The criteria of aggressiveness and other prognostic factors for predicting relapses of primary tumors and imatinib (IM) treatment outcomes in advanced KIT immunopositive gastrointestinal stromal tumors (GIST): A report of the Polish Clinical GIST Registry (PCGR)

Abstract

9544 Background: The development of adjuvant treatment trials with imatinib in GIST has raised the debate about the accuracy of NIH risk criteria consensus and about the significance of other prognostic factors. Methods: We analyzed the criteria of aggressiveness and other clinico-pathological and genetic factors influencing disease-free survival (DFS) in patients with primary CD117-positive tumors (group I: 274 patients; median follow-up 29 months; calculated from primary tumor resection) and progression-free survival (PFS) in metastatic/unresectable GIST patients treated with IM (group II: 179 patients; median follow-up 19 months; calculated from the start of imatinib therapy) enrolled into PCGR. Results: In group I statistically significant (p<0.05) factors negatively influencing DFS both in univariate (log-rank test) and multivariate (Cox’s model) analysis were: primary tumor size > 5 cm, mitotic index > 5/50HPF, male gender, primary tumor R1 resection or tumor rupture, non-gastric primary tumor localization and intermediate/high risk group (3-year DFS for high, intermediate and low/very low risk group was: 28%, 75% and 99%, respectively). In group II we identified 5 factors negatively affecting PFS statistically significant both in univariate and multivariate analyses (p<0.05): tumor genotype indicating other than exon 11 KIT mutation, mitotic index > 10/50HPF, age below 45 years at diagnosis, high baseline pre-IM granulocyte count and poor WHO performance status ≥ 2. Conclusions: We validated the value of criteria of risk groups for the assessment of the natural course of primary GIST, but we also identified additional independent prognostic factors. For the prediction of PFS during IM therapy for advanced GIST we detected 5 different, independent biological and pathological factors. No significant financial relationships to disclose.