Prospective Study of Chromogranin A as a Predictor of Progression in Patients with Pancreatic, Small-Intestinal, and Unknown Primary Neuroendocrine Tumors

Neuroendocrinology. 2020;110(3-4):217-224. doi: 10.1159/000503833. Epub 2019 Oct 2.

Abstract

Background: Retrospective studies are conflicting but most of them report that an increase in plasma chromogranin A (CgA) predicts tumor progression in neuroendocrine tumor (NET) patients. Prospectively, we investigated if a change in plasma CgA is associated with tumor burden changes in NET patients with disseminated disease.

Methods: We included 239 patients treated at 5 NET centers from December 2010 to December 2013. CgA was measured within 6 weeks of a CT or MRI in a patient undergoing at least 2 scan examinations performed over a period of 1-24 months. In a post hoc analysis, CgA measured 3-6 months prior to the CT/MRI was analyzed. Changes in tumor size were evaluated by RECIST1.1. A 25% change in CgA was chosen to discriminate between increased, decreased, or unchanged levels.

Results: In 671 events (2 CT/MRI scans and 2 corresponding CgA measurements), we found a weak positive correlation between the RECIST 1.1 responses and change in plasma CgA from baseline (Spearman's rank correlation coefficient: 0.15; p < 0.05). Of 304 events in the post hoc analysis, 58 showed progression, 228 showed stable disease, and 18 showed regression, with a median change in CgA of 19% (IQR: 57 to -20%), -12% (23 to -38%), and -73% (-55 to -83%), respectively. The correlation coefficient for all sites was 0.17 (p = 0.003), and it was 0.16 (p = 0.07), 0.18 (p = 0.04), and 0.20 (p = 0.21) for small-intestinal (n = 137), pancreatic (n = 123), and unknown primary NET (n = 40), respectively. In the 58 patients showing tumor progression, the sensitivity and specificity of an increased CgA concentration were 36 and 82%, respectively, with positive and negative predictive values of 32 and 85%.

Conclusions: In this prospective study of gastroenteropancreatic NET patients, we observed only a weak association between a change in plasma CgA and changes in tumor burden. CgA as a single biomarker was thus inadequate to predict tumor progression.

Keywords: Biomarkers; Chromogranin A; Gastroenteropancreatic neuroendocrine tumors.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Chromogranin A / blood*
  • Cross-Sectional Studies
  • Disease Progression*
  • Female
  • Humans
  • Intestinal Neoplasms / blood
  • Intestinal Neoplasms / diagnosis*
  • Intestinal Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasms, Unknown Primary / blood
  • Neoplasms, Unknown Primary / diagnosis*
  • Neoplasms, Unknown Primary / pathology
  • Neuroendocrine Tumors / blood
  • Neuroendocrine Tumors / diagnosis*
  • Neuroendocrine Tumors / pathology
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / pathology
  • Prospective Studies

Substances

  • Biomarkers, Tumor
  • CHGA protein, human
  • Chromogranin A