Jina Kim, Jee Suk Chang, Seo Hee Choi, Yong Bae Kim,

Ki Chang Keum, Chang-Ok Suh, Jun Won Kim, Ik Jae Lee

Department of Radiation Oncology, Gangnam Severance Hospital,

Yonsei University College of Medicine, Seoul, Korea

Radiotherapy for Initial Clinically Internal mammary node-positive Breast cancer

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Eur J Nucl Med Mol Imaging (2014)

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June 2009-December 2015T1-4, N2b or 3b Breast cancer patientsBCS or MRM, followed by radiotherapy (CW+RNI)Clinically IMN-positive, either by MRI or PET

M1 stage at diagnosis IMN dissection No regional LN RT Incomplete RT

(e.g. patient refusal)

Final cohort N = 95

Simulation

3D CRT

IMRT

No Boost

Sequential

Conventional

Hypofraction

SIB

No Boost

Breast boardMev Green

• Reverse hockey stick • Standard tangent +ant beam • Partial wide tangential • Photon-electron mixed

• Partial Two arc VMAT

Variables n %

Age

Median 46

Range 20-73

icT

1-2 60 63.1

3-4 35 36.9

IMN detection

MRI only 19 20.0

PET 75 80.0

IMN size

Variables n %

Neoadj. CTx

No 18 18.9

Yes 77 81.1

Neoadj. CTx response

Down-staging (+) 59 76.6

Down-staging (-) 18 23.4

Surgery

BCS 22 23.2

Mastectomy 73 76.8

Resection Margin

Negative 87 91.6

Close/positive 8 8.4

Variables n %

RT modality

3D CRT 67 70.5

IMRT 28 29.5

RT schedule

Conventional 75 78.9

Hypofx 20 21.1

IMN RT

w/o boost 83 87.3

IMN boost 12 12.7

IMN boost dose in EQD2 (α/β=4.0)

Median 10 Gy

IQR 9-12 Gy

IMN response after neoadj. CTx- SD, n = 6 (7.8%) - PR, n = 19 (24.6%) - CR, n = 52 (67.5%)

IMN boost (-) IMN boost (+) P

N % N %

Age ≤ 40 22 26.5 2 16.7 0.463

> 40 61 73.5 10 83.3

cT 1-2 51 61.4 9 75.0 0.458

3-4 32 18.6 3 25.0

IMN size < 1cm 35 42.2 3 25.0 0.256

≥ 1cm 48 57.8 9 75.0

Neoadj. Response Down-staging (+) 54 77.1 5 71.4 0.095

Down- staging (-) 16 22.9 2 28.6

LVI Yes 18 21.7 5 41.7 0.131

Lum type Lum A 9 10.8 0 0.0 0.221

Lum B 32 38.6 3 25.0

Non-Lum 22 26.5 3 25.0

TNBC 20 24.1 6 50.0

H grade 1, 2 44 62.9 5 45.5 0.421

3 26 37.1 6 54.5

RM Close/(+) 6 7.2 2 16.7 0.271

IMN

co

ntr

ol r

ate

(%

)

Time (Month)

Dis

eas

e fr

ee s

urv

ival

(%

)

IMN recur, 3 cases5-yr IMN control 96.4%

Any recur, 24 cases5-yr DFS 70.6%

Time (Month)

No. at risk12 12 11 10 9 9 9

No. at risk95 93 81 77 73 72 7195 90 88 86 85 84 83

5-yr OS 84.2%

case 1 2 3

Age 55 31 29

Initial stage cT3N3 cT2N3 cT2N3

Initial IMN One, 1.6 cm One, 1.1 cm One, 1 cm

Neoadj. CTx AC-T #4 (no visible IMN+) AC-T #4 (no visible IMN+) AC-T #4 (0.4 cm IMN+)

Surgery MRM c ALND MRM c ALND MRM c ALND

P stage pT0N0 pT1N1 pT2N0

RM negative negative Close

LUM type Lum B, Her2 + TNBC TNBC

Adj. CTx/HTx Adj. Herceptin None None

RT CW, RNI 50 Gy w/o boost CW, RNI 40 Gy w/o boost CW, RNI 50 Gy w/o boost

Recur site IMN SCL, AXL, IMN, Rt. Paratracheal, paraaortic, AP window LNs

SCL, AXL, IMN, neck Lv IV-VI, T7 spine, sternum, liver

DFS 30.7 mo 19.9 mo 25.3 mo

OS 87.1 mo 2018.09 alive 28.4 mo

Univariate

n % 3yr-rate P

Age ≤ 40 ＞40

2471

25.374.7

91.798.1

0.132

cT 1-23-4

6035

63.236.8

96.596.3

0.942

IMN size < 1cm≥ 1cm

3857

40.060.0

10094.1

0.156

Neoadj. response

Down-staging (+)Down-staging (-)

