鼻咽癌患者同步放化疗过程中营养状况变化及其临床意义

发布时间：2017-12-27 06:04

本文关键词：鼻咽癌患者同步放化疗过程中营养状况变化及其临床意义　出处：《广西医科大学》2017年博士论文　论文类型：学位论文

【摘要】：第一部分鼻咽癌同步放化疗过程中营养状况及相关血液学指标的变化目的:通过对鼻咽癌同步放化疗过程中营养状况及相关血液学指标变化的分析,了解同步放化疗对鼻咽癌患者营养状况的影响,探讨鼻咽癌营养不良的可靠监测因子。方法:回顾性分析了2010年8月-2011年12月初治于广西医科大学附属肿瘤医院放疗科的134例鼻咽癌患者,其符合下列条件:年满18周岁;病理确诊为非角化性鼻咽癌,放疗采用调强适形放疗(intensity-modulated radiotherapy,IMRT)技术,排除远处转移和其它恶性肿瘤病史者。具有完整个人资料、营养状况和相关血液学指标信息:年龄、性别、个人疾病史、吸烟、饮酒、营养支持、身高、卡式评分(Karnofsky performance status,KPS),同步化疗,体重指数(Body mass index,BMI),临床分期TNM(Tumor-node metastasis classification),病理分型,以及营养风险筛查(Nutritional risk screening,NRS),患者主观整体评估(Patient-generated subjective global assessment,PG-SGA)定性和定量测定,相关血液学指标,如总蛋白(Total Protein,TP),血清白蛋白(albumin,ALB),球蛋白(Globulin,GLOB),铁蛋白(Transferrin,TRF),肌酐(Creatinine,Cre),尿素氮(Blood urea nitrogen,BUN),血小板(Blood platelet,PLT),白细胞(White blood cell,WBC),中性粒细胞计数(Neutrophil count,NC),淋巴细胞计数(Lymphocyte count,LC),红细胞(Red blood corpuscle,RBC),血红蛋白(Hemoglobin,Hb)水平。探讨放化疗过程中鼻咽癌患者营养状况和相关血液学指标的变化。对于服从正态分布或近似正态分布的计量数据采用均数±标准差(±s)的形式来描述,比较同组不同时间点之间的定量资料用方差分析,进一步使用LSD-t检验对其进行两两比较,用Pearson相关分析和Spearman秩和检验分析相关血液学指标与NRS2002和PG-SGA-定性的相关关系,0.05表示差异有统计学意义。结果:l、鼻咽癌患者在放化疗治疗前,BMI18.5的患者(低体重营养不良者)有5.97%(8/134),有27.61%(37/134)的患者在过去3个月内丢失5%的体重。NRS总分≥3.0分(即有营养不良的风险,需营养支持治疗)的患者有30.6%(41/134),PG-SGA-定性C级者(≥9分)为3.73%(5/134),B级(2-8分)者为43.28%(58/134)。2.放疗中期,BMI18.5的患者(低体重营养不良者)有11.9%(16/134),体重减轻者的比例范围-5.45%~11.32%,平均值为2.4%。其中体重减轻者占82.09%(110/134),减轻超过5%者占21.64%(29/134),减轻超过10%者占7.46%(10/134)。NRS总分≥3.0分患者有75.37%(101/134),PG-SGA-定性C级者(≥9分)为20.9%(28/134),B级(2-8分)者为55.97%(75/134)。3放疗结束时,BMI18.5的患者(低体重营养不良者)有18.66%(25/134)。体重减轻比例的范围-3.64%~19.51%,平均值为6.27%。其中体重减轻者占89.55%(120/134),减轻超过5%者占32.09%(43/134),减轻超过10%者占28.36%(38/134)。NRS总分≥3.0分的患者有85.82%(115/134),PG-SGA-定性C级者(≥9分)为32.09%(43/134),B级(2-8分)者为58.96%(79/134)。4.与治疗前相比,鼻咽癌患者在放疗中期以及放疗结束时,体重指数、NRS和PG-SGA均较之前明显变差(p0.001),相对应的血液学指标,除了肌酐无明显变化外,总蛋白,血清白蛋白,球蛋白,尿素氮,白细胞,中性粒细胞计数,淋巴细胞计数,红细胞,血红蛋白水平均持续性下降,铁蛋白持续性升高,差异具有统计学意义(p0.001)。5.治疗前白蛋白与NRS2002评分,红细胞和血红蛋白与NRS2002评分和PG-SGA评分均呈负相关(p0.001)。在治疗4周时的总蛋白、白蛋白和血红蛋白均与PG-SGA呈中度负相关(p0.001)。治疗结束时白细胞、中性粒细胞计数、淋巴细胞计数、红细胞及血红蛋白与NRS2002评分呈中度负相关,而总蛋白和白蛋白与PG-SGA评分呈中度负相关,白细胞、中性粒细胞、淋巴细胞、红细胞和血红蛋白与PG-SGA评分呈高度负相关。结论:鼻咽癌患者在治疗前就有较高的营养不良的风险,并在同步放化疗过程中,相应的营养状况和血液学指标均表现为持续的恶化。白蛋白、红细胞和血红蛋白与营养状况评分有一定的相关性,因此可以作为患者营养状况的监测因子。第二部分鼻咽癌患者同步放化疗过程中营养不良的影响因素目的:研究鼻咽癌患者同步放化疗过程中营养不良的影响因素方法:回顾性分析了134例经病理证实的初治的并完成IMRT的鼻咽癌病例。由2名放疗科医生和影像科医生在治疗前的MR图像上对肿瘤进行测量,按照肿瘤侵犯的范围在MRI上逐层勾画肿瘤边界,得到每层肿瘤的面积,计算肿瘤体积(Gross tumor volume,GTV)。鼻咽及颈部MR图像记录肿瘤侵犯的解剖部位:咽旁间隙,腭肌/椎前肌,鼻腔,口咽,下咽,颅底骨质,翼腭窝,鼻旁窦,翼内肌,翼外肌,颅内。根据1991年WHO鼻咽癌病理组织学分型,选取WHO-Ⅱ和Ⅲ型,分为分化型和未分化型组。研究患者的一般特征(性别,年龄,同步化疗,放疗前体重量减轻,BMI指数,伴随疾病,吸烟习惯,饮酒史和营养支持情况)和肿瘤情况(TNM分期,分化程度,肿瘤体积以及侵犯的部位),评估鼻咽癌放化疗前中后的血液学指标(总蛋白,白蛋白,球蛋白,铁蛋白,肌酐,尿素氮,血小板,白细胞,中性粒细胞计数,淋巴细胞计数,红细胞,血红蛋白)和营养状况评分(NR2002评分和PG-SGA评分)的变化,从而对鼻咽癌患者营养状况变化和影响因素进行综合分析。对于服从正态分布或近似正态分布的计量数据采用均数±标准差(±s)的形式来描述,组间差异的比较使用独立样本t检验来分析。用Pearson相关分析和spearman秩和检验分析相关关系,P0.05为差异具有统计学意义。结果:1.