楊 濤,劉雁冰,張朝蓬,劉 廣,穆殿斌,王永勝.山東省腫瘤醫(yī)院乳腺病中心,山東 濟(jì)南 2507;2.連云港市第一人民醫(yī)院放療科,江蘇 連云港 222002
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MRI對(duì)新輔助化療后乳腺原發(fā)腫瘤退縮模式預(yù)測(cè)的準(zhǔn)確度
楊 濤1,2,劉雁冰1,張朝蓬1,劉 廣1,穆殿斌1,王永勝1
1.山東省腫瘤醫(yī)院乳腺病中心,山東 濟(jì)南 250117;
2.連云港市第一人民醫(yī)院放療科,江蘇 連云港 222002
[摘要]背景與目的:新輔助化療(neoadjuvant chemotherapy,NAC)可使原發(fā)腫瘤較大的乳腺癌患者獲得保乳治療(breast-conserving therapy,BCT)機(jī)會(huì),但NAC后原發(fā)腫瘤退縮模式影響保乳率及預(yù)后。本研究旨在觀察MRI對(duì)NAC后乳腺原發(fā)腫瘤退縮模式預(yù)測(cè)的準(zhǔn)確度。方法:61例ⅡA~ⅢC期乳腺浸潤(rùn)性導(dǎo)管癌患者,NAC后手術(shù)標(biāo)本制作次連續(xù)病理大切片,顯微鏡下勾畫殘余腫瘤范圍,Photoshop軟件配準(zhǔn),3D-DOCTOR軟件三維重建病理及MRI圖像殘余腫瘤模型,評(píng)價(jià)NAC后原發(fā)腫瘤的病理退縮模式。將其分為外科pCR(無殘留灶)、孤立狀、結(jié)節(jié)狀、團(tuán)塊伴散在狀和彌散狀。結(jié)合病理退縮模式,將臨床-病理退縮模式分為退縮明顯型(distinct shrinkage mode,DSM,相比NAC前原發(fā)腫瘤最長(zhǎng)徑,NAC后殘余腫瘤最長(zhǎng)徑退縮比率≥50%且≤2 cm)和非退縮明顯型(non-distinct shrinkage mode,NDSM)。結(jié)果:MRI和病理的退縮模式呈外科pCR、孤立狀、結(jié)節(jié)狀、團(tuán)塊伴散在狀和彌散狀模式分別為23例、17例、5例、9例、7例和18例、3例、13例、20例、7例(P=0.001)。MRI預(yù)測(cè)病理退縮模式的準(zhǔn)確度、靈敏度和特異度分別為86.2%,65.6%和91.4%。MRI和病理呈DSM比例分別為62.3%和59.0%(κ=0.863,P=0.000)。MRI預(yù)測(cè)臨床-病理退縮模式的準(zhǔn)確度、靈敏度和特異度分別為91.0%、64.0%和94.8%,其中預(yù)測(cè)DSM和NDSM差異均無統(tǒng)計(jì)學(xué)意義(P均>0.05)。MRI預(yù)測(cè)臨床-病理退縮模式的受試者工作特征(receiver operating characteristic,ROC)曲線下面積為0.928(P=0.000)。結(jié)論:NAC后MRI三維重建圖像能準(zhǔn)確模擬并預(yù)測(cè)殘余腫瘤的立體空間位置,有助于選擇NAC后降期BCT患者。
[關(guān)鍵詞]乳腺癌;退縮模式;新輔助化療;三維重建;MRI
Correspondence to: WANG Yong-sheng E-mail: wangysh2008@aliyun.com
對(duì)于初始腫瘤較大的可手術(shù)乳腺癌患者,新輔助化療(neoadjuvant chemotherapy,NAC)的主要優(yōu)點(diǎn)在于可以降低臨床分期,使有保乳意愿但不適合保乳治療(breast-conserving therapy,BCT)的患者獲得更多的保乳機(jī)會(huì),縮小手術(shù)范圍,改善患者的生活質(zhì)量[1-4]。NAC后原發(fā)腫瘤退縮成多中心殘余腫瘤被證實(shí)是BCT后同側(cè)乳房腫瘤復(fù)發(fā)(ipsilateral breast tumor recurrence,IBTR)的影響因素[5-6]。因此,NAC后原發(fā)腫瘤退縮模式的準(zhǔn)確評(píng)估對(duì)于BCT患者的選擇至關(guān)重要。本研究試圖通過NAC后殘余腫瘤的病理及MRI三維重建,觀察MRI對(duì)乳腺癌NAC后原發(fā)腫瘤退縮模式預(yù)測(cè)的準(zhǔn)確度。
1.1 一般資料
