The role of quantitative tumor burden based on [68 Ga]Ga-DOTA-NOC PET/CT in well-differentiated neuroendocrine tumors: beyond prognosis

Abstract

Purpose: We aimed to elucidate the role of quantitative tumor burden based on PET/CT of somatostatin receptors in well-differentiated neuroendocrine tumors (NETs).

Methods: This study enrolled patients with [⁶⁸ Ga]Ga-DOTA-NOC PET/CT-positive advanced NETs who did not receive medical treatment prior to PET/CT. Tumor burden was calculated using methods based on the background threshold and relative fixed threshold values (30%, 40%, and 50%). The prognostic value of the measured tumor burden in reference to overall survival (OS) and progression-free survival (PFS) on treatment with octreotide long-acting repeatable (LAR) was assessed using Cox regression analysis, Harrell's C-index, and survival analysis. A classification and regression tree (CART) was used to determine the optimal threshold for tumor burden.

Results: A total of 204 patients were included. Somatostatin receptor-expressing tumor volume (SRETV) and liver SRETV derived from a relative fixed threshold of 30% (SRETV₃₀ and liver SRETV₃₀) were statistically significantly associated with OS (C-index: 0.802 [95% confidence interval (CI), 0.658-0.946] and 0.806 [95% CI, 0.664-0.948], respectively). Extrahepatic tumor burden was not correlated with OS (hazard ratio: 0.617, 95% CI: 0.241-1.574, P = 0.312). Among 155 patients with non-functional NETs with a ki-67 index of ≤ 10%, those with a high SRETV₃₀ (P = 0.016) or high liver SRETV₃₀ (P = 0.014) showed statistically significantly worse PFS on treatment with octreotide LAR. Patients receiving a higher dose of octreotide LAR normalized by SRETV₃₀ or liver SRETV₃₀ (a normalized dose or a liver normalized dose) showed prolonged PFS on treatment with octreotide LAR and a prolonged OS.

Conclusion: Quantitative tumor burden based on [⁶⁸ Ga]Ga-DOTA-NOC PET/CT was correlated with OS and PFS in patients with non-functional NETs with a ki-67 index of ≤ 10% who received octreotide LAR. Calculating normalized and liver normalized doses may help in selecting the starting dose of octreotide LAR.

Keywords: Neuroendocrine tumors; Octreotide LAR; Overall survival; Progression-free survival; Tumor burden; [68 Ga]Ga-DOTA-NOC PET/CT.