Abstract
PurposeSmall 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.MethodsA retrospective cohort study of 184 patients with siNET Grade 2 treated with somatostatin analogues (SSA), interferon-alpha (IFN) or peptide receptor radionuclide therapy (PRRT).ResultsBaseline 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.ConclusionsBaseline 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.
Highlights
Supplementary information The online version of this article contains supplementary material, which is available to authorized users.Neuroendocrine neoplasms (NENs) of the small intestine are the third largest subgroup of NENs in the gastroenteropancreatic system [1]
In this retrospective cohort study, all patients with metastatic siNETs with a Ki-67 proliferation index between 3 and 20% (WHO grade 2) that were treated at the Department of Endocrine Oncology, Uppsala University Hospital, a tertiary referral centre, and at the Department of Oncology, Ryhov County Hospital, a regional hospital, between 1 January 2000 and 31 May 2017 were eligible for inclusion and were retrieved from an internal database
Four patients were rechallenged with IFN and 13 with peptide receptor radionuclide therapy (PRRT), and were included as separate treatment events
Summary
In a recent Surveillance Epidemiology and Ends Results database analysis, which uses an older slightly different classification system, well differentiated NETs were approximately four times more common than intermediate grade tumours [3]. [7,8,9] When dichotomizing these biomarkers, different authors have been using various cut-offs ranging from 1 to 10 times the upper limit of normal (×ULN), leading to results that are not entirely comparable [7, 10,11,12,13,14,15,16]. Limited data shows that early reduction of CgA and/or 5HIAA may correlate with treatment effect of some, but not all anti-tumoural agents, and with the survival of the patient [17, 18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
