same multidisciplinary team. ResultsWe had fourteen patients (male/female 2:1), with a mean age of 49 years for chordoma and 32 for chondrosarcoma. The most common clinical presentation was diplopia in 78.5% of cases, followed by dysphagia in 28.6%. Histologically, 71.4% were chordomas and 28.6% were chondrosarcomas. In addition, invasion of at least two-thirds or more of the clivus was found in 81% of the cases; in 57.1% there was intradural invasion, and in 35.7% invasion of the sella turcica. In 42.8% of cases, the degree of resection was total and in 21.5% subtotal. The most common complication was CSF fistula, occurring in 28.6% of the cases, with only one case requiring surgery to repair it. Adjuvant treatment with Proton Beam was performed in 35.7% of cases and with conventional radiotherapy in 21.5%. Mean follow-up was 53.5 months and tumour recurrence or progression was found in 21.5% of the cases, two of which had not received adjuvant treatment. There were no deaths. ConclusionThe extended endoscopic endonasal approach (EEEA) performed by an experienced team is a good alternative for the management of these lesions. Intradural invasion may be related to an increased risk of complications and worse clinical presentation, in addition to a lower rate of total resection.

Tumour Volume and Dose Influence Outcome after Surgery and High-dose Photon Radiotherapy for Chordoma and Chondrosarcoma of the Skull Base and Spine

AimsTo evaluate the long-term outcomes of patients with chordoma and low-grade chondrosarcoma after surgery and high-dose radiotherapy. Materials and methodsHigh-dose photon radiotherapy was delivered to 28 patients at the Neuro-oncology Unit at Addenbrooke's Hospital (Cambridge, UK) between 1996 and 2016. Twenty-four patients were treated with curative intent, 17 with chordoma, seven with low-grade chondrosarcoma, with a median dose of 65 Gy (range 65–70 Gy). Local control and survival rates were calculated using the Kaplan–Meier method. ResultsThe median follow-up was 83 months (range 7–205 months). The 5 year disease-specific survival for chordoma patients treated with radical intent was 85%; the local control rate was 74%. The 5 year disease-specific survival for chondrosarcoma patients treated with radical intent was 100%; the local control rate was 83%. The mean planning target volume (PTV) was 274.6 ml (median 124.7 ml). A PTV of 110 ml or less was a good predictor of local control, with 100% sensitivity and 63% specificity. For patients treated with radical intent, this threshold of 110 ml or less for the PTV revealed a statistically significant difference when comparing local control with disease recurrence (P = 0.019, Fisher's exact test). Our data also suggest that the probability of disease control may be partly related to both target volume and radiotherapy dose. ConclusionOur results show that refined high-dose photon radiotherapy, following tumour resection by a specialist surgical team, is effective in the long-term control of chordoma and low-grade chondrosarcoma, even in the presence of metal reconstruction. The results presented here will provide a useful source for comparison between high-dose photon therapy and proton beam therapy in a UK setting, in order to establish best practice for the management of chordoma and low-grade chondrosarcoma.

The top 50 cited articles on chordomas.

Chordomas are rare malignant primary tumors of the spine. In the mobile spine and sacrum an en-bloc resection is associated with decreased rates of recurrence. Our objective was to identify the top cited articles in chordoma research and to further analyze characteristics of these articles. In March 2017, we used ISI Web of Science (v5.11, Thomas Reuter, Philadelphia, Pennsylvania, USA) to search for the following key word: "chordoma". Articles were searched from 1900 to 2017. Articles were ranked based on number of citations. The results were evaluated to determine articles most clinically relevant to the management of chordomas. The top 50 articles that met the search criteria were further characterized on the basis of: title, author, citation density, journal of publication, year (and decade) of publication, institution and country of origin and paper topic. A total of 1,043 articles matched the search criteria. The most influential 50 articles were cited 65 to 290 times. The articles were published between 1926 and 2012, and all articles were published in English. Thirty-three publications (66%) originated from the United States and seven (14%) from Italy. Cancer accounted for the most frequent (n=9) destination journal followed by Journal of Bone and Joint Surgery (n=4). A total of 41 institutions contributed to the top 50 articles. The most common article types were: clinical 44% (n=22), papers that combined clinical and pathology findings 18% (n=9) and basic science research 14% (n=7). The top 50 cited articles on chordomas are predominantly clinical papers, arising from the United States and most frequently published in Cancer and Journal of Bone and Joint Surgery.

