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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

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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, Vol. 14, No. 5, 2019, p. e0216781.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Wetz, C, Genseke, P, Apostolova, I, Furth, C, Ghazzawi, S, Rogasch, JMM, Schatka, I, Kreissl, MC, Hofheinz, F, Grosser, OS & Amthauer, H 2019, 'The association of intra-therapeutic heterogeneity of somatostatin receptor expression with morphological treatment response in patients undergoing PRRT with [177Lu]-DOTATATE', PLOS ONE, vol. 14, no. 5, pp. e0216781. https://doi.org/10.1371/journal.pone.0216781

APA

Wetz, C., Genseke, P., Apostolova, I., Furth, C., Ghazzawi, S., Rogasch, J. M. M., Schatka, I., Kreissl, M. C., Hofheinz, F., Grosser, O. S., & Amthauer, H. (2019). The association of intra-therapeutic heterogeneity of somatostatin receptor expression with morphological treatment response in patients undergoing PRRT with [177Lu]-DOTATATE. PLOS ONE, 14(5), e0216781. https://doi.org/10.1371/journal.pone.0216781

Vancouver

Wetz C, Genseke P, Apostolova I, Furth C, Ghazzawi S, Rogasch JMM et al. The association of intra-therapeutic heterogeneity of somatostatin receptor expression with morphological treatment response in patients undergoing PRRT with [177Lu]-DOTATATE. PLOS ONE. 2019;14(5):e0216781. https://doi.org/10.1371/journal.pone.0216781

Bibtex

@article{b12cb02cfadc4b25b4ee0db1934c082a,
title = "The association of intra-therapeutic heterogeneity of somatostatin receptor expression with morphological treatment response in patients undergoing PRRT with [177Lu]-DOTATATE",
abstract = "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.",
keywords = "Aged, Aged, 80 and over, Bone Neoplasms/diagnostic imaging, Disease-Free Survival, Female, Gastrointestinal Neoplasms/diagnostic imaging, Humans, Liver Neoplasms/diagnostic imaging, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Proteins/metabolism, Neuroendocrine Tumors/diagnostic imaging, Octreotide/administration & dosage, Pancreatic Neoplasms/diagnostic imaging, Receptors, Somatostatin/metabolism, Retrospective Studies, Single Photon Emission Computed Tomography Computed Tomography, Survival Rate",
author = "Christoph Wetz and Philipp Genseke and Ivayla Apostolova and Christian Furth and Sammy Ghazzawi and Rogasch, {Julian M M} and Imke Schatka and Kreissl, {Michael C} and Frank Hofheinz and Grosser, {Oliver S} and Holger Amthauer",
year = "2019",
doi = "10.1371/journal.pone.0216781",
language = "English",
volume = "14",
pages = "e0216781",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

RIS

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 -