李依霞,崔園園,崔豹,馬露,陳思,楊娜,張愛蓮,蔡劍鳴, 2*
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擴(kuò)散加權(quán)成像對非手術(shù)喉癌和下咽癌患者同步放化療前后的療效評價
李依霞1,崔園園1,崔豹1,馬露1,陳思1,楊娜1,張愛蓮1,蔡劍鳴1, 2*
[摘要]目的 探討磁共振擴(kuò)散加權(quán)成像聯(lián)合常規(guī)MRI檢查評價非手術(shù)喉癌下咽癌同步放化療療效的應(yīng)用價值。材料與方法 搜集喉癌下咽癌患者(僅接受放化療,未行手術(shù)治療)共25例,全部病例均于患病局部活檢或手術(shù)病理證實(shí)。所有患者治療前均行常規(guī)MRI及擴(kuò)散加權(quán)成像(DWI)掃描,分析患者M(jìn)RI特點(diǎn)、測量腫瘤最大橫截面積及表觀擴(kuò)散系數(shù)(ADC)值(包括平均ADC值、最低和最高ADC值);治療后(放化療結(jié)束后1個月內(nèi))再次行MRI檢查,測殘留腫瘤面積及ADC值,并計算腫瘤緩解率。分析治療前及治療后腫瘤ADC值與腫瘤緩解率相關(guān)性;分析治療后完全緩解患者(CR組)與非完全緩解患者(非CR組)治療前、后ADC值及變化的差異。結(jié)果 25例喉癌下咽癌患者治療前腫瘤面積4.81 (0.83~14.12) cm2,治療后腫瘤面積2.42 (0~7.92) cm2,腫瘤緩解率為74.8% (6.0%~100%),其中有11 (11/25,44.0%)例患者治療后腫瘤消失。治療前腫瘤平均ADC值及最高ADC值與治療后腫瘤緩解率呈負(fù)相關(guān)(r=–0.922、–0.691,P<0.05),治療后平均ADC值與緩解率呈正相關(guān)(r=0.678,P<0.05);非CR組治療前腫瘤平均、最高ADC值高于CR組,CR組治療后平均ADC值及治療前后平均ADC值的變化高于非CR組,差異有統(tǒng)計學(xué)意義(P值均<0.05)。結(jié)論 治療前腫瘤ADC值以及治療前后腫瘤ADC值的變化對評價非手術(shù)喉癌下咽癌放化療后早期緩解率有一定意義。
[關(guān)鍵詞]喉腫瘤;下咽腫瘤;彌散磁共振成像;放射療法;化學(xué)療法,輔助
作者單位:
1. 中國人民解放軍總醫(yī)院放射診斷科,北京 100853
2. 解放軍總醫(yī)院第一附屬醫(yī)院放射科,北京 100048
蔡劍鳴,E-mail: beili12345@sina.cn
接受日期:2016-01-25
李依霞, 崔園園, 崔豹, 等. 擴(kuò)散加權(quán)成像對非手術(shù)喉癌和下咽癌患者同步放化療前后的療效評價. 磁共振成像, 2016, 7(3): 185-190.
