Local treatments and radiotherapy
comparisons
- Increased local control survival effects
- Equivalence? : BCS + RT vs Mastectomy
- Predictive factors: BCS ± RT
(Lancet 378: 1707-16, 2011)
- Mastectomy ± RT
- Late iatrogenic effects
SEER.
Darby SC et al. Lancet, 2005
• 308 861 pacientes
• 1973-2001, en ero2002
• 115 165 avec RT
Dose moyenne
cardiaque meilleur
facteur
pronostique / dose
coronaire ant. G
+ 7% / Gy dose
moyenne
cardiaque
Pas de seuil
Développement de la RCMI
Pour l’homogénéité de la dose
Gray IJROBP 91, Moody Radiother Oncol 94, Taylor IJROBP 95…
n F.U. (months) p
II Late iatrogenic effects
• Trials of RT were combined with those of RT vs more surgery.
• Excess incidence of contralateral breast cancer (rate ratio 1.18, SE 0.06, 2p = 0.002).
• Excess of non-breast-cancer mortality (rate ratio 1.12, SE 0.04, 2p = 0.001)
• Both excesses were slight during the first 5 years, but continued after year 15.
EBCTCG, Lancet 366: 2087-106, 2005
Effect of RT on CBC incidence and on non-breast-
cancer mortality (46 trials of adding radiotherapy,
and 17 trials of radiotherapy vs more surgery)
(29 623 women)
EBCTCG, Lancet 366: 2087-106, 2005
-100
-50
0
50
100
150
200
250
Pe
rce
nt in
cre
ase
in
he
art
dis
ea
se
de
ath
ra
te (
95
% C
I)
0 5 10 15 20Mean heart dose (Gy)
EBCTCG 2012. Provisional results. Not for citation or publication
Heart disease mortality
Trials of radiotherapy given versus not
Mean heart dose
Excess RR per Gy: 4.7% (SE 1.0%, 2p<0.00001)
Long term toxicity of
radiation therapy
Results of other studies
10
• Dosimetry
• Observational data
1 million women irradiated worldwide
• RACE – case control study in Sweden and Denmark
Darby SC, et al. N Engl J Med 368, 13, 2013
Dose moyenne
cardiaque meilleur
facteur
pronostique / dose
coronaire ant. G
+ 7% / Gy dose
moyenne
cardiaque
Pas de seuil
010
20
30
He
art
do
se
(G
y)
Right 6MVbreast tangential pair
Left 6MVbreast tangential pair
Right 6MV directinternal mammary field
Left 6MV directinternal mammary field
Target and field arrangement
Dosimetry: Variability in heart dose
20 consecutive patients from CT planning
database in the year 2006, UK
02
04
06
08
01
00
LA
D d
ose
(G
y)
Right 6 MVbreast tangential pair
Left 6 MVbreast tangential pair
Right 6 MVdirect IMC field
Left 6 MVdirect IMC field
Target and field arrangement
0
10
20
30
40
50
Dosimetry: Variability in LAD coronary artery dose
20 consecutive patients from CT planning database in the year
2006, UK
Cardiac mortality ratio, left-sided versus right-sided breast cancer,
in 1 million women given radiotherapy in 24 countries in 4 continents
COBS: preliminary results not for publication of citation K. Henson
Objective: Derive dose-response relationships for radiation-induced heart disease
Radiation Associated Cardiac Events (RACE)
Case control study in Sweden and Denmark
• Population: Irradiated breast cancer patients (1958-2002)
– Population - Denmark
– Population - Stockholm, Sweden
• 963 cases with a major coronary event (MCE) (ie, incident MI, coronary revascularisation, or IHD death)
• 1205 controls without a MCE matched to cases for country, age, and calendar period
Darby SC, et al. N Engl J Med 368, 13, 2013
RACE: Major coronary event increase (%)
and mean radiation dose to heart (Gy)
Increase per Gy:
7.4 % (2.9 –14.5)
Darby SC, et al. N Engl J Med 368, 13, 2013
RACE: Death risk from ischemic heart disease
It is better:
Darby SC, et al. N Engl J Med 368, 13, 2013
RACE: Death risk from ischemic heart disease
It is better:
- Not to have risk factors
Darby SC, et al. N Engl J Med 368, 13, 2013
RACE: Death risk from ischemic heart disease
It is better:
- Not to have risk factors
- Not receive RT
Darby SC, et al. N Engl J Med 368, 13, 2013
RACE: Death risk from ischemic heart disease
It is better:
- Not to have risk factors
- Not receive RT
- To be young
Tecnicas RT.
Mean dose (Gy)
Year Heart
Left anterior
descending
artery
Right
coronary
artery
Circumflex
coronary
artery
1970sEBCTCG trials
13.3 31.8 9.1 6.9
1990sEBCTCG trials
4.7 21.9 2.0 2.8
2002 -201225 studies
worldwide
4.5
Doses to cardiac structures from left
tangential radiotherapy
Taylor et al. IJROBP 2008. Updated 2012
RT ET CARDIOTOXICITE.
Irradiación de mama y regiones
ganglionares
Prono
Conclusions for long-term effects
• In the EBCTCG RT vs no RT trials, ~3% more women had died
of non-breast cancer causes by 20 years in the RT group
• Many of the excess deaths were from heart disease
• The proportional increase in heart disease death rate was
greater in left-sided breast cancer and in younger women
• Radiation-related risk started within 5 years of exposure and
continued beyond 20 years
• In EBCTCG the death rate from heart disease increased by
4.7% per Gray to the heart (40,000 women in R trials)
• In RACE, the incidence rate of ischaemic heart disease
increases by 7.4% per Gray (2,168 women in database)
Effects of adjuvant RT in breast cancer
Late iatrogenic effects
• Long-term follow-up of good quality is
extremely important
• It should also be applied to all others
adjuvant treatments evaluated in
randomised trials
• If not, long-term complications will remain
unknown
Long-term iatrogenic effects of breast cancer
Radiotherapy
Time scale: minimal time of observation
5 10 15 20 25Years
Event
Loco-regional recurrence
Iatrogenic
Mortality
Arriagada R, Acta Oncol, 45: 514-6, 2006
Local treatments and radiotherapy comparisons
Summary
- BCS ± RT
- Decrease of recurrences and improved BCM
- Similar relative reduction on recurrence in all subgroups
- Predictive factors on the importance of absolute recurrence
reduction to be further analysed, mainly in N- patients
- BCS + RT vs Mastectomy
- BCS + RT: more LR, but mainly in younger patients (< 40)
- Mastectomy ± RT
- Effective in reducing recurrence, BCM and overall mortality in
all N+ patients
EBCTCG Next Round: Oxford, October 2014
