CSPOR-BC年会 2014 2 1 2月2日於かずさアカデミアホールAvoiding axillary surgery 2....

CSPOR-BC年会 20142014年2月1日(土)～2月2日(日) 於かずさアカデミアホール

※CSPOR乳がんグループへの閲覧限定資料につき、その他への転用を禁ずる 1

2013 ASCO2013 ASCO and SABCS : Reviewand SABCS : Review

Local therapyLocal therapy

Tadahiko Shien, MD, PhD.Tadahiko Shien, MD, PhD.Okayama University HospitalOkayama University Hospital

ASCOASCO annual annual meeting 2013 : Local therapymeeting 2013 : Local therapy

Sentinel Lymph node biopsy 10 rpts.Axillary lymph node metastasis 4 rpts.

Adjuvant radiation therapy 8 rpts.

Sentinel Lymph node biopsy 10 rpts.Axillary lymph node metastasis 4 rpts.

Adjuvant radiation therapy 8 rpts.

Breast conserving therapy and IBTR 6 rpts.

Reconstruction 2 rpts.

Stage IV breast cancer 2 rpts.

Others 7 rpts.

Breast conserving therapy and IBTR 6 rpts.


Stage IV breast cancer 2 rpts.

Others 7 rpts.

SABCS 2013 : Local therapySABCS 2013 : Local therapy

Axillary staging and Sentinel Lymph node biopsy 26 rpts.

Surgery 16 rpts.

Axillary staging and Sentinel Lymph node biopsy 26 rpts.

Surgery 16 rpts.

Breast conservation 9 rpts.


Radiation 20 rpts.

Breast conservation 9 rpts.


Radiation 20 rpts.

Sentinel NodesSentinel Nodes


Radiation therapyRadiation therapy

ImagingImaging




ImagingImaging



The feasibility of the proposed SNIPE Trial;Sentinel lymph node biopsy vs. No-SLNB In Patients with Early breast cancerNadeem R MDepartment of Breast surgery, Lancashire Teaching Hospital NHS Founding Trust, Chorley, UK

Patients with invasive breast cancer who underwent SLNB between October 2006-April 2012 were identified from prospectively maintained d t b i i tit ti database in our institution.

Patients with tumours < 2 cm in size who underwent breast conserving surgery (BCS), and suitable for tangential-field whole-breast radiotherapy without regional nodal irradiation (RNI) and neo-adjuvant therapy were analyzed.

The feasibility of the proposed SNIPE Trial;Sentinel lymph node biopsy vs. No-SLNB In Patients with Early breast cancerNadeem R M

Patients were further divided into different groups; those who fulfil the criteria of SOUND trial and those who were suitable for our proposed trial and others. Different groups of patients were analyzed to identify the possible group of patients most suitable to this approach in terms of risks of ALNs metastasis, further non-SLNs metastasis and patients with > 4 total number of nodes (SLNs + non-SLNs). with 4 total number of nodes (SLNs non SLNs). We also calculated the number of SLNB procedures that could have been avoided in view of the protocol set by both strategies and cost effectiveness analysis by calculating the money saved per procedure and theatre time. An NHS tariff for SLNB is approximately £ 750. Similarly patients with > 4 total number of nodes in different groups were identified who would be candidate of level III axillary/supraclavicular radiotherapy to determine the patients at disadvantage.

Abandoning sentinel lymph node biopsy in early breast cancer? A new trial in progress at the European Institute of Oncology of Milan (SOUND: Sentinel node vs Observation after axillary UltraSouND)

Oreste Gentilini and Umberto Veronesi

Breast. 2012 Oct;21(5):678-81. doi: 10.1016/j.breast.2012.06.013. Epub 2012 Jul 25.

Breast cancer ≤2 cm, and a clinically negative axilla

Any age

Candidates to receive breast conserving surgery + radiotherapy

SOUND trial: Eligibility criteria.

Negative preoperative assessment of the axilla (ultrasound with or without FNAC in case one doubtful node is found)

Written informed consent must be signed and dated by the patient and the investigator prior to inclusion.

Patients must be accessible for follow-up

SOUND trial: study design.Primary endpoint:Distant disease free survival

Secondary endpoint:Cumulative incidence of distant reci.Cumulative incidence of axillary reciDFS, OS.

N=1560 (780 per arm) non-inferiority

1. Avoiding axillary surgery2. Absence of pathological information3. Pre-operative imaging of AX.

2012 Feb~



194 patients met the inclusion criteria The mean patient age

Results

The feasibility of the proposed SNIPE Trial;Sentinel lymph node biopsy vs. No-SLNB In Patients with Early breast cancerNadeem R M

194 patients met the inclusion criteria. The mean patient age was 58.5 years ;75% of the patients were 50 years of age.The incidence of tumour positive ALNs is 5% in T1b, G1-2 tumours where SLNB could be omitted without compromising the surgical outcomes. The burden of axillary nodal disease is shown in Table1.

