Transcript Document

Radiation Therapy Update:
SABCS 2005
Janice Ryu, M.D.
UC Davis
Radiation Oncology
SABCS Update 2005
3 oral presentations
 Abstract 7: Bijker et al, EORTC
DCIS
 Abstract 8: Gnant et al, ABCCSG
low risk invasive breast CA
 Abstract 22: Gadd et al, MGH
+ sentinel LN dz: axillary RT w/o AND
Radiotherapy in breast-conserving treatment
for ductal carcinoma in situ (DCIS): ten-year
result of European Organization for
Research and Treatment of Cancer
(EORTC) randomized trial 10853
Bijker N, Meijnen PH, Bogaerts J, Peterse JL,
on behalf of EORTC Breast Cancer Group
& Radiotherapy Group. The Netherlands
Cancer Institute, Amsterdam, Netherlands;
EORTC, Brussels, Belgium
EORTC 10853: DCIS

Objective: To determine the role of breast
RT post-WLE in DCIS
 Median f/u 10.2 yrs
 Sample size: 1010 women
 Clinically detected: 29% vs.
mammographically detected: 71%
EORTC - 10853 Design
< 5.0 cm
Excise with Negative Margins*
Randomize
Radiation
50 Gy
Observe
*If repeat excision still has + margins
mastectomy
EORTC 10853
4 Year Recurrence Rates
No Further Treatment
Radiation
503 pts.
507 pts.
83 (17%)
53 (10%) p.005
54 % of recurrences in each group were DCIS
46 % of recurrences in each group were Invasive
Julien, J. P. et. al.
Lancet;355;p528-532; 2000
EORTC 10853: 10-Yr Results
Treatment
Group
WLE
WLE+RT
Local Control
at 10 yrs (%)
75
85
p
HR
< 0.0001
0.55
EORTC 10853: Results

Risk of DCIS and invasive local recurrence
both reduced by 42% (p=0.009 & p=0.006)
 Risk of contralateral breast cancer similar
 No difference in distant metastases and
death
 22 pts (2%) developed metastases due to
invasive local recurrence
EORTC 10853: Results
Multivariate analysis for factors predicting local
recurrence
Factors
HR
Age < 40
1.95
Clinical detection
1.53
Higher grades (2/3)
1.77
Solid/cribriform pattern
2.21
Doubtful margin status
1.82
WLE only
1.74
EORTC 10853: Conclusion

RT after WLE reduced the number of
ipsilateral breast recurrences by 45% at 10
yrs.
 RT reduced the risk of local recurrence in
all clinical and pathological subgroups.
 Women at high risk of local recurrence even
after RT include young age < 40 yrs (27%)
and close/involved margins (23%).
NSABP-17: 12-yr Results
Lumpectomy
Lumpectomy
+ Radiation
No. Patients
403
410
Recurrence
149 (31.7%)
101 (15.7%)
Annual Rate Breast
Cancer events /100 pts.
4.8
2.8
% of Recurrences -Invasive
53%
47%
57% Relative Reduction In Recurrence For Pts. Receiving XRT
Fisher, E. et.al. Sem. In Oncology August 2001
Breast Conservation without radiotherapy
in low risk breast cancer patients – results
of 2 prospective clinical trials of the
Austrian Breast and Colorectal Cancer
Study Group involving 1,518
postmenopausal patients with endocrine
responsive breast cancer.
Gnant MFX, Poetter R, Kwasny W, Tausch C,
Handle-Zeller E, Pakesch B, Schmid M,
Hausmaninger H, Stierer M, Kubista E, Sedlmayer
F, Draxler W, Luschin-Ebengreuth G, Jakesz R,
Austrian Breast and Colorectal Cancer Study
Group. Medical Universities of Vienna, Graz,
Salzburg, and Innsbruck, Vienna, Austria
Breast conservation without radiotherapy

1.
2.
3.
4.
5.
Eligible pts:
Older age
Significant co-morbid diseases
Hormone receptor positive
Early stage, small tumors
Candidates for systemic hormonal therapy
Breast conservation without radiotherapy

Is hormonal therapy as a local therapy
option as effective as breast RT?
 Is hormonal therapy as safe as breast RT?
 Is hormonal therapy as cost-effective as
breast RT?
Prospective study of axillary radiation
without axillary dissection for breast
cancer patients with a positive sentinel
node
Gadd M, Harris J, Taghian A, Hughes K,
O’Neill A, Powell S, Christian R,
Lesnikoski B, Kaelin C, Rhei E, Iglehart J,
Habin K, Oberg J, Younger J, Winer E,
Smith B, Massachusettes General Hospital,
Boston, MA; Brigham and Women’s
Hospital, Boston, MA; Dana-Farbar Cancer
Institute, Boston, MA
Axillary RT for SLN +:
Background





Std of care for SLN+ pts: completion AD
50% have no additional LN disease on further
ALND
Complications of ALND: 15-25% lymphedema or
chronic pain
Axillary RT: equivalent axillary local control, less
lymphedema
Systemic therapy decisions less dependent on the
number of involved ALN’s
Axillary RT for SLN +: Methods

