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The 5th Annual Update in Breakthrough in Hematology and Oncology (AUBHO 2015)
28-29th August 2015 At the Nai Lert Park
Swissotel Bangkok ,Thailand
Updates in Radiotherapy for Breast Cancer
Prasert
Lertsanguansinchai,M.D. Radiation Oncologist Wattanosoth Hospital
50 Years of Advances in Radiotherapy for Breast cancer
Radiation Therapy (RT) : What have we Learned ?
Where are we Now ?
Where are we Going ?
What have we learned ?
Breast Cancer
Radiation Therapy (RT) 50 years ag0
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
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.
Where are we now ?
Breast Cancer
Radiation Therapy (RT)
Tumor Biology
Breast cancer is a systemic disease needs
1.Locoregional control.
2.Prevent and get rid of microdistant metastasis.
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
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
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
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.
Where are we going ?
Breast Cancer
Radiation Therapy (RT)
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
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
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
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
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
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
Modern Radiotherapy Techniques Imaging Treatment Planning System New Radiation Machine
Results Improved efficacy Decreased toxicity Faster and convenient treatment
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
LINAC with MLC
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
2D-Tangential beams 3D-CRT/IMRT
High exposure dose to lung and heart and also hot spot at periphery area
More precise beam to targetwith dose homogeneity
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
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
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
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)
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
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
Partial Breast Irradiation (PBI)
ImplantationMammosite
(3D-CRT / IMRT)
Intrabeam
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
Patients : - Lumpectomy , age >/= 45 years - IDC , node negative
Treatment :-ARM I :- WBRT 40-56 Gy +/- Boost 10-16 Gy VSARM II :- IORT single dose 20 Gy ( low –energy X-ray 50 KV)
TARGIT – A trial 3,451 pts
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
Currently, standard of care after conserving breast surgery is still whole breast irradiation.
APBI :- awaiting the prospective setting (RTOG 0413/NSABP B-39)
Summary
B-39/0413 Protocol DesignEligible patient treated with
lumpectomy
StratificationDisease stage-DCIS, invasive N0, invasive N1(1-3)
Age ≤ 49, ≥ 50Hormone receptor status (ER-,ER+)
Randomization
WBI50-50.4 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
APBI34 Gy in 3.4 Gy bid x 5-7 days
Interstitial BrachytherapyOr
34 Gy in 3.4 Gy bid x 5-7 days Mammosite Balloon Catheter
Or38.5 Gy in 3.85 Gy bid x 5-6 days
3D Conformal External Beam
VS
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
Proton Beam Therapy VS IMRT for Breast Radiation
MDACC
THANK YOU FOR YOUR
ATTENSION
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