Chordoma Foundation


Understanding Chordoma

Fast Facts

» Location: bones of the skull base and spine
» Types: conventional, chondroid, dedifferentiated
» Incidence: 1 case per million per year
» Average Survival: 7-9 years
» Approved Drugs: none

Overview

Chordoma is a rare type of cancer that occurs in the bones of the skull and spine. It is part of a family of cancers called sarcoma, which include cancers of the bones, cartilage, muscles and other connective tissue.

Chordomas are thought to arise from remnants of the embryonic notochord, a rod-shaped, cartilage-like structure that serves as a scaffold for the formation of the spinal column. Notochord cells normally persist after birth lodged inside the spine and skull, and rarely these cells can undergo a malignant transformation that leads to the formation of a chordoma.

Chordomas are generally slow growing, but are relentless and tend to recur after treatment. Because of their proximity to critical structures such as they spinal cord, brainstem, nerves and arteries, they are difficult to treat and require highly specialized care.

Tumor Location  |  Types of Chordoma  |  Incidence and Prevalence  |  Demographics  |  Risk Factors
Signs and Symptoms  |  Treatment  |  Prognosis and Survival | Further Reading

Tumor Location


Chordomas can occur anywhere along the spine, from the head to the tailbone. The most common locations are in the clivus (a bone in the middle of the head) (32%) and sacrum or coccyx (vertebrae at the bottom of the spine) (29%). Less frequently, chordomas can occur in the cervical (neck), thoracic (upper back), and lumbar (lower-back) vertebrae of the spine.[1] Extremely rare cases of chordoma occurring away from the spine have been reported in the ribs, legs and feet.[2]

Chordomas occurring in the head are sometimes called brain tumors because they grow inside the skull toward the brain, however they do not actually develop from brain cells. Metastasis (spread of tumor to other body parts) occurs in 20-40% of patients with chordomas of the spine [3] [4] and less than 10% of patients with skull-base tumors.[5] The most common sites of distant metastasis are the lungs, liver, bones, and skin. Metastasis usually only occurs when the primary tumor is advanced or uncontrolled and rarely is reported at the time of initial diagnosis.

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Types of Chordoma


There are three histological subtypes of chordoma: conventional (sometimes called classic), chondroid, and dedifferentiated. Chondroid chordomas tend to be less aggressive than conventional chordomas, while dedifferentiated chordomas are more aggressive, faster growing and more likely to metastasize.

Chordomas are sometimes misdiagnosed as chondrosarcomas, and vice versa.[6] Both types of tumor can occur in the same locations and often look similar under a microscope. Chondrosarcomas tend to be more responsive to radiation and have a better prognosis.[6]

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Incidence and Prevalence


The annual incidence of chordoma is approximately one new case per million people per year.[1] That means that roughly 300 patients are diagnosed with chordoma each year in the United States. The incidence in Europe appears to be similar, but is unknown in other continents. Chordomas account for about 3% of all bone tumors and about 20% of primary spinal tumors.[7] Chordomas are the most common tumor of the sacrum and cervical spine.

With an average overall survival of 7-9 years, the number of people living with chordoma (prevalence) is approximately 8 per million, or about 2400 in the United States and 3600 in Europe.

Chordoma is one of many rare cancers which together account for approximately a quarter of all cancer cases.[8] [9]

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Demographics


Chordomas occur in people of all ages, from infants to the elderly. The median age of diagnosis is 49 for skull base chordomas and 69 for sacral chordomas. Skull base chordomas occur more frequently in younger patients, while spinal chordomas are more common later in life. Overall, the ratio of males to females with chordoma is approximately 1.6 to 1. [1]

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Risk Factors


There are no known environmental, dietary or lifestyle risk factors. Several genetic risk factors listed below are associated with chordoma. The National Cancer Institute is conducting a genetics study to identify additional hereditary causes of chordoma.

Brachyury SNP

The vast majority of chordomas are sporadic, meaning that they occur at random, and not as a direct result of an inherited genetic change. However, nearly all patients who develop sporadic chordoma harbor a genetic variant called a SNP in a gene called brachyury [10]. This SNP causes a substantial increase in the risk of developing chordoma, but does not by itself cause chordoma. To use a metaphor, the brachyury SNP loads the gun but something else pulls the trigger. A large fraction of the general population has this SNP but individuals who have the SNP are still very unlikely to develop chordoma. To learn more about the implications of this SNP for chordoma patients and family members, click here.

