Updates in Radiotherapy for Breast Cancer. By Prasert Lertsanguansinchai

1. The 5th Annual Update in Breakthrough in
Hematology and Oncology (AUBHO 2015)
28-29th August 2015
At the Nai Lert Park Swissotel
Bangkok ,Thailand

2.  Updates in Radiotherapy for Breast Cancer
Prasert Lertsanguansinchai,M.D.
Radiation Oncologist
Wattanosoth Hospital

3. 50 Years of Advances in
Radiotherapy for Breast cancer
Radiation Therapy (RT) :
What have we Learned ?
Where are we Now ?
Where are we Going ?

4. What have we learned ?
Breast Cancer
Radiation Therapy (RT) 50 years ag0

5. The overview of eight unconfounded randomized
trials of radiotherapy initiated before 1975
(total 7,941 women)
Surgery = radical mastectomy or simple mastectomy
None of the patients received chemotherapy
Surgery alone VS Surgery + Radiation
J. Cuzick JCO 12: 447-453,1994

6. JCO 12 : 447-453,1994
The overall mortality rate was similar in the first 10 years .
A divergence in favor of patients not given radiotherapy is apparent
after approximately 15 years in the radical mastectomy trials .
For the simple mastectomy trials, the overall survival curves remain
similar after 10 and 20 years.

7. Where are we now ?
Breast Cancer
Radiation Therapy (RT)

8. Tumor Biology
Breast cancer is a systemic disease needs
1.Locoregional control.
2.Prevent and get rid of microdistant metastasis.

9. Local Radiation Treatment
The additional of radiotherapy to surgery resulted in
an improvement rate of local recurrence by ⅔ to ¾ (70%)
as compare to surgery alone.
Radiation contribute to improve overall
survival when combined with systemic
therapy.
NEJM 1995 ; 333 : 1444-1455
Lancet 2000 ; 355 ; 1757-1770

10. Radiotherapy after Mastectomy and axillary clearance
5-Y Isolated LRR No PMRT PMRT
Node-negative 6.3% 2.3% (p=0.0002)
No significant reduction in 15 year breast cancer mortality
Node-positive 22.8% 5.8%
15-Y breast cancer mortality 60.1% 54.7% (reduction 5.4%)
(p=0.0002)
15-y overall mortality reduction 4.4 % (p=0.0009)
EBCTCG PMRT

11. BCS alone BCS + RT
5-Y LRR 26% 7% (reduction 19%)
15-Y breast cancer mortality 35.9% 30.5% (reduction 5.4%)
(p=0.0002)
Radiotherapy after BCS (7311 women in 10 trials),
most had node-negative disease
15-y overall mortality reduction 5.3% p=0.005
EBCTCG BCT

12. 50 Years of Progress :
 Integration of RT with surgery and systemic treatment has
made RT more effective.
 Postmastectomy Radiation in high risk disease improve
locoregional control.
 Combining BCS and Breast RT (BCT) as an alternative to
mastectomy.

13. Where are we going ?
Breast Cancer
Radiation Therapy (RT)

14.  Postmastectomy Radiation :- 45-50.4 Gy /25-28F in 5-51/2 weeks.
 Conserving Breast Surgery followed by whole breast irradiation 45-
50.4Gy/25-28F in 5-51/2 wks with/without tumor bed boost 10-16Gy/5-8F
in 1-1 1/2 weeks (total 5-6 ½ wks).
 However, for convinence and cost, hypofractionated RT for breast has
been explored.
 Lancet 2005; 366:2087-2106
Radiation Schedules

15. CANADA START A START B
 Energy Co-60, 4-6 MV 6 MV 6MV
 2D + Wedge Yes Yes Yes
 Planning 2D 2D/3DCRT 2D/3DCRT
 Central Axis Dose +/- 7% +/- 5% +/- 5%
 Tumor bed boost 0% 61 % 39 %
 Boost dose - 10 Gy/5 F 10 Gy/5F
 Energy of boost - Electron Electron
 Regional nodal RT 0 % 14.2% 7.3 %
The Breast 19 ( 2010) : 163-167
Hypofractionation WBI VS
CONVENTIONAL WBI

