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High-Dose Single-Fraction Radiotherapy for the Management of Chordomas of the Spine and Sacrum

High-Dose Single-Fraction Radiotherapy for the Management of Chordomas of the Spine and Sacrum. Yoshiya Yamada M.D., Ilya Laufer M.D., Brett W. Cox M.D., Michael D. Lovelock M.D., Robert G. Maki M.D. Ph. D., Joan M. Zatcky N.P., Patrick J. Boland M. D., Mark H. Bilsky M.D.

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High-Dose Single-Fraction Radiotherapy for the Management of Chordomas of the Spine and Sacrum

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  1. High-Dose Single-Fraction Radiotherapyfor the Management of Chordomasof the Spine and Sacrum Yoshiya Yamada M.D., Ilya Laufer M.D., Brett W. Cox M.D., Michael D. Lovelock M.D., Robert G. Maki M.D. Ph. D., Joan M. Zatcky N.P., Patrick J. Boland M. D., Mark H. Bilsky M.D. Memorial Sloan-Kettering Cancer Center

  2. Chordoma treatment • Surgery – primary treatment • Goal - En bloc, Wide margin • Radiation • Inoperable/intralesional • Previous surgery • Recurrence • Chemotherapy • Salvage/palliation

  3. Surgical Summary • Wide margin – 57% (35-75) • Recurrence-free survival – 45% (40-67) • 5y – 62% (52-66) • 10y – 46% (33-52) • Survival • Tumor-related death – 26% (21-47) • 5y – 74% (54-97) • 10y – 53% (21-71) York 1999, Fourney 2005, Bergh 2000, Fuchs 2005, Boriani 2006, Hanna 2008, Schwab 2009, Ruggieri 2010, Stacchiotto 2010

  4. Radiation Summary • Photon Therapy • Resistant to conventional fractionation • Proton Therapy • 5y Recurrence – 10%1, 27%2, 32%3, • Carbon Therapy • 5y Recurrence – 12%4 • Factors • GTV, implants 1DeLaney 2009 2Wagner 2009 3Staab 2011 4Imai 2011

  5. Necrosis After SRS • 2m post- SRS • 4m post- SRS • L3 chordoma after single-fraction 2400 cGy SRS showing ghost outlines of epitheliod cells and extensive necrosis

  6. Single-Fraction Radiation • More irreparable damage to DNA • Endothelial apoptosis1 • Overcomes stem cell resistance2 1Garcia-Barros 2003 2Chang 2005

  7. Hypothesis • Single-fraction SRS can be safely administered as a treatment of chordomas in the mobile spine and sacrum with good short-term local control

  8. Methods • Study design: Retrospective review • Study population • Patients with chordomas of the mobile spine and sacrum treated between 2006 and 2010 • Inclusion criteria • Single-fraction SRS • Exclusion criteria • Follow-up less than 6 months

  9. Methods • 62F presented with odynophagia secondary to a C3 chordoma

  10. Methods • 73M presented with bowel incontinence and left foot numbness

  11. Methods • 59F presented with back pain and high-grade spinal cord compression secondary to chordoma metastasis to T7

  12. Methods • SRS • Inverse optimized treatment plan • Onboard orthogonal KV and cone beam imaging • Median prescribed dose – 2400 cGy (1800-2400 cGy) • Primary endpoint • Local tumor control • Secondary endpoint • Treatment-related toxicity (CTAE v.4)

  13. Methods • Stratification variables • Histologic subtype • Location • Size • Dose • Follow-up • Clinical data and serial MRIs obtained every 3-4 months • Data sources • Chart and imaging review

  14. Tumor Characteristics Tumor volume – 88cc (26-859cc) 2 Dedifferentiated Chordomas

  15. Treatment Characteristics V100 – median 95% (72-100%)

  16. Local Progression • 1 recurrence – 95% local control • 11 months after SRS, died of progressive systemic chordoma • 5 patients died from chordoma

  17. Case Example • 62F presented with odynophagia secondary to a C3 chordoma • Single-fraction 24 Gy with surgery planned 3 months after SRS • Patient elected to defer surgery and 3-year MRI shows decrease in tumor size

  18. Post-SRS Tumor Histology

  19. Toxicity • Grade 1 skin reaction (temporary erythema) • Grade 1 or 2 odynophagia (temporary) • Sciatic neuropathy (foot drop and neuropathic pain) • Tumor encased the sciatic nerve • Partial vocal cord paralysis (vocal cord augmentation)

  20. Limitations • Short follow-up • Heterogeneous group

  21. Conclusions • Single-fraction SRS can be safely used to treat patients with chordomas of the mobile spine and sacrum. • Single-fraction SRS provides good short-term tumor control. • Long term follow-up will be necessary in order to determine if SRS can be used as definitive chordoma therapy or as a neoadjuvant or adjuvant treatment. • Single-fraction SRS represents a good treatment option in patients who cannot undergo wide-margin chordoma excision.

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