Long-Term Results Following Surgical Resection of Chordomas in the Craniocervical Junction and the Upper Cervical Spine: Review of 12 Consecutive Cases.

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. To analyze long-term surgical results of cervical chordomas. 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. 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. Gross total intralesional piecemeal resection with perioperative radiation therapy is an acceptable strategy for CCJ and the upper cervical chordoma management.

Management of Chordoma and Chondrosarcoma with Fractionated Stereotactic Radiotherapy.

To evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) for chordoma and chondrosarcoma. Twenty consecutive patients with a histopathologic diagnosis of chordoma (n = 16) or chondrosarcoma (n = 4) treated between 2010 and 2016 were retrospectively identified. All patients underwent FSRT in five fractions to a median dose of 37.5 Gy (range: 25-40 Gy) and followed with serial magnetic resonance imaging. Overall survival (OS), local recurrence-free survival (LRFS), and event-free survival (EFS) were estimated using the Kaplan-Meier method. With a median follow-up of 28 months after FSRT and 40 months after initial surgery, crude OS and LRFS were 90%. Nine patients (45%) reported grade 1-3 acute toxicity, and two patients (10%) experienced grade 4, 5 late toxicity. One patient previously treated with proton therapy died from radiation vasculopathy 9 months after FSRT. The use of FSRT for recurrent disease or in patients with prior radiation therapy was associated with significantly decreased EFS. FSRT for chordoma and chondrosarcoma is associated with high rates of OS and local control. Although many patients experience acute toxicity, there is a low incidence of late toxicity or irreversible treatment related morbidity despite the frequency of prior radiotherapy in this population. FSRT is an effective adjuvant or salvage treatment for chordoma and chondrosarcoma.

(P017) Management of Chordoma and Chondrosarcoma With Fractionated Stereotactic Radiotherapy

(P017) Management of Chordoma and Chondrosarcoma With Fractionated Stereotactic Radiotherapy

Management of Chordoma in a Tertiary Hospital in Hong Kong

Management of Chordoma in a Tertiary Hospital in Hong Kong

Extended maxillotomy for skull base access in contemporary management of chordomas: Rationale and technical aspect

Minimally invasive approaches to the central skull base have been popularized over the last decade and have to a large extent displaced ‘open’ procedures. However, traditional skull base surgery still has its role especially when dealing with a large clival chordoma where maximal surgical resection is the principal goal to maximize patient survival. In this paper, we present a case of a 25year-old male patient with chordoma in the inferior clivus which was initially debulked via a transnasal endoscopic approach. He unfortunately had a large recurrence of tumor requiring re-do resection. With the aim to achieve maximal surgical resection, we then chose the technique of a transoral approach with Le Fort 1 maxillotomy and midline palatal split. Post-operative course for the patient was uneventful and post-operative MRI confirmed significant debulking of the clival lesion. The technique employed for the surgical procedure is presented here in detail as is our experience over two decades using this technique for tumors, inflammatory lesions and congenital abnormalities at the cranio-cervical junction.

An Atypical Presentation of Chordoma: Case Report and Review

Chordoma is a rare, slow-growing but locally aggressive malignant tumour for which little improvement in outcome has been reported. The management of chordoma is controversial and challenging because of their location and often large size at presentation. We report the case of a 57 year old male with radicular compression associated with an L3 chordoma that was successfully treated with a wide excision which responded well to postoperative radiotherapy. Its rare occurrence precludes controlled studies of chordoma; therefore, any response merits reporting.

Clival Chordoma Management: A Single Centre Experience

Clival chordomas are a rare and difficult to manage disease. There is little consensus on the optimum surgical management and adjuvant therapy. A variety of surgical approaches have been suggested in the literature, and endoscopic approaches have gained popularity in recent years.

Contemporary management of clival chordomas.

