Body Stereotactic
Radiation Therapy:
Clinical Experience and
Rationale
SRS: Rethinking
radiotherapy
Danny Y. Song, MD
Department of Radiation Oncology
The Sidney Kimmel Comprehensive
Cancer Center at Johns Hopkins
AAPM 46th Annual Meeting, Pittsburgh, PA
Conventional radiotherapy
Potential tumor?
Radiosurgery
CTV (GTV + ~ 10 mm)
PTV ~ 5-10 mm margin
PTV (CTV + ~ 10-15 mm)
<< Normal tissue irradiated
Normal tissue irradiated
GTV
GTV = CTV
1
What has been
accomplished with SRS?
Reduced toxicity from radiation
Brain metastases
Meningiomas
Alternative to surgery with less morbidity
Meningiomas
Arteriovenous malformations
Acoustic schwannomas
Improved tumor control and survival
Karolinska Institute
42 tumors, 31 patients
Tumors of liver, lung, retroperitoneal space
Mean peripheral dose to PTV = 30.2 Gy in 14 fractions
Toxicity: fever/nausea in patients treated to
liver
50% tumor response rate; 80% local control
Brain metastases (RTOG 95-08)
Meningioma
Blomgren and Lax et al., Acta Oncologica 34(6):861-870, 1995.
Suitable applications
Small to moderate volume target
No need for prophylactic coverage (ie CTV =
GTV)
Need to spare radiosensitive normal tissue or
surrounding structure
Normal tissue has parallel architecture
Local control important to overall patient
outcome
Dose-response relationship exists
2
Results of Conventional
RT
# of patients
152
103
43
53
108
50
77
77
44
141
3 yr OS
36%
19%
31%
33%
17%
21%
55%
24%
5 yr OS
10%
13%
21%
6%
15%
17%
14%
17%
32%
13%
60
Percent local failure
Author
Dosoretz
Graham
Haffty
Kaskowitz
Krol
Noordijk
Sandler
Talton
Zhang
Sibley
Stage I NSCLC – doseresponse
50
40
30
20
10
0
Kaskowitz
Zhang
Lower dose
Dosoretz
Higher dose
Sibley, Cancer 82:433,1998.
Stage I NSCLC –
treatment-related
morbidity
Grade 3 pneumonitis
50
Change score
40
30
20
10
0
Start
During
2w
6w
3m
6m
12m
18m
24m
Dyspnea (shortness of breath)
Seppenwoolde Y et al, IJROBP 55:724, 2003.
Langendijk J et al, IJROBP 53:847, 2002.
3
Stage I NSCLC - Results
with ESR
Author
# of patients
Timmerman
37
Uematsu
43
Nagata
31
Wulf
12
Hara
5
Hof
10
Lee
9
Onishi*
241
Median f/u
15 m
20 m
16 m
8m
20 m
15 m
18 m
18 m
Local control
83%
100%
100%
85%
100%
80%
90%
90%
Dose selection in lung
Indiana University Phase I study
37 patients with medically inoperable
Stage I NSCLC
Elekta body frame with abdominal
compression plate
Dose escalation beginning 8 Gy per
fraction, 3 fractions total
Stratified by T-stage (T1 vs T2)
Timmerman et al: Chest, 2003.
Indiana University
Phase I study
MTD not reached at 20 Gy per fraction (3
fractions = 60 Gy)
Toxicity: 1 pneumonitis grade 3, 1 hypoxia
grade 3 (n = 37)
Six local failures
All occurred in patients treated < 18 Gy per
fraction
Timmerman et al: Chest, 2003.
Dose comparisons
Author
Dose
2 Gy eq dose
Standard Rx
2 Gy x 30-33 60-66 Gy
Timmerman
20 Gy x 3
150 Gy
Nagata
12 Gy x 4
88 Gy
Onimaru
7.5 Gy x 8
87 Gy
Hara
30 Gy x 1
100 Gy
Linear quadratic method, / = 10
4
Lung SRS Complications
Dose-response curve for NSC lung cancer
100
NSCLC:
Response-dose
- 50 = 1.5
curve calc. from
D - 50 = 84.5 Gy
80
clinical parameters
analysed by Martel
et al. Lung Cancer,
60
24: 31-37, 1999.
