The association of intra-therapeutic heterogeneity of somatostatin receptor expression with morphological treatment response in patients undergoing PRRT with [177Lu]-DOTATATE
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The association of intra-therapeutic heterogeneity of somatostatin receptor expression with morphological treatment response in patients undergoing PRRT with [177Lu]-DOTATATE. / 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.
in: PLOS ONE, Jahrgang 14, Nr. 5, 2019, S. e0216781.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The association of intra-therapeutic heterogeneity of somatostatin receptor expression with morphological treatment response in patients undergoing PRRT with [177Lu]-DOTATATE
AU - Wetz, Christoph
AU - Genseke, Philipp
AU - Apostolova, Ivayla
AU - Furth, Christian
AU - Ghazzawi, Sammy
AU - Rogasch, Julian M M
AU - Schatka, Imke
AU - Kreissl, Michael C
AU - Hofheinz, Frank
AU - Grosser, Oliver S
AU - Amthauer, Holger
PY - 2019
Y1 - 2019
N2 - AIM: 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]).MATERIALS AND METHODS: 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.RESULTS: 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).CONCLUSION: Pre- and intra-therapeutic ASP shows a strong correlation and might be an useful tool for therapy monitoring.
AB - AIM: 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]).MATERIALS AND METHODS: 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.RESULTS: 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).CONCLUSION: Pre- and intra-therapeutic ASP shows a strong correlation and might be an useful tool for therapy monitoring.
KW - Aged
KW - Aged, 80 and over
KW - Bone Neoplasms/diagnostic imaging
KW - Disease-Free Survival
KW - Female
KW - Gastrointestinal Neoplasms/diagnostic imaging
KW - Humans
KW - Liver Neoplasms/diagnostic imaging
KW - Lymphatic Metastasis
KW - Male
KW - Middle Aged
KW - Neoplasm Proteins/metabolism
KW - Neuroendocrine Tumors/diagnostic imaging
KW - Octreotide/administration & dosage
KW - Pancreatic Neoplasms/diagnostic imaging
KW - Receptors, Somatostatin/metabolism
KW - Retrospective Studies
KW - Single Photon Emission Computed Tomography Computed Tomography
KW - Survival Rate
U2 - 10.1371/journal.pone.0216781
DO - 10.1371/journal.pone.0216781
M3 - SCORING: Journal article
C2 - 31091247
VL - 14
SP - e0216781
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 5
ER -