Different factors are responsible for predicting relapses after primary tumors resection and for imatinib treatment outcomes in gastrointestinal stromal tumors
Piotr Rutkowski, Maria Debiec-Rychter, Zbigniew I Nowecki, Agnieszka Wozniak, Wanda Michej, Janusz Limon, Janusz A Siedlecki, Anna Jerzak vel Dobosz, Urszula Grzesiakowska, Anna Nasierowska-Guttmejer, Jacek Sygut, Pawel Nyckowski, Marek Krawczyk, Włodzimierz Ruka
Med Sci Monit 2007; 13(11): CR515-522
Background: The development of accurate diagnostic methods in gastrointestinal stromal tumors (GISTs) and the introduction of imatinib (IM) therapy has focused attention on the factors influencing the prognosis of patients with primary lesions as well as of patients with advanced disease treated with imatinib.
Material/Methods: The clinico-pathological and genetic factors influencing disease-free survival (DFS) in 335 patients with primary CD117-immunopositive tumors (group A; calculated from primary tumor resection) and progression-free survival (PFS) in 232 metastatic/unresectable GIST patients treated with IM (group B; calculated from the start of imatinib therapy) were analyzed.
Results: In group A, statistically significant factors negatively influencing DFS(five-year DFS: 38%), both in univariate and multivariate analysis, were: primary tumor size >5 cm, mitotic index >5/50 HPF (high-power fields), male gender, primary tumor R1 resection or tumor rupture, non-gastric primary tumor localization. In group B, five factors negatively affecting PFS (three-year PFS: 54%) were identified, which were statistically significant both in univariate and multivariate analyses: WHO performance status ≥2, tumor genotype indicating other than exon 11 KIT mutation, high baseline pre-IM granulocyte count, mitotic index >10/50 HPF, and age <45 years at diagnosis.
Conclusions: Different sets of independent biological and pathological prognostic factors were identified for the assessment of the natural course of primary GIST and for the prediction of PFS during IM therapy for advanced GIST.
Keywords: Receptor, Platelet-Derived Growth Factor alpha - genetics, Pyrimidines - therapeutic use, Proto-Oncogene Proteins c-kit - genetics, Prospective Studies, Prognosis, Piperazines - therapeutic use, Mutation, Multivariate Analysis, Adult, Gastrointestinal Stromal Tumors - surgery, Disease-Free Survival, Child, Benzamides, Antineoplastic Agents - therapeutic use, Aged, 80 and over, Adolescent