1. Place
et
rôle
du
radiothérapeute
dans
le
TNA
Place
of
the
radiotherapy
in
NA
treatment
marc.bollet@horg.fr
Jerusalem, 30th April 2014

2. Place
et
rôle
du
radiothérapeute
dans
le
TNA
Place
of
the
radiotherapy
in
NA
treatment
marc.bollet@horg.fr
Jerusalem, 30th April 2014

3. Place
et
rôle
du
radiothérapeute
dans
le
TNA
Place
of
the
radia9on
oncologist
in
NA
treatment
marc.bollet@horg.fr
Jerusalem, 30th April 2014

4. Could it alter the locoregional strategy?
Could be part of the NeoAdjuvant treatment?
- Concurrently with HT?
- Concurrently with ChT?
How to improve the use of RT in the neoadjuvant setting?
- Better patient selection
- Better regimen
Could RT replace surgery after neoadjuvant CT?
Conclusion
Why should a breast cancer patient meet a radiation in the
neo-adjuvant setting?

5. Contra-­‐indica9on
for
breast
conserving
treatment?

6. Contra-­‐indica9on
for
breast
conserving
treatment?
Pendulous
breasts?
Grann et al., IJROBP 2000
Prone Lateral Decubitus
Campana et al., IJROBP 2005
Alterna9ve
techniques

7. Contra-­‐indica9on
for
breast
conserving
treatment?
Pexctus
Excavatum?
Alterna9ve
techniques
Bollet et al. BJR 2006

8. Contra-­‐indica9on
for
breast
conserving
treatment?
Previous
RT
(Hodgkin
Lymphoma)?
Haberer, et al. Bollet, IJROBP 2012
72 women with history of HL 32 BCS (44%) 17 Breast RT with ILD

9. Contra-­‐indica9on
for
breast
conserving
treatment?
Precluding
heart
or
lung
co-­‐morbidi9es?
Deep Inspiration Breath-Hold
Irradiated
lung & heart↓
CTV to PTV
margin ↓
Synchronization
Saliou et al., Cancer Radiother 2005

10. Could it alter the locoregional strategy?
Could be part of the NeoAdjuvant treatment?
- Concurrently with HT?
- Concurrently with ChT?
How to improve the use of RT in the neoadjuvant setting?
- Better patient selection
- Better regimen
Could RT replace surgery after neoadjuvant CT?
Conclusion
Why should a breast cancer patient meet a radiation in the
neo-adjuvant setting?

11. Could
RT
be
part
of
the
NA
treatment?
In
associa9on
with
HT?
Bollet et al. Radiotherapy&Oncology 2006
40% T4b and/or ≥ 70mm
Med age 71 years
5-OS 85%, 5-RFS 84%, 5-LC 97%

12. Could it alter the locoregional strategy?
Could be part of the NeoAdjuvant treatment?
- Concurrently with HT?
- Concurrently with ChT?
How to improve the use of RT in the neoadjuvant setting?
- Better patient selection
- Better regimen
Could RT replace surgery after neoadjuvant CT?
Conclusion
Why should a breast cancer patient meet a radiation in the
neo-adjuvant setting?

13. Could
RT
be
part
of
the
NA
treatment?
In
associa9on
with
CT?
. H&N SCC +4% in 5-OS
Pignon et al. Lancet 2000
. NSCLC +4% in 2-OS
Schaake-Koning et al. NEJM 1992
. Cervix +6% in 5-OS
Vale et al. JCO 2008
. Anal canal +18% 5-LRC
Bartelink et al. JCO 1997
Radiochemotherapy
Models with proven efficacy
Spatial and temporal collaboration
. Rectum +10% 4-OS
O’Connel et al. NEJM 1994
. Esophagus SCC +25% in 5-OS
Cooper et al. JAMA 1999

