Correlation between different C-KIT exon mutations & clinical outcome to imatinib mesylate treatment in GIST patients /
(GIST) و النتائج الاكلينيكية بعد العلاج بعقار الايماتينيب في مرضي الجهاز الهضمي (C-KIT EXON MUTATIONS)العلاقة بين
Ghada Yehia Zakaria ; Supervised Nasr Allahloubi , Abeer Bahanasy , Ola Khorshid
- Cairo : Ghada Yehia Zakaria , 2018
- 59 P. : charts ; 25cm
Thesis (M.Sc.) - Cairo University - National Cancer Institute - Department of Oncology (Medical)
Background The clinical behavior of GISTs is highly variable. This study aims at detection of different histo-pathological tumor features and correlation with different clinical aspects after treatment with Imatinib, based on C-KIT exon mutation status. Methods This is a retrospective study that included all cases diagnosed as GIST who presented to NCI from 2005 till 2017 , The following data were collected from the patients files ,age, gender, tumor site, size, mitotic rate, histological grade, capsular rupture, risk stratification by Joensuu criteria ,treatment setting, date of start and end of treatment, dose and toxicity, KIT mutation was assessed on tumor tissues of all patients ,clinical correlation between different clinical aspects after treatment with Imatinib ,based on C-KIT exon mutation status was done. Results Eighty-nine cases of GIST presented to National cancer institute in the period from September 2005 to January 2017. Median age at diagnosis was 48 years old with a median follow up of 22 months. More than 75 % of the patients had positive C-Kit mutation while it was negative in 24.7 % of the patients. C-kit positive mutations were significantly associated with tumors more than 5 cm, high mitosis, and with high tumor risk stratification by Joensuu criteria in more than fifty percent of the patients. Exon 9 mutations had poor ORR (55.6 %) compared to those with exon 11(67.6%) (P=0.33), with the latter having PFS of 55 months compared 120 months for exon 9 mutations, (P=0.002). No statistically difference in OS was observed with exon 9 (70 months) compared to exon 11 mutations (77 months). (P=0.55) Conclusion C-kit positive mutation per-se is an independent poor risk factor, associated with more aggressive tumor features whereas response to Imatinib was affected by exon mutations with exon 11 having tendency for better ORR, compared to exon 9 mutation , with the latter having longer PFS compared to exon 11 , with no statistically difference in OS with exon 9 compared to exon 11 mutations