A post hoc observational study from the phase III EORTC 62024 trial of adjuvant imatinib in patients with localized gastrointestinal stromal tumors (GIST) showed that improvement in survival with R0 vs R1 resection was no longer evident when tumor rupture was excluded from the R1 category. The study was reported in JAMA Surgery by Alessandro Gronchi, MD, and colleagues.
“The difference in overall survival 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 overall survival.”— Alessandro Gronchi, MD
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Study Details
In the intergroup trial, performed between December 2004 and October 2008 at sites in 12 countries, 908 patients were randomly assigned after surgery to receive imatinib at 400 mg/d for 2 years (n = 454) or no adjuvant treatment (n = 454). Stratification factors included R0 and R1 resection, with tumor rupture included in the R1 category.
Patients had to have primary GIST with intermediate or high risk of relapse, no evidence of residual disease after surgery, and no prior malignancies or concurrent severe/uncontrolled medical conditions. The primary outcome measure for the current analysis was overall survival.
Key Findings
Median follow-up was 9.1 years. Overall, 743 patients (81.1%) underwent R0 resection (375 in the imatinib group and 368 in the observation group and 162 (17.8%) underwent R1 resection (77 and 85 patients). Of those with R1 resection, 97 (59.9%) had a tumor rupture.
Ten-year overall survival was 64.4% among patients with R1 resection vs 82.6% among patients with R0 resection. R1 resection was associated with poorer overall survival among all patients (hazard ratio [HR] = 2.05, 95% confidence interval [CI] =1.45–2.89) and in both the imatinib group (HR = 2.65, 95% CI = 1.37–3.75) and the observation group (HR = 1.86, 95% CI = 1.16–2.99).
When tumor rupture was excluded from the R1 category, there was no significant difference in overall survival for R1 vs R0 resection (HR = 1.05, 95% CI = 0.54–2.01).
R1 resection was also associated with significantly poorer relapse-free survival overall (HR = 1.98, 95% CI = 1.55–2.53) and in both the imatinib group (HR = 2.32, 95% CI = 1.64–3.30) and observation group (HR = 1.81, 95% CI = 1.29–2.54). With the exclusion of tumor rupture, the difference was no longer significant (HR = 1.35, 95% CI = 0.91–1.99).
The investigators concluded, “The difference in overall survival 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 overall survival.”
Dr. Gronchi, of the Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, is the corresponding author for the JAMA Surgery article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
