肺癌脑转移患者神经认知功能分析
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摘要
目的评估肺癌脑转移患者放疗前神经认知功能基线水平,确定导致患者神经认知功能损害的危险因素。方法回顾性分析74例肺癌脑转移患者的临床资料,所有患者均在头部放疗前1～2周进行神经认知功能量表评估。心理测量师根据各项量表得分,评估患者的神经认知功能水平,分为正常、轻度损害、中度损害及重度损害4个等级。应用R软件与EmpowerStats(易侕软件)分析认知评估结果与各临床特征的关系。采用Kappa检验比较体格检查与认知量表评估患者认知功能结果的一致性。对相关的因素作单因素分析及多因素分析。结果 74例患者中,临床体格检查发现认知下降21例(28. 4%),认知正常53例(71. 6%);神经认知量表评估结果显示认知正常6例(8. 1%)、轻度损害26例(35. 1%)、中度损害2例(2. 7%)、重度损害40例(54. 1%)。用Kappa检验比较两种评估方法的一致性,Kappa <0. 4,提示两种评估方法的差异显著。对认知功能损害的相关因素作单因素分析,结果显示可能影响患者神经认知功能损害程度的因素有年龄、KPS评分、GPA评分、RPA分级、转移瘤个数。多因素分析结果表明年龄≥60岁、RPAⅡ级以上是影响认知功能损害程度的独立危险因素。结论肺癌脑转移瘤患者在头部放疗前大多已出现程度不同的神经认知功能损害。年龄≥60岁、RPAⅡ级以上是神经认知功能损害的独立危险因素。
Objective To assess the baseline neurocognitive functions in patients with brain metastasis of lung cancer before radiotherapy,thus to determine the risk factors for neurocognitive function impairment. Methods The clinical data of patients suffering from brain metastasis from lung cancer were retrospectively analyzed. One-two weeks before radiotherapy for brain metastasis,several scales were used to assess the neurocognitive functions in the 74 patients.According to neurocognitive functions,the patients were assigned into 4 levels,normal,mild impairment,moderate impairment and severe impairment. All analyses were performed using the statistical package R. The correlations between cognitive assessment results and clinical characteristics were analyzed. And Kappa test was used to analyze the consistency of physical examination and cognitive scales. The related factors were analyzed with univariate and multivariate analysis.Results There were 21 cases of cognitive decline( 28. 4%) and 53 cases of normal cognition( 71. 6%),while the results of cognitive scales revealed that there were 6 cases of normal cognition( 8. 1%),26 cases of mild impairment( 35. 1%),2 cases of moderate impairment( 2. 7%) and 40 cases of severe impairment( 54. 1%). The result of Kappa test showed Kappa < 0. 4,indicating that the differences between cognitive scale results and physical examination were significant. The univariate analysis on the factors related to neurocognitive function impairment revealed that the risk factors that may affect the degree of neurocognitive function impairment included age,KPS score,GPA score,RPA class and the number of metastatic tumors. Multivariate analysis showed that age≥60 years old and RPA class > Ⅱ were the independent risk factors for neurocognitive function impairment. Conclusion Patients with brain metastasis of lung cancer have various degrees of neurocognitive function impairment before radiotherapy. Age≥60 years old and RPA class > Ⅱ are considered as independent risk factors for neurocognitive function impairment.
Objective To assess the baseline neurocognitive functions in patients with brain metastasis of lung cancer before radiotherapy,thus to determine the risk factors for neurocognitive function impairment. Methods The clinical data of patients suffering from brain metastasis from lung cancer were retrospectively analyzed. One-two weeks before radiotherapy for brain metastasis,several scales were used to assess the neurocognitive functions in the 74 patients.According to neurocognitive functions,the patients were assigned into 4 levels,normal,mild impairment,moderate impairment and severe impairment. All analyses were performed using the statistical package R. The correlations between cognitive assessment results and clinical characteristics were analyzed. And Kappa test was used to analyze the consistency of physical examination and cognitive scales. The related factors were analyzed with univariate and multivariate analysis.Results There were 21 cases of cognitive decline( 28. 4%) and 53 cases of normal cognition( 71. 6%),while the results of cognitive scales revealed that there were 6 cases of normal cognition( 8. 1%),26 cases of mild impairment( 35. 1%),2 cases of moderate impairment( 2. 7%) and 40 cases of severe impairment( 54. 1%). The result of Kappa test showed Kappa < 0. 4,indicating that the differences between cognitive scale results and physical examination were significant. The univariate analysis on the factors related to neurocognitive function impairment revealed that the risk factors that may affect the degree of neurocognitive function impairment included age,KPS score,GPA score,RPA class and the number of metastatic tumors. Multivariate analysis showed that age≥60 years old and RPA class > Ⅱ were the independent risk factors for neurocognitive function impairment. Conclusion Patients with brain metastasis of lung cancer have various degrees of neurocognitive function impairment before radiotherapy. Age≥60 years old and RPA class > Ⅱ are considered as independent risk factors for neurocognitive function impairment.
