3a. M. Gold - 6671-0233 Update Presentation
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Transcript of 3a. M. Gold - 6671-0233 Update Presentation
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ACRIN Abdominal Committee
ACRIN Gynecologic Committee
ACRIN 6671 GOG 0233
UPDATE
ACRIN PI: M. ATRI
GOG PI: M. GOLD
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ACRIN Gynecologic Committee
Lymph Node Evaluation
What is the utility oflymph nodeevaluation in:
Cervical Carcinoma Endometrial Carcinoma
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Cervical Carcinoma
Early stage
Any (+) LN Lymph node metastases high risk factors for
recurrence
Identifies population needing adjuvant
chemoradiation
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Early Stage Cervical Carcinoma
Chemo-RT if one of the following:High Risk: Positive margin, parametrial extension, positivenode (87% of CRT vs. 84% of RT)
GOG 109 (Peters WA et. al. . J Clinic Oncol 18:1606-1613, 2000)
PFS
4-yr PFS 80% vs. 63%; p=0.003
OS
4-yr OS 81% vs. 71%; p=0.007
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Cervical Carcinoma
Early stage
Any (+) LN Lymph node metastases high risk factors for
recurrence
Identifies population needing adjuvant
chemoradiation
Locoregionally Advanced(+) PA LN
Pelvic lymph nodes included in standard pelvic
radiation field
Para-Aortic (Abdominal) lymph node metastases
results in extended field primary chemoradiation
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Locoregionally Advanced Cervical Carcinoma
Risk of lymph node metastases increases with stage
Stage % PALN (+)
IB1 1.7
IB2 11.9
2A 2.4-18.2
2B 16.7-32.8
3A 33.3
3B 24.9-31.1
4A 12.5-33
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Impact of Para-Aortic Evaluation on Survival
Adjusted RR 1.51 (95% CI: 0.99-2.31), p=0.055
Adjusted RR 1.60 (95% CI: 1.03-2.48), p=0.038Adjusted RR 1.51 (95% CI: 0.99-2.31), p=0.055
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Three-year Progression Free Interval & Overall Survival
Importance of Detecting PALN Metastases
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Endometrial Carcinoma
Any (+) Lymph Node
Lymph node metastases high risk factors for
recurrence
Identifies population needing adjuvant
chemotherapy
Avoids unnecessary post-operative treatment
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Endometrial Carcinoma
Cannot reliably identify who does and does nothave LN mets based on pathologic variables Only 10% of (+) nodes are palpable
37% of nodal mets are < 2 mm
3-5% of low risk pts (+) nodes
In LN (+) patients, PALN involved in ~50%,only (+) site 8-17%
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LN Mets in Endometrial Carcinoma
Depth ofInvasion
GradeG1
(N= 180)
G2
(N= 288)
G3
(N= 153)
Endo Only(N= 86) 0 3% 0
Inner 1/3(N= 281) 3% 5% 9%
Mid 1/3(N=115) 0 9% 4%
Outer 1/3(N= 139) 11% 19% 34%
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Distribution of Disease in Node (+) EM Patients
0
10
20
30
40
50
60
70
Pelvic Only Pel + PALN PALN only Any PALN
Creasman
SchorgeOnda
McMeekin
Otsuka
Katz
Cancer 1987; Gyn Onc 1996; Br J Ca 1997,Gyn Onc 2001,Br J Ca 2002; Am J OB-GYN 2001
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Endometrial Carcinoma
PALN failure reduced from 39 to 13% inpts undergoing LN resection(Corn, Int J RBP 1992;24:223)
Failure to sample systematicallyPLN/PALN leads to increasedretroperitoneal failures(Chaung, Gyn Onc 1995;58:189)
Less failures, improved PFS/OS inpatients undergoing PALND(Mariani, Gyn Onc 2000;76:348)
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Survival Benefit Associated withExtensive Lymphadenectomy
High Risk:Stage IB
Grade 3Stage ICStage IIStage IIIStage IV
5-Year DS Survival1-8 Nodes: 90.4%
9-16 Nodes: 91.3%16 Nodes: 94.0%
0 50 100 150 200
100
75
0
Time (months)
P
ercentSurvival(%)
(p=0.048)
1-8 Nodes9-16 Nodes16 Nodes
Chan et al, Cancer 2006
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Endometrial Carcinoma
GOG 33 - 621 Clinical Stage I patients
153 pts w/ G3
18% (+)PLN & 11% (+)PALN
97 pts w/ Cervical involvement
16% (+)PLN & 14% (+)PALN
GOG 210 Restricted enrollment 947 patients
129 (13.6%) Stage IIIC
51 (5.4%) Stage IVB
University of Oklahoma
607 staged patients 47 (8%) w/ (+) Lymph Nodes
43% (+)PLN / 40% (+)P&PALN / 17% (+)PALN
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ACOG Practice BulletinManagement of Endometrial CancerNumber 65, August 2005
Most women with endometrial cancer benefit from
systematic surgical staging