5918

76.623.4

94.6100

0.407

LVSI NoYes

7223

75.824.2

96.994.7

0.549

LUM type Lum ALum BNon-Lum, Her2 (+)TNBC

9352526

9.536.826.327.4

10096.710090.4

0.309

H grade 1 or 23

4932

60.539.5

10092.6

0.062

RM (-)Close or (+)

878

91.68.4

97.575.0

0.009

IMN boost NoYes

8312

87.312.7

96.0100

0.538

IMN size

< 1 cm (n=38)

≥ 1 cm (n=57)

IMN boost (+)

(n=3)

IMN boost (-)(n=35)

IMN boost (+)

(n=9)

IMN boost (-)(n=38)

IMN failure n=0

IMN failure n=0

IMN failure n=0

IMN failure n=3 (6.3%)

P = 0.095

IMN >1cm, no boost (n=48)

Others (n=47)

5yr IMN control100 % vs. 93.2%

Time (Month)IM

N c

on

tro

l rat

e (

%)

IMN size

< 1 cm (n=38)

≥ 1 cm (n=57)

IMN boost (+)

(n=3)

IMN boost (-)(n=35)

IMN boost (+)

(n=9)

IMN boost (-)(n=48)

Any recurn=0 (0%)

Any recurn=9 (26%)

Any recurn=2 (13%)

Any recurn=13 (27%)

P = 0.499

5yr DFS83.3% vs. 71.9%

no boost (n=83)

IMN boost (n=12)

Time (Month)

Dis

eas

e fr

ee

surv

ival

(%

)

Univariate Multivariate

n % 3yr DFS P Hazard R P

Age ≤ 40 ＞40

2471

25.374.7

87.575.1

0.092

cT 1-23-4

6035

63.236.8

84.567.6

0.010 2.959 0.016

IMN size < 1cm≥ 1cm

3857

40.060.0

78.278.6

0.770

Neoadj. response

Down-staging (+)Down-staging (-)

5918

76.623.4

85.852.9

0.002 1.121 0.713

LVSI NoYes

7223

75.824.2

86.852.2

0.000 4.376 0.002

LUM type Lum ALum BNon-Lum, Her2 (+)TNBC

9352526

9.536.826.327.4

55.685.285.969.0

0.043

H grade 1 or 23

4932

60.539.5

78.671.7

0.185

RM (-)Close or (+)

878

91.68.4

81.245.0

0.012 4.251 0.013

IMN boost NoYes

8312

87.312.7

77.683.3

0.499

Adverse effect Grade IMN boost (-) (n = 59) IMN boost (+) (n = 8) P

N % N %

Any lung toxicity G1 (Radiologic) 3 5.1 3 37.5 0.003

G2 (Symptomatic) 1 1.7 0 0 0.711

Cardiac toxicity Any grade 0 0 0 0

Skin reaction G1 12 20.3 3 37.5 0.275

G2 8 13.6 4 50.0 0.012

Esophagitis G1 1 1.7 1 12.5 0.092

Adverse effect Grade IMN boost (-) (n = 24) IMN boost (+) (n = 4) P

N % N %

Any lung toxicity G1 (Radiologic) 0 0 0 0

G2 (Symptomatic) 1 4.2 0 0 0.678

Cardiac toxicity Any grade 0 0 0 0

Skin reaction G1 5 20.8 0 0 0.314

G2 1 4.2 0 0 0.678

Esophagitis G1 0 0 0 0

3D CRT

IMRT

• Radiotherapy alone shows high control of initial clinically positive IMN without surgery • 5-yr IMN control rate 96.4%

• IMN control rate may be maximized by addition of IMN boost RT, especially in case of IMN ≥ 1cm

• IMN boost RT was not associated with increased severeacute and late toxicity

• Compared to historical data, IMN+ patients had relatively higher disease-free (70.6%) and overall survival (84.2%)

• Due to small number of boost RT pts, we could not find the impact of IMN boost RT and dose-response relationship on DFS or OS

• The present findings continue to support that RT including IMN can provide excellent IMN control without surgery in patients with initial clinically positive IMN in breast cancer

• Further studies are required to investigate the impact of IMN boost RT and optimal boost dose