喉癌和下咽癌是頭頸部常見的惡性腫瘤之一,以鱗癌為主,發(fā)病率近年呈逐漸上升趨勢[1]。頭頸部腫瘤的治療需要綜合考慮兩方面因素,一是盡可能提高局部控制率,二是盡可能保留器官的功能,故喉部和下咽部中、晚期鱗癌的治療方法已從常規(guī)手術(shù)切除加放療方式逐步轉(zhuǎn)變?yōu)槁?lián)合放化療治療方案。因此,如何早期預(yù)測、評估腫瘤對放化療的反應(yīng),對于制定個體化治療方案具有重要臨床意義。目前多項(xiàng)研究表明,擴(kuò)散加權(quán)成像(diffusion weighted imaging,DWI)在腫瘤診斷、鑒別診斷、腫瘤治療后改變、腫瘤復(fù)發(fā)或殘留等方面發(fā)揮重要作用[2-4]。筆者旨在探討表觀擴(kuò)散系數(shù)(apparent diffusion coefficient,ADC)值在預(yù)測及評價喉癌和下咽癌患者放化療后早期治療效果方面的作用。
1.1 一般資料
選取2014年1月至2015年8月在我院(中國人民解放軍總醫(yī)院)耳鼻咽喉科就診的25例喉癌下咽癌患者為研究對象,其中男21例,女4例;年齡42~77歲,平均58.8歲;下咽癌16例,喉癌9例。腫瘤分期:T1期0例,T2期3例(患者拒絕手術(shù)),T3期9例,T4期13例。全部病例均經(jīng)鼻咽鏡或喉鏡下活檢證實(shí)為鱗狀細(xì)胞癌,且均接受放化療綜合治療,未行手術(shù)治療。本研究經(jīng)我院倫理委員會批準(zhǔn),所有患者在檢查前均了解檢查內(nèi)容,并簽署了知情同意書。
1.2 治療方法
25例患者先行誘導(dǎo)化療,采用TP方案,TP方案即多西他賽(Docetaxel,T) 70 mg/m2,第1天,順鉑(Cisplatine,P) 40 mg/m2,第1~2天,每21 d為1個周期,共2周期。誘導(dǎo)化療結(jié)束后,行同步放化療。同步放化療期間化療采用TP方案,在放療期間同步進(jìn)行。采用調(diào)強(qiáng)放射治療。放療總劑量70 Gy,每次2.12 Gy,每周5次,共30~33次,近7周。
1.3 檢查方法
25例患者均采用GE MR360 1.5 T超導(dǎo)型MR掃描儀進(jìn)行檢查,采用8通道頭頸專用聯(lián)合線圈。患者取仰臥位,平靜呼吸,檢查中盡量避免咳嗽、吞咽等動作。所有患者于治療前、治療后(1個月內(nèi))行常規(guī)MRI平掃、增強(qiáng)掃描、DWI檢查。
常規(guī)MRI平掃加增強(qiáng)掃描:橫軸面、矢狀面、冠狀面脂肪抑制序列FSE T2WI (TR 6220 ms, TE 55 ms),橫軸面脂肪抑制序列T1WI (TR 529 ms,TE 20 ms) ,增強(qiáng)掃描橫軸面、冠狀面、矢狀面脂肪抑制T1WI,注射對比劑Gd-DTPA (馬根維顯,德國拜爾公司) ,劑量為0.2 ml/kg。層厚7 mm,層距1 mm,橫軸面視野(FOV) 220 mm×220 mm,矩陣256×256,信號平均次數(shù)(NEX) 2次;掃描范圍從顱底至頸根部。
DWI檢查:采用單次激發(fā)SE-EPI序列行橫軸面掃描。TR 4500 ms,TE 80.5 ms,b=0及600 s/mm2,F(xiàn)OV 220 mm×220 mm,矩陣256×256,層厚7 mm,層距1 mm。
1.4 圖像分析
MRI圖像分析所有MRI圖像均由2名具有豐富MRI診斷經(jīng)驗(yàn)的放射科醫(yī)師在不知其病理及療效的情況下共同閱片診斷、評估及測量,以2名醫(yī)師共同意見為診斷結(jié)果。主要觀測病變區(qū)域治療前、后的MRI表現(xiàn)。
感興趣區(qū)選擇及數(shù)據(jù)測量以平掃T2WI及DWI序列為參照,在橫軸面增強(qiáng)T1WI圖像上測量治療前、治療后腫瘤最大橫截面積。于GE AW 4.5工作站采用Functool軟件勾畫治療前腫瘤最大橫截面作為ROI治療前,獲取平均ADC值;依據(jù)腫瘤最大橫截面ADC圖,于擴(kuò)散受限最輕及最重處分別勾畫ROI最高及ROI最低(面積10~30 mm2,注意避開出血或壞死區(qū)域),獲取最高ADC值及最低ADC值。勾畫治療后CR組原腫瘤區(qū)域解剖結(jié)構(gòu)(如:治療前聲門型喉癌累及聲門旁間隙,治療后未見明顯腫塊,則勾畫原腫瘤區(qū)域聲帶、聲門旁間隙解剖結(jié)構(gòu)作為ROI);非CR組殘存腫瘤最大橫截面積為ROI治療后,獲取該區(qū)域平均ADC值。