14. Could
RT
be
part
of
the
NA
treatment?
In
associa9on
with
CT?
N
F-­‐U
Surg
CT
OS
LRC
Arcangeli
206
5
TCA
CMFx6
NS
NS
IJROBP
2006
Rouësse
638
5
T/M-­‐CA
FEC60x4
Seq
NS
NS
IJROBP
2006
FNCx4
Conco
S
for
BCS
Toledano
695
5
TCA
FNCx6
NS
NS
JCO
2006
S
for
pN1
3 randomized studies on concomitant vs sequential radiochemotherapy
in the adjuvant setting for BC

15. Could
RT
be
part
of
the
NA
treatment?
In
associa9on
with
CT?
LRC
Breast-conserving surgery, pN+
99200A
5-LRC 97% vs 91% p=0.01
Rouesse, de la Lande et al. IJROBP 2006 Toledano, Azria et al. JCO 2007
At the cost of increased acute and late toxicities
ARCOSEIN
5-LRC 97% vs 91% p=0.02

16. No. Stage ChT RT* pCR Epid. Grade 3
%
Formenti et al 35 T3-4 5FU-ci 50 Gy 20 26
IJROBP 1997 Preop 200mg/m2
%
Could
RT
be
part
of
the
NA
treatment?
In
associa9on
with
CT?

17. RCC
preop
Ins9tut
Curie
S14
Phase
II,
2001-­‐2003,
Unifocal
breast
cancers,
59
women
T2-­‐3,
N0-­‐1,
M0.
not
ini9ally
amenable
to
breast-­‐conserving
surgery
Bollet, Sigal-Zafrani et al. Eur J Cancer, 2006
Age (ans)! Median 49 (31-65)!
Menopausal! pre! 59%!
cT! T2! 73%!
cN! N0! 54%!
Ellis-Elston! Grade 1-2! 75%!

18. FUN 1
FUN 2
FUN 3
FUN 4
RT
Inclusion workup
Preop. workup
MCA TCA RT
Pathological response and HR
No pCR 4 FEC100
HR+ TAM x 5 years
5FU pc 500 mg/m2 D1-D5
Vinorelbine IV 25 mg/m2 D1;D5
Breast, IMC, supra/infra-
clav
50 Gy / 25 f
Normal acute toxicity
Normal compliance
No perop complication
I.Curie S14

19. • Median
9me-­‐lapse
before
surgery
– Since
end
of
RT
43
days
(13-­‐73)
– Since
biopsy
123
days
(106-­‐162)
• 69%
(41
pa9ents)
:
breast-­‐conserving
• 31%
(18
pa9ents)
:
mastectomy
• +
axillary
lymph
node
dissec9on
in
all
cases
Abcess in 8% (required surgery in 3%)
Bollet, Sigal-Zafrani et al. Eur J Cancer, 2006
pathological Complete Response = 27%
RCC
neoadjuvant
Ins9tut
Curie
S14

20. RCC
neoadjuvant
Ins9tut
Curie
S14
How
to
evaluate
the
response?
=
MRI,
best
method
RECIST
≥
50%
YES>
50%
chance
of
pCR
NO
<
10%
chance
of
pCR
Bollet, Thibault et al, Int J Radiation Onc Biol Phys 2007

21. RCC
neoadjuvant
Ins9tut
Curie
S14
Long-­‐term
Results
Bollet, Belin et al, Radiother Oncol 2012
@ 5 years :
• OS 88% [95% CI 80–97]
• LRC 90% [95% CI 82–98]
• LC 97% [95% CI 92–100]
Toxicity
• 8% with ≥ 1 grade 3 (telangiectasia, fibrosis)
• 31% with ≥ 1 grade 2 (telangiectasia, fibrosis, lymphoedema and dyspnea)
Cosmetic
• 46% without (11%) or only minor modification (34%)
• 11% deformed breast

22. Could it alter the locoregional strategy?
Could be part of the NeoAdjuvant treatment?
- Concurrently with HT?
- Concurrently with ChT?
How to improve the use of RT in the neoadjuvant setting?
- Better patient selection
- Better regimen
Could RT replace surgery after neoadjuvant CT?
Conclusion
Why should a breast cancer patient meet a radiation in the
neo-adjuvant setting?

