Home About us Contact
|
Home About us Contact | ||
|
|
||
Metastatic GISTs (metastatic + gist)
Selected AbstractsThe successful management of two pregnancies with wild type metastatic gastrointestinal stromal tumorsASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 3 2009Thean Hsiang TAN Abstract Aim: To discuss the management of the uncommon situation of metastatic gastrointestinal tumour coexisting with pregnancy. Method: We describe two cases of women with metastatic gastrointestinal stromal tumor (GIST) who successfully achieved a full-term pregnancy without complications and with the delivery of healthy infants. In both cases, treatment with imatinib mesylate was withheld during pregnancy because of its unknown effects and questionable safety for the developing fetus. The available data in the medical literature regarding the use and safety of imatinib and pregnancy are reviewed. We also examine whether the knowledge of the exon mutational status would have influenced treatment decisions. Results: Both women had wild type GIST, but with different tumor growth characteristics, treatment responses and outcomes. The first patient deferred imatinib therapy to fall pregnant and her disease progressed rapidly off treatment. The second patient had a more indolent GIST where active surgical management allowed her to experience a long durable clinical response. She potentially belongs to a pediatric subgroup which carries a better prognosis despite being off imatinib. Conclusion: While we have successfully managed two pregnant women with metastatic GIST, the issue of initiating imatinib therapy in treatment-naive women, and treatment interruption in women already on therapy, remain difficult areas. Patients and their partners need to make an informed choice regarding the associated risks and the potential long-term sequelae if pregnancies are contemplated. Further research into the natural history of wild type GIST and how to tailor subsequent treatment are needed. [source] Hepatic artery chemoembolization for 110 gastrointestinal stromal tumorsCANCER, Issue 12 2006Response, prognostic factors, survival Abstract BACKGROUND. The efficacy of hepatic artery chemoembolization (HACE) was evaluated for gastrointestinal stromal tumors (GISTs) metastatic to the liver. METHODS. Records for patients with metastatic GIST who underwent HACE between January 1993 and March 2005 were reviewed and cross-sectional images were used to determine objective tumor response. Progression-free survival in the liver (PFS-liver) and overall survival (OS) were calculated with the Kaplan,Meier method. Patient, tumor, and treatment variables were analyzed to identify factors influencing survival. RESULTS. Of the 110 patients identified, the radiologic response to HACE could be evaluated in 85 patients, 12 of whom (14%) demonstrated partial responses, 63 of whom (74%) demonstrated stable disease, and 10 of whom (12%) demonstrated progressive disease. PFS-liver rates were 31.2%, 8.2%, and 5.4% at 1, 2, and 3 years, respectively; the median PFS time was 8.2 months. OS rates were 62% at 1 year, 32% at 2 years, and 20% at 3 years; the median OS time was 17.2 months. Patients who had >5 liver metastases and received only 1 HACE treatment were found to have a shorter PFS compared with patients with fewer metastases or those who received ,2 HACE sessions. Extensive liver involvement, the presence of extrahepatic metastases, and progression of liver disease after HACE were associated with poor OS. Use of imatinib prolonged OS time. CONCLUSIONS. HACE produced a durable tumor response or disease stabilization in the majority of patients with GISTs metastatic to liver. Extent of liver disease, presence of extrahepatic disease, number of embolization treatments, and use of imatinib were found to have prognostic influence on PFS, OS, or both. Cancer 2006. © 2006 American Cancer Society. [source] Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumoursHISTOPATHOLOGY, Issue 3 2008J Lasota Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Despite clinicopathological differences, GISTs share oncogenic KIT or platelet-derived growth factor-alpha (PDGFRA) mutations. Imatinib, KIT and PDGFRA inhibitor, has been successfully used in the treatment of metastatic GISTs. There are primary KIT or PDGFRA mutations diagnosed before imatinib treatment, linked to GIST pathogenesis, and secondary mutations detected during treatment, causing drug resistance. KIT exon 11 mutations are the most common. Gastric GISTs