Spinal column chordoma: prognostic significance of clinical variables and T (brachyury) gene SNP rs2305089 for local recurrence and overall survival.
Background
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.


Methods
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.


Results
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).


Conclusions
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.
['Bettegowda|Chetan|C|', 'Yip|Stephen|S|', 'Lo|Sheng-Fu Larry|SL|', 'Fisher|Charles G|CG|', 'Boriani|Stefano|S|', 'Rhines|Laurence D|LD|', 'Wang|Joanna Y|JY|', 'Lazary|Aron|A|', 'Gambarotti|Marco|M|', 'Wang|Wei-Lien|WL|', 'Luzzati|Alessandro|A|', 'Dekutoski|Mark B|MB|', 'Bilsky|Mark H|MH|', 'Chou|Dean|D|', 'Fehlings|Michael G|MG|', 'McCarthy|Edward F|EF|', 'Quraishi|Nasir A|NA|', 'Reynolds|Jeremy J|JJ|', 'Sciubba|Daniel M|DM|', 'Williams|Richard P|RP|', 'Wolinsky|Jean-Paul|JP|', 'Zadnik|Patricia L|PL|', 'Zhang|Ming|M|', 'Germscheid|Niccole M|NM|', 'Kalampoki|Vasiliki|V|', 'Varga|Peter Pal|PP|', 'Gokaslan|Ziya L|ZL|', '|||']
D014408:Biomarkers, Tumor D002817:Chordoma D005260:Female D005326:Fetal Proteins D005500:Follow-Up Studies D006801:Humans D008297:Male D008875:Middle Aged D060787:Neoplasm Grading D020641:Polymorphism, Single Nucleotide D011379:Prognosis D011446:Prospective Studies D012189:Retrospective Studies D013125:Spinal Neoplasms D015996:Survival Rate D020825:T-Box Domain Proteins
chordoma brachyury SNP rs2305089 spine T gene