Brachyury duplication

Very rarely, multiple members of the same family are affected by chordoma, indicating that in some cases a strong genetic predisposition for chordoma can be inherited. Some families with familial chordoma have an extra copy of a gene called brachyury. [11] Currently, there is no available test for the presence of extra copies of the brachyury gene.

Tuberous Sclerosis Complex

Chordomas have been reported at a higher incidence in children with the genetic disease Tuberous Sclerosis Complex (TSC). [12] Changes in either of two genes involved in Tubersous Sclerosis Complex (TSC1 and TSC2) can cause a predisposition to developing chordoma.

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Signs and Symptoms


The most common signs of chordoma are pain and neurological changes. Skull base chordomas most often cause headache, neck pain or double vision. If large enough, they may affect facial sensation or movement, voice, speech, and swallowing function. Chordomas of the spine and sacrum can cause changes in bowel and/or bladder function, pain, aching, tingling, numbness, or weakness of the arms and legs. Often sacral chordomas do not cause symptoms until the tumor is quite large and sometimes a lump is the first sign of a sacral chordoma.[13]

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Treatment


Surgery is the mainstay of treatment for chordomas. The goal of surgery is to remove as much of the tumor as possible without causing unacceptable harm. Complete resection (removing the entire tumor) during the first surgery provides the best chances for local control and long-term survival.[14] [15] Radiation therapy can reduce the risk of recurrence after surgery and prolong survival for chordoma patients. Even after surgery and/or radiation, chordomas tend to return in the same location or in the areas around the original tumor. Many patients undergo multiple surgeries over several years to treat these local recurrences. For patients with advanced or inoperable disease, chemotherapy may slow or temporarily stop the progression of the tumor. Because chordomas are slow growing, standard cytotoxic chemotherapy agents that kill fast-growing cells are generally ineffective. Some chordomas have been reported to respond to molecularly targeted cancer drugs; however, no drugs are currently approved for the treatment of chordoma.

For detailed information about treatment options, see the Treatment section of our website.

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Prognosis and Survival


According to the latest and most comprehensive population-based study, the median overall survival for chordoma patients in the United States is approximately 7 years, and the overall 5, 10 and 20 year survival rates are 68%, 40% and 13%, respectively.[1] Current, unpublished data from the same population-based study presented at the Third International Chordoma Research Workshop, indicates that the median survival is now closer to 9 years. This increase in survival is likely attributable to recent advances in surgery, radiation and imaging techniques.

It is important to realize that the prognosis for each person is different depending on age, size and location of the tumor, histological subtype, method of treatment, extent of resection, and other factors. Only your doctor(s) can advise you about your prognosis and risks.

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Further Reading


The following review articles provide comprehensive information about the diagnosis, treatment, epidemiology and prognostic factors of chordoma.

The following articles and tutorials provide an overview of the basic principles of cancer biology and treatment.

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Reviewed 3/1/2012 by:


The information provided herein is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician with any questions you may have regarding your medical care. Never disregard professional medical advice or delay in seeking it because of something you have read on this Website.