1.5 療效評價標(biāo)準(zhǔn)
2名有經(jīng)驗(yàn)放射診斷科醫(yī)生分別在治療末(治療結(jié)束1個月內(nèi))未知療效的情況下評價腫瘤的緩解情況。按照實(shí)體腫瘤療效評價標(biāo)準(zhǔn) RECIST (response evaluation criteria in solid tumors)[5]對病灶區(qū)域腫瘤緩解情況評價療效:(1)完全緩解(complete response,CR):腫瘤完全消失,腫瘤緩解率為100%;(2)部分緩解(partial response,PR):腫瘤部分緩解,未完全消失,但腫瘤緩解率大于等于30%;(3)病變穩(wěn)定(stable disease,SD):腫瘤穩(wěn)定進(jìn)展,腫瘤緩解率小于30%。腫瘤緩解率=(治療前面積-治療后面積)/治療前面積×100%。
1.6 統(tǒng)計方法
所有統(tǒng)計分析采用SPSS22.0 統(tǒng)計軟件完成。采用Kolmogorov-Smirnov Z檢驗(yàn)進(jìn)行正態(tài)性檢驗(yàn),經(jīng)正態(tài)性檢驗(yàn)顯示,所有相關(guān)測量項(xiàng)目的結(jié)果均服從正態(tài)分布(P>0.05)。以Pearson線性相關(guān)分析分析不同分期腫瘤ADC值與腫瘤緩解率的相關(guān)性。采用兩獨(dú)立樣本t檢驗(yàn)進(jìn)行CR組與非CR組腫瘤治療前、后平均ADC值、最高及最低ADC值的差異比較。P<0.05為差異有統(tǒng)計學(xué)意義。
圖1 男,61歲,下咽癌(T4bN2M0)。治療前(A~D):T2WI (A)示病灶位于左側(cè)下咽部,累及左側(cè)喉旁間隙;左側(cè)頸內(nèi)靜脈旁淋巴結(jié)明顯腫大;增強(qiáng)掃描(B),病灶呈不均勻強(qiáng)化,軸面最大橫截面積為4.43 cm2(A、B);DWI (C)示病灶呈明顯高信號;ADC圖(D)測病灶平均ADC值為0.97×10–3mm2/s,最高ADC值為1.05×10–3mm2/s,最低ADC值為0.86×10–3mm2/s。治療后(E~H):T2WI (E)和增強(qiáng)掃描(F)示治療后未見明顯腫塊,原腫大淋巴結(jié)明顯縮小,未見確切顯示;腫瘤緩解率為100%;DWI (G)未見明顯異常高信號;ADC圖(H)測得原腫瘤區(qū)域解剖結(jié)構(gòu)平均ADC值為2.21×10–3mm2/s。評價治療療效為CRFig. 1 Male, 61 years old, hypopharyngeal carcinoma (T4bN2M0). Pre-Tx (A—D): There was a lesion located in the left side of the hypopharynx, involving the left laryngeal space, which showed hyperintensity on T2WI and obvious inhomogeneousenhancement. The lymph node near the left internal jugular vein was significantly enlarged. The axial maximum cross sectional area was 4.43 cm2(A,B). The lesion showed hyperintensity on DWI (C). ADC map (D) showed ADCmean=0.97×10–3mm2/s, ADChigh=1.05×10–3mm2/s, and ADClow=0.86×10–3mm2/s. Post-Tx (E—H): No tumor mass and enlarged lymph nodes were detected on the matched T2WI (E) and post-T1WI (F) The remission rate of the tumor was 100%. There was no obviously high signal on DWI (G). The ADCmeanof the corresponding regional anatomical structure was 2.21×10–3mm2/s on ADC map (H). The curative effect was CR.