16. 
 Median FU IBTR LRR DFS OS
 CANADA 12 yrs
50Gy/25F 7.5% 84.4%
42.5Gy/16F 7.4% 84.6%
 START A 5.1 yrs
50Gy/25F 3.2% 3.6% 86% 89 %
41.6Gy/13F 3.2% 3.5% 88% 89%
 START B 6.0 yrs
50Gy/25F 3.3% 3.3% 86% 89%
40Gy/15F 2.0% 2.2% 89% 92%
Results

17.  Trial Median FU TD/F Cosmesis (good+excellence)
 CANADA 5 / 10 y 50/25 79.2 / 71.3 %
42.5/16 77.9 / 69.8 %
 START A 5 y 50/25 59.0 %
41.6/ 13 58.1 %
 START B 5y 50/25 58.8%
40/15 64.5 %
The Breast 19 (2010) : 163-167
Result :- Cosmesis

18. HF –WBRT is an acceptable treatment option for patient with
 pT1-2 tumor
 p N0 disease
 Age > 50 years
 Especially for patient who do not receive chemotherapy or do not require
tumor bed boost
 Patient who do not have plan for breast reconstruction
 World Journal of Clinical Oncology 2014 Aug 10;5(3):425-439
ASTRO Guideline

19.  acute skin toxicity :- moist desquamation in 30%-50% of patients
 erythema and edema of the irradiated breast
 telangiectasia and fibrosis of the skin
 effect cosmetic result and QOL
Clin Oncol 2004 ; 16 :12-16
Eur J Cancer 2008 ; 44 : 2587-2599
Radiother Oncol 1994 ;33: 106-112
IJROBP 2007 ; 68 : 1375-1380
With Conventional 2D-RT :-cause

20. Modern Radiotherapy Techniques
 Imaging
 Treatment Planning System
 New Radiation Machine
Results
 Improved efficacy
 Decreased toxicity
 Faster and convenient treatment

21. Modern RT techniques
(3D-CRT/IMRT)
 Advances of computed tomography can now
demonstrate three dimensional tissues/organs
 Advances in radiation treatment planning system
 Advance in radiation machine
We can now give high radiation doses to the
tumor while sparing the normal surrounding tissue

22. LINAC
with MLC

23. We are moving from 2D-RT to
1. Three-dimension RT (3D-CRT)
2. Intensity Modulated RT (IMRT)
IMRT has been shown to improve homogeneity and reduce acute toxicity
with improve QOL
CO 2008 ,May 1 : 28 (13):2085; 2085-2072
New RT techniques

24. 2D-Tangential beams 3D-CRT/IMRT
High exposure dose to lung and heart
and also hot spot at periphery area
More precise beam to target
with dose homogeneity

25. LUNG: V20 = 22% (wedge) = 19% (IMRT)
HEART: V5 = 0% (wedge) = 10% (IMRT)
V25 = 0% (wedge) = 0% (IMRT)
VOLUME : 2288.09 cc
Breast Separation : 29.5 cm
Pt.1

26.  Showed no statistically significant difference in 5- year
 Locoregional recurrence 2.56% VS 1.35 %
Overall survival 92.5 % VS 91.7 %
JCO 2013 ;31 : 4488-4495
IJROBP 2008 ;72 :1031-1040
Standard Wedge-based tangential fields VS IMRT

27. Acute reaction Conventional Wedge IMRT
Dermatitis grade >/= 2 85% 41%
Breast edema 28% 1%
Hyperpigmentation 50% 5%
Change in breast appearance 58% 40%
Late toxicity :- no difference in the reported occurrence of reaction pneumonitis,
fat necrosis , or second malignancy
IJROBP 2008 ;72 :1031-1040
IJROBP 2007; 68 : 1375-1380
IJROBP 2012 ; 84 : 888-893
Side effects

