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. 2022 Aug 4;20(3):15593258221117354.
doi: 10.1177/15593258221117354. eCollection 2022 Jul-Sep.

Evaluation of Clinical and Genetic Determinants of Treatment OutCome In EGFR Mutation Positive Advanced Lung Adenocarcinoma

Vera Jokic  1 , Katarina Savic-Vujovic  2 , Jelena Spasic  1 , Zoran Bukumiric  3 , Mladen Marinkovic  4 , Davorin Radosavljevic  1 , Milena Cavic  5
Affiliations

Evaluation of Clinical and Genetic Determinants of Treatment OutCome In EGFR Mutation Positive Advanced Lung Adenocarcinoma

Vera Jokic et al. Dose Response. .

Abstract

Background: The aim of this research was to evaluate clinical and low-cost genetic determinants of treatment outcome in EGFR mutation positive advanced lung adenocarcinoma patients.

Material and methods: EGFR mutation testing and EGFR 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 P < .05.

Results: 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 (P < .001) and adrenal glands metastases (P = .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.

Conclusions: EGFR mutation subtype and the EGFR 181946 C>T SNP had a significant effect on the response to TKI inducing an indirect anti-dolorous effect.

Keywords: EGFR; lung cancer; pain; tyrosine kinase inhibitors.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
(a) Progression free survival (PFS) and (b) overal survival (OS) curves of patients with and without pain at diagnosis.
Figure 2.
Figure 2.
(a) PCR and RFLP results and (b) genotype distribution of EGFR 181946 CT polymorphic variants in patients with and without pain at diagnosis. Column 1: 244 bp PCR product. Column 2: CC (wild type), Column 3: CT (heterozygot, Column 4: TT (recessive homozygote). L – High-sensitivity DNA ladder (Agilent Technologies). 1500 bp upper and 15 bp lower marker are present in each column.
Figure 3.
Figure 3.
The effect of (a) EGFR mutation types and (b) EGFR 181946 CT polymorphic variants on pain management and (c) response to TKI treatment.
See this image and copyright information in PMC

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