L29 - IMRT and IGRT For Pelvic Abdomen Cancer - de Crevoisier

ESTRO course
IMRT/IGRT for pelvic/abdomen

cancer
R. de Crevoisier
Centre Eugne Marquis, Rennes, France
October 2012, New Dehli
IMRT and IGRT for pelvic/abdomen cancer:

Exclusion of practical aspects (already presented in clinical cases)
OUTLINE
1. Prostate cancer:
- primary tumor
- after prostatectomy
2. Gynaecological cancers:
- cervix carcinoma
- endometrial cancer
3. Digestive cancer:
- anal canal
- rectum
- pancreas
pelvic lymph nodes +++
IMRT and IGRT for prostate

cancer
IMRT-IGRT in prostate
Outline
1.Total dose in the prostate?
2. Dosimetric benefit of IMRT (> standard 3DCRT) ?
3. Clinical benefit of IMRT (> standard 3DCRT) ?
4. Benefit of arc-IMRT ?
5. Strategies of IGRT ?
6. Clinical benefit of IGRT ?
7. New approaches of IMRT + IGRT ?
Outline
n
i
n
o
i
lat
a
c
s
e
e
s
r
o
e
d
c
r
n
o
a
f
c
l
e
a
t
n
a
o
t
i
s
t
o
a
R
pr
Randomized studies showing the benefit of dose

escalation (without IMRT and androgen deprivation)
Standard dose (67-70 Gy)
Randomization
High dose (76-80 Gy)
Randomized studies showing the benefit of dose

escalation (without IMRT and androgen deprivation)
Nb of
Pts
Tumors
Dose
(Gy)
Volume
Shipley
1995
202
T3-4
N0-N2
67
76
pelvis (50 Gy) + boost

proton
Pollack,,Kuban
2000, 2002, 2008
305
T1-T3
70
78
pelvis (46 Gy) + boost
Zietman
2005
393
T1b-2b and
PSA<15
70
79
Prostate + SV
proton
Dutch
2008
669
T1b-T4N0
68
78
Prostate + SV
GETUG 06
2010
306
(low risk:18%, int:27%, high: 55%)
Intermediate risk
70
80
(+ AD =143 pts)
Prostate + SV
Randomized studies showing the benefit of dose escalation

Local control
(negative
biospy)
Freedom from
biochemical failure
Freedom from
clinical failure
Specific
survival
Shipley
1995
Gl 8:
19% vs 64%
No PSA available
NS
NS
Pollack, Kuban
2000, 2002, 2008
72% vs 65%
NS
Zietman
2005
48% vs 67%
(p<0.001)
Dutch 2008
NS
GETUG 06
2010
NS
Median folow-up = 10 years
PSA<10
PSA>10
7% vs 15%
(p= 0.01)
P<0.05
61% vs 80%
(p<0.001)
including low risk group
NS
NS
45% vs 56% (p<0.001),

mainly intermediate risk
group
NS
NS
NS
NS
PSA>15
NS
p=0.012
p=0.03
IMRT-IGRT in Prostate
Price of non-IMRT dose escalation

in prostate cancer ?
Randomized studies
GETUG 06
70
14
80
22
NS
10
.04
18
Cahlon, Seminars in Radiation Oncology 2008
risk of toxicity x2
n
o
i
t
a
l
a
c
s
e
e
u
s
o
o
y
d
r
r
e
o
f
v
e
l
a
w
)
n
o
T
o
h
R
i
t
M
r
a
I
e
r
o
c
n
g
n
if
a
n
(
c
o
t
i
r
e
t
r
St
a
o
t
f
s
e
o
c
r
i
p
r
p
in
a
y
a
p
l
l
i
w
Outline
Dosimetric benefit of IMRT over 3DCRT
3DCRT
- concave dose distributions

- tight dose gradients
Dosimetric study comparing 3DCRT with IMRT

31 pts
T1b-T2c
3DCRT:
2 lat et 4 oblique (310, 50, 230,130)
IMRT:
- 5 beams: 0, 45, 135, 225, 315
- 7 beams: 0, 40, 80, 120, 240, 280, 320
Target volume :
- prostate only (74 Gy)

- prostate (74 Gy) et VS (50 Gy)
Luo, IJROBP 2006
PROSTATE only
V60, V70, mean: p<0.05
BLADDER
V60, V70, mean: p<0.05
3DRT
RECTUM
IMRT
Luo, IJROBP 2006
PROSTATE only
V60, V70, mean: p<0.05
V60, V70, mean: p<0.05
3DRT
BLADDER
RECTUM
IMRT
PROSTATE and SV
V60, V70, mean: p<0.05
V60, V70, mean: p<0.05
Dosimetric benefit of IMRT in pelvis
IMRT versus 3D-CRT to treat the pelvis

2 LN target volumes compared (> limit): - small pelvis (L5-S1)
- large pelvis (> L5-S1,
lower para-aortic nodes)
35 pts
2 EBRT techniques compared:
- bony landmarks 3DCRT

