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ASTROINTESTINAL STROMAL tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Gastrointestinal stromal tumors are usually found in the stomach or the small intestine but can occur at any site along the gastrointestinal tract and rarely elsewhere within the abdominal cavity. 1 The median age at presentation is 60 to 65 years, and the annual incidence approximately 10 cases per million. 2-4 Most GISTs (75% to 80%) harbor an activating mutation in the KIT oncogene and 5% to 10% in platelet-derived growth factor receptor-␣ (PDGFRA), which are important for tumor molecular pathogenesis. 5 The ma-For editorial comment see p 1312.

Gastrointestinal stromal tumors (GIST) are characterized by a strong KIT receptor activation most often resulting from KIT mutations. In a smaller subgroup of tumors without KIT mutations, analogous activating mutations are found in the platelet-derived growth factor receptor a (PDGFRa) gene. Both PDGFRa and KIT receptors are targets of the tyrosine kinase inhibitor imatinib (Glivec) which has improved the treatment of advanced GISTs significantly. However, a subgroup of tumors show a secondary progress under therapy with imatinib after initial response. One possible mechanism of secondary resistance is the development of newly acquired KIT mutations. In the present study, we evaluated the frequency of such secondary KIT mutations in a series of GIST patients in which tumor tissue was resected under treatment. We examined one to seven different tumor areas in 32 cases (total of 104 samples) and found up to four newly acquired KIT mutations in 14 patients (43.8%). These were always located in exons encoding the first or second tyrosine kinase domain (exon 13, 14, or 17). Mutations were found only in a subset of samples analyzed from each case whereas others retained the wild-type sequence in the same region. There was never more than one new mutation in the same sample. Consistent with a secondary clonal evolution, the primary mutation was always detectable in all samples from each tumor. According to our results, the identification of newly acquired KIT mutations in addition to the primary mutation is dependent on the number of tissue samples analyzed and has high implications for further therapeutic strategies.

Three years of adjuvant imatinib therapy results in longer survival than 1 year of imatinib. High 5-year survival rates are achievable in patient populations with high-risk GIST.

clinicaltrials.gov Identifier: NCT00116935.

No abstract

Patients with a rupture of GIST into the abdominal cavity have a risk of recurrence of nearly 100 per cent. In patients with deletion mutations involving codons 557-558, recurrence-free survival was less than 1 year. All patient groups are clear candidates for adjuvant drug therapy.

Purpose: To determine if diffusion-weighted imaging (DWI) can be used as a surrogate marker of tumor response to anticancer therapy in patients with soft-tissue sarcomas. Materials and Methods:Magnetic resonance imaging (MRI) including echo-planar DWI sequences was performed prospectively in 23 consecutive patients with soft-tissue sarcomas before and after initiation of regional or systemic chemotherapy. The mean interval between initial and follow-up MRI was 56.9 Ϯ 23.2 days. Tumor volumes were determined by manual segmentation of tumor borders on contrast-enhanced T1-weighted images. The apparent diffusion coefficient (ADC) was calculated from corresponding sections of ADC maps on initial and follow-up DWI. Subsequently, changes in tumor volumes and ADC were correlated using the Pearson correlation coefficient.Results: A high degree of correlation was found when changes in tumor volumes and ADC values were compared (r ϭ Ϫ0.925, P Ͻ 0.0001), regardless of the effectiveness of anticancer therapy expressed as changes of tumor volume.Conclusion: DWI can be used as a supplement to morphologic imaging for the evaluation of tumor response to anticancer therapy in patients with soft-tissue sarcomas. As cellular changes are expected to precede morphologic changes in treated tumors, DWI performed at an early stage of fractionated therapy may provide unique prognostic information of its effectiveness.