-
2015年,恶性肿瘤流行情况调查结果显示,我国恶性肿瘤的发病率约为285.83/10万,随着诊疗技术的提高,恶性肿瘤患者的生存率逐年上升,截至2015年,我国恶性肿瘤患者的5年生存率约为40.5%[1-2]。化疗是恶性肿瘤治疗的最基础方法,系统性的辅助化疗能够显著延长患者的生存期,但化疗往往伴随着系统或器官的损伤,影响肿瘤患者的生活质量。化疗导致的认知功能损害(chemotherapy-induced cognitive impairments,CICI)可对患者产生持续的严重影响[3]。
CICI包括化疗期间及化疗结束后患者的记忆力、注意力、学习能力、执行能力及信息处理速度等下降。Wefel等[4]研究结果显示,13%~70%的癌症患者化疗后出现了不同程度的认知功能损害。以往关于乳腺癌患者的CICI的研究较多,结果显示,65%的乳腺癌患者在化疗结束后短期内出现了认知功能损害,61%的患者在长期随访中出现了认知功能减退,而21%的患者在化疗前就已经出现了认知功能障碍[5-6]。越来越多的研究结果表明,在直肠癌、淋巴瘤、肺癌等其他肿瘤中亦存在CICI[7-9]。然而,CICI的机制尚不明确。其原因可能与DNA损伤和氧化应激、端粒缩短、线粒体功能障碍等有关[10-12]。笔者对肿瘤患者CICI的神经影像学研究进展进行综述,旨在解释CICI的机制及可能的防治措施。
肿瘤患者化疗后认知功能损害的影像学研究进展
Advances in imaging studies of cognitive impairments in tumor patients after chemotherapy
-
摘要: 非中枢系统的肿瘤患者经化疗等相关治疗后,生存期不断延长,但随之出现的不良反应,即化疗导致的认知功能损害(CICI)逐渐引起重视。CICI的患者的学习能力、记忆力、注意力、执行能力和信息处理速度等均下降,严重影响其生活质量。近年来,有很多研究报道了CICI的神经影像学改变,包括结构和功能MRI显示的以额叶、颞叶、顶叶为主的脑白质的减少,以及18F-氟脱氧葡萄糖(FDG) PET/CT显示的以额叶、部分边缘系统为主的脑葡萄糖代谢水平降低。笔者综述了肿瘤患者CICI的神经影像学研究进展,旨在解释CICI的潜在机制及可能的防治措施。
-
关键词:
- 药物疗法 /
- 认知损害 /
- 磁共振成像 /
- 正电子发射断层显像术 /
- 肿瘤
Abstract: The survival period of patients with noncentral system is greatly prolonged after chemotherapy and other related treatments. The side effects caused by chemotherapy, that is, chemotherapy-induced cognitive impairments (CICI), have received increasing attention. The reduced learning, memory, attention, executive function, and information processing speed of cancer survivors with CICI seriously impairs the quality of life of the survivors. In recent years, many studies have reported on the neuroimaging changes in CICI. These changes include the decreases in white matter in the frontal lobe, temporal lobe, and parietal lobe shown by structural and functional MRI, and the decreases in glucose metabolism in the frontal lobe and part of limbic system revealed by 18F-fluorodeoxyglucose (FDG) PET/CT. This article reviews the progress of neuroimaging research tumor patients on CICI to explain the potential mechanism and the possible prevention and treatment measures of CICI. -
[1] 郑荣寿, 孙可欣, 张思维, 等. 2015年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2019, 41(1): 19−28. DOI: 10.3760/cma.j.issn.0253-3766.2019.01.005.