- IMRT
3D-CRT
large pelvis
(above L5-S1
)
IMRT
Wang-Chesebro IJROBP 2006
IMRT improves lymph nodes coverage compared with 3DCRT
small pelvis
large pelvis
IMRT decreases dose to critical structures compared with 3DCRT
IMRT decreases dose to critical structures compared with 3DCRT
Outline
y
l
t
n
a
c
i
f
i
,
n
r
g
i
e
s
d
s
d
e
a
s
l
a
b
e
e
r
c
h
t
e
,
d
2. Dosimetric benefit
of
IMRT
(>
standard
3DCRT)
?
b
l
m
T
u
u
R
t
b
c
l
e
M
i
I
r
n
,
e
e
s
p
h
e
3. Clinical
oftIMRT (> standard
3DCRT)
?
e
Y benefit
o
h
t
t
e
d
s
n
o
a
d
l
e
e
4. Benefit
?
w
th of arc-IMRT
o
b
e
h
t
Outline
IMRT-IGRT in Prostate
Clinical benefit of IMRT
IMRT=dose escalation tool
increasing biochemical control while not
increasing toxicity
no randomized studies comparing 3DCRT and IMRT
Up to 86.4 Gy !!!
86.4 Gy
86.4 Gy
Low risk
High risk
Intermediate
risk
Zelefsky, J Urol 2001
IMRT allows dose escalation while limiting acute

toxicity
81 - 86,4 Gy
Median follow-up= 24 months (6-60)
Zelefsky, IJROBP 2002
IMRT provides very low GI toxicity despite high dose

in the prostate
170 patients received 81Gy with IMRT
median follow-up =8.2 years
Alicikus Cancer 2011
IMRT decreases GI toxicity compared to 3DCRT

(non randomized study)
3DCRT (without IMRT)
IMRT
Zelefsky, J Urol 2001

N= 284 pts
- 3DCRT: 74 Gy (n=94)
- IMRT-seq: 78 Gy (n=138)
- IMRT-SIB: 82 Gy (2 Gy) + 73.8 (1.8 Gy) (n=52)
Dolezel,Strahlenther Onkol 2010

Grade 3 late GI toxicity
Dolezel,Strahlenther Onkol 2010
= Low rates of toxicity despite dose escalation in the prostate
Toxicity:
Standard dose without IMRT = High dose with IMRT
51 pts
median age = 65 years (4677)
unilateral or bilateral nerve-sparing prostatectomy

33 pts (64.7%) impotent after nerve-sparing
prostatectomy
IMRT
mean dose = 69.6 Gy (64.0 72.3)
All 18 patients (100%) who were potent post-operatively remained potent after RT
(median follow-up = 27 months)
Bastasch IJROBP 2002, and Teh AJCO 2007
Outline
e
m
o
c
t
u
o
e
t
s
p
o
s
d
e
o
v
t
o
s
r
k
p
n
2. Dosimetric benefitim
of IMRT (> h
standard
3DCRT) ?
a
t
T
)
R
y
t
i
M
c
I
i
x
,
s
o
3. Clinical
benefit
of
IMRT
(>
standard
3DCRT)
?
t
/
n
l
Ye
o
o
i
r
t
s)
t
e
a
i
n
l
d
o
a
tu
c
s
c
l
d
s
e
a
e
4. Benefit
(loc of arc-IMRT ? ndomiz
ra
n
o
in n
(
5. Strategies of IGRT
?

Outline
Static-IMRT versus VMAT in prostate ?

10 pts
74 Gy 74 Gy
3DCRT
5-fields
IMRT
VMAT
Constant
Variable
dose rate
dose rate
Palma IJROBP 2008
10 pts
Palma IJROBP 2008
10 pts
Palma IJROBP 2008
Clinical study
80 pts
80 pts
74 Gy in the prostate
respecting the dose
constrains in the OAR
Standard
IMRT
Clinical
outcome
VMAT
Ruchaud, ESTRO 2010

Efficiency study
standard
Treatment time/5
Decrease intrafractional motion ?

Ruchaud, ESTRO 2010

Clinical study
CTCAE V3
acute toxicity: relatively low and not different

between the 2 IMRT modalities
Ruchaud, ESTRO 2010
Time sparing approach
Dose optimization
approach
std IMRT
VMAT
std IMRT
VMAT
Dose
distribution
++++ (?)
Radiation
delivery time
Monitor
Units
Tomotherapy
intra-fraction
motion / cost
standard RT protocol
Dose escalation/painting
Outline
IGRT in prostate: strategies

On-line
Prostate (rigid)
registration
Indirect prostate
visualisation
Fiducials/markers
Direct prostate
visualisation
CBCT/Tomotherapy/CT on rails

On-line
Prostate rotation
Prostate (rigid)
registration (translation)
Indirect prostate
visualisation
Fiducials/markers
SV volume
variations
Adaptive RT
Re-plannning
Direct prostate
visualisation
Adaptive RT: ON-line