28.  70%-90% of IBTRs occurred at or in close proximity
to the lumpectomy cavity.
 APBI may offer equivalent local control to WBRT
NEJM 2002 ; 347 : 1233-1241
NEJM 2002 ; 347 : 1227-1232
Accelerated Partial Breast Irradiation
(APBI)

29. Include
 short treatment time :- from 5-6 weeks to 1-2 weeks
 decreased breast , heart and lung RT volume
 Possible improved cosmesis
 reduce cost and waiting time
Potential Disadvantage :- the possibility that occult foci of cancer
exist elsewhere in the breast and will not be treated.
Ann Surg Oncol 2012 ;19 : 3275-3281
Potential advantages of APBI

30. Brachytherapy : - Interstitial brachytherapy
- Intracavitary brachytherapy
- Intraoperative radiation
External beam RT : - 3DCRT
- IMRT/VMAT
Ongoing trial : - NSABP B-39 RTOG 0413
- WBRT VS APBI
Modalities for APBI

31. Partial Breast Irradiation (PBI)
Implantation
Mammosite
(3D-CRT / IMRT)
Intrabeam

32. Patients :
- Quadrantectomy , age >/= 48 years
- IDC , T </= 2.5 cm Lancet Oncol 2013;14:1269-1277
- Node negative BreastCancer Res treat 2010;124:141-151
Treatment :
ARM I :- WBRT 50Gy/25F , +/- 10 Gy boost
ARM II :- IORT 21 Gy x 1 F ( electron up to 9 MeV)
Results :
- median FU 5.8 y WBRT IORT
-IBTR 4 pts 35 pts p=0.0001
- 5-y OS 96.95% 96.8% p=0.59
ELIOT trial 1,305 patients

33. Patients : - Lumpectomy , age >/= 45 years
- IDC , node negative
Treatment :-
ARM I :- WBRT 40-56 Gy +/- Boost 10-16 Gy
VS
ARM II :- IORT single dose 20 Gy ( low –energy
X-ray 50 KV)
TARGIT – A trial 3,451 pts

34. Results : TARGIT –A
results WBRT IORT
 4-y LR 0.95% 1.2 % p=0.4
 5-y LR 1.3 % 3.3 % p=0.042
 Breast cancer death 1.9 % 2.6 % p= 0.56
 Non-breast cancer death 3.5% 1.41%
 The overall mortality was similar
 Major toxicity 3.3% 3.9 % P = 0.44
 14% of patient received WBRT in addition to IORT according to the final pathological
report.
Lancet 2010 ; 376 ; 91-102
Lancet 2014 ; 383 ; 603-613

35.  Currently, standard of care after conserving
breast surgery is still whole breast
irradiation.
 APBI :- awaiting the prospective setting
(RTOG 0413/NSABP B-39)
Summary

36. B-39/0413 Protocol Design
Eligible patient treated with lumpectomy
Stratification
Disease stage-DCIS, invasive N0, invasive N1(1-3)
Age ≤ 49, ≥ 50
Hormone receptor status (ER-,ER+)
Randomization
WBI
50-50.4 Gy in 1.8-2.0 Gy fractions
to whole breast, followed by
electron boost to surgical bed
with margin for total dose of 60-
66.6 Gy
APBI
34 Gy in 3.4 Gy bid x 5-7 days
Interstitial Brachytherapy
Or
34 Gy in 3.4 Gy bid x 5-7 days
Mammosite Balloon Catheter
Or
38.5 Gy in 3.85 Gy bid x 5-6 days
3D Conformal External Beam
VS

37.  WBRT 50 Gy/ 25 F
 VS
 HF 6 Gy x 5 F once weekly
 HF 5.7 Gy x 5 F once weekly
 The preliminary results showed inferior outcome for HF regimen
Radiother Oncol 2011 ; 93- 100
Semin Radiat Oncol 2008;18:257-264
Semin Radiat Oncol 2008 ;18:215-222
Ongoing Trial-UK FAST trial

38.  Proton Beam Therapy VS IMRT
for Breast Radiation
MDACC