23. S14 Phase II Trial
A histological grade 3 was the only clinicopathological
factor independently associated with pCR (p = 0.004)
Tumors which did not express FGFR1 protein on pretreatment biopsies were more
resistant to chemoradiotherapy than those with FGFR1 expression
The FGFR1 tumoral expression was independent from the proliferative markers (histological grade and
mitotic index), meaning that this gives us an additional information on the tumoral phenotype.
Massabeau, Sigal-Zafrani et al BCRT 2012
RCC
neoadjuvant
Ins9tut
Curie
S14
predic9ve
factors
of
tumour
response

24. RT
in
the
preopera9ve
secng
predic9ve
factors
of
late
toxicity?
Rodningen R&O 2008
TGFβ
Polymorphism
(SNP)
Kelsey IJROBP 2012
Radiation Induced
CD8 Lymphocyte Apoptosis
RILA
Azria Lancet Oncol 2012

25. Could it alter the locoregional strategy?
Could be part of the NeoAdjuvant treatment?
- Concurrently with HT?
- Concurrently with ChT?
How to improve the use of RT in the neoadjuvant setting?
- Better patient selection
- Better regimen
Could RT replace surgery after neoadjuvant CT?
Conclusion
Why should a breast cancer patient meet a radiation in the
neo-adjuvant setting?

26. Op9misa9on
of
RT
technique
Better dose homogeneity
Better Organs@Risk
preservation

27. Alle Ding sind Gift und nichts ohn‘ Gift; allein
die Dosis macht, das ein Ding kein Gift ist.
Everything is poison and nothing is poison; only
the dose makes the poison
Paracelsus said
Maybe it is time to bring down some dogma.
Duenas González JCO 2011
Low dose Gemcitabine CDDP
Concomitantly with RT for cervical SCC
Op9misa9on
of
concomitant
CT

28. Could it alter the locoregional strategy?
Could be part of the NeoAdjuvant treatment?
- Concurrently with HT?
- Concurrently with ChT?
How to improve the use of RT in the neoadjuvant setting?
- Better patient selection
- Better regimen
Could RT replace surgery after neoadjuvant CT?
Conclusion
Why should a breast cancer patient meet a radiation in the
neo-adjuvant setting?

29. Taxanes
232 Inflammatory Breast Cancer
Abrous-Anane et al, Bollet IJROBP 2010

30. Could
RT
replace
surgery
ader
NA
CT
for
early
breast
cancers?
Neoadjuvant therapy, compared with adjuvant therapy, was associated
with a statistically significant increased risk of loco- regional
recurrence when radiotherapy without surgery was adopted
Mauri et al. JNCI 2005

31. Year of diagnosis
RT
Surgery
165 pts with cCR after 4 cycles of NA CT: 100 RT, 65 surgery (12 mastectomies)
Larger tumours treated with RT
Trend towards younger with RT
Ring et al JCO 2003
5-LR in the no surgery CR/US: only 8%.

32. Rousseau et al JCO 2006
FDG PET capability to predict pCR of NA CT was, after 2 courses, associated with a
sensitivity, specificity, and negative predictive value of 89%, 95%, and 85%
What about now, with MRI, 18 FDG PET-scan?

33. Punglia
NEJM
2007

34. Could it alter the locoregional strategy?
Could be part of the NeoAdjuvant treatment?
- Concurrently with HT?
- Concurrently with ChT?
How to improve the use of RT in the neoadjuvant setting?
- Better patient selection
- Better regimen
Could RT replace surgery after neoadjuvant CT?
Conclusion
Why should a breast cancer patient meet a radiation in the
neo-adjuvant setting?

