Original article—liver, pancreas, and biliary tract
Plasma Chromogranin A as Marker for Survival in Patients With Metastatic Endocrine Gastroenteropancreatic Tumors

https://doi.org/10.1016/j.cgh.2008.02.052Get rights and content

Background & Aims: The prognostic role of plasma chromogranin A in patients with neuroendocrine tumors is unclear. We investigated the role of chromogranin A in predicting survival and hypothesized that chromogranin A mirrors tumor burden and that a rapid increase after a phase of stable plasma chromogranin A levels might predict exploding tumor growth. Methods: Three hundred forty-four patients with metastatic, well-differentiated neuroendocrine tumors were included. A subsample of 102 patients was investigated to correlate radiologically classified tumor burden with plasma chromogranin A. Hepatic tumor burden (0%, 0%–25%, 25%–50%, >50%) was assessed from computed tomography/magnetic resonance imaging scans. Follow-up information until death was generated in regular intervals. Results: Plasma chromogranin A levels (U/L) vary between tumor entities (Kruskal–Wallis, P < .001) and were associated with survival time (hazard ratio [hours], 2.14 per one unit in the log10 CgA level scale; 95% confidence interval [CI], 1.75–2.62; P < .001). Chromogranin A levels correlated with hepatic tumor burden (Spearman P = .57; 95% CI, 0.44–0.70; P < .001). Additional extrahepatic tumor load did not relevantly affect plasma chromogranin A. A sudden increase observed in individual patients was paralleled by rapid tumor progress and short survival. Conclusions: Increased plasma chromogranin A in patients with metastatic neuroendocrine tumors is predictive for shorter survival. There was a modest correlation between chromogranin A levels and hepatic tumor burden. We hypothesized further that a sudden increase in individual chromogranin A levels indicates unfavorable outcome.

Section snippets

Patients

In 1988 a tumor register was initiated with data on clinical presentation and treatment, histopathology, and laboratory values of 641 patients with GEP tumors admitted in our institution. CgA levels reported in this study were used only if estimated in our laboratories by using an enzyme-linked immunosorbent assay that has not changed since January 1, 1995. Three hundred forty-four patients fulfilled this criterion and were used for the first part of the study investigating plasma CgA levels as

Characteristics of Enrollees

Table 1, Table 2 provide descriptive information on patient characteristics of both parts of the study. For 6 patients the primary was unknown (Table 2). However, the exclusion of a pancreatic or bronchial origin according to CT, MRI, and Octreoscan suggested that these tumors originated from the midgut. Both subsamples listed in Table 1, Table 2 consisted primarily of midgut and nonfunctioning pancreatic tumors.

Plasma Chromogranin A as a Prognostic Marker for Survival

As shown in Table 1, Table 3, elevated plasma CgA levels were associated with

Discussion

This study demonstrated in accordance with previous reports that plasma CgA is a valuable marker for malignant GEP tumors of different origins, with the highest CgA plasma levels in patients with carcinoid syndrome.8, 10, 15, 16, 17, 18, 19, 20 As shown in the first part of this study, survival was reduced if plasma CgA levels were >200 U/L at the time of diagnosis. The cutoff value was chosen as the rounded value of 210 U/L, the median of plasma CgA for the whole group of patients. It is

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    Supported by grants from Novartis, Nürnberg, Germany.

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