Rarer Bone Tumors

Thomas F. DeLaney, M.D.Co-Director: Sarcoma Program

Medical Director: F. H. Burr Proton CenterMassachusetts General Hospital

Survival-Advanced InoperableChondrosarcoma (Picci et al)Survival-Advanced InoperableChondrosarcoma (Picci et al)

Overall survival for all 171 pts was:

48% at 1 year

24% at 2 years

12% at 3 years

6% at 4 years

2% at 5 years

Median time to death was 11 months-

Useful benchmark for future studies

Overall survival for all 171 pts was:

48% at 1 year

24% at 2 years

12% at 3 years

6% at 4 years

2% at 5 years

Median time to death was 11 months-

Useful benchmark for future studies

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0 12 24 36 48 60 72 84 96 108 120months

OS and stage of inoperable diseaseOS and stage of inoperable disease

P-Value 0.0049P-Value 0.0049

multiple sites

lung only

local + lung

local only

OS and Medical Treatment (all pts) OS and Medical Treatment (all pts)

P-Value 0.0487P-Value 0.0487

Pts with metastasis only (local & local + met excluded)Pts with metastasis only (local & local + met excluded)

P-Value 0.0082P-Value 0.0082

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Cum. Survival (YES)

Cum. Survival (NO)

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Cum. Survival (YES)

Cum. Survival (NO)

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months

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0 12 24 36 48 60 72 84 96 108 120months

OS and Radiotherapy (all pts) OS and Radiotherapy (all pts)

P-Value0.1052P-Value0.1052

OS and Radiotherapy (Local only)OS and Radiotherapy (Local only)P-Value 0.0032P-Value 0.0032

OS and Radiotherapy (Local + met)OS and Radiotherapy (Local + met)

P-Value0.1063P-Value0.1063

Cum. Survival (YES)Cum. Survival (NO)

Cum. Survival (YES)

Cum. Survival (NO)

Cum. Survival (YES)

Cum. Survival (NO)

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High-Dose Single-Fraction RTfor the Management of Chordomas

of the Spine and Sacrum (Yamada et al)• 24 pts (21 1º tumors) rx’ed with single-fraction SRS

– Median follow-up 24 months

• SRS was administered as definitive (10), neoadjuvant (6) or adjuvant (8) treatment

• 95% control rate-High rates of LC in 1º chordomas– Radical surg, surg (en bloc) + high dose RT, definitive RT+/- TKI

• Limited toxicity (to date)– 1 sciatic neuropathy -1 vocal cord paralysis

• Will need longer follow-up on this regimen– Neuropathies are late events→H. Suit: “Late events occur late”– How to do phase 1 studies in Radiation Oncology- ? Surrogate endpoints?

IG-SRS for Spine Sarcoma(Folkert et al, MSKCC)• Conventional RT of spine sarcomas: prolonged RT course

– Conventional doses ~ 50 Gy not effective– High doses ~ 70-77 Gy by sophisticated techniques/particles

effective for 1º tumors->~85% LC– Hypofx and single-fx image-guided stereotactic RT (IG-SRS)

may be more convenient/cost effective Rx– 33% pts 1º and 66% pts met tumors Rx’ed since 2005– Myelogram-CT simulation and inverse RT planning

• Image-guided Rx: KV imaging/cone-beam CT scan.– 117 patients/147 lesions Rx’ed with hypofx (3-6 fx; n=49,

33.3%) or single-fx IG-SRS (n=98, 66.7%)• 88% local control with single-fraction IG-SRS.

– A Phase II clinical trial is being developed to use single-fx IG-SRS in the definitive management of sarcoma.

• Exercise caution for 1º tumor pts at risk for late effects

Outcomes, IG-SRS

24 months

Local Progression-Free Survival (LPFS) 

Full Cohort82.6%

(95% CI 74.4-90.8%)

Metastatic lesions80.6%

(95% CI 70.6-90.6%)

Primary lesions88%

(95% CI 74.6-100%)

Hypofractionated IG-SRS

68.2% (95% CI 47.8-88.6%)

Single-fraction IG-SRS

88.2% (95% CI 80.2-96.2%)

Overall Survival (OS)

Full Cohort51%

(95% CI 40.6-61.4%)

Metastatic patients39%

(95% CI 26.6-51.4%)

Primary patients77.1%

(95% CI 61.7-92.5%)

Hypofractionated IG-SRS patients

42.7% (95% CI 23.1-62.3%)

Single fraction IG-SRS patients

54.4% (95% CI 42-66.8%)

Local progression-free survival and overall survival, full cohort.

Local progression-free survival and overall survival, lesions

treated with single-fraction and hypofractionated IG-SRS

P=.005

P=.020

24Gy x1

Single

Hypo

Hypo

Multivariate analysis: single-fraction IG-SRS retained its significance in terms of reduction in local recurrence (P=.002): HR 0.251 (95% CI: 0.103-0.612).