Quality of Surgery and Outcome in Localized Gastrointestinal Stromal Tumors Treated Within an International Intergroup Randomized Clinical Trial of Adjuvant Imatinib

IMPORTANCE: The association between quality of surgery and overall survival in patients affected by localized gastrointestinal stromal tumors (GIST) is not completely understood. OBJECTIVE: To assess the risk of death with and without imatinib according to microscopic margins status (R0/R1) using da...

Full description

Saved in:
Bibliographic Details
Published inJAMA surgery Vol. 155; no. 6; p. e200397
Main Authors Gronchi, Alessandro, Bonvalot, Sylvie, Poveda Velasco, Andres, Kotasek, Dusan, Rutkowski, Piotr, Hohenberger, Peter, Fumagalli, Elena, Judson, Ian R, Italiano, Antoine, Gelderblom, Hans J, van Coevorden, Frits, Penel, Nicolas, Kopp, Hans-Georg, Duffaud, Florence, Goldstein, David, Broto, Javier Martin, Wardelmann, Eva, Marréaud, Sandrine, Smithers, Mark, Le Cesne, Axel, Zaffaroni, Facundo, Litière, Saskia, Blay, Jean-Yves, Casali, Paolo G
Format Journal Article
LanguageEnglish
Published United States American Medical Association 01.06.2020
SeriesJAMA SURGERY
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:IMPORTANCE: The association between quality of surgery and overall survival in patients affected by localized gastrointestinal stromal tumors (GIST) is not completely understood. OBJECTIVE: To assess the risk of death with and without imatinib according to microscopic margins status (R0/R1) using data from a randomized study on adjuvant imatinib. DESIGN, SETTING, AND PARTICIPANTS: This is a post hoc observational study on patients included in the randomized, open-label, phase III trial, performed between December 2004 and October 2008. Median follow-up was 9.1 years (IQR, 8-10 years). The study was performed at 112 hospitals in 12 countries. Inclusion criteria were diagnosis of primary GIST, with intermediate or high risk of relapse; no evidence of residual disease after surgery; older than 18 years; and no prior malignancies or concurrent severe/uncontrolled medical conditions. Data were analyzed between July 17, 2017, and March 1, 2020. INTERVENTIONS: Patients were randomized after surgery to either receive imatinib (400 mg/d) for 2 years or no adjuvant treatment. Randomization was stratified by center, risk category (high vs intermediate), tumor site (gastric vs other), and quality of surgery (R0 vs R1). Tumor rupture was included in the R1 category but also analyzed separately. MAIN OUTCOMES AND MEASURES: Primary end point of this substudy was overall survival (OS), estimated using Kaplan-Meier method and compared between R0/R1 using Cox models adjusted for treatment and stratification factors. RESULTS: A total of 908 patients were included; 51.4% were men (465) and 48.6% were women (440), and the median age was 59 years (range, 18-89 years). One hundred sixty-two (17.8%) had an R1 resection, and 97 of 162 (59.9%) had tumor rupture. There was a significant difference in OS for patients undergoing an R1 vs R0 resection, overall (hazard ratio [HR], 2.05; 95% CI, 1.45-2.89) and by treatment arm (HR, 2.65; 95% CI, 1.37-3.75 with adjuvant imatinib and HR, 1.86; 95% CI, 1.16-2.99 without adjuvant imatinib). When tumor rupture was excluded, this difference in OS between R1 and R0 resections disappeared (HR, 1.05; 95% CI, 0.54-2.01). CONCLUSIONS AND RELEVANCE: The difference in OS by quality of surgery with or without imatinib was associated with the presence of tumor rupture. When the latter was excluded, the presence of R1 margins was not associated with worse OS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00103168
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ObjectType-Undefined-3
ObjectType-News-4
ISSN:2168-6254
2168-6262
DOI:10.1001/jamasurg.2020.0397