560 pts with CS T1/2 N0 treated by
WLE/SLND from 1/00-2/04
 73 pts with +SLN treated with axillary RT
 +SLN defined as any met. deposit on H&E
 RT: tangents and 3rd field (49 Gy / 27 fxs)
 F/U: q 6 months arm circumference & grip
strength measurements, QOL questionnaires
Axillary RT for SLN +: Results

Median F/U: 32 months
 All pts received systemic therapy
 Axillary recurrence: 1/73 pt at 17 months,
currently NED after salvage AD
 Lymphedema: 1 pt with transient
lymphedema at 6 months, but none at 4 yrs
 Minimal arm pain, numbness, better ROM,
less time off work
Axillary RT for SLN +:
Discussion

Extremely low rates of axillary recurrence
and arm symptoms after axillary RT for
SLN + disease
 Can axillary RT replace completion
dissection?
 Data may be premature: median f/u only 32
months, need longer follow-up
Poster Presentations:
SABCS 2005
1.
2.
3.
4.
5.
Abstract 1003: lymphedema risk of ax RT after ax
sampling
Abstracts 4035 & 4041: CVD risk with RT
Abstract 4037: IMRT for L breast
Abstract 4046: IMN recurrence without IMC RT
Abstracts 4038 & 4051: Mammosite brachytherapy
# 1003: Comparative study of lymphedema with axillary
node dissection and axillary sampling with radiotherapy
in women undergoing breast conservative surgery for
breast cancer. Mathew et al, Ysbyty Gwynedd, UK

Retrospective review of pts undergoing breast conservation
 Axillary sampling + AxRT if LN +(Group 1): 312 pts,
1994-98
 Axillary clearance (Group 2): 194 pts 2000-02
 Minimum f/u 2 yrs
 Lymphedema defined as 2 cm difference in circumference
of arms
Groups
1
2
1 +LN 2 +LN
Lymphedema rate 2.2% 12.3%
6.2%
15.4%
#4035: Long term risk of cardiovascular disease in 10year survivors of breast cancer. Hooning et al,
Netherlands Cancer Institute

Retrospective review of CVD incidence in a group of 10-yr
survivors (N=4,368) w/ early BC, 1970-1987

Med f/u 18 yrs

942 CV events (MI, angina, CHF): standardized excess risk (SIR)
of 1.3, 63/10,000 person-yrs absolute excess risk
Treatment period #pts
RT/no RT
HR
<1980
1,882
80/20%
1.5
>1980
2,486
90/10%
1.3
Risk of CVD increased with IMC RT in period <1980
RT to left CW assoc’ed with increased CVD, but not to right CW
RT to breast only not assoc’ed with increased CVD
MI: RT+smoking: HR 3.0, RT-smoking: HR 1.3, smoking-RT: HR 1.4
After 1979, increased MI w/ RT to L CW, CHF w/ R & L IMC RT
#4041: Radiation therapy and cardiac toxicity in breast
cancer patients 65 years and older: a population-based
study. Doyle et al, Columbia University, New York




SEER-Medicare database, St. I-III breast CA pts of > 65
age (N=31,748), 1992-99
36% BCS, 63% MRM, 46% RT (73% of BCS)
L-sided RT assoc’ed w/ increased MI (HR=1.26), but not
other cardiac outcome, compared to R-sided RT
Increased MI risk highest with L chest wall RT (HR=1.71)
#4037: Inverse-planned, dynamic, multi-beam, intensity
modulated radiation therapy (IMRT) for left-sided breast
cancer: comparison to best standard of care. Olivotto,
British Columbia, Canada


11-beam IMRT plan vs. best standard plans compared for
30 consecutive L-sided breast CA pts undergoing BCRT
Homogeneity of dose (H.I.), conformity(C.I.), and doses to
heart, lungs, R breast, and “Healthy tissue” (CT dataset
minus PTV)
L breast IMRT: Olivotto et al

Benefits of IMRT
Structure
Parameter
PTV
H.I.
C.I.
Heart
Mean V30
L Lung
Mean V20
 Costs of IMRT
Healthy tissue Mean dose
V5(%)
R breast
Mean dose
V5 (%)
R lung
Mean dose
V5 (%)
Best Std
0.74
0.48
12.5%
26.6%
IMRT
0.95
0.91
1.7%
17.1%
p value
<0.001
<0.001
<0.001
<0.001
6.9 Gy
23.6%
2.9 Gy
7.9%
1.5 Gy
2.0%
6.0 Gy
31.7%
4.3 Gy
29.2%
3.6 Gy
13.7%
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
#4046: Risk of internal mammary recurrence after
mastectomy in absence of internal mammary chain
radiation therapy. A retrospective study. Lerouge et al,
Centre Francois Baclesse, Caen, France
 1,353 pts treated by mastectomy & postop RT 1985-96
 RT: 50 Gy to the chest wall +/- SCF, no IMC RT for
incomplete resection or extensive axillary LN involvement
 T3-4 37%, pN0 37%, pN1 1-3 34%, N+>3 27%
 RT 52%, CTX 42%, hormones 66%
 5-yr rate of IMN recurrence 2%
 IMN recurrence greatest in LN+ >9 group (8%)
 No IMN recurrence in the historical control group of 1,226
pts treated with IMC RT 1973-84, but these pts had worse
survival (probably due to less use of systemic therapy)