35. Conclusions
. Is there a real contra-indication to a breast RT?
. Could pre-operative RT be called for?
Meeting early with the radiation oncologist could be of value in some cases
Different CT regimen are tested concurrently to RT to ameliorate
therapeutic ratio (Taxanes, Vinorelbine…)
Interesting Neoadjuvant results, and non randomised data in rescue
Optimisation of radiotherapy techniques, and prediction of response
to chemoradiotherapy are warranted
Chemoradiotherapy is an option for Inoperable breast Cancers under
Neoadjuvant chemotherapy (≈2%), and Inflammatory breast cancers (> 5%)
Patients should be refered for surgery whenever possible in a M0 setting

36. Place
et
rôle
du
radiothérapeute
dans
le
TNA
Place
of
the
radiotherapy
in
NA
treatment
marc.bollet@horg.fr
Jerusalem, 30th April 2014
Merci ! ‫תודה‬

37. Acute
toxicity
! Rouesse! ! Arcosein!
! Seq! Conc! p! Seq! Conc! p!
Epidermitis! Grade ≥2! 21%! 29%! 0.03! Grade ≥1! 37%! 41%! NS!
Fever!
Febrile
Neutropenia! <1! 1! 0.007! Fever! 5! 7! NS!
Cardiac! LVEF ↓15%! 2! 6! 0.02! Grade ≥1! 1! 1! NS!
Neutropenia! Grade ≥3! <1! 14! 0.0001! Grade ≥1! 36! 37! NS!
Esophagitis! Grade ≥1! 13! 17! 0.02!
Rouesse, de la Lande et al. IJROBP 2006 Calais Cancer Radiothérapie 2004

38. (grade >=2)" Seq" Conc" p"
Fibrosis" 5" 25" 0.003"
Telangectasia" 7" 25" 0.001"
Atrophy" 20" 44" 0.001"
Hyperpigmentation" 15" 30" 0.02"
Deformation" 14" 29" 0.002 "
Pain" 12" 22" 0.07"
Œdema" 0" 1" "
Lymphoedema" 7" 5" "
Toledano, Garaud et al. IJROBP 2006 Toledano, Bollet et al. IJROBP 2006
Late
toxicity

39. Pourquoi associer RT et CT ?
1. Pas de retard entre initiation de la RT et de la CT
2. Potentialisation de la RT et augmentation du CLR
3. Diminution du temps de traitement global
NSABP : RT-CT conco = 0,5% RLR/an CT puis RT >1% RLR/an
Pourquoi ne pas associer RT et CT ?
1. RT = risque d’impacter le capital médullaire et la dose intensité de la CT
2. Les CT (ex anthracycline) ne sont pas toutes compatibles de façon
concomitante avec la RT
3. Augmentation des toxicités
Bénéfices
et
Risques
théoriques
Kurtz Ann Oncol 1999

40. • Retrospective study, 535 patients
• 109 RT-CT, 276 CT + RT, 106 RT + CT, 44 RT- CT « sandwich »
• Facteurs pronostiques + péjoratifs dans le groupe conco
• Control Local : Conco 92% vs Séquentiel 83% p<0,001

41. RCC
neoadjuvant
Ins9tut
Curie
S14
Tumours
Type histo.! CCI! 69%!
EE! Grade I! 22%!
Grade II! 49%!
Grade III! 25%!
CIC! Oui! 27%!
HER2 +++! Oui! 17%!
HR! HR+! 69%!
Bollet, Sigal-Zafrani et al. Eur J Cancer, 2006

42. RCC
neoadjuvant
Ins9tut
Curie
S14
Acute
Toxicity
% Grade 3 % Grade 4
Epidermite 14 -
Hématologique 24 22
Digestive 12 2
Cardiovasculaire 5* -
* Les 3 patientes l’ont eu pendant leur premier cycle de ChT,
avant le début de la radiothérapie
Bollet, Sigal-Zafrani et al. Eur J Cancer, 2006

