early breast cancer treatment radiotherapy

Early Breast Cancer Treatment Radiotherapy

MD. Yan Carlos Vargas Caycho

MR Radiation Oncology Edgardo Rebagliati Martins Hospital

Lima - PERU

IA: T1 N0

IB: T1 N1mic

IIA: T1 N1, T2 N0

IIB: T2 N1, T3 N0

T1: < 2cm

T2: 2 – 5cm

T3: > 5cm

Early Breast Cancer 80%

AJCC 7th edition 2011

SEER Registry - Surveillance, Epidemiology, and End Results Program

National Cancer Institute 2003 - 2009

IA: T1 N0

IB: T1 N1mic

IIA: T1 N1, T2 N0

IIB: T2 N1, T3 N0

cN1: any Ax N movable

ipsi levels I - II

pN1mic: > 0.2mm/200cell

< 2.0mm

pN1a: 1 – 3 AxN

pN1b:

Internal Mammary m/m

pN1c: pN1b + pN1c

Early Breast Cancer

80%

AJCC 7th edition 2011

IA: T1 N0

IB: T1 N1mic

IIA: T1 N1, T2 N0

IIB: T2 N1, T3 N0

Localized : 98.6%

Confined to primary site

Regional : 84.4 % Spread to LNs

Distant : 24.3 % Cancer has metastasided

5 yr Survival

SEER Registry - Surveillance, Epidemiology, and End Results Program

National Cancer Institute 2003 - 2009

Clinically –

axilla

Mets at LND

40 %

NSABP B 04

Clinically –

axilla

Not LND

20 %

National Surgical Adjuvant Breast and Bowel Project

Palpable

Radiologically

visible

ALND

Surgery

Axilla Stage

Non Palpable

Non

Radiologically

visible

SLND

Mastectomy or

lumpectomy

to SLN Bx

+ ALND

NSABP B 32 5,611 pts

Mastectomy or

lumpectomy

to SLN Bx alone

10 yr

OS 88.9% 87.8%

DFS 76.9% 76.9%

LR 4.0% 4.3%

Krag DN et al. Lancet Oncology 2010; 10 yr update ASCO 2013

NSABP-32: Phase III, Randomized Trial Comparing Axillary Resection with

Sentinal Lymph Node Dissection: A Description of the Trial

http://www.nsabp.pitt.edu/Abstract_129.asp































Mastectomy or

lumpectomy

to SLN Bx

+ ALND 516

ALMANAC trial

1,031 pts

Mastectomy or

lumpectomy

to SLN Bx alone 515

1 yr

lymphedema 13% 5%

sensory loss 31% 11%

J Natl Cancer Inst 98:599-609, 2006

lumpectomy

to SLN Bx

+ ALND

Milan trial

280 pts

65 – 80 yo

T < 2cm N0

Tamoxifeno 5 yr

lumpectomy

to SLN Bx alone

15 yr

Axillary disease 0% 6%

Ann Surg 256:920-924, 2012

445

ALND

+ WIB

+ SLND

900 pts

891 close early

5 yr SLND did not result in inferior

OS 92.5% 91.8%

DFS 82.2% 83.9%

LRR-free survival 96.7% 95.7%

Giuliano AE et al. JAMA 2011

T1 T2 tumor

1 or 2 + SLN

Lumpectomy

WBI

No Neoadj systemic therapy

NCCN 2014

ACOSOG Z0011

445

SLND

+ WIB

Treatment Early Breast Cancer

Total mastectomy

+/- systemic therapy

+/- RT

Breast

Conservation

Therapy

Breast

Conservation

Surgery + RT

+/- systemic therapy

Mastectomy vs BCT

NSABP B06 (longest 20yr)

Milan III

Ontario

Royal Marsden

EORT 10801

Oxford meta-analysis ( most recent)

Mastectomy vs BCT

NSABP B06

Total

Mastectomy

Lumpectomy

+ RT 50Gy

20 yr follow up. Not difference DFS, OS, DM

1851 pct

Stage I, II

Randomized

Fisher B et al. NEJM 2002

Mastectomy vs BCT

EBCTCG Oxford meta analysis

BCS + RT BCS alone

10 yr recurrence : 19.3% 15.7% 35%

15 yr mortality 21.4 3.8 25.8

pN0 reduction risk rec 15.4 3.3

pN+ reduction risk rec 21.2 8.5

10 801 women

17 Trials

EBCTCG Lancet 2011

RT decrease 50% recurrence, 16.6% mortality

For every women prevented to have LR, 1 woman is saved

Mastectomy vs BCT

Contraindications

1.- Prior RT to the chest ………… IOR

2. – Extend of Disease that excision could not achieve margins with

acceptable cosmetic result … Multicentricidad and multifocality.

3. – Diffuse microcalcifications.

4.- 1er or 2do trimestre of pregnancy

5. – Persistently +margin.

6.- Collagen vascular disease (escleroderma)

NCCN 20014

Positive family history breast cancer

BRCA mutations (contralateral?, oophorectomy? Tamoxifen?,

mastectomy?