TCP
3yr 40
%
20
Total Dose @
2 Gy/fr (Gy):
0
50
/ = 10 Gy
= 0.35 / Gy
Tk = 28 days
Tp = 3 days
60
70
32
39
46
Overall Time (days)
72
84
BED no prolif (Gy-10) 60
BED Tp=3d & Tk=28d 57.4 64.7 72.1
80
53
96
79.5
(J Fowler, J Welsh)
90 100 110 120 130
60 67
108 120
86.9
94.3
74
132
81
144
Gy
88 days
156 Gy-10
Author
# of patients
Dose
Uematsu
66
30-76 Gy, 5-15 fx
Grade 3 Toxicity
0%
Nakagawa
22
15-24 Gy, 1 fx
0%
Nagata
40
40-48 Gy, 4 fx
0%
Wulf
61
26-37.5 Gy, 1-3 fx
3%
Hara
23
20-30 Gy, 1 fx
4%
Hof
10
19-26 Gy, 1 fx
0%
Onishi
241
18-75 Gy, 1-22 fx
2%
0%
Lee
28
30-40 Gy, 3-4 fx
Blomgren
13
15-45 Gy, 1-3 fx
Timmerman
37
24-60 Gy, 3 fx
5.4%
101.6 109.0 116.4 Gy-10
(J Fowler and J Welsh)
5
Lung metastases Results of ESR
Author
# of targets
Median f/u
Uematsu
Nakagawa
Nagata
Blomgren
Wulf
Hara
Lee
Song
23
21
9
14
11
18
19
25
20 m
10 m
18 m
8m
8m
12 m
18 m
15 m
Local
control
100%
95%
66%
92%
85%
78%
88%
92%
Liver metastases
Colorectal Ca metastatic to liver
Incidence = 40,000 per year in US
40% 5-year survival with resection of met1
Favorable prognosis following resection:
4 metastases
Low CEA
Smaller size
Margin of resection > 10 mm
No extrahepatic disease
Gastric
38% 5-year overall survival2
Favorable prognosis:
Solitary metastasis
1Belli
et al, J Hep Pancr Surg 2002. 2Sakamoto et al, Surgery 2003.
Liver mets: surgery for other histologies
Primary
# cases
5-yr OS
Renal
Wilm’s
Adrenocort.
Breast
Ovarian
Melanoma
Testicular
Sarcoma
GYN
18
16
15
63
17
26
9
48
10
38.8%
37.5%
26.6%
14.3%
11.7%
11.5%
11.1%
10.4%
10%
Ravikumar, Oncology 16(9), 2002.
6
Dose responsiveness
Liver volume dependence
Dawson et al, JCO 18:2210-18, 2000.
Dose threshold
Dawson L; IJROBP 53:810-21, 2002.
Liver tumors - Results of
SRS
Author
# of targets
Median f/u
Blomgren
Herfarth
Sato
Wulf
Schefter
41
60
23
36
15
9-12 m
6m
10 m
9m
10 m
Local
control
95%
80%
100%
83%
47%
Dawson L; IJROBP 53:810-21, 2002.
7
Liver toxicity of SRS
Other applications
Nausea, low grade fever common
Responsive to premedication
Blomgren
5/21 patients: intractable ascites, subcapsular
bleed, or GI ulcers
Herfarth, Sato, Schefter, Wulf
No major side effects
Spine
Metastases
Boost after tolerance dose delivered to cord
Primary tumors in paraspinal locations
Adrenal gland
Lung cancer metastases
Prostate
Low / ratio favors hypofractionated approach
What is possible with
ESR?
Reduced toxicity of treatment
Alternative to conventional surgery or
other invasive treatments
Improved tumor control
Improved patient survival
8