2.1 病變治療前、后MRI表現(xiàn)
不同部位腫瘤治療前均侵犯周圍鄰近組織結(jié)構(gòu)(如治療前腫瘤可累及咽后壁、環(huán)后區(qū)、梨狀窩、左右室?guī)?、聲帶、杓會厭皺襞以及周圍各間隙等,黏膜明顯增厚),T1WI上呈不均勻等、低信號,T2WI上呈均勻或不均勻稍高、高信號,增強(qiáng)后病變呈不同程度明顯強(qiáng)化,DWI呈稍高或高信號。治療后,腫瘤均明顯減小或消失,病變區(qū)域T1WI等或稍低信號,T2WI呈稍高或高信號,增強(qiáng)后呈均勻或不均勻強(qiáng)化,DWI呈等或稍高信號(圖1,2)。
圖2 男,60歲,下咽癌(T4N2M0)。治療前(A~D): T2WI (A)示病灶位于右側(cè)下咽部,累及右側(cè)喉旁間隙、室?guī)Ъ奥晭?;增?qiáng)掃描(B),病灶呈明顯不均勻強(qiáng)化,軸面最大橫截面積為8.01 cm2;DWI (C)示病灶呈稍高信號;ADC圖(D)測病灶平均ADC值為1.22×10–3mm2/s,最高ADC值為1.37×10–3mm2/s,最低ADC值為0.91×10–3mm2/s。治療后(2E-2H): T2WI (E)和增強(qiáng)掃描(F)示治療后仍見腫塊,殘存腫瘤最大橫截面積為4.89 cm2,腫瘤緩解率為38.9%;DWI (G)病灶呈稍高信號;ADC圖(H)測得殘存腫瘤平均ADC值為1.56×10–3mm2/s。評價治療療效為非CRFig. 2 Male, 60 years old, hypopharyngeal carcinoma (T4N2M0). Pre-Tx(A—D): There was a lesion located in the right side of the hypopharynx, involving the right of laryngeal space, the right ventricular fold and vocal cord. The lesion showed obviously inhomogeneous enhancement. The axial maximum cross sectional area was 8.01 cm2(A, B). The lesion shows hyperintensity on DWI (C). ADC map showed ADCmean=1.22×10–3mm2/s, ADChigh=1.37×10–3mm2/s, and ADClow=0.91×10–3mm2/s. Post-Tx (E—H): The size of the mass was decreased on T2WI (E) and post T1wi (F) after the treatment. The maximum cross-sectional area was 4.89 cm2and the remission rate of the tumor was 38.9%. The residual lesion showed slight hyperintensity on DWI (G). The ADCmeanof the residual tumor was 1.56×10–3mm2/s on ADC map (H). The curative effect was non-CR.
2.2 病變面積變化及療效評價
25例患者治療前腫瘤最大橫截面積平均為4.81 (0.83~14.12) cm2,治療后腫瘤最大橫截面積平均為2.42 (0~7.92) cm2。11例患者于治療后1個月內(nèi)復(fù)查腫瘤完全消失。CR組患者11例(11/25,44.0%),非CR組患者14例(14/25,56.0%)。緩解率為74.8% (6.0%~100%)。
2.3 不同分期腫瘤ADC值與腫瘤緩解率相關(guān)性分析
T3期患者治療前腫瘤平均ADC值與緩解率呈負(fù)相關(guān)。T4期患者治療前腫瘤平均、最高、最低ADC值與緩解率呈負(fù)相關(guān)。所有患者治療前腫瘤平均和最高ADC值與緩解率呈負(fù)相關(guān),治療后平均ADC值與緩解率呈正相關(guān)(表1)。
2.4 CR組及非CR組腫瘤ADC值比較
非CR組治療前腫瘤平均、最高ADC值均高于CR組,CR組治療后腫瘤平均ADC值及治療前后腫瘤平均ADC值變化高于非CR組,差異有統(tǒng)計學(xué)意義(P<0.001;表2)。
表1 各時期ADC值與腫瘤緩解率的相關(guān)系數(shù)Tab. 1 Correlation between ADC value and the remission rate of the tumor
表2 CR組和非CR組治療前后ADC值比較Tab. 2 Comparison of Pre-Tx and Post-TxADCmeanbetween the CR group and the Non-CR group
