Should radiotherapy be omitted in some early breast cancer patients?

26 

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(1)

Should radiotherapy be

omitted in some early breast

cancer patients?

Yong Bae Kim MD

Dept. of Radiation Oncology, Yonsei Cancer Center

(2)

Introduction

Breast-conserving surgery (BCS) followed by

radiation therapy (RT)

 Standard treatment for the majority of women with

early-stage invasive breast cancer

50.4 Gy/ 28 fractions to whole breast

10 Gy/ 5 fractions to tumor bed

(3)

Reasons to avoid RT

Inconvenience

 RT schedule of 6~6.5 weeks (30~33 fractions)

Radiation toxicity

 Breast swelling, muscle pain, breast discomfort, fibrosis  Radiation pneumonitis

 Cardiac toxicity

Secondary malignancies

(4)

RT in low risk early breast cancer

N F/U (yrs) Age >50 (%) ER/PR + (%) TAM/AI (%) G 1-2 (%) IBTR (%) RT No RT NSABP B21 1009 8 80 56.5 67 67 9.3 2.8 16.5 PMH 769 5.6 100 80.5 100 68.3 0.6 7.7 ABSCG Study 8a 869 4.48 99 100 100 95 0.4 5.1 CALGB 9343 626 10.5 100 97 100 - 2 8 GBSG-V 347 9.9 91.4 88 50 97.2 6 20 BASO II 1172 4.5 - - 25 100 1.3 3.6 PRIME 255 5 100 - - 94.5 0 6

(5)

RT in low risk early breast cancer

Small absolute local recurrence risk reduction

→ small mortality benefit

Should we omit RT?

However, it is clear that RT is effective on reducing

local recurrence, even though RT may not affects

survival in these patients.

(6)

Accelerated whole breast irradiation (AWBI)

(7)

Accelerated whole breast irradiation (AWBI)

These studies demonstrate that hypofractionation (HF)

yields equivalent or improved outcomes in all essential end

point parameters: efficacy, toxicity, cosmesis, and

cost-effectiveness.

HF-WBI also results in greater patient convenience and

resource efficiency.

(8)

Accelerated Partial breast irradiation (APBI)

External beam radiation therapy

(EBRT)

Brachytherapy

 Multicatheter interstitial

brachytherapy

 Intracavitary brachytherapy

Intraoperative radiation therapy

(IORT)

(9)

Accelerated Partial breast irradiation (APBI)

(10)

Reasons to avoid RT

Inconvenience

 RT schedule of 6.5 weeks (33 fractions)

Radiation toxicity

 Breast swelling, muscle pain, breast discomfort, fibrosis  Radiation pneumonitis

 Cardiac toxicity

Secondary malignancies

(11)

RT induced cardiac toxicity

Population-based case-control study of major

coronary events

 Sweden and Denmark, 1958-2001, age <70 or 75 years  n=2168: 963 case, 1205 controls

 Major coronary events: myocardial infarction, coronary

revascularization, death from ischemic heart disease (IHD)

 Dose-volume histogram for the whole heart and for the left

anterior descending coronary artery

(12)

RT induced cardiac toxicity

Risk factors

Lt. breast (RR 1.32, p=0.002), LN (+) (p=0.06)

History of IHD (RR 6.67, p<0.001)

History of other circulatory disease, DM, COPD,

current smoker, high BMI, regular analgesic use,

hormone-replacement

(13)

RT induced cardiac toxicity

Effect of RT

Mean doses to heart: 4.9 Gy (overall), 6.6 Gy (Lt), 2.9 Gy (Rt)

↑7.4 % / Gy (95% CI 2.9-14.5) p<0.001 ↑8.4 % / Gy (95% CI 3.6-15.9) p<0.001 Average (Gy)

Correlation with mean dose to whole heart

Cases

Whole heart 5.4 -

Lt. ant descending coronary a. 9.9 -

Whole heart (EQD2 Gy) 4.4 -

Controls

Whole heart 4.5 -

Lt. ant descending coronary a. 9.0 -

Whole heart (EQD2 Gy) 3.5 -

All

Whole heart 4.9 -

Lt. ant descending coronary a. 9.4 0.76 Whole heart (EQD2 Gy) 3.9 0.98

P<0.001 P=0.001

(14)

Reducing cardiac dose

Deep inspirational breathing hold (DIBH) technique

 The maximum separation between the target area and heart

can be achieved only at or near maximum inspiration

 Respiration control

 Active breathing control (ABC) device, Real-time Position

Management (RPM) system, Self respiration monitoring (SRM) system, Abches etc.

