本文關(guān)鍵詞：鼻咽癌患者同步放化療過程中營(yíng)養(yǎng)狀況變化及其臨床意義　出處：《廣西醫(yī)科大學(xué)》2017年博士論文　論文類型：學(xué)位論文

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【摘要】：第一部分鼻咽癌同步放化療過程中營(yíng)養(yǎng)狀況及相關(guān)血液學(xué)指標(biāo)的變化目的:通過對(duì)鼻咽癌同步放化療過程中營(yíng)養(yǎng)狀況及相關(guān)血液學(xué)指標(biāo)變化的分析,了解同步放化療對(duì)鼻咽癌患者營(yíng)養(yǎng)狀況的影響,探討鼻咽癌營(yíng)養(yǎng)不良的可靠監(jiān)測(cè)因子。方法:回顧性分析了2010年8月-2011年12月初治于廣西醫(yī)科大學(xué)附屬腫瘤醫(yī)院放療科的134例鼻咽癌患者,其符合下列條件:年滿18周歲;病理確診為非角化性鼻咽癌,放療采用調(diào)強(qiáng)適形放療(intensity-modulated radiotherapy,IMRT)技術(shù),排除遠(yuǎn)處轉(zhuǎn)移和其它惡性腫瘤病史者。具有完整個(gè)人資料、營(yíng)養(yǎng)狀況和相關(guān)血液學(xué)指標(biāo)信息:年齡、性別、個(gè)人疾病史、吸煙、飲酒、營(yíng)養(yǎng)支持、身高、卡式評(píng)分(Karnofsky performance status,KPS),同步化療,體重指數(shù)(Body mass index,BMI),臨床分期TNM(Tumor-node metastasis classification),病理分型,以及營(yíng)養(yǎng)風(fēng)險(xiǎn)篩查(Nutritional risk screening,NRS),患者主觀整體評(píng)估(Patient-generated subjective global assessment,PG-SGA)定性和定量測(cè)定,相關(guān)血液學(xué)指標(biāo),如總蛋白(Total Protein,TP),血清白蛋白(albumin,ALB),球蛋白(Globulin,GLOB),鐵蛋白(Transferrin,TRF),肌酐(Creatinine,Cre),尿素氮(Blood urea nitrogen,BUN),血小板(Blood platelet,PLT),白細(xì)胞(White blood cell,WBC),中性粒細(xì)胞計(jì)數(shù)(Neutrophil count,NC),淋巴細(xì)胞計(jì)數(shù)(Lymphocyte count,LC),紅細(xì)胞(Red blood corpuscle,RBC),血紅蛋白(Hemoglobin,Hb)水平。探討放化療過程中鼻咽癌患者營(yíng)養(yǎng)狀況和相關(guān)血液學(xué)指標(biāo)的變化。對(duì)于服從正態(tài)分布或近似正態(tài)分布的計(jì)量數(shù)據(jù)采用均數(shù)±標(biāo)準(zhǔn)差(±s)的形式來描述,比較同組不同時(shí)間點(diǎn)之間的定量資料用方差分析,進(jìn)一步使用LSD-t檢驗(yàn)對(duì)其進(jìn)行兩兩比較,用Pearson相關(guān)分析和Spearman秩和檢驗(yàn)分析相關(guān)血液學(xué)指標(biāo)與NRS2002和PG-SGA-定性的相關(guān)關(guān)系,0.05表示差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:l、鼻咽癌患者在放化療治療前,BMI18.5的患者(低體重營(yíng)養(yǎng)不良者)有5.97%(8/134),有27.61%(37/134)的患者在過去3個(gè)月內(nèi)丟失5%的體重。