How Are We Going to Define
RT Targets in 2030?
…it will be very
different from now!
Søren M Bentzen, Ph.D., D.Sc.
Departments of Human Oncology; Medical Physics; Biostatistics and Medical Informatics,
UW Paul P. Carbone Comprehensive Cancer Center, Madison, Wisconsin, USA
bentzen@humonc.wisc.edu
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The dose-volume trade-off
IGRT: The bad old days….
Geographical miss
Dose-dependent failure
DOSE
HOW MUCH?
TY
CI
XI
O
T
VOLUME
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WHERE?
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Target volume SELECTION in HNSCC
Intensity versus volume
T2N1 tonsil cancer
rS=0.55
2P=0.015
Hong et al. ASTRO (2004)
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Chemotherapy and target volume
Bentzen et al. ASTRO (2005)
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Bentzen et al. ASTRO (2005)
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Auto-delineation from 18F-FDG PET
van Bardwijk et al. IJROBP 68: 771 (2007)
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Auto-delineation from 18F-FDG PET
Microscopic extension in stage I NSCLC
Reduced inter-observer variability with observeredited auto-delineation compared to CT in 33
NSCLC cases (5 observers)
van Bardwijk et al. IJROBP 68: 771 (2007)
Lower inter-observer variability with contrastenhanced CT than with FDG-PET in 10 HNSCC
cases (8 observers)
Breen et al. IJROBP 68: 763 (2007)
Thanks to
Noah Arvidson
Reproducibly wrong or reproducibly right?
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From CTV to RTV
GTVPET
INF: Isolated nodal failure after chemo-radiation therapy for lung cancer
Histology
N
INF
NSCLC
44
1
2%
10%
De Ruysscher 2005
LD-SCLC
27
3
11%
29%
De Ruysscher 2006
11%
van Loon 2010
LC-SCLC
60
2
Crude Upper
prop. 95% CL
3%
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Grills et al. IJROBP 69: 334, 2007
Lung cancer: Irradiating PET+ nodes only
Is involved node irradiation an alternative to elective
mediastinal irradiation?
Distance from
ME Coverage
GTV (mm)
(%)
1
0
2
0
3
4
4
13
5
25
6
32
7
42
8
52
9
68
10
78
11
84
12
86
13
95
14
97
15
100
Abbreviations: GTV = gross tumor
volume; ME = microscopic
extensions
Real
Target
Volume
Clinical
Target
Volume
Reference
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Planning
Target
Volume
Bentzen IJROBP 58: 320 (2004)
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The radiotherapeutic blind spot
DRUGS
20 Gy
35 Gy
Cancer
stem
cells?
70 Gy
CT/MRI
RT-PCR
PET
Log # cells in mass
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Dirks Nature 444: 687 (2006)
Incidence of pN+ nodes in oral cavity SCC
Patients undergoing prophylactic radical neck dissection
Site
No.
pts.
I
II
III
IV
V
Tongue
58
14%
19%
16%
3%
0%
Floor of mouth
57
16%
12%
7%
2%
0%
Gum
52
27%
21%
6%
4%
2%
Retromolar trigone
16
19%
12%
6%
6%
0%
Cheek
9
44%
11%
0%
0%
0%
192
20%
17%
9%
3%
1%
Total
http://www.rtog.org/pdf_document/atlasneck_CTV.pdf
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Shah et al., Cancer 66: 109 (1990)
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N0
63%
T
N+
37%
N0: N(+) or N(-) ?
CHART HNSCC Trial
QUESTION: Can we select patients for elective irradiation?
PROBLEM: Low incidence of events → low statistical power
SOLUTION: Analyse molecular risk factors in N+ v N0 & apply to N0 patients
ANSWER:
Ki-67 pattern, p53 index, p53 staining intensity all associated with N+
Bentzen, Wilson, Saunders (submitted)
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Modeled failure-specific rates in HNSCC
2-year distant relapse rate
Management of the N0 neck in HNSCC
0.8
309 head & neck SCC
0.6
8%
0.4
0.2
38%
54%
0
0
0.2
0.4
0.6
0.8
2-year local relapse rate
Ataman et al. EJC 40: 2738 (2004)
Bentzen Sem Rad Onc 8: 75 (2008)
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Target volume selection - efficacy:toxicity
BUT….
If the benefit:risk is high
SUPERSIZE IT!
treatment failure after RT is about
biology as much as about geometry!
If the benefit:risk is low
GO LEAN!
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Dose-painting by numbers
Dose-painting by numbers
0.18
0.16
Frequency
0.14
0.12
0.1
0.08
0.06
0.04
0.02
0
0.0423 0.889 1.73
2.58
3.43
4.27
5.12
5.96
61Cu-ATSM
6.81
SUV
Normo-oxic
70
Anoxic
75
80
85
85
Dose in 35 F (Gy)
Bentzen Lancet Oncology 6: 112 (2005)
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Target selection and delineation 2030
Think for a moment where we were 20 years ago!
A number of new imaging and molecular finger-printing
tools are at our disposal – the challenge is to demonstrate
clinical benefit and cost-effectiveness
The gold standard is clinical outcome
• Do not develop surrogates of surrogates
Choosing to irradiate a given voxel to a given dose
involves a (local) trade-off between cost and benefit
Imaging & radiation therapy: the perfect match!
• But in many cases BIOLOGY > GEOMETRY
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Bentzen Lancet Oncology 6: 112 (2005)
Bowen et al. (in preparation)
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