{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:09:29Z","timestamp":1790021369183,"version":"4.0.1"},"reference-count":34,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal (GI) system. Most GISTs originate from the interstitial cells of Cajal (ICC), the pacemaker cell situated between the circular and longitudinal layers of the muscularis propria along the GI tract. In this population-based study using the SEER database, we sought to identify demographic, clinical, and pathologic factors that affect the prognosis and survival of patients with this neoplasm. Molecular genetic advances, current management guidelines, and advances in targeted therapy are discussed. Methods: Demographic and clinical data from GIST patients were retrieved from the SEER research plus database for the period 2000\u20132018. Statistical analysis was performed with IBM SPSS\u00ae v20.2 software using the Chi-square test, paired t-test, multivariate analysis, and Kaplan\u2013Meier functions. Results: A total of 10,833 patients with GIST were identified. Most patients were between 60\u201374 years of age: 40%, Caucasian: 68%, and the male to female ratio was 1.1:1. The most common primary tumor sites were stomach: 63%, small intestine: 30%, rectum: 3%, and esophagus: 0.7%. When reported, the grade of differentiation was well: 38%, moderately: 32%, undifferentiated: 19%, poorly: 12%. The size of most tumors ranged between 6\u201310 cm: 36% and they were treated by surgical intervention: 82% and\/or chemotherapy\/targeted therapy: 39%. The stage was localized: 66%, advanced: 19%, and regional: 15%. The 5-year survival was 74% (95% confidence interval (95% CI) = 72.6\u201374.7), and the 5-year cause-specific survival 82% (95% CI = 80.7\u201382.6). The 5-year cause-specific survival by treatment included surgery at 86% (95% CI = 85.4\u201387.3), chemotherapy\/targeted therapy with or without surgery at 77% (95% CI = 75.7\u201378.9), and radiation at 75% (95% CI = 74.5\u201380). On multivariable analysis tumor size &gt; 5 cm, poorly and undifferentiated grade, age &gt; 60, and distant metastases at presentation were associated with worse overall survival. Conclusion: GISTs comprise 1\u20132% of malignancies of the GI tract, usually affect male Caucasians between the ages of 60 and 74 years, most tumors occur in the stomach and small intestine, and are usually &gt;5 cm, but still localized, at the time of diagnosis. Most tumors receive multimodality surgical and chemotherapy\/targeted therapy treatment, with a 5-year overall survival of 74% and cause-specific survival of 82%. GIST patients would benefit from enrollment in large clinical trials to establish better therapy guidelines for unresectable, treatment-refractory, and recurrent tumors.<\/jats:p>","DOI":"10.3390\/cancers14153689","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T20:49:28Z","timestamp":1659041368000},"page":"3689","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Gastrointestinal Stromal Tumors (GIST): A Population-Based Study Using the SEER Database, including Management and Recent Advances in Targeted Therapy"],"prefix":"10.3390","volume":"14","author":[{"given":"Jaffar","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9435-9625","authenticated-orcid":false,"given":"Asad","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9992-6051","authenticated-orcid":false,"given":"Abdul","family":"Waheed","sequence":"additional","affiliation":[{"name":"Department of Surgery, San Joaquin General Hospital, French Camp, CA 95231, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabin Raj","family":"Karki","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Department of Hematology Oncology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawaraj","family":"Adhikari","sequence":"additional","affiliation":[{"name":"Department of Medicine, Bon Secours Memorial Regional Medical Center, Mechanicsville, VA 23116, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Vemavarapu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Charlie Norwood Veterans Affairs Medical Center, Augusta, GA 30904, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami","family":"Belakhlef","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samy Malik","family":"Bendjemil","sequence":"additional","affiliation":[{"name":"Department of Surgery, San Joaquin General Hospital, French Camp, CA 95231, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siamak","family":"Mehdizadeh Seraj","sequence":"additional","affiliation":[{"name":"Department of Surgery, San Joaquin General Hospital, French Camp, CA 95231, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feroze","family":"Sidhwa","sequence":"additional","affiliation":[{"name":"Department of Surgery, San Joaquin General Hospital, French Camp, CA 95231, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Intisar","family":"Ghleilib","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahin","family":"Foroutan","sequence":"additional","affiliation":[{"name":"Department of Surgery, San Joaquin General Hospital, French Camp, CA 95231, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5013-3851","authenticated-orcid":false,"given":"Andrew M.","family":"Blakely","sequence":"additional","affiliation":[{"name":"National Cancer Institute (NCI), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9710-4030","authenticated-orcid":false,"given":"Jaydira","family":"Del