3048365-1 American College of Surgeons Oncology Group Heidi Nelson, M.D. David M. Ota, M.D

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American College of Surgeons Oncology Group

American College of Surgeons Oncology Group

Heidi Nelson, M.D.

David M. Ota, M.D.

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Who are we?Who are we?

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ACOSOG

Operations and Membership Center

Members

Scientific Leadership

Statistics and Data Center

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Members

37%

6%

18%

4%

35%

Specialty Hospital type

37%

15%2%

46%

Medical oncology

Radiation oncology

Surgeon

CRA / nurse

Other

Teaching affiliate

Academic / university

Community

Other

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WA

OR

CA

NV

ID

UTCO

WY

MT

AZNM

TX

OK

KS

NE

SD

ND

MN

IA

MO

AR

LA

MS AL

TN

KY

IL IN OH

WIMI

PA

WVVA

NC

SC

GA

FL

NY

VT

ME

NH

CT

MA

RINJ

DE

MDDC

British Columbia, CanadaOntario, Canada

Breast IDIGs

GI IDIGsThoracic IDIGs

Key

Members – ACOSOG Networks

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Executive Committee Chair

A. Marilyn Leitch, M.D.

Group Co-Chairs

Heidi Nelson, M.D.

David M. Ota, M.D.

Scientific Committees Chairs

Kelly K. Hunt, M.D.; Breast

Peter W.T. Pisters M.D.; GI

Mitchell C. Posner, M.D.; GI

Joe B. Putnam, Jr., M.D.; Thoracic

Elaine Mardis, Ph.D.; BTSC*

Modality (Administrative) Committees Chairs

Bettye L. Greene, R.N.; Patient Advocate

Mark Watson, M.D.; CSBPC

Chaitanya Divgi, M.D.; Diagnostic Imaging*

Matthew Ellis, M.D.; Medical Oncology

Charles Thomas, Jr., M.D.; Radiation Oncology*

Jennifer B. Zoole, RN; Nursing/CRA

Peer Review Committees Chairs

Lee Wilke, M.D.; CSRC

Dennis Wigle, M.D., Ph.D.; TSRC*

Operations and Membership Center

Elizabeth D. Martinez, BS; Group Administrator

Statistics and Data Center

Karla V. Ballman, Ph.D.; Group Statistician

Administrative Committees Chairs

Lisa K. Jacobs, M.D.; Audit

Gerard M. Doherty, M.D.; Constitution and Bylaws

Henry M. Kuerer, M.D., Ph.D.; Education

Peter Angelos, M.D., Ph.D.; Ethics

A. Marilyn Leitch, M.D.; Membership

Lisa A. Newman, M.D.; Special Populations

Robin McLeod, M.D.; DMC

Executive Committee Members-at-Large

Ross Abrams, M.D.

Steven Brower, M.D.

Jeffrey Drebin, M.D.

Bryan Meyers, M.D.

Raphael Pollock, M.D.

Merrick Ross, M.D.

Scientific Leadership – Group Stability

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American College of Surgeons

The American College of Surgeons is a scientific and educational association of surgeons that was founded in 1913 to improve the quality of care for the surgical

patient by setting high standards for surgical education and practice.

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American College of Surgeons

• 73,000 U.S. members

• Several cancer programs or initiatives• Commission on Cancer

• National Cancer Database

• AJCC Staging

• ACOSOG

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American College of SurgeonsCommission on Cancer

• Established by the American College of Surgeons in 1922

• Consortium of 50 professional organizations

• 1,500 hospitals with CoC-accredited cancer programs

• Network of more than 1,600 volunteer Cancer Liaison Physicians

• ACOSOG – CoC Goals:• To establish, disseminate and monitor new clinical practice standards

based on emerging clinical trial evidence

• To develop and implement skills verification programs

• To serve as research arm of ACS including for emerging technologies

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What do we do?What do we do?

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MissionACOSOG is dedicated to improving the care of the surgical oncology patient

• Increase response and cure rates

• Reduce morbidities and disabilities

• Better understand the biologic basis of early-stage disease and its treatment

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Investigate novel surgical and targeted therapies to maintain oncologic outcomes while reducing toxicities and disabilities

• Key Scientific Highlights: Z9001, Z0030, Z0011

Test molecular and imaging profiling to enhance the accuracy of risk stratification

Apply neoadjuvant therapies to improve overall response rates and monitor individual responses

Theme 1

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0

20

40

60

80

100

0 6 12 18 24 30 36

Novel Targeted Therapy Z9001

P<0.0001Rec

urr

ence

-fre

e an

dal

ive

(%)

Months

Lancet 2009

Total Events

Imatinib 359 30

Placebo 354 70

Recurrence free survival

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Novel Surgical Therapy Z0030S

urv

ival

(%

)

Survival (years)

Overall survival

P=0.5310

20

40

60

80

100

0 2 4 6 8

AATS 2010

MLNS

MLND

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0

20

40

60

80

100

0 2 4 6 8 10

Novel Surgical Therapy Z0030S

urv

ival

(%

)

Survival (years)

Disease-free survival

P=0.655

MLNS

MLND

AATS 2010

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0

20

40

60

80

100

0 2 4 6 8

Ali

ve (

%)

Years

Overall Survival by Treatment Arm

ALND

No ALND

P=0.25Median follow-up: 6.3 yr

Novel Surgical Therapy Breast/Z0011

ASCO 2010

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Investigate novel surgical and targeted therapies to maintain oncologic outcomes while reducing toxicities and disabilities