Clival chordomas are rare malignant tumors associated with a poor prognosis. In this article, we review the current literature to identify a variety of strategies that provide guidelines toward the optimal management for this aggressive tumor. Molecular disease, particularly, the development of characterized chordoma cell lines, has become one of the new cornerstones for the histological diagnosis of chordomas and for the development of effective chemotherapeutic agents against this tumor. Brachyury, a transcription factor in notochord development, seems to provide an excellent diagnostic marker for chordoma and may also prove to be a valuable target for chordoma therapy. Aggressive cytoreductive surgery aiming for gross total resection with maintenance of key neurovascular structures, followed by proton beam or hadron radiation, provides the best local recurrence and overall survival rates. Clival chordomas are locally aggressive tumors that are challenging to treat because of their unique biology, proximity to key neurovascular structures and poor prognosis. Currently, chordomas are optimally managed with aggressive surgery, whilst preserving key structures, and postoperative radiation in a multidisciplinary setting with an experienced team. The advancement of molecular techniques offers exciting future diagnostic and therapeutic options in the management of chordomas.

Genomic and epigenetic instability in chordoma: current insights

Genomic and epigenetic instability in chordoma: current insights Yong Feng,1,2 Jacson K Shen,1,3 Francis J Hornicek,1,3 Zhenfeng Duan1,3 1Department of Orthopedic Surgery, Massachusetts General Hospital, Boston, MA, USA; 2Department of Orthopedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, MA, USA Abstract: Chordoma is a malignant bone tumor, which currently can only be defined by histologic and immunohistochemical criteria. There are no prognostic biomarkers to predict the clinical outcome or response to treatment yet. Currently, chordoma pathogenesis is very poorly understood; however, recent large-scale genetic and epigenetic studies have identified some of the underlying mechanisms and pathways that may contribute to the disease. In this review, we summarize the most recent findings in the field of chordoma genomics and epigenomics, from comparative genomic hybridization to evaluate chromosomal alteration, large-scale deoxyribonucleic acid (DNA) sequencing to determine the gene mutation, microarray to access messenger ribonucleic acid (RNA) and microRNA gene expression, and DNA-methylation profiling. These studies may also hold valuable clinical potential in the management of chordoma. Keywords: chordoma, chromosomal alterations, sequencing, miRNA, DNA methylation

Surgical management of primary tumors of the cervical spine: surgical considerations and avoidance of complications

Objective:Primary cervical spinal tumors are rare tumors of the spine and are associated with significant morbidity and mortality. Such tumors include multiple myeloma, chordomas, giant cell tumors, hemangiomas, osteosarcomas, chondrosarcomas, synovial sarcomas, aneurysmal bone cysts (ABC), hemangiomas, eosinophilic granulomas, osteoid osteomas, and osteoblastomas. We review the surgical decision-making process and identify critical key steps for surgical complication avoidance. We also present case illustrations demonstrating such pathological diagnoses and surgical treatments performed.Methods:We retrospectively review the literature regarding the most common primary cervical spinal tumors that have undergone surgical resection with or without adjuvant treatment.Results:En bloc resection of primary cervical tumors resulted in significantly increased progression-free survival and overall survival. From the limited data, adjuvant treatment with proton-beam therapy for chordomas has potential benefit. Neo-adjuvant chemotherapy for Ewing’s sarcoma and osteogenic sarcoma has shown some promise, with en bloc resection demonstrating stronger benefit for osteogenic sarcoma.Discussion:En bloc resection for primary spinal tumors has proven to be the standard of care in spinal oncology. Adjuvant and neo-adjuvant treatments such as chemotherapy and radiotherapy variants (conventional, proton beam, cyberknife) need to be studied further in most primary tumor types to become standard of care. Chordoma management is more widely studied with en bloc resection and adjuvant proton-beam therapy demonstrating improved progression-free survival and overall survival. Surgical management and adjuvant treatment strategies are case dependent, depending on tumor histology, patient neurological examination, prior surgeries at that level, and prior adjuvant treatment.