選取山東省腫瘤醫(yī)院乳腺病中心2010年7月—2013年8月接受6~8個(gè)周期NAC的ⅡA~ⅢC期女性乳腺癌患者,共61例,年齡31~70歲(中位年齡49歲)。NAC前后均行MRI檢查。入選標(biāo)準(zhǔn):① NAC前所有腫瘤均經(jīng)空芯針穿刺活檢病理證實(shí)為浸潤(rùn)性導(dǎo)管癌;② MRI圖像及臨床檢查示原發(fā)孤立腫瘤;③ 美國(guó)東部腫瘤協(xié)作組(Eastern Cooperative Oncology Group,ECOG)評(píng)分為0~1分;④ 主要器官功能正常,且Hb≥90 g/L,WBC≥2.0×109/ L,ANC≥1.5×109/L,PLT≥100×109/L,ALT和AST≤2.5×ULN,血肌酐≤1.5×ULN;⑤ 無明顯心功能障礙;⑥NAC后完全切除殘余腫瘤(乳腺癌改良根治術(shù)/保乳手術(shù))。排除標(biāo)準(zhǔn):① 既往接受過新輔助治療(包括NAC和新輔助內(nèi)分泌治療);② 既往其他惡性腫瘤病史;③ 炎性乳腺癌;④ 妊娠哺乳期婦女;⑤ NAC后病灶評(píng)價(jià)疾病穩(wěn)定(stable disease,SD)或疾病進(jìn)展(progressive disease,PD);⑥ 正在接受其他臨床試驗(yàn),可能對(duì)本研究產(chǎn)生影響的患者。
1.2 新輔助化療方案
采用AC-P方案者32例(52.5%),TAC方案者23例(37.7%),F(xiàn)EC方案者2例(3.3%),AC-PH方案者2例(3.3%),TCH方案者1例(1.6%),TP方案者1例(1.6%)。
1.3 次連續(xù)病理大切片制作
1.3.1 乳房切除術(shù)后標(biāo)本
根據(jù)NAC前超聲引導(dǎo)下美蘭標(biāo)記的原發(fā)腫瘤范圍,放射狀地向外擴(kuò)大3 cm切除乳腺標(biāo)本,標(biāo)本放進(jìn)-20 ℃冰箱12~24 h。乳腺皮膚表面平行劃取數(shù)道刀痕,平行注射器針道雙色涂抹法標(biāo)記定位點(diǎn),乳腺標(biāo)本放置自制大切片取材臺(tái),間隔3 mm,平行Y軸取材,平均切30個(gè)層面(圖1)。切片標(biāo)記計(jì)數(shù),放入鐵夾,防止組織變形。自制病理大切片包埋臺(tái)對(duì)組織切片包埋。Leica Microm TP 1020大組織切片機(jī)切片,每個(gè)蠟塊切片2~3張,切片厚度4~6 μm。HE染色封片(表1)。
表1 制作步驟Tab.1 Processing schedules
1.3.2 乳腺癌保乳術(shù)后標(biāo)本
根據(jù)NAC前超聲引導(dǎo)下美蘭標(biāo)記的原發(fā)腫瘤范圍,術(shù)者放射狀地外擴(kuò)1 cm切除腺體標(biāo)本,平行針道埋線標(biāo)記點(diǎn)位點(diǎn)。以下步驟如上述乳房切除術(shù)后標(biāo)本制作(圖1)。
1.4 病理三維重建
在顯微鏡下勾畫出每張切片殘余腫瘤邊界及鈣化點(diǎn)。將Epson V600掃描儀分辨率設(shè)定為360 bpi,掃描勾畫切片。Photoshop軟件導(dǎo)入勾畫的切片,乳房切除標(biāo)本以皮膚刀痕和染料定位點(diǎn)為基準(zhǔn),保乳術(shù)后標(biāo)本以腺體刀痕和線孔為基準(zhǔn),進(jìn)行切片配準(zhǔn)。配準(zhǔn)后的切片導(dǎo)入3D-DOCTOR軟件,依據(jù)顯微鏡下勾畫的殘余腫瘤范圍及鈣化點(diǎn),在軟件中用不同的顏色標(biāo)記:紅色代表浸潤(rùn)性導(dǎo)管癌,綠色代表導(dǎo)管原位癌,紫色代表鈣化灶。選擇 “Edit/ Calibrations”指令,彈出圖像校準(zhǔn)參數(shù)對(duì)話框,X、Y軸輸入0.07,Z軸輸入3,單位為mm。使用“3D Rendering/Surface Rendering/Simple Surface”指令,呈現(xiàn)出NAC后殘余腫瘤病理三維模型(圖2)。
1.5 MRI三維重建
乳腺M(fèi)RI檢查采用飛利浦3.0 T MRI成像系統(tǒng)。乳腺M(fèi)RI圖像以DICM格式刻錄到CD光盤,將其導(dǎo)入3D-DOCTOR軟件。勾畫每張動(dòng)態(tài)增強(qiáng)圖像的乳腺腫瘤范圍,選擇“3D Rendering/ Surface Rendering/Simple Surface”指令,三維重建出NAC前后乳腺M(fèi)RI三維圖像模型(圖2)。
圖1 乳腺次連續(xù)病理大切片制作Fig.1 Breast part-mount sub-serial section processing
圖2 病理及MRI三維模型Fig.2 3D mode of pathology and MRI
1.6 NAC后三維退縮模式
1.6.1 病理退縮模型
① 外科pCR:無殘留灶,即乳腺組織所有的浸潤(rùn)性癌和原位癌細(xì)胞無殘留;② 孤立狀:殘留孤立腫瘤并周圍無散在癌灶;③ 結(jié)節(jié)狀:癌灶呈結(jié)節(jié)狀散在分布,相互無關(guān)聯(lián);④ 團(tuán)塊伴散在狀:孤立團(tuán)狀腫瘤伴散在癌灶;⑤ 彌散狀:腫瘤原位消融,呈蜂巢狀散在分布(圖3)。
1.6.2 臨床-病理退縮模型
