title: Surgical Management of Wild-Type Gastrointestinal Stromal Tumors: A Report From the National Institutes of Health Pediatric and Wildtype GIST Clinic.
abstract: Purpose Wild-type gastrointestinal stromal tumors (WT-GISTs) that lack KIT or PDGFRA mutations represent a unique subtype of GIST that predominantly affects children. We sought to determine the effect on event-free survival (EFS) of staging variables, extent of resection, and repeat resection of tumors. Methods In 2008, a WT-GIST clinic was established at the National Cancer Institute, allowing the development of a large clinical database. We included participants who underwent resection of WT-GIST. Associations with EFS (ie, freedom from disease progression or recurrence) were evaluated using the Kaplan-Meier method and Cox proportional hazards modeling. Results Among 76 participants with WT-GISTs, the median follow-up was 4.1 years. Overall EFS (± SE) was 72.6 ± 5.4% at 1 year, 57.6 ± 6.2% at 2 years, 23.7 ± 6.0% at 5 years, and 16.3 ± 5.5% at 10 years postoperatively. Hazard of disease progression or recurrence was significantly increased for patients with metastatic disease (adjusted hazard ratio [AHR], 2.3; 95% CI, 1.0 to 5.1; P = .04) and > 5 mitoses per 50 high-power fields (AHR, 2.5; 95% CI, 1.1 to 6.0; P = .03), whereas there was no significant effect of negative microscopic resection margins (AHR, 0.9; 95% CI, 0.4 to 2.2; P = 0.86). There was no association between type of gastric resection (ie, anatomic v partial/wedge) and EFS ( P = .67). Repeated resection after the initial resection was significantly associated with decreasing postoperative EFS ( P < .01). Five patients (6%) died after initial enrollment in 2008. Conclusion WT-GIST is an indolent disease, and most patients survive with disease progression. We found no improvement in EFS with more extensive or serial resections. Disease progression or recurrence may be more closely related to tumor biology than surgical management. These data suggest that resections for WT-GISTs be restricted to the initial procedure and that subsequent resections be performed only to address symptoms such as obstruction or bleeding.
authors.affiliation: Christopher B. Weldon and Arin L. Madenci, Boston Children's Hospital; Christopher B. Weldon, Arin L. Madenci, Katherine A. Janeway, and Suzanne George, Harvard Medical School; Christopher B. Weldon, Katherine A. Janeway, and Suzanne George, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Sosipatros A. Boikos, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Margaret von Mehren, Fox Chase Cancer Center, Philadelphia, PA; Alberto S. Pappo, St Jude Children's Research Hospital, Memphis, TN; Joshua D. Schiffman and Jennifer Wright, Huntsman Cancer Institute, Salt Lake City, UT; Jonathan C. Trent, Sylvester Comprehensive Cancer Center, Miami, FL; Karel Pacak and Constantine A. Stratakis, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Lee J. Helman, National Cancer Institute, Bethesda, MD; and Michael P. La Quaglia, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Weldon
authors.affiliation: Christopher B. Weldon and Arin L. Madenci, Boston Children's Hospital; Christopher B. Weldon, Arin L. Madenci, Katherine A. Janeway, and Suzanne George, Harvard Medical School; Christopher B. Weldon, Katherine A. Janeway, and Suzanne George, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Sosipatros A. Boikos, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Margaret von Mehren, Fox Chase Cancer Center, Philadelphia, PA; Alberto S. Pappo, St Jude Children's Research Hospital, Memphis, TN; Joshua D. Schiffman and Jennifer Wright, Huntsman Cancer Institute, Salt Lake City, UT; Jonathan C. Trent, Sylvester Comprehensive Cancer Center, Miami, FL; Karel Pacak and Constantine A. Stratakis, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Lee J. Helman, National Cancer Institute, Bethesda, MD; and Michael P. La Quaglia, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Arin L
authors.initials: AL
authors.lastname: Madenci
authors.affiliation: Christopher B. Weldon and Arin L. Madenci, Boston Children's Hospital; Christopher B. Weldon, Arin L. Madenci, Katherine A. Janeway, and Suzanne George, Harvard Medical School; Christopher B. Weldon, Katherine A. Janeway, and Suzanne George, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Sosipatros A. Boikos, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Margaret von Mehren, Fox Chase Cancer Center, Philadelphia, PA; Alberto S. Pappo, St Jude Children's Research Hospital, Memphis, TN; Joshua D. Schiffman and Jennifer Wright, Huntsman Cancer Institute, Salt Lake City, UT; Jonathan C. Trent, Sylvester Comprehensive Cancer Center, Miami, FL; Karel Pacak and Constantine A. Stratakis, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Lee J. Helman, National Cancer Institute, Bethesda, MD; and Michael P. La Quaglia, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Sosipatros A
authors.initials: SA
authors.lastname: Boikos
