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

• Published in: PloS one 2019-05, Vol.14 (5), p.e0216781-e0216781
• Main Authors: Wetz, Christoph, Genseke, Philipp, Apostolova, Ivayla, Furth, Christian, Ghazzawi, Sammy, Rogasch, Julian M M, Schatka, Imke, Kreissl, Michael C, Hofheinz, Frank, Grosser, Oliver S, Amthauer, Holger
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0216781

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