Zheng RS, Sun KX, Zhang SW, et al. Report of cancer epidemiology in China, 2015[J]. Chin J Oncology, 2019, 41(1): 19−28. DOI: 10.3760/cma.j.issn.0253-3766.2019.01.005.[2] Zeng H, Chen W, Zheng R, et al. Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries[J/OL]. Lancet Glob Health, 2018, 6(5): e555−e567 [2020-03-12]. http:www.sciencedirect.com/science/article/pii/S2214109X1830127X?via%3Dihub. DOI: 10.1016/S2214-109X(18)30127-X. [3] Janelsins MC, Heckler CE, Peppone LJ, et al. Cognitive complaints in survivors of breast cancer after chemotherapy compared with age-matched controls: an analysis from a nationwide, multicenter, prospective longitudinal study[J]. J Clin Oncol, 2017, 35(5): 506−514. DOI: 10.1200/JCO.2016.68.5826. [4] Wefel J, Vardy J, Ahles T, et al. International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer[J]. Lancet Oncol, 2011, 12(7): 703−708. DOI: 10.1016/S1470-2045(10)70294-1. [5] Wefel JS, Saleeba A, Buzdar A, et al. Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer[J]. Cancer, 2010, 116(14): 3348−3356. DOI: 10.1002/cncr.25098. [6] Li X, Chen HJ, Lv Y, et al. Diminished gray matter density mediates chemotherapy dosage-related cognitive impairment in breast cancer patients[J/OL]. Sci Rep, 2018, 8(1): 13801 [2020-03-12]. http:www.ncbi.nlm.nih.gov/pmc/articles/PMC6138678. DOI: 10.1038/s41598-018-32257-w. [7] Machado AM, Fagundes TC, Mafra A, et al. Effects on 18F-FDG PET/CT brain glucose metabolism in rectal cancer patients undergoing neoadjuvant chemotherapy[J]. Clin Nucl Med, 2017, 42(12): e484−e490. DOI: 10.1097/RLU.0000000000001862. [8] Trachtenberg E, Mashiach T, Ben Hayun R, et al. Cognitive impairment in hodgkin lymphoma survivors[J]. Br J Haematol, 2018, 182(5): 670−678. DOI: 10.1111/bjh.15448. [9] Bromis K, Gkiatis K, Karanasiou I, et al. Altered brain functional connectivity in small-cell lung cancer patients after chemotherapy treatment: a resting-state fMRI study[J/OL]. Comput Math Methods Med, 2017, 2017: 1403940 [2020-03-10]. http:www.ncbi.nlm.nih.gov/pmc/articles/PMC5535744. DOI: 10.1155/2017/1403940. [10] Carozzi VA, Canta A, Chiorazzi A. Chemotherapy-induced peripheral neuropathy: what do we know about mechanisms?[J]. Neurosci Lett, 2015, 596: 90−107. DOI: 10.1016/j.neulet.2014.10.014. [11] Li DW, Sun JY, Wang K, et al. Attenuation of cisplatin-induced neurotoxicity by cyanidin, a natural inhibitor of ROS-mediated apoptosis in PC12 cells[J]. Cell Mol Neurobiol, 2015, 35(7): 995−1001. DOI: 10.1007/s10571-015-0194-6. [12] Lomeli N, Di K, Czerniawski J, et al. Cisplatin-induced mitochondrial dysfunction is associated with impaired cognitive function in rats[J]. Free Radic Biol Med, 2017, 102: 274−286. DOI: 10.1016/j.freeradbiomed.2016.11.046. [13] Wefel JS, Kesler SR, Noll KR, et al. Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer-related cognitive impairment in adults[J]. CA Cancer J Clin, 2015, 65(2): 123−138. DOI: 10.3322/caac.21258. [14] Kesler SR. Default mode network as a potential biomarker of chemotherapy-related brain injury[J]. Neurobiol Aging, 2014, 35(Suppl 2): S11−19. DOI: 10.1016/j.neurobiolaging.2014.03.036. [15] Correa DD, Root JC, Kryza-Lacombe M, et al. Brain structure and function in patients with ovarian cancer treated with first-line chemotherapy: a pilot study[J]. Brain Imaging Behav, 2017, 11(6): 1652−1663. DOI: 10.1007/s11682-016-9608-4. [16] Inagaki M, Yoshikawa E, Matsuoka Y, et al. Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy[J]. Cancer, 2007, 109(1): 146−156. DOI: 10.1002/cncr.22368. [17] Amidi A, Agerbæk M, Wu LM, et al. Changes in cognitive functions and cerebral grey matter and their associations with inflammatory markers, endocrine markers, and APOE genotypes in testicular cancer patients undergoing treatment[J]. Brain Imaging Behav, 2017, 11(3): 769−783. DOI: 10.1007/s11682-016-9552-3. [18] Concha L. A macroscopic view of microstructure: using diffusion-weighted images to infer damage, repair, and plasticity of white matter[J]. Neuroscience, 2014, 276: 14−28. DOI: 10.1016/j.neuroscience.2013.09.004. [19] Kesler SR, Watson CL, Blayney DW. Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer[J]. Neurobiol Aging, 2015, 36(8): 2429−2442. DOI: 10.1016/j.neurobiolaging.2015.04.015. [20] Stouten-Kemperman MM, de Ruiter MB, Koppelmans V, et al. Neurotoxicity in breast cancer survivors ≥10 years post-treatment is dependent on treatment type[J]. Brain Imaging Behavior, 2015, 9(2): 275−284. DOI: 10.1007/s11682-014-9305-0. [21] Billiet T, Emsell L, Vandenbulcke M, et al. Recovery from chemotherapy-induced white matter changes in young breast cancer survivors?[J]. Brain Imaging Behavior, 2018, 12(1): 64−77. DOI: 10.1007/s11682-016-9665-8. [22] Cimprich B, Reuter-Lorenz P, Nelson J, et al. Prechemotherapy alterations in brain function in women with breast cancer[J]. J Clin Exp Neuropsychol, 2010, 32(3): 324−331. DOI: 10.1080/13803390903032537. [23] Vardy JL, Stouten-Kemperman MM, Pond G, et al. A mechanistic cohort study evaluating cognitive impairment in women treated for breast cancer[J]. Brain Imaging Behav, 2019, 13(1): 15−26. DOI: 10.1007/s11682-017-9728-5. [24] McDonald BC, Conroy SK, Ahles TA, et al. Alterations in brain activation during working memory processing associated with breast cancer and treatment: a prospective functional magnetic resonance imaging study[J]. J Clin Oncol, 2012, 30(20): 2500−2508. DOI: 10.1200/JCO.2011.38.5674. [25] Silverman DHS, Dy CJ, Castellon SA, et al. Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5–10 years after chemotherapy[J]. Breast Cancer Res Treat, 2007, 103(3): 303−311. DOI: 10.1007/s10549-006-9380-z. [26] Chiaravalloti A, Pagani M, Di Pietro B, et al. Is cerebral glucose metabolism affected by chemotherapy in patients with Hodgkin's lymphoma?[J]. Nucl Med Commun, 2013, 34(1): 57−63. DOI: 10.1097/MNM.0b013e32835aa7de. [27] Chiaravalloti A, Pagani M, Cantonetti M, et al. Brain metabolic changes in Hodgkin disease patients following diagnosis and during the disease course: an 18F-FDG PET/CT study[J]. Oncol Lett, 2015, 9(2): 685−690. DOI: 10.3892/ol.2014.2765. [28] Shrot S, Abebe-Campino G, Toren A, et al. Fluorodeoxyglucose detected changes in brain metabolism after chemotherapy in pediatric non-Hodgkin lymphoma[J]. Pediatr Neurol, 2019, 92: 37−42. DOI: 10.1016/j.pediatrneurol.2018.10.019. [29] Deprez S, Kesler SR, Saykin AJ, et al. International Cognition and Cancer Task Force recommendations for neuroimaging methods in the study of cognitive impairment in non-CNS cancer patients[J]. J Natl Cancer Inst, 2018, 110(3): 223−231. DOI: 10.1093/jnci/djx285.
计量
- 文章访问数: 3441
- HTML全文浏览量: 2502
- PDF下载量: 19