A analysis of the spatial distribution characteristics of brain metastasis and the risk of hippocampus metastasis in patients with EGFR mutant lung cancer
Wu Junlan1,2, Fan Xingwen1, Wang Hongbing1, Wu Kailiang1
1Department of Radiation Oncology,Fudan University Shanghai Cancer Center,Shanghai 200032,China; 2Department of Oncology, Shanghai Armed Police General Hospital,Shanghai 201103,China
Abstract：Objective To analyze the spatial distribution of brain metastases in EGFR-mutant lung cancer and the risk of hippocampal metastasis. Methods Patients with lung cancer brain metastases diagnosed and treated in the Shanghai Cancer Center Fudan University from 2006 to 2016 were enrolled. The brain metastasis with positive mutation of EGFR gene was screened. The magnetic resonance images of the patients were reviewed and the distribution characteristics of brain metastasis were analyzed. Results A total of 920 lung cancer patients with brain metastases were screened,266 of whom had EGFR gene mutation detection,and 131(49%) were identified as EGFR gene mutations. Excluding 17 patients who did not have a head magnetic resonance examination in our hospital,a total of 114 patients and 738 lesions were enrolled in this study. The proportion of brain metastases distributed in each brain region was 22.8%,19.5%,22.0%,13.4%,3.3%,16.7%,and 2.2% for frontal,temporal,parietal,occipital lobe,insula,cerebellum,and brainstem,respectively. The number of metastases and cases located in the hippocampus,<5mm from the hippocampus,<10mm from the hippocampus,and<15mm from the hippocampus were 6(0.8%),10(1.3%),11(1.4%),and 14(1.8%),5 cases (4.4%),8 cases (7.0%),9 cases (7.9%),and 11 cases (9.6%),respectively. Conclusion EGFR-mutant lung cancer brain metastasis is low risk in the hippocampus and its surrounding 15mm.
Wu Junlan,Fan Xingwen,Wang Hongbing et al. A analysis of the spatial distribution characteristics of brain metastasis and the risk of hippocampus metastasis in patients with EGFR mutant lung cancer[J]. Chinese Journal of Radiation Oncology, 2019, 28(11): 817-820.
[1] Magnuson WJ,Lester-Coll NH,Wu AJ,et al. Management of brain metastases in tyrosine kinase inhibitor-naive epidermal growth factor receptor-mutant non-small-cell lung cancer:a retrospective multi-institutional analysis[J]. J Clin Oncol,2017,35(10):1070-1077. DOI:10.1200/JCO.2016.69.7144. [2] Makale MT,McDonald CR,Hattangadi-Gluth JA,et al. Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours[J]. Nat Rev Neurol,2017,13(1):52-64. DOI:10.1038/nrneurol.2016.185. [3] Magnuson WJ,Yeung JT,Guillod PD,et al. Impact of deferring radiation therapy in patients with epidermal growth factor receptor-mutant non-small cell lung cancer who develop brain metastases[J]. Int J Radiat Oncol Biol Phys,2016,95(2):673-679. DOI:10.1016/j.ijrobp.2016.01.037. [4] 范兴文,吴开良. 放射性认知功能障碍的机制研究进展[J]. 中华放射医学与防护杂志,2014,34(11):876-880. DOI:10.3760/cma.j.issn.0254-5098.2014.11.022. Fan XW,Wu KL. Progress in the mechanism of radiation cognitive impairment[J]. Chin J Radiol Med Protect,2014,34(11):876-880. DOI:10.3760/cma.j.issn.0254-5098.2014.11.022. [5] Gondi V,Pugh S L,Tome W A,et al. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG0933):a phase Ⅱ multi-institutional trial[J]. J Clin Oncol,2014,32(34):3810-3816. DOI:10.1200/JCO.2014.57.2909. [6] Ghia A,Tome W A,Thomas S,et al. Distribution of brain metastases in relation to the hippocampus:implications for neurocognitive functional preservation[J]. Int J Radiat Oncol Biol Phys,2007,68(4):971-977. DOI:10.1016/j.ijrobp.2007.02.016 [7] Gondi V,Tome WA,Marsh J,et al. Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy:safety profile for RTOG 0933[J]. Radiother Oncol,2010,95(3):327-331. DOI:10.1016/j.radonc.2010.02.030. [8] Harth S,Abo-Madyan Y,Zheng L,et al. Estimation of intracranial failure risk following hippocampal-sparing whole brain radiotherapy[J]. Radiother Oncol,2013,109(1):152-158. DOI:10.1016/j.radonc.2013.09.009. [9] Sekine A,Kato T,Hagiwara E,et al. Metastatic brain tumors from non-small cell lung cancer with EGFR mutations:distinguishing influence of exon 19 deletion on radiographic features[J]. Lung Cancer,2012,77(1):64-69. DOI:10.1016/j.lungcan.2011.12.017. [10] Sun B,Huang Z,Wu S,et al. Incidence and relapse risk of intracranial metastases within the perihippocampal region in 314 patients with breast cancer[J]. Radiother Oncol,2016,118(1):181-186. DOI:10.1016/j.radonc.2015.11.010. [11] Wu SG,Sun JY,Tong Q,et al. Clinical features of brain metastases in breast cancer:an implication for hippocampal-sparing whole-brain radiation therapy[J]. Ther Clin Risk Manag,2016,12:1849-1853. DOI:10.2147/TCRM. S124212. [12] Hong AM,Suo C,Valenzuela M,et al. Low incidence of melanoma brain metastasis in the hippocampus[J]. Radiother Oncol,2014,111(1):59-62. DOI:10.1016/j.radonc.2014.01.012. [13] Kundapur V,Ellchuk T,Ahmed S,et al. Risk of hippocampal metastases in small cell lung cancer patients at presentation and after cranial irradiation:a safety profile study for hippocampal sparing during prophylactic or therapeutic cranial irradiation[J]. Int J Radiat Oncol Biol Phys,2015,91(4):781-786. DOI:10.1016/j.ijrobp.2014.12.026. [14] Zhao L,Shen Y,Guo JD,et al. Analyses of distribution and dosimetry of brain metastases in small cell lung cancer with relation to the neural stem cell regions:feasibility of sparing the hippocampus in prophylactic cranial irradiation[J]. Radiat Oncol,2017,12(1):118. DOI:10.1186/s13014-017-0855-3. [15] Takano K,Kinoshita M,Takagaki M,et al. Different spatial distributions of brain metastases from lung cancer by histological subtype and mutation status of epidermal growth factor receptor[J]. Neuro Oncol,2016,18(5):716-724. DOI:10.1093/neuonc/nov266. [16] Delattre JY,Krol G,Thaler HT,et al. Distribution of brain metastases[J]. Arch Neurol,1988,45(7):741-744. [17] Hwang TL,Close TP,Grego JM,et al. Predilection of brain metastasis in gray and white matter junction and vascular border zones[J]. Cancer,1996,77(8):1551-1555. [18] Quattrocchi CC,Errante Y,Gaudino C,et al. Spatial brain distribution of intra-axial metastatic lesions in breast and lung cancer patients[J]. J Neurooncol,2012,110(1):79-87. DOI:10.1007/s11060-012-0937-x. [19] Iuchi T,Shingyoji M,Itakura M,et al. Frequency of brain metastases in non-small-cell lung cancer,and their association with epidermal growth factor receptor mutations[J]. Int J Clin Oncol,2015,20(4):674-679. DOI:10.1007/s10147-014-0760-9. [20] Heon S,Yeap BY,Britt GJ,et al. Development of central nervous system metastases in patients with advanced non-small cell lung cancer and somatic EGFR mutations treated with gefitinib or erlotinib[J]. Clin Cancer Res,2010,16(23):5873-5882. DOI:10.1158/1078-0432. CCR-10-1588. [21] Rangachari D,Yamaguchi N,VanderLaan PA,et al. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers[J]. Lung Cancer,2015,88(1):108-111. DOI:10.1016/j.lungcan.2015.01.020. [22] Ge M,Zhuang Y,Zhou X,et al. High probability and frequency of EGFR mutations in non-small cell lung cancer with brain metastases[J]. J Neurooncol,2017,135(2):413-418. DOI:10.1007/s11060-017-2590-x. [23] Wang R,Zhang Y,Pan Y,et al. Comprehensive investigation of oncogenic driver mutations in Chinese non-small cell lung cancer patients[J]. Oncotarget,2015,6(33):34300-34308. DOI:10.18632/oncotarget.5549. [24] Shi Y,Au J S,Thongprasert S,et al. A prospective,molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER)[J]. J Thorac Oncol,2014,9(2):154-162. DOI:10.1097/JTO.0000000000000033.
2019, Vol. 28 