MRI成像可清楚顯示軟組織結(jié)構(gòu),目前已成為頭頸部腫瘤治療后隨訪檢查的重要方法,可以準(zhǔn)確地觀測病灶于治療前、治療后的變化情況。DWI以施加擴(kuò)散敏感梯度場測量組織信號強(qiáng)度的變化,反映活體組織在生理和病理生理狀態(tài)下水分子微觀運(yùn)動的情況,提供腫瘤細(xì)胞密度、細(xì)胞膜完整性的組織病理學(xué)信息,對腫瘤治療前后的微環(huán)境變化較為敏感,并能監(jiān)測腫瘤治療過程中組織成分的變化和病理學(xué)改變[6-7]。DWI采用表觀擴(kuò)散系數(shù)對活體內(nèi)水分子擴(kuò)散運(yùn)動狀態(tài)進(jìn)行定量描述。惡性腫瘤細(xì)胞往往呈堆積生長,細(xì)胞密度升高,細(xì)胞外間隙減少,水分子擴(kuò)散受限程度較重,因此常表現(xiàn)為DWI高信號、ADC值減低的特點(diǎn)[8]。
研究證實(shí)DWI在腫瘤診斷及鑒別診斷中有顯著作用,并發(fā)現(xiàn)DWI成像更適用于腫瘤的療效監(jiān)測及評估。治療前腫瘤的ADC值越小,治療效果越好;ADC值越大,療效越差[3, 9]。Kim等[9]通過對40例頭頸部鱗癌患者研究,完全緩解者與部分緩解者治療前的ADC值分別為1.04 ± 0.19×l0–3mm2/s 及1.35 ± 0.30×l0–3mm2/s,完全緩解者明顯低于部分緩解者,兩者有統(tǒng)計學(xué)意義(P<0.05),同時發(fā)現(xiàn)同步放化療第1周時ADC值就有所上升,完全緩解者比部分緩解者有更大的升幅。說明治療前ADC值的測定及治療后ADC值變化的幅度可以預(yù)測頭頸部惡性腫瘤放化療的效果。Vandecaveye等[10]通過監(jiān)測30例頭頸部鱗癌患者治療前、同步放化療后第2周及第4周ADC值的變化,發(fā)現(xiàn)完全緩解患者較復(fù)發(fā)患者治療早期的ADC值變化更為顯著(P<0.01)。Lambrecht等[11]利用多b值平估治療前頭頸部鱗狀細(xì)胞癌患者的治療療效,單變量分析發(fā)現(xiàn),ADChigh、ADCavg越高,病變復(fù)發(fā)可能性越大;而多變量分析發(fā)現(xiàn),ADChigh越高、腫瘤體積越大,則病變預(yù)后越差。研究表明,ADChigh是評價頭頸部鱗狀細(xì)胞癌預(yù)后的獨(dú)立影響因素。林蒙等[12]應(yīng)用DWI成像對65例鼻咽癌同步放化療患者進(jìn)行研究,研究結(jié)果顯示治療前ADC值預(yù)測鼻咽癌療效價值較高,治療前腫瘤平均和最高ADC值與腫瘤消退率均呈負(fù)相關(guān)(P<0.001),以腫瘤治療前平均ADC值1.09×10-3mm2/s為界值預(yù)測腫瘤CR,其敏感度、特異度和準(zhǔn)確性分別為82.5%、76.0%和80.0%,AUC為0.816,顯示DWI及ADC值能夠較好地預(yù)測鼻咽癌治療療效,可為鼻咽癌個體化治療提供客觀依據(jù)。不過,也有研究[13-14]顯示治療前腫瘤ADC值對區(qū)分治療有效組和無效組無意義。
我們希望尋求一種無創(chuàng)、快速、高效的檢查手段來準(zhǔn)確評判、預(yù)測非手術(shù)喉癌下咽癌患者同步放化療的治療效果,從而為腫瘤治療策略的制定、修改提供依據(jù)。本次研究結(jié)果顯示,治療前腫瘤平均及最高ADC值與緩解率呈負(fù)相關(guān),治療后腫瘤平均ADC值與緩解率呈正相關(guān)(P<0.05)。非CR組治療前腫瘤平均、最高ADC值均高于CR組,CR組治療后腫瘤平均ADC值及治療前后腫瘤平均ADC值變化高于非CR組,差異有統(tǒng)計學(xué)意義(P<0.001),表明放化療造成腫瘤細(xì)胞變性、壞死,細(xì)胞外間隙變大,水分子擴(kuò)散受限降低,ADC值升高,腫瘤內(nèi)部出現(xiàn)乏氧區(qū)域、放化療不敏感區(qū)域,治療前后ADC的變化可作為治療效果監(jiān)測指標(biāo)。但是本次研究尚有諸多不足:(1)僅研究治療前及治療后1個月內(nèi)的腫瘤變化情況,為短期隨訪;(2)ROI的選擇方面,人為因素較大,位置上的偏差及區(qū)域勾畫都會對結(jié)果產(chǎn)生影響;(3)病例數(shù)較少,并缺乏對PR、SD患者的單獨(dú)分析;(4)治療后部分患者會存在局部水腫、急性放射損傷等會造成治療后ADC值偏高,可能會夸大ADC值變化對療效判斷的作用。今后會進(jìn)一步改進(jìn),擴(kuò)大病例數(shù),以獲得更準(zhǔn)確的結(jié)果為臨床提供治療依據(jù)。
綜上所述,治療前腫瘤ADC值以及治療前后腫瘤ADC值的變化對評價非手術(shù)喉癌下咽癌患者放化療后早期緩解率有一定意義。
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The value of diffusion-weighted imaging for clinical evaluation of chemoradiatiotherapy of non-surgical laryngeal and hypopharyngeal carcinoma patients
LI Yi-xia1, CUI Yuan-yuan1, CUI Bao1, MA Lu1, CHEN Si1, YANG Na1, ZHANG Ailian1, CAI Jian-ming1, 2*1Department of Radiology, Chinese PLA General Hospital, Beijing 100853, China
