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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
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 re...
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| Published in: | PloS one 2019-05, Vol.14 (5), p.e0216781-e0216781 |
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| creator | 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 |
| description | 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 |
| doi_str_mv | 10.1371/journal.pone.0216781 |
| format | article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0216781</identifier><identifier>PMID: 31091247</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><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</subject><ispartof>PloS one, 2019-05, Vol.14 (5), p.e0216781-e0216781</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Wetz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Wetz et al 2019 Wetz et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-600549fc8730d47de5bc20629e414462835afbb76b759e164362970c10fabccc3</citedby><cites>FETCH-LOGICAL-c692t-600549fc8730d47de5bc20629e414462835afbb76b759e164362970c10fabccc3</cites><orcidid>0000-0002-7392-1375</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2225825170/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2225825170?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25751,27922,27923,37010,37011,44588,53789,53791,74896</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31091247$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Hsieh, Jason Chia-Hsun</contributor><creatorcontrib>Wetz, Christoph</creatorcontrib><creatorcontrib>Genseke, Philipp</creatorcontrib><creatorcontrib>Apostolova, Ivayla</creatorcontrib><creatorcontrib>Furth, Christian</creatorcontrib><creatorcontrib>Ghazzawi, Sammy</creatorcontrib><creatorcontrib>Rogasch, Julian M M</creatorcontrib><creatorcontrib>Schatka, Imke</creatorcontrib><creatorcontrib>Kreissl, Michael C</creatorcontrib><creatorcontrib>Hofheinz, Frank</creatorcontrib><creatorcontrib>Grosser, Oliver S</creatorcontrib><creatorcontrib>Amthauer, Holger</creatorcontrib><title>The association of intra-therapeutic heterogeneity of somatostatin receptor expression with morphological treatment response in patients undergoing PRRT with [177Lu]-DOTATATE</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Asphericity</subject><subject>Biology and Life Sciences</subject><subject>Bone Neoplasms - diagnostic imaging</subject><subject>Bone Neoplasms - metabolism</subject><subject>Bone Neoplasms - mortality</subject><subject>Cancer metastasis</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>CAT scans</subject><subject>Chemotherapy</subject><subject>Computed tomography</subject><subject>Correlation</subject><subject>Correlation coefficient</subject><subject>Correlation coefficients</subject><subject>Disease-Free Survival</subject><subject>Everolimus</subject><subject>Female</subject><subject>Gastrointestinal Neoplasms - diagnostic imaging</subject><subject>Gastrointestinal Neoplasms - metabolism</subject><subject>Gastrointestinal Neoplasms - mortality</subject><subject>Health aspects</subject><subject>Heterogeneity</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Information technology services</subject><subject>Lesions</subject><subject>Liver</subject><subject>Liver Neoplasms - diagnostic imaging</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - mortality</subject><subject>Lutetium isotopes</subject><subject>Lymph nodes</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Medical imaging</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Morphology</subject><subject>Movement disorders</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Neoplasms</subject><subject>Neuroendocrine tumors</subject><subject>Neuroendocrine Tumors - diagnostic imaging</subject><subject>Neuroendocrine Tumors - metabolism</subject><subject>Neuroendocrine Tumors - mortality</subject><subject>Nuclear medicine</subject><subject>Octreotide - administration & dosage</subject><subject>Octreotide - analogs & derivatives</subject><subject>Oncology</subject><subject>Pancreas</subject><subject>Pancreatic Neoplasms - diagnostic imaging</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - mortality</subject><subject>Peptides</subject><subject>Public relations</subject><subject>Radiation therapy</subject><subject>Radioisotopes</subject><subject>Radiology</subject><subject>Receptors, Somatostatin - metabolism</subject><subject>Research and Analysis Methods</subject><subject>Retrospective Studies</subject><subject>Separation</subject><subject>Single photon emission computed tomography</subject><subject>Single Photon Emission Computed Tomography Computed Tomography</subject><subject>Somatostatin</subject><subject>Spatial heterogeneity</subject><subject>Survival Rate</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk8Fu1DAQhiMEoqXwBggiISE47GI7sR1fkKpSoNJKi8rCBSHLcSaJqyQOtgPtS_GMOOy26qIekA-Jxt__j2fsSZKnGC1xxvGbCzu5QXXL0Q6wRAQzXuB7ySEWGVkwgrL7t_4PkkfeXyBEs4Kxh8lBhpHAJOeHye9NC6ny3mqjgrFDauvUDMGpRWjBqRGmYHTaQgBnGxjAhKsZ8bZXwfoQNUPqQMMYrEvhcnTg_Wzzy4Q27a0bW9vZxmjVpcGBCj0MIQp8PLWHmCkdo0WM-XQaKnCNNUOTfjo_32wdvmHOV9P3xbv15jiu08fJg1p1Hp7svkfJl_enm5OPi9X6w9nJ8WqhmSBhwWKpuah1wTNU5bwCWmqCGBGQ4zxnpMioqsuSs5JTAZjlWdzjSGNUq1JrnR0lz7e-Y2e93LXaS0IILQjFHEXibEtUVl3I0ZleuStplZF_A9Y1UrnYuw5kiShjXJBCEJXjKleiqlDBFcdlRQWdvd7usk1lD5WG-QK6PdP9ncG0srE_JaNYFEJEg1c7A2d_TOCD7I3X0HVqADvN584Iynme44i--Ae9u7od1ahYgBlqG_Pq2VQe04LSLOOMRmp5BxVXBb3R8V3WJsb3BK_3BJEJcBkaNXkvzz6f_z-7_rrPvrzFtqC60HrbTfOL9vtgvgW1s947qG-ajJGcx-q6G3IeK7kbqyh7dvuCbkTXc5T9AVpqH7U</recordid><startdate>20190515</startdate><enddate>20190515</enddate><creator>Wetz, Christoph</creator><creator>Genseke, Philipp</creator><creator>Apostolova, Ivayla</creator><creator>Furth, Christian</creator><creator>Ghazzawi, Sammy</creator><creator>Rogasch, Julian M M</creator><creator>Schatka, Imke</creator><creator>Kreissl, Michael C</creator><creator>Hofheinz, Frank</creator><creator>Grosser, Oliver S</creator><creator>Amthauer, Holger</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-7392-1375</orcidid></search><sort><creationdate>20190515</creationdate><title>The association of intra-therapeutic heterogeneity of somatostatin receptor expression with morphological treatment response in patients undergoing PRRT with [177Lu]-DOTATATE</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-600549fc8730d47de5bc20629e414462835afbb76b759e164362970c10fabccc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Asphericity</topic><topic>Biology and Life Sciences</topic><topic>Bone Neoplasms - diagnostic imaging</topic><topic>Bone Neoplasms - metabolism</topic><topic>Bone Neoplasms - mortality</topic><topic>Cancer metastasis</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>CAT scans</topic><topic>Chemotherapy</topic><topic>Computed tomography</topic><topic>Correlation</topic><topic>Correlation coefficient</topic><topic>Correlation coefficients</topic><topic>Disease-Free Survival</topic><topic>Everolimus</topic><topic>Female</topic><topic>Gastrointestinal Neoplasms - diagnostic imaging</topic><topic>Gastrointestinal Neoplasms - metabolism</topic><topic>Gastrointestinal Neoplasms - mortality</topic><topic>Health aspects</topic><topic>Heterogeneity</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Information technology services</topic><topic>Lesions</topic><topic>Liver</topic><topic>Liver Neoplasms - diagnostic imaging</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - mortality</topic><topic>Lutetium isotopes</topic><topic>Lymph nodes</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Medical imaging</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Morphology</topic><topic>Movement disorders</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Neoplasms</topic><topic>Neuroendocrine tumors</topic><topic>Neuroendocrine Tumors - diagnostic imaging</topic><topic>Neuroendocrine Tumors - metabolism</topic><topic>Neuroendocrine Tumors - mortality</topic><topic>Nuclear medicine</topic><topic>Octreotide - administration & dosage</topic><topic>Octreotide - analogs & derivatives</topic><topic>Oncology</topic><topic>Pancreas</topic><topic>Pancreatic Neoplasms - diagnostic imaging</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - mortality</topic><topic>Peptides</topic><topic>Public relations</topic><topic>Radiation therapy</topic><topic>Radioisotopes</topic><topic>Radiology</topic><topic>Receptors, Somatostatin - metabolism</topic><topic>Research and Analysis Methods</topic><topic>Retrospective Studies</topic><topic>Separation</topic><topic>Single photon emission computed tomography</topic><topic>Single Photon Emission Computed Tomography Computed Tomography</topic><topic>Somatostatin</topic><topic>Spatial heterogeneity</topic><topic>Survival Rate</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wetz, Christoph</creatorcontrib><creatorcontrib>Genseke, Philipp</creatorcontrib><creatorcontrib>Apostolova, Ivayla</creatorcontrib><creatorcontrib>Furth, Christian</creatorcontrib><creatorcontrib>Ghazzawi, Sammy</creatorcontrib><creatorcontrib>Rogasch, Julian M M</creatorcontrib><creatorcontrib>Schatka, Imke</creatorcontrib><creatorcontrib>Kreissl, Michael C</creatorcontrib><creatorcontrib>Hofheinz, Frank</creatorcontrib><creatorcontrib>Grosser, Oliver S</creatorcontrib><creatorcontrib>Amthauer, Holger</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health Medical collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>ProQuest Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wetz, Christoph</au><au>Genseke, Philipp</au><au>Apostolova, Ivayla</au><au>Furth, Christian</au><au>Ghazzawi, Sammy</au><au>Rogasch, Julian M M</au><au>Schatka, Imke</au><au>Kreissl, Michael C</au><au>Hofheinz, Frank</au><au>Grosser, Oliver S</au><au>Amthauer, Holger</au><au>Hsieh, Jason Chia-Hsun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The association of intra-therapeutic heterogeneity of somatostatin receptor expression with morphological treatment response in patients undergoing PRRT with [177Lu]-DOTATATE</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-05-15</date><risdate>2019</risdate><volume>14</volume><issue>5</issue><spage>e0216781</spage><epage>e0216781</epage><pages>e0216781-e0216781</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31091247</pmid><doi>10.1371/journal.pone.0216781</doi><tpages>e0216781</tpages><orcidid>https://orcid.org/0000-0002-7392-1375</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2019-05, Vol.14 (5), p.e0216781-e0216781 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2225825170 |
| source | Publicly Available Content Database; PubMed |
| 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 |
| title | 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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