為了滿足NAC后保乳患者的殘余腫瘤長(zhǎng)徑的選擇標(biāo)準(zhǔn),結(jié)合病理退縮模式形態(tài),推導(dǎo)出臨床-病理退縮模型,分為退縮明顯型(distinct shrinkage mode,DSM)和非退縮明顯型(nondistinct shrinkage mode,NDSM)。
DSM包括外科pCR、孤立狀、結(jié)節(jié)狀和團(tuán)塊伴散在狀。以上4種模式滿足:相比NAC前原發(fā)腫瘤最長(zhǎng)徑,NAC后殘余腫瘤最長(zhǎng)徑退縮比率≥50%且≤2 cm。
NDSM包括孤立狀、結(jié)節(jié)狀、團(tuán)塊伴散在狀和彌散狀。以上4種退縮模式滿足:相比NAC前原發(fā)腫瘤最長(zhǎng)徑,NAC后殘余腫瘤最長(zhǎng)徑退縮比率<50%和(或)>2 cm。采用MRI測(cè)量NAC前原發(fā)腫瘤最長(zhǎng)徑,病理測(cè)量NAC后殘余腫瘤最長(zhǎng)徑(圖4)。
圖3 病理三維退縮模型Fig.3 3D pathological shrinkage modes
圖4 臨床-病理三維退縮模型Fig.4 3D clinical-pathological shrinkage modes
1.7 統(tǒng)計(jì)學(xué)處理
采用SPSS 17.0軟件進(jìn)行數(shù)據(jù)分析。使用χ2檢驗(yàn)分析率之間的差異。以病理檢查為金標(biāo)準(zhǔn),建立受試者工作特征(receiver operating characteristic,ROC)曲線,計(jì)算MRI預(yù)測(cè)的曲線下面積。P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2.1 病理退縮模式
MRI圖像退縮模式呈外科pCR、孤立狀、結(jié)節(jié)狀、團(tuán)塊伴散在狀和彌散狀分別為23例(37.7%)、17例(27.9%)、5例(8.2%)、9例(14.8%)和7例(11.5%),病理檢查分別為18例(29.5%)、3例(4.9%)、13例(21.3%)、20例(32.8%)和7例(11.5%),差異有統(tǒng)計(jì)學(xué)意義(P=0.006,表2)。MRI預(yù)測(cè)病理退縮模式的準(zhǔn)確度、靈敏度、特異度、陽性預(yù)測(cè)值和陰性預(yù)測(cè)值分別為86.2%、65.6%、91.4%、65.6%和91.4%。
MRI預(yù)測(cè)彌散狀模式的準(zhǔn)確度與外科pCR相似(P=0.119),顯著優(yōu)于其他模式(P均<0.05)。預(yù)測(cè)孤立狀模式的特異度和陽性預(yù)測(cè)值最低(75.9%和17.6%),均劣于外科pCR、團(tuán)塊伴散在狀和彌散狀(P均<0.05)。預(yù)測(cè)外科pCR、孤立狀和彌散狀模式的陰性預(yù)測(cè)值最高(100.0%),顯著優(yōu)于結(jié)節(jié)狀、團(tuán)塊伴散在狀(P均<0.05,表3)。
2.2 臨床-病理退縮模式
MRI圖像呈向心性退縮和非向心性退縮 DSM和NDSM分別為38例(62.3%)和23例(37.7%);病理檢查分別為36例(59.0%)和26例(41.0%),差異無統(tǒng)計(jì)學(xué)意義(P=0.854)。兩者評(píng)價(jià)臨床-病理退縮模式具有顯著的一致性(κ=0.863,P=0.000,表4)。
在MRI評(píng)價(jià)向心性退縮者DSM中,23例(37.7%)呈外科pCR,10例(16.4%)呈孤立狀,2例(3.3%)呈團(tuán)塊伴散在狀;在非向心性退縮者NDSM中,6例(9.8%)呈孤立狀,3例(4.9%)呈結(jié)節(jié)狀,10例(16.4%)呈團(tuán)塊伴散在狀,7例(11.5%)呈彌散狀。
在病理檢查評(píng)價(jià)向心性退縮者DSM中,18例(29.5%)呈外科pCR,3例(4.9%)呈孤立狀,10例(16.4%)呈結(jié)節(jié)狀,5例(8.2%)呈團(tuán)塊伴散在狀;在非向心性退縮者NDSM中,15例(24.6%)呈團(tuán)塊伴散在狀,3例(4.9%)呈結(jié)節(jié)狀,7例(11.5%)呈彌散狀(表5)。
MRI預(yù)測(cè)臨床-病理退縮模式的準(zhǔn)確度、靈敏度、特異度、陽性預(yù)測(cè)值和陰性預(yù)測(cè)值分別為91.0%、64.0%、94.8%、64.0%和94.8%。MRI預(yù)測(cè)向心性退縮和非向心性退縮DSM和NDSM的準(zhǔn)確度、靈敏度、特異度、陽性預(yù)測(cè)值和陰性預(yù)測(cè)值分別為89.8%、63.9%、94.2%、65.7%、93.8%和92.2%、64.0%、95.4%、61.5%、95.9%,差異無統(tǒng)計(jì)學(xué)意義(P均>0.05,表6)。MRI預(yù)測(cè)臨床-病理退縮模式的ROC下面積為0.928(95%CI:0.832~0.978,P=0.000,圖5)。
