Assessment of NETest Clinical Utility in a U.S. Registry-Based Study

Oncologist. 2019 Jun;24(6):783-790. doi: 10.1634/theoncologist.2017-0623. Epub 2018 Aug 29.

Abstract

Background: The clinical relevance of molecular biomarkers in oncology management has been recognized in breast and lung cancers. We evaluated a blood-based multigene assay for management of neuroendocrine tumors (NETs) in a real-world study (U.S. registry NCT02270567). Diagnostic accuracy and relationship to clinical disease status in two cohorts (treated and watch-and-wait) were evaluated.

Materials and methods: Patients with NETs (n = 100) were followed for 6-12 months. Patients' primary tumors were gastroenteropancreatic (68%), lung 20%, and of unknown origin (12%). Characteristics included well-differentiated, low-grade tumors (97%), stage IV disease (96%); treatment with surgery (70%); and drug treatment (56%). NETest was measured at each visit and disease status determined by RECIST. Scores categorized as low (NETest 14%-40%) or high (≥80%) defined disease as stable or progressive. Multivariate analyses determined the strength of the association with progression-free survival (PFS).

Results: NETest diagnostic accuracy was 96% and concordant (95%) with image-demonstrable disease. Scores were reproducible (97%) and concordant with clinical status (98%). The NETest was the only feature linked to PFS (odds ratio, 6.1; p < .0001). High NETest correlated with progressive disease (81%; median PFS, 6 months), and low NETest correlated with stable disease (87%; median PFS, not reached). In the watch-and-wait cohort, low NETest was concordant with stable disease in 100% of patients, and high NETest was associated with management changes in 83% of patients. In the treated cohort, all low NETest patients (100%) remained stable. A high NETest was linked to intervention and treatment stabilization (100%). Use of NETest was associated with reduced imaging (biannual to annual) in 36%-38% of patients.

Conclusion: Blood NETest is an accurate diagnostic and can be of use in monitoring disease status and facilitating management change in both watch-and-wait and treatment cohorts.

Implications for practice: A circulating multigene molecular biomarker to guide neuroendocrine tumor (NET) management has been developed because current biomarkers have limited clinical utility. NETest is diagnostic (96%) and in real time defines the disease status (>95%) as stable or progressive. It is >90% effective in guiding treatment decisions in conjunction with diagnostic imaging. Monitoring was effective in watch-and-wait or treatment groups. Low levels supported no management change and reduced the need for imaging. High levels indicated the need for management intervention. Real-time liquid biopsy assessment of NETs has clinical utility and can contribute additional value to patient management strategies and outcomes.

Keywords: Biomarker; Carcinoid; Liquid biopsy; NET transcripts; Neuroendocrine; Registry.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Clinical Decision-Making / methods*
  • Disease Progression
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Liquid Biopsy / instrumentation
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neuroendocrine Tumors / blood
  • Neuroendocrine Tumors / diagnosis*
  • Neuroendocrine Tumors / mortality
  • Neuroendocrine Tumors / therapy
  • Prognosis
  • Reagent Kits, Diagnostic*
  • Registries / statistics & numerical data
  • Watchful Waiting
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Reagent Kits, Diagnostic

Associated data

  • ClinicalTrials.gov/NCT02270567