Present Status ofPresent Status ofPartial Irradiation

Of the Breast

Breast Conservation Therapy

• alternative to mastectomy: equal outcome

• outcomes have improved over time

Outcome of BCT in 2013Outcome of BCT in 2013

• outcomes have improved over time

– screening: early stage

– improved breast imaging

– improved pathology/surgery

– use of systemic therapy

– improve radiation delivery

Low Rates of Local RecurrenceLow Rates of Local Recurrence

96%

Breast Recurrence Rates At MDACC Over Time

96.5%96%

Cabiogula, Cancer, 2005

96.5%

Radiation Plays a Critical Radiation Plays a Critical Role in Achieving TheseRole in Achieving These

Excellent OutcomesExcellent Outcomes

Early Breast Cancer Trialist’s Group• meta-analysis of lumpectomy +/- XRT• long term outcome

Radiation and Breast Conservation: Radiation and Breast Conservation: Invasive Breast CancerInvasive Breast Cancer

• long term outcome• 17 trials, 10,801 patients• conclusions

– XRT reduces breast recurrence– XRT improves overall survival

Lancet 378, 2011

Oxford MetaOxford Meta--Analysis of Analysis of BCT +/BCT +/-- Radiation TrialsRadiation Trials

Lancet 378, 2011

Oxford MetaOxford Meta--Analysis of Analysis of BCT +/BCT +/-- Radiation TrialsRadiation Trials

Lancet Lancet

378, 2011

New Research Focus:New Research Focus:Make Radiation Less Make Radiation Less Make Radiation Less Make Radiation Less

BurdensomeBurdensome

6-7 weeks of daily treatment

• impractical for some

– pts who live away from facility

There Is a Need to MakeThere Is a Need to MakeWhole Breast Radiation FasterWhole Breast Radiation Faster

– pts who live away from facility

– countries with limited number of rad onc depts

• forces many to have mastectomy

• expensive

New Research Strategies

• hypofractionated whole breast radiation

• intraoperative single fraction PBI

Four Approaches ToFour Approaches ToDecreasing Radiation BurdenDecreasing Radiation Burden

• intraoperative single fraction PBI

• 3D conformal PBI

• brachytherapy PBI

• interstitial

• catheters

Can the Rx be shorten from 5 wks to 3 wks• two prospective trials: Canada and UK • both mostly enrolled LN- disease, postmen

Whole Breast HypofractionationWhole Breast Hypofractionation

• both mostly enrolled LN- disease, postmen• Fractionation

– Canada: 42.5 Gy/16 fx vs 50 Gy/25 fx– UK START B: 40/15 fx vs. 50/25 fx

Canadian• 10 yr result equivalent

– breast recurrence: 6.2% vs. 6.7%

ResultsResults

– good/excellent cosmesis: 70% vs. 71%

UK• 5 yr result equivalent

– breast recurrence: 2.8% vs. 2.8%– good/excellent cosmesis: equivalent

Can the Rx be shorten to 1 – 5 days• most tumors recur at tumor bed site • treat limited breast volume

Partial Breast IrradiationPartial Breast Irradiation

• treat limited breast volume• target tumor bed + 1 cm

– allows for treating with fewer fractions– possible lower complications

Treatment of a small volume around tumor Treatment of a small volume around tumor bedbedmay not prevent all recurrencesmay not prevent all recurrences

Treatment Volume Rationale(Con Side of Debate)

Pathology

• Vaidya JS et al.: 30 cases

– 63% had other foci of disease

Disease Extent DataDisease Extent Data

– 79% of these outside index quadrantMRI Data

• International collaborative study– 24% had incidental lesions

• Bedrosian et al.– 18% had additional disease found

Treated with a surgical PBI target volume

• 85% T1 primary, 67% LN -

Milan Quadrantectomy TrialMilan Quadrantectomy Trial

24%

Veronsi et al, Ann Oncol, 12:997, 2001

Intraoperative XRTIntraoperative XRT

(Veronesi U, et al.

Eur J Cancer

2001;37:2178-83)

(Vaidya JS, et al.

Eur J Surg Oncol

2002;28:447-54)

Targit Trial Lancet 2010Targit Trial Lancet 2010

•• 1113 patients randomized trial1113 patients randomized trial–– favorable disease cohortfavorable disease cohort–– 14% of 14% of targittargit pts received whole breastpts received whole breast–– 14% of 14% of targittargit pts received whole breastpts received whole breast–– most ER+, still receiving most ER+, still receiving tamoxifentamoxifen

•• 4 year results excellent4 year results excellent–– 1% local recurrence in both arms1% local recurrence in both arms

ELIOT Trial EBCC 2012ELIOT Trial EBCC 2012

•• Whole breast vs. Whole breast vs. IntraoperativeIntraoperative ElectronElectron–– 66--fold higher LR in IO Electron Armfold higher LR in IO Electron Arm–– 66--fold higher LR in IO Electron Armfold higher LR in IO Electron Arm

