Gastrointestinal Stromal Tumors With KIT Exon 11 Deletions Are Associated With Poor Prognosis

Abstract Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gut and are distinguished by expression of CD117 (c-Kit). Oncogenic mutations in the KIT or PDGFRA gene are detected in approximately 85% of sporadic GISTs. In recent years, examples of familial GIST have been reported in which germline mutations of KIT or PDGFRA result in multiple GISTs, skin disorders, and other abnormalities. The most common germline mutations are in KIT exon 11, mutations in exons 8 and 17 have also been described, and there are 2 families with germline PDGFRA mutations. We present a case in which a germline KIT exon 13 mutation (K642E) was discovered in a patient with multiple GISTs of rectum, small intestine, and esophagus, as well as diffuse hyperplasia of the interstitial cells of Cajal. To our knowledge, this is only the second germline example of this particular mutation. The patient's esophageal tumors were stabilized with imatinib.

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CT texture analysis can be a potential tool to differentiate gastrointestinal stromal tumors without KIT exon 11 mutation

European Journal of Radiology ◽

10.1016/j.ejrad.2018.07.025 ◽

2018 ◽

Vol 107 ◽

pp. 90-97 ◽

Cited By ~ 10

Author(s):

Fei Xu ◽

Xiaohong Ma ◽

Yichen Wang ◽

Yuan Tian ◽

Wei Tang ◽

...

Keyword(s):

Texture Analysis ◽

Gastrointestinal Stromal Tumors ◽

Stromal Tumors ◽

Ct Texture Analysis ◽

Exon 11 ◽

Potential Tool

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Abstract 3107: A single ddPCR assay to detect KIT exon 11 mutations in tumor and cell free plasma DNA of patients with gastrointestinal stromal tumors

10.1158/1538-7445.am2016-3107 ◽

2016 ◽

Cited By ~ 1

Author(s):

Pieter A. Boonstra ◽

Marco Tibbesma ◽

Lisette J. Bosman ◽

Ron H.J. Mathijssen ◽

Frits van Coevorden ◽

...

Keyword(s):

Gastrointestinal Stromal Tumors ◽

Plasma Dna ◽

Stromal Tumors ◽

Exon 11 ◽

Free Plasma

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Pharmacokinetics of escalated dose of imatinib in patients with advanced gastrointestinal stromal tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.10085 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 10085-10085

Author(s):

Changhoon Yoo ◽

Min-Hee Ryu ◽

Baek-Yeol Ryoo ◽

Inkeun Park ◽

Mo Youl Beck ◽

...

Keyword(s):

Dose Escalation ◽

Gastrointestinal Stromal Tumors ◽

Standard Dose ◽

Progression Free Survival ◽

Hematologic Toxicity ◽

Pharmacokinetic Data ◽

Stromal Tumors ◽

Percent Change ◽

Liquid Chromatography Tandem Mass ◽

Exon 11

10085 Background: Although escalated dose (ED, 800 mg daily) of imatinib (IM) is one of important options in resistant gastrointestinal stromal tumors (GIST) on standard dose (SD, 400mg daily), there has been lack of pharmacokinetic data at ED. We therefore explore the potential relationship between IM plasma trough level (Cmin), and clinical outcomes or toxicities in patients treated with ED. Methods: Between 2008 and 2011, steady-state IM Cmin was measured in 66 patients with GIST who received ED of IM using liquid chromatography-tandem mass spectrometry. Percent change from IM Cmin at SD was calculated in 43 patients that both SD and ED IM Cmin were measured. The association with efficacy and toxicity was analyzed with grouping patients into quartiles according to IM Cmin at ED and percent change. Results: Median age was 59 years (range, 36–77) and 40 patients were male. KIT exon 11 and 9 mutation was detected in 32 and 18 patients, respectively. At ED, partial response was achieved in 4 patients (6%) and stable disease was in 32 patients (48%). The median progression-free survival was 4.2 months (95% CI, 1.8-6.6) and overall survival was 38.5 months (95% CI, 7.6-69.3). The mean (± standard deviation) IM Cmin at ED was 3552 (± 1540) ng/mL. IM Cmin was significantly increased after dose escalation (p <0.001), and mean percent change from IM Cmin at SD was 162% (± 100). Body surface area (p=0.01), hemoglobin (p=0.001), and neutrophil count (p=0.006) were significant covariates for IM Cmin at ED in multivariate analysis. The group of quartiles of IM Cmin at ED and percent change was not associated with response and survival outcomes. However, grade 3-4 hematologic or grade 2-4 non-hematologic toxicity was observed in 9% (1/11) of patients in the lowest percent change quartile (Q1, <90%) compared with 56% (18/32) in Q2 to Q4 (p=0.012), although absolute values were not associated with toxicity. Conclusions: In GIST patients treated with ED of IM, IM Cmin was not associated with response and survival. Clinically significant toxicity following dose escalation was correlated with percent change of IM Cmin, rather than absolute values. Monitoring of IM Cmin might help to predict or manage ED of IM induced toxicity.

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Treatment of nonresectable and metastatic gastrointestinal stromal tumors: Experience with the use of tyrosine kinase inhibitors in a third-level hospital in Mexico city.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.224 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 224-224

Author(s):

Abdel Karim Dip Borunda ◽

Alejandro J. Silva

Keyword(s):

Overall Survival ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Gastrointestinal Stromal Tumors ◽

Poor Prognosis ◽

Kinase Inhibitors ◽

Systemic Treatment ◽

Progression Free Survival ◽

Free Survival ◽

Stromal Tumors

224 Background: Stromal tumors of the digestive tract are uncommon malignant diseases, and are subclassified as leiomyosarcomas and gastrointestinal stromal tumors (GIST) depending on the molecular expression of CD117 (KIT). GISTs represent 1% of malignant tumors affecting this anatomical site. Located diseases are reasonably well controlled by surgical resection and several criteria define the need for adjuvant therapy. In the case of metastatic disease a poor prognosis has been reported with systemic treatment based on chemotherapy. Recently, significant advances have been shown since Tyrosine – kinase inhibitors were introduced, with median overall survival close to 5 years. Unfortunately in Mexico, even though the therapy has been long used there are no published data of the experience in the treatment of these tumors. Methods: We used an electronic data base to obtain clinical, radiological and histological data of patients diagnosed with GIST and treated in the oncological center of the Mexican Institute of Social Security, patients were subclassified by stage, symptoms at diagnosis as well as the initial and subsequent systemic treatment. Finally we made an analysis for progression free survival and overall survival identifying prognostic factors. Results: We obtained information of 71 patients with metastatic, nonresectable or recurrent GIST, treated with a TKI, we observed a predominant relation for women (60.4%), with median age of 58 years. Stage at diagnosis was predominantly metastatic (46.5%) most frequently affected sites were lung, liver and retroperitoneum. Median progression free survival was 23.6m and overall survival was 81.3 months. All patients were initially treated with imatinib at a dose of 400mg per day. Treatment was well tolerated in most cases. Conclusions: Metastatic GIST evaluated in our center shows a different affection in gender and age, our population shows a different response to TKI’s, than reported in other series with superior overall survival, Poor prognosis is associated with lung affection. Biological studies will be started for the molecular evaluation of these tumors.

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