Rivero","sequence":"additional","affiliation":[{"name":"National Cancer Institute (NCI), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8913-793X","authenticated-orcid":false,"given":"Nagla Abdel","family":"Karim","sequence":"additional","affiliation":[{"name":"Inova Schar Cancer Institute, Department of Medicine, University of Virginia, Fairfax, VA 22031, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6578-178X","authenticated-orcid":false,"given":"Eric","family":"Vail","sequence":"additional","affiliation":[{"name":"Molecular Pathology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleh","family":"Heneidi","sequence":"additional","affiliation":[{"name":"Molecular Pathology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1833-4642","authenticated-orcid":false,"given":"Hector","family":"Mesa","sequence":"additional","affiliation":[{"name":"Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"ref_1","unstructured":"Moch, H. (2020). Soft Tissue and Bone Tumours, WHO Classification of Tumours, IARC. [5th ed.]. Available online: https:\/\/publications.iarc.fr\/Book-And-Report."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.canep.2015.10.031","article-title":"Global epidemiology of gastrointestinal stromal tumours (GIST): A systematic review of population-based cohort studies","volume":"40","author":"Soreide","year":"2016","journal-title":"Cancer Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S-1","DOI":"10.6004\/jnccn.2010.0116","article-title":"NCCN Task Force report: Update on the management of patients with gastrointestinal stromal tumors","volume":"8","author":"Demetri","year":"2010","journal-title":"J. Natl. Comp. Cancer Netw."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1097\/PAS.0b013e3181a90e1a","article-title":"DOG1 antibody in the differential diagnosis of gastrointestinal stromal tumors: A study of 1840 cases","volume":"33","author":"Miettinen","year":"2009","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1002\/cncr.20862","article-title":"Gastrointestinal stromal tumors: The incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era\u2014A population-based study in western Sweden","volume":"103","author":"Nilsson","year":"2005","journal-title":"Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1158\/1055-9965.EPI-14-1002","article-title":"Epidemiology of gastrointestinal stromal tumors in the era of histology codes: Results of a population-based study","volume":"24","author":"Ma","year":"2015","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1097\/00000658-200001000-00008","article-title":"Two hundred gastrointestinal stromal tumors: Recurrence patterns and prognostic factors for survival","volume":"231","author":"DeMatteo","year":"2000","journal-title":"Ann. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1097\/01.pas.0000146010.92933.de","article-title":"Gastrointestinal stromal tumors of the stomach: A clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up","volume":"29","author":"Miettinen","year":"2005","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"86","DOI":"10.4253\/wjge.v3.i5.86","article-title":"Endoscopic ultrasonography for gastric submucosal lesions","volume":"3","author":"Papanikolaou","year":"2011","journal-title":"World J. Gastrointest. Endosc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1007\/s00330-016-4515-z","article-title":"Computed tomography features and predictive findings of ruptured gastrointestinal stromal tumors","volume":"27","author":"Kim","year":"2017","journal-title":"Eur. Radiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1200\/EDBK_351231","article-title":"The GIST of Advances in Treatment of Advanced Gastrointestinal Stromal Tumor","volume":"42","author":"Schaefer","year":"2022","journal-title":"Am. Soc. Clin. Oncol. Educ. Book."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1097\/00000478-200407000-00007","article-title":"KIT-negative gastrointestinal stromal tumors: Proof of concept and therapeutic implications","volume":"28","author":"Medeiros","year":"2004","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/modpathol.2015.56","article-title":"PDGFRA-mutant syndrome","volume":"28","author":"Ricci","year":"2015","journal-title":"Mod. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1053\/j.gastro.2010.05.083","article-title":"Kitlow stem cells cause resistance to Kit\/platelet-derived growth factor alpha inhibitors in murine gastrointestinal stromal tumors","volume":"139","author":"Bardsley","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4856","DOI":"10.1111\/jcmm.13748","article-title":"Telocytes are the physiological counterpart of inflammatory fibroid polyps and PDGFRA-mutant GISTs","volume":"22","author":"Ricci","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1097\/PAS.0b013e3182671178","article-title":"Immunohistochemical loss of succinate dehydrogenase subunit A (SDHA) in gastrointestinal stromal tumors (GISTs) signals SDHA germline mutation","volume":"37","author":"Miettinen","year":"2013","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1001\/jamaoncol.2016.0256","article-title":"Molecular Subtypes of KIT\/PDGFRA Wild-Type Gastrointestinal Stromal Tumors: A Report From the National Institutes of Health Gastrointestinal Stromal Tumor