2Department of Radiology, the First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China
*Correspondence to: Cai JM, E-mail: beili12345@sina.cn
Received 2 Dec 2015, Accepted 25 Jan 2016
AbstractObjective: To investigate the value of the magnetic resonance diffusion weighted imaging combined with conventional MRI for predicting clinical effect of chemoradiotherapyin non-surgical laryngeal and hypopharyngeal carcinoma. Materials and Methods: A total of 25 cases of patients with non-surgical laryngeal and hypopharyngeal carcinoma, which was confirmed by biopsy or surgical pathology, were included. All patients underwent conventional MRI and DWI scan for pre- and post-treatment. The maximum cross sectional area and apparent diffusion coefficient (ADC) value (the mean, the highest and lowest ADC value) of the tumor were measured before treatment. The residual tumor size and ADC values were measured after treatment, and tumor regression rate was calculated. The differences of ADC values with complete response (CR) and non-CR before and after treatment were analyzed. Results: The maximum cross sectional area [2.42 (0—7.92) cm2] of the tumor after treatment was significantly reduced (P<0.05) than that from pre-treatment [4.81 (0.83—14.12) cm2]. The total tumor remission rate was 74.8% (6.0%—100%) and CR was in 11 (11/25, 44.0%) patients. Pre-treatment ADC(mean)and the highest ADC value were negatively correlated with the rate of tumor regression (r=-0.922, -0.691, P<0.05), and post-treatment ADC(mean)value was positively correlated with thebook=186,ebook=33regression rate (P<0.05, r=0.678). Pre-treatment ADC(mean)and ADC(high)values in non CR group were higher than those in the CR group. Post-treatment ADC(mean)value and differences of the ADC value between pre- and post-treatment of CR group were significantly higher than those of non CR group (P<0.05). Conclusions: The pre-treatment ADC values and the differences of the ADC value between pre- and post-treatment might be useful to predict and evaluate the response of radiotherapy and chemotherapy in the non-surgical laryngeal and hypopharyngeal carcinoma patients.
Key wordsLaryngeal neoplasms; Hypopharyngeal neoplasms; Diffusion magnetic resonance imaging; Radiotherapy; Chemotherapy, adjuvant
DOI:10.12015/issn.1674-8034.2016.03.005
文獻(xiàn)標(biāo)識碼:A
中圖分類號:R445.2;R739.65
收稿日期:2015-12-02
通訊作者: