Radiolabelled somatostatin analogue treatment in gastroenteropancreatic neuroendocrine tumours: factors associated with response and suggestions for therapeutic sequence: response to comments by Ezziddin et al.

Abstract

Dear Sir, We thank Ezziddin et al. for their comments [1] on our article [2]. The aim of our study was to determine the time to progression of patients treated with radiolabelled somatostatin analogues and to identify the prognostic factors related to treatment response. Regarding the prognostic factors related to treatment response [2] and in accordance with the report by Ezziddin et al., we did not find any correlation between the response rate at 6 months after radiolabelled somatostatin analogue treatment (PRRT) and either the WHO2010 classification [3] or Ki67 as a continuous variable. On the contrary, we reported the role of the WHO 2010 classification in terms of progression-free survival after PRRT. Moreover, our data confirm that Ki67 is a major prognostic factor in neuroendocrine tumours (NETs) [4–6]. In addition, both our study and that of Ezziddin et al. showed that Ki67 does not influence the PRRT response in terms of the RECIST criteria but is a crucial prognostic factor for progression-free survival. Our results, in accordance with those of many other studies, indicate the key role of Ki67 as a prognostic factor. Concerning this key role, neither Kwekkeboom et al. [7] nor Imhof et al. [8] evaluated Ki67 in their large series. Imhof et al. reported the prognostic factors regarding overall survival and severe kidney toxicities after PRRTwith Y, but, despite being large, the series included a wide spectrum of neuroendocrine neoplasms (gastroenteropancreatic NETs, bronchial carcinoids, rare NETs, unknown primary NETs) [8]. However, in a large and more homogeneous series of patients (with gastroenteropancreatic NETs and unknown primary NETs), Kwekkeboom et al. investigated the presence of bone metastases, the extent of liver involvement, and gastrinoma, insulinoma or VIPoma tumour types as prognostic factors for tumour progression in a multivariate analysis [7]. Our series, with respect to the two previous studies, evaluated the role of major prognostic factors [9, 10] in patients treated with PRRT in a smaller but even more homogeneous series (only pancreatic and gastrointestinal NETs). In this study, the more recent classifications in terms of TNM [11, 12] and WHO [3] were used to update the findings regarding prognostic factors. We agree with Ezziddin et al. as far as the need for caution in the use of multivariate analyses with a large number of variables in a relatively small number of patients is concerned. However, in order to reduce the impact of too many variables, the forward stepwise method was used. We also agree that prospective and comparative studies in larger homogeneous series are obviously necessary to better assess the value of the data reported. D. Campana : P. Tommassetti Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy