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. 2021 Jan-Dec:20:15330338211011968.
doi: 10.1177/15330338211011968.

Continuous Low-Dose Apatinib Combined With WBRT Significantly Reduces Peritumoral Edema and Enhances the Efficacy of Symptomatic Multiple Brain Metastases in NSCLC

Yue Ren  1   2 , Shan-Bing Wang  2 , Lin Zhou  3 , Si-Qiao Liu  4 , Lei-Ya Du  2 , Ting Li  2 , Mao-Qiong Jiang  2 , Kai-Jian Lei  2 , Bang-Xian Tan  1 , Yu-Ming Jia  2
Affiliations

Continuous Low-Dose Apatinib Combined With WBRT Significantly Reduces Peritumoral Edema and Enhances the Efficacy of Symptomatic Multiple Brain Metastases in NSCLC

Yue Ren et al. Technol Cancer Res Treat. 2021 Jan-Dec.

Abstract

Background: Symptomatic multiple brain metastases with peritumoral brain edema (PTBE) occur in non-small cell lung cancer patients (NSCLC) 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. Previous studies have shown that bevacizumab can reduce the volume of PTBE and improve efficiency of radiotherapy. This study evaluated the effects and safety of apatinib combined with WBRT in NSCLC patients with symptomatic multiple brain metastases and PTBE.

Methods: We performed a retrospective review of 34 patients with symptomatic multiple brain metastases from NSCLC (number >4, and at least 1 measurable brain metastasis lesion with cerebral edema). 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) and median overall survival (mOS) were also analyzed.

Results: Thirteen cases received apatinib (125 mg or 250 mg, QD, oral) combined with WBRT and 21 cases received chemotherapy combined with WBRT were inclued. Apatinib combination group can better reduce the volume of intracranial tumors and PTBE and total steroid dosage used. It was associated with a better IORR (84.6% vs 47.6%, P = 0.067), longer mIPFS (6.97 vs 4.77months; P = 0.014). There was no significant difference in mOS(7.70 vs 6.67 months; P = 0.14) between the 2 groups. The most common adverse events of apatinib combination WBRT included grade 1/2 nausea (4/13), fatigue (3/13), hypertension (2/13) and white blood cell decrease (2/13). No grade 3/4 AEs were observed.

Conclusion: Apatinib plus WBRT is well tolerated and may be a potential choice for relapsed or drug-resistant advanced NSCLC patients with symptomatic multiple brain metastases and PTBE.

Keywords: apatinib; brain metastases; non-small cell lung cancer; peritumoral brain edema; radiation therapy; whole brain radiotherapy.

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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.
Contours demonstrating volumes of tumor (red) and PTBE (yellow) on CT images obtained pretreatment (A) and post-treatment (B).
Figure 2.
Figure 2.
Timelins showing the clinical course of diseases of patients in the apatinib combined with WBRT. Each row represents a patient. The time point of WBRT is set to 0. The primary tumor is demonstrated on the left, and previous therapies are listed below. SRS, radiosurgery; TT, EGFR-TKIs; Chemo+ES, chemotherapy combined with endostatin; Chemo+Bev, chemotherapy combined with bevacizumab; BM, brain metastasis.
Figure 3.
Figure 3.
Box plots demonstrating the change in edematous, tumor volumes in the 2 groups.
Figure 4.
Figure 4.
Kaplan–Meier intracranial progression-free survival (iPFS) and overall survival (OS) curves in 2 for peer review groups. (A) iPFS. (B) OS.
See this image and copyright information in PMC

References

    1. Villano JL, Durbin EB, Normandeau C, Thakkar JP, Moirangthem V, Davis FG. Incidence of brain metastasis at initial presentation of lung cancer. Neuro Oncol. 2015;17(1):122–128. doi:10.1093/neuonc/nou099 - PMC - PubMed
    1. Davis FG, Dolecek TA, McCarthy BJ, Villano JL. Toward determining the lifetime occurrence of metastatic brain tumors estimated from 2007 United States cancer incidence data. Neuro Oncol. 2012;14(9):1171–1177. doi:10.1093/neuonc/nos152 - PMC - PubMed
    1. Thomas SR, Khuntia D. Motexafin gadolinium injection for the treatment of brain metastases in patients with non-small cell lung cancer. Int J Nanomedicine. 2007;2(1):79–87. doi:10.2147/nano.2007.2.1.79 - PMC - PubMed
    1. Lu Y, Fan Y. Combined action of EGFR tyrosine kinase inhibitors and whole-brain radiotherapy on EGFR-mutated non-small-cell lung cancer patients with brain metastasis. Onco Targets Ther. 2016;9:1135–1143. doi:10.2147/OTT.S95871 - PMC - PubMed
    1. Varlotto JM, Flickinger JC, Niranjan A, Bhatnagar AK, Kondziolka D, Lunsford LD. Analysis of tumor control and toxicity in patients who have survived at least one year after radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys. 2003;57(2):452–464. doi:10.1016/S0360-3016(03)00568-6 - PubMed

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