Groups SOUND Tri-al(T1,G1-3)

T1, G1-2 T1, G1-2,no LVI

T1b tumours

T1b, G1-2SNIPE Trial T1, G1 < 15mm

G1-2< 15mm G1

Total patients with T1 tumours and clinically negative axilla with no multifocality=194

Number of patients

194 151 139 49 43 57 92 43

Incidence of ALNs mets

30/194(15.5%) 20/151(13.3%) 16/139(11.5%) 6/49(12.4%) 4/43(9.3%) 8/57(14%) 15/92(16%) 7/43(16%)

Incidence and burden of axillary metastasis in different groups.

Incidence of ALNs mets excludingmicromets

13.4% 11.9% 10% 6.1% 4.6% 10.5% 13% 11.6%

Incidence of non-SLNs

metastasis

9/30(30%) 7/20(35%) 3/16(18.8%)1/6(16.7%)

0% 2/8(25%) 3/15(20%) 2/7(28.6%)

Incidence of > 4 total number oftumour positive

ALNs

5/194(2.5%) 4/151(2.6%) 2/139(1.4%) 1/49(2%) 0% 1/57(1.7%) 1/92(1.1%) 1/43(2.3%)

Differences between SOUND Trial and SNIPE Trial

SOUND Trial SNIPE Trial

Inclusion criteria T1, clinically Node negative T1b, G1-2, clinically Node

Post SLNB treatment

Macromets in SLNs

Axillary clearance 1-2 positive SLNs= observe

>3 positive SLNs=>3 positive SLNs=

SPINE trial:

T1b,G1-2

Arm 1- WLE+SLNB

Arm 2- WLE only

WBI+adjuvant systemic therapyR

WLE: Whole lymph node evaluationWBI: Whole Breast Irradiation

Sentinel nodesSentinel nodes今後今後

温存後照射有症例における SN+ の⾮郭清は世界的にほぼagree?

全摘後症例でも PMRTの併⽤により SN+でも⾮郭清の⽅向へ。

温存＋RT症例では SN⾮施⾏の⽅向へすでに進みはじめている。

〜現在この流れに対して⽇本は静観・・・・薬剤と違って外科臨床試験は国際試験への参加はない・・・・




ImagingImaging



Novel combination of toll-like receptor (TLR)-7 agonist imiquimod and local radiotherapy in the treatment of breast cancer chest wall recurrences or skin metastases.Janosky M1, Demaria S1, Novik Y1, Oratz R1, Tiersten A1, Goldberg J1, Wang E2, Marincola F2, Formenti S1, Adams S11New York University Cancer Institute, NYU School of Medicine, New York NY, 2National Institute of Health

PURPOSEPURPOSE

•To assess the local and systemic effects of the novel combination of local radiotherapy (RT) with imiquimod (IMQ) applied topically to breast cancer metastatic to skin, and measure immunologic correlates.

SUMMARY

•IMQ inhibited growth of murine TSA breast cancer, which was associated with increased tumor infiltration by CD11c, CD4, and CD8 cells, and abolished by depletion of CD8 cells.

IMQ + RT s nergi ed in local t mor control leading to complete t mor regressions •IMQ + RT synergized in local tumor control, leading to complete tumor regressions and improved survival in the TSA model.•Topical IMQ and RT resulted in growth inhibition of a secondary tumor outside of the radiotherapy field, which was enhanced by the application of IMQ to the secondary tumor, suggestive of IMQ’s ability to enhance the effector phase T cell response as well.



RT and imiquimod synergize in inducing TSA tumor regression.

Topical imiquimod sensitizes a secondary tumor to the abscopal effect induced by

treatment with IMQ + RT of a primary tumor.

Design and Treatment: Single arm, open label phase II trial.

Radiotherapy: RT is delivered to Area A of skin metastases selected by radiotherapy oncology in 5 fractions of 6 Gy on days 1, 3, 5, 8 and 10. Tumor responsesare evaluated outside of areas A and B.

Imiquimod: IMQ 5% cream is applied topically to Areas A and B overnight 5 days / week

Current Trial

for 8 weeks starting day 1.

Primary endpoint:Response rate in untreated distant metastases (abscopal effect), assessed by immune-related response criteria.

