Patterns of Failure seen in
the SBRT Treatment of
Paraspinal Disease
Michael Lovelock Ph.D
Medical Physics Department,
Memorial Sloan-Kettering Cancer Center,
New York City, NY
Acknowledgements
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Josh Yamada MD – Radiation Oncology
Mark Bilsky MD - Neurosurgery
Eric Lis MD - Neuroradiology
Tom Losasso PhD – Physics
Jennifer Keam MD - Radiation Oncology
Joan Zatcky N.P. – Radiation Oncology
Treatment of Paraspinal Disease
at MSKCC
• Single or hypo-fractionated radiotherapy
has been given to patients with metastatic
disease to the spine or paraspinal sites
since April 2000.
• Two patients cohorts:
1. Single or oligo-metastatic patient with no
prior radiation
2. Patients who have been previously treated
and have experienced local failure
Cohort #1:
• Patients with no prior radiation to the site,
and with either a single metastasis or
oligo-metastatic condition
• Initially prescription dose 18 Gy,
(maximum cord point dose 12 Gy).
• Prescription dose now 24 Gy
(maximum cord point dose 14 Gy)
Cohort # 2:
• Patients who have had prior treatment to
the site, and have experienced local failure
• Initially, patients received 20 Gy in 5
fractions
• (more recently, Not part of this analysis,
this has been changed to 30 Gy in 5 frac._
• Maximum dose to the myelogram defined
cord is 2.8 Gy/.frac
Local Control – Cohort 1
–single frac
A significant difference in dose response is seen between 18-23 Gy and
24 Gy prescription
Under-dosed
sub-volume
24 Gy
18 - 23 Gy
Yamada et al, I.J.R.O.B.P 2008 71(2) p. 484-90.
Local Control – Cohort 2
–hypo-frac
Wright et al, Am J Clin Oncol. 2006 29(5) 495-502
Objective:
• Examine the patterns of failures seen in
the two patient cohorts to see what can be
learned about:
– Prescribed dose sufficiency
– Margins / geometrical miss
– Cold spots due to proximity of spinal cord
Delivery Technique
• Treatment Planning:
– All plans developed using a inverse-planning
technique
– Dose delivered using ‘sliding window’
intensity-modulation
• Delivery
– Image guidance (formerly MV + implanted
markers, now kv radiographs or cone beam
without implants) used for all fractions
Immobilization Cradle
• Designed to
maximize patient
comfort
• 4 lateral paddles
help maintain
patient position
Real time monitoring of patient
position
Stereoscopic infra-red
camera
Marker Displacement (cm)
• Infra-red reflectors taped to patient’s skin
• Positions monitored in real time to check
patient still and breathing regularly
Marker Locations
- Left chest
- Right chest
- Belly
Time (seconds)
Characteristics of the
Recurrence Volumes
• Recurrence was identified by a radiologist
on followup (every 3-4 months) MR scans
• Radiologist delineated the MR volume of
failure
• After registration, the volumes were
transferred to the planning CT, permitting
the spatial and dosimetric characteristics
to be evaluated.
Failure volumes of the 5 fraction
patient cohort
1
2
4
5
3
6
Recurrence
GTV
PTV
Recurrence volumes – 5 frac
-continued
7
8
9
10
11
12
Recurrence volumes 5-frac
-continued
13
Recurrence volumes singlefraction treatment cohort
1
4
2
5
3
6
Recurrence volumes – single
fraction cohort - continued
7
Characteristics of Failure Volumes
5 Fraction Cohort
1 Fraction Cohort
• Volumes
Location with respect to
the GTV
Generally large, covering
the vertebral body
Generally at the edge of
the GTV, smaller
Volume
Median: 67.1 cc
Range: 14.6 – 341 cc
Median: 10.3 cc
Range: 2.9 – 52.1 cc
Dosimetric Characteristics of the
Failure Volumes
Failure Volume
• Was the existence of a cold
spot in the GTV associated
GTV
with the failure volume –
Did the failure volume
encompass the cold spot in
the GTV?
