本文選題：鼻咽癌　切入點(diǎn)：擴(kuò)散加權(quán)成像　出處：《北京協(xié)和醫(yī)學(xué)院》2014年博士論文

【摘要】：第一部分：擴(kuò)散加權(quán)成像對(duì)鼻咽癌同步放化療療效的預(yù)測(cè)研究 [目的]：探討3.0T MR擴(kuò)散加權(quán)成像(diffusion-weighted imaging, DWI)及表觀擴(kuò)散系數(shù)(apparent diffusion coefficient, ADC)值預(yù)測(cè)鼻咽癌同步放化療療效的價(jià)值。 [材料與方法]：2009年10月至2012年12月于我院鼻咽鏡活檢病理證實(shí)并行同步放化療的鼻咽癌患者共65例。所有患者于治療前行DWI檢查(b=0,800s/mm2),測(cè)量腫瘤平均、最高及最低ADC值。并于治療中(劑量達(dá)50Gy)、治療末(常規(guī)放化療結(jié)束時(shí))再次行MR檢查,分別計(jì)算治療中、末的腫瘤消退率。依據(jù)治療末腫瘤消退率分為完全緩解組(complete response, CR)及非CR組,后者包括部分緩解組(partial response, PR)及病變穩(wěn)定組(stable disease, SD)。將治療前腫瘤ADC值分別與治療中、末腫瘤消退率進(jìn)行Spearman目關(guān)性分析,采用獨(dú)立樣本T檢驗(yàn)比較CR組與非CR組治療前腫瘤ADC值的差異,并采用受試者工作特征曲線(receiver operating characteristic curve, ROC)分析治療前ADC值預(yù)測(cè)治療末CR的閾值及診斷效能。 [結(jié)果]：治療前腫瘤平均ADC值、最高ADC值與治療中、末腫瘤消退率均呈負(fù)相關(guān)(r=-0.463～-0.552, P0.001)。CR組及非CR組的治療前平均ADC值分別為0.98±0.12×10-3mm2/s VS1.14±0.13×10-3mm2/s、最高ADC值分別為1.16±0.21±0.13×10-3mm2/s VS.1.42±0.23×10"3mm2/s,組間差異有統(tǒng)計(jì)學(xué)意義(P均0.001)。ROC顯示以腫瘤治療前平均ADC值1.09×10"3mm2/s為閾值,預(yù)測(cè)同步放化療后CR組的敏感性、特異性及準(zhǔn)確性分別為82.50%(33/40)、76.00(19/25)%及80.00%(52/65),曲線下面積0.816(P0.001)。 [結(jié)論]：DWI及ADC值能夠較好的預(yù)測(cè)鼻咽癌治療后消退情況,有望為鼻咽癌個(gè)體化治療提供依據(jù)。 第二部分：動(dòng)態(tài)增強(qiáng)MRI對(duì)鼻咽癌同步放化療療效的預(yù)測(cè)研究 [目的]：探討動(dòng)態(tài)增強(qiáng)MRI (dynamic contrast enhanced magnetic resonance imaging, DCE-MRI)預(yù)測(cè)鼻咽癌同步放化療療效的價(jià)值。 [材料與方法]：2009年10月至2012年12月于我院鼻咽鏡活檢病理證實(shí)并行同步放化療的鼻咽癌患者共61例。所有患者于治療前行DCE-MRI檢查,測(cè)量并計(jì)算腫瘤最大截面的平均、高強(qiáng)化區(qū)及低強(qiáng)化區(qū)時(shí)間信號(hào)強(qiáng)度曲線類型(time-signal intensity curve, TIC)及半定量參數(shù),包括達(dá)峰時(shí)間(time to peak, TTP)、正性增強(qiáng)積分(positive enhancement integral, PEI)、最大上升斜率(maximum slope of increase,MSI)、最大下降斜率(maximum slope of decrease, MSD)。于治療中(放療50Gy)及治療末(常規(guī)治療結(jié)束)再次行MR檢查。依據(jù)治療末腫瘤消退率分為完全緩解組(complete response, CR組)及非CR組,后者包括部分緩解組(partial response,PR)及病變穩(wěn)定組(stable disease, SD)。采用Spearman相關(guān)性檢驗(yàn)分析治療前腫瘤DCE-MRI參數(shù)與治療中、末腫瘤消退率的相關(guān)性。采用非參數(shù)檢驗(yàn)Mann-WhitneyU法比較CR及非CR組間治療前各參數(shù)的差異。并選取與治療末消退率相關(guān)系數(shù)最高的參數(shù),采用受試者工作特征曲線(receiver operating characteristic curve, ROC)分析其預(yù)測(cè)治療敏感的閾值及效能。 [結(jié)果]：與治療中和/或治療末消退率具有統(tǒng)計(jì)學(xué)意義相關(guān)性的參數(shù)包括：治療前腫瘤平均、高強(qiáng)化區(qū)及低強(qiáng)化區(qū)的曲線類型、TTP、高強(qiáng)化區(qū)的PEI(r:-0.307～-0.724,P：0.001-0.016)、腫瘤平均及低強(qiáng)化區(qū)的MSI、腫瘤平均、高強(qiáng)化區(qū)及低強(qiáng)化區(qū)的MSD(r:0.262～0.329, P:0.001～0.037)。