Prospective study of chromogranin A as a predictor of progression in patients with pancreatic, small intestinal and unknown primary neuroendocrine tumors

Gitte Dam, Henning Grønbæk, Halfdan Sorbye, Espen Thiis Evensen, Björn Paulsson, Anders Sundin, Claus Jensen, Dyveke Ebbesen, Ulrich Knigge, Eva Tiensuu Janson

30 Citations (Scopus)

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.

Original languageEnglish
JournalNeuroendocrinology
Volume110
Issue number3-4
Pages (from-to)217-224
Number of pages8
ISSN0028-3835
DOIs
Publication statusPublished - 2020

Keywords

  • Biomarkers
  • Chromogranin A
  • Gastroenteropancreatic neuroendocrine tumors

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