Transcript - North Central Cancer Treatment Group

American College of Surgeons
Oncology Group
Heidi Nelson, M.D.
David M. Ota, M.D.
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Who are we?
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ACOSOG
Operations and Membership Center
Members
Scientific Leadership
Statistics and Data Center
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Members
Specialty
Hospital type
6%
2%
18%
15%
4%
46%
37%
35%
CRA / nurse
Surgeon
37%
Academic / university
Community
Medical oncology
Teaching affiliate
Radiation oncology
Other
Other
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Members – ACOSOG Networks
British Columbia, Canada
Ontario, Canada
WA
MT
ME
ND
OR
VT
NH
MN
ID
SD
WI
NY
WY
MI
CT
IA
NV
PA
NE
IL
UT
IN
OH
CO
CA
MO
RI
NJ
DE
WV
KS
MA
VA
KY
MD
DC
NC
AZ
OK
NM
TN
AR
SC
MS
TX
AL
GA
Key
LA
FL
Breast IDIGs
GI IDIGs
Thoracic IDIGs
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Scientific Leadership – Group Stability
Executive Committee Chair
Operations and Membership Center
A. Marilyn Leitch, M.D.
Elizabeth D. Martinez, BS; Group Administrator
Group Co-Chairs
Statistics and Data Center
Heidi Nelson, M.D.
David M. Ota, M.D.
Karla V. Ballman, Ph.D.; Group Statistician
Administrative Committees Chairs
Scientific Committees Chairs
Lisa K. Jacobs, M.D.; Audit
Kelly K. Hunt, M.D.; Breast
Peter W.T. Pisters M.D.; GI
Mitchell C. Posner, M.D.; GI
Gerard M. Doherty, M.D.; Constitution and Bylaws
Henry M. Kuerer, M.D., Ph.D.; Education
Joe B. Putnam, Jr., M.D.; Thoracic
Peter Angelos, M.D., Ph.D.; Ethics
Elaine Mardis, Ph.D.; BTSC*
A. Marilyn Leitch, M.D.; Membership
Modality (Administrative) Committees Chairs
Lisa A. Newman, M.D.; Special Populations
Bettye L. Greene, R.N.; Patient Advocate
Robin McLeod, M.D.; DMC
Mark Watson, M.D.; CSBPC
Chaitanya Divgi, M.D.; Diagnostic Imaging*
Executive Committee Members-at-Large
Ross Abrams, M.D.
Matthew Ellis, M.D.; Medical Oncology
Steven Brower, M.D.
Charles Thomas, Jr., M.D.; Radiation Oncology*
Jennifer B. Zoole, RN; Nursing/CRA
Peer Review Committees Chairs
Jeffrey Drebin, M.D.
Bryan Meyers, M.D.
Lee Wilke, M.D.; CSRC
Raphael Pollock, M.D.
Dennis Wigle, M.D., Ph.D.; TSRC*
Merrick Ross, M.D.
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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 Surgeons
Commission 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?