– compare the mean dose of the GTV
with the mean dose of the GTV – failure
volume overlap
Failure Volume
GTV
Mean Dose in
GTV – Failure
volume overlap
(cGy)
Mean Dose in
the GTV (cGy)
Difference:
Overlap – GTV
(cGy)
1 fraction cohort
2102
2280
-178
5 fraction cohort
2304
2327
-23
One interpretation
• For the single fraction treatments, there is
evidence that the cold spots in the target are
associated with recurrence
• This is not observed in the 5-fraction patients.
The analysis is confounded by the large size of
these failure volumes.
• This may indicate that the 5-fraction doses are
simply too low, resulting in many surviving
clonogens. This leads to rapid tumor regrowth,
not necessarily associated with a GTV cold spot
Cold spot exists because of the proximity of
the spinal cord
The maximum dose to any point
on the spinal cord is limited to
12 – 14 Gy
Under-dosed
sub-volume
The cord, visualized with either a
co-registered MR scan, or a with a
myelogram, may be in close
proximity to the target volume
The steepest dose gradient
achievable with IMRT is around
10% per mm.
Cord
Tumor (gross
target volume)
Prescription
isodose
This may lead to a cold spot if the
target is within 3-4 mm of the cord
The dependence of local failure on dose insufficiency with the tumor was
investigated by comparing treatment plans of patients with long term local
control with those who experienced local failure
Cold Spot Analysis
• The minimum doses received by the hottest 95%,
98%, and 100% (D95, D98, and Dmin) of the
gross target volume (GTV) were
computed for 91 consecutively treated lesions
seen in 79 patients
• A Wilcoxan rank-sum statistic was used to assess
difference between local failure and local control.
Dmin, D98, and D95
• Dose distributions computed by
calculating the dose at 5000
points placed in the target quasirandomly
• In paraspinal targets with an
adjacent region with a steep dose
gradient, Dmin, a single point
dose, may be affected by small
clinically insignificant changes,
such as a 1 pixel shift in a contour
• D98 and D95 are more stable
measures of low dose, although
less sensitive to the presence of a
small region of under-dose.
Results
1:renal
2:GI
3:melanoma
4:prostate
5:headandneck
6:sarcoma
7:breast
8:bladder
9:lung
10:leydig
Target (GTV) Minimum Dose
3000
Dose (cG y)
2500
2000
1500
1000
500
0
2
4
6
8
10
12
Histology
• With a 15 month median followup, 7 local failures have occurred
P-Values
Distributions of D95, D98, and Dmin for the Gross Target
Volumes of treatments that resulted in local failure were found to
be statistically different from the treatments that resulted in local
control
Dmin
Histology
Ignored
0.005
Histology
accounted for
0.012
D98
0.012
0.012
D95
0.044
0.040
Correlation between local failure
and GTV volume
Local Failure as a Function of
GTV Volume and Vertebral Position
120
100
GTV Volume (cc)
Local control
80
Local failure
60
40
20
0
1
6
11
16
21
Vertebra Number: Sup --> Inf
With only 7 local failures, no correlation was seen with GTV volume
26
Conclusion
• In both the 20 Gy 5-fraction and 24 Gy single fraction treatments,
insufficient dose may be a factor in the observed local failures
• For the 20 Gy 5-fraction treatments, the relatively high local failure
rate, the large tumor recurrence region, and the lack of correlation
with cold spots on the edge of the GTV may indicate the dose is too
low
• For the 24 Gy single fraction treatments, measures of tumor dose
insufficiency that indicate the presence of a cold spot such as D95,
D98, and Dmin may be important risk factors for local failure
No local failures in any histology were observed when
Dmin > 15 Gy
suggesting this metric may be a predictor of local control
• Confirmation of these results awaits the accrual and followup of
more patients
Additional Slides
D98
1:renal
2:GI
3:melanoma
4:prostate
5:headandneck
6:sarcoma
7:breast
8:bladder
9:lung
10:leydig
GTV D98
2800
2600
2400
2200
2000
1800
1600
1400
1200
0
2
4
6
8
10
12
D95
1:renal
2:GI
3:melanoma
4:prostate
5:headandneck
6:sarcoma
7:breast
8:bladder
9:lung
10:leydig
GTV D95
2800
2600
2400
2200
2000
1800
1600
1400
0
2
4
6
8
10
12