3a. M. Gold - 6671-0233 Update Presentation

8/2/2019 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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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


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



Three-year Progression Free Interval & Overall Survival

Importance of Detecting PALN Metastases



Endometrial Carcinoma

Any (+) Lymph Node

Lymph node metastases high risk factors for

recurrence


chemotherapy

Avoids unnecessary post-operative treatment




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%



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%



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




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)



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




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



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



COMBIDEX MRI review

Update on ACRIN6671/GOG0233

OUTLINE



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



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 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

Documents

3a. M. Gold - 6671-0233 Update Presentation