1. KONTROVERSEN IN DER RADIOTHERAPIE DES MAMMAKARZINOMS
GUENTHER GRUBER
Institut für Radio-Onkologie
Klinik Hirslanden, Zuerich
hirslanden.ch

2. KONTROVERSEN - RT
INDIKATION
VOLUMINA
RT - PLANUNG
RT – APPLIKATION

3. Bei welchen Pat. kann auf eine RT nach
KONTROVERSEN – RT
BRUSTERHALTUNG
Bei welchen Pat. kann auf eine RT nach
Brusterhaltung verzichtet werden?

4. EBCTCG 2000 RT metaanalysis, Lancet 12/05
BREAST CONSERVATION
EBCTCG 2000 RT metaanalysis, Lancet 12/05
N N+/N?
n= n=1214 %
p< p= p< p<0.01

5. BREAST CONSERVATION

6. BREAST CONSERVATION
CONCLUSION
BC surgery: No omission of RT !

7. BREAST CONSERVATION
INVASIVE CANCER
Omission of RT in ‚low risk‘ ?

8. median tu-size: 12mm; n=1187;
BREAST CONSERVATION
BC surgery +/- RT
Swedish Breast Cancer Group, EJC 2003
median tu-size: 12mm; n=1187;
median F-up: 8J
14% 4%

9. BC surgery +/- RT, pT1a/pT1b pN0
BREAST CONSERVATION
BC surgery +/- RT, pT1a/pT1b pN0
16.5
9.3
p<0.0001
p=0.01
2.8
NSABP B-21, n=1009; JCO 2002

10. Local relapse rates, pT1a/pT1b pN0
BREAST CONSERVATION
Local relapse rates, pT1a/pT1b pN0
Age 70+ ?
Therapy,-ies n LR
TAM (7%)
RT (8%)
TAM+RT
RT vs. TAM => HR 1.06 ( ) !
NSABP B-21, n=1009
JCO, 2002

11. … in T1, N0, R0, ER+ (in 97%), >70yrs
BREAST CONSERVATION
… in T1, N0, R0, ER+ (in 97%), >70yrs
CALGB, RTOG, ECOG (Hughes et al. NEJM, 9/2004)
n=636 (75+ years: 55%)
median F-up: 5J
LOCAL RELAPSE
with tamoxifen 4%
with tamoxifen and RT 1%
p<0.001

12. T1/T2, >50yrs: 769 randomised (of 1572 ‚eligible‘ pts.)
BREAST CONSERVATION
T1/T2, >50yrs: 769 randomised (of 1572 ‚eligible‘ pts.)
5yrs LR
-2cm, R0, HR+ n=611
Tam %
Tam + WB-RT % (p<0.001)
-1cm, R0, HR+ n=263
Tam %
Tam + WB-RT 0% (p=0.02)
Files et al., NEJM 2004

13. T1/T2, >50yrs: 769 randomised (of 1572 ‚eligible‘ pts.)
BREAST CONSERVATION
T1/T2, >50yrs: 769 randomised (of 1572 ‚eligible‘ pts.)
5yrs LR 8yrs LR
-2cm, R0, HR+ n=611
Tam % %
Tam + WB-RT % (p<0.001) %
-1cm, R0, HR+ n=263
Tam %
Tam + WB-RT 0% (p=0.02)
+ 3J
x 5 !
Files et al., NEJM 2004

14. T1/T2, >50yrs: 769 randomised (of 1572 ‚eligible‘ pts.)
BREAST CONSERVATION
T1/T2, >50yrs: 769 randomised (of 1572 ‚eligible‘ pts.)
5yrs LR 8yrs LR
-2cm, R0, HR+ n= (B21)
Tam % % (16.5%)
Tam + WB-RT % (p<0.001) % ( 2.8%)
-1cm, R0, HR+ n=263
Tam %
Tam + WB-RT 0% (p=0.02)
+ 3J
x 5 !
Files et al., NEJM 2004

15. postmenop., T <3cm, N0, ER+ and/or PR+
BREAST CONSERVATION
postmenop., T <3cm, N0, ER+ and/or PR+
ABCSG 8 (8A) (Pötter et al. ASTRO, OEGRO, ECCO 13, 11/2005)
n=826 (60+ years: about two thirds)
median F-up: 42 mo
LOCAL RELAPSE 5yrs
with Tamoxifen/AI 4.5%
with Tamoxifen/AI and RT 0.6%
p=0.001

16. BREAST CONSERVATION „low risk“ – studies summary
Follow up still too short !
No subgroup of pts.
which does not profit from RT!
IMPORTANT: Trade-offs !
If overall survival > 5yrs: RT !