Deformable
registration based
re-optimization
IMRT
Modification of multileaf
collimator leaf positions using
slice by slice registration
Court IJROBP 2005
Ahunbay IJROBP 2010
Key issue = duration

of the re-planning
realistic ??
Wi Phys Med Bio 2008

On-line
Prostate (rigid)
registration
Indirect prostate
visualisation
Off-line
Adaptive RT
Re-plannning
customized
reduced PTV
Direct prostate
visualisation
few 3D imaging
(before/during RT)
Fiducials/markers
Adaptive RT: OFF-line
planning CT +
first 4 repeat
CT scans
Before RT
During RT
Hoogeman
Radiother Oncol 2005
Ghilezan, Seminars RO 2010

On-line
Off-line
Prostate rotation
Prostate (rigid)
Indirect prostate
visualisation
SV volume
variations
Adaptive RT
Re-plannning
customized
reduced PTV
Direct prostate
visualisation
few 3D imaging
(before/during RT)
Fiducials/markers
If prostate rotation
(outside PTV)
Adaptive RT: hybrid OFF/ON line

NKI
average prostate position and rectum shape
-1rst plan: initial 10 mm PTV margin

- new plan: 6 CBCT: average CTV and rectum: 7 mm PTV margin
-Weekly CBCT for monitoring
Nijkamp IJROBP 2007

On-line
Off-line
Prostate rotation
Prostate (rigid)
Indirect prostate
visualisation
Fiducials/markers
SV volume
variations
Direct prostate
visualisation
Adaptive RT
Re-plannning
pre-treatment
plan library
(SV)
customized
reduced PTV
few 3D imaging
(before/during RT)

On-line
Off-line
Cumulative dose
(elastic registration)
Prostate rotation
Prostate (rigid)
Indirect prostate
visualisation
Fiducials/markers
SV volume
variations
Direct prostate
visualisation
Adaptive RT
Re-plannning
pre-treatment
plan library
(SV)
If prostate
rotation
customized
reduced PTV
few 3D imaging
(before/during RT)

r
o
f
e
t
On-line
Off-line
a
s
n
e
e
p
r
m
o
o
m
c
o
o
t
t
s
e
l
e
i
p
Cumulative
dose
g
e
m
i
t
s
a
r
t
m
s
o
(elastic
registration)
r
T
f
(
R
s
G
n
I
o
l
i
)
t
a
e
a
r
x
i
e
e RT
r
l
a
ev
p
?
v
SProstate
Adaptive
customized
t
m
c
(rigid)
i
i
o
f
c
e
m
nreduced PTV
o
e
t
a
b
l
n
registration
(translation)
a
Re-plannningica
n
i
l
c
o
t
n
i
te
Indirect prostate
Direct prostate nsla
a
r
visualisation
visualisation
pre-treatment
t
t
i
s
plan library
few 3D imaging
Doe
(SV)
(before/during RT)
Fiducials/markers
If prostate
rotation
Outline
IGRT for prostate cancer
Daily IGRT
- Quantification of prostate
displacement
Random
202 pt seach arm

(12% difference at 5 years ofbiochemical
control)
-Biochemical and clinical

control /toxicity
- Cost (2D versus 3D and daily versus
weekly)
Day 1,2,3 and

weekly IGRT
De Crevoisier, ASTRO 2009
Preliminary results
Feasibility of prostate registration
-
Analysis = 107 pts (410 updated) treated by IGRT = 4078 displacements
Median total dose = 76 Gy (70-80 Gy)
- IGRT =
- Cone Beam CT (67%)
- Fiducial markers (28%)
- Ultrasounds (5%)
- Prostate registration performed in 94% of cases

- Bone registration in 5% of cases
IGRT reduces rectal toxicity
Acute toxicity (CTCAE v.3)

Rectal
Bladder
Grade 2
7%
36%
Grade 3
0%
4%

Reducing margins thanks to IGRT and therefore toxicity
25 pts
10 pts
73.8 Gy in the prostate
15 pts
Chung IJROBP 2008

Dosimetric impact of reducing PTV margin
Chung IJROBP 2008
IGRT reduces toxicity

Acute toxicity
/5-6
Chung IJROBP 2008

PTV < 5 mm ???

Risk of mistargeting and
decreased local control ?
- delineation uncertainties
- intra-fraction prostate motion
- uncertainties in registration
Chung IJROBP 2008
Clinical benefit of IGRT in prostate

Biochemical control by RT technique
(Beaumont group, 3064 pts)
Biochemical control by RT technique

(Beaumont group, 3064 pts)
d
n
a
y
t
i
c
i
x
o
t
l
a
t
l
c
e
o
r
r
t
s
n
e
)
o
c
d
c
e
u
t
l
i
d
a
e
m
i
c
r
l
o
l
l
l
i
T
t
e
s
R
v
e
o
r
G
a
r
I
s
p
,
t
l
s
u
m
e
s
i
e
Y
r
y
l
a
m
nica
(alth
i
l
c
h
ou g
- dose escalation / hypofractionation (SIB) in large target volume
- Toward dose-tumor painting (dominant lesion)
N=103 pts
-Prostate delineation: CT-MRI co-registration