Clinic","volume":"2","author":"Boikos","year":"2016","journal-title":"JAMA Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1002\/path.5552","article-title":"A smooth muscle-derived, Braf-driven mouse model of gastrointestinal stromal tumor (GIST): Evidence for an alternative GIST cell-of-origin","volume":"252","author":"Kondo","year":"2020","journal-title":"J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"IJzerman, N.S., Drabbe, C., den Hollander, D., Mohammadi, M., van Boven, H., Desar, I.M.E., Gelderblom, H., Gr\u00fcnhagen, D.J., Reyners, A.K.L., and van Noesel, M.M. (2020). Gastrointestinal Stromal Tumours (GIST) in Young Adult (18\u201340 Years) Patients: A Report from the Dutch GIST Registry. Cancers, 12, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/32244864.","DOI":"10.3390\/cancers12030730"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"G\u00fcller, U., Tarantino, I., Cerny, T., Schmied, B.M., and Warschkow, R. (2015). Population-based SEER trend analysis of overall and cancer-specific survival in 5138 patients with gastrointestinal stromal tumor. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1554-9"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1002\/jso.23873","article-title":"Gastrointestinal stromal tumors (GISTs) at uncommon locations: A large population based analysis","volume":"111","author":"Kukar","year":"2015","journal-title":"J. Surg. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/ijc.21167","article-title":"Gastrointestinal stromal tumors in Iceland, 1990\u20132003: The icelandic GIST study, a population-based incidence, and pathologic risk stratification study","volume":"117","author":"Tryggvason","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_23","first-page":"49","article-title":"Revisiting a dogma: Similar survival of patients with small bowel and gastric GIST. A population-based propensity score SEER analysis","volume":"20","author":"Guller","year":"2017","journal-title":"Gastric Cancer Off. J. Int. Gastric Cancer Assoc. Jpn. Gastric Cancer Assoc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/jso.20230","article-title":"Gastric GI stromal tumors (GISTs): The role of surgery in the era of targeted therapy","volume":"90","author":"Heinrich","year":"2005","journal-title":"J. Surg. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1002\/jso.21892","article-title":"Surgical options for localized and advanced gastrointestinal stromal tumors","volume":"104","author":"Frankel","year":"2011","journal-title":"J. Surg. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ceccarelli, G., Costa, G., De Rosa, M., Codacci Pisanelli, M., Frezza, B., De Prizio, M., Bravi, I., Scacchi, A., Gallo, G., and Amato, B. (2021). Minimally Invasive Approach to Gastric GISTs: Analysis of a Multicenter Robotic and Laparoscopic Experience with Literature Review. Cancers, 13.","DOI":"10.3390\/cancers13174351"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2806","DOI":"10.3748\/wjg.v24.i26.2806","article-title":"Current clinical management of gastrointestinal stromal tumor","volume":"24","author":"Akahoshi","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Nishida, T., Yoshinaga, S., Takahashi, T., and Naito, Y. (2021). Recent Progress and Challenges in the Diagnosis and Treatment of Gastrointestinal Stromal Tumors. Cancers, 13.","DOI":"10.3390\/cancers13133158"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/annonc\/mdy095","article-title":"Gastrointestinal stromal tumors: ESMO-EURACAN Clinical Practice Guidelines diagnosis, treatment, and follow-up","volume":"29","author":"Casali","year":"2018","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"466","DOI":"10.21037\/jgo.2016.09.15","article-title":"Gastrointestinal stromal tumors (GISTs): Point mutations matter in management, a review","volume":"8","author":"Oppelt","year":"2017","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1097\/PAS.0b013e3182986b88","article-title":"Gastrointestinal stromal tumors with KIT exon 9 mutations: Update on genotype-phenotype correlation and validation of a high-resolution melting assay for mutational testing","volume":"37","author":"Huss","year":"2013","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/modpathol.2008.2","article-title":"Clinicopathologic profile of gastrointestinal stromal tumors (GISTs) with primary KIT exon 13 or exon 17 mutations: A multicenter study on 54 cases","volume":"21","author":"Lasota","year":"2008","journal-title":"Mod. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"144","DOI":"10.21037\/jgo.2018.08.20","article-title":"Gastrointestinal stromal tumors: A comprehensive review","volume":"10","author":"Parab","year":"2019","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/S1470-2045(20)30168-6","article-title":"Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): A double-blind, randomized, placebo-controlled, phase 3 trial","volume":"21","author":"Blay","year":"2020","journal-title":"Lancet Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/15\/3689\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:58:33Z","timestamp":1760140713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/15\/3689"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,28]]},"references-count":34,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["cancers14153689"],"URL":"https:\/\/doi.org\/10.3390\/cancers14153689","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,28]]}}}