Secondary endpoints:Secondary endpoints:1. To determine the local tumor response of the combination of IMQ+RT.2. Safety3. To examine whether IMQ+RT augments tumor specific T cell immunity and induces a tumor microenvironment signature consistent with immunological rejection.

Eligibility Criteria1. Patients with biopsy-confirmed breast cancer.2. Patients with measurable skin metastases and distant, measurable metastases.3. ECOG performance status 0-2 and adequate organ and bone marrow function.4. Concurrent systemic cancer therapy (hormones, biologics or chemotherapy) can be continued if distant metastases are non-responsive (i.e. no CR or PR) on that regimen for >8 weeks.

Current Status:The phase I study portion completed with six patients without dose limiting toxicity (3-3 design). The phase II portion is ongoing with the goal of 25 additional patients.




薬剤と併⽤することで RTの効果を最⼤限に得られるような試みが進む。

RTの効果を予測した治療戦略も考慮していく？RTの効果を予測した治療戦略も考慮していく？

RT+薬剤、⼿術＋薬剤、薬剤のみといった治療選択が乳がんのタイプに応じて⾏われていく・・・。




ImagingImaging



Perioperative Breast MRI Is Not Associated with Lower LocoregionalRecurrence Rates in DCIS Patients Treated With or Without Radiation

Melissa Pilewskie, Cristina Olcese, Anne Eaton, Sujata Patil, Elizabeth Morris, Monica Morrow and Kimberly J. Van Zee

Ann Surg Oncol. 2014 Jan 3. [Epub ahead of print] Ann Surg Oncol. 2014 Jan 3. [Epub ahead of print]



Summary of literature on association of perioperative MRI and breast cancer locoregional recurrence rates a8-year LRR reported for invasive carcinoma b8-year LRR reported for DCIS patients

Autho, year Total patients

DCIS patientsN (%)

Patients with MRIN (%)

Patients with DCIS and MRIN (%)

Patients with DCIS without RTN (%)

Variables controlled for on multivariable analysis

Time interval for which LRR reported (years)

Reported LRR

p valueMRI (%)No MRI (%)

Fischer et al. 2004 346 23 (7) 121 (35) 15 (4) 0 3.4 1.2 6.5 <0.001

Solin et al. 2008 756 136 (18) 215 (28) 31 (4) 0 Age, year 8 3a

6b3a

6b0.320.51

Hwang et al. 2009 463 0 127 (27) 0 0

Age, year, adjuvant chemotherapy/endocrine therapy, tumor grade, LVI, hormone receptor status, HER2 status

8 1.8 2.5 0.67

Shin et al. 2012 794 87 (11) 572 (72) 62 (8) 13 (2) 5 1.2 2.3 0.33

Current series 2,321 2,321

(100) 596 (26) 596 (26) 904 (39)

Age, menopausal status, family history, presentation, margin status, number excisions, year, RT, endocrine therapy

8 14.6 10.2 0.42

ImagingImaging

何のためにそれぞれの検査を⾏っているのか意識する必要がある

Local therapyLocal therapyまとめまとめ

今後Local therapyのみの改善（診断、術式、RT）でOSを改善することはない・・・？

Local therapyと薬剤を組み合わせたり、Local therapyの適応を予測してその効果を最⼤限に利⽤する治療戦略を考えていく必要がある。

[GENERAL SESSION 2 #S2-02]

Surgical removal of primary tumor and axillary lymph nodes in women with metastatic breast cancer at

first presentation: A randomized controlled trial

Rajendra AB, et al.Tata Memorial Centre, Mumbai, Maharashtra, India

Rajendra AB, et al. SABCS2013 Abst #S2-02

TRIAL SCHEMA

MBCMBC

Loco-RegionalRx

Loco-RegionalRx

RRAnthracycliens +/- taxanes

（CR/PR）Anthracycliens +/- taxanes

（CR/PR）No Loco-

Regional RxNo Loco-

Regional RxStratificationStratification


Site of metastases

Visceral

Bone

Visceral + bone

Site of metastases

Visceral

Bone

Visceral + bone

No of metastases

≦3

＞3

No of metastases

≦3

＞3

ER/PgR

Positive

Negative

ER/PgR

Positive

Negative

StratificationStratification



RESULTS

Loco-Regional Rx（n=173）

Loco-Regional Rx（n=173）

Randomization（n=350）

Randomization（n=350）

No Loco-Regional Rx（n=177）

No Loco-Regional Rx（n=177）


* Loco-regional Therapy: BCT/MRM with supraciavicular lymph node clearness whenever indicated tamoxifen in pre menopausal women and AI in Post menopausal women/post Oophorectomy in pre menopausal women No HER2 positive patient received HER2 targeted therapy

