- Case report
- Open Access
- Open Peer Review
Chordoma: a case series and review of the literature
© The Author(s). 2018
- Received: 5 April 2018
- Accepted: 24 July 2018
- Published: 27 August 2018
Chordoma is a rare malignant tumor of the skull base and axial skeleton, with an incidence of less than 0.1/100,000 per year. Patients with advanced chordoma have a poor prognosis due to locoregional recurrence with infiltration and destruction of surrounding bone and soft tissue. Cytotoxic chemotherapy or other systemic therapies have not been proven to be effective for these diseases. Therefore, several molecularly targeted therapies have been proposed as potentially beneficial, including tyrosine kinase inhibitors such as imatinib, sorafenib, lapatinib, and others.
We present three cases of advanced chordoma treated with molecular targeted therapies: a 52-year-old Caucasian man, a 72-year-old Caucasian woman, and a 38-year-old Caucasian woman.
Chordoma has few systemic treatment options and they have limited benefit. Randomized trials with large patient numbers are unfeasible in this rare disease. Targeted therapy might be a reasonable alternative treatment for chordoma. Still, new treatment strategies are needed for this rare disease.
- Advanced chordoma
- Tyrosine kinases
- Rare disease
- Targeted therapy
Overview of patients
Prior local treatment
First-line systemic tx
Second-line systemic tx
Imatinib 400 mg 
Best supportive care
PD 16 months
Sunitinib 37.5 mg 
SD 20 months
Imatinib 400 mg 
Sunitinib 37.5 mg 
Imatinib PD 25 months
Sunitinib PD 6 months
Laboratory findings of cases
Bilirubin total (mg/dl)
A 72-year-old Caucasian woman who had type 2 diabetes and hypertension presented with diplopia in February 2010. Her vital signs were abnormal. Her blood pressure was high (150/95 mmHg), and her pulse rate and temperature were 65/minute and 37.1 °C. A neurological examination showed preserved muscular and neurological function and no signs of paresthesia or hypoesthesia; a general examination showed no other abnormality. There was no significant family or psychosocial history. She was taking perindopril 10 mg/day, metformin 2000 mg/day, and nateglinide 360 mg/day. She was a housewife and lived with her husband in a small town. She never smoked tobacco and did not consume alcohol. A brain and sella MRI showed a 3 cm x 2 cm x 2 cm mass in the sellar and parasellar region. She was operated on via transsphenoidal surgery. A postoperative pathology examination revealed chordoma. After the surgery, gamma-knife radiotherapy was performed. She came back in March 2014 and a 12 mm × 30 mm clivus mass was revealed on her brain MRI. She was operated on again and a pathology examination revealed chordoma. Postoperative stereotactic radiotherapy to residual mass in her clivus at a total dose of 12 Gray in one fraction with gamma-knife was done. Two years later, she had a recurrent mass in her clivus. As neither further surgery nor radiotherapy were suitable for her, sunitinib 37.5 mg per day was started in April 2016 and she has been receiving the same treatment ever since. The laboratory results are given in Table 2. She reported intermittent grade 1 nausea and grade 1 fatigue; no serious side effects were reported. The best response to sunitinib treatment was assessed as stable disease. In June 2018, she continues with the same dose of treatment. There is no detected progression of her disease.
We presented three patients whose tumor progressed after local treatment and who then received systemic tyrosine kinase treatment. Systemic tyrosine kinase treatment plays an important role in the treatment of recurrent chordoma. The tumors of cases 1 and 3 progressed during the treatment. Case 2 continues to be treated with sunitinib. The best radiological response was evaluated as stable disease. No radiological regression response was detected according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria. All of the patients reported no significant side effects during treatment. Treatment was well tolerated.
