{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T18:13:13Z","timestamp":1789841593126,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T00:00:00Z","timestamp":1556496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["13GW0198E"],"award-info":[{"award-number":["13GW0198E"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008792","name":"Novartis Pharma","doi-asserted-by":"publisher","award":["CSTI5781BDE78T"],"award-info":[{"award-number":["CSTI5781BDE78T"]}],"id":[{"id":"10.13039\/100008792","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2019,10,15]]},"abstract":"<jats:p>This prospective trial aimed to investigate whether tumor\u2010specific <jats:italic>cKIT<\/jats:italic> and <jats:italic>PDGFRA<\/jats:italic> mutations can be detected and quantified in circulating tumor (ct)DNA in patients with active GIST, and whether detection indicates disease activity. We included 25 patients with active disease and <jats:italic>cKIT<\/jats:italic> or <jats:italic>PDGFRA<\/jats:italic> mutations detected in tissue. Mutant ctDNA was detected in the peripheral blood plasma using allele\u2010specific ligation (L\u2010)PCR and droplet digital (d)PCR. CtDNA harboring tumor\u2010specific <jats:italic>cKIT<\/jats:italic> or <jats:italic>PDGFRA<\/jats:italic> mutations was detected at least once in 16 out of 25 patients using L\u2010PCR (64%) and in 20 out of 25 patients with dPCR (80%). Using dPCR, the absolute numbers of ctDNA fragments (DNA copies\/ml) and the mutant allele frequency (MAF; in percent of wild\u2010type control) strongly correlated with tumor size expressed as RECIST1.1 sum of diameter (SOD) in mm (\u03c1\u2009= 0.3719 and 0.408, respectively, <jats:italic>p<\/jats:italic> &lt; 0.0001) and response status (\u03c1\u2009= 0.3939 and 0.392, respectively, <jats:italic>p<\/jats:italic> &lt; 0.0001 and <jats:italic>p<\/jats:italic> &lt; 0.001). Specificity of dPCR for detection of progression was 79.2% with a sensitivity of 55.2% and dPCR discriminated CR from active disease with a specificity of 96% and s sensitivity of 44.7%. With L\u2010PCR, correlations of MAF with tumor size and response status were less prominent. Serial ctDNA measurement reflected individual disease courses over time. Targeted panel sequencing of four patients detected additional driver mutations in all cases and secondary resistance mutations in two cases. Thus, ctDNA indicates disease activity in patients with GIST and should be incorporated as companion biomarker in future prospective trials.<\/jats:p>","DOI":"10.1002\/ijc.32282","type":"journal-article","created":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T15:57:37Z","timestamp":1552924657000},"page":"2292-2303","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Circulating <i>cKIT<\/i> and <i>PDGFRA<\/i> DNA indicates disease activity in Gastrointestinal Stromal Tumor (GIST)"],"prefix":"10.1002","volume":"145","author":[{"given":"Stefanie","family":"Jilg","sequence":"first","affiliation":[{"name":"III Medical Department for Hematology and Oncology, Klinikum Rechts der Isar Technische Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Rassner","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Maier","sequence":"additional","affiliation":[{"name":"Center for Internal Medicine, Department of Hematology\/Oncology and Hemostaseology University of Leipzig  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Waldeck","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine University of Freiburg  Freiburg Germany"},{"name":"German Cancer Consortium (DKTK) partner site Freiburg and German Cancer Research Center (DKFZ)  Heidelberg Germany"},{"name":"Faculty of Biology University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Kehl","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Statistics, and Epidemiology, Klinikum Rechts der Isar Technische Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Follo","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Philipp","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Sauter","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology, Klinikum Rechts der Isar Technische Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Specht","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Klinikum Rechts der Isar Technische Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Mitschke","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine University of Freiburg  Freiburg Germany"},{"name":"German Cancer Consortium (DKTK) partner site Freiburg and German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thoralf","family":"Lange","sequence":"additional","affiliation":[{"name":"Asklepios Klinik Wei\u00dfenfels  Wei\u00dfenfels Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Bauer","sequence":"additional","affiliation":[{"name":"Sarcoma Center, West German Cancer Center University Hospital Essen, University Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp J.","family":"Jost","sequence":"additional","affiliation":[{"name":"III Medical Department for Hematology and Oncology, Klinikum Rechts der Isar Technische Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Peschel","sequence":"additional","affiliation":[{"name":"III Medical Department for Hematology and Oncology, Klinikum Rechts der Isar Technische Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justus","family":"Duyster","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine University of Freiburg  Freiburg Germany"},{"name":"German Cancer Consortium (DKTK) partner site Freiburg and German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Gaiser","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Mannheim Ruprecht\u2010Karl University of Heidelberg  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hohenberger","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology and Thoracic Surgery University Medical Center Mannheim, Ruprecht\u2010Karl University of Heidelberg  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9593-8947","authenticated-orcid":false,"given":"Nikolas","family":"von Bubnoff","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine University of Freiburg  Freiburg Germany"},{"name":"German Cancer Consortium (DKTK) partner site Freiburg and German Cancer Research Center (DKFZ)  Heidelberg Germany"},{"name":"Department of Hematology and Oncology, Medical Center University of Schleswig Holstein  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2004-829035"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2004-812691"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdn080"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.24.2099"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2011.29.15_suppl.10016"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.74.9705"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69446-4"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(11)70299-6"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2008.06.025"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semdp.2006.09.001"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.57.4970"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.347"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00117-009-1852-9"},{"key":"e_1_2_7_15_1","first-page":"357","article-title":"Comparison of PET, CT, and dual\u2010modality PET\/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors","volume":"45","author":"Antoch G","year":"2004","journal-title":"J Nucl Med"},{"key":"e_1_2_7_16_1","first-page":"1S","article-title":"A tabulated summary of the FDG PET literature","volume":"42","author":"Gambhir SS","year":"2001","journal-title":"J Nucl Med"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5350.577"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0765"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.11.020"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2245"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007094"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000478864"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0715-827b"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3143"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24493"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2013.206359"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw037"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.66.7162"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.7461"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-1211"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-18-0174"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3519"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1105422108"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-17-0436"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1159\/000442948"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-015-0361-1"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40291-016-0203-6"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdr442"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2014.53"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0193048"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.0256"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S155214"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.48.7488"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3520"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1789"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.32282","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32282","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.32282","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32282","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T23:34:03Z","timestamp":1741736043000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.32282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,29]]},"references-count":44,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,10,15]]}},"alternative-id":["10.1002\/ijc.32282"],"URL":"https:\/\/doi.org\/10.1002\/ijc.32282","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,29]]},"assertion":[{"value":"2018-08-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}