68 Ga-DOTATATE Positron Emission Tomography-Computed Tomography Quantification Predicts Response to Somatostatin Analog Therapy in Gastroenteropancreatic Neuroendocrine Tumors

Abstract

Background: Somatostatin analogs (SSAs) are the frontline antitumor therapy in advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A subset of patients demonstrate early disease progression on SSA therapy, yet the currently known predictors for treatment failure lack specificity to affect therapeutic decision. SSAs target tumor somatostatin receptors, the level of which can be quantitatively assessed with ⁶⁸ Ga-DOTATATE positron emission tomography-computed tomography (PET/CT). We investigated the ability of ⁶⁸ Ga-DOTATATE PET/CT to predict response to SSA therapy.

Materials and methods: The records of 108 consecutive patients with well-differentiated grade 1-2 GEP-NETs on SSA monotherapy who received ⁶⁸ Ga-DOTATATE PET/CT scans were retrospectively reviewed to obtain baseline characteristics, ⁶⁸ Ga-DOTATATE maximum standardized uptake value (SUVmax), and progression-free survival (PFS) data. The optimal SUVmax cutoff for patient stratification was obtained with receiver operating characteristic curve analysis. PFS in the high versus low SUVmax groups was compared with Kaplan-Meier survival analysis. The effects of baseline characteristics and SUVmax on PFS were examined with univariate and multivariate Cox regression.

Results: ⁶⁸ Ga-DOTATATE SUVmax predicted therapeutic failure with sensitivity and specificity of 39% and 98%, respectively. SUVmax of <18.35 was associated with shorter PFS, which was reproduced in the subgroup analysis of SSA-naïve patients. Low SUVmax was the only predictor of early treatment failure (hazard ratio, 6.85) in multivariate analysis, as well as in the subgroup analysis of grade 2 GEP-NETs.

Conclusion: Low SUVmax on ⁶⁸ Ga-DOTATATE PET/CT independently predicts early failure on SSA monotherapy in patients with well-differentiated grade 1-2 GEP-NET. Patients with lack of expected benefit from SSA therapy can be readily identified using routine ⁶⁸ Ga-DOTATATE PET/CT with very high specificity.

Implications for practice: Based on ⁶⁸ Ga-DOTATATE positron emission tomography-computed tomography imaging, clinicians can better inform patients on the expected benefit of somatostatin analog therapy for gastroenteropancreatic neuroendocrine tumors, especially when access to the therapy is difficult, and offer proactive discussion on alternative management options.

Keywords: 68Ga-DOTATATE; Computed tomography; Gastroenteropancreatic neuroendocrine tumor; Lanreotide; Octreotide; Positron emission tomography.