Radiation Therapy Update: Radiation Therapy Update: SABCS 2005SABCS 2005

Janice Ryu, M.D.

UC Davis

Radiation Oncology

SABCS Update 2005SABCS Update 2005

3 oral presentations Abstract 7: Bijker et al, EORTC

DCISAbstract 8: Gnant et al, ABCCSG

low risk invasive breast CAAbstract 22: Gadd et al, MGH

+ sentinel LN dz: axillary RT w/o AND

Radiotherapy in breast-conserving treatment Radiotherapy in breast-conserving treatment for ductal carcinoma in situ (DCIS): ten-year for ductal carcinoma in situ (DCIS): ten-year

result of European Organization for result of European Organization for Research and Treatment of Cancer Research and Treatment of Cancer (EORTC) randomized trial 10853(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: DCISEORTC 10853: DCIS

Objective: To determine the role of breast RT post-WLE in DCIS

Median f/u 10.2 yrsSample size: 1010 womenClinically detected: 29% vs.

mammographically detected: 71%

EORTC - 10853 DesignEORTC - 10853 Design

Randomize

Radiation50 Gy

Excise with Negative Margins*

Observe

< 5.0 cm

*If repeat excision still has + margins mastectomy

EORTC 10853 EORTC 10853

4 Year Recurrence Rates 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 ResultsEORTC 10853: 10-Yr Results

Treatment Local Control p

Group at 10 yrs (%) HR

WLE 75 < 0.0001

WLE+RT 85 0.55

EORTC 10853: ResultsEORTC 10853: Results

Risk of DCIS and invasive local recurrence both reduced by 42% (p=0.009 & p=0.006)

Risk of contralateral breast cancer similarNo difference in distant metastases and

death22 pts (2%) developed metastases due to

invasive local recurrence

EORTC 10853: ResultsEORTC 10853: Results

Multivariate analysis for factors predicting local recurrence

Factors HRAge < 40 1.95Clinical detection 1.53Higher grades (2/3) 1.77Solid/cribriform pattern 2.21Doubtful margin status 1.82WLE only 1.74

EORTC 10853: ConclusionEORTC 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 ResultsNSABP-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 XRTFisher, E. et.al. Sem. In Oncology August 2001

Breast Conservation without radiotherapy Breast Conservation without radiotherapy in low risk breast cancer patients – results in low risk breast cancer patients – results

of 2 prospective clinical trials of the of 2 prospective clinical trials of the Austrian Breast and Colorectal Cancer Austrian Breast and Colorectal Cancer

Study Group involving 1,518 Study Group involving 1,518 postmenopausal patients with endocrine postmenopausal patients with endocrine

responsive breast cancer.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 radiotherapyBreast conservation without radiotherapy

Eligible pts:

1. Older age

2. Significant co-morbid diseases

3. Hormone receptor positive

4. Early stage, small tumors

5. Candidates for systemic hormonal therapy

Breast conservation without radiotherapyBreast 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 Prospective study of axillary radiation without axillary dissection for breast without axillary dissection for breast

cancer patients with a positive sentinel cancer patients with a positive sentinel nodenode

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 +: Axillary RT for SLN +: BackgroundBackground

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 +: MethodsAxillary 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&ERT: tangents and 3rd field (49 Gy / 27 fxs)F/U: q 6 months arm circumference & grip

strength measurements, QOL questionnaires

Axillary RT for SLN +: ResultsAxillary RT for SLN +: Results

Median F/U: 32 monthsAll pts received systemic therapyAxillary recurrence: 1/73 pt at 17 months,

currently NED after salvage ADLymphedema: 1 pt with transient

lymphedema at 6 months, but none at 4 yrsMinimal arm pain, numbness, better ROM,

less time off work

Axillary RT for SLN +: Axillary RT for SLN +: DiscussionDiscussion

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: Poster Presentations: SABCS 2005SABCS 2005

1. Abstract 1003: lymphedema risk of ax RT after ax sampling

2. Abstracts 4035 & 4041: CVD risk with RT

3. Abstract 4037: IMRT for L breast

4. Abstract 4046: IMN recurrence without IMC RT

5. Abstracts 4038 & 4051: Mammosite brachytherapy

# 1003: Comparative study of lymphedema with axillary # 1003: Comparative study of lymphedema with axillary node dissection and axillary sampling with radiotherapy node dissection and axillary sampling with radiotherapy in women undergoing breast conservative surgery for in women undergoing breast conservative surgery for breast cancer. Mathew et al, Ysbyty Gwynedd, UKbreast 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 10-#4035: Long term risk of cardiovascular disease in 10-year survivors of breast cancer. Hooning et al, year survivors of breast cancer. Hooning et al,

Netherlands Cancer InstituteNetherlands 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 riskTreatment period #pts RT/no RT HR

<1980 1,882 80/20% 1.5 >1980 2,486 90/10% 1.3Risk of CVD increased with IMC RT in period <1980RT to left CW assoc’ed with increased CVD, but not to right CWRT to breast only not assoc’ed with increased CVDMI: RT+smoking: HR 3.0, RT-smoking: HR 1.3, smoking-RT: HR 1.4After 1979, increased MI w/ RT to L CW, CHF w/ R & L IMC RT

#4041: Radiation therapy and cardiac toxicity in breast #4041: Radiation therapy and cardiac toxicity in breast cancer patients 65 years and older: a population-based cancer patients 65 years and older: a population-based

study. Doyle et al, Columbia University, New Yorkstudy. 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 #4037: Inverse-planned, dynamic, multi-beam, intensity modulated radiation therapy (IMRT) for left-sided breast modulated radiation therapy (IMRT) for left-sided breast cancer: comparison to best standard of care. Olivotto, cancer: comparison to best standard of care. Olivotto,

British Columbia, CanadaBritish 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 alL breast IMRT: Olivotto et al

Benefits of IMRTStructure Parameter Best Std IMRT p valuePTV H.I. 0.74 0.95 <0.001

C.I. 0.48 0.91 <0.001Heart Mean V30 12.5% 1.7% <0.001L Lung Mean V20 26.6% 17.1% <0.001 Costs of IMRTHealthy tissue Mean dose 6.9 Gy 6.0 Gy <0.001

V5(%) 23.6% 31.7% <0.001R breast Mean dose 2.9 Gy 4.3 Gy <0.001

V5 (%) 7.9% 29.2% <0.001R lung Mean dose 1.5 Gy 3.6 Gy <0.001

V5 (%) 2.0% 13.7% <0.001

#4046: Risk of internal mammary recurrence after #4046: Risk of internal mammary recurrence after mastectomy in absence of internal mammary chain mastectomy in absence of internal mammary chain

radiation therapy. A retrospective study. Lerouge et al, radiation therapy. A retrospective study. Lerouge et al, Centre Francois Baclesse, Caen, FranceCentre 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)