with exon 11 deletions are more aggressive than those with substitutions. KIT exon 11 mutants respond well to imatinib. Less common KIT exon 9 Ala502_Tyr503dup mutants occur predominantly in intestinal GISTs and are less sensitive to imatinib. An Asp842Val substitution in exon 18 is the most common PDGFRA mutation. GISTs with such mutation are resistant to imatinib. PDGFRA mutations are associated with gastric GISTs, epithelioid morphology and a less malignant course of disease. GISTs in neurofibromatosis 1, Carney triad and paediatric tumours generally lack KIT and PDGFRA mutations. Secondary KIT mutations affect exons 13,17. GISTs with secondary mutations in exon 13 and 14 are sensitive to sunitinib, another tyrosine kinase inhibitor. KIT and PDGFRA genotyping is important for GIST diagnosis and assessment of sensitivity to tyrosine kinase inhibitors. [source] Pleomorphic phenotypes of gastrointestinal stromal tumors at metastatic sites with or without imatinib treatmentCANCER SCIENCE, Issue 5 2010Kazuha Sakamoto Secondary resistance of gastrointestinal stromal tumors (GISTs) to tyrosine kinase inhibitors occurs after several years' administration. However, the mechanism of resistance has not been fully clarified. In this study, we analyzed the genotypes and the histologic and immunohistochemical phenotypes of metastatic GISTs with and without imatinib treatment, and clarified the pleomorphic nature of metastatic GISTs. We examined 31 autopsy cases in which the patients died of multiple metastases of GISTs, and two surgically resected specimens with and without imatinib treatment. A total of 152 primary and metastatic lesions in 33 cases of GISTs were examined for histologic and immunohistochemical expression of KIT and CD34. We analyzed the expression of other receptor tyrosine kinases (RTKs) in KIT-negative lesions, including human EGFR-related 2 (HER2), epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (MET), platelet-derived growth factor receptor-, (PDGFRA), and platelet-derived growth factor receptor-, (PDGFRB). Fifteen lesions in seven cases (9.9%) lacked KIT expression, and 74 (49%) in 22 cases lacked CD34 expression. Eight KIT-negative lesions in five cases expressed PDGFRB, one of which also expressed EGFR, and three lesions in one case expressed MET. Results for the other RTKs were negative. Missense point mutations at PDGFRB gene exon 12 were detected in one PDGFRB-positive case. Our results indicate that histomorphology, immunohistochemical phenotypes, and genotypes of metastatic GISTs vary among lesions, even in cases without imatinib treatment. A KIT-independent mechanism, such as activation of other RTKs, might participate in the proliferation of late-stage GISTs and might be a cause of secondary imatinib resistance. (Cancer Sci 2010; 101: 1270,1278) [source] Alterations of the c-kit gene in testicular germ cell tumorsCANCER SCIENCE, Issue 6 2003Yuji Sakuma Expression and gain-of-function mutation of the c-kit gene, that encodes a receptor tyrosine kinase (KIT), have been reported in mast cell tumors and gastrointestinal stromal tumors (GISTs). Among human testicular germ cell tumors (GCTs), seminomas and seminoma components of mixed GCTs have also been shown to express KIT, but only one study has found the c-kit gene mutation at exon 17 in seminoma. To elucidate the frequency and location of the c-kit gene mutation of testicular GCTs, we analyzed the whole coding region of the c-kit complementary DNA along with 4 mutational hot spots (exons 9, 11, 13 and 17) of the c-kit genomic DNA by polymerase chain reaction and direct sequencing. Somatic mutations were found in 4 pure seminomas of 34 testicular GCTs (11.8%). One mutation was found in exon 11 (W557R) and the others were observed in exon 17 (D816H and D816V). These types of mutations were reported in GISTs (W557R), seminoma (D816H) and mastocytosis (D816V) and were considered to be gain-of-function mutations, although there were no differences of any clinicopathological factors or outcome between patients with and without mutations. Additionally, we also demonstrated coexpression of Gly-Asn-Asn-Lys510,513 (GNNK)+ and GNNK- isoforms of the c-kit gene with dominance of the GNNK- transcript in all testicular GCTs. The mutations and/or preferential expression of GNNK- isoform of the c-kit gene might play an important role in the development of testicular GCTs, and these tumors may also be targets for STI571, which is a promising drug for advanced and metastatic GISTs. [source] | ||||||||||