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Mission
ACOSOG 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 earlystage disease and its treatment
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Theme 1
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
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Novel Targeted Therapy
Z9001
Recurrence free survival
Recurrence-free and
alive (%)
100
80
60
40
Imatinib
Placebo
20
Total
359
354
Events
30
70
P<0.0001
0
0
6
12
18
24
30
36
Months
Lancet 2009
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Novel Surgical Therapy
Z0030
Overall survival
100
Survival (%)
80
60
40
MLNS
MLND
20
P=0.531
0
0
2
4
6
8
Survival (years)
AATS 2010
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Novel Surgical Therapy
Z0030
Disease-free survival
100
Survival (%)
80
60
40
MLNS
MLND
20
P=0.655
0
0
2
4
6
8
10
Survival (years)
AATS 2010
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Novel Surgical Therapy
Breast/Z0011
Overall Survival by Treatment Arm
100
Alive (%)
80
60
40
ALND
No ALND
20
Median follow-up: 6.3 yr
P=0.25
0
0
2
4
6
8
Years
ASCO 2010
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Theme 2
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
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Molecular Profiling
Z9001
Recurrence-free and
alive (%)
RFS For Exon
11-Mutant Cases by Arm
RFS For Wildtype
Cases by Arm
100
100
80
80
60
60
40
40
Imatinib (n=173)
Imatinib (n=32)
Placebo (n=173)
Placebo (n=32)
20
20
Treatment
Treatment
P<0.0001 at 24 months
P=0.6123 at 24 months
0
0
0
6
12
18
24
30
36
0
Months
6
12
18
24
30
36
ASCO 2010
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Molecular Profiling
Z0010
Overall Survival by Bone Marrow Status
100
Alive (%)
80
60
40
20
Negative
Positive
P=0.01
0
0
2
4
6
8
10
Years
ASCO 2010
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Molecular Profiling
Z0010
Survival by SLN Status
100
Alive (%)
80
60
40
20
H&E and IHC Negative
H&E Negative and IHC Positive
P=0.64
0
0
2
4
6
8
10
Years
ASCO 2010
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Molecular Profiling
Z0040
Overall survival
100
Alive (%)
80
60
40
H&E (-) LN
20
IHC (+)
IHC (-)
0
0
1
2
3
4
5
Survival (years)
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Theme 3
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
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Neoadjuvant Therapies
GI / Z6041
Results
T2 N0
rectal
cancer
by ERUS
or MRI
Radiation
combined
with
Capecitabine
+
Oxaliplatin
L
o
c
a
l
E
x
c
i
s
i
o
n
T0-T2:
Observation
T3 or positive
margins:
Further
treatment
pT0 43%
pT1 20%
pT2 30%
pT3 5%
Significance
• Highest path CR rate (43%) reported for early rectal cancer
• Near 100% margin negative LE rate
• Successor trial – reduce toxicity & improve pCR rate
ASCO 2010
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Neoadjuvant Therapies
Breast/Z1031
51% converted to breast conserving surgery
Prior to aromatase
inhibitor
After aromatase
inhibitor
ASCO 2010
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Z1031 Specimen Acquisition, Processing and Analysis
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Z1031 Specimen Acquisition, Processing and Analysis
Genome Consent
ocurement Banking
Tracking
Specimen Procurement
Banking and Tracking
Pathology Review and
Analysis of Cellularity
Pathology Review and Analysis
of Cellularity
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Z1031 Specimen Acquisition, Processing and Analysis
Genome Consent
Specimen Procurement
Banking and Tracking
Pathology Review and
Analysis of Cellularity
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Z1031 Specimen Acquisition, Processing and Analysis
Genome Consent
Specimen Procurement
Banking and Tracking
Novel Genomic Predictive Models
of AI outcome
Novel Genomic
Predictive Models of
AI outcome
Molecular Profiling
Pathology Review and
Analysis of Cellularity
Molecular Pr
High Quality RNA and
DNA Isolation
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Z1031 Specimen Acquisition, Processing and Analysis
Genome Consent
Specimen Procurement
Banking and Tracking
Pathology Review and
Analysis of Cellularity
377 cases collected
344 reviewed;261 > 70% tumor cellularity
245 expression arrays
163 aCGH
arrays
Novel Genomic
Predictive Models of
AI outcome
50 whole
genome
sequences
Molecular Profiling
High Quality RNA and
DNA Isolation
246 cases with high quality RNA
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Matthew J. Ellis3,4*
Mark Watson9,
Elaine R. Mardis1,2,4
Primary tumor
Brain Metastasis
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How do we do it?
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Trial Monitoring
and Reporting
Scientific Proposal
Generation
Members
OMC
Scientific
SDC
Leadership
Protocol Development
Trial Implementation
Peer Review
and Prioritization
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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 Committee
Translational Science Review Committee
Central Specimen Bank and Pathology Committee
Basic 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
Z0010
Z0020
Z0030
Z0360
Z6041
Z4032
Z1072
Z4033
Z6051
Surgical endpoints
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ACOSOG
Z1031
Individualized
Response
Monitoring Therapies
Neoadjuvant
Z6051
Risk
Stratification
Requires
mastectomy
Novel
Surgical
Therapies
Molecular Profiling
Prior to aromatase
inhibitor
Central
Specimen
Bank
After aromatase
inhibitor
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Thank You
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