LR surgery* + RTLR surgery* + RTHormone Rx （n=106） as indicated including ovarian ablation （n=34）Hormone Rx （n=106） as indicated including ovarian ablation （n=34）

Hormone Rx （n=102） as indicated including ovarian ablation （n=40）Hormone Rx （n=102） as indicated including ovarian ablation （n=40）

BASELINE CHARACTERISTICSNo LRRx （n=177）

n （%）LRRx （n=173）

n （%）Total

Site of metastasisBoneVisceralBone + Visceral

50 （28.2）77 （43.6）50 （28.2）

50 （28.9）75 （43.4）48 （27.7）

10098152

No. of metastasis


No. of metastasis≦3＞3

45 （26.0）132 （74.0）

44 （25.4）129 （74.6）

89261

ER/PgRPositiveNegative

106 （59.9）71 （40.1）

102 （59.0）71 （41.0）

208142

Age（Median） 47 48 47

Menopausal statusPrePost

88 （49.7）89 （50.3）

74 （42.8）99 （57.2）

162186

DEVIATIONS IN SURGICAL TREATMENT

No LRRx （n=177）n （%）

LRRx （n=173）n （%）

Total

Protocol violations 3 （1.7%） 9 （5.2%） 12


Palliative mastectomy（per protocol）

18 （10.2%） 1 （0.6%） 19

OVERALL SURVIVALsu

rviv

al

1.0

0.8

0.6

HR=1.04, 95% CI=0.80-1.34, p=0.79

LRRx （n=173）No LRRx （n=177）


0

Cum

s

0.4

0.0

0.2

LRRxNo LRRx

Time in monthsAt risk

12 24 36 48 60 72

20.5%

19.2%

177 101 50 24 12 8 3173 105 49 21 6 3 1

DISTANT PROGRESSION-FREE SURVIVAL

surv

ival

1.0

0.8

0.6

HR=1.42, 95% CI=1.08-1.85, p=0.01

LRRx （n=173）No LRRx （n=177）


0

Cum

s

0.4

0.0

0.2

LRRxNo LRRx

Time in monthsAt risk

12 24 36 48 60 72

47.5%

28.3%

177 74 38 17 8 6 2173 66 26 12 4 2 1

この結果からわかったこと・・・

初診時より遠隔転移を有するStage IV乳癌に対して乳癌のサブタイプに応じた薬物療法を⾏わず、アンスラサイクリンまたはタキサンをNAC⽅式で⾏って原発巣を切除してもそれだけでは⽣存期間は伸びない。

術後薬物療法を適切に⾏わなければむしろ転移巣は憎悪する可能性あり。

Stage IV乳癌に対して原発巣を切除しなくても局所症状がでる可能性は10%程度。局所を考えて全例早めに切除する必要はない。



[GENERAL SESSION 2 #S2-03]

Early follow up of a randomized trial evaluating resection of the primary breast tumor in women presenting with de novo stage IV breast cancer;

Turkish study （protocol MF07-01）

Atilla S, et al.Turkish Federation of Societies for Breast Diseases, Istanbul, Turkey