Intensity modulated RT (IMRT)

Prone positioning

(15)

DIBH using Abches

Left-sided breast cancer, n=25

Respiratory control using Abches system

Free breathing (FP) vs. DIBH

(16)

DIBH using Abches

FB plan DIBH plan P

Heart

Mean dose (Gy) 4.53 2.52 <0.001

V30 (%) 6.31 2.80 <0.001

V30 absolute volume (cm3) 45.13 16.48 <0.001

V20 (%) 7.64 3.16 <0.001

V20 absolute volume (cm3) 54.55 21.35 <0.001

LAD Mean dose (Gy) 26.26 16.01 <0.001

Dmax 0.2cm3 47.27 41.65 0.017

Lung

Mean dose (Gy) 8.04 7.53 0.073

V20 (%) 15.72 14.63 0.060

(17)

IMRT

Left-sided breast cancer, n=12

3D CRT vs. IMRT

Radiather Oncol (2013) 248-253

3D CRT with BH IMRT with BH

(18)

IMRT

3D CRT plan IMRT plan P

Heart

Mean dose (Gy) 1.8 1.5 <0.01

Dmax (Gy) 15.8 8.6 <0.01

V30 (%) 1.0 0.2 <0.01

V20 (%) 1.5 0.6 <0.01

LAD

Mean dose (Gy) 9.6 6.7 <0.01

Dmax (Gy) 25.2 18.8 <0.01

V20 (%) 17.8 9.7 <0.01

Lung

Mean dose (Gy) 3.0 2.6 <0.01

V20 (%) 6.2 5.1 <0.01

(19)

Prone positioning

(20)
(21)

Approximate cardiac doses associated with various

selected techniques

 The absolute benefits of radiation are likely to be increased with modern techniques.  Most studies of patients treated with modern techniques do not report

cardiotoxicity.

 Nevertheless, the effects seen at low doses in the study by Darby et al. highlight the

need for continued diligence.

(22)

Reasons to avoid RT

Inconvenience

 RT schedule of 6.5 weeks (33 fractions)

Radiation toxicity

 Breast swelling, muscle pain, breast discomfort, fibrosis  Radiation pneumonitis

 Cardiac toxicity

Secondary malignancies

(23)

3. Secondary malignancies after breast RT

EBCTCG meta-analysis

 Incidence of contralateral breast cancer: RR 1.18 (p=0.002)  Incidence of other specified cancer: RR 1.20 (p=0.001)

 Lung (RR 1.61, p=0.0007), esophagus (RR 2.06, p=0.05),

leukemia (RR 1.71, p=0.04), soft tissue sarcoma (RR 2.34, p=0.03)

 Mortality by other cause; heart disease etc.

(24)

3. Secondary malignancies after breast RT

SEER database

 1973-2002, 15 cancer that are routinely treated with RT

 Breast cancer: RT (n=90,613, 40%) vs. no RT (n=137,191, 60%)

RR of second solid cancer

Overall: 1.1 (95% CI 1.07-1.13)

Low (<1 Gy), medium (1-5 Gy), high (>5 Gy): p-trend <0.0001 Attributable risk: 5% (95% CI 4-7)

Lancet Oncol 2011; 12; 353-60

A relatively small proportion of second cancers are related

to radiotherapy in adults, suggesting that most are due to

other factors, such as lifestyle or genetics.

(25)

Summary

 Some physicians suggest the omission of RT in patients with

low risk early breast cancer.

 However, new RT modality can be applied to achieve maximal

local control and pt’s safety and convenience in early breast cancer

 Modification of RT fractionation (HF-WBI, PBI) ⇒ increase convenience of patients

 Decreased cardiac toxicity through reducing cardiac dose using DIBH, prone position or IMRT

 Only small proportion of secondary malignancy after RT was related with RT.

(26)

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