引文
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[2]Gondi V,Pugh SL,Tome WA,et al. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases(RTOG 0933):a phaseⅡmulti-institutional trial[J]. J Clin Oncol,2014,32(34):3810-3816.
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[8]Newton HB. Symptom management and supportive care of the patient with brain metastases[J]. Cancer Treat Res,2007,136:53-73.
[9]Pinkham MB,Sanghera P,Wall GK,et al. Neurocognitive Effects Following Cranial Irradiation for Brain Metastases[J]. Clin Oncol,2015,27(11):630-639.
[10]Chang E,Wefel J,Hess K,et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation:a randomised controlled trial[J]. Lancet Oncol,2009,10(11):1037-1044.
[11]Brown PD,Jaeckle K,Ballman KV,et al. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases:A Randomized Clinical Trial[J]. JAMA,2016,316(4):401-409.
[12]Barani IJ,Benedict SH,Lin PS. Neural stem cells:implications for the conventional radiotherapy of central nervous system malignancies[J]. Int J Radiat Oncol Biol Phys,2007,68(2):324-333.
[13]Sun A,Bae K,Gore EM,et al. PhaseⅢtrial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung cancer:neurocognitive and quality-of-life analysis[J]. J Clin Oncol,2011,29(3):279-286.
[14]Saito H,Tanaka K,Kanemoto A,et al. Factors Affecting the Baseline and Post-Treatment Scores on the Hopkins Verbal Learning Test-Revised Japanese Version before and after WholeBrain Radiation Therapy[J]. Int J Mol Sci,2016,17(11):E1834.
[15]Hoops S,Nazem S,Siderowf AD,et al. Validity of the Mo CA and MMSE in the detection of MCI and dementia in Parkinson disease[J]. Neurology,2009,73(21):1738-1745.
[16]Chang EL,Wefel JS,Maor MH,et al. A pilot study of neurocognitive function in patients with one to three new brain metastases initially treated with stereotactic radiosurgery alone[J]. Neurosurgery,2007,60(2):277-283.
[17]Gerstenecker A,Nabors LB,Meneses K,et al. Cognition in patients with newly diagnosed brain metastasis:profiles and implications[J]. J Neuro Oncol,2014,120(1):179-185.
[18]Day J,Gillespie DC,Rooney AG,et al. Neurocognitive Deficits and Neurocognitive Rehabilitation in Adult Brain Tumors[J].Curr Treat Options Neurol,2016,18(5):22.
[19]Habets EJ,Dirven L,Wiggenraad RG,et al. Neurocognitive functioning and health-related quality of life in patients treated with stereotactic radiotherapy for brain metastases:a prospective study[J]. Neuro Oncol,2016,18(3):435-444.
[20]Meyers CA,Smith JA,Bezjak A,et al. Neurocognitive function and progression in patients with brain metastases treated with wholebrain radiation and motexafin gadolinium:results of a randomized phaseⅢtrial[J]. J Clin Oncol,2004,22(1):157-165.
[21]Aoyama H,Tago M,Kato N,et al. Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone[J]. Int J Radiat Oncol Bio Physics,2007,68(5):1388-1395.
[22]Meyers CA. Neurocognitive dysfunction in cancer patients[J].Oncology(Williston Park),2000,14(1):75-79.