NRS總分≥3.0分(即有營(yíng)養(yǎng)不良的風(fēng)險(xiǎn),需營(yíng)養(yǎng)支持治療)的患者有30.6%(41/134),PG-SGA-定性C級(jí)者(≥9分)為3.73%(5/134),B級(jí)(2-8分)者為43.28%(58/134)。2.放療中期,BMI18.5的患者(低體重營(yíng)養(yǎng)不良者)有11.9%(16/134),體重減輕者的比例范圍-5.45%~11.32%,平均值為2.4%。其中體重減輕者占82.09%(110/134),減輕超過5%者占21.64%(29/134),減輕超過10%者占7.46%(10/134)。NRS總分≥3.0分患者有75.37%(101/134),PG-SGA-定性C級(jí)者(≥9分)為20.9%(28/134),B級(jí)(2-8分)者為55.97%(75/134)。3放療結(jié)束時(shí),BMI18.5的患者(低體重營(yíng)養(yǎng)不良者)有18.66%(25/134)。體重減輕比例的范圍-3.64%~19.51%,平均值為6.27%。其中體重減輕者占89.55%(120/134),減輕超過5%者占32.09%(43/134),減輕超過10%者占28.36%(38/134)。NRS總分≥3.0分的患者有85.82%(115/134),PG-SGA-定性C級(jí)者(≥9分)為32.09%(43/134),B級(jí)(2-8分)者為58.96%(79/134)。4.與治療前相比,鼻咽癌患者在放療中期以及放療結(jié)束時(shí),體重指數(shù)、NRS和PG-SGA均較之前明顯變差(p0.001),相對(duì)應(yīng)的血液學(xué)指標(biāo),除了肌酐無明顯變化外,總蛋白,血清白蛋白,球蛋白,尿素氮,白細(xì)胞,中性粒細(xì)胞計(jì)數(shù),淋巴細(xì)胞計(jì)數(shù),紅細(xì)胞,血紅蛋白水平均持續(xù)性下降,鐵蛋白持續(xù)性升高,差異具有統(tǒng)計(jì)學(xué)意義(p0.001)。5.治療前白蛋白與NRS2002評(píng)分,紅細(xì)胞和血紅蛋白與NRS2002評(píng)分和PG-SGA評(píng)分均呈負(fù)相關(guān)(p0.001)。在治療4周時(shí)的總蛋白、白蛋白和血紅蛋白均與PG-SGA呈中度負(fù)相關(guān)(p0.001)。治療結(jié)束時(shí)白細(xì)胞、中性粒細(xì)胞計(jì)數(shù)、淋巴細(xì)胞計(jì)數(shù)、紅細(xì)胞及血紅蛋白與NRS2002評(píng)分呈中度負(fù)相關(guān),而總蛋白和白蛋白與PG-SGA評(píng)分呈中度負(fù)相關(guān),白細(xì)胞、中性粒細(xì)胞、淋巴細(xì)胞、紅細(xì)胞和血紅蛋白與PG-SGA評(píng)分呈高度負(fù)相關(guān)。結(jié)論:鼻咽癌患者在治療前就有較高的營(yíng)養(yǎng)不良的風(fēng)險(xiǎn),并在同步放化療過程中,相應(yīng)的營(yíng)養(yǎng)狀況和血液學(xué)指標(biāo)均表現(xiàn)為持續(xù)的惡化。白蛋白、紅細(xì)胞和血紅蛋白與營(yíng)養(yǎng)狀況評(píng)分有一定的相關(guān)性,因此可以作為患者營(yíng)養(yǎng)狀況的監(jiān)測(cè)因子。第二部分鼻咽癌患者同步放化療過程中營(yíng)養(yǎng)不良的影響因素目的:研究鼻咽癌患者同步放化療過程中營(yíng)養(yǎng)不良的影響因素方法:回顧性分析了134例經(jīng)病理證實(shí)的初治的并完成IMRT的鼻咽癌病例。由2名放療科醫(yī)生和影像科醫(yī)生在治療前的MR圖像上對(duì)腫瘤進(jìn)行測(cè)量,按照腫瘤侵犯的范圍在MRI上逐層勾畫腫瘤邊界,得到每層腫瘤的面積,計(jì)算腫瘤體積(Gross tumor volume,GTV)。鼻咽及頸部MR圖像記錄腫瘤侵犯的解剖部位:咽旁間隙,腭肌/椎前肌,鼻腔,口咽,下咽,顱底骨質(zhì),翼腭窩,鼻旁竇,翼內(nèi)肌,翼外肌,顱內(nèi)。根據(jù)1991年WHO鼻咽癌病理組織學(xué)分型,選取WHO-Ⅱ和Ⅲ型,分為分化型和未分化型組。研究患者的一般特征(性別,年齡,同步化療,放療前體重量減輕,BMI指數(shù),伴隨疾病,吸煙習(xí)慣,飲酒史和營(yíng)養(yǎng)支持情況)和腫瘤情況(TNM分期,分化程度,腫瘤體積以及侵犯的部位),評(píng)估鼻咽癌放化療前中后的血液學(xué)指標(biāo)(總蛋白,白蛋白,球蛋白,鐵蛋白,肌酐,尿素氮,血小板,白細(xì)胞,中性粒細(xì)胞計(jì)數(shù),淋巴細(xì)胞計(jì)數(shù),紅細(xì)胞,血紅蛋白)和營(yíng)養(yǎng)狀況評(píng)分(NR2002評(píng)分和PG-SGA評(píng)分)的變化,從而對(duì)鼻咽癌患者營(yíng)養(yǎng)狀況變化和影響因素進(jìn)行綜合分析。對(duì)于服從正態(tài)分布或近似正態(tài)分布的計(jì)量數(shù)據(jù)采用均數(shù)±標(biāo)準(zhǔn)差(±s)的形式來描述,組間差異的比較使用獨(dú)立樣本t檢驗(yàn)來分析。用Pearson相關(guān)分析和spearman秩和檢驗(yàn)分析相關(guān)關(guān)系,P0.05為差異具有統(tǒng)計(jì)學(xué)意義。結(jié)果:1.年齡與放療前PG-SGA定量評(píng)分呈弱相關(guān)(相關(guān)系數(shù)=0.212,P=0.014),同步化療與放療后PG-SGA呈高度相關(guān)(相關(guān)系數(shù)=0.751,P0.001),性別、吸煙、飲酒和個(gè)人疾病與放療前PG-SGA定量評(píng)分無相關(guān)關(guān)系。年齡、性別、個(gè)人疾病史、吸煙、飲酒和腸外營(yíng)養(yǎng)均與放療后PG-SGA無相關(guān)關(guān)系(P均0.05)。2.T分期與治療結(jié)束時(shí)的白蛋白、血紅蛋白和第三次體重減輕為中度相關(guān)(相關(guān)系數(shù)為-0.441,-0.395,0.781和0.493,p均0.001),與PG-SGA定量評(píng)分為高度相關(guān)關(guān)系(相關(guān)系數(shù)0.781,0.001)。3.腫瘤N分期與白蛋白、血紅蛋白和PG-SGA均為弱相關(guān)(相關(guān)系數(shù)為-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、顱底骨質(zhì)、咀嚼肌間隙、鼻旁竇、顱內(nèi)侵犯與PG-SGA定量評(píng)分呈中度正相關(guān)(相關(guān)系數(shù)為-0.507,-0.469,0.618,0.467,0.527和0.548,p均0.001)。5.治療前腫瘤體積與治療結(jié)束時(shí)白蛋白、血紅蛋白為負(fù)相關(guān),與PG-SGA定量評(píng)分和第三次體重減輕為正相關(guān)(相關(guān)系數(shù)為-0.423,-0.24,0.786和0.502,p分別為0.001,0.005,0.001,0.001)。大腫瘤體積(≥24.7cm3)與小腫瘤體積(24.7cm3)在同步放化療前和后的PG-SGA定量評(píng)分之間有顯著統(tǒng)計(jì)學(xué)差異(P均0.001)。6.不能認(rèn)為病理類型與白蛋白、血紅蛋白、第三次體重減輕和PG-SGA定量評(píng)分之間存在相關(guān)關(guān)系(相關(guān)系數(shù)分別為-0.004,-0.045,0.004,0.049,P均0.05)。結(jié)論:1.