43. • No
per-­‐op.
or
immediately
post-­‐op.
complica9on
• Median
hospital
stay
7
days
(3-­‐12)
• 5
abcesses
– 2
with
drainage
• 2
hematomas
• 34%
lymphocele
aspira9on
RCC
neoadjuvant
Ins9tut
Curie
S14
Post-­‐op.
Toxicity

44. RCC
neoadjuvant
Ins9tut
Curie
S14
compliance
• Chemotherapy
weekly
dose-­‐intensity
median
(%
theorical
dose)
– 5
Fluorouracil
98
61-­‐112
– Vinorelbine
98
50-­‐105
• Radiotherapy
– Median
breast
Dose
(Gy)
50
46-­‐52
– Treatment
interrup9on
>
7
d
8%
Median
2
days
2-­‐15

45. RCC
neoadjuvant
Ins9tut
Curie
S14
Results
No. %
Clinical Response
Complete 20 34
Partial 20 34
Stable 19 32
Breast-conserving surgery 41 69
pathological Complete Response* 16 27
Axillary Lymph Nodes
pN+ 26 44
pN- 33 56
* < 5% residual disease, without mitosis

46. « We believe that the only realistic benefit that one can expect using concurrent
chemotherapy with radiotherapy is improvement in local control rates… »
« we must consider late toxicity after BCT as an
important end- point in breast cancer clinical trials »

47. Adjuvant breast cancer treatment : The longer is not the better !
Toledano et al. Cancer Radiother 2008
Reflexion on treatment duration : The shroter seems
to be better for patients, but …

48. . The ARCOSEIN « late toxicities and Cosmesis »
evaluated population
. 120 reassessed for depression
. 8,1 years Follow Up
. 6.7% with probable depression,
and 12.5% with possible depression.

49. . Adjuvant Chemoradiotherpy :
. Rational
. 3 Phase III randomized trials
. Late toxicities and cosmetic effects
. Neoadjuvant Chemoradiotherapy :
. Breast Conservative treatment
. Preoperative rescue
. Biological selection of patients candidats
PLAN
. Novel chemotherapies regimen (phase II trials)

50. « We believe that the only realistic benefit that one can expect using concurrent
chemotherapy with radiotherapy is improvement in local control rates… »
« we must consider late toxicity after BCT as an
important end- point in breast cancer clinical trials »

51. Adjuvant breast cancer treatment : The longer is not the better !
Toledano et al. Cancer Radiother 2008
Reflexion on treatment duration : The shroter seems
to be better for patients, but …

52. . The ARCOSEIN « late toxicities and Cosmesis »
evaluated population
. 120 reassessed for depression
. 8,1 years Follow Up
. 6.7% with probable depression,
and 12.5% with possible depression.

53. . Adjuvant Chemoradiotherpy :
. Rational
. 3 Phase III randomized trials
. Late toxicities and cosmetic effects
. Neoadjuvant Chemoradiotherapy :
. Breast Conservative treatment
. Preoperative rescue
. Biological selection of patients candidats
PLAN
. Novel chemotherapies regimen (phase II trials)

54. No. Stage ChT RT* pCR Epid. Grade 3
%
Formenti et al 35 T3-4 5FU-ci 50 Gy 20 26
IJROBP 1997 Preop 200mg/m2
Formenti et al. 44 IIB-III Paclitaxel 45 Gy 16 7
JCO 2003 Preop
Kao et al. 16 IIIB-C VLB + P 60 Gy 46 50
IJROBP 2004 Preop or P
* Breast + Lymph nodes
%
Could
RT
be
part
of
the
NA
treatment?
In
associa9on
with
other
regimens
of
CT?
Bollet et al. 59 IIB-III FU-N 50 Gy 27 17
EJC 2006 Preop

