Influences Of EGFR Or KRAS Gene Mutation Status On The Efficacy Of Postoperative Chemotherapy In Stageâ… B To â…¢A Lung Adenocarcinoma Patients By Pemetrexed Combined With Platinum Adjuvant Chemotherapy

Objective:We analyzed epidermal growth factor receptor(EGFR) or KRAS gene mutation status in stageⅠB to ⅢA lung adenocarcinoma patients.To investigate influences of EGFR or KRAS gene mutation status on the efficacy of postoperative chemotherapy in lung adenocarcinoma patients by pemetrexed combined with platinum adjuvant chemotherapy.Guide individualized treatment in the early and middle stages lung adenocarcinoma patients.Methods:This study selected 51 cases of stageⅠB to ⅢA lung adenocarcinoma patients after radical surgery in Air Force General Hospital from August 2010 to August 2014.All patients were received pemetrexed combined with platinum(pemetrexed plus cisplatin, carboplatin, nedaplatin, oxaliplatin) adjuvant chemotherapy after radical surgery at least 4 cycles. Lung cancer tissues were obtained by intraoperative cut. EGFR or KRAS mutations were detected with x TAG liquidchip technology(x TAG-LCT).The disease free survival(DFS) of all patients were followed up.Results:(1) In 51 cases of stageⅠB to ⅢA lung adenocarcinoma patients, EGFR and KRAS gene mutation rate was 49.0%(25/51) and 23.5%(12/51). EGFR mutation rate in female patients(65.2%,15/23) was higher than that in male patients(35.7%,10/28)(P = 0.036); EGFR mutation rate in patients who had no smoking history(61.3%, 19/31) was higher than that in patients had smoking history(30.0%, 6/20)(P =0.029).But EGFR mutation rate was not relevant to age, TNM stages, tumor pathological grade and lymph node metastasis(P> 0.05). KRAS gene mutation rate in male patients(35.7%, 10/28) was higher than that in female patients(8.7%,2/23)(P=0.024),but was not relevant to smoking history, age, TNM stages, tumor pathological grade and lymph node metastasis(P> 0.05).(2) We found that the median DFS(36 months) of the patients with EGFR mutations was longer than that(27 months)of the patients with EGFR wild-type in stageⅠB to ⅢA patients by Kaplan-Meier survival analysis, the difference is statistically significant(P = 0.010).But KRAS mutations were not relevant to the patients’ DFS(P = 0.102). We analyzed that the relationship of different EGFR gene mutations(exon 19,20,21) and patients’ DFS.We found that only median DFS(44 months) of patients with EGFR gene exon 19 mutation was longer than that(33 months)of the patients with EGFR wild-type, the difference was statistically significant(P = 0.005).There was no significant contrast among the other groups(P> 0.05).We analyzed that the relationship of different KRAS gene mutations(codon 12 of exon 2, codon 13 of exon 2 and exon 3) and patients’ DFS. We found that there was no significant contrast among the groups(P> 0.05).(3) We analyzed that the relationship of patients’ DFS with clinical and pathological features.We found that patient’ DFS were correlated to TNM stages(P = 0.021),and were not correlated to gender, smoking history, age and lymph node metastasis(P> 0.05).We also found that the median DFS(46 months) of the patients with EGFR mutations was longer than that(33 months)of the patients with EGFR wild-type in stageⅠB patients, the difference is statistically significant(P = 0.017).But KRAS mutations were not relevant to the patients’ DFS(P = 0.823).The median DFS(30 months) of the patients with EGFR mutations was longer than that(25 months)of the patients with EGFR wild-type in stageⅡ-ⅢA patients, the difference is statistically significant(P = 0.035), whereas the median DFS(25 months) of the patients with KRAS mutations was shorter than that(29 months)of the patients with KRAS wild-type in stageⅡ-ⅢA patients, the difference is statistically significant(P = 0.027).(4) COX regression analysis revealed that TNM stage and EGFR mutation were the independent prognostic factor in stageⅠB to ⅢA lung adenocarcinoma patients.Conclusions:(1) In stageⅠB to ⅢA lung adenocarcinoma patients, EGFR mutation rate of the patients with female and non-smoking history were higher,however KRAS mutation rate of the patients with male were higher.(2) In stageⅠB to ⅢA lung adenocarcinoma patients by pemetrexed combined with platinum adjuvant chemotherapy after radical surgery,EGFR mutation status had effects on the patients’ DFS.The patients with EGFR mutations had a longer DFS compared with patients with EGFR wild-type. Only the patients with EGFR exon 19 mutant had a longer DFS compared with patients with EGFR wild-type,and patients with EGFR other sites mutation had no effects on the patients’ DFS.(3) In stageⅡto ⅢA lung adenocarcinoma patients by pemetrexed combined with platinum adjuvant chemotherapy after radical surgery,KRAS mutation status had effects on the patients’ DFS.The patients with KRAS wild-type had a longer DFS compared with patients with KRAS mutations.However KRAS mutation status had no effects on the patients’ DFS in stageⅠB lung adenocarcinoma patients.(4) TNM stages and EGFR mutation were dependent prognostic factors in stageⅠB to ⅢA lung adenocarcinoma patients.(5) EGFR and KRAS mutation status not only had a important value on efficacy of TKI drug,but also had a influence on efficacy of chemotherapy. However every patient must had a individualized treatment depending on the TNM stage and gene mutation sites,and can not be generalized.If so it allows the patient to get more benefits.