同步化療、腫瘤體積、T分期、腭肌/椎前肌、口咽、顱底骨質(zhì)、咀嚼肌間隙、鼻旁竇、顱內(nèi)侵犯是鼻咽癌同步放化療患者營(yíng)養(yǎng)不良的主要相關(guān)因素。2.年齡、女性、吸煙、飲酒、N分期和分化程度與鼻咽癌患者同步放化療后營(yíng)養(yǎng)不良的弱相關(guān)或無相關(guān)關(guān)系。第三部分鼻咽癌患者同步放化療過程中營(yíng)養(yǎng)不良的預(yù)后意義目的:分析鼻咽癌患者一般特征和放化療前中后主要的血液學(xué)指標(biāo)和營(yíng)養(yǎng)狀況,評(píng)價(jià)營(yíng)養(yǎng)不良對(duì)鼻咽癌患者的預(yù)后價(jià)值。方法:回顧性分析了2010年8月-2011年12月在廣西醫(yī)科大學(xué)附屬腫瘤醫(yī)院134例經(jīng)病理證實(shí)的初治的并完成IMRT的鼻咽癌病例。研究患者的一般特征(性別,年齡,伴隨疾病,吸煙,飲酒史和營(yíng)養(yǎng)支持情況)、鼻咽癌放化療前中后的血液學(xué)指標(biāo)(白蛋白,紅細(xì)胞,血紅蛋白)和營(yíng)養(yǎng)評(píng)分(NR2002評(píng)分和PG-SGA評(píng)分)對(duì)患者預(yù)后的影響。評(píng)價(jià)患者一般情況、血液學(xué)指標(biāo)和營(yíng)養(yǎng)狀況評(píng)分以及臨床T分期對(duì)5年累計(jì)生存(OS)、局部無復(fù)發(fā)生存(LRFS)、遠(yuǎn)處無轉(zhuǎn)移生存(DMFS)的影響。懫用Cox比例風(fēng)險(xiǎn)回歸模型對(duì)影響鼻咽癌的預(yù)后因素進(jìn)行分析。結(jié)果:1.T1-T4的5年OS分別為89.7%,87.5%,78.4%和63.9%(p=0.04),但組間比較,T1和T2,T2和T3,T3和T4的p值均0.05。T1-T4期的5年LRFS分別為89.7%,90.6%,81.1%和88.9%(p=0.573),5年DMFS分別為89.7%,90.6%,81.1%和66.7%(p=0.029)。2.5年OS的獨(dú)立預(yù)后因素為治療前PG-SGA定量評(píng)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);治療中PG-SGA定量評(píng)分和血紅蛋白,治療后PG-SGA定量評(píng)分(HR0.77,95%CI0.687-0.863,p=0)和治療后血紅蛋白。5年LRFS的獨(dú)立預(yù)后因素為治療前紅細(xì)胞,治療前血紅蛋白和治療后紅細(xì)胞(HR0.01,95%CI0.002-0.063,p=0.000)。5年DMFS的獨(dú)立預(yù)后因素治療前PG-SGA定量評(píng)分(HR1.369,95%CI1.169-1.604,p=0.000),治療中PG-SGA定量評(píng)分(HR1.202,95%CI1.091-1.323,p=0.000),治療后PG-SGA定量評(píng)分(HR0.869,95%CI0.762-0.99,p=0.035)和治療后紅細(xì)胞。結(jié)論:1.T分期不再是同步放化療鼻咽癌獨(dú)立的預(yù)后因素,T分期的亞組對(duì)于預(yù)后的預(yù)測(cè)缺乏分辨能力。2.PG-SGA定量評(píng)分在5年OS和DMFS表現(xiàn)出了較好的預(yù)測(cè)能力。但是對(duì)于局部無復(fù)發(fā)生存率,并沒有發(fā)現(xiàn)獨(dú)立的影響因素。
[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.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R739.63

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