17. BREAST CONSERVATION CONCLUSION BC surgery: No omission of RT !
No omission of RT in ‚low risk‘ !

18. BREAST CONSERVATION INVASIVE CANCER
Breast conserving surgery: Omission of RT ?
Omission of RT in ‚low risk‘ ?
PBI for ‚low risk‘ ?

19. BREAST CONSERVATION CONCLUSION BCT + Mastectomy equivalent !
BC surgery: No omission of RT !
No omission of RT in ‚low risk‘ !
The target is the whole breast !

20. BREAST CONSERVATION INVASIVE CANCER BCT vs mastectomy ?
Breast conserving surgery: Omission of RT ?
Omission of RT in ‚low risk‘ ?
PBI for ‚low risk‘ ?
Altered fractionation?

21. BREAST CONSERVATION altered fractionation Stage I/II n=1234 R
42.5Gy/2.65Gy
22 days
n=622
50Gy/2Gy
35 days
n=612
median f-up : 69 months
Whelan et al., JNCI 94, 2002

22. BREAST CONSERVATION altered fractionation LRFS DFS 100% 95%
Whelan et al., JNCI 94, 2002

23. BREAST CONSERVATION altered fractionation T1-3 N0-1 n=1410 R
42.9Gy/3.3Gy
5 wks
n=466
39Gy/3Gy
5 wks
n=474
50Gy/2Gy
5 wks
n=470
median f-up : 9.7 years
Owen et al., Lancet Oncol, 2006

24. BREAST CONSERVATION altered fractionation
Owen et al., Lancet Oncol, 2006

25. BREAST CONSERVATION CONCLUSION BC surgery: No omission of RT !
No omission of RT in ‚low risk‘ !
The target is the whole breast !
There are equivalent schedules !

26. BREAST CONSERVATION INVASIVE CANCER
Breast conserving surgery: Omission of RT ?
Omission of RT in ‚low risk‘ ?
PBI for ‚low risk‘ ?
Altered fractionation?
Increase of dose (boost) ?

27. Local recurrences after BCS + RT BOOST versus NO BOOST
BREAST CONSERVATION
Local recurrences after BCS + RT BOOST versus NO BOOST
no boost boost H.R.
Lyon y % % (10 Gy) p = 0.044
n = 1024
French M.C y % % (16Gy) p = 0.13
n = 664
EORTC y % % (15Gy) p =
n = 5569

28. BREAST CONSERVATION BREAST-RT +/- BOOST Bartelink et al., NEJM 2001
- 40J (n=449)
41-50J (n=1334)
p=0.002
p=0.02
51-60J (n=1803)
> 60J (n=1732)
p=0.07
p=0.11
Bartelink et al., NEJM 2001

29. BREAST CONSERVATION CONCLUSION BCT + Mastectomy equivalent !
BC surgery: No omission of RT !
No omission of RT in ‚low risk‘ !
The target is the whole breast !
There are equivalent schedules !
Boost efficient (! <50yrs !)