authors.affiliation: Christopher B. Weldon and Arin L. Madenci, Boston Children's Hospital; Christopher B. Weldon, Arin L. Madenci, Katherine A. Janeway, and Suzanne George, Harvard Medical School; Christopher B. Weldon, Katherine A. Janeway, and Suzanne George, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Sosipatros A. Boikos, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Margaret von Mehren, Fox Chase Cancer Center, Philadelphia, PA; Alberto S. Pappo, St Jude Children's Research Hospital, Memphis, TN; Joshua D. Schiffman and Jennifer Wright, Huntsman Cancer Institute, Salt Lake City, UT; Jonathan C. Trent, Sylvester Comprehensive Cancer Center, Miami, FL; Karel Pacak and Constantine A. Stratakis, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Lee J. Helman, National Cancer Institute, Bethesda, MD; and Michael P. La Quaglia, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Janeway
authors.affiliation: Christopher B. Weldon and Arin L. Madenci, Boston Children's Hospital; Christopher B. Weldon, Arin L. Madenci, Katherine A. Janeway, and Suzanne George, Harvard Medical School; Christopher B. Weldon, Katherine A. Janeway, and Suzanne George, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Sosipatros A. Boikos, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Margaret von Mehren, Fox Chase Cancer Center, Philadelphia, PA; Alberto S. Pappo, St Jude Children's Research Hospital, Memphis, TN; Joshua D. Schiffman and Jennifer Wright, Huntsman Cancer Institute, Salt Lake City, UT; Jonathan C. Trent, Sylvester Comprehensive Cancer Center, Miami, FL; Karel Pacak and Constantine A. Stratakis, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Lee J. Helman, National Cancer Institute, Bethesda, MD; and Michael P. La Quaglia, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Suzanne
authors.initials: S
authors.lastname: George
authors.affiliation: Christopher B. Weldon and Arin L. Madenci, Boston Children's Hospital; Christopher B. Weldon, Arin L. Madenci, Katherine A. Janeway, and Suzanne George, Harvard Medical School; Christopher B. Weldon, Katherine A. Janeway, and Suzanne George, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Sosipatros A. Boikos, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Margaret von Mehren, Fox Chase Cancer Center, Philadelphia, PA; Alberto S. Pappo, St Jude Children's Research Hospital, Memphis, TN; Joshua D. Schiffman and Jennifer Wright, Huntsman Cancer Institute, Salt Lake City, UT; Jonathan C. Trent, Sylvester Comprehensive Cancer Center, Miami, FL; Karel Pacak and Constantine A. Stratakis, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Lee J. Helman, National Cancer Institute, Bethesda, MD; and Michael P. La Quaglia, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Margaret
authors.initials: M
authors.lastname: von Mehren
authors.affiliation: Christopher B. Weldon and Arin L. Madenci, Boston Children's Hospital; Christopher B. Weldon, Arin L. Madenci, Katherine A. Janeway, and Suzanne George, Harvard Medical School; Christopher B. Weldon, Katherine A. Janeway, and Suzanne George, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Sosipatros A. Boikos, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Margaret von Mehren, Fox Chase Cancer Center, Philadelphia, PA; Alberto S. Pappo, St Jude Children's Research Hospital, Memphis, TN; Joshua D. Schiffman and Jennifer Wright, Huntsman Cancer Institute, Salt Lake City, UT; Jonathan C. Trent, Sylvester Comprehensive Cancer Center, Miami, FL; Karel Pacak and Constantine A. Stratakis, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Lee J. Helman, National Cancer Institute, Bethesda, MD; and Michael P. La Quaglia, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Alberto S
authors.initials: AS
authors.lastname: Pappo
authors.affiliation: Christopher B. Weldon and Arin L. Madenci, Boston Children's Hospital; Christopher B. Weldon, Arin L. Madenci, Katherine A. Janeway, and Suzanne George, Harvard Medical School; Christopher B. Weldon, Katherine A. Janeway, and Suzanne George, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Sosipatros A. Boikos, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Margaret von Mehren, Fox Chase Cancer Center, Philadelphia, PA; Alberto S. Pappo, St Jude Children's Research Hospital, Memphis, TN; Joshua D. Schiffman and Jennifer Wright, Huntsman Cancer Institute, Salt Lake City, UT; Jonathan C. Trent, Sylvester Comprehensive Cancer Center, Miami, FL; Karel Pacak and Constantine A. Stratakis, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Lee J. Helman, National Cancer Institute, Bethesda, MD; and Michael P. La Quaglia, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Schiffman
authors.affiliation: Christopher B. Weldon and Arin L. Madenci, Boston Children's Hospital; Christopher B. Weldon, Arin L. Madenci, Katherine A. Janeway, and Suzanne George, Harvard Medical School; Christopher B. Weldon, Katherine A. Janeway, and Suzanne George, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Sosipatros A. Boikos, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Margaret von Mehren, Fox Chase Cancer Center, Philadelphia, PA; Alberto S. Pappo, St Jude Children's Research Hospital, Memphis, TN; Joshua D. Schiffman and Jennifer Wright, Huntsman Cancer Institute, Salt Lake City, UT; Jonathan C. Trent, Sylvester Comprehensive Cancer Center, Miami, FL; Karel Pacak and Constantine A. Stratakis, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Lee J. Helman, National Cancer Institute, Bethesda, MD; and Michael P. La Quaglia, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wright
