Spinal column chordoma: prognostic significance of clinical variables and T (brachyury) gene SNP rs2305089 for local recurrence and overall survival.
Chordomas are rare, locally aggressive bony tumors associated with poor outcomes. Recently, the single nucleotide polymorphism (SNP) rs2305089 in the T (brachyury) gene was strongly associated with sporadic chordoma development, but its clinical utility is undetermined.



In 333 patients with spinal chordomas, we identified prognostic factors for local recurrence-free survival (LRFS) and overall survival and assessed the prognostic significance of the rs2305089 SNP.



The median LRFS was 5.2 years from the time of surgery (95% CI: 3.8-6.0); greater tumor volume (≥100cm3) (hazard ratio [HR] = 1.99, 95% CI: 1.26-3.15, P = .003) and Enneking inappropriate resections (HR = 2.35, 95% CI: 1.37-4.03, P = .002) were independent predictors of LRFS. The median overall survival was 7.0 years (95% CI: 5.8-8.4), and was associated with older age at surgery (HR = 1.11 per 5-year increase, 95% CI: 1.02-1.21, P = .012) and previous surgical resection (HR = 1.73, 95% CI: 1.03-2.89, P = .038). One hundred two of 109 patients (93.6%) with available pathologic specimens harbored the A variant at rs2305089; these patients had significantly improved survival compared with those lacking the variant (P = .001), but there was no association between SNP status and LRFS (P = .876).



The ability to achieve a wide en bloc resection at the time of the primary surgery is a critical preoperative consideration, as subtotal resections likely complicate later management. This is the first time the rs2305089 SNP has been implicated in the prognosis of individuals with chordoma, suggesting that screening all patients may be instructive for risk stratification.
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Chetan
C
Bettegowda
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Stephen
S
Yip
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Sheng-Fu Larry
SL
Lo
Division of Spine, Department of Orthopaedics, University of British Columbia and Vancouver Coastal Health, Vancouver, British Columbia, Canada.
Charles G
CG
Fisher
Department of Degenerative and Oncological Spine Surgery, Rizzoli Institute, Bologna, Italy.
Stefano
S
Boriani
Department of Neurosurgery, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA.
Laurence D
LD
Rhines
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Joanna Y
JY
Wang
National Center for Spinal Disorders and Buda Health Center, Budapest, Hungary.
Aron
A
Lazary
Department of Pathology, Rizzoli Institute, Bologna, Italy.
Marco
M
Gambarotti
Department of Pathology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA.
Wei-Lien
WL
Wang
Oncologia Ortopedica e Ricostruttiva del Rachide, Istituto Ortopedico Galeazzi, Milano, Italy.
Alessandro
A
Luzzati
Department of Orthopedics, CORE Institute, Phoenix, Arizona, USA.
Mark B
MB
Dekutoski
Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Mark H
MH
Bilsky
Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
Dean
D
Chou
Division of Neurosurgery and Spinal Program, Department of Surgery, University of Toronto and Toronto Western Hospital, Toronto, Ontario, Canada.
Michael G
MG
Fehlings
Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
Edward F
EF
McCarthy
Center for Spine Studies and Surgery, Queens Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Nasir A
NA
Quraishi
Spinal Division, Oxford University Hospital NHS Trust, Oxford, UK.
Jeremy J
JJ
Reynolds
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Daniel M
DM
Sciubba
Department of Orthopaedics, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Richard P
RP
Williams
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jean-Paul
JP
Wolinsky
Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Patricia L
PL
Zadnik
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ming
M
Zhang
Research Department, AOSpine International, Davos, Switzerland.
Niccole M
NM
Germscheid
AO Clinical Investigation and Documentation, AO Foundation, Duebendorf, Switzerland.
Vasiliki
V
Kalampoki
National Center for Spinal Disorders and Buda Health Center, Budapest, Hungary.
Peter Pal
PP
Varga
Department of Neurosurgery, The Warren Alpert Medical School of Brown University, Providence, Rhode Island.
Ziya L
ZL
Gokaslan
D014408:Biomarkers, Tumor / Q000235:genetics*; D002817:Chordoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D005260:Female; D005326:Fetal Proteins / Q000235:genetics*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D013125:Spinal Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D020825:T-Box Domain Proteins / Q000235:genetics*; D000098908:Brachyury Protein
D014408:Biomarkers, Tumor; D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein
SNP; brachyury; chordoma; rs2305089; spine; T gene
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