1. “Minimal vs
extended local
management”
Umberto Veronesi, MD
Swedish, June 30 2008

2. New Paradigms
1969
From To
Maximum Minimum
tolerable effective
treatment treatment

3. Milan Conservation
Programme (1969-2008)
Conservation of the
1970 - 1981 breast
Conservation of
1995 - 2000 axillary nodes
Partial
1999 - 2008 Intraoperative
Radiotherapy

4. Phase 1
Conservation of
the breast

5. W.H.O. Meeting Geneva, December 1969
Agenda

6. (December 1969)

7. 1969 - Lobectomy (Quadrantectomy,
Sector or Segmental Resection)

8. QUADRANTECTOMY- 1971

9. 1981

11. Milan I - Survival
1.0
0.8
Probability
Probability
0.6
0.4
Halsted (n. 349)
0.2 Quadrantectomy + RT ( 50Gy + 10Gy boost) (n. 352)
0.0
0 60 120 180 240 300
Months
Veronesi U, et al. N Engl J Med, 2002

12. Cases of breast conserving
surgery per year worldwide
350
300
x 1000
250
200
150
100
50
0
1980 1990 2000 2010
Milan NSABP
Trial Trial

13. Lumpectomy is a reductive surgery
based on the concept that breast cancer is a
disseminated disease from the beginning

14. Milan II - Local Failure
%
I Lumpectomy +
n
c Radiotherapy (63/345)
i (18.3%)
d
e
n Quadrantectomy +
z
a Radiotherapy (25 / 360)
(7.5%)
C
u
m.
years

15. Phase 2
Conservation of
axillary nodes

16. Sentinel Node
Biopsy
15.386 EIO cases

17. European Institute of Oncology
1998-1999 (516 cases)
T1 N0
R
Axillary Sentinel Node Biopsy
Dissection Dissection if S.N.
positive

18. Overall Survival
(Sentinel Node)
Proportion of patients surviving (%)
(Axillary Dissection)
Follow-up (years)
Veronesi U, et al. Lancet Oncology 2006

19. TRIAL 23-01
T ≤ 3 cm cN0
SNB
MICROMETASTASES
R
FOLLOW UP AXILLARY
DISSECTION
686 patients randomized

20. Phase 3
Reduction of
Radiotherapy

21. Premises
Milan 3
273 Patients
treated
with conservative
surgery - no
radiotherapy
• True recurrence
• New ipsilateral and
contralateral
primary carcinomas

22. ELIOT
(Electron
IntraOperative
Therapy)
3.150 Cases
Radiotherapy
full dose
(21 Gy) in
three minutes

23. ELIOT
(Electron IntraOperative
Therapy
1. Cancer removal
2. Breast gland reconstruction
3. Chest wall protection
4. Collimator placement
5. Radiation treatment

24. Quadrantectomy

25. Breast gland reconstruction

26. Thoracic wall protection

27. Collimator placement

28. Advantages of ELIOT
The applicator is placed under direct
visual control of the surgeon on the
operative field.
Radiation exposure of the lung and
of contralateral breast is dramatically
reduced.
The problem of difficult access to
radiotherapy centres is solved.

29. Many women live a long
way from radiotherapy
centres

30. ELIOT 21Gy
2-7 year follow-up
of 1,246 cases (1999-2006)
treated with ELIOT 21Gy

31. First unfavourable event (66 out of 1,246 cases)
Event N %
Local recurrence 17 1.4
Ipsilateral II breast carcinoma 9 0.7
Axillary metastases 1 0.1
Contralateral carcinoma 7 0.6
Distant metastases 20 1.6
Other carcinoma 12 1.0
TOTAL 66 5.3
Deaths (12)
N %
Deaths due to breast cancer 7 0.6
Deaths due to other causes 5 0.4
TOTAL DEATHS 12 1.0

32. IEO TRIAL
November 2000 – December 2007
1,306 patients
T <2.5 cm
AGE > 48
R
651 655
Breast Conserving Breast Conserving
Surgery + Conventional Surgery +ELIOT (21 Gy)
Radiotherapy (60 Gy)

33. Accrual per year
Year Total Ext. RT ELIOT
2000 25 12 13
2001 175 87 88
2002 137 70 67
2003 190 94 96
2004 215 110 105
2005 189 97 92
2006 186 91 95
2007 189 94 95
TOTAL 1306 655 651

34. Primary carcinoma - Average size
and median patient age
Total Ext. RT ELIOT
(n. 1,306) (n. 651) (n. 655)
Tumor size cm. 1.3 cm. 1.3 cm. 1.3
Patients age 60.0 years 60.2 years 59.8 years

35. ELIOT Trial at European Institute
of Oncology (1,306 cases)
Axillary dissection
1000 Total
900 Ext. RT
800 Eliot
700
600
500
400
300
200
100 No Axillary Dissection
N. N. Axillary Dissection
0
N. No Axillary Dissection N. Axillary Dissection

36. ELIOT Trial at European Institute of Oncology
- ER and PgR -
Total
(n. (%) Ext.RT (%) ELIOT (%)
1,294)
ER and PgR
ER+PgR+ 967 74.7 492 76.0 475 73.4
ER+PgR- 201 15.5 95 14.7 106 16.4
ER-PgR+ 1 0.1 1 0.2 0 0.0
ER-PgR- 120 9.3 57 8.8 63 9.7
Missing 5 0.4 2 0.3 3 0.5

37. Overall Survival

38. ELIOT AS A BOOST Accelerated Breast RT
226 Women < 48 years
Postoperative
Intraoperative boost (ELIOT)
Whole breast RT
12 Gy
2.85 Gy x 13 Fr.

39. Radiotherapy is concluded in 30 days (and
not delayed after chemotherapy)
Surgery + Accelerated External Systemic
ELIOT boost Radiotherapy treatments
1 14 days
30

40. Risk of local recurrence
according to the timing of
Radiotherapy.
1% increase of absolute
risk per month of delay
(Chen Z, et al 2008)

41. If the risk of local
recurrence is 10% (when
immediate RT is applied)
it becomes 16% if RT is
delayed six months.
(Chen Z, et al 2008)

42. Nipple-Sparing Mastectomy
A total mastectomy sparing
the skin and the nipple with
intraoperative radiotherapy to
the nipple areola complex
and prosthesis placement.

43. Nipple-Sparing Mastectomy
ELIOT (16 Gy)
to the Nipple-
areola complex

44. Nipple-sparing with ELIOT
March 2002-September 2007
1,010 Nipple-sparing
mastectomies

45. Conclusions
The new paradigm (minimum
effective treatment) leads to
better quality of life which in
turn motivates women to
earlier detection, which in turn
will reduce mortality.

46. Relative Risk of Breast Cancer Mortality in European Union, 1973-2000
Standardized Mortality Ratio Reduced Mortality
1.00
0.95
0.90
1970 1975 1980 1985 1990 1995 2000
Years