Letter: the response to somatostatin analogues in neuroendocrine tumours is influenced by Ki67 score--authors' reply.

Abstract

We thank Faggiano et al. for their comments on our review article on gastric neuroendocrine tumours (NETs).1, 2 They sought to determine the anti-proliferative effects of long-acting somatostatin analogues (SSAs) in patients with gastroenteropancreatic (GEP)-NETs according to the Ki67 score. They describe a small cohort of G1 and G2 GEP-NETs treated with SSAs over a 9-year period. They report no differences in progression-free survival (PFS) with the current threshold in Ki67 score for G1 and G2 NETs (≤2%), but a significant difference in PFS when a threshold of 5% was considered. Further detail on sites of primary NETs, the burden of hepatic disease, somatostatin receptor expression avidity from functional imaging and progression pre-SSA may be informative. As described in our article, the threshold of 5% is debated to be more discriminatory in predicting tumour biology. The data from Faggiano et al. adds to the body of evidence for adjusting the histological grade threshold between G1 and G2 GEP-NETs from a Ki67 of ≤2% to 5%. This adjustment may more accurately define prognostic cohorts of GEP-NET patients by unmasking differences in tumour biology through outcomes like PFS, as well as help to delineate therapeutic responses that are dependent on tumour proliferation. However, the study does not clearly demonstrate the anti-proliferative properties of SSAs beyond this phenomenon of unmasking PFS differences through Ki67 adjustment. Proving that Ki67 influences the response to SSA therapy would require sub-analysis of prospective, placebo controlled studies, like CLARINET, at the proposed adjusted thresholds.3 In the context of gastric NETs, there is no robust data on the unmasking effect on PFS through Ki67 adjustment, and only limited data for the anti-proliferative effect of SSAs. The authors' declarations of personal and financial interests are unchanged from those in the original article.2