Multidisciplinary approach in diagnosis and treatment of gastrointestinal stromal tumors.

Abstract

Gastrointestinal stromal tumors (GIST) constitute from 0.1% to 3% of all malignant neoplasms of the gastrointestinal tract. Immunohistochemistry plays a key role in the differential diagnosis of GIST and other mesenchymal tumors. The main immunohistochemical marker for GIST is the CD117 (c-Kit), which hyperexpression observed in 95% tumors. When planning treatment of GIST a multidisciplinary approach involving surgeon-oncologist, pathologist, oncologist and radiologist-chemotherapist is required. Surgical treatment remains the main method of treatment in the absence of dissemination of the disease. Tumor size, mitotic index, location of tumor and mutation status of tumor affect on the prognosis of disease progression. Imatinib is a small molecule inhibitor of tyrosine kinase c-Kit, PDGFR, Abl, Bcr-Abl and the main drug in treatment of metastatic GIST. Imatinib is applied in a dose of 400 mg/day, and allows to achieve a clinical improvement (partial response + stabilization) in 90% of patients. Using of imatinib in adjuvant therapy during first year after the operation significantly increases progression-free survival up to 98%. High-risk patients need adjuvant treatment with imatinib for 3 years after the operation according to the ESMO 2012 recommendations. Neoadjuvant therapy with imatinib leads to a reduction of the tumor mass, increase resectability and frequency of performing organ-preserving operations. In case of progression of GIST during therapy with imatinib the last dose may be doubled or a second-line treatment with sunitinib (tyrosine kinase inhibitor of VEGFR, PDGFR, KIT, Flt3) can be used. Sunitinib is applied in a dose of 50 mg/day for 4 weeks daily with an interval of 2 weeks. Treatment with sunitinib allowed to achieve clinical improvement in 24.2% of imatninib-resistant patients. It is necessary to take into account not only the size but also the density and structure of the tumor when performing radiological assessment of response of the tumor to therapy. Currently, the phase II clinical studies are conducted with the aim to investigate the new targeted therapies for the treatment of GIST.