Chetan Bettegowda1, Stephen Yip2, Sheng-Fu Larry Lo1, Charles G Fisher3, Stefano Boriani4, Laurence D Rhines5, Joanna Y Wang1, Aron Lazary6, Marco Gambarotti7, Wei-Lien Wang8, Alessandro Luzzati9, Mark B Dekutoski10, Mark H Bilsky11, Dean Chou12, Michael G Fehlings13, Edward F McCarthy14, Nasir A Quraishi15, Jeremy J Reynolds16, Daniel M Sciubba1, Richard P Williams17, Jean-Paul Wolinsky1, Patricia L Zadnik18, Ming Zhang19, Niccole M Germscheid20, Vasiliki Kalampoki21, Peter Pal Varga6, Ziya L Gokaslan22. 1. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 2. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. 3. Division of Spine, Department of Orthopaedics, University of British Columbia and Vancouver Coastal Health, Vancouver, British Columbia, Canada. 4. Department of Degenerative and Oncological Spine Surgery, Rizzoli Institute, Bologna, Italy. 5. Department of Neurosurgery, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA. 6. National Center for Spinal Disorders and Buda Health Center, Budapest, Hungary. 7. Department of Pathology, Rizzoli Institute, Bologna, Italy. 8. Department of Pathology, MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA. 9. Oncologia Ortopedica e Ricostruttiva del Rachide, Istituto Ortopedico Galeazzi, Milano, Italy. 10. Department of Orthopedics, CORE Institute, Phoenix, Arizona, USA. 11. Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA. 12. Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA. 13. Division of Neurosurgery and Spinal Program, Department of Surgery, University of Toronto and Toronto Western Hospital, Toronto, Ontario, Canada. 14. Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland, USA. 15. Center for Spine Studies and Surgery, Queens Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK. 16. Spinal Division, Oxford University Hospital NHS Trust, Oxford, UK. 17. Department of Orthopaedics, Princess Alexandra Hospital, Brisbane, Queensland, Australia. 18. Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 19. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 20. Research Department, AOSpine International, Davos, Switzerland. 21. AO Clinical Investigation and Documentation, AO Foundation, Duebendorf, Switzerland. 22. Department of Neurosurgery, The Warren Alpert Medical School of Brown University, Providence, Rhode Island.
Abstract
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.
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.
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