-IMRT in 2 sequential phases:
- P, SV and LN: 55.1 Gy in 29 fractions of 1.9 Gy
+ consecutive boost in P + SV of 24.7 Gy in 13 fractions of 1.9 Gy (=79.8 Gy)
- IGRT: intraprostatic markers

Bayley IJROBP 2009
N=123 pts
IMRT in 2 phases: 55.1 Gy + 24.7 Gy (=79.8 Gy)
median follow-up = 23 months
Acute toxicity
Bayley IJROBP 2009
PELVIC IMRT WITH SIMULTANEOUS INTEGRATED BOOST TO

PROSTATE
low / ratio for prostate cancer (=1.5 to 3)
hypofractionation
30 pts
Intermediate/
high risk
cancer
Prostate: 70 Gy in 28 fractions (2.5 Gy/fr)
77-80 Gy
Pelvic LN: 50.4 Gy in 28 fractions (1.8 Gy/fr)
+ androgen suppression
McCammon IJROBP 2009
IMRT (high dose with SIB)+IGRT provides low toxicity
median follow-up
= 24 months (1243)
McCammon IJROBP 2009
35 pts
pelvic LN = 52 Gy
prostate = 74,2 Gy (concomitant boost)
Intestinal cavity
HTT very efficient in

sparing the IC even at
dose levels < 30-35 Gy.
Significant sparing of
rectum and bladder
even at intermediatelow doses (20-40 Gy).
Very low incidence

( 5%) of Grade 2 acute
GU and GI TOX.
Disappearance of acute
G3 TOX.
Cozzarini, Fiorino, Radiother Oncol 2007
- Toward dose-tumor painting (dominant lesion)
230 patients
- Intra-prostatic lesion defined by MRI (pelvic coil+spectroscopic endorectal coil) (+ 4 mm PTV)
- Total Dose:
- in the prostate =76 Gy in 38 fractions (2 Gy/fr)
- in the IPL= 82 Gy in 38 fractions (2,16 Gy/fr)
Criteria for planning acceptance
Fonteyne IJROBP 2008
230 patients
Total Dose (to the MRI + spectroscopy-detected Intra Prostatic Lesion) =82 Gy
Grade 3 or 4 acute GI toxicity = 0

Grade 3 acute GU toxicity = 7%
Fonteyne IJROBP 2008
Dose-tumor painting
Prostate (+ 5 mm PTV)
Dosimetric study
Peripheral zone (+ 5 mm PTV)

Dominant lesion (+ 5mm PTV)
MRI
Planning CT (VMAT)
CBCT (IGRT)
Prostate registration performed thanks to fiducials

Jouyaux, Cancer Radiother 2010
Dose-tumor painting (VMAT)
High dose in the tumor while respecting the dose constraints in the
OARs (no patients treated)
GTV=PET = tumour-to background

choline uptake ratio >2 (studies correlating choline
PET results with histopathologic examinations)
- Prostate = 66.6 Gy in 37 fractions (1.8 Gy/ fr)

- GTV-PET=83.25 Gy in 37 fractions (2.25 Gy/ fr)
(no patients treated)
Pinkawa, radiother Oncol 2010
g
n
i
t
d
n
n
i
a
a
)
p
GTV=PET
= tumour-to background
I
e
R
s
o
M
( correlating choline
d
(studies
choline
uptake
ratioi>2
g
r
n
o
f PET resultsim
g
r
withahistopathologic
examinations)
o
t
c
n
a
e
f
e
g
w
)
t
n
r
e
i
t
o
b
i
m
n
Lim elatio
y (tu
s
k
c
a
l
=
r
r
o
c
of
g
e
i
o
l
d
o
u
p at h d f or s t
ne-eProstate = 66.6 Gy in 37 fractions (1.8 Gy/ fr)
- GTV-PET=83.25 Gy in 37 fractions (2.25 Gy/ fr)
Pinkawa, radiother Oncol 2010
Conclusions: IMRT-IGRT in prostate

= dose escalation (impact on specific survival)

= yes, in all OARs

= yes, it allows dose escalation without increasing toxicity (no randmzd st)
4. Benefit of arc-IMRT ? Time sparing/ improvement in dose distribution

5. Strategies of IGRT ? = gradient of complexity
6. Clinical benefit of IGRT ? = yes, decrease toxicity
7. IMRT + IGRT opens news approaches:
- toward dose-tumor painting (dominant lesion)
TUMOR DELINEATION
Functional imaging (MRI)