年龄与放疗前PG-SGA定量评分呈弱相关(相关系数=0.212,P=0.014),同步化疗与放疗后PG-SGA呈高度相关(相关系数=0.751,P0.001),性别、吸烟、饮酒和个人疾病与放疗前PG-SGA定量评分无相关关系。年龄、性别、个人疾病史、吸烟、饮酒和肠外营养均与放疗后PG-SGA无相关关系(P均0.05)。2.T分期与治疗结束时的白蛋白、血红蛋白和第三次体重减轻为中度相关(相关系数为-0.441,-0.395,0.781和0.493,p均0.001),与PG-SGA定量评分为高度相关关系(相关系数0.781,0.001)。3.肿瘤N分期与白蛋白、血红蛋白和PG-SGA均为弱相关(相关系数为-0.190,-0.203和0.235,p=0.028,0.018和0.006)。4.侵犯部位中腭肌/椎前肌、口咽、颅底骨质、咀嚼肌间隙、鼻旁窦、颅内侵犯与PG-SGA定量评分呈中度正相关(相关系数为-0.507,-0.469,0.618,0.467,0.527和0.548,p均0.001)。5.治疗前肿瘤体积与治疗结束时白蛋白、血红蛋白为负相关,与PG-SGA定量评分和第三次体重减轻为正相关(相关系数为-0.423,-0.24,0.786和0.502,p分别为0.001,0.005,0.001,0.001)。大肿瘤体积(≥24.7cm3)与小肿瘤体积(24.7cm3)在同步放化疗前和后的PG-SGA定量评分之间有显著统计学差异(P均0.001)。6.不能认为病理类型与白蛋白、血红蛋白、第三次体重减轻和PG-SGA定量评分之间存在相关关系(相关系数分别为-0.004,-0.045,0.004,0.049,P均0.05)。结论:1.同步化疗、肿瘤体积、T分期、腭肌/椎前肌、口咽、颅底骨质、咀嚼肌间隙、鼻旁窦、颅内侵犯是鼻咽癌同步放化疗患者营养不良的主要相关因素。2.年龄、女性、吸烟、饮酒、N分期和分化程度与鼻咽癌患者同步放化疗后营养不良的弱相关或无相关关系。第三部分鼻咽癌患者同步放化疗过程中营养不良的预后意义目的:分析鼻咽癌患者一般特征和放化疗前中后主要的血液学指标和营养状况,评价营养不良对鼻咽癌患者的预后价值。方法:回顾性分析了2010年8月-2011年12月在广西医科大学附属肿瘤医院134例经病理证实的初治的并完成IMRT的鼻咽癌病例。研究患者的一般特征(性别,年龄,伴随疾病,吸烟,饮酒史和营养支持情况)、鼻咽癌放化疗前中后的血液学指标(白蛋白,红细胞,血红蛋白)和营养评分(NR2002评分和PG-SGA评分)对患者预后的影响。评价患者一般情况、血液学指标和营养状况评分以及临床T分期对5年累计生存(OS)、局部无复发生存(LRFS)、远处无转移生存(DMFS)的影响。懫用Cox比例风险回归模型对影响鼻咽癌的预后因素进行分析。结果:1.T1-T4的5年OS分别为89.7%,87.5%,78.4%和63.9%(p=0.04),但组间比较,T1和T2,T2和T3,T3和T4的p值均0.05。T1-T4期的5年LRFS分别为89.7%,90.6%,81.1%和88.9%(p=0.573),5年DMFS分别为89.7%,90.6%,81.1%和66.7%(p=0.029)。2.5年OS的独立预后因素为治疗前PG-SGA定量评分(HR 1.264,95%CI 1.071-1.491,P=0.006)和NRS2002(HR 3.903,95%CI 1.302-11.701,P=0.015);治疗中PG-SGA定量评分和血红蛋白,治疗后PG-SGA定量评分(HR0.77,95%CI0.687-0.863,p=0)和治疗后血红蛋白。5年LRFS的独立预后因素为治疗前红细胞,治疗前血红蛋白和治疗后红细胞(HR0.01,95%CI0.002-0.063,p=0.000)。5年DMFS的独立预后因素治疗前PG-SGA定量评分(HR1.369,95%CI1.169-1.604,p=0.000),治疗中PG-SGA定量评分(HR1.202,95%CI1.091-1.323,p=0.000),治疗后PG-SGA定量评分(HR0.869,95%CI0.762-0.99,p=0.035)和治疗后红细胞。结论:1.T分期不再是同步放化疗鼻咽癌独立的预后因素,T分期的亚组对于预后的预测缺乏分辨能力。2.PG-SGA定量评分在5年OS和DMFS表现出了较好的预测能力。但是对于局部无复发生存率,并没有发现独立的影响因素。
[Abstract]:Changes in nasopharyngeal carcinoma radiotherapy and chemotherapy in the process of nutritional status and related blood indexes: through the analysis of nasopharyngeal carcinoma radiotherapy and chemotherapy in the process of nutritional status and related blood index changes, radiotherapy and to understand the impact of chemotherapy on the nutritional status of patients with nasopharyngeal carcinoma, and to discuss the reliable monitoring factors of malnutrition in nasopharyngeal carcinoma. Methods: a retrospective analysis of 134 cases of nasopharyngeal carcinoma patients with initial treatment in August 2010 -2011 year in December the Department of radiation oncology Affiliated Hospital of Guangxi Medical University, which meet the following conditions: 18 years of age; pathological diagnosis of non keratinizing nasopharyngeal carcinoma radiotherapy using IMRT (intensity-modulated radiotherapy IMRT) technology, to exclude distant metastases and other malignant tumors history. With complete personal information, nutritional status and related blood indicators: information age and