Kinase Mutations and Imatinib Mesylate Response for 64 Taiwanese with Advanced GIST: Preliminary Experience from Chang Gung Memorial Hospital

Yeh, Chun‐Nan; Chen, Tsung-Wen; Lee, Hsiang-Lin; Liu, Yuyin; Chao, Tzu‐Chieh; Hwang, Tsann‐Long; Jan, Yi-Yin; Chen, Miin‐Fu

doi:10.1245/s10434-006-9288-1

Cited by 30 publications

(25 citation statements)

References 21 publications

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“…However, we did not find any differences in clinical outcome according to which codon of KIT exon 11 had undergone mutation. Consistent with our findings, a small study in Taiwanese patients found that clinical outcome to imatinib did not differ according to kinase mutational status [20]. The mutation rate for KIT in 54 Taiwanese GIST patients was 90.7%, and included 40 patients with KIT exon 11 mutations and nine patients with KIT exon 9 mutations.…”

Section: Discussionsupporting

confidence: 89%

“…The higher relative dose of imatinib given to the Korean patients (using a fixed-dose strategy) could in part explain responses in these mutation-negative patients. The responses seen in Taiwanese patients are more similar to the results of the present study than to those of prior studies in western populations [13,14,20]. To confirm this hypothesis, a comparison of pharmacokinetic parameters between Asian and western GIST patients is needed.…”

Section: Discussionsupporting

confidence: 85%

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Kinase Mutations and Efficacy of Imatinib in Korean Patients with Advanced Gastrointestinal Stromal Tumors

et al. 2009

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Purpose. This study analyzed the relationship between treatment outcome and kinase mutational status in Korean patients with advanced gastrointestinal stromal tumors (GISTs).Experimental Design. Clinical data were collected from 113 consecutive patients with metastatic or unresectable GISTs treated with imatinib from June 2001 through June 2005 at five institutions in Korea. KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were examined.Results. The median patient age was 57 years (range, 31-82 years). The overall response rate was 67.2%. KIT mutations were found in exon 11 (n ‫؍‬ 92, 81.4%) and exon 9 (n ‫؍‬ 10, 8.8%). One patient had a PDGFRA exon 18 mutation. The overall mutation rate was 91.2%. Response rates were 68.4%, 50.0%, and 80.0% in patients with KIT exon 11 mutations, KIT exon 9 mutations, and no kinase mutations, respectively. With a median follow-up of 49.0 months, the median progression-free survival (PFS) time was 42.0 months and median overall survival (OS) time was not reached. PFS and OS times did not differ significantly according to KIT genotype.Conclusion. This study was unable to find an association between KIT mutational status and clinical outcome of imatinib in Korean patients with advanced GISTs. There was a trend toward better outcomes for patients with wild-type KIT or exon 11

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 85%

Kinase Mutations and Efficacy of Imatinib in Korean Patients with Advanced Gastrointestinal Stromal Tumors

et al. 2009

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“…VEGF expression has been shown previously to be related to aggressive tumor behavior in these tumors (19,20); however, it was not related to necrosis following imatinib treatment in our study. Although we showed a phenotypic correlation between CD34 and cystic change of GISTs following imatinib treatment, the precise roles of CD34 and VEGF in GISTs are not yet well understood and further studies will be required to elucidate functions of these molecules.…”

contrasting

confidence: 75%

The Lack of CD34 Expression in Gastrointestinal Stromal Tumors is Related to Cystic Degeneration Following Imatinib Use

Koh

Lee

et al. 2012

Japanese Journal of Clinical Oncology

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Objective: We evaluated the characteristics of the gastrointestinal stromal tumors that showed discrepancies between their assessment using the Response Evaluation Criteria in Solid Tumor (RECIST) and Choi's criteria. We also investigated the clinical applicability of Choi's criteria to Korean gastrointestinal stromal tumor patients undergoing imatinib therapy. Methods: Patients with advanced gastrointestinal stromal tumors treated with frontline imatinib were analyzed. Computed tomography images of these patients were reviewed and genotyping for the KIT and PDGFRA genes was performed. Immunohistochemical staining of c-KIT, CD34, platelet derived growth factor receptor-alpha, platelet derived growth factor receptor-beta, AKT, P-ERK and vascular endothelial growth factor was followed. Results: Ninety-five patients were enrolled. When using Choi's criteria to evaluate the 61 patients who achieved at least partial response by Choi's criteria, 27 patients showed discrepancies in their response to treatment between these two sets of criteria. A lack of CD34 expression in tumors was found to be related to cystic degeneration after imatinib treatment (P ¼ 0.001). Patients who showed partial response by Choi's criteria but stable disease by RECIST criteria had a similar progression-free survival to cases who showed a partial response under both systems (P ¼ 0.951). Conclusions: Gastrointestinal stromal tumors showing cystic degeneration after imatinib treatment lack CD34 expression. Choi's criteria have a clinical value in terms of the progressionfree survival in Korean patients treated with imatinib.

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“…Only 1/134 patients revealed a PDGFRα mutation in exon 12 and no mutations in the more prevalent exon 18 were identified (20,28). By contrast, a Chinese study was consistent with western trends described above (29).…”

Section: Kit Pdgfrα Number Of Studies/ ------------------------------supporting

confidence: 78%

Molecular characterisation of gastrointestinal stromal tumours in a South African population

et al. 2012

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Abstract. Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive tract. Pathogenesis is linked to activating mutations identified in two proto-oncogenes, v-kit Hardy/Zuckerman 4 feline sarcoma viral oncogene homologue KIT (KIT) and the platelet-derived growth factor α (PDGFRα). In addition, these mutations affect response to treatment with tyrosine kinase inhibitors. In the present study, we report on the molecular characterisation of GISTs in the South African population. Tumour DNA was extracted from 46 GIST samples, followed by cycle sequencing of KIT exons 11, 13 and 17 and PDGFRα exons 12, 14 and 18. Fragment length analysis was used to detect a 6-bp duplication in KIT exon 9. Wild-type duplications were analysed further by PCR and sequencing of additional KIT and PDGFRα exons was performed. Overall, 78.3% of the samples had a mutation in KIT or PDGFRα. Of these, mutations were detected in KIT exon 11 (88.9%), PDGFRα exon 18 (8.3%) and KIT exon 9 (2.8%). Mutations varied from simple substitutions and duplications to large deletions (some with nucleotide insertions) resulting in missense mutations. In addition, seven single nucleotide polymorphisms were detected in 17 patients, one of which appears novel. The incidence of mutations in KIT exon 11 and PDGFRα exon 18 is consistent with the literature, however, the low incidence of KIT exon 9 mutations detected was unexpected. In contrast to previous western and Asian studies, this mutation appears to be rare in the South African population. The present study contributes to the molecular understanding of GISTs in the South African population.

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Kinase Mutations and Imatinib Mesylate Response for 64 Taiwanese with Advanced GIST: Preliminary Experience from Chang Gung Memorial Hospital

Cited by 30 publications

References 21 publications

Kinase Mutations and Efficacy of Imatinib in Korean Patients with Advanced Gastrointestinal Stromal Tumors

Kinase Mutations and Efficacy of Imatinib in Korean Patients with Advanced Gastrointestinal Stromal Tumors

The Lack of CD34 Expression in Gastrointestinal Stromal Tumors is Related to Cystic Degeneration Following Imatinib Use

Molecular characterisation of gastrointestinal stromal tumours in a South African population

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