30. RT – Tamoxifen: simultaneous vs sequential
RT – BREAST CANCER
‚TIMING‘
RT – Tamoxifen: simultaneous vs sequential
Journal of Clinical Oncology, Vol 23, No 1, 2005
* 3 (small) retrospective studies
z.B. Ahn et al, 2005 OS
LRFS

31. RT – Tamoxifen: simultaneous vs sequential
RT – BREAST CANCER
‚TIMING‘
RT – Tamoxifen: simultaneous vs sequential
Lokalrezidiv
Bentzen, S. M. et al. JCO; 23:

32. RT – 6xCMF: ‚RT first‘ vs ,CMF first‘
RT – BREAST CANCER
‚TIMING‘
RT – 6xCMF: ‚RT first‘ vs ,CMF first‘
Breast conservation; n=244
DFS
No significant difference!
Bellon, J. R. et al. JCO; 23: ; 2005

33. RT – 6xCMF: ‚RT first‘ vs ,CMF first‘
RT – BREAST CANCER
‚TIMING‘
RT – 6xCMF: ‚RT first‘ vs ,CMF first‘
Breast conservation; n=244
DFS
DMFS
No significant difference!
Bellon, J. R. et al. JCO; 23: ; 2005

34. RT – 6xCMF: ‚RT first‘ vs ,CMF first‘
RT – BREAST CANCER
‚TIMING‘
RT – 6xCMF: ‚RT first‘ vs ,CMF first‘
Breast conservation; n=244
DFS
DMFS OS
No significant difference!
Bellon, J. R. et al. JCO; 23: ; 2005

35. ‚ChT => RT‘ vs ,simChT/RT‘
RT – BREAST CANCER
‚TIMING‘
‚ChT => RT‘ vs ,simChT/RT‘
ChT= mitoxantrone, 5-FU, cyclophosphamide; 6 cycles
RT= 50Gy/2Gy; +/- boost
ARCOSEIN III trial (n=214 for late toxicity)
! No difference in acute toxicity !
(skin, esophagus, infections, neutropenia)
! No statistical difference in grade 2 or higher
breast edema, lymphedema, pain !
! simChT/RT: Significant more breast atrophy,
subcutaneous fibrosis, teleangiectasia, skin pigmentation !
Toledano et al.; Int J Radiat Oncol Biol Phys; 2006

36. RT – BREAST CANCER ‚TIMING‘
RT – Herceptin ®
N9831: AC->T->H vs AC->TH->H
RT (after BCS or Mx4+LN sim to H allowed)
1460 available for adverse events analyses
median f-up: 1.5yrs
Skin reaction (p=0.78); pneumonitis (p=0.78), dyspnea (p=0.87)
Cough (p=0.54); dysphagea (p=0.26); neutropenia (p=0.16)
Concurrent H-RT is not associated with acute RT adverse events
Further follow up is needed for late adverse events
Halyard MY et al. ASCO; 2006

37. RT – BREAST CANCER ‚TIMING‘
How to combine RT with systemic therapies ?
Individual
HT:
simultaneous possible
ChT :
In most centers: ChT -> RT
simultaneous RChT possible
but more side effects!
=> Not recommended
Herc: simultaneous possible (heart!)

38. BREAST CONSERVATION
TECHNIQUE / RT APPLICATION

39. BREAST CONSERVATION

40. BREAST CONSERVATION
Hurkmans et al., 2001
Lung
HEART
42 mm

42. BREAST CONSERVATION IMRT „Open“ homogeneous beam (OB)
Intensity modulated beam (IMB)

43. BREAST CONSERVATION
IMRT
IMRT
IMRT

44. 5yrs – Differences in breast appearence (Photos)
BREAST CONSERVATION
IMRT
n=306 R
Standard 2D 3D IMRT
5yrs – Differences in breast appearence (Photos)
60% 48%
p=0.06
(QoL no difference)
Yarnold et al., ECCO 13; 2005

45. BREAST CONSERVATION 6MV + 12e Protons IMRT IMRT Lomax et al.
IJROBP 2003

46. TARGET VOLUME ?
SCHLUSSFOLGERUNG

47. MAMMARIA INTERNA – RT: SFRO trial
TARGET VOLUME ?
MAMMARIA INTERNA – RT: SFRO trial
PATIENTS / METHODS RESULTS
n=1281 (1/91 – 12/97); MI-RT MI-RT
Median f-up: 65mo Death 19% %
Mastectomy Cancer 11% %
LR 4% %
Meta 17% %
CW+Supra CW+Supra+MI R

48. RT – BREAST CANCER
RE-IRRADIATION