Registration
tool
Years 1990
Years 2000
Years 2010
DOSE DISTRIBUTION
Box technique
3D conformal EBRT
IMRT
Image-guided RT
Portal imaging
TUMOR LOCALIZATION
Arc IMRT
Dose -guided RT
Dose painting (MRI+VMAT+IGRT)
n
n
o
i
o
t
i
a
s
e
n
l
o
t
i
t
n
c
a
a
n
r
i
f
m
po
o
y
d
H
n
i
n
o
i
t
a
l
a
c
s
e
se
o
D
Respect of the dose contraints in the OAR
IMRT/IGRT
for gynaecological cancers
IMRT-IGRT in gyn: goal nb 1= decreasing side effects

> Grade 3 complications = 10-12% at 10 yrs
Late grade 3 complications:
- Small Bowel 3%
- Rectum 5%
- Bladder 5%
- Sigmoid < 0.2%
Minimal TOXICITY
+ CDDP
-Rectum
-Bladder
Decreasing the dose in the OARs
-Small bowel
Cervical cancer
-Bone marrow
Endometrial cancer
Increasing the dose in the tumor
Vulvar carcinoma
Ovarian cancer
Large target volumes + CDDP

Pelvic, inguinal, lombo-aortic
lymph nodes
Maximal LOCAL CONTROL
Why IMRT in gynecological malignancies ?

To spare:
In the lower pelvis:
- the rectum
- the bladder
- the bone marrow
In the upper pelvis:

- the small bowel
- the bone marrow
In the abdomen:
- the kidneys
- the small bowel
Roeske, IJROBP 2000
IMRT-IGRT in gyn: goal nb 2=improving local control
Minimal TOXICITY
Cervical cancer
Endometrial cancer
Decreasing the dose in the OARs
Vulvar carcinoma
Ovarian cancer
Pelvic, inguinal, lombo-aortic

lymph nodes
Why IMRT in gynecological malignancies ?

To escalate the dose in locally advanced cervical
cancer (tumor and nodes)
PET guided IMRT
IMRT in gynaecological tumor
Minimal TOXICITY
DOSIMETRIC
benefit of IMRT
(/3DCRT) ?
Decreasing the
dose in the OARs

DOSIMETRIC
benefit of IMRT ?
Minimal TOXICITY
IMRT reduces the

dose to the:
Decreasing the
dose in the OARs
-small bowel
-rectum
-bladder
-bone marrow
-kidney
DOSIMETRIC STUDY: standard 3DCRT versus IMRT

IMRT spares the small bowel
36 gynecological tumor pts
IMRT
4 fields
Mundt, IJROBP 2003

DOSIMETRIC
benefit of IMRT?
Minimal TOXICITY
IMRT reduces the

dose to the:
Decreasing the
dose in the OARs
-small bowel
-rectum
-bladder
-bone marrow
-kidney

10 pts: cervical (5) or endometrial (5)
- CTV: proximal vagina, parametrial tissues, uterus (if present) + regional lymph nodes
- PTV: CTV expanded uniformly by 1 cm
45 Gy
average PTV doses:
4-field box
IMRT
47.8 Gy
47.4 Gy
Roeske, IJROBP 2002

IMRT spares the rectum
average volume of rectum

irradiated at the prescription
dose reduced by 23%
(p<0.001)
Roeske, IJROBP 2002

DOSIMETRIC
benefit of IMRT ?
Minimal TOXICITY
IMRT reduces the

dose to the:
Decreasing the
dose in the OARs
-small bowel
-rectum
-bladder
-bone marrow
-kidney

IMRT spares the bladder
average volume of bladder

irradiated at the prescription
dose reduced by 23%
(p<0.001)
Roeske, IJROBP 2002

DOSIMETRIC
benefit of IMRT?
Minimal TOXICITY
IMRT reduces the

dose to the:
Decreasing the
dose in the OARs
-small bowel
-rectum
-bladder
-bone marrow
-kidney
7 pts
+ CDDP
7 pts
IMRT
AP/PA
4 field box
Mell, IJROBP 2008
IMRT spares the bone marrow
Lower pelvic bone marrow
Mell, IJROBP 2008

DOSIMETRIC
benefit of IMRT?
Minimal TOXICITY
IMRT reduces the

dose to the:
Decreasing the
dose in the OARs
-small bowel
-rectum
-bladder
-bone marrow
-kidney
Extended irradiation to the para-aortic area

IMRT spares the kidneys
2 fields vs 4 fields vs IMRT
- Significant dose reduction to kidneys

- No dose level above 18 Gy
Salama, IJROBP 2006

DOSIMETRIC
benefit of IMRT
Minimal TOXICITY
Decreasing the
dose in the OARs
CLINICAL benefit of
IMRT?
IMRT in gynecological cancer

Clinical experience relatively limited:
- Limited number of series
- Limited number of pts/series
- Limited follow-up

CLINICAL
benefit of IMRT?
Minimal TOXICITY
IMRT reduces the

toxicity :
Decreasing the
dose in the OARs
- GI toxicity (acute/late)
- GU toxicity (acute/late)
- hematological
Clinical benefit of IMRT in gynecological cancer

Locally advanced cervical cancer
111 patients, 3 institutions (2000-2007), all IMRT
45 Gy in 1.8-Gy daily fractions
Median follow-up = 27 months
Hasselle, IJROBP 2011

TOXICITY
111 patients, 3 institutions (2000-2007)
Low late toxicity (<3% grade 3 and 4)

Hasselle, IJROBP 2011

Kidd, IJROBP 2010

GI/GU toxicity
non IMRT
IMRT
Kidd, IJROBP 2010
IMRT for gynecological tumor is safe:

provides high local control and survival
Kidd, IJROBP 2010

CLINICAL
benefit of IMRT?
Minimal TOXICITY
IMRT reduces the

toxicity :
Decreasing the
dose in the OARs
- hematological
36 pts
Absolute Neutrophil Count
Pelvic bone marrow
Brixey, IJROBP 2002

CLINICAL
benefit of IMRT ?
Minimal TOXICITY
IMRT reduces the

toxicity :
Decreasing the
dose in the OARs
- hematological
IMRT allows new RT

indications
IMRT for recurrence (re-irradiation)
Recurrence in the right common iliac lymph nodes
Recurrence in the para-aortic nodes
Eifel, IG-IMRT Springer 2006
IMRT allows to irradiate large volumes
8 pts
-Target volume
whole abdomen +
(retroperitoneal, para-aortic and pelvic) nodal areas
-Total dose
30 Gy in 1.5 Gy fractions and 4 weeks (5 1.5 Gy per week)
Rochet, BMC Cancer 2007
IGRT in gynaecological tumor

DOSIMETRIC
benefit
Anatomic
variations
IGRT ?
Cervix and uterus move considerably due to

bladder and rectal filling variations and tumor regression
(displacement of the uterine fundus up to 48 mm !!)
CLINICAL
benefit
PTV margins
- For set-up uncertainties= 5-7 mm
(Stroom IJROBP 2000)
- For internal organ motion =10-15 mm
(Tyagi IJROBP 2011)
PTV margins should be around 15 mm

(less for the LN=7 mm)
IGRT in gynecological tumors: strategies

EPIDs, kV imaging
Bony anatomy registration

(minimize the set-up error)

EPIDs, kV imaging

CBCT, tomotherapy
Soft tissue visualisation
check the CTV (uterus) inside the PTV
Yes
Treatment

EPIDs, kV imaging
CBCT, tomotherapy

No (and systematic)
Off-line:
Increase PTV margins
Yes<
Treatment

EPIDs, kV imaging
CBCT, tomotherapy

No (and systematic)
Off-line:
Yes
Treatment
Adaptive RT (New plan)
2 hypothetical treatment scenarios:

- a 3-mm margin plan with no replanning
- a 3-mm margin plan with an automated replan performed on the updated weekly
patient geometry
Stewart IJROBP 2010
Weekly
replanning
improves PTV
coverage
Replan
No
replan
Stewart IJROBP 2010
11 cervical cancer patients
IMRT plan
PTV
(primary and nodal)
4 weekly IMRT plans per

pt, based on weekly MRI
scans (to simulate an onlineIMRT approach).
4 mm
1 reference IMRT plan

based on the pre-treatment
MRI scan (pre- IMRT)
10-15 mm
Comparison
-Bladder
- rectum
- bowel
- sigmoid:
-Contours
-6dose levels:
V10Gy,V20Gy,V30Gy,V40Gy,
V42.8Gy,V45Gy
Kerkhof, IJROBP 2008
Online-IMRT in cervix
Online IMRT compared to pre-IMRT decreases

the dose in the OARs (by decreasing PTV margins)
Online IMRT compared to pre-IMRT decreases

the dose in the OARs (by decreasing PTV margins)
o
d
to
w
o
h
t
?
u
e
b ctic
y
r
a
o
r
e
p
h
t
n
i
n
i
T
g
R
n
i
t
M
s
I
e
r
e
e
n
t
i
In on-l

EPIDs, kV imaging
CBCT, tomotherapy

No (and systematic)
Yes
On-line:
Off-line:
treatment plan
library
Adaptive RT (New plan)
Treatment
Predict uterus/cervix shape and position

based on bladder filling
2 series of
CT-scans
customized ITV that could replace the conventional PTV

adaptive strategy based on a pre-treatment generated treatment plan library
Bondar, adiother Oncol 2011
IMRT in gynecological cancer

Conclusions
- IMRT experience is relatively limited (nb of series, nb of pts/series, follow-up)
- IMRT compared to 3DCRT provides:
- dosimetric benefit: in rectum/bladder/small bowel/bone marrow
- clinical benefit:
- is safe
- lower acute +late toxicity (GU/GI/hematological)
- new RT indications: whole abdomen RT / re-irradiation
- IGRT: strong rational due to uterus motion, almost no-clinical
experience
Cervix cancer +++
IMRT-IGRT for anal canal
Dosimetric benefit of IMRT in anal canal ?