Breast Conservation Therapy

Radiation Therapy

WBI +/- boost

Hypofractionated WBI +/- boost

APBI External beam, interstitial, intracavitary

IOR

Radiation Therapy

WBI

Dose fractionation schedules

Standard

50 Gy in 2 Gy fx

45 – 50.4 Gy in 1.8 Gy fx

Hypofractionated

42.56 Gy in 2.67 Gy fx

40.05 Gy in 2.67 Gy fx

Hypofractionated WBI

Canadian regimen

Whelan TJ et al. NEJM 2010

42.5 Gy in 16 fx

(2.65 Gy fx)

50 Gy in 25 fx

(2.0 Gy fx)

1 234 women randomized

T1 – 2 N0

Negative Surgical margin

Women with > 25 cm breast width

10 yr follow-up: no difference in LR, DFS or cosmesis


British regimen

START A/B trials, Lancet 2008

40 Gy in 15 fx

(2.67 Gy fx)

50 Gy in 25 fx

(2.0 Gy fx)


pT1 – 3 N0 - 1

Boost and adj systemic optional

6 yr follow-up: no difference IBRT 2% vs. 3%

10 yr no difference in LR (San Antonio Breast Cancer 2012)


ASTRO Guidelines

1. > 50 yo

2. pT1-2 N0, treated with BCS

3. No systemic chemo

4. Good homogeneity: +/- 7%

boost

EORTC boost trial

(Bartelink K et al. JCO 2007)

50 Gy in 25 fx

50 Gy in 25 fx

16 Gy boost SM -


All boost

Brachytherapy, electrons, photons

10 yr LF: 6.2% + boost vs. 10.2% - boost

< 50 yo: LR 24% - boost, 13.5% +boost

11.3 yr no difference LC (251 pct 16 Gy vs 26 Gy )

50 Gy in 25 fx

26 Gy boost SM +

Total Mastectomy + RT

British Columbia retrospective study

( Truong PT et al, IJROBP 2004)

41 pt SM +

PMRT 94 pt SM+

2 570 women

< 50 yrs

T2 tumor

G3

LVI

53 pt SM +

No RT

BCS and systemic therapy

without RT

Princess Margaret Hospital / Canadian trial

(Fyles AW et al. NEJM 2004)

Tamoxifeno alone 50 yo

T1 or T2 ER +

- nodes

-SM

769 women randomized

8 yr follow-up

LR 17.6 % 3.5%

Tumors < 1cm 2.6 % 0%

>60 yo, T < 1cm 1.2 % 0%

Tamoxifeno

+ RT

40Gy

Boost 12.5 Gy

BCS and systemic therapy

without RT

CALGB 9343/Intergroup trial

(Hughes KS et al., NEJM 2004; updated JCO 2013

Tamoxifeno alone > 70 yo

T1 ER +

- nodes

-SM


12.6 yr follow-up

LR 10 % 2%

Tamoxifeno

+ RT

45 Gy

Boost 14 Gy

Axillary nodal dissection vs RT

AMAROS

The Lancet Oncology, November 2014,

2402 / 744

ALND

T1–2 (< 3cm)

no palpable nodes

positive sentinel node

1425

randomly (1:1)

phase 3 non-inferiority


5 yr follow-up axillary recurrence 0.43% 1.19%

Lymphoedema

2404 / 681

RT ASC

50 Gy


Adj Chemo

- LN

TN or HER2/neu: tumor > 1cm(0.6 – 1.0cm)

ER+ and HER2/neu – and tumor > 0.5cm

Oncotype: Low recurrence score(<18): adj endocrine

Intermediate score( 18 – 30): adj endocrine +/-chemo

High recurrence score (> 31): adj endocrine + chemo


Adj Chemo

+ LN

HER2/neu+

HER2/neu-

AC: adriamicina + ciclofosfamida

T: paclitaxel

Trastuzumab


Adj endocrine therapy

ER + and tumor > 0.5 cm (< 0.5cm)

Premenopausal : TAMOXIFENO 5 years

20mg/day

Postmenopausal: AI 5 years

Chemo - RT Sequenced

JCRT sequencing trial

(Bellon J et al. JCO 2005)

CHEMO first

CHEMO first

CONVENTION

5 yr follow-up distant recurrence 20% 32%

11 yr follow up up date no diference DS LR DM OS

- SM LR 6% 13%

RT first

Image-based Conformal Radiation Therapy:

Left Breast

60 Gy

62 Gy

50 Gy 45 Gy 20 Gy

axial sagittal

BREAST RADIOTHERAPY

RT Prono

Transaxial

Sagittal

3-DCRT for left prone breast radiation:

Improved targeting and avoidance of lung

60 Gy

50 Gy

45 Gy

Lumpectom

y

PTV

BRACHYTHERAPY

Multi-Catheter Brachytherapy

Dose Distribution of MultiCatheter PBI

PTV

100% isodose

5 years post treatment

Breast Appearance Following Multi-catheter Brachytherapy

Spherical applicators

1.5 to 5cm diameter in 0.5cm steps

Uniform surface dose-rate

RADIATION ONCOLOGY TEAM

Edgardo Rebagliati Martins National

Hospital

Lima - PERU

early breast cancer treatment radiotherapy

Health & Medicine