gender, disease history, smoking, drinking, nutritional support, height, KPS score (Karnofsky performance status, KPS), chemotherapy, body mass index (Body mass index BMI TNM (Tumor-node), clinical stage, pathological metastasis classification) type and nutritional risk screening (Nutritional risk, screening, NRS) in patients with subjective global assessment (Patient-generated subjective global assessment, PG-SGA) of qualitative and quantitative determination, hematological indicators such as total protein (Total, Protein, TP), serum albumin (albumin, ALB), immunoglobulins (Globulin, GLOB), iron protein (Transferrin, TRF), creatinine (Creatinine, Cre), blood urea nitrogen (Blood urea, nitrogen, BUN), platelet (Blood platelet, PLT), white blood cell (White blood cell, WBC), neutrophil count (Neutro Phil count, NC), lymphocyte count (Lymphocyte count, LC), red blood cell (Red blood corpuscle, RBC), hemoglobin (Hemoglobin, Hb) level. To investigate the changes of nutritional status and related hematological indexes in patients with nasopharyngeal carcinoma during radiotherapy and chemotherapy. For a normal distribution or approximate normal distribution of the data is measured by the mean and standard deviation (s) in the form of description, comparison between groups at different time points of the quantitative data by variance analysis, further use of LSD-t to test the 22 comparison, correlation with Pearson correlation analysis and Spearman test analysis the hematological indicators of NRS2002 and PG-SGA- and qualitative, 0.05 said the difference was statistically significant. Results: l and nasopharyngeal carcinoma patients had 5.97% (8/134) of BMI18.5 before radiotherapy and chemotherapy, and 27.61% (37/134) patients lost 5% of their weight in the past 3 months. The total score of NRS is greater than or equal to 3 points (i.e., risk of malnutrition need nutritional support therapy) 30.6% patients (41/134), PG-SGA- qualitative C grade (9 minute) was 3.73% (5/134), B (2-8) was 43.28% (58/134). 2. in the mid-term of radiotherapy, 11.9% (16/134) was found in patients with BMI18.5 (low weight malnutrition), and the proportion of people with weight loss was -5.45%~11.32%, with an average of 2.4%. Among them, the weight loss was 82.09% (110/134), more than 5% accounted for 21.64% (29/134), and 7.46% (10/134) was reduced by more than 10%. Score of NRS were higher than 3 in 75.37% (101/134), PG-SGA- qualitative C grade (9 minute) was 20.9% (28/134), B (2-8) was 55.97% (75/134). 3 at the end of radiotherapy, 18.66% (25/134) of BMI18.5 patients (low weight dystrophy) were found. The range of weight loss was -3.64%~19.51%, with an average of 6.27%. Among them, the weight loss was 89.55% (120/134), more than 5% accounted for 32.09% (43/134), and 28.36% (38/134) was reduced by more than 10%. The total score of NRS is greater than or equal to 3 points with 85.82% (115/134), PG-SGA- qualitative C grade (9 minute) was 32.09% (43/134), B (2-8) was 58.96% (79/134). 