Atilla S, et al. SABCS2013 Abst #S2-03

DESIGN MF07-01

Systemic therapy

Systemic therapy

Presentation Randomization Follow-up

Local therapy for local progressionLocal therapy for local progression


Stage Ⅳbreast cancer

Stage Ⅳbreast cancer

therapytherapy

Initial local therapy of

breast±Axillaplus systemic

therapy

Initial local therapy of

breast±Axillaplus systemic

therapy

Time to local progression

overall survival


overall survival


overall survival


overall survival

BASELINE CHARACTERISTICSInitial surgery （n=140） Systemic Tx （n=138） p

Age （mean years±SD）BMI （kg/m2）Mean follow-up （months）Median follow-up （min-max）

51.8±12.927.6±5.121±14.618 （1-55）

51.5±13.528.0±5.520.9±14.517 （1-54）

nsnsnsns

% （n） % （n）

Tumor sizeT1T2

8.6 （12）52 1 （73）

8.0 （11）42 8 （59） ns


T2T3T4

52.1 （73）22.1 （31）17.1 （24）

42.8 （59）21.7 （30）27.5 （38）

ns

Histology gradeGrade ⅠGrade ⅡGrade Ⅲ

4.3 （6）40.0 （56）55.7 （78）

9.5 （10）32.4 （34）58.1 （61）

ns

Tumor typeInvasive ductalInvasive lobular

79.3 （111）10.7 （15）

84 （116）8.7 （12）

ns

ER/PgR （+） 86.4 （121） 72.3 （99） ns

HER2 （+） 30.7 （43） 30.4 （42） ns

Triple （-） 7.1 （10） 17.4 （24） ns

BASELINE CHARACTERISTICS （THERAPY）Initial surgery

（n=140）% （n）

Systemic Tx（n=138）% （n）

p

BCS + Axillary evaluation 25.7 （36）

M + axillary evaluationSLNB

74.3 （104）17 （24）


ALNDPositive LN

90 （126）88.6 （124）

Surgery to met site % 6.4 （9） 5.1 （7）

RT to met site % 18.6 （26） 28.3 （39）

Anthracyline based CT 82.9 （115） 79 （109） ns

Bisphosphonates 22.9 （32） 20.3 （28）

BASELINE CHARACTERISTICS （METASTASIS）

Metastasis siteSurgery （N=140）

% （n）

Systemic Tx（N=138）% （n）

p

1 organ

＞1 organ

76 （106）

24 （34）

65 （89）

35 （49）ns

Bone only 52 （73） 40 （55）


Bone onlyBone +othersOthers （no bone）

52 （73）24 （33）24 （34）

40 （55）27 （37）33 （46）

ns

Solitary bone

Multiple bone

24 （33）

29 （40）

15 （20）

25 （35）ns

Solitary pulmonary or liver

Multiple pulmonary or liver

9 （13）

9 （13）

12 （16）

12 （16）ns

OVERALL SURVIVAL

all s

urvi

val

1.0

0.8

0.6

0 4

SurgeryST


0

Ove

ra 0.4

0.0

0.2

Months10 20 30 40 50 60

n Death Median （months） HR （95% CI） p

Surgery 140 38 46 0.76 （0.49-1.16） 0.20

ST 138 48 42



OVERALL SURVIVAL

1.0

ll su

rviv

al

0.8

0.6

Solitary bone Met1.0

ll su

rviv

al

0.8

0.6

Multiple bone Met


00.0

Ove

ral

0.4

0.2

10 20 30 40 50 60

Months

Solitary bone n Death Median Mean HR （95% CI） p

Surgery 33 3 NR 47.5 0.23 （0.06-0.89） 0.02

ST 20 8 42 33.1

00.0

Ove

ral

0.4

0.2

10 20 30 40 50

Months

All others n Death Median HR （95% CI） p

Surgery 40 11 46 1.02 （0.43-2.43） 0.94

ST 35 10 42

60

Surgery

ST

Surgery

ST

この結果からわかったこと・・・

いきなりStage IV全例に⼿術を⾏っても、⼿術のみで予後の改善は⾒込めない可能性あり。

⾻転移単独の場合（特に単発の場合）転移診断をしっかりと⾏うことは必要⾻転移単独の場合（特に単発の場合）転移診断をしっかりと⾏うことは必要。（原発巣切除しないことで、予後を悪くする可能性あり）

2つの試験結果からわかったこと・・・・

適切な薬物療法なしに原発巣切除のみを⾏っても予後の改善はなく、逆に原発巣切除を⾏わなくても局所コントロールは多くの症例で保たれるだろう。

サブタイプに合わせた効果的な薬剤＋原発巣切除の意義はどうか？

RANDOMIZED TRIALS ADDRESSING THE IMPACT OF PRIMARY SITE LOCAL THERAPY

CountryInitial

therapyAccrual period

Sample size

Accrual As of …

India CAF±T 2005-12 350 350 （done） 2012

JapanSystemic therapy

2011-16 500/410 176/109 Dec 2013

Seema AK, et al. SABCS2013 Abst #S2-04

therapy

USA and Canada

Systemic therapy

2011-16 368/258 174/141 Nov 2013

Turkey Surgery 2008-12 281 271 （done） 2013

Netherlands Surgery 2011-16 516 Low Oct 2013

Austria Surgery 2010-19 254 62 Dec 2013

CSPOR-BC年会 2014 2 1 2月2日於かずさアカデミアホールAvoiding axillary surgery 2....

Documents

Transcript of CSPOR-BC年会 2014 2 1 2月2日於かずさアカデミアホールAvoiding axillary surgery 2....

CSPOR-BC年会 2014 2 1 2月2日 於かずさアカデミアホールAvoiding axillary surgery 2....

Documents

Transcript of CSPOR-BC年会 2014 2 1 2月2日 於かずさアカデミアホールAvoiding axillary surgery 2....

CSPOR-BC年会 2014 2 1 2月2日於かずさアカデミアホールAvoiding axillary surgery 2....

Transcript of CSPOR-BC年会 2014 2 1 2月2日於かずさアカデミアホールAvoiding axillary surgery 2....