Jokic Vera, Savic-Vujovic Katarina, Spasic Jelena, Bukumiric Zoran, Marinkovic Mladen, Radosavljevic Davorin, Cavic Milena
Clinic for Medical Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia.
Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Dose Response. 2022 Aug 4;20(3):15593258221117354. doi: 10.1177/15593258221117354. eCollection 2022 Jul-Sep.
The aim of this research was to evaluate clinical and low-cost genetic determinants of treatment outcome in mutation positive advanced lung adenocarcinoma patients.
mutation testing and 181946C>T genotyping were performed in 101 advanced lung adenocarcinoma patients using qRT-PCR and PCR-RFLP, respectively. Progression-free survival was defined as the time from the start of TKI therapy to date of progression, and overall survival as the time from diagnosis to death from any cause. Pain level was evaluated using a Numerical Rating Scale and the Verbal Descriptor Scale. Statistical significance was considered for < .05.
Patients were treated with EGFR-TKIs for a period of 1-39months (median 9), with a median PFS of 12.0 months (10.4-13.6, CI 95%), and a median OS of 19.0 months (15.1-22.7, CI 95%). The presence of pain was significantly correlated with the existence of bone ( < .001) and adrenal glands metastases ( = .029). Genetic factors did not have a direct impact on pain management but had a significant effect on the response to TKIs leading to pain alleviation.
mutation subtype and the 181946 C>T SNP had a significant effect on the response to TKI inducing an indirect anti-dolorous effect.
本研究旨在评估突变阳性晚期肺腺癌患者治疗结果的临床和低成本遗传决定因素。
分别采用qRT-PCR和PCR-RFLP对101例晚期肺腺癌患者进行突变检测和181946C>T基因分型。无进展生存期定义为从TKI治疗开始至进展日期的时间,总生存期定义为从诊断至任何原因死亡的时间。使用数字评定量表和言语描述量表评估疼痛程度。P<0.05被认为具有统计学意义。
患者接受EGFR-TKIs治疗1至39个月(中位时间9个月),中位无进展生存期为12.0个月(10.4 - 13.6,95%CI),中位总生存期为19.0个月(15.1 - 22.7,95%CI)。疼痛的存在与骨转移(P<0.001)和肾上腺转移(P = 0.029)显著相关。遗传因素对疼痛管理没有直接影响,但对导致疼痛缓解的TKI反应有显著影响。
突变亚型和181946C>T单核苷酸多态性对TKI反应有显著影响,从而产生间接的镇痛作用。