Conformal External Beam Conformal External Beam

Arthur, DW et al. J Clin Oncol 23:1726-1735, 2005

Canadian RAPID TrialCanadian RAPID Trial

Whole Breast Irradiation after Partial Breast Irradiation prior

2135 Patients with Lumpectomy

RANDOMIZED

Whole Breast Irradiation after Adjuvant Chemotherapy

50 Gy (2.0 Gy/fraction) or42.5 Gy in 16 fractions

Partial Breast Irradiation prior to Adjuvant Chemotherapy

38.5 Gy in 3.85 Gy fractions3D Conformal External Beam

ASTRO plenary session 2012

• no data on local recurrence

• Cosmetic data assessed by nurses, photos

Cosmetic Outcome DataCosmetic Outcome Data

• prior to XRT, both arms had 18% adverse cosmesis

• 3 yrs after XRT, adverse cosmesis rates were

– 32% in partial breast arm

– 19% in whole breast arm• also had increase rates of G1/G2 late toxicity

NSABP BNSABP B--39/RTOG 041339/RTOG 0413Phase III APBI TrialPhase III APBI Trial

Whole Breast Irradiation after Partial Breast Irradiation prior

Eligible Patients with Lumpectomy

RANDOMIZED

Whole Breast Irradiation after Adjuvant Chemotherapy

50 Gy (2.0 Gy/fraction) or50.4 Gy (1.8 Gy/fraction) to whole

breast, followed by optional boost to > 60 Gy

Partial Breast Irradiation prior to Adjuvant Chemotherapy

For a total of 10 treatments given on 5 days over 5 to 10 days:

34 Gy in 3.4 Gy fractionsInterstitial Brachytherapy or

Mammosite Balloon Catheter or

38.5 Gy in 3.85 Gy fractions3D Conformal External Beam

Fractionated Brachytherapy Fractionated Brachytherapy

Mammosite Double Plane Implant

(Rt-image.com)(mammosite.com)

Mammosite DataMammosite Data

American Society of Breast Surgery RegistryAmerican Society of Breast Surgery Registry•• 1440 pts with invasive disease1440 pts with invasive disease•• 5 yr breast recurrence rate: 3%5 yr breast recurrence rate: 3%•• 5 yr breast recurrence rate: 3%5 yr breast recurrence rate: 3%•• 88% good/excellent cosmesis @ 5 yrs88% good/excellent cosmesis @ 5 yrs•• not a former clinical trialnot a former clinical trial

Vicini, ASTRO 2009

•• 130,535 women130,535 women•• medicaremedicare billing claimsbilling claims•• age ≥ 67 yearsage ≥ 67 years

MDACC Study Population

•• age ≥ 67 yearsage ≥ 67 years•• invasive breast cancer diagnosed 2000 invasive breast cancer diagnosed 2000 –– 20072007•• treated with lumpectomy + radiation treated with lumpectomy + radiation

Smith et al, JAMA, 2012Smith et al, JAMA, 2012

P for trend < 0.001

Brachy Use Over Time

4%

Subsequent Mastectomy Risk

P < 0.001

2%

LN +LN +

HR

4.69

95% CI

2.83 – 7.76

P

<0.001

MV Analysis By LN Status

LN ─LN ─ 2.06 1.73 – 2.45 <0.001

No modifying effect seen with:

Age, race, comorbidity, chemotherapy, year, region

OutcomeOutcome

AnyAny

Brachy (%)

24

WBI (%)

14

P

<0.001

Postoperative Complications

AnyAny

InfectiousInfectious

NonNon--infectiousinfectious

24

16

16

14

10

8

<0.001

<0.001

<0.001

AnyAny

Rib fractureRib fracture

26

4.2

Outcome Brachy (%) WBI (%) P

18

3.6

<0.001

0.03

Post-radiation Complications

Rib fractureRib fracture

Fat necrosisFat necrosis

Breast painBreast pain

RT pneumonitisRT pneumonitis

4.2

9

15

0.1

3.6

4

12

0.8

0.03

<0.001

<0.001

<0.001

Many new catheters to deliver APBI• combination of interstitial/intraluminal• allow greater sparing of skin

New DirectionsNew Directions

• allow greater sparing of skin• greater conformality over chest wall

Depth Markers

5 Radiation Lumens

Variably Inflatable Balloon

Contura™ MLB

Stiffening StyletStiffening Stylet

Vacuum Ports Vacuum Lumen

Inflation Lumen

ConturaContura™MLB Target Coverage™MLB Target Coverage

SAVISAVI™™

ASTRO Consensus StatementASTRO Consensus StatementSuitable for Suitable for APBIAPBI Unsuitable for APBIUnsuitable for APBI

ABPI may prove to be an exciting advance• much more convenient for some• may extend the option of BCT

ConclusionConclusion

• may extend the option of BCT• selection criteria likely important• efficacy data and safety data yet to mature• await outcome of phase III studies