Assessment of hormonal levels as prognostic markers and of their optimal cut-offs in small intestinal neuroendocrine tum
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ORIGINAL ARTICLE
Assessment of hormonal levels as prognostic markers and of their optimal cut-offs in small intestinal neuroendocrine tumours grade 2 Dimitrios Papantoniou 1,2 Malin Grönberg1 Kalle Landerholm3 Staffan Welin1 Barbara Ziolkowska4 Dennis Nordvall5 Eva Tiensuu Janson1 ●
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Received: 6 June 2020 / Accepted: 24 October 2020 © The Author(s) 2020
Abstract Purpose Small intestinal neuroendocrine tumours (siNETs) with a Ki-67 proliferation index between 3 and 20% belong to WHO grade 2. Response to treatment may be monitored by blood chromogranin A (CgA) and urine 5-hydroxyindoleacetic acid (5HIAA). The aim of this retrospective study was to investigate the prognostic value of baseline CgA and 5HIAA and of the early biochemical response to treatment, and to compare different cut-off values used in the literature. Methods A retrospective cohort study of 184 patients with siNET Grade 2 treated with somatostatin analogues (SSA), interferon-alpha (IFN) or peptide receptor radionuclide therapy (PRRT). Results Baseline CgA was a statistically significant prognostic marker for both cancer-specific survival (CSS) and progression-free survival (PFS). A cut-off of 5 × ULN (upper limit of normal) was best discriminative in most cases, but 2 × ULN discriminated better for SSA. Baseline 5HIAA was a prognostic marker for CSS in treatment with IFN and PRRT, but not for single SSA. Early changes of CgA and 5HIAA correlated well with CSS (HR 3.18, 95% CI 1.82–5.56 and HR 1.47, 95% CI 1.16–1.86) and PFS (HR 3.08, 95% CI 1.86–5.10 and HR 1.37, 95% CI 1.11–1.68) for SSA, but not for PRRT. Conclusions Baseline CgA and to a lesser extent 5HIAA are associated with CSS irrespective of treatment used, and with PFS after PRRT, and 5 × ULN provides best discrimination in many, but not all, cases. Early reductions of CgA and 5HIAA are prognostic for treatment with SSA, but not PRRT. Keywords Chromogranin A 5HIAA Small intestinal neuroendocrine tumours Biomarker Carcinoids Cut-offs ●
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Introduction
Supplementary information The online version of this article (https:// doi.org/10.1007/s12020-020-02534-8) contains supplementary material, which is available to authorized users. * Dimitrios Papantoniou [email protected] 1
Department of Medical Sciences, Endocrine Oncology, Uppsala University, Uppsala, Sweden
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Department of Oncology, Ryhov County Hospital, Jönköping, Sweden
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Department of Surgery, Ryhov County Hospital, Jönköping, Sweden
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Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland
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Qulturum, Region Jönköping, Jönköping, Sweden
Neuroendocrine neoplasms (NENs) of the small intestine are the third largest subgroup of NENs in the gastroenteropancreatic system [1]. According to the WHO classification from 2019, they are grouped on the basis of their proliferation index into well differentiated grade 1 (G1, Ki-67 < 3%), grade 2 (G2, Ki-67 3–20%) and grade 3 (G3, Ki-67 > 20%) neuroendocrine tumours (NETs) and the rare, poorly
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