Slide 1
Extracranial Stereotactic
Radiotherapy:
Clinical Experience and
Rationale
Danny Y. Song, MD
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Medical College of Virginia at Virginia
Commonwealth University
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AAPM 45th Annual Meeting, San Diego, CA
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Slide 2
SRS: Rethinking radiotherapy
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Slide 3
Conventional radiotherapy
CTV (GTV + ~ 10 mm)
Potential tumor?
PTV (CTV + ~ 10-15 mm)
Normal tissue irradiated
GTV
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Slide 4
Radiosurgery
PTV ~ 5-10 mm margin
<< Normal tissue irradiated
GTV = CTV
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Slide 5
What has been accomplished
with SRS?
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Reduced toxicity from radiation
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Alternative to surgery with less morbidity
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Brain metastases
Meningiomas
Meningiomas
Arteriovenous malformations
Acoustic schwannomas
Improved tumor control and survival
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Brain metastases (RTOG 95-08)
Meningioma
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Slide 6
Karolinska Institute
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42 tumors, 31 patients
Tumors of liver, lung, retroperitoneal space
Mean peripheral dose to PTV = 30.2 Gy in 1-4
fractions
Toxicity: fever/nausea in patients treated to
liver
50% tumor response rate; 80% local control
Blomgren and Lax et al., Acta Oncologica 34(6):861-870, 1995.
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Slide 7
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Suitable applications
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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
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Slide 8
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Slide 9
Results of Conventional RT
Author
Dosoretz
Graham
Haffty
Kaskowitz
Krol
Noordijk
Sandler
Talton
Zhang
Sibley
# 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%
Sibley, Cancer 82:433,1998.
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Slide 10
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Grade 3 pneumonitis
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Seppenwoolde Y et al, IJROBP 55:724, 2003.
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Slide 11
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Stage I NSCLC – treatmentrelated morbidity
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50
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Change score
40
30
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20
10
0
Start
During
2w
6w
3m
6m
12m
18m
24m
Dyspnea (shortness of breath)
Langendijk J et al, IJROBP 53:847, 2002.
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Stage I NSCLC – doseresponse
60
Percent local failure
Slide 12
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50
40
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30
20
10
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0
Kaskowitz
Zhang
Lower dose
Dosoretz
Higher dose
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Slide 13
Stage I NSCLC - Results with
ESR
Author
# of patients
Timmerman
37
Uematsu
43
Nagata
31
Wulf
12
Hara
5
Hof
10
Onimaru
19
Median f/u
15 m
20 m
16 m
8m
20 m
15 m
17 m
Local control
83%
100%
100%
85%
100%
80%
85% (2yr)
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Slide 14
Dose selection in lung
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Indiana University Phase I study
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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, in press
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Slide 15
Indiana University Phase I
study
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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
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All occurred in patients treated < 18 Gy per
fraction
Timmerman et al: Chest, in press
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Slide 16
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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
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100 Gy
Linear quadratic method, α/β = 10
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Slide 17
Dose-response curve for NSC lung cancer
100
NSCLC:
Response-dose
γ - 50 = 1.5
curve calc. from
D - 50 = 84.5 Gy
clinical parameters 80
analysed by Martel
et al. Lung Cancer,
60
24: 31-37, 1999.
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TCP
3yr 40
%
20
Total Dose @
2 Gy/fr (Gy):
α/β = 10 Gy
α = 0.35 / Gy
Tk = 28 days
Tp = 3 days
0
50
60
32
Overall Time (days)
BED no prolif (Gy-10) 60
39
72
BED Tp=3d & Tk=28d
57.4 64.7
70
46
84
72.1
80
53
96
79.5
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90 100 110 120 130
60 67
108 120
86.9
94.3
74
132
81
144
Gy
88 days
156 Gy-10
101.6 109.0 116.4 Gy-10
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Slide 18
Lung SRS - Complications
Author
Uematsu
Nakagawa
Nagata
Wulf
Hara
Hof
Onimaru
Whyte
Blomgren
# of
patients
66
22
40
61
23
10
57
23
17
Dose
30-76 Gy, 5-15 fx
15-24 Gy, 1 fx
40-48 Gy, 4 fx
26-37.5 Gy, 1-3 fx
20-30 Gy, 1 fx
19-26 Gy, 1 fx
48-60 Gy, 8 fx
15 Gy, 1 fx
30 Gy, 2-3 fx
Grade 3
Toxicity
0%
0%
0%
3%
4%
0%
2%
0%
6%
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Slide 19
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Slide 20
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Slide 21
Lung metastases - Results of
ESR
Author
# of targets
Median f/u
Uematsu
Nakagawa
Nagata
Wulf
Hara
Onimaru
23
21
9
11
18
20
20 m
10 m
18 m
8m
12 m
18 m
Local
control
100%
95%
66%
85%
78%
90%
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Slide 22
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Slide 23
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Liver metastases
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Colorectal Ca metastatic to liver
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Incidence = 40,000 per year in US
40% 5-year survival with resection of met1
Favorable prognosis following resection:
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≤ 4 metastases
Lower preoperative CEA
Lesion < 5 cm diameter
Margin of resection > 10 mm
Lack of extrahepatic disease
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1Belli
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38% 5-year overall survival2
Favorable prognosis:
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Gastric
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Solitary metastasis
et al, J Hep Pancr Surg 9:607, 2002. 2Sakamoto et al, Surgery 133:507-11, 2003.
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Slide 24
Liver mets: surgery for other histologies
Primary
# reported
cases
Renal
18
Wilm’s
16
Adrenocort. 15
Breast
63
Ovarian
17
Melanoma 26
Testicular 9
Sarcoma
48
GYN
10
5-yr OS
38.8%
37.5%
26.6%
14.3%
11.7%
11.5%
11.1%
10.4%
10%
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Slide 25
Dose responsiveness
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Dawson et al, JCO 18:2210-18, 2000.
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Slide 26
Liver volume dependence
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Dawson L; IJROBP 53:810-21, 2002.
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Slide 27
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Dose threshold
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Dawson L; IJROBP 53:810-21, 2002.
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Slide 28
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Liver tumors - Results of SRS
Author
# of targets
Median f/u
Blomgren
Herfarth
Sato
Wulf
41
60
23
36
9-12 m
6m
10 m
9m
Local
control
95%
80%
100%
83%
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Slide 29
Liver toxicity of SRS
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Nausea, low grade fever common
Responsive to premedication
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Blomgren
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Herfarth
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Sato
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Wulf
5/21 patients: intractable ascites, subcapsular
bleed, or GI ulcers
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No major side effects
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No major toxicity
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No grade 3-5 toxicity
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Slide 30
Other applications
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Spine
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Metastases (Ryu et al, Cancer 97:2013, 2003).
Primary tumors (Ryu et al, Neurosurg 49:838, 2001).
Head and neck tumors
Prostate
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Low α/β ratio favors hypofractionated approach
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Slide 31
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What is possible with ESR?
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Reduced toxicity of treatment
Alternative to conventional surgery or
other invasive treatments
Improved tumor control
Improved patient survival
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