Staging is prognostic and facilitates targeted therapy to
maximize survival and minimize the effects of under-treatment and over-treatment
Retroperitoneal lymph node assessment is a critical
component of surgical staging and is associated with
improved survival
Palpation of the retroperitoneum is an inaccurate
measure and cannot substitute for surgical dissection of
nodal tissue
Reaffirmed 2009
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COMBIDEX MRI review
Update on ACRIN6671/GOG0233
OUTLINE
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Interim analysis after 30 positivepatients
Sensitivity > 60% to continue
Combidex provider stopped providingthe agent in October 2009
New Amendment to include
endometrial cancer ACRIN/GOG approval to review
Combidex MRI data
COMBIDEX MRI REVIEWStudy Protocol Requirement
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COMBIDEX MRI REVIEWStudy Protocol Requirement
Seven central readers
Initial training on 3 test cases
Submission and approval of forms
Two step review
Combidex insensitive sequence review
Data submission and query
All sequence review
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REVIEW PROCESS
5 NA, 2 European readers
All academic abdominal imagers
5/7 had experience with USPIO review
Effect of experience
3 at ACRIN headquarter, 4 at theirinstitutions
Review process complete
Abstract submission to ASCO 2011
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COMBIDEX MRI REVIEWChallenges (N: 33 Patients)
Reader selection Handful of experienced readers
2 of more experienced readers dropped
out/replaced Difficult to bring reviewers to ACRIN
headquarter
Difficult to entice them to meettimelines (5 months)
Long review process [3 days (3x8hrs)]
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IMAGING REVIEWLiterature
Pubmed & Google Scholar
Keywords
Imaging review
Imaging review and clinical trial
radiology review study
Off-site vs. On-site imaging review
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NUMBER OF ARTICLES
0Tumour Size Measurement in an Oncology Clinical Trial:Comparison Between Off-site and On-site MeasurementsClinical Radiology, 58:311
IMAGING REVIEW
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IMAGING REVIEWQuestions
On-site vs. Off-site
Reviewer fatigue
Familiarity with PACS system
Role of experience
Role of sub-specialization
Reviewer accountability
IMAGING REVIEW
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IMAGING REVIEWQuestions
Role of experience
Role of fatigue
Accountability
PACS system
Combination of Rev.
Compare half days
Authorship
ACRIN vs. Commercial
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Evidence of disease outsideof the pelvis or abdominal
nodal region amenable tobiopsy or sampling (i.e.
intrahepatic, pulmonary, orthoracic or supraclavicular
lymphadenopathy onPET/CT)
No evidence of disease outside of
the pelvis or abdominal nodalregion amenable to biopsy or
sampling (i.e. intrahepatic,pulmonary, or thoracic or
supraclavicular lymphadenopathyon PET/CT)
SCHEMA (ENDOMETRIUM)
AdvancedLymph
adenopathynot
amenable tosurgery
Endometrial cancer patients eligible for lymphadenectomy
Grade 3 endometrioid; clear-cell, serous papillary, or carcinosarcoma(any grade); and Grade 1 or 2 endometrioid with cervical stromalinvolvement overt on clinical examination
or confirmed by endocervical curettage
Pre-operative PET/CT Scan of the abdomen and pelvis and chest
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Evidence of diseaseoutside of the pelvis or
abdominal nodal region onPET/CT
No evidence of disease outside ofpelvis or abdominal nodal region
on PET/CT
Lymphadenectomy
abandoned, Chemotherapy
Protocol for Advanced
/Recurrent Disease
Bx (+)
Biopsy of metastatic diseaseoutside of the pelvis orabdominal nodal region by
FNA, core biopsy, or surgicalbiopsy
Bx (-)
Advanced
Lymphadenopathynot
amenable tosurgery
Chemo-Radiation Therapyto start within four weeks
of enrollment into thestudy
Total abdominal hysterectomy,bilateral salpingo-oopherectomy,
and abdominal & pelvic lymphnode sampling
SCHEMA (ENDOMETRIUM)
Standard institutional treatment
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ACRIN Gynecologic Committee
ACRIN 6671/GOG 0233 UPDATE
Required sample size
Cervix 165
Endometrium 215
Number of accruing centers ???
Number of accrued patients
Cervix ?
Endometrium ?
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ACRIN G l i C i
DISCUSSION
Possibility of review during accrual
Suggestions to increase accrual