Test molecular and imaging profiling to enhance the accuracy of risk stratification

• Key Scientific Highlights: Z9001, Z0010, Z0040

Apply neoadjuvant therapies to improve overall response rates and monitor individual responses

Theme 2

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0

20

40

60

80

100

0 6 12 18 24 30 36

RFS For Exon 11-Mutant Cases by Arm

Rec

urr

ence

-fre

e an

dal

ive

(%)

Months

P<0.0001 at 24 months

Imatinib (n=173)

Placebo (n=173)

RFS For Wildtype Cases by Arm

Treatment TreatmentP=0.6123 at 24 months

Imatinib (n=32)

Placebo (n=32)

Molecular Profiling Z9001

ASCO 2010

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Ali

ve (

%)

Years

Overall Survival by Bone Marrow Status

P=0.010

20

40

60

80

100

0 2 4 6 8 10

Molecular Profiling Z0010

ASCO 2010

NegativePositive

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0

20

40

60

80

100

0 2 4 6 8 10Years

Survival by SLN Status

H&E and IHC NegativeH&E Negative and IHC Positive P=0.64

Molecular Profiling Z0010

ASCO 2010

Ali

ve (

%)

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0

20

40

60

80

100

0 1 2 3 4 5

H&E (-) LN

IHC (+)

IHC (-)

Molecular Profiling Z0040

Survival (years)

Overall survival

Ali

ve (

%)

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Investigate novel surgical and targeted therapies to maintain oncologic outcomes while reducing toxicities and disabilities

Test molecular and imaging profiling to enhance the accuracy of risk stratification

Apply neoadjuvant therapies to improve overall response rates and monitor individual responses

• Key Scientific Highlights: Z6041, Z1031

Theme 3

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Significance • Highest path CR rate (43%) reported for early rectal cancer • Near 100% margin negative LE rate• Successor trial – reduce toxicity & improve pCR rate

Neoadjuvant Therapies GI / Z6041

ASCO 2010

pT0 43%pT1 20%pT2 30%T2 N0

rectalcancer

by ERUSor MRI

Radiationcombined

with Capecitabine

+Oxaliplatin

T0-T2:Observation

T3 or positive margins:Further

treatment

Local

Excision

pT3 5%

Results

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Prior to aromatase inhibitor

After aromatase inhibitor

51% converted to breast conserving surgery

Neoadjuvant Therapies Breast/Z1031

ASCO 2010

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Z1031 Specimen Acquisition, Processing and Analysis

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Genome ConsentSpecimen Procurement Banking and Tracking

Pathology Review and Analysis of Cellularity

Specimen Procurement Banking and Tracking

Pathology Review and Analysis of Cellularity

Z1031 Specimen Acquisition, Processing and Analysis

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Genome ConsentSpecimen Procurement Banking and Tracking

Pathology Review and Analysis of Cellularity

Z1031 Specimen Acquisition, Processing and Analysis

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Genome ConsentSpecimen Procurement Banking and Tracking

Pathology Review and Analysis of Cellularity

Z1031 Specimen Acquisition, Processing and Analysis

Novel Genomic Predictive Models of

AI outcomeMolecular Profiling

High Quality RNA and DNA Isolation

Novel Genomic Predictive Models of AI outcome Molecular Profiling

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Genome ConsentSpecimen Procurement Banking and Tracking

Pathology Review and Analysis of Cellularity

Novel Genomic Predictive Models of

AI outcomeMolecular Profiling

High Quality RNA and DNA Isolation

Z1031 Specimen Acquisition, Processing and Analysis

377 cases collected 344 reviewed;261 > 70% tumor cellularity

245 expression arrays

163 aCGH arrays

50 whole genome

sequences

246 cases with high quality RNA

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Mark Watson9,Elaine R. Mardis1,2,4

Matthew J. Ellis3,4*

Primary tumor Brain Metastasis

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How do we do it?How do we do it?

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Scientific Proposal Generation

Peer Review and PrioritizationProtocol Development

Trial Implementation

Trial Monitoring and Reporting

OMC

SDC

Members

Scientific

Leadership

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Scientific Proposal Generation

Idea generation – Scientific Committee

Study team development of concept• Multidisciplinary and statistical input• External collaborations (QARC, other groups…)

Feasibility estimates• National Cancer Database – case numbers• Network surveys – MD interest• Patient Advocacy input – patient interest

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Peer Review and Prioritization

Clinical Scientific Review CommitteeTranslational Science Review Committee

Central Specimen Bank and Pathology CommitteeBasic and Translational Science Committee• Opportunities: biospecimen acquisition, basic and correlative studies

Scientific Steering Committee • Prioritization: portfolio and resource balance

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Protocol Development/Trial Implementation

NCI Steering Committee review

Protocol development •Protocol Editor•Study Team•Statistics

Engagement of ACOSOG networks

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Trial Monitoring - Suite of Tools

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Surgical QA/QC

Technical credentialing

Ongoing Audits

Surgical endpoints

Z0010Z0020Z0030Z0360Z6041Z4032Z1072Z4033Z6051

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Risk Stratification

Central Specimen

Bank

IndividualizedResponseMonitoring

ACOSOG

Z6051

Novel Surgical Therapies

Molecular ProfilingPrior to aromatase

inhibitorAfter aromatase

inhibitor

Requiresmastectomy

Z1031 Neoadjuvant Therapies

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Thank You