表2 NAC后原發(fā)腫瘤的病理與MRI退縮模式Tab.2 Shrinkage modes of the primary breast tumor after NAC by pathology and MRI [n(%)]
表3 MRI預(yù)測(cè)NAC后原發(fā)腫瘤的病理退縮模式Tab.3 MRI predicting the pathological shrinkage modes of the primary breast tumor after NAC
表4 NAC后原發(fā)腫瘤的臨床-病理退縮模式Tab.4 Clinical-pathological shrinkage modes of the primary breast tumor after NAC
表5 NAC后原發(fā)腫瘤的臨床-病理退縮模式的亞組Tab.5 The subgroups of clinical-pathological shrinkage modes of the primary breast tumor after NAC [n(%)]
圖5 MRI預(yù)測(cè)臨床-病理退縮模式ROC曲線Fig.5 ROC curves of MRI predicting clinical-pathological shrinkage mode
表6 MRI預(yù)測(cè)NAC后原發(fā)腫瘤的臨床-病理退縮模式Tab.6 MRI predicting the clinical-pathological shrinkage modes of the primary breast tumor after NAC
NAC可以使部分初始需要乳房切除的患者降期接受BCT,并獲得良好的美容效果[1-4]。NAC后行BCT是否會(huì)增加后期的IBTR是被普遍關(guān)注的問題。NSABP B-18試驗(yàn)[7]中位隨訪16年,證實(shí)NAC后BCT患者的IBTR高于BCT后輔助化療患者,但差異無統(tǒng)計(jì)學(xué)意義(P=0.21)。EORTC 10902試驗(yàn)[8]中位隨訪10年的數(shù)據(jù)顯示,對(duì)比初始可行BCT的患者,計(jì)劃接受乳房切除術(shù)的患者NAC后改行保乳手術(shù)后的局部復(fù)發(fā)率并未顯著增加,但總生存期更短。Ishitobi等[5]研究發(fā)現(xiàn),NAC后發(fā)生IBTR的患者預(yù)后更差,且證實(shí)了NAC后殘余腫瘤呈多中心模式是IBTR的獨(dú)立影響因素之一。因此,為了成功施行BCT降低IBTR,必須考慮原發(fā)腫瘤的范圍和腫瘤的退縮模式,并需謹(jǐn)慎檢測(cè)切緣狀況。
目前,MRI已成為NAC后評(píng)估殘余腫瘤和化療反應(yīng)的最佳方法[9-16]。MRI通過對(duì)比增強(qiáng)的病灶信號(hào)是否降低判斷NAC反應(yīng),較鉬靶和B超能更精確地評(píng)估NAC反應(yīng),對(duì)殘余腫瘤范圍的評(píng)估與病理具有較好的一致性[17]。同時(shí)MRI可鑒別殘留組織及NAC后引起的纖維增生或壞死組織,有助于幫助選擇NAC行保乳手術(shù)的患者[16]。但NAC后原發(fā)腫瘤退縮的多樣性,特別是蜂窩樣或散在分布的退縮,降低MRI對(duì)NAC后殘余腫瘤范圍測(cè)量的精確性[18]。因此,本研究通過聯(lián)合NAC后殘余腫瘤模型的病理和MRI三維重建,促進(jìn)殘余腫瘤空間關(guān)系的可視化,促使MRI更全面、立體、直觀地預(yù)測(cè)NAC后原發(fā)腫瘤退縮模式,同時(shí)可以提供一項(xiàng)測(cè)量腫瘤范圍更準(zhǔn)確的方法,有助于選擇NAC后適合行BCT的患者。
NAC后獲得pCR者行BCT后的LRR率較低,且有更好的預(yù)后[7]。TBCRC Trial017試驗(yàn)[19]報(bào)道,NAC后MRI預(yù)測(cè)外科pCR的準(zhǔn)確度、靈敏度和特異度分別為74.0%、83.0%和47.0%。本研究采用次連續(xù)病理大切片技術(shù),提高了殘余腫瘤的檢出率和MRI預(yù)測(cè)外科pCR的特異度。另外,由于化療藥物作用于乳腺組織和血管后破壞了MRI造影劑的傳導(dǎo)通路,可能提高了MRI預(yù)測(cè)外科pCR的靈敏度。Wasser等[20]研究證實(shí),NAC后原發(fā)腫瘤無反應(yīng)者,MRI預(yù)測(cè)病理的殘余腫瘤范圍準(zhǔn)確度高。同樣,本研究證實(shí)NAC后呈彌散狀退縮模式者,化療反應(yīng)評(píng)價(jià)均為1級(jí),且腫瘤范圍未縮小。