Abstract

BackgroundLanreotide is a long-acting somatostatin analogue with proven antitumour effects against well-differentiated (WD) gastroenteropancreatic-neuroendocrine tumours (GEP-NETs). However, there are no globally established prognostic factors associated with the efficacy of lanreotide as a treatment for GEP-NETs. We investigated the prognostic value of [68Ga]Ga-DOTA-TOC positron emission tomography (PET)/computed tomography (CT) somatostatin receptor imaging for patients with WD GEP-NETs treated with lanreotide.MethodsIn this retrospective study, we included 31 patients with unresectable or metastatic WD GEP-NETs who received lanreotide and underwent [68Ga]Ga-DOTA-TOC PET/CT before receiving lanreotide. We captured the following clinicopathological variables: Eastern Cooperative Oncology Group (ECOG) performance status, primary tumour site, NET World Health Organization grade, existence of carcinoid symptoms, previous surgery, previous chemotherapy, and hepatic tumour volume assessed by CT or magnetic resonance imaging (MRI). We also assessed the following [68Ga]Ga-DOTA-TOC PET/CT variables: Krenning score, tumour-to-liver ratio (TLR), maximum standardized uptake value (SUVmax), whole tumour volume (WTV), and total receptor expression (TRE, WTV multiplied by SUVmean). The associations between these markers and progression-free survival (PFS) with lanreotide were analysed.ResultsThe mean age was 55.1 ± 15.5 years (range 16.0–81.0). The most common primary tumour site was the pancreas, followed by the stomach, and rectum. The median PFS interval with lanreotide was 14.4 months (range 1.3–34.9), with identified disease progression in 20 patients (64.5%). Among the [68Ga]Ga-DOTA-TOC PET/CT variables, TLR (< 8.1 vs. ≥ 8.1; p = 0.013), SUVmax (< 42.9 vs. ≥ 42.9; p = 0.037), and WTV (≥ 58.9 cm3 vs. < 58.9 cm3; p = 0.030) were significantly associated with PFS in the univariate analyses, but only TLR (hazard ratio 3.182 [95% CI 1.189–8.514], p = 0.021) remained an independent factor for PFS in the multivariate analysis.ConclusionsLow TLR, determined via [68Ga]Ga-DOTA-TOC PET/CT, can be a factor of worse prognosis in patients with advanced WD GEP-NETs treated with lanreotide.

Highlights

  • Lanreotide is a long-acting somatostatin analogue with proven antitumour effects against well-differentiated (WD) gastroenteropancreatic-neuroendocrine tumours (GEP-Neuroendocrine tumour (NET))

  • Among the [68Ga]Ga-DOTA-TOC positron emission tomography (PET)/CT variables, to-liver ratio (TLR) (< 8.1 vs. ≥ 8.1; p = 0.013), SUVmax (< 42.9 vs. ≥ 42.9; p = 0.037), and Whole tumour volume (WTV) (≥ 58.9 cm3 vs. < 58.9 cm3; p = 0.030) were significantly associated with progression-free survival (PFS) in the univariate analyses, but only TLR remained an independent factor for PFS in the multivariate analysis

  • Low TLR, determined via [68Ga]Ga-DOTA-TOC PET/CT, can be a factor of worse prognosis in patients with advanced WD GEP-NETs treated with lanreotide

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Summary

Introduction

Lanreotide is a long-acting somatostatin analogue with proven antitumour effects against well-differentiated (WD) gastroenteropancreatic-neuroendocrine tumours (GEP-NETs). Neuroendocrine tumours (NETs) are a heterogeneous group of malignancies arising from neuroendocrine cells throughout the body [1]. As most NETs overexpress somatostatin receptors (SSTRs) in their cell membranes, SSTRs are an interesting target for NET therapy and imaging [4]. Examples of SSTR-targeting therapies include somatostatin analogues, such as lanreotide and octreotide [5]. Lanreotide (lanreotide autogel) is a long-acting somatostatin analogue whose antitumour effects against metastatic, well-differentiated (WD) GEP-NETs were proven in the pivotal CLARINET phase III clinical trial [6]. Based on the success of this trial, lanreotide is a globally recommended first-line systemic therapy for metastatic, WD GEP-NETs [7]

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