10 pts
CTV= tumor, anal canal, inguinal, peri-rectal, and internal/external iliac nodes (+ pre-sacral for T4/N2-3)
45 Gy/25 followed by a 14.4 Gy/8 boost
AP/PA 3D-RT
IMRT
Menkarios, Radiation Oncol 2007
Dosimetric benefit of IMRT in anal canal
AP/PA 3DCRT
IMRT
>
Menkarios, Radiation Oncol 2007
IMRT in anal canal tumor

DOSIMETRIC
benefit of IMRT
Minimal TOXICITY
Decreasing the
dose in the OARs
CLINICAL benefit of
IMRT?
Clinical benefit of IMRT in anal canal
Salama
53 pts with anal cancer

IMRT:
45Gy in: GTV, internal/external iliac + inguinal nodal group
+ 9 Gy in primary sites and involved nodes
9 equally spaced fields (0, 40, 80, 120, 160, 200, 240, 280, and
320 degrees)
+ cc chemo (5FU /mitomycin C)
IMRT in anal canal decreases toxicity

comparison with results from RTOG 98-11 (no IMRT)
Concomitant chemo-RT (5-FU/mitomycin) vs.
Induction with 5-FU/Cisplatin followed by concomitant chemo-RT
58% completed treatment without interruption

GI toxicity: Grade 3 in 15% with no Grade 4
Better than RTOG 98-11: 34% had Grade 3 - 4
Dermatologic: Grade 3 in 38%

Similar to studies with 2-wk treatment breaks
Better than RTOG 98-11: 48%
Hematologic toxicities: Grade 3 and 4 in 58% of patients

Similar to RTOG 98-11 rates of 60% (however no bone IMRT
constraints)
Salama, JCO 2007
IMRT in anal canal is safe

Carcinologic results
Salama
Complete response: 92%

Local recurrence rate: 13% @ 18 months
18-month colostomy free survival: 83.7%
18-month distant recurrence free survival: 92.3%
Static IMRT versus VMAT in anal canal ?

DOSIMETRIC study
10 patients
Plans generated for each case:
- fixed beam IMRT
- single (RA1) + double (RA2)-modulated arcs
Dose prescription: simultaneous integrated boost:

- 59.4 Gy to the primary tumour (at 1.8 Gy/fraction)
- 49.5 Gy to risk area including inguinal nodes
Planning objectives:
-PTV: minimum dose >95%, maximum dose < 107%
-OARs:
- bladder (mean < 45 Gy, D2% < 56 Gy, D30% < 35 Gy)
- femurs (D2% < 47 Gy)
- small bowel (mean < 30 Gy, D2% < 56 Gy)
Clivio, Radiother Oncol 2010
Static IMRT versus VMAT in anal canal
Number of computed MU/fraction:

-1531 206 for IMRT
- 468 95 for RA1
/3
- 545 80 for RA2
Treatment time:
- 9.4 1.7 min for IMRT
- 1.1 0.0 min for RA1
- 2.6 0.0 min for double arcs
/5
Dosimetric benefit of arc-IMRT for the

bladder/femurs
IMRT/IGRT
in rectal cancer
Dosimetric benefit of IMRT in rectum ?

10 pts T3 pre-op 45 Gy
Mok, Radiation Oncol 2011
Dosimetric benefit of IMRT in rectum
IMRT reduces significantly the dose to the small bowel
Mok, Radiation Oncol 2011
IMRT in rectum tumor

DOSIMETRIC
benefit of IMRT
Minimal TOXICITY
Decreasing the
dose in the OARs
CLINICAL benefit of
IMRT?
Clinical benefit of IMRT in rectum

92 pts
50.4
Gy
Samuelian, IJROBP 2011
Samuelian, IJROBP 2011
IGRT in rectum tumor

DOSIMETRIC
benefit
mobility + shape variation of

the rectum and the mesorectum
Anatomic
variations
IGRT ?
(CT scans, CBCT scans, tomography

scans, cine-MRI, clips)
CLINICAL
benefit
IGRT for rectal cancer

Step 1: quantification of anatomic variations and PTV
margins
Lee IJROBP
2006
DEnittis
IJROBP 2008
Brierley Ann
Oncol 2007
Tournel
IJROBP 2008
Anisotropic margins
Gwynne Clin Oncol 2011
IGRT for rectal cancer

Step 2: Define a strategy to correct for
the anatomical variations
- Prone position (however set-up variation and discomfort)
- Bony anatomy registration (setup uncertainties)
- Soft tissue visualisation: check the CTV inside the PTV:
EPIDs, kV imaging
CBCT, tomotherapy
-laxatives or rectal enemas (preventive/if distension)

-treatment plan library
-adaptive re-planning
Very few clinical results
Gwynne Clin Oncol 2011
IMRT for pancreatic tumors
Dosimetric benefit of IMRT in pancreas ?