因此,MRI預(yù)測(cè)該病理模式的準(zhǔn)確度、靈敏度和特異度較高,NAC后退縮呈該模式的患者不適合行BCT。目前認(rèn)為,NAC后MRI顯示腫瘤退縮成孤立狀的患者更適合行保乳手術(shù)[21]。然而,本研究發(fā)現(xiàn)MRI預(yù)測(cè)孤立狀模式的特異度和陽性預(yù)測(cè)值均最低,原因可能為NAC后腫瘤內(nèi)部組織纖維化、壞死及炎性反應(yīng)引起MRI圖像持續(xù)強(qiáng)化。因此,對(duì)于NAC 后MRI顯示腫瘤呈孤立狀退縮模式的患者,選擇行BCT時(shí)需謹(jǐn)慎對(duì)待。
本研究通過MRI與病理檢查比較發(fā)現(xiàn),兩者評(píng)價(jià)臨床-病理退縮模式具有顯著的一致性。同時(shí),MRI預(yù)測(cè)臨床-病理退縮模式的ROC下面積為0.928,故可認(rèn)為MRI預(yù)測(cè)臨床-病理退縮模式準(zhǔn)確度高,能夠指導(dǎo)NAC后行保乳手術(shù)者的篩選。
NAC后MRI三維重建圖像能準(zhǔn)確模擬并預(yù)測(cè)殘余腫瘤的立體空間位置,有助于選擇NAC后降期保乳患者。乳腺次連續(xù)病理大切片制作和MRI、病理三維重建提供了一種全新的殘余腫瘤評(píng)價(jià)方法,為該領(lǐng)域的研究提供了嶄新的平臺(tái)。
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Accuracy of MRI for predicting shrinkage modes of primary breast tumor following neoadjuvant chemotherapy with three-dimensional reconstruction technique
YANG Tao1,2, LIU Yanbing1, ZHANG Zhaopeng1, LIU Guang1, MU Dianbin1, WANG Yongsheng1(1.Breast Cancer Center, Shandong Cancer Hospital, Jinan 250117, Shandong Province, China; 2.Department of Radiotherapy, the First People's Hospital of Lianyungang, Lianyungang 222002, Jiangsu Province, China)
[Key words]Breast Cancer; Shrinkage mode; Neoadjuvant chemotherapy; Three-dimensional reconstruction; MRI
[Abstract]Background and purpose: The most clearly recognized benefit of neoadjuvant chemotherapy (NAC) is that it can increase the proportion of patients who can be treated with breast-conserving therapy (BCT).However, the shrinkage modes of the primary breast tumor after NAC have been confirmed as a predictor of BCT rate and prognosis.This study is to evaluate the accuracy of MRI predicting the shrinkage mode of the primary breast tumor after NAC with three-dimensional reconstruction technique.Methods: Sixty-one women with pathologically proven solitary invasive ductal carcinoma (ⅡA-ⅢC) were recruited.Breast specimens were prepared with PMSS, and residual tumors were microscopically outlined, scanned and registered by PHOTOSHOP software.The 3D model of residual tumors was reconstructed with 3D-DOCTOR software based on pathology and MRI imaging characteristics to evaluate