Significant Effect of Anti-tyrosine Kinase Inhibitor (Gefitinib) on Overall Survival of the Glioblastoma Multiforme Patients in the Backdrop of Mutational Status of Epidermal Growth Factor Receptor and PTEN Genes.
Significant Effect of Anti-tyrosine Kinase Inhibitor (Gefitinib) on Overall Survival of the Glioblastoma Multiforme Patients in the Backdrop of Mutational Status of Epidermal Growth Factor Receptor and PTEN Genes.
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DOI：
10.4103/ajns.ajns_95_17
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Bhat AR
中科院分区：
文献类型：
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作者：
Arif SH;Pandith AA;Tabasum R;Ramzan AU;Singh S;Siddiqi MA;Bhat AR
我们旨在评估抗酪氨酸激酶抑制剂（TKIs）（吉非替尼）在表皮生长因子受体（EGFR）和PTEN基因突变状态下对多形胶质母细胞瘤（GBM）患者总生存期（OS）的影响。所有切除或活检的患者均给予吉非替尼治疗，并按医院方案进行放疗。通过单链构象多态性和DNA测序分析EGFR和PTEN突变谱。总的来说，50%的GBM肿瘤有EGFR或PTEN突变。EGFR +ve/PTEN - ve患者的中位无进展生存期（PFS）和OS分别为9（7,11）个月和20（16,24）个月，显著优于PTEN +ve/EGFR - ve患者的6（4,8）个月和13（7,19）个月（P < 0.05）。与EGFR/PTEN阴性患者的6（5,7）和14（12,24）个月相比，EGFR/PTEN阳性患者的无病生存期和OS（6个月和9个月）较低。我们得出结论，野生型PTEN的EGFR基因改变与抗tkis（吉非替尼）治疗的患者的PFS和OS显着改善相关。就中位OS而言，EGFR和PTEN基因联合突变与对吉非替尼的不良反应显著相关。
We aimed to assess the effect of anti-tyrosine kinase inhibitors (TKIs) (gefitinib) in overall survival (OS) of the glioblastoma multiforme (GBM) patients in the backdrop of mutational status of epidermal growth factor receptor (EGFR) and PTEN genes. All the patients subjected to resection or biopsies were put on gefitinib, and radiotherapy was delivered as per the hospital protocol. EGFR and PTEN mutational spectrum was performed by single-strand conformation polymorphism followed by DNA sequencing. In total, 50% GBM tumors had mutation either in EGFR or PTEN. Median progression-free survival (PFS) and OS observed in patients with EGFR +ve/PTEN −ve were significantly favorable (P < 0.05) which aggregated to 9(7, 11) months and 20 (16, 24) months, respectively, than 6 (4, 8) months and 13 (7, 19) months in patients with PTEN +ve/EGFR −ve. Patients positive for both EGFR/PTEN had lower disease-free survival and OS of 6 and 9 months as compared to 6 (5, 7) and 14 (12, 24) months for those negative for both EGFR/PTEN. We conclude that EGFR gene alterations with wild-type PTEN are associated with significantly better PFS and OS in patients treated with anti-TKIs (gefitinib). Combined EGFR and PTEN gene mutation is associated with significantly poor response to gefitinib in terms of median OS.