Preliminary Results of High-Dose Single-Fraction Radiotherapy for the Management of Chordomas of the Spine and Sacrum

En bloc wide-margin excision significantly decreases the risk of chordoma recurrence. However, a wide surgical margin cannot be obtained in many chordomas because they arise primarily in the sacrum, clivus, and mobile spine. Furthermore, these tumors have shown resistance to fractionated photon radiation at conventional doses and numerous chemotherapies. To analyze the outcomes of single-fraction stereotactic radiosurgery (SRS) in the treatment of chordomas of the mobile spine and sacrum. Twenty-four patients with chordoma of the sacrum and mobile spine were treated with high-dose single-fraction SRS (median dose, 2400 cGy). Twenty-one primary and 3 metastatic tumors were treated. Seven patients were treated for postoperative tumor recurrence. In 7 patients, SRS was administered as planned adjuvant therapy, and in 13 patients, SRS was administered as neoadjuvant therapy. All patients had serial magnetic resonance imaging follow-up. The overall median follow-up was 24 months. Of the 24 patients, 23 (95%) demonstrated stable or reduced tumor burden based on serial magnetic resonance imaging. One patient had radiographic progression of tumor 11 months after SRS. Only 6 of 13 patients who underwent neoadjuvant SRS proceeded to surgery. This decision was based on the lack of radiographic progression and the patient's preference. Complications were limited to 1 patient in whom sciatic neuropathy developed and 1 with vocal cord paralysis. High-dose single-fraction SRS provides good tumor control with low treatment-related morbidity. Additional follow-up is required to determine the long-term recurrence risk.

Diagnosis and Treatment of Chordoma

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.

Bone Cancer

Primary bone cancers are extremely rare neoplasms, accounting for fewer than 0.2% of all cancers. The evaluation and treatment of patients with bone cancers requires a multidisciplinary team of physicians, including musculoskeletal, medical, and radiation oncologists, and surgeons and radiologists with demonstrated expertise in the management of these tumors. Long-term surveillance and follow-up are necessary for the management of treatment late effects related to surgery, radiation therapy, and chemotherapy. These guidelines discuss the management of chordoma, giant cell tumor of the bone, and osteosarcoma.

Current Concepts on the Management of Chordoma

Current Concepts on the Management of Chordoma

High-dose Radiation Therapy After Surgical Resection for the Management of Chordoma of the Skull Base: Early Clinical Experience With Helical Tomotherapy

High-dose Radiation Therapy After Surgical Resection for the Management of Chordoma of the Skull Base: Early Clinical Experience With Helical Tomotherapy

Abstract 2418: Establishment and characterization of a primary chordoma xenograft

Abstract Chordomas are slow growing, malignant cancers believed to originate from notochord remnants. Chordoma accounts for 1% of cancers of the central nervous system with an annual incidence of 0.08 cases per 100,000 individuals. There are 3 different histologic subtypes- classic chordoma, chondroid chordoma, and dedifferentiated chordoma. Chordomas are characterized by the presence of physaliphorous cells with vacuolated cytoplasm and high expression of the transcription factor T Brachury. Management of chordoma is primarily surgical – chemotherapy and radiation therapy have limited effect. The development of effective treatments for this tumor is hampered by the lack of adequate animal models. We report here the establishment of the first primary xenograft model of chordoma. Tumor excised from a patient diagnosed with classic chordoma was implanted adjacent to the right proximal tibia in a NOD/SCID/IL2Rγ (null) mouse. The resulting tumor has been serially transplanted at least 10 times with no diminution in growth rate over time. Histologically, the xenograft does not appear to be a classic chordoma; interestingly, the patient from whom the xenograft was derived relapsed with a dedifferentiated morphology. To confirm the identity of the tumor xenograft, T brachyury expression was demonstrated by immunohistochemistry and PCR. We have begun to characterize this xenograft by gene expression profiling and comparative genomic hybridization. Expression profiling results were verified by RT-PCR. Cells isolated from xenografts were analyzed by the Aldefluor assay to assess the levels of expression of aldehyde dehydrogenase activity. A cell line was generated from this xenograft as well and is being characterized. In summary, we report here the establishment of the first primary chordoma xenograft. Initial molecular characterization of the xenograft and a cell line derived from this tumor is ongoing. These tools will shed valuable light on the pathophysiology of this rare tumor and allow the preclinical development of novel treatment strategies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2418. doi:10.1158/1538-7445.AM2011-2418