the shrinkage mode.We devided the pathological shrinkage modes into surgical pCR (no residual tumors), solitary lesions without surrounding lesions, multinodular lesions, solitary lesions with adjacent spotty lesions and diffuse lesions.Further, the clinical-pathological shrinkage modes were divided into 2 categories: distinct shrinkage mode(DSM, the longest diameter of the pathological residual tumors was less than 50% and ≤2 cm in comparison with the primary tumor before NAC) and non-distinct shrinkage mode (NDSM, the longest diameter of the pathological residual tumors was more than 50% and/or >2 cm in comparison with the primary tumor before NAC).Results: The surgical pCR, solitary lesions without surrounding lesions, multinodular lesions, solitary lesions with adjacent spotty lesions and diffuse lesions were observed in 23, 17, 5, 9, 7 and 18, 3, 13, 20, 7 patients by MRI and pathology, respectively (P=0.001).The accuracy, sensitivity and specificity of MRI for predicting pathological shrinkage modes were 86.2%,65.6% and 91.4%, respectively.The DSM was observed in 36 (59.0%) patients by pathology, and 38 (62.3%) patients by MRI.Two methods had a high consistency in clinical-pathological shrinkage modes (κ=0.863, P=0.000).The accuracy, sensitivity and specificity of MRI for predicting clinical-pathological shrinkage modes were 91.0%, 64.0% and 94.8%, respectively.There was not a statistic difference in prediction between DSM and NDSM by MRI (P>0.05).Receiver operating characteristic (ROC) curve analysis showed an AUC of 0.928 (P=0.000) for MRI to predict the clinical-pathological shrinkage mode.Conclusion: Three-dimensional MRI reconstruction after NAC could simulate and predict spatial location of residual tumors, and can be helpful in selecting patients who received BCT after NAC with tumor downstaging.
DOI:10.3969/j.issn.1007-3969.2016.02.009
中圖分類號(hào):R737.9
文獻(xiàn)標(biāo)志碼:A
文章編號(hào):1007-3639(2016)02-0168-09
基金項(xiàng)目:山東省醫(yī)藥衛(wèi)生科技發(fā)展計(jì)劃項(xiàng)目(2011HD012);山東省科技發(fā)展計(jì)劃項(xiàng)目(2013YD18030)。
通信作者:王永勝 E-mail:wangysh2008@aliyun.com
收稿日期:(2014-08-07 修回日期:2015-03-08)