High-Dose Single-Fraction Radiotherapy for the Management of Chordomas of the Spine and Sacrum...
Transcript of High-Dose Single-Fraction Radiotherapy for the Management of Chordomas of the Spine and Sacrum...
High-Dose Single-Fraction Radiotherapyfor 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
Chordoma treatment
• Surgery – primary treatment– Goal - En bloc, Wide margin
• Radiation– Inoperable/intralesional– Previous surgery– Recurrence
• Chemotherapy– Salvage/palliation
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
• 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 20092Wagner 20093Staab 20114Imai 2011
Radiation Summary
Necrosis After SRS
• L3 chordoma after single-fraction 2400 cGy SRS showing ghost outlines of epitheliod cells and extensive necrosis
2m post- SRS 4m post- SRS
Single-Fraction Radiation
• More irreparable damage to DNA• Endothelial apoptosis1
• Overcomes stem cell resistance2
1Garcia-Barros 20032Chang 2005
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
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
Methods
• 59F presented with back pain and high-grade spinal cord compression secondary to chordoma metastasis to T7
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)
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
Tumor Characteristics
All tumors De Novo Tumors Recurrent Tumors Metastases
NMedian
follow-up (m) NMedian
follow-up (m) NMedian
follow-up (m) NMedian
follow-up (m)
Mobile 14 31 9 37 2 33 3 12
Cervical 7 32 5 18 1 36 1 32
Thoracic 4 31.5 2 55.5 0 -- 2 11
Lumbar 3 30 2 30 1 30 0 --
Sacrum / Pelvis 10 22 6 16 4 38 0 --
Total 24 24 15 22 6 34 3 12
Tumor volume – 88cc (26-859cc)2 Dedifferentiated Chordomas
Treatment Characteristics
All tumors De Novo Tumors Recurrent Tumors Metastases
N
Median follow-up
(m) N
Median follow-up
(m) N
Median follow-up
(m) N
Median follow-up
(m)No surgery 10 28.5 6 30 3 30 1 32
Initially planned surgery 7 -- 4 -- 2 -- 1 --
Neoadjuvant 6 36 5 40 1 32 0 --Adjuvant 8 14 4 14 2 37 2 11
V100 – median 95% (72-100%)
Local Progression
• 1 recurrence – 95% local control– 11 months after SRS, died of progressive systemic chordoma
• 5 patients died from chordoma
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
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 4 >90% 32
Sacrum 5 50% 19
Sacrum 5 5% 13
Sacrum 8 >90% 40
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)
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.