Chordoma Explained

Chordoma should not be confused with Chondroma.

Chordoma

Chordoma is a rare slow-growing neoplasm thought to arise from cellular remnants of the notochord. The evidence for this is the location of the tumors (along the neuraxis), the similar immunohistochemical staining patterns, and the demonstration that notochordal cells are preferentially left behind in the clivus and sacrococcygeal regions when the remainder of the notochord regresses during fetal life.

In layman's terms, chordoma is a type of spinal cancer.[1]

Presentation

Chordomas can arise from bone in the skull base and anywhere along the spine. The two most common locations are cranially at the clivus and in the sacrum at the bottom of the spine.[2]

Sacral chordoma is presented with chronic low back pain.

Genetics

A small number of families have been reported in which multiple relatives have been affected by chordoma. In four of these families, duplication of the brachyury gene was found to be responsible for causing chordoma.[3]

A possible association with tuberous sclerosis complex (TSC1 or TSC2) has been suggested.[4]

Mechanism

Diagnosis

In 2015 the first consensus guidelines for the diagnosis and treatment of chordoma were published in The Lancet Oncology.[12] These tumors express brachyury and cytokeratin, which can be detected by immunohistochemistry.

Classification

There are three histological variants of chordoma: conventional,[13] chondroid and dedifferentiated.

Treatment

In most cases, complete surgical resection followed by radiation therapy offers the best chance of long-term control.[14] Incomplete resection of the primary tumor makes controlling the disease more difficult and increases the odds of recurrence. The decision whether complete or incomplete surgery should be performed primarily depends on the anatomical location of the tumor and its proximity to vital parts of the central nervous system.

Chordomas are relatively radioresistant, requiring high doses of radiation to be controlled. The proximity of chordomas to vital neurological structures such as the brain stem and nerves limits the dose of radiation that can safely be delivered. Therefore, highly focused radiation such as proton therapy and carbon ion therapy are more effective than conventional x-ray radiation.[15]

There are no drugs currently approved to treat chordoma; however, several have shown modest benefit in clinical trials, such as the following:

Prognosis

In one study, the 10-year tumor free survival rate for sacral chordoma was 46%.[20] Chondroid chordomas appear to have a more indolent clinical course.

Epidemiology

In the United States, the annual incidence of chordoma is approximately 1 in one million (300 new patients each year).[21]

Sacral chordomas make up 2 to 4% of all primary bone tumours and 44% of all primary sacral tumours, thus making it the most common malignant sacral tumour. About 50 to 60% of chordomas are located in the sacrococcygeal region. Males aged between 40 and 50 years are twice as likely as women to get sacral chordoma.[22]

There are currently no known environmental risk factors for chordoma. As noted above germline duplication of brachyury has been identified as a major susceptibility mechanism in several chordoma families.[23]

While most people with chordoma have no other family members with the disease, rare occurrences of multiple cases within families have been documented. This suggests that some people may be genetically predisposed to develop chordoma. Because genetic or hereditary risk factors for chordoma may exist, scientists at the National Cancer Institute are conducting a Familial Chordoma Study to search for genes involved in the development of this tumor.[24]

Society

Expert Recommendations for the Diagnosis and Treatment of Chordoma is a handbook produced by the Chordoma Foundation, that summarizes recommendations developed by a group of over 40 leading doctors who specialize in caring for chordoma patients. It is available electronically in English, Chinese, Italian, Dutch, and Spanish and hardcopies are available in English and Spanish.[25]

Notable cases

NFL player Craig Heyward was treated for a chordoma in 1998, which ended his career. While initially thought to be successfully removed, the tumor returned in 2005, and caused Heyward's death in May 2006.

Pro skateboarder Ray Underhill, a member of the Powell-Peralta Bones Brigade, battled chordoma for two years before succumbing to his disease in August 2008.

Cary Tennis, the popular advice columnist for Salon, announced in his column of November 19, 2009, that he had been diagnosed with a chordoma.

Former Spanish footballer José Enrique was diagnosed with chordoma in May 2018 and underwent surgery to remove the tumour in June of that year. He announced in April 2019 that he had been given the all clear.

