Research Papers:

Clinical utility of gene-expression profiling for tumor-site origin in patients with metastatic or poorly differentiated cancer: impact on diagnosis, treatment, and survival

J Scott Nystrom, John C. Hornberger _, Gauri R. Varadhachary, Richard J. Hornberger, Hialy R. Gutierrez, W. David Henner, Shawn H. Becker, Mahul B. Amin and Michael G. Walker

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Oncotarget. 2012; 3:620-628. https://doi.org/10.18632/oncotarget.521

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J. Scott Nystrom1, John C. Hornberger2,3, Gauri R. Varadhachary4, Richard J. Hornberger3, Hialy R. Gutierrez3, W. David Henner5, Shawn H. Becker5, Mahul B. Amin6, and Michael G. Walker2

1 Department of Medicine, Tufts Medical Center, Boston, MA, USA

2 Department of Medicine, Stanford University, Stanford, CA, USA

3 Cedar Associates LLC, Menlo Park, CA, USA

4 Department of Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA

5 Pathwork Diagnostics, Inc., Redwood City, CA, USA

6 Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Received: May 22, 2012; Accepted: June 08, 2012; Published: June 9, 2012;

Keywords: cancer of unknown primary, diagnosis, genomics, clinical utility, tissue of origin


John Hornberger, email:


PURPOSE: The primary tissue-site origin in over 4% of cancers remains uncertain despite thorough clinicopathological evaluation. This study assessed the effect of a Food and Drug Administration-cleared 2,000-gene–expression-profiling (GEP) test on primary tissue-site working diagnoses and management for metastatic and poorly differentiated cancers.

METHODS: Clinical information was collected from physicians ordering the GEP test for patients with difficult to diagnose cancers. Endpoints included diagnostic procedures, physicians’ working diagnoses and treatment recommendations before and after GEP result availability, and physician reports of the test’s usefulness for clinical decision making. Patient date of death was obtained, with a minimum of one year follow-up from date of biopsy.

RESULTS: Sixty-five physicians participated in the study (n=107 patients). Before GEP, patients underwent 3.2 investigations on average (e.g., radiology, endoscopy). Ten immunohistochemistry tests were used per biopsy (SD 5.2). After GEP testing, physicians changed the primary working diagnosis for 50% of patients (95% CI: 43%,58%) and management for 65% of patients (95% CI: 58%,73%). With GEP results, the recommendation for guideline-consistent chemotherapy increased from 42% to 65% of patients, and the recommendation for non-guideline-consistent regimens declined from 28% to 13%. At last follow-up, 69 patients had died, and median survival was 14.0 months (95% CI: 10.2,18.6). Thirty-three percent of patients were alive at 2 years.

CONCLUSION: In patients with difficult-to-diagnose cancers, GEP changed the working diagnosis and management for the majority of patients. Patients for whom the GEP test was ordered had longer median survival than that historically reported for patients enrolled in treatment trials for cancer of unknown primary.

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