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

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Abstract

The purpose

To analyze the outcomes of treatment and factors predicting effects of imatinib (IM) therapy in inoperable/metastatic gastrointestinal stromal tumors (GIST) CD117(+) patients.

Materials and methods

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.

Results

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 ≥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 ≥2, high baseline neutrophils count (>5 × 109/l), tumor genotype indicating the presence of non-exon 11 KIT mutant and mitotic index >10/50 HPF.

Conclusions

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.

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Acknowledgments

We thank all specialists devoted to GIST problem participating in Clinical GIST Registry; M. Rosinska, MD for statistical advice and J. Lasota, MD from Armed Forces Institute of Pathology, Washington, DC., for mutational analysis of the subset of tumors.

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Authors and Affiliations

  1. Department of Soft Tissue/Bone Sarcoma and Melanoma, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland

    Piotr Rutkowski, Zbigniew I. Nowecki & Włodzimierz Ruka

  2. Center for Human Genetics, University of Leuven, Leuven, 3000, Belgium

    Maria Dębiec-Rychter

  3. Department of Radiology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781, Warsaw, Poland

    Urszula Grzesiakowska

  4. Department of Pathology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781, Warsaw, Poland

    Wanda Michej

  5. Department of Biology and Genetics, Medical University of Gdansk, Gdansk, Poland

    Agnieszka Woźniak & Janusz Limon

  6. Department of Molecular Biology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781, Warsaw, Poland

    Janusz A. Siedlecki & Anna Jerzak vel Dobosz

  7. Regional Oncological Center, Gdansk, Poland

    Michał Kąkol

  8. Department of General Surgery, Jagiellonian University, Cracow, Poland

    Czesław Osuch

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  1. Piotr Rutkowski
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  9. Anna Jerzak vel Dobosz
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  12. Włodzimierz Ruka
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Correspondence to Piotr Rutkowski.

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Rutkowski, P., Nowecki, Z.I., Dębiec-Rychter, M. et al. Predictive factors for long-term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs). J Cancer Res Clin Oncol 133, 589–597 (2007). https://doi.org/10.1007/s00432-007-0202-4

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