55. Bellon et al. IJROBP 2000
A
retrospec9ve
study
of
concurrent
RT
and
taxanes
(pacli
or
doce)
in
high
risk
BC

56. 2-LC 74%,
2-OS 66%.
Weekly Docetaxel
20mg/m2 x2/week
Karasawa et al Breast Cancer 2003

57. CT (4 AC60)
RT-CT (12 Paclitaxel weekly 60 mg/m2)
RT-CT (4 Paclitaxel 135-175 mg/m2/ 3 weeks)
Surgery
Skin Toxicity (no G3-4)
Lung Toxicity (P hebdo)
RT interruption 25%
Burstein et al., IJROBP 2006
phase II trial
40 patients breast cancer stage II-III
RT (1.8 Gy/#) DT 39,6Gy (breast) 45Gy (chest wall)
Concurrent treatment with weekly paclitaxel and
radiation therapy is not feasible (…) Concurrent
treatment using a less frequent paclitaxel dosing
schedule may be possible, but caution is
warranted in light of the apparent possibility of
pulmonary injury
A
phase
II
trial
of
adjuvant
concurrent
RT
and
paclitaxel

58. CT (4 AC60)Surgery RT-CT (4Taxol 175 mg/m2/ 3 weeks)
Chen et al., IJROBP 2012
44 patients
39.6 Gy / 22# + 14 Gy / 7#
Median F-U > 6y
The 5-DFS 88%, 5-OS 93%, 5-LC 100%
No cases of radiation pneumonitis
No significant change in the diffusing capacity for carbon monoxide either
immediately after RT or with extended F-U.
Acute Grade 3 skin toxicity in 2 pts. Late cosmesis was not adversely affected.
Conclusions: excellent LC & well tolerated.
A
phase
II
trial
of
concurrent
RT
and
paclitaxel
ader
BCS
in
pN+
BC

59. CT (3 FEC100) RT-CT (9Docetaxel 35mg/m2/week)
Chow et al., Acta Oncol 2014
32 patients
45 Gy / 25# + (5.4Gy/3# or 9Gy/5#)
A
phase
II
trial
of
concurrent
RT
and
weekly
docetaxel
Early close due to high rate of symptomatic radiation pneumonitis
17 (55%) symptomatic radiation pneumonitis (RP).
8 (25%) grade 3 pneumonitis
1 (3%) grade 5, died of acute respiratory distress syndrome associated with RP

60. Ismaili et al., BMC Res Notes 2010
6 cycles of (AC60, FAC50; FEC75) or CMF
After mastectomy or BCT, the adjuvant
treatment based on RT and concurrent
anthracycline CHT (vs CMF) reduced
breast cancer relapse rate, and
significantly improved LRFS, EFS and OS
in the patients receiving more than 1 cycle
of concurrent CT. There were more
hematologic and non hematologic toxicities
in the anthracycline group

61. Concomitant adjuvant chemo-radiation therapy with anthracycline-based
regimens in breast cancer: a single centre experience
Livi L, Meattini I, Scotti V, Saieva C, Simontacchi G, Marrazzo L, Franzese C, Cassani S, Paiar
F, Di Cataldo V, Nori J, Jose Sanchez L, Bianchi S, Cataliotti L, Biti G.
PURPOSE:
This study was done to evaluate the toxicity related to concurrent radiotherapy and anthracycline
(AC)-based chemotherapy in the adjuvant treatment of early breast cancer and to investigate the
impact of treatment interruptions and the feasibility of this uncommon therapeutic approach
.MATERIALS AND METHODS:
From September 2002 to December 2007, 60 patients were treated at our Centre.
The mean age at presentation was 48.5 (range 38-64) years. All patients underwent conservative
surgery, and radiotherapy to the entire breast (mean dose 50 Gy; range 46-52 Gy). AC-based
regimens consisted of four cycles of AC (doxorubicin plus cyclophosphamide) or four cycles of
epirubicin (EPI) followed by four courses of cyclophosphamide, methotrexate and 5-fluorouracil
(CMF).
RESULTS:
Concomitant treatment caused acute skin G3 toxicity in 8.9% of patients and one case of G4
toxicity (1.7%). Concerning cardiac assessment, six of the 56 evaluable patients (10.7%) developed
an asymptomatic decline of left ventricular ejection fraction >10% and <20% of the baseline value.
Radiotherapy was temporarily stopped in 21.3% and chemotherapy in 57.1% of patients.
CONCLUSIONS:
In our experience, concomitant chemotherapy did not emerge as a significant factor in
radiotherapy interruption. Moreover, no severe cardiac events were recorded.