Chordoma is a primary bone tumor originating from a non-differentiated notochordal residue and developed in the vertebrae; it is most frequently seen in sacral (50%), skull base (30%) and mobile spine (20%) . The pathogenesis of chordoma is unclear but tumor cells are characterized by a notochordal differentiation. Chordoma is more frequent in men than in women. The average age at diagnosis is approximately 60 years, while the skull base presentation affects teenagers and children. Three subtypes have been described as pathological. The classical form and chondroid form are generally low grade and locally aggressive tumors, but the dedifferentiated form shows aggressive behavior . Stacchiotti and Sommer published the first guidelines for the diagnosis and treatment of chordoma in 2015 . Complete surgical resection with negative surgical margin in localized disease is the mainstay of care. Standard adjuvant radiotherapy is recommended for cervical spine and skull base chordoma. Definitive radiotherapy is the option in cases where resection is not suitable. Radiotherapy is recommended after R1 resected sacral chordomas. On the other hand, another retrospective study showed that local progression-free time is longer with the addition of radiotherapy . Ten-year local progression-free survival (PFS) was 35-50% in patients with sacral chordoma who treated by adjuvant radiotherapy . Twenty-nine patients with chordomas of the mobile spine and sacrum who were treated by surgery and high-dose proton−/photon irradiation were evaluated in a phase II trial . In this trial, no significant difference between R0 and R1/R2/biopsy could be shown regarding local control . Retrospective data of 17 patients compared surgery only with carbon ion therapy. The local recurrence-free survival rate at 5 years was 62.5% for the surgery group and 100% for the carbon ion radiotherapy group, and the disease-specific survival rate at 5 years was 85.7% and 53.3%, respectively . Metastases can occur in 30–40% of the patients and that usually occurs after local relapse and at a later stage of the disease .
Survival data with prospective phase 2 trials and retrospective series
We presented three cases of advanced chordoma. Cases 1 and 3 were treated with first-line imatinib: PFS 16 months and 25 months respectively. Case 2 was treated with first-line sunitinib and stable disease was evaluated. She continues to receive treatment. After tumor progression with imatinib, Case 3 treated with sunitinib (PFS was 6 months). None of our cases achieved a partial response. The best response of the three cases to TKIs treatment was assessed as stable disease. Before the systemic therapy, the patients were treated with local treatment (surgery and radiotherapy). The results of local treatments were evaluated: median PFS were over 2 years. Post-local treatment PFS was longer than post-TKI treatment PFS.
Treatment planning in chordoma is challenging when local therapy is not an option after several relapses. Chordoma has few systemic treatment options with limited benefit. Randomized trials with large patient numbers are unfeasible in this rare disease. Targeted therapy might be a reasonable alternative treatment for chordoma. However, as in our case series, the best response with targeted therapy in the literature is stable disease. Although treatment options for patients with recurrent chordoma are increasing nowadays, chordoma causes severe morbidity and mortality. Therefore, still, new treatment strategies are needed for this rare disease.
OA is the corresponding author and drafted the manuscript. TAT: evaluation of patients’ follow-up and drug toxicity. OE: evaluation of patients’ follow-up and drug toxicity. ETS: evaluation of patients’ follow-up and drug toxicity. TBT: evaluation of patients’ follow-up and drug toxicity. AM edited paper and drafted manuscript. RH: radiological response assessment. SK: radiological response assessment. NAB: radiological response assessment. FD: design of the writing and support of the literature. PFY: design of the writing and support of the literature. All authors read and approved the final manuscript.
Ethics approval and consent to participate
Consent for publication
Written informed consent was obtained from the patients for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
The authors declare that they have no competing interests.
