The 20-30% rate of recurrence after surgical resection of stage II colon cancer (CC) suggests inadequate nodal sampling and/or inadequately sensitive and specific histologic assessment. Preliminary findings from our sentinel node (SN) study (CA 90484) demonstrate a 23% rate of nodal micrometastases (MM) missed by conventional sampling and histologic assessment. Our goal is to standardize the pathologic and surgical evaluation of stage II CC by focused analysis of a minimum number of nodes. We hypothesize that use of immunohistochemistry (IHC) and multimarker quantitative real-time PCR (qRT) assay to examine at least 12 LNs (a number recently endorsed by the National Quality Forum) will detect clinically relevant MM missed by standard hematoxylin and eosin (H&E) assessment of fewer than 12 nodes. In collaboration with the United States Military Cancer Institute (USMCI) Clinical Trials Group, which recently reported a Phase III randomized trial of nodal staging in CC, we will conduct a multicenter prospective trial of focused staging in 300 patients whose resected stage II CC specimens contain at least 12 nodes that stain negative with H&E. IHC will be performed and reviewed by USMCI pathologists, qRT assays and transcriptional analysis will be performed by UCLA scientists. Because patients will not receive adjuvant chemotherapy, we will be able to determine whether nodal MM identified by IHC and/or qRT have an impact on disease-free survival. As a corollary to this trial, we will also perform a comprehensive transcript analysis of the primary tumor specimens;the long-term goal is to create a prognostic index based on the primary tumor and LNs. This index should be helpful in identifying candidates for adjuvant therapy.
Specific Aim I. To determine prospectively whether IHC and/or molecular (qRT) evidence of nodal MM in a specimen containing =12 H&E-negative LNs correlates with disease-free survival after resection of stage II CC.
Specific Aim II. To evaluate the prognostic significance of molecular biomarkers detected in the primary tumor from patients with stage II CC.

Public Health Relevance

Using quality surgery, standardized pathology and sophisticated molecular assays this trial will provide important information in determining which patients with early colon cancer are cured by surgery alone and which patients may benefit from chemotherapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA090848-09
Application #
8301475
Study Section
Clinical Oncology Study Section (CONC)
Program Officer
Timmer, William C
Project Start
2001-04-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
9
Fiscal Year
2012
Total Cost
$260,355
Indirect Cost
$34,580
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Nissan, Aviram; Protic, Mladjan; Bilchik, Anton J et al. (2012) United States Military Cancer Institute Clinical Trials Group (USMCI GI-01) randomized controlled trial comparing targeted nodal assessment and ultrastaging with standard pathological evaluation for colon cancer. Ann Surg 256:412-27
Stojadinovic, Alexander; Nissan, Aviram; Wainberg, Zev et al. (2012) Time-dependent trends in lymph node yield and impact on adjuvant therapy decisions in colon cancer surgery: an international multi-institutional study. Ann Surg Oncol 19:4178-85

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