Gary Sinise's son, McCanna "Mac" Anthony Sinise, who was a musician, died on January 5, 2024 at the age of 33 from chordoma. He had been diagnosed with chordoma in 2018 and eventually became paralyzed from the waist down.[26]

External links

Notes and References

  1. Web site: Chordoma. National Cancer Institute. National Cancer Institute. February 27, 2019.
  2. Web site: Primary Malignant Bone Tumors: Tumors of Bones and Joints: Merck Manual Professional . 2009-01-04.
  3. Chordoma: current concepts, management, and future directions. . 2012 . 22300861 . 10.1016/S1470-2045(11)70337-0 . 13 . 2 . Lancet Oncol . e69–76 . Walcott BP, Nahed BV, Mohyeldin A, Coumans JV, Kahle KT, Ferreira MJ.
  4. Lee-Jones L, Aligianis I, Davies PA . Sacrococcygeal chordomas in patients with tuberous sclerosis complex show somatic loss of TSC1 or TSC2 . Genes Chromosomes Cancer . 41 . 1 . 80–5 . September 2004 . 15236319 . 10.1002/gcc.20052. 13136963 . etal.
  5. Han S, Polizzano C, Nielsen GP, Hornicek FJ, Rosenberg AE, Ramesh V . Aberrant Hyperactivation of Akt and Mammalian Target of Rapamycin Complex 1 Signaling in Sporadic Chordomas . Clinical Cancer Research . March 2009 . 19276265 . 15 . 6 . 1940–6 . 10.1158/1078-0432.CCR-08-2364 . 2701205 .
  6. Presneau N, Shalaby A, Idowu B, Gikas P, Cannon SR, Gout I, Diss T, Tirabosco R, Flanagan AM . Potential therapeutic targets for chordoma: PI3K/AKT/TSC1/TSC2/mTOR pathway . British Journal of Cancer . May 2009 . 19401700 . 100 . 9 . 1406–14 . 10.1038/sj.bjc.6605019 . 2694420 .
  7. Fasig JH, Dupont WD, LaFleur BJ, Olson SJ, Cates JM . Immunohistochemical analysis of receptor tyrosine kinase signal transduction activity in chordoma. . Neuropathology and Applied Neurobiology . February 2008 . 17973908 . 34 . 1 . 95–104 . 10.1111/j.1365-2990.2007.00873.x . 22858447 .
  8. Hallor KH, Staaf J, Jönsson G, Heidenblad M, Vult von Steyern F, Bauer HC, Ijszenga M, Hogendoorn PC, Mandahl N, Szuhai K, Mertens F . Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation. . British Journal of Cancer . January 2008 . 18071362 . 98 . 2 . 434–42 . 10.1038/sj.bjc.6604130 . 2361468 .
  9. Schwab JH, Boland PJ, Agaram NP, Socci ND, Guo T, O'Toole GC, Wang X, Ostroumov E, Hunter CJ, Block JA, Doty S, Ferrone S, Healey JH, Antonescu CR . Chordoma and chondrosarcoma gene profile: implications for immunotherapy. . Cancer Immunology, Immunotherapy . March 2009 . 18641983 . 58 . 3 . 339–49 . 10.1007/s00262-008-0557-7 . 3426285.
  10. Web site: Gene Duplication Identified in an Uncommon Form of Bone Cancer . 2009 . 2009-10-09 . https://web.archive.org/web/20091009093559/http://www.nih.gov/news/health/oct2009/nci-04.htm . 2009-10-09 . dead .
  11. Familial Chordoma: a case report and review of the literature. Oncology Letters. 10. 5. Wang. Ke. Zhen. Wu. November 2015. Oncology Letters 10(5). 2937–2940. 4665336. Tian. Kaibing. Hao. Shuyu. Zhang. Liwei. Zhang. Junting. 26722267. 10.3892/ol.2015.3687.
  12. Web site: First clinical guidelines for chordoma treatment published in The Lancet Oncology. 2015-02-19.
  13. Chugh R, Tawbi H, Lucas DR, Biermann JS, Schuetze SM, Baker LH . Chordoma: the nonsarcoma primary bone tumor . The Oncologist . 12 . 11 . 1344–50 . November 2007 . 18055855 . 10.1634/theoncologist.12-11-1344 . 2027.42/139965 . 34916915 . free .
  14. Park L, Delaney TF, Liebsch NJ, Hornicek FJ, Goldberg S, Mankin H, Rosenberg AE, Rosenthal DI, Suit HD . Sacral chordomas: Impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor.. 16757128 . 10.1016/j.ijrobp.2006.02.059 . 65 . 2006 . Int J Radiat Oncol Biol Phys . 5 . 1514–21.
  15. Delaney TF, Liebsch NJ, Pedlow FX, Adams J, Dean S, Yeap BY, McManus P, Rosenberg AE, Nielsen GP, Harmon DC, Spiro IJ, Raskin KA, Suit HD, Yoon SS, Hornicek FJ . Sacral chordomas: Phase II Study of High-Dose Photon/Proton Radiotherapy in the Management of Spine Sarcomas.. 19095372 . 10.1016/j.ijrobp.2008.08.058 . 74 . 2734911 . 2009 . Int J Radiat Oncol Biol Phys . 3 . 732–9.