CR及非CR組間治療前DCE-MRI參數(shù)差異有統(tǒng)計(jì)學(xué)意義的參數(shù)包括：腫瘤的平均、高強(qiáng)化區(qū)及低強(qiáng)化區(qū)的曲線類型、TTP、腫瘤低強(qiáng)化區(qū)的MSI、腫瘤平均及高強(qiáng)化區(qū)的的MSD (P:0.001～0.038)。ROC分析顯示,以腫瘤低強(qiáng)化區(qū)TTP70s為閾值預(yù)測(cè)腫瘤治療敏感,其敏感性、特異性及準(zhǔn)確性分別為83.33%(30/36),76.00%(19/25)及80.33%(49/61),曲線下面積0.817(P0.001)。 [結(jié)論]：DCE-MRI半定量參數(shù)能夠較好的預(yù)測(cè)鼻咽癌治療后消退情況與治療敏感性,有望為鼻咽癌個(gè)體化治療提供依據(jù)。 第三部分：動(dòng)態(tài)增強(qiáng)MRI半定量及定量模型對(duì)鼻咽癌同步放化療療效的預(yù)測(cè)研究 [目的]：探討動(dòng)態(tài)增強(qiáng)MRI (dynamic contrast enhanced magnetic resonance imaging, DCE-MRI)半定量及定量Tofts模型參數(shù)預(yù)測(cè)鼻咽癌同步放化療療效的價(jià)值。 [材料與方法]：2013年1月至2013年12月于我院鼻咽鏡活檢病理證實(shí)并行同步放化療的鼻咽癌患者共36例。所有患者于治療前行DCE-MRI,并采用Tofts模型及GenIQ軟件計(jì)算腫瘤半定量及定量參數(shù),包括最大上升斜率MaxSlop、最大對(duì)比增強(qiáng)比率(Contrast Enhancement Ratio, CER)、初始釓曲線下面積(initial area under the gadolinium curve, IAUGC)、容量轉(zhuǎn)移常數(shù)(volume transfer constant, Ktrans)、速率常數(shù)(rate constant, Kep)及血管外細(xì)胞外間隙容積(the extravascular-extracellular volume fraction, Ve)。于治療中(劑量達(dá)50Gy)及治療末(常規(guī)放化療結(jié)束時(shí))再次行MRI檢查,分別計(jì)算腫瘤治療中、末腫瘤消退率。依據(jù)治療末腫瘤消退率分為完全緩解組(complete response, CR組)及非CR組,后者包括部分緩解組(partial response, PR)及病變穩(wěn)定組(stable disease, SD)。將治療前腫瘤DCE-MRI參數(shù)與治療中、末腫瘤消退率進(jìn)行Spearman相關(guān)性分析,并比較CR組與非CR組療前DCE-MRI的參數(shù)差異。采用受試者工作特征曲線(receiver operating characteristic curve, ROC)分析治療前DCE-MRI參數(shù)對(duì)預(yù)測(cè)腫瘤治療敏感性的閾值及效能。 [結(jié)果]：治療前全部腫瘤的平均及熱點(diǎn)IAUGC、Ktrans、Kep、平均MaxSlop,熱點(diǎn)CER與治療中、末腫瘤消退率均呈正相關(guān)(r：0.341-0.608,P：0.001-0.042)；治療前腫瘤的平均CER僅與治療末腫瘤消退率呈正相關(guān)(r=0.350,P=0.036)。治療末CR與非CR組間治療前腫瘤的熱點(diǎn)CER (1.802±0.297VS.1.567±0.293)、 IAUGC (0.236±0.040VS.0.193±0.031)、平均Ktrans (0.178±0.033min-1VS.0.136±0.033min-1)、熱點(diǎn)Ktrans (0.228±0.042min-1VS.0.177±0.031min-1)、平均Kep(1.246±0.313min-1VS.0.925±0.228min-1)的差異均有統(tǒng)計(jì)學(xué)意義(P=0.001～0.024)。ROC分析顯示治療前平均Kep值≥1.11min-1為閾值預(yù)測(cè)腫瘤治療末CR,其敏感性、特異性及準(zhǔn)確性分別為71.43%(15/21)、86.67%(13/15)及77.78%(28/36),曲線下面積為0.832(P=0.001)。 [結(jié)論]：DCE-MRI半定量及定量參數(shù)均能夠較好的預(yù)測(cè)鼻咽癌治療后消退情況與治療敏感性,有望為鼻咽癌個(gè)體化治療提供依據(jù)。
[Abstract]:The first part: the prediction of the effect of diffusion weighted imaging on the efficacy of concurrent chemoradiotherapy for nasopharyngeal carcinoma
[Objective] to explore the value of 3.0T MR diffusion weighted imaging (diffusion-weighted imaging, DWI) and apparent diffusion coefficient (apparent diffusion coefficient, ADC) in predicting the efficacy of concurrent chemoradiotherapy for nasopharyngeal carcinoma.
