Predictive factors for long-term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs).

Department of Soft Tissue/Bone Sarcoma and Melanoma, M. Sklodowska-Curie Memorial Cancer Center, Institute of Oncology, Warsaw, Poland. rutkowskip@coi.waw.pl

Journal of cancer research and clinical oncology 2007 Sep

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To analyze the outcomes of treatment and factors predicting effects of imatinib (IM) therapy in inoperable/metastatic gastrointestinal stromal tumors (GIST) CD117(+) patients. We identified 232 patients in a prospectively collected Clinical GIST Registry with advanced inoperable/metastatic GIST treated with IM 400-800 mg daily (129 males and 103 females and median age 56 years). Median follow-up time was 26 months. The estimated 3-year progression-free survival (PFS; calculated from the date of the start of IM) was 54% and median PFS was 40.5 months. The following factors significantly and negatively influenced PFS in univariate analysis: poor baseline World Health Organization (WHO) performance status > or = 2 (P < 0.00001), tumor genotype indicating other than KIT exon 11 isoform (P = 0.005), baseline high neutrophils count (P < 0.00001), age <45 years at the diagnosis (P = 0.04), mitotic index >10/50 high-power fields (HPF) (P = 0.001), GIST histological type other than spindle-cell (P = 0.03), baseline low albumin level (P = 0.0005), low baseline hemoglobin level (P < 0.00001), and primary overtly malignant tumors (unresectable and/or metastatic lesions at presentation) (P = 0.05). We identified four factors negatively affecting PFS, statistically significant (P < 0.05) in multivariate analysis: baseline poor WHO performance status > or = 2, high baseline neutrophils count (>5 x 10(9)/l), tumor genotype indicating the presence of non-exon 11 KIT mutant and mitotic index >10/50 HPF. We confirmed that many advanced GIST patients benefit from IM therapy for a prolonged time, although resistance to therapy is observed. We identified four independent biological factors influencing the PFS during long-term IM therapy.

Citation

Piotr Rutkowski, Zbigniew I Nowecki, Maria Debiec-Rychter, Urszula Grzesiakowska, Wanda Michej, Agnieszka Woźniak, Janusz A Siedlecki, Janusz Limon, Anna Jerzak vel Dobosz, Michał Kakol, Czesław Osuch, Włodzimierz Ruka. Predictive factors for long-term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs). Journal of cancer research and clinical oncology. 2007 Sep;133(9):589-97