A Clincal Observation Of Gefitinib Combined With Whole Brain Radiotherapy With Hippocampal Avoidance For Patients With Brain Metastases From EGFR-Mutant Non-Small Lung Cancer

Objective:To investigate the efficacies of gefitinib combined with whole brain radiotherapy with hippocampal avoidance (WBRT-HA) for patients with brain metastases from EGFR-mutant non-small lung cancer (NSCLC), and to observe the change of cognitive function of patients received gefitinib combined with WBRT-HA.Methods:98 cases diagnosed with EGFR-mutant NSCLC between July 5,2010 and April 10, 2015 treated in Northern Jiangsu People’s Hospital. All these patients were diagnosed with EGFR-mutant (exon 19 deletion or exon 21 L858R mutant) NSCLC by pathology and gene tests, and diagnosed with brain metastases by MRI.56 cases received gefitinib 250mg/d orally and WBRT with intensity-modulated radiation therapy were divided into the combined treatment group (gefitinib combined with WBRT-HA). The therapeutic dose of WBRT was 30Gy/15F with the maximum dose of hippocampe not exceeding 24Gy.42 cases received gefitinib 250mg/d alone were divided into the control group. Then objective response rate (ORR), diease control rate (DCR), progression free survival (PFS), orall survival (OS) and adverse reactions of the two groups were compared. Cognitive function of patients in the combined treatment group were assessed and comparative analyzed 1 week before radiotherapy,3 months after radiotherapy,6 months after radiotherapy and 12 months after radiotherapy using Mine-Mental State Examination (MMSE) form.Results:In the combined treatment group, complete response (CR) of intracranial lesions in 6 cases (10.7%), partial response (PR) in 35 cases (62.5%), stable disease (SD) in 12 cases (21.4%) and progressive disease (PD) in 3 cases (5.4%). In the contral group, CR in 3 cases (7.1%), PR in 18 cases(42.9%), SD in 17 cases (40.5%) and PD in 4 cases (9.5%). ORR of the combined treatment group was 73.2%, significantly higher than that in control group (50%), and the difference was statistically significant (P<0.05). DCR of the combined treatment group was 94.6%, higher than that in control group, but the difference was not statistically significant (P>0.05). Median PFS of the combined treatment group was 16.5 months, significantly higher than that in control group (12.1 months), and the difference was statistically significant (P<0.05). Median OS of the combined treatment group was higher than that in control group (19.6 vs 16.4 months), and the difference was statistically significant (P=0.022). The main adverse reactions were rash and diarrhea. The incidence of alopecia in the patients received WBRT was significantly higher than the patients of control group (33.9% vs 7.1%, P=0.02). There was no serious adverse reaction in both groups. Compared with the scores of cognitive function assessed in 1 week before radiotherapy, the differences of the scores assessed in 3 months,6 months and 12 months after radiotherapy were not statistically significant in the combined treatment group (P<0.05)Conclusion:1. In the treatment of brain metastases from EGFR-mutant NSCLC, the ORR gefiitinib combined with WBRT-HA group was significantly higher than the control group, and median PFS and median OS were significantly longer.2. The side effects of gefiitinib were mild, which ensured the sustainability of the combination therapy.3. The cognitive function of patients received gefitinib combined with WBRT-HA was no decreased obviously. It illustrated there was no damage effect on cognitive function of patients received the combination therapies.