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SNMMI 2016: A Blood-Based Multi-Transcript Test May Predict Success of Neuroendocrine Cancer Therapy

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Key Points

  • Results showed that peptide receptor radionuclide therapy led to a 68% rate of overall disease control, with median progression-free survival not achieved at the end of follow-up.
  • 73% of low-grade tumors responded to treatment, as did half of high-grade tumors.
  • The NETest exceeded SRI evaluation and predicted both therapy response and nonresponse. The predictive response index of select NETest genes associated with metabolism, signaling, and grading was found to be more than 90% accurate.

Malignant neuroendocrine tumors (NETs) are relatively rare, notoriously difficult to treat, and associated with poor long-term survival. According to research presented at the 2016 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI), an investigative blood test could predict how patients will respond to peptide receptor radionuclide therapy before they commit to a course of treatment (Scientific Paper 43).

Cancerous NETs can develop in a variety of places where hormone signaling occurs between nerve cells and organs of the endocrine system, but the most common origins of these tumors are in the gastrointestinal tract, the lungs, and the pancreas. Most cases are diagnosed until the disease has become metastatic. A targeted treatment established in the early 2000s called peptide receptor radionuclide therapy zeroes in on active peptide receptors that are overexpressed on the surface of NETs. The injected drug binds specifically to these receptors and irradiates tumors with a powerful dose of short-range radioactive material, while sparing healthy tissues nearby.

Peptide receptor radionuclide therapy has helped many patients and is associated with lower systemic side effects, but not all patients respond to the therapy. For this reason, researchers are working to predict patient response prior to the start of treatment with molecular imaging. A visualization of NET receptor activity informs clinicians of the potential path of peptide receptor radionuclide therapy in the body prior to therapy. A number of methods have been used, including somatostatin receptor imaging (SRI), since NET tumors commonly express somatostatin receptor activity; but not all do.

In this study, researchers investigated a genetic blood test called a NETest, which measures the specific NET genes circulating in the blood that appear to define and predict responsiveness to peptide receptor radionuclide therapy.

“This research shows that the molecular information obtained from a simple blood draw can be easily integrated with radiological and molecular imaging to provide a more accurate assessment of tumor behavior and response to therapy,” said Lisa Bodei, MD, PhD, of the European Institute of Oncology Division of Nuclear Medicine in Milan, Italy, and a member of the Molecular Imaging and Therapy Service at Memorial Sloan Kettering Cancer Center.

Study Findings

For this study, researchers evaluated a total of 72 NETs being treated with peptide receptor radionuclide therapy by using a potent radionuclide agent called Lu-177 DOTATATE over the course of 33 months. Subjects underwent SRI, histological evaluations, a bioassay that tracks a common protein in NETs called chromogranin A, and the NETest. Researchers performed statistical analyses and developed a predictive response index of select NETest genes as a predictor of peptide receptor radionuclide therapy success and categorized patients’ response to treatment as either responsive or nonresponsive.

Results showed that peptide receptor radionuclide therapy led to a 68% rate of overall disease control, with median progression-free survival not achieved at the end of follow-up. Researchers were able to determine that 73% of low-grade tumors responded to treatment, as did half of high-grade tumors.

Histological grading, SRI, and chromogranin were not able to predict peptide receptor radionuclide therapy effectiveness. The NETest exceeded SRI evaluation and predicted both therapy response and nonresponse. The predictive response index of select NETest genes associated with metabolism, signaling, and grading was found to be more than 90% accurate.

“Using this method, a patient would be able to know if [peptide receptor radionuclide therapy] would be an effective cancer therapy for them,” said Dr. Bodei. “Additionally, further blood tests could be used to monitor the progress of treatment, rather than relying on statistics that are not specific to them as individuals.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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