Radiotherap

py Planning in
breast can
ncer patients

Desire van den Bongard

B
MD, PhD
Radiation Oncologist,
Oncologist UM
MC Utrecht
Utrecht, the Netherlands

B
Breast
t cancer treatm
t tmentt
B
Breast-conserving
t
i
therapy:
the
Breast-conserving
g surgery
Whole breast irrad
diation
+/- boost tu
umor bed
Mastectomy
+/- axillary lymph
+/
h node dissection
+/- (loco)regionall irradiation

Breast--conserving su
Breast
surgery
rgery +/
+/-- WBI

EBCTCG Lancet 2005

I
Innovation
ti off breast
b
t RT
R planning
l
i techniques
t h i

Hypofractionation

Simultaneously integrateed boost (SIB)

Breathhold technique

Regional radiotherapy in
nstead of axillary surgery

Partial breast irradiation

n

RT planning techniques

Hypofrac
yp
ctionation
instead of standard
d scheme 25x2 Gy

Hypofractionation
Breast cancer is more sensitive to fraction size:
/ 4.6 No advantage in usinng 2 Gy fractions
4 phase III studies:
Standard fractionation (25 x 2 Gy)
G Hypofractionation
Canada: 16 x 2.66 Gyy
UK: 15x 2.67 Gy / 13 x 3 or
o 3.2 Gy
n = 7,000 patients; FU 5-10 yeaars
Yarnold RO 2005, Whelann NEJM 2010, START B Lancet 2008,
START A Lancet Oncol 20008, Owen Lancet Oncol 2006

Hypofractionation vs. Standa

ard scheme
Local recurrence
Local control:

Surrvival:

Overall survival

Whelan et al. NEJM 2010

Hypofractionation Conve
entional scheme
N significant
No
i ifi
difference
diff
in:
i
toxicity
lung, cardiac, rib fracturees, shoulder movement
cosmetic result

Haviland NEJM 2010, Whelan NEJM 2010, START B Lancet 2008,

START A Lancet Oncol 2008, Owen Lancet Oncol 20006

Hypofractionation Clinical practice

In the Netherlands (NL): 16 x 2.666 Gy (5x/week)
Canadian scheme: longesst follow-up

Simultaneousllyy Integrated
g
Boost
(
(SIB)

Boost tumor bed decreased lo

ocal recurrence
40

51 60
51-60

41-50

61 70
61-70

Bartelink
Bartelink,
H. JCO
et al. JCO 2007

Boost tumor bed increased fibrosis

Bartelink
Bartelink,
H. JCO
et al. JCO 2007

RT boost tu
tumor
o bed

Increased risk of fibrosis Decreased cosmetic result

Simultaneouslyy in
ntegrated
g
boost ((SIB))
SIB compared to Sequential boo
ost:
Increased dose homogeneity
Less unintended excessive dosse outside tumorbed

Sequential boost
central

SIB
central

95%

5%

5%

caudal

caudal

95%

Simultaneouslyy integ
g
grated boost ((SIB))
SIB compared to Sequential boo
ost:
Increased dose homogeneity
Less unintended excessive dosse outside tumorbed

Higher dose per fraction to tum

morbed
Equal toxicity and cosmetic result
Bantema-Joppe IJROBP 2012
2

Recente literatuur

Breath ho
old technique

Left-sided breast cance

er
L ft id b
Left-side
breasstt cancer and
d RT
The heart

RT-- induced perfusion de

RT
efects

Perfusion defects 6 to13 months afterr RT

More often: > 25 Gy
H
Hardenbergh
et al. IJROBP 2001

Cardiac toxicity and mortality

Conflicting
C fli ti results
lt in
i literature
lit t
due
d tto:
Long interval between RT ex
xposure and cardiac toxicity
(> 10 years)
More successful treatment of
o coronary artery disease
No dosimetric parameter for cardia
ac morbidity and mortality
7% increased risk on cardiac toxicitty per 1 Gy increase in heart dose

ALARA!