[2]Gondi V,Pugh SL,Tome WA,et al. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases(RTOG 0933):a phaseⅡmulti-institutional trial[J]. J Clin Oncol,2014,32(34):3810-3816.
[3]Lin SY,Yang CC,Wu YM,et al. Evaluating the impact of hippocampal sparing during whole brain radiotherapy on neurocognitive functions:A preliminary report of a prospective phaseⅡstudy[J]. Biomed J,2015,38(5):439-449.
[4]Brown PD,Pugh S,Laack NN,et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy:a randomized,double-blind,placebo-controlled trial[J]. Neuro Oncol,2013,15(10):1429-1437.
[5]Rapp SR,Case LD,Peiffer A,et al. Donepezil for Irradiated Brain Tumor Survivors:A PhaseⅢRandomized Placebo-Controlled Clinical Trial[J]. J Clin Oncol,2015,33(15):1653-1659.
[6]吴江.神经病学[M].北京:人民卫生出版社,2005.
[7]van der Meer PB,Habets EJJ,Wiggenraad RG,et al. Individual changes in neurocognitive functioning and health-related quality of life in patients with brain oligometastases treated with stereotactic radiotherapy[J]. J Neuro Oncol,2018,139(2):359-368.
[8]Newton HB. Symptom management and supportive care of the patient with brain metastases[J]. Cancer Treat Res,2007,136:53-73.
[9]Pinkham MB,Sanghera P,Wall GK,et al. Neurocognitive Effects Following Cranial Irradiation for Brain Metastases[J]. Clin Oncol,2015,27(11):630-639.
[10]Chang E,Wefel J,Hess K,et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation:a randomised controlled trial[J]. Lancet Oncol,2009,10(11):1037-1044.
[11]Brown PD,Jaeckle K,Ballman KV,et al. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases:A Randomized Clinical Trial[J]. JAMA,2016,316(4):401-409.
[12]Barani IJ,Benedict SH,Lin PS. Neural stem cells:implications for the conventional radiotherapy of central nervous system malignancies[J]. Int J Radiat Oncol Biol Phys,2007,68(2):324-333.
[13]Sun A,Bae K,Gore EM,et al. PhaseⅢtrial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung cancer:neurocognitive and quality-of-life analysis[J]. J Clin Oncol,2011,29(3):279-286.
[14]Saito H,Tanaka K,Kanemoto A,et al. Factors Affecting the Baseline and Post-Treatment Scores on the Hopkins Verbal Learning Test-Revised Japanese Version before and after WholeBrain Radiation Therapy[J]. Int J Mol Sci,2016,17(11):E1834.
[15]Hoops S,Nazem S,Siderowf AD,et al. Validity of the Mo CA and MMSE in the detection of MCI and dementia in Parkinson disease[J]. Neurology,2009,73(21):1738-1745.
[16]Chang EL,Wefel JS,Maor MH,et al. A pilot study of neurocognitive function in patients with one to three new brain metastases initially treated with stereotactic radiosurgery alone[J]. Neurosurgery,2007,60(2):277-283.
[17]Gerstenecker A,Nabors LB,Meneses K,et al. Cognition in patients with newly diagnosed brain metastasis:profiles and implications[J]. J Neuro Oncol,2014,120(1):179-185.
[18]Day J,Gillespie DC,Rooney AG,et al. Neurocognitive Deficits and Neurocognitive Rehabilitation in Adult Brain Tumors[J].Curr Treat Options Neurol,2016,18(5):22.
[19]Habets EJ,Dirven L,Wiggenraad RG,et al. Neurocognitive functioning and health-related quality of life in patients treated with stereotactic radiotherapy for brain metastases:a prospective study[J]. Neuro Oncol,2016,18(3):435-444.
[20]Meyers CA,Smith JA,Bezjak A,et al. Neurocognitive function and progression in patients with brain metastases treated with wholebrain radiation and motexafin gadolinium:results of a randomized phaseⅢtrial[J]. J Clin Oncol,2004,22(1):157-165.
[21]Aoyama H,Tago M,Kato N,et al. Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone[J]. Int J Radiat Oncol Bio Physics,2007,68(5):1388-1395.
[22]Meyers CA. Neurocognitive dysfunction in cancer patients[J].Oncology(Williston Park),2000,14(1):75-79.