Blood mRNA Measurement (NETest) for Neuroendocrine Tumor Diagnosis of Image-Negative Liver Metastatic Disease.

Abstract

Context:

Early cancer detection is critical to optimize treatment. This is particularly problematic in neuroendocrine tumors (NETs), which exhibit an ∼5-year diagnostic delay due to covert symptoms, limitations in imaging, and circulating biomarkers. Despite development of continuous monitoring strategies utilizing advanced modalities [CT/MRI or 68Gallium positron emission tomography (PET)/CT] or a repertoire of monoanalyte biomarkers [e.g., chromogranin A (CgA), pancreastatin, serotonin], detection of minimal residual disease or microrecurrence remains elusive. Emerging molecular liquid biopsies (e.g., NETest) provide a substantially improved threshold for disease detection.

Case Description:

We describe the utility of a blood-based multigene PCR neuroendocrine measurement (NETest), which is representative of core molecular drivers of neuroendocrine tumorigenesis, to detect hepatic micrometastases in a patient with negative blood biomarkers and negative anatomical/functional imaging. The 52-year-old woman, who had undergone margin-negative resection for a NET of the ileocecal valve, developed persistently elevated NETest levels 8 months later. CT/MRI/68Gallium PET and biomarkers remained negative. Blood multigene analysis identified disease, and peptide receptor radionuclide therapy (PRRT) was undertaken. Over 9 months, NETest levels increased (conventional biomarkers/imaging remained normal). Liver biopsy was undertaken, and foci of a 3-mm NET in segment VI were histologically documented. At 3.3 years after PRRT, the disease remained as a microscopic burden and stable biomarker/68Gallium PET/MRI occult despite elevated blood levels of NET genes.

Conclusions:

Blood measurement of NET transcripts can identify image- and CgA-negative disease. A NET liquid biopsy strategy has clinical utility in the early identification of residual or metastatic disease and optimizes consideration of adjuvant therapeutic intervention.

• Authors: Anna Malczewska, Lisa Bodei, Mark Kidd, Irvin M Modlin
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 104 Issue 3 Pg. 867-872 (03 01 2019) ISSN: 1945-7197 [Electronic] United States
• PMID: 30358858 (Publication Type: Case Reports, Journal Article)

Chemical References

• Biomarkers, Tumor
• RNA, Messenger

Topics

• Biomarkers, Tumor (blood, genetics)
• Biopsy
• Early Detection of Cancer (methods)
• Female
• Humans
• Liquid Biopsy (methods)
• Liver (diagnostic imaging, pathology)
• Liver Neoplasms (blood, diagnosis, secondary)
• Middle Aged
• Neuroendocrine Tumors (blood, diagnosis, secondary)
• Positron-Emission Tomography
• RNA, Messenger (blood)