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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
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Chordoma treatment Surgery – primary treatment Radiation Chemotherapy
Goal - En bloc, Wide margin Radiation Inoperable/intralesional Previous surgery Recurrence Chemotherapy Salvage/palliation
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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
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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
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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
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Single-Fraction Radiation
More irreparable damage to DNA Endothelial apoptosis1 Overcomes stem cell resistance2 1Garcia-Barros 2003 2Chang 2005
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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
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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
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Methods 62F presented with odynophagia secondary to a C3 chordoma
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Methods 73M presented with bowel incontinence and left foot numbness
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Methods 59F presented with back pain and high-grade spinal cord compression secondary to chordoma metastasis to T7
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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)
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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
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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
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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%)
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Local Progression 1 recurrence – 95% local control
11 months after SRS, died of progressive systemic chordoma 5 patients died from chordoma
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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
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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
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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)
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Limitations Short follow-up Heterogeneous group
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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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