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- Stiller CA, Trama A, Serraino D, Rossi S, Navarro C, Chirlaque MD, Casali PG, RARECARE Working Group. Descriptive epidemiology of sarcomas in Europe: report from the RARECARE project. Eur J Cancer. 2013;49(3):684–95. https://doi.org/10.1016/j.ejca.2012.09.011. Epub 2012 Oct 15.View ArticlePubMedGoogle Scholar
- Fletcher CDM, Bridge JA, Hogendoorn P, Mertens F, editors. WHO Classification of Tumours of Soft Tissue and Bone. Fourth Edition. Lyon: IARC Press; 2013. p. 328–9.Google Scholar
- Stacchiotti S, Sommer J, Chordoma Global Consensus G. Building a global consensus approach to chordoma: a position paper from the medical and patient community. Lancet Oncol. 2015;16:e71–83.View ArticlePubMedGoogle Scholar
- Moojen WA, Vleggeert-Lankamp CL, Krol AD, Dijkstra SP. Long-term results: adjuvant radiotherapy in en bloc resection of sacrococcygeal chordoma is advisable. Spine. 2011;36:E656–61.View ArticlePubMedGoogle Scholar
- 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. Phase II study of high-dose photon/proton radiotherapy in the management of spine sarcomas. Int J Radiat Oncol Biol Phys. 2009;74:732–9. https://doi.org/10.1016/j.ijrobp.2008.08.058.View ArticlePubMedGoogle Scholar
- Nishida Y, Kamada T, Imai R, Tsukushi S, Yamada Y, Sugiura H, Shido Y, Wasa J, Ishiguro N. Clinical outcome of sacral chordoma with carbon ion radiotherapy compared with surgery. Int J Radiat Oncol Biol Phys. 2011;79:110–6. https://doi.org/10.1016/j.ijrobp.2009.10.051.View ArticlePubMedGoogle Scholar
- Radelli S, Stacchiotti S, et al. Sacral Chordoma: long-term outcome of a large series of patients surgically treated at two reference centers. Spine (Phila Pa 1976). 2016;41(12):1049–57.View ArticleGoogle Scholar
- Tamborini E, Miselli F, Negri T, et al. Molecular and biochemical analyses of platelet-derived growth factor receptor (PDGFR) B, PDGFRA and KIT receptors in chordomas. Clin Cancer Res. 2006;12:6920–8.View ArticlePubMedGoogle Scholar
- Weinberger PM, Yu Z, Kowalski D, et al. Differential expression of EGFR, c-Met, and HER2/neu in chordoma compared with 17 other malignancies. Arch Otolaryngol Head Neck Surg. 2005;131:707–11.View ArticlePubMedGoogle Scholar
- Stacchiotti S, Longhi A, Ferraresi V, et al. Phase II study of imatinib in advanced chordoma. J Clin Oncol. 2012;30:914–20.View ArticlePubMedGoogle Scholar
- Hindi N, Casali PG, Morosi C, Messina A, Palassini E, Pilotti S, et al. Imatinib in advanced chordoma: a retrospective case series analysis. Eur J Cancer. 2015;51(17):2609–14.View ArticlePubMedGoogle Scholar
- Stacchiotti S, Tamborini E, Lo Vullo S, et al. Phase II study on lapatinib in advanced EGFR-positive chordoma. Ann Oncol. 2013;24:1931–6.View ArticlePubMedGoogle Scholar
- Bompas E, Le Cesne A, Tresch-Bruneel E, et al. Sorafenib in patients with locally advanced and metastatic chordomas: a phase II trial of the French Sarcoma Group (GSF/GETO). Ann Oncol. 2015;26:2168–73.View ArticlePubMedPubMed CentralGoogle Scholar
- George S, Merriam P, Maki RG, et al. Multicenter phase II trial of sunitinib in the treatment of nongastrointestinal stromal tumor sarcomas. J Clin Oncol. 2009;27:3154–60.View ArticlePubMedPubMed CentralGoogle Scholar
- Lebellec L, Chauffert B, Blay JY, Le Cesne A, Chevreau C, Bompas E, et al. Advanced chordoma treated by first-line molecular targeted therapies: outcomes and prognostic factors. A retrospective study of the French Sarcoma Group (GSF/GETO) and the Association des Neuro-Oncologues d'Expression Française (ANOCEF). Eur J Cancer. 2017;79:119–28.View ArticlePubMedGoogle Scholar
- Lipplaa A, Dijkstra S, Gelderblom H. Efficacy of pazopanib and sunitinib in advanced axial chordoma: a single reference center case series. Clin Sarcoma Res. 2016;6:19.View ArticlePubMedPubMed CentralGoogle Scholar