Total lesion somatostatin receptor expression (TLS) for response assessment and survival prediction in neuroendocrine neoplasms undergoing PRRT
Clinical and Translational Imaging, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Publication Date: 2026
- Doi Number: 10.1007/s40336-026-00779-3
- Journal Name: Clinical and Translational Imaging
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aerospace Database, EMBASE, Health Research Premium Collection (ProQuest), Technology Collection (ProQuest)
- Keywords: Ga-68 DOTATATE PET, Neuroendocrine tumours, PERCIST, PFS, RECIST, SSTR PET, Therapy response, Tumour volume
- Hacettepe University Affiliated: Yes
Abstract
Purpose: This study aimed to evaluate the utility of Total Lesion Somatostatin Receptor expression (TLS), a volumetric imaging biomarker integrating tumour burden and tumour somatostatin receptor density, for early response assessment and progression-free survival (PFS) prediction in patients with neuroendocrine neoplasms (NENs) undergoing peptide receptor radionuclide therapy (PRRT). Methods: We retrospectively evaluated the baseline and post-therapy [68Ga] Ga-DOTATATE PET/CT scans of 49 patients. TLS was calculated for every target lesion. The therapeutic response defined by TLS was compared with RECIST 1.1 and PERCIST criteria. The prognostic significance of baseline parameters, including Ki-67 index, hemograms, liver and renal function tests and metabolic parameters derived from imaging was analysed using Cox regression. Results: At a median follow-up of 32.6 months, TLS-based response assessment demonstrated superior PFS stratification compared to RECIST 1.1 and PERCIST. Notably, TLS reclassified 76% (29/38) of patients initially categorized as Stable Disease (SD) by RECIST 1.1 into the Partial Response (PR) group. These TLS-responders had significantly longer PFS than those classified as SD by both methods (34.7 vs. 24.8 months; p < 0.001). Additionally, these two groups of patients had different characteristics, such as Ki-67 and baseline SUVmax. Among these response assessment methods, only TLS demonstrated a clear decreasing trend in survival across all response tiers (PR > SD > PD) in our cohort. Patients with higher baseline SUVmax (p: 0.038) and lower TLS (p: 0.033) had better PFS. Multivariate analysis identified Ki-67 index (HR: 1.099; p = 0.003) and baseline haemoglobin (HR: 0.555; p = 0.003) as independent predictors of PFS. Conclusion: TLS provides a more accurate reflection of therapeutic efficacy in NENs by integrating tumour burden and receptor density. It effectively refines the prognostic stratification of heterogeneous RECIST-SD patient group, offering a promising tool for early response evaluation in clinical practice. The Ki-67 proliferation index is a strong predictor of response to PRRT. Baseline haemoglobin may be used as a predictive factor for patient outcomes.