Darby NEJM 2013, Hooning IJROBP 2006, Fisher NEJM 20022, Rutqvist IJRBOP 1998, Wood-ward IJROBP 2003,
Nixon JCO 1998, Vallis JCO 2002, Harris JCO 2006, Darby BM
MJ 2005, Borger IJROBP 2007, Doyle IJROBP 2007,
Hjris Lancet 1999, Jagsi RO 2007, Shimizu BMJ 2011

Breath Hold technique

Optimal cardiac sparing:

Free Breathing

B
Breath
hold technique

Heart dose reduction due to breath hold

compared to fre
ee breathing

UMC Utrecht Breath

B
hold technique
q

Audio coaching
Instruction: session + home traiining + DVD
2 days later: planning CT-scan (+/(
BH)
Delineation: target volumes and
d organs at risk
RT Planning on Breath hold CT (XiO), 4
4-6
6 fields

Breath hold analysis

Breath hold analysis

y

Compliance
p
Bre
eath hold technique
q
Pulmonary disease, e.g. COP
PD
Unable to follow breathing in
nstructions, e.g. language barrier

Recente literatuur

Locoregiona
al treatment:
Regional RT (or no
o axillary treatment)
instead
d off axillary
ll
lly
ymph
h node
d dissection
d

AMAROS trial (EORTC)

R di th
Radiotherapy
orr Surgery
S
off the
th axilla
ill
4,806
8 6 BC patients
i
( N )
(cN0)
Tumorpositive sentinel node(s)::
Axillary RT (n=681) vs ALN
ND (n=744)
Median follow-up 6.1 years:
Regional recurrence rate att 5 years: 0.54% ALND vs. 1.03% ART
Toxicity i.e. arm edema: 28
8% ALND vs. 14% ART
Clinical practice: Increased use of
o regional RT

Rutgers JCO 2013

Dia Tristan

Regional lymph
h node irradiation
d li
delineation
ti on planning
l
i CT

MRI regiona
al lymph nodes
MRI:
MRI B
Better
tt visualization
i
li ti off llym
mph
h nodes
d compared
d tto CT
C
Currentt di
diagnostic
ti MRI nott optttimized
ti i d for
f regional
i
l RT planning
l
i
- In prone instead of RT su
upine position
- Contrast
C
(T
(T1w)) and
db
breastt coil
il are not suitable
i bl to visualize
i
li
all lymph nodes
Development of MRI regional lyymph nodes in RT supine
position

MRI in RT supine position

Future studies: MRI-guided

d regional RT
Addition of MRI to standard CT-based planning
her reduction of RT-induced toxicity?
Smaller target volumes and furth

van Heijst AAPM 2014

Partial Breasst
st Irradiation

Partial breast RT - Ratio

onale
Recurrences occur mainly in or near
n
excision cavity
Occurrence of elsewhere
elsewhere recurre
ences is equal after Breast
ences
Breastconserving surgery +/- whole breast irradiation (WBI)

Fisher NEJM 2002, Veronnesi Ann Oncol 2001, Liljegren JCO 1999

Partial breast RT - Adva

antages
g

Smaller RT volume:
Less fibrosis, fat necrosis Better
B
cosmetic outcome?
Lower RT dose in organs at ris
sk, i.e. heart, lungs, contralateral breast
Shorter treatment time Accelerated partial breast RT (APBI)
Cheaper?
depends on technique

Offersen RO 2009, Njeh RO 2010, Theberge Sem Rad Oncol 2011

APBI low-risk patientss

Theberge Sem Rad Oncol 2011

APBI- Methods
1 Brachytherapy (postoperative)
1.
Interstitial: multiple needles of
o catheters
Balloon-catheter: Mammosite
e (most applied in US)
2. Intraoperative RT (postoperative
e)
3. External Beam RT

Offersen et al. RO 2009, Njeh et al. RO

R 2010, Thebergen Sem Rad Oncol 2011

Partial breast RT Interstittial brachytherapy

Partial breast RT Mamm

mosite balloon

5 days,
y , 2 fractions per
p dayy

Partial breast RT - Meth

hods
1 Brachytherapy (postoperative)
1.
Interstitial: multiple needles of
o catheters
Balloon-catheter: Mammosite
e (most applied in US)

