Low-dose Apatinib Combined With Whole-brain Radiotherapy Compared With Whole-brain Radiotherapy Alone In The Treatment Of Symptomatic Multiple Brain Metastases In Advanced Non-small Cell Lung Cancer

Objective:Symptomatic multiple brain metastases with peritumoral brain edema(PTBE)occur in non-small cell lung cancer(NSCLC)patients who are without driver-mutations or are resistant to epidermal growth factor tyrosine kinase(EGFR-TKI),are often associated with an unfavorable prognosis.Whole brain radiation therapy(WBRT)which comes with many complications and unsatisfactory effects,is the only option for the treatment.Whole-brain radiotherapy(WBRT)is still the main treatment method,but the effect is not satisfactory.Previous studies have shown that the combination of the anti-angiogenic drug bevacizumab and WBRT can increase the effectiveness of treatment and prolong survival.This study evaluated the effects and safety of the vascular endotheliol growth factor receptortyrosine kinase inhibitor(VEGFR-TKI)apatinib combined with WBRT compared with WBRT alone in advanced NSCLC patients with symptomatic multiple brain metastases without driver gene mutations or resistance to targeted drugs.Methods:A retrospective analysis of recurrent or drug-resistant symptomatic multiple brain metastases of advanced non-small cell lung cancer in the Department of Oncology,Yibin Second People’s Hospital from January 2018 to June 2020.Intracranial objective response rate(IORR),peritumoral edema and intracranial tumor volumetric measurement,Karnofsky performance status(KPS)and adverse events(AEs)were evaluated.Median intracranial progression-free survival(mIPFS),media extracranial disease-free survival time(mEPFS)and median overall survival(mOS)were also analyzed.Results:A total of 44 patients were collected and followed up in this study.Among them,23 patients received WBRT combined with apatinib and 21 patients not combined with apatinib.The IORR of the apatinib combined with WBRT group was better than that the group without apatinib(82.6%VS 47.6%,P<0.05).There was no significant difference in EORR between the two groups(43.5%VS 33.3%,P>0.05).Compared the group without apatinib,apatinib combined with WBRT can better reduce the volume of PTBE[(48.4±24.7cm3)VS(22.6 ±23.1cm3),P<0.05],and has a longer mIPFS(6.6 VS 4.8 months;P=0.004).There was no significant difference in mEPFS(5.2 VS 5.1 months;P=0.364)and mOS between the two groups(7.7 VS 6.6 months;P=0.104).Cox regression analysis suggests that whether combined with apatinib is an independent risk factor affecting IPFS.The most common adverse events of apatinib combined with WBRT include grade 1/2 hypertension(9,39.1%),fatigue(8,34.8%),hand-foot syndrome(7,30.4%),nausea(4,17.4%),leukopenia(6,26.1%)and neutropenia(4,17.4%),no grade 3/4 adverse reactions were observed.Conclusion:1.Compared with the group without apatinib,apatinib combined with WBRT improved IORR,enhanced the ability to reduce peritumoral edema,and prolonged mIPFS.2.The majority of patients with apatinib combined with WBRT progressed after multi-line therapy and without systemic chemotherapy,and the baseline KPS score was poor.However,the mOS of the apatinib combined with WBRT group has a prolonged trend than that of the group without apatinib.3.The side effects of apatinib combined with WBRT are tolerable.