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

• 62F presented with odynophagia secondary to a C3 chordoma

Methods

• 73M presented with bowel incontinence and left foot numbness

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)

Limitations• Short follow-up• Heterogeneous group

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.