1. 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.
Memorial Sloan-Kettering Cancer Center

2. Chordoma treatment Surgery – primary treatment Radiation Chemotherapy
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 Proton Therapy Carbon Therapy Factors
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 Primary endpoint Secondary endpoint
Inverse optimized treatment plan
Onboard orthogonal KV and cone beam imaging
Median prescribed dose – 2400 cGy ( cGy)
Primary endpoint
Local tumor control
Secondary endpoint
Treatment-related toxicity (CTAE v.4)

13. Methods Stratification variables Follow-up Data sources
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
All tumors
De Novo Tumors
Recurrent Tumors
Metastases N
Median follow-up (m)
Median follow-up (m)
Mobile 14 31 9 37 2 33 3 12
Cervical 7 32 5 18 1 36
Thoracic 4
31.5
55.5 -- 11
Lumbar 30
Sacrum / Pelvis 10 22 6 16 38
Total 24 15 34
Tumor volume – 88cc (26-859cc)
2 Dedifferentiated Chordomas

15. Treatment Characteristics
All tumors
De Novo Tumors
Recurrent Tumors
Metastases N
Median follow-up (m)
Median follow-up (m)
No surgery 10
28.5 6 30 3 1 32
Initially planned surgery 7 -- 4 2
Neoadjuvant 36 5 40
Adjuvant 8 14 37 11
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
Level
Time from SRS (m)
Extent of necrosis
Follow-up (m) L2 2
conventional chordoma 60 L3 4
>90% 46
Sacrum 32 5
50% 19 5% 13 8 40

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.