62. Which Chemotherapy Regimen ?

63. 5FU pc 500 mg/m2 J1 à J5
Vinorelbine IV 25 mg/m2 J1 et J5
RT – CT (4 FUN) à Surgery à 4 FEC 100
Phase II, 2001-2003
Unifocal breast cancers, T2-3, N0-1, M0.
Conservative surgery impossible
60 patients assessed, 59 evaluables
BCS was performed in 69% (n=41) patients !

64. « Progression of inoperable breast cancer under NACT is a rare event (less than 2%) for which
XUN/FUN-based chemo-radiotherapy could be proposed as locoregional ‘‘rescue’’ therapy »

67. A feasibility study of neo-adjuvant low-dose fractionated radiotherapy with two different
concurrent anthracycline-docetaxel schedules in stage IIA/B-IIIA breast cancer.
Nardone L et al.
Tumori. 2012 Jan-Feb;98(1):79-85.
AIMS AND BACKGROUND:
The aim of the study was to evaluate the feasibility of neoadjuvant low-dose fractionated radiotherapy, in combination
with two anthracycline-docetaxel regimens, in breast cancer treatment.
MATERIALS AND METHODS:
Women with stage IIA/B-IIIA breast cancer were assigned to receive the treatment of low-dose fractionated radiotherapy
(0.4 Gy/per fraction, 2 fractions per day, for 2 days, every 21 days for 8-6 cycles) with concomitant neoadjuvant
chemotherapy with non-pegylated liposomal doxorubicin and docetaxel. Two chemotherapy schedules were planned to
be combined with low-dose fractionated radiotherapy. The first schedule consisted of four cycles of non-pegylated
liposomal doxorubicin sequentially followed by four cycles of docetaxel, and the second schedule consisted of six
cycles of non-pegylated liposomal doxorubicin plus concomitant docetaxel. Acute toxicity was evaluated according to
the Radiation Therapy Oncology Group score system. Pathological response was evaluated by the Mandard score and
expressed as tumor regression grade.
RESULTS:
Between March 2008 and February 2009, 10 patients underwent low-dose fractionated radiotherapy and concomitant
chemotherapy. No grade 3-4 breast toxicity was observed. Five patients had a clinical complete response. Seven
patients underwent conservative surgery. Overall, tumor regression grade 1 (absence of residual cancer) was achieved
in one patient (10%) and grade 2 (residual isolated cells scattered through the fibrosis) in 4 patients (40%). The
pathologic major response rate (tumor regression grade 1 + 2) was 20% in patients receiving low-dose fractionated
radiotherapy and sequential non-pegylated liposomal doxorubicin and docetaxel and 80% in the group receiving low-
dose fractionated radiotherapy and concurrent non-pegylated liposomal doxorubicin and docetaxel treatment.
CONCLUSIONS:
Concomitant low-dose fractionated radiotherapy combined with anthracycline and docetaxel is feasible. The toxicity
profile of radio-chemotherapy was similar to that of chemotherapy alone: there was no acute skin or cardiac toxicity.
The concurrent application of liposomal doxorubicin and docetaxel with low-dose fractionated radiation led to higher
histological response rates compared to the sequential application of the same two drugs.