  16. Kesari . Santosh . Wagle . Naveed . Carrillo . Jose A. . Sharma . Akanksha . Nguyen . Minhdan . Truong . Judy . Gill . Jaya M. . Nersesian . Raffi . Nomura . Natsuko . Rahbarlayegh . Elnaz . Barkhoudarian . Garni . Sivakumar . Walavan . Kelly . Daniel F. . Krauss . Howard . Bustos . Matias A. . 2023-12-04 . Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma . Clinical Cancer Research. 30 . 2 . OF1–OF11 . 10.1158/1078-0432.CCR-23-2317 . 1557-3265 . 38047868. 265606784 .
  17. Blay . Jean-Yves . Chevret . Sylvie . Le Cesne . Axel . Brahmi . Mehdi . Penel . Nicolas . Cousin . Sophie . Bertucci . Francois . Bompas . Emmanuelle . Ryckewaert . Thomas . Soibinet . Pauline . Boudou-Rouquette . Pascaline . Saada Bouzid . Esma . Soulie . Patrick . Valentin . Thibaud . Lotz . Jean-Pierre . August 2023 . Pembrolizumab in patients with rare and ultra-rare sarcomas (AcSé Pembrolizumab): analysis of a subgroup from a non-randomised, open-label, phase 2, basket trial . The Lancet. Oncology . 24 . 8 . 892–902 . 10.1016/S1470-2045(23)00282-6 . 1474-5488 . 37429302. 259576882 .
  18. Liu . Chao . Jia . Qi . Wei . Haifeng . Yang . Xinghai . Liu . Tielong . Zhao . Jian . Ling . Yan . Wang . Chenguang . Yu . Hongyu . Li . Zhenxi . Jiao . Jian . Wu . Zhipeng . Yang . Cheng . Xiao . Jianru . September 2020 . Apatinib in patients with advanced chordoma: a single-arm, single-centre, phase 2 study . The Lancet. Oncology . 21 . 9 . 1244–1252 . 10.1016/S1470-2045(20)30466-6 . 1474-5488 . 32888455. 221503024 .
  19. Stacchiotti . Silvia . Longhi . Alessandra . Ferraresi . Virginia . Grignani . Giovanni . Comandone . Alessandro . Stupp . Roger . Bertuzzi . Alexia . Tamborini . Elena . Pilotti . Silvana . Messina . Antonella . Spreafico . Carlo . Gronchi . Alessandro . Amore . Paola . Vinaccia . Vincenza . Casali . Paolo Giovanni . 2012-03-20 . Phase II study of imatinib in advanced chordoma . Journal of Clinical Oncology. 30 . 9 . 914–920 . 10.1200/JCO.2011.35.3656 . 1527-7755 . 22331945. free .
  20. Fuchs B, Dickey ID, Yaszemski MJ, Inwards CY, Sim FH . Operative management of sacral chordoma . The Journal of Bone and Joint Surgery. American Volume . 87 . 10 . 2211–6 . 2005 . 16203885 . 10.2106/JBJS.D.02693.
  21. Web site: College student fights his own cancer - Yahoo! News . 2008-02-20 . https://web.archive.org/web/20080226003647/http://news.yahoo.com/s/ap/20080220/ap_on_re_us/fight_of_his_life . 2008-02-26 . dead .
  22. Senne J, Nguyen V, Staner D, Stensby JD, Bhat AP . Demystifying Sacral Masses: A Pictorial Review . The Indian Journal of Radiology & Imaging . 31 . 1 . 185–192 . January 2021 . 34316126 . 8299490 . 10.1055/s-0041-1729766 .
  23. Familial Chordoma Study of the T Gene . 24990759 . 10.1007/s00439-014-1463-z . 133 . 10 . Kelley MJ, Shi J, Ballew B, Hyland PL, Li WQ, Rotunno M, Alcorta DA, Liebsch NJ, Mitchell J, Bass S, Roberson D, Boland J, Cullen M, He J, Burdette L, Yeager M, Chanock SJ, Parry DM, Goldstein AM, Yang XR. Hum Genet . 1289–97. 2014 . 6938388 .
  24. Web site: Familial Chordoma Study . 2009-02-03 . https://web.archive.org/web/20090214001902/http://www.cancer.gov/clinicaltrials/ft-NCI-78-C-0039 . 2009-02-14 . dead .
  25. Expert Recommendations for the Diagnosis and Treatment of Chordoma
  26. Web site: February 27, 2024 . Gary Sinise's Son McCanna Dead at 33 After Rare Cancer Battle . February 27, 2024 . ET Online.com . EN . February 27, 2024 . https://web.archive.org/web/20240227213644/https://www.etonline.com/gary-sinises-son-mccanna-dead-at-33-after-rare-cancer-battle-220570 . live .

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