Journal Article

The association of intra-therapeutic heterogeneity of somatostatin receptor expression with morphological treatment response in patients undergoing PRRT with 177Lu-DOTATATE

Schatka, Imke, Kreissl, Michael C., Wetz, Christoph, Furth, Christian, Rogasch, Julian M. M., Amthauer, Holger, Hofheinz, Frank, Genseke, Philipp, Apostolova, Ivayla, Grosser, Oliver S., Ghazzawi, Sammy

2019

Overview

Purpose of this study was to evaluate the association of the spatial heterogeneity (asphericity, ASP) in intra-therapeutic SPECT/ CT imaging of somatostatin receptor (SSR) positive metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) for morphological treatment response to peptide receptor radionuclide therapy (PRRT). Secondly, we correlated ASP derived form a pre-therapeutic OctreoScan (ASP[In]) and an intra-therapeutic [177Lu]-SPECT/CT (ASP[Lu]). Data from first therapy cycle [177Lu-DOTA0-Tyr3]octreotate ([177Lu]-DOTATATE)-PRRT was retrospectively analyzed in 33 patients (m = 20; w = 13; median age, 72 [46-88] years). The evaluation of response to PRRT was performed according to RECIST 1.1 in responding lesions [RL (SD, PR, CR), n = 104] and non-responding lesions [NRL (PD), n = 27]. The association of SSR tumor heterogeneity with morphological response was evaluated by Kruskal-Wallis test and receiver operating characteristic curve (ROC). The optimal threshold for separation (RL vs. NRL) was calculated using the Youden-index. Relationship between pre- and intra-therapeutic ASP was determined with Spearman's rank correlation coefficient (ρ) and Bland-Altman plots. A total of 131 lesions (liver: n = 59, lymph nodes: n = 48, bone: n = 19, pancreas: n = 5) were analyzed. Lesions with higher ASP values showed a significantly poorer response to PRRT (PD, median: 11.3, IQR: 8.5-15.5; SD, median: 3.4, IQR: 2.1-4.5; PR, median 1.7, IQR: 0.9-2.8; CR, median: 0.5, IQR: 0.0-1.3); Kruskal-Wallis, p<0.001). ROC analyses revealed a significant separation between RL and NRL for ASP after 4 months (AUC 0.85, p<0.001) and after 12 months (AUC 0.94, p<0.001). The optimal threshold for ASP was >5.45% (sensitivity 96% and specificity 82%). The correlation coefficient of pre- and intra-therapeutic ASP revealed ρ = 0.72 (p <0.01). The mean absolute difference between ASP[In] and ASP[Lu] was -0.04 (95% Limits of Agreement, -6.1-6.0). Pre- and intra-therapeutic ASP shows a strong correlation and might be an useful tool for therapy monitoring.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aged / Aged, 80 and over / Asphericity / Biology and Life Sciences / Bone Neoplasms - diagnostic imaging / Bone Neoplasms - metabolism / Bone Neoplasms - mortality / Cancer metastasis / Cancer therapies / Care and treatment / CAT scans / Chemotherapy / Computed tomography / Correlation / Correlation coefficient / Correlation coefficients / Disease-Free Survival / Everolimus / Female / Gastrointestinal Neoplasms - diagnostic imaging / Gastrointestinal Neoplasms - metabolism / Gastrointestinal Neoplasms - mortality / Health aspects / Heterogeneity / Hospitals / Humans / Information technology services / Lesions / Liver / Liver Neoplasms - diagnostic imaging / Liver Neoplasms - metabolism / Liver Neoplasms - mortality / Lutetium isotopes / Lymph nodes / Lymphatic Metastasis / Male / Medical imaging / Medical prognosis / Medical research / Medicine and Health Sciences / Metastases / Metastasis / Middle Aged / Morphology / Movement disorders / Neoplasm Proteins - metabolism / Neoplasms / Neuroendocrine tumors / Neuroendocrine Tumors - diagnostic imaging / Neuroendocrine Tumors - metabolism / Neuroendocrine Tumors - mortality / Nuclear medicine / Octreotide - administration & dosage / Octreotide - analogs & derivatives / Oncology / Pancreas / Pancreatic Neoplasms - diagnostic imaging / Pancreatic Neoplasms - metabolism / Pancreatic Neoplasms - mortality / Peptides / Public relations / Radiation therapy / Radioisotopes / Radiology / Receptors, Somatostatin - metabolism / Research and Analysis Methods / Retrospective Studies / Separation / Single photon emission computed tomography / Single Photon Emission Computed Tomography Computed Tomography / Somatostatin / Spatial heterogeneity / Survival Rate / Tumors