[materials and methods]:2009 from October to December 2012 in our hospital epipharyngoscope biopsy of nasopharyngeal carcinoma patients with parallel chemoradiotherapy were 65 cases. All the patients in the treatment of DWI examination before (b=0800s/mm2), measuring tumor average, maximum and minimum value of ADC. And in the treatment (dose of 50Gy), at the end of treatment (conventional radiotherapy at the end of chemotherapy) again underwent MR, were calculated at the end of treatment, the rate of tumor regression. Based on the treatment of late cancer remission rate divided into remission group (complete, response, CR) and non CR group, the latter including partial remission group (partial response, PR) and stable disease group (stable disease, SD). Before treatment and treatment of tumor ADC values were, at the end of Spearman related tumor regression rate were analyzed, compared with independent sample T test group CR before treatment difference of tumor ADC values with non CR group, and the receiver operating characteristic curve (receiver operating Characteristic curve, ROC) was used to analyze the threshold and diagnostic efficiency of CR at the end of the treatment of ADC at the end of treatment.
[results]: before treatment, the mean tumor ADC values, and the highest ADC value at the end of treatment, the tumor regression rate were negatively correlated (r=-0.463, -0.552, P0.001).CR group and non CR group before treatment the average ADC = 0.98 + 0.12 + 0.13 VS1.14 * 10-3mm2/s * 10-3mm2/s, the highest ADC value was 1.16 + 0.21 + 0.13 + 0.23 * 10-3mm2/s VS.1.42 * 10 3mm2/s, there was significant difference between the groups (P 0.001).ROC display with an average ADC value of 1.09 * 10 3mm2/s tumor before treatment for the threshold, prediction of the concurrent chemoradiotherapy group CR sensitivity, specificity and accuracy were 82.50% (33/40), 76 (19/25)% and 80% (52/65), the area under the curve of 0.816 (P0.001).
[conclusion]:DWI and ADC values can be used to predict the regression of nasopharyngeal carcinoma after treatment, and it is expected to provide a basis for the individualized treatment of nasopharyngeal carcinoma.
The second part: the prediction of the effect of dynamic enhanced MRI for nasopharyngeal carcinoma with concurrent chemoradiotherapy
[Objective] to explore the value of dynamic enhanced MRI (dynamic contrast enhanced magnetic resonance imaging, DCE-MRI) to predict the curative effect of concurrent chemoradiotherapy for nasopharyngeal carcinoma.
[materials and methods]:2009 from October to December 2012 in our hospital epipharyngoscope biopsy of nasopharyngeal carcinoma patients with parallel chemoradiotherapy were 61 cases. All the patients in the treatment of DCE-MRI examination before, measure and calculate the maximum average section of tumor, high intensity region and low enhancement area time signal intensity curve type (time-signal intensity curve, TIC) and semi quantitative parameters, including the peak time (time, to, peak, TTP) positive enhancement integral (positive enhancement, integral, PEI), the maximum rise slope (maximum slope of increase, MSI), the largest decline (maximum slope of decrease slope, MSD). In the treatment (radiotherapy 50Gy) and the end of treatment (the end of the routine treatment) again examined by MR. According to the treatment at the end of the tumor regression rate divided into remission group (complete response, CR group) and non CR group, the latter including partial remission group (partial response, PR) and stable disease (Group Stable disease, SD). Using the Spearman correlation analysis before treatment and treatment of tumor DCE-MRI parameters, at the end of tumor regression rate correlation. The difference with non parametric test method of Mann-WhitneyU CR and non CR groups before treatment and select the parameters. The extinction rate of phase relationship with the highest number of parameters and the end of treatment, the subjects operating characteristic curve (receiver operating characteristic curve, ROC) to analyze the prediction of treatment and efficacy of threshold sensitive.