OARs:
Liver
Kidney
Spinal cord
Small bowel
CTV:
- GTV or tumor bed
- draining lymphatics (portahepatis, pancreaticoduodenal,
celiac, and periaortic)
= 45 to 54 Gy
3D CRT
6 pts
IMRT
(7 to 9 fields)
Milano, IJROBP 2004
Dosimetric benefit of IMRT in pancreas
3D4D
IMRT
Milano, IJROBP 2004
Clinical benefit of IMRT in pancreas

46 pts with pancreatic cancer:
IMRT (50.4 Gy) + concurrent chemo ((5-FU + capecitabine)
Yovino, IJROBP 2011
Clinical benefit of IMRT in pancreas

46 pts with pancreatic cancer:
IMRT (50.4 Gy) + concurrent chemo ((5-FU + capecitabine)
acute GI toxicity compared with those from RTOG 97-04 (3DCRT witout IMRT)
>
Yovino, IJROBP 2011
IMRT/IGRT in pelvis/abdomen :
conclusions
IMRT
Experience
Prostate
Gynecol
Digestive
in place
+++++++
+ pelvic LN
+++++
post-op
+++
cervix
++
endometrium
++
anal canal
++
rectum
++
pancreas
Dosimetric
benefit
IGRT
Rational
Experience
+++++
+++
++
++
- local control
++
- rectum
- bladder
- bowel
- kidney
- bone
- ParaoLN
-GU/GI toxicity
(acute/late)
-hemato toxicity
+++
- rectum
- bladder
- bowel
- kidney
- bone
- perineum
- GI toxicity
- dermato toxicity
GI toxicity (acute)
+++
- rectum
- bladder
- bowel
- kidney
GI toxicity (acute)
-rectum
-bladder
-bowel
Clinical
benefit
-GU/GI toxicity
(acute/late)
++
-local control ?
Thank you !
Belle Ile, Bretagne, France

L29 - IMRT and IGRT For Pelvic Abdomen Cancer - de Crevoisier

Încărcat de

Informații document

Titlu original

Drepturi de autor

Formate disponibile

Partajați acest document

Partajați sau inserați document

Opțiuni de partajare

Vi se pare util acest document?

Este necorespunzător acest conținut?

Drepturi de autor:

Formate disponibile

L29 - IMRT and IGRT For Pelvic Abdomen Cancer - de Crevoisier

Încărcat de

Drepturi de autor:

Formate disponibile

ESTRO course

IMRT/IGRT for pelvic/abdomen

October 2012, New Dehli

IMRT and IGRT for pelvic/abdomen cancer:

pelvic lymph nodes +++

IMRT and IGRT for prostate

Randomized studies showing the benefit of dose

Standard dose (67-70 Gy)

Randomized studies showing the benefit of dose

High dose (76-80 Gy)

pelvis (50 Gy) + boost

pelvis (46 Gy) + boost

(low risk:18%, int:27%, high: 55%)

Randomized studies showing the benefit of dose escalation

High dose (76-80 Gy)

Median folow-up = 10 years

45% vs 56% (p<0.001),

Price of non-IMRT dose escalation

Cahlon, Seminars in Radiation Oncology 2008

Cahlon, Seminars in Radiation Oncology 2008

Dosimetric benefit of IMRT over 3DCRT

- concave dose distributions

Dosimetric study comparing 3DCRT with IMRT

- prostate only (74 Gy)

V60, V70, mean: p<0.05

Luo, IJROBP 2006

V60, V70, mean: p<0.05

V60, V70, mean: p<0.05

Dosimetric benefit of IMRT in pelvis

IMRT versus 3D-CRT to treat the pelvis

2 EBRT techniques compared:

- bony landmarks 3DCRT

IMRT improves lymph nodes coverage compared with 3DCRT

Wang-Chesebro IJROBP 2006

IMRT decreases dose to critical structures compared with 3DCRT

Wang-Chesebro IJROBP 2006

IMRT decreases dose to critical structures compared with 3DCRT

Wang-Chesebro IJROBP 2006

Zelefsky, J Urol 2001

IMRT allows dose escalation while limiting acute

Zelefsky, IJROBP 2002

IMRT provides very low GI toxicity despite high dose

median follow-up =8.2 years

Alicikus Cancer 2011

IMRT decreases GI toxicity compared to 3DCRT

3DCRT (without IMRT)

Zelefsky, J Urol 2001

IMRT decreases GI toxicity compared to 3DCRT

Dolezel,Strahlenther Onkol 2010

IMRT decreases GI toxicity compared to 3DCRT

Grade 3 late GI toxicity

Dolezel,Strahlenther Onkol 2010

= Low rates of toxicity despite dose escalation in the prostate

Cahlon, Seminars in Radiation Oncology 2008

Cahlon, Seminars in Radiation Oncology 2008

unilateral or bilateral nerve-sparing prostatectomy

Bastasch IJROBP 2002, and Teh AJCO 2007

6. Clinical benefit of IGRT ?

Static-IMRT versus VMAT in prostate ?

Palma IJROBP 2008

Static-IMRT versus VMAT in prostate ?

Palma IJROBP 2008

Static-IMRT versus VMAT in prostate ?