authors.affiliation: Christopher B. Weldon and Arin L. Madenci, Boston Children's Hospital; Christopher B. Weldon, Arin L. Madenci, Katherine A. Janeway, and Suzanne George, Harvard Medical School; Christopher B. Weldon, Katherine A. Janeway, and Suzanne George, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Sosipatros A. Boikos, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Margaret von Mehren, Fox Chase Cancer Center, Philadelphia, PA; Alberto S. Pappo, St Jude Children's Research Hospital, Memphis, TN; Joshua D. Schiffman and Jennifer Wright, Huntsman Cancer Institute, Salt Lake City, UT; Jonathan C. Trent, Sylvester Comprehensive Cancer Center, Miami, FL; Karel Pacak and Constantine A. Stratakis, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Lee J. Helman, National Cancer Institute, Bethesda, MD; and Michael P. La Quaglia, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Trent
authors.affiliation: Christopher B. Weldon and Arin L. Madenci, Boston Children's Hospital; Christopher B. Weldon, Arin L. Madenci, Katherine A. Janeway, and Suzanne George, Harvard Medical School; Christopher B. Weldon, Katherine A. Janeway, and Suzanne George, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Sosipatros A. Boikos, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Margaret von Mehren, Fox Chase Cancer Center, Philadelphia, PA; Alberto S. Pappo, St Jude Children's Research Hospital, Memphis, TN; Joshua D. Schiffman and Jennifer Wright, Huntsman Cancer Institute, Salt Lake City, UT; Jonathan C. Trent, Sylvester Comprehensive Cancer Center, Miami, FL; Karel Pacak and Constantine A. Stratakis, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Lee J. Helman, National Cancer Institute, Bethesda, MD; and Michael P. La Quaglia, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
authors.affiliation: Christopher B. Weldon and Arin L. Madenci, Boston Children's Hospital; Christopher B. Weldon, Arin L. Madenci, Katherine A. Janeway, and Suzanne George, Harvard Medical School; Christopher B. Weldon, Katherine A. Janeway, and Suzanne George, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Sosipatros A. Boikos, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Margaret von Mehren, Fox Chase Cancer Center, Philadelphia, PA; Alberto S. Pappo, St Jude Children's Research Hospital, Memphis, TN; Joshua D. Schiffman and Jennifer Wright, Huntsman Cancer Institute, Salt Lake City, UT; Jonathan C. Trent, Sylvester Comprehensive Cancer Center, Miami, FL; Karel Pacak and Constantine A. Stratakis, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Lee J. Helman, National Cancer Institute, Bethesda, MD; and Michael P. La Quaglia, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
authors.affiliation: Christopher B. Weldon and Arin L. Madenci, Boston Children's Hospital; Christopher B. Weldon, Arin L. Madenci, Katherine A. Janeway, and Suzanne George, Harvard Medical School; Christopher B. Weldon, Katherine A. Janeway, and Suzanne George, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Sosipatros A. Boikos, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Margaret von Mehren, Fox Chase Cancer Center, Philadelphia, PA; Alberto S. Pappo, St Jude Children's Research Hospital, Memphis, TN; Joshua D. Schiffman and Jennifer Wright, Huntsman Cancer Institute, Salt Lake City, UT; Jonathan C. Trent, Sylvester Comprehensive Cancer Center, Miami, FL; Karel Pacak and Constantine A. Stratakis, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Lee J. Helman, National Cancer Institute, Bethesda, MD; and Michael P. La Quaglia, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Helman
authors.affiliation: Christopher B. Weldon and Arin L. Madenci, Boston Children's Hospital; Christopher B. Weldon, Arin L. Madenci, Katherine A. Janeway, and Suzanne George, Harvard Medical School; Christopher B. Weldon, Katherine A. Janeway, and Suzanne George, Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Sosipatros A. Boikos, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Margaret von Mehren, Fox Chase Cancer Center, Philadelphia, PA; Alberto S. Pappo, St Jude Children's Research Hospital, Memphis, TN; Joshua D. Schiffman and Jennifer Wright, Huntsman Cancer Institute, Salt Lake City, UT; Jonathan C. Trent, Sylvester Comprehensive Cancer Center, Miami, FL; Karel Pacak and Constantine A. Stratakis, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Lee J. Helman, National Cancer Institute, Bethesda, MD; and Michael P. La Quaglia, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Michael P
authors.initials: MP
authors.lastname: La Quaglia
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D018450:Disease Progression; D005260:Female; D005743:Gastrectomy / Q000379:methods*; D005770:Gastrointestinal Neoplasms / Q000235:genetics / Q000601:surgery*; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000601:surgery*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009154:Mutation; D009316:National Institutes of Health (U.S.); D009364:Neoplasm Recurrence, Local; D017063:Outcome Assessment, Health Care / Q000379:methods* / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D014481:United States; D055815:Young Adult
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha