{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:38:26Z","timestamp":1788903506041,"version":"build-2803163510"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BJC Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>While advanced gastrointestinal stromal tumors (GISTs) are primarily treated with tyrosine kinase inhibitors (TKIs), acquired resistance from specific mutations in <jats:italic>KIT<\/jats:italic> or <jats:italic>PDGFRA<\/jats:italic> frequently occurs. We aimed to assess the utility of circulating tumor DNA (ctDNA) as a modality of therapeutic decision-making in advanced GIST.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We conducted a pooled analysis of SCRUM-Japan studies for advanced GIST patients. We compared patient characteristics analyzed with tissue and blood samples, assessed gene alteration profiles, and evaluated prognostic implications from ctDNA status.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In 133 patients, tissue and blood samples were analyzed for 89 and 44 patients, respectively. ctDNA was detected in 72.7% of cases; no prior treatment or progressive disease was significantly associated with ctDNA-positivity. ctDNA-positive patients had significantly shorter progression-free survival compared with ctDNA-negative patients (hazard ratio\u2009=\u20093.92; <jats:italic>P<\/jats:italic>\u2009=\u20090.007). ctDNA genotyping revealed a complex landscape of gene alterations, characterized by multi-exonic mutations in <jats:italic>KIT<\/jats:italic>, compared with tissue-based analysis. Patients who received TKIs matched to the identified <jats:italic>KIT<\/jats:italic> mutation in ctDNA demonstrated significantly longer PFS than those with unmatched treatment (median, 8.23 vs. 2.43 months; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>ctDNA-based analysis facilitates assessment of disease status and genomic profiles, thus potentially assisting in identifying optimal therapeutic strategies for advanced GIST patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/s44276-024-00073-7","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T10:03:04Z","timestamp":1721901784000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Different efficacy of tyrosine kinase inhibitors by KIT and PGFRA mutations identified in 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YN reports grants from Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Guardant Health, Inc., Genomedia, Inc., Roche Diagnostics, and Seagen, Inc.; and honoraria from Chugai Pharmaceutical Co., Ltd., and Guardant Health AMEA outside the submitted work. YK reports grants from Novartis, Yakult Honsha Co., Ltd., Pfizer, Bayer, and Taiho Pharmaceutical Co., Ltd. outside the submitted work. SY reports honoraria from Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bayer Yakuhin Ltd., Bristol-Myers Squibb K.K., Takeda Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., MSD K.K., Ono Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Daiichi Sankyo Co., Ltd. outside the submitted work; NT reports honoraria from Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K. outside the submitted work; NO reports honoraria from Taiho Pharmaceutical Co., Ltd., Eli Lilly Japan, Eisai, Bayer Yakuhin, Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical, Takeda Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., AstraZeneca, MSD, and Incyte outside the submitted work.; HH reports honoraria from Bristol-Myers Squibb Japan, Chugai Pharmaceutical Co., Ltd., Novartis, Taiho Pharmaceutical Co., Ltd., Fujifilm Pharmaceuticals, Teijin Pharma, and Ono Pharmaceutical outside the submitted work; TO reports grants from Takeda Pharmaceutical Co. Ltd. and honoraria from Eli Lilly, Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., EA Pharma Co., Ltd., Bristol-Myers Squibb K.K., Ono Pharmaceutical, Eisai Co., Ltd., Yakult Honsha Co., Ltd., and Otsuka Pharmaceutical Co., Ltd. outside the submitted work; EO reports research funding from Guardant Health, Inc. and reports honoraria from Chugai Pharmaceutical Co., Ltd., Eli Lilly, Takeda Pharmaceutical Co., Ltd., Bristol and Ono Pharmaceutical outside the submitted work; T. Nishina reports honoraria from Daiichi Sankyo Co., Ltd., Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb, Eli Lilly Japan K.K., Takeda Pharmaceutical Co., Ltd., Merck Serono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd and Yakult Honsha Co., Ltd. outside the submitted work; H.K reports grants from Eisai Co. Ltd., Taiho Pharmaceutical Co. Ltd., Kobayashi Pharmaceutical. Co., Ltd., Bristol-Myers Squibb Co. Ltd., Daiichi Sankyo Co. Ltd. consulting fees from Daiichi Sankyo Co. Ltd., and honoraria from Bristol-Myers Squibb Co. Ltd., Bayer Yakuhin Ltd., Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co. Ltd., Yakult Pharmaceutical Industry, Teijin Pharma Ltd., Taiho Pharmaceutical Co. Ltd., and Otsuka Pharmaceutical Co., Ltd. outside the submitted work; TE reports grants from MSD, Daiichi Sankyo Co., Ltd., Pfyzer, Astellas, Quintiles, SyneosHealth, Chugai Pharmaceutical Co., Ltd., Amgen, Ono, Novartis, Astellas Amgen Biopharma, Asahikasei Pharma, and IQVIA, and honoraria from Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Eli Lilly, Bristol, and MSD outside the submitted work; YY reports honoraria from Ono Pharmaceutical, Taiho Pharmaceutical Co., Ltd., Bristol Myers Squibb, Servier, Yakult, Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Lily, Astrazeneca, Bayer, and Incyte outside the submitted work; TD reports research funds from MSD, Amgen, Bristol Myers Squibb Foundation, Pfizer, and Ono Pharmaceutical and honoraria from Sysmex, Ono Pharmaceutical, Sawai Pharmaceutical Co and Daiichi Sankyo Co., Ltd., outside the submitted work; MG reports grants from Nippon Kayaku CO., Ltd., Chugai Pharmaceutical CO., Ltd., Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical CO., Ltd., Eli Lilly Japan K.K., and MSD K.K. outside the submitted work; MI reports honoraria from Caris Life Sciences and consulting fee from Sumitomo Corp. outside the submitted work; TF reports honoraria from Amelief outside the submitted work; HB reports research funding from Ono Pharmaceutical and honoraria from Taiho Pharmaceutical Co., Ltd. Pharmaceutical and Eli Lilly, Japan outside the submitted work; YN reports grants from ABBVIE, Ono, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Pfizer, Boehringer Ingelheim, Eli Lilly, Eisai, AstraZeneca, Chugai Pharmaceutical Co., Ltd., and Bayer, and honoraria from AstraZeneca, Eisai, Ono, Guardant Health, Inc., Takeda Pharmaceutical Co., Ltd., Eli Lilly, Novartis, Pfizer, Chugai Pharmaceutical Co., Ltd., PDR pharma, Nihon Kayaku, Taiho Pharmaceutical Co., Ltd., Bristol, Bayer, Daiichi Sankyo Co., Ltd., and MSD outside the submitted work; TY reports honoraria from Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Merck, Bayer Yakuhin, Ono Pharmaceutical and MSD K.K; consulting fee from Sumitomo Corp.; and research grant from Amgen, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai, FALCO Biosystems, Genomedia Inc., Molecular Health, MSD, Nippon Boehringer Ingelheim, Ono, Pfizer, Roche Diagnostics, Sanofi, Sysmex and Taiho Pharmaceutical Co., Ltd., outside the submitted work. No disclosures were reported by the other authors.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study included patients with advanced GIST who participated in SURUM-Japan trials, including GI-SCREEN (UMIN000016344), GOZILA (UMIN000029315), MONSTAR-SCREEN (UMIN000036749), and MONSTAR-SCREEN-2 (UMIN000043899). The study protocol was approved by the Institutional Review Board of National Cancer Center Hospital East (UMIN000049334).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All subjects have written informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"54"}}