2. Intraoperative RT (postoperative
e) e.g. ELIOT
3. External RT (pre- or postoperativve)

Offersen et al. RO 2009, Njeh et al. RO

R 2010, Thebergen Sem Rad Oncol 2011

Partial breast RT Intraoperatieve technique

Partial breast RT - Meth

hods
1 Brachytherapy (postoperative)
1.
Interstitial: multiple needles of catheters
Balloon-catheter: Mammositte (most applied in US)

2. Intraoperative RT (postoperative
e)
3. External beam RT
i.e. IRMA study 10x3.85 Gy BID
B (postoperative)

Offersen et al. RO 2009, Njeh et al. RO

R 2010, Thebergen Sem Rad Oncol 2011

APBI- External Beam RT

Courtesy of
P. Elkhuizen

Partial breast RT phase III studies

WBI vss APBI

- Targit trial en polgar trial zijn

gepubliceerd

Partial breast RT phase III studies

- Low local recu

urrence risk in lowrisk patients
- Targit trial en polgar trial zijn
- Toxicitygepubliceerd
and co
osmetic outcome:
conflicting
g resullts
Longer follow-up
p needed

Optimization of planning techniques

X-ray
X
ray planning locoregional RT
X-ray planning
g Breast irradiation

Acute toxicity - Skin

Grade 1:
Erythema

J Am Acad Dermatol 2006;54:28-46

Late toxicity: > 3 months

Telangiectasia

Fibros
sis, fat necrosis, hyperpigmentation
Fibbrosis and hyperpigmentation

Radiation pneumonitis
p

More advanced planning techniques

i b
in
breastt can
ncer patients
ti t
Aim: Further reduction of RT-induceed toxicity
2D-RT compared to 3D-CRT (tangen
ntial - IMRT)

3D-CRT: less acute toxicity (derm

matitis, edema)
Pignol JCO 2008

After follow-up of 5 years:

2D-RT: 1.7 times more likely to ha
ave change in breast appearance
Donovan RO 2007

After follow-up of 2 years:

forward IMRT: Reduction in telan
ngiectasia less breast shrinkage
ngiectasia,
Barnett RO 2009

3-D CRT planning Breast

Breast irradiation
Field-in-field technique / forward IMRT:
Tangential
g
mediolateral and lateromedial
fields

Small segments are added to achieve a

more homogeneous dose distribution
(Aims: V95 PTV > 99%, Dmax 107%
Mixture of 6 and 10 MV photon beams

Comparison of 3D-CRT, IMRT, VMAT

locoregional R
RT including IMN
VMAT
VMAT:
Improved / similar dose conformity
Reduction in mean heart and ipsilaterall lung dose
Shorter delivery time
Reduced number of monitor units
However,
Slight increase in mean contralatera
al lung and breast dose
Volume of the heart receiving low do
ose was higher
Onlyy mean
O
ea heart
ea t dose reduction
educt o if 3..2 Gy o
or higher
g e

Osman RO 2014, Popescu IJROBP 2010

Estimation of se
econd cancer risk

Lack of significant increased risk of co

ontralateral breast cancer after
conventional RT breast cancer

Increased second cancer risk in VMAT

T and multibeam IMRT compared to 3DCRT and tangential-IMRT
More beams larger volume of norrmal tissue is exposed to a low-dose-bath
Require a longer beam-on time in
ntegral dose can increase because of head
leakage and collimator scatter

In patients < 40 years: radiation-indu

uced secondary contralateral breast cancer
if dose > 1 Gyy

Multibeam-IMRT and VMAT: valid trreatment option for young patients with
left-sided cancer with high
g cardiac do
ose using
g3
3D-CRT or t-IMRT,, in RT IMN,, in
special anatomy reduction in the riisk of cardiac complications

Abo Madyan RO 2014, Ibrahim BMC Caancer 2012, Stovall M IJROBP 2008, Boyce NEJM 2002

Conclusions
Hypofractionation instead of stand
dard RT scheme
Use of SIB results in acceptable tox
xicity and cosmetic outcome
Optimal cardiac sparing with Breatth hold technique
Regional RT instead of axillary lym
mph node dissection
Accelerated partial breast RT:
RT
longer follow-up is needed before standard of care

VMAT may be promising in breast radiotherapy in special cases

e.g IMN RT, funnel chest, high card
diac RT dose

Thank yyou for yyour atte

ention!