4. compared with before treatment, patients with nasopharyngeal carcinoma radiotherapy in the middle and at the end of radiotherapy, body mass index, NRS and PG-SGA were significantly worse than before (p0.001), corresponding to the hematological indexes, but no obvious change of creatinine, total protein, serum albumin, globulin, urea nitrogen, leukocyte, neutrophil count, lymphocyte count, erythrocyte, hemoglobin levels decreased progressively, ferritin increased, the difference was statistically significant (p0.001). 5. pre - treatment albumin and NRS2002 score, red blood cell and hemoglobin, NRS2002 score and PG-SGA score were negatively correlated (p0.001). The total protein, albumin and hemoglobin at the 4 week of treatment were negatively correlated with PG-SGA (p0.001). At the end of treatment, WBC, neutrophil count, lymphocyte count, red blood cell and hemoglobin and NRS2002 score were negatively correlated, while the total protein and albumin and PG-SGA score were negatively correlated, white blood cells, neutrophils, lymphocytes and red blood cells and red blood protein and PG-SGA score was negatively correlated. Conclusion: Patients with nasopharyngeal carcinoma have a higher risk of malnutrition before treatment. During the concurrent radiotherapy and chemotherapy, the corresponding nutritional status and hematological indexes all showed continuous deterioration. Albumin, red blood cells and hemoglobin have a certain correlation with the nutritional status score, so it can be used as a monitoring factor for the nutritional status of patients. The second part is about the influencing factors of malnutrition in patients with nasopharyngeal carcinoma during concurrent chemoradiotherapy. Objective: To study the influencing factors of malnutrition in nasopharyngeal carcinoma patients during concurrent chemoradiotherapy. Methods: a retrospective analysis of 134 cases of newly diagnosed nasopharyngeal carcinoma with IMRT confirmed by pathology was performed. The tumor was measured on the MR images of 2 radiology doctors and radiology doctors before treatment. According to the extent of tumor invasion, the tumor boundaries were delineated on MRI, and the area of each tumor was obtained, and the Gross tumor volume (GTV) was calculated. Nasopharyngeal and neck MR images were used to record anatomical locations of tumor invasion: parapharyngeal space, palatine muscle / anterior vertebral muscles, nasal cavity, oropharynx, hypopharynx, skull base, pterygopalatine fossa, paranasal sinus, pterygoid muscle, lateral pterygoid muscle, and intracranial. According to the histopathological classification of WHO nasopharyngeal carcinoma in 1991, WHO- II and type III were selected and divided into two types.
【学位授予单位】：广西医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R739.63

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