[results]: at the end of treatment and treatment and / or extinction rate has statistical significance correlation parameters including: before treatment, the average tumor area and low, high strength enhancement curve type, TTP District, PEI District high strength (r:-0.307 ~ -0.724, P:0.001-0.016), and low average tumor enhancement area MSI, the average tumor. High strength and low area enhancement area MSD (r:0.262 ~ 0.329, P:0.001 ~ 0.037) including parameter differences before DCE-MRI treatment parameters.CR and non CR groups had statistical significance: the average tumor, high strength and low area enhancement curve type, area TTP, tumor enhancement area of low MSI, and the average tumor high enhancement area MSD (P:0.001 ~ 0.038).ROC analysis showed that with low tumor enhancement area TTP70s threshold prediction of tumor treatment sensitivity, the sensitivity, specificity and accuracy were 83.33% (30/36), 76% (19/25) and 80.33% (49/61), the area under the curve of 0.817 (P0.001).
[conclusion]:DCE-MRI semi quantitative parameters can be used to predict the retrogression and treatment sensitivity of nasopharyngeal carcinoma, and it is expected to provide a basis for the individualized treatment of nasopharyngeal carcinoma.
The third part: a dynamic enhanced MRI semi quantitative and quantitative model for the prediction of the efficacy of concurrent chemoradiotherapy for nasopharyngeal carcinoma
[Objective] to explore the value of MRI dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) semi quantitative and quantitative Tofts model parameters in predicting the efficacy of concurrent chemoradiotherapy for nasopharyngeal carcinoma.
[materials and methods]:2013 from January to December 2013 in our hospital epipharyngoscope biopsy of nasopharyngeal carcinoma patients with parallel chemoradiotherapy were 36 cases. All patients underwent DCE-MRI in the treatment of tumors were calculated, semi quantitative and quantitative parameters of the Tofts model and GenIQ software, including the maximum rise slope of MaxSlop, the maximum contrast enhancement ratio (Contrast Enhancement Ratio, CER), the area under the curve (initial area initial GD under the gadolinium curve IAUGC (volume), volume transfer constant transfer constant, Ktrans), the rate constants (rate constant, Kep) and extravascular extracellular space volume (the extravascular-extracellular volume fraction, Ve). In the treatment (dose of 50Gy) and at the end of treatment (conventional chemotherapy end) again examined by MRI were calculated in the treatment of cancer, tumor regression rate. Based on the end of treatment at the end of the tumor regression rate is slow The solution group (complete response, CR group) and non CR group, the latter including partial remission group (partial response, PR) and stable disease group (stable disease, SD). Before treatment and treatment of tumor DCE-MRI parameters, the late Spearman associated tumor regression rate were analyzed, and the difference ratio parameters compared with the CR group and non CR group before treatment DCE-MRI. The receiver operating characteristic curve (receiver operating characteristic curve, ROC) of DCE-MRI before the treatment parameters to predict the threshold and efficiency of treatment of tumor sensitivity.
[results]: the average and hot IAUGC, before treatment, all of the tumor Ktrans, Kep, average MaxSlop, CER and hot in the treatment of late cancer remission rate were positively correlated (r:0.341-0.608, P:0.001-0.042); the average CER before treatment and treatment of tumors only at the end of tumor regression rate was positively correlated (r=0.350, P=0.036) CER for the treatment of hot. CR and non CR groups before cancer treatment at the end of (1.802 + 0.297VS.1.567 + 0.293), IAUGC (0.236 + 0.040VS.0.193 + 0.031), average Ktrans (0.178 + 0.033min-1VS.0.136 + 0.033min-1), hot Ktrans (0.228 + 0.042min-1VS.0.177 + 0.031min-1), average Kep (1.246 + 0.313min-1VS.0.925 + 0.228min-1) had significant difference (P=0.001 ~ 0.024).ROC analysis showed that before treatment the average Kep value is greater than or equal to 1.11min-1 for the prediction of tumor treatment at the end of the CR threshold, the sensitivity, specificity and accuracy were 71.43% (15/21), 86.67% (13/15) and 77.78% (28/36), The area under the curve is 0.832 (P=0.001).
[conclusion]:DCE-MRI semi quantitative and quantitative parameters can better predict the regression and therapeutic sensitivity of nasopharyngeal carcinoma after treatment, which is expected to provide a basis for individualized treatment of nasopharyngeal carcinoma.

【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R739.63;R445.2

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