References

  1. M.L. McMaster, A.M. Goldstein, C.M. Bromley, N. Ishibe, and D.M. Parry, "Chordoma: incidence and survival patterns in the United States, 1973-1995.", Cancer causes & control : CCC, 2001. http://www.ncbi.nlm.nih.gov/pubmed/11227920
  2. R. Tirabosco, D.C. Mangham, A.E. Rosenberg, S. Vujovic, K. Bousdras, S. Pizzolitto, G. De Maglio, M.A. den Bakker, L. Di Francesco, R.K. Kalil, N.A. Athanasou, P. O'Donnell, E.F. McCarthy, and A.M. Flanagan, "Brachyury expression in extra-axial skeletal and soft tissue chordomas: a marker that distinguishes chordoma from mixed tumor/myoepithelioma/parachordoma in soft tissue.", The American journal of surgical pathology, 2008. http://www.ncbi.nlm.nih.gov/pubmed/18301055
  3. P. Bergh, L.G. Kindblom, B. Gunterberg, F. Remotti, W. Ryd, and J.M. Meis-Kindblom, "Prognostic factors in chordoma of the sacrum and mobile spine: a study of 39 patients.", Cancer, 2000. http://www.ncbi.nlm.nih.gov/pubmed/10813725
  4. R. Volpe, and A. Mazabraud, "A clinicopathologic review of 25 cases of chordoma (a pleomorphic and metastasizing neoplasm).", The American journal of surgical pathology, 1983. http://www.ncbi.nlm.nih.gov/pubmed/6859391
  5. E. Gay, L.N. Sekhar, E. Rubinstein, D.C. Wright, C. Sen, I.P. Janecka, and C.H. Snyderman, "Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60 patients.", Neurosurgery, 1995. http://www.ncbi.nlm.nih.gov/pubmed/7791978
  6. A.E. Rosenberg, G.P. Nielsen, S.B. Keel, L.G. Renard, M.M. Fitzek, J.E. Munzenrider, and N.J. Liebsch, "Chondrosarcoma of the base of the skull: a clinicopathologic study of 200 cases with emphasis on its distinction from chordoma.", The American journal of surgical pathology, 1999. http://www.ncbi.nlm.nih.gov/pubmed/10555005
  7. S.P. Kelley, R.U. Ashford, A.S. Rao, and R.A. Dickson, "Primary bone tumours of the spine: a 42-year survey from the Leeds Regional Bone Tumour Registry.", European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 2006. http://www.ncbi.nlm.nih.gov/pubmed/16865376
  8. R.T. Greenlee, M.T. Goodman, C.F. Lynch, C.E. Platz, L.A. Havener, and H.L. Howe, "The occurrence of rare cancers in U.S. adults, 1995-2004.", Public health reports (Washington, D.C. : 1974)http://www.ncbi.nlm.nih.gov/pubmed/20402194
  9. G. Gatta, J.M. van der Zwan, P.G. Casali, S. Siesling, A.P. Dei Tos, I. Kunkler, R. Otter, L. Licitra, S. Mallone, A. Tavilla, A. Trama, R. Capocaccia, and . , "Rare cancers are not so rare: the rare cancer burden in Europe.", European journal of cancer (Oxford, England : 1990), 2011. http://www.ncbi.nlm.nih.gov/pubmed/22033323
  10. N. Pillay, V. Plagnol, P.S. Tarpey, S.B. Lobo, N. Presneau, K. Szuhai, D. Halai, F. Berisha, S.R. Cannon, S. Mead, D. Kasperaviciute, J. Palmen, P.J. Talmud, L. Kindblom, M.F. Amary, R. Tirabosco, and A.M. Flanagan, "A common single-nucleotide variant in T is strongly associated with chordoma.", Nature genetics, 2012. http://www.ncbi.nlm.nih.gov/pubmed/23064415
  11. X.R. Yang, D. Ng, D.A. Alcorta, N.J. Liebsch, E. Sheridan, S. Li, A.M. Goldstein, D.M. Parry, and M.J. Kelley, "T (brachyury) gene duplication confers major susceptibility to familial chordoma.", Nature genetics, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19801981
  12. M.L. McMaster, A.M. Goldstein, and D.M. Parry, "Clinical features distinguish childhood chordoma associated with tuberous sclerosis complex (TSC) from chordoma in the general paediatric population.", Journal of medical genetics, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21266383
  13. T.A. Rich, A. Schiller, H.D. Suit, and H.J. Mankin, "Clinical and pathologic review of 48 cases of chordoma.", Cancer, 1985. http://www.ncbi.nlm.nih.gov/pubmed/2408725
  14. S. Di Maio, N. Temkin, D. Ramanathan, and L.N. Sekhar, "Current comprehensive management of cranial base chordomas: 10-year meta-analysis of observational studies.", Journal of neurosurgery, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21819197
  15. D.M. Sciubba, J.J. Cheng, R.J. Petteys, K.L. Weber, D.A. Frassica, and Z.L. Gokaslan, "Chordoma of the sacrum and vertebral bodies.", The Journal of the American Academy of Orthopaedic Surgeons, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19880681
  16. B.P. Walcott, B.V. Nahed, A. Mohyeldin, J. Coumans, K.T. Kahle, and M.J. Ferreira, "Chordoma: current concepts, management, and future directions.", The Lancet. Oncology, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22300861
  17. R.J. Diaz, and M.D. Cusimano, "The biological basis for modern treatment of chordoma.", Journal of neuro-oncology, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21384217
  18. M. Koutourousiou, C.H. Snyderman, J. Fernandez-Miranda, and P.A. Gardner, "Skull base chordomas.", Otolaryngologic clinics of North America, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21978899
  19. D. Hanahan, and R.A. Weinberg, "Hallmarks of cancer: the next generation.", Cell, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21376230