Abstract
Abstract BACKGROUND: Serum chromogranin A (CgA) or alkaline phosphatase (ALP) are often assessed in patients with advanced neuroendocrine tumor (NET) patients but their prognostic significance continues to be debated. We evaluated whether elevated CgA or ALP levels were associated with shorter survival in a large, prospectively collected cohort of NET patients. METHODS: We identified patients with metastatic NET enrolled in an institutional database between 2003-10. We used the single measurement of serum CgA or ALP levels collected with shortest time after metastatic diagnosis and classified them as binary variables (elevated/normal) based on clinical laboratory specification of elevated value. Elevated biomarker levels were correlated with overall survival using the log-rank test. Hazard ratios for each biomarker were calculated using multivariate Cox regression, adjusting for baseline characteristics of age, gender, tumor histology, and tumor subtype. Each biomarker was modeled as a time-varying covariate to account for variability in time from initial metastatic diagnosis to time of biomarker test. RESULTS: We identified 526 patients who presented at our institution with metastatic NET. Of these, 349 had available CgA values and 350 had available ALP values. There were 146 and 153 deaths among those tested for CgA and ALP, respectively. The median survival time from time of metastatic diagnosis (yrs, (95%CI)) for patients with elevated CgA was 5.98 (5.04, 7.3), as compared to 13.27 (9.51, -) for those at normal CgA limits (p<0.0001). The median survival time from time of metastatic diagnosis (yrs, (95%CI)) for patients with elevated ALP was 4.51 (3.27, 5.93), as compared to 8.87 (7.07, 9.64) for those at normal ALP levels (p=0.0001). Using the adjusted time-varying model, either elevated CgA (aHR 3.97 (2.73, 5.75) p=3.15E-13) or elevated ALP (aHR 2.4 (1.7, 3.4) p=7.96E-07) were adverse prognostic factors for patients with advanced NET. Elevated CgA was significantly associated with shorter survival in all NET subgroups (pancreatic NET, carcinoid, other NET). Elevated ALP was also a predictor of shorter survival in advanced NET patients, with the exception of those with advanced pancreatic NET. CONCLUSION: Elevated serum CgA or elevated ALP is an independent adverse prognostic factor in patients with advanced NET. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3633. doi:1538-7445.AM2012-3633
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