于麗娟,孫艷芹,徐繼有哈爾濱醫(yī)科大學(xué)附屬腫瘤醫(yī)院PET/CT-MRI中心,黑龍江 哈爾濱 150081
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18F-脫氧葡萄糖PET/CT及血清糖類抗原125檢測(cè)在卵巢癌術(shù)后復(fù)發(fā)和轉(zhuǎn)移診斷中的價(jià)值
于麗娟,孫艷芹,徐繼有
哈爾濱醫(yī)科大學(xué)附屬腫瘤醫(yī)院PET/CT-MRI中心,黑龍江 哈爾濱 150081
于麗娟,主任醫(yī)師,博士生導(dǎo)師?,F(xiàn)任哈爾濱醫(yī)科大學(xué)附屬腫瘤醫(yī)院PET/CT-MRI中心主任,哈爾濱醫(yī)科大學(xué)醫(yī)學(xué)圖像信息研究中心主任,黑龍江省醫(yī)學(xué)科學(xué)院影像研究所副所長。擅長惡性腫瘤PET/CT及MRI診斷。主要社會(huì)職務(wù)有中國抗癌協(xié)會(huì)腫瘤核醫(yī)學(xué)專業(yè)委員會(huì)副主任委員,中國醫(yī)師協(xié)會(huì)核醫(yī)學(xué)醫(yī)師分會(huì)委員,中華醫(yī)學(xué)會(huì)核醫(yī)學(xué)分會(huì)PET分子顯像學(xué)組委員,中國生物物理協(xié)會(huì)輻射與環(huán)境專業(yè)委員會(huì)委員,黑龍江省核醫(yī)學(xué)會(huì)副主任委員(兼任PET/CT學(xué)組組長),黑龍江省抗癌協(xié)會(huì)常務(wù)理事,《實(shí)用腫瘤學(xué)雜志》副主編。發(fā)表國內(nèi)外專業(yè)論文60余篇,主編國家“十一五”本科規(guī)劃教材《PET/CT診斷學(xué)》,參編“十二五”國家重點(diǎn)圖書《PET與分子影像學(xué)》以及《PET/CT疑難病例精解》。
【摘要】目的:探討18F-脫氧葡萄糖(18F-fluorodeoxyglucose,18F-FDG)PET/CT及血清糖類抗原125(carbohydrate antigen 125,CA125)診斷卵巢癌術(shù)后復(fù)發(fā)及轉(zhuǎn)移的價(jià)值。方法:收集101例術(shù)后行18F-FDG PET/CT檢查的卵巢癌患者資料,所有患者均施行腫瘤細(xì)胞減滅術(shù)及血清CA125檢測(cè)(與PET/CT檢查間隔時(shí)間<7 d)。復(fù)發(fā)及轉(zhuǎn)移的判斷以二次手術(shù)病理或穿刺病理為金標(biāo)準(zhǔn);沒有病理結(jié)果者以臨床隨訪結(jié)果為標(biāo)準(zhǔn)(最短隨訪時(shí)間>6個(gè)月)。應(yīng)用SPSS 18.0軟件進(jìn)行分析,P<0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:18F-FDG PET/CT和血清CA125對(duì)卵巢癌術(shù)后病變定性診斷的靈敏度、特異度、陽性預(yù)測(cè)值、陰性預(yù)測(cè)值、準(zhǔn)確率分別為94.1%、97.1%,81.8%、12.1%,91.4%、69.5%,87.1%、66.7%,90.1%、69.3%。以最大標(biāo)準(zhǔn)化攝取值(maximum standardized uptake value,SUVmax)≥2.5、SUVmax≥1.3為閾值,對(duì)卵巢癌術(shù)后復(fù)發(fā)及轉(zhuǎn)移診斷的靈敏度、特異度、陽性預(yù)測(cè)值、陰性預(yù)測(cè)值和準(zhǔn)確率分別為94.1%、95.6%,81.8%、84.8%,91.4%、92.9%,87.1%、90.3%,90.1%、92.1%。以CA125≥35 U/mL、CA125≥65 U/mL為閾值,對(duì)卵巢癌術(shù)后復(fù)發(fā)及轉(zhuǎn)移診斷的靈敏度、特異度、陽性預(yù)測(cè)值、陰性預(yù)測(cè)值和診斷準(zhǔn)確率分別為97.1%、88.2%,12.1%、72.7%,69.5%、87.0%,66.7%、75.0%,69.3%、83.2%。SUVmax與血清CA125值之間具有線性關(guān)系(R2=0.595)。結(jié)論:對(duì)于卵巢癌術(shù)后復(fù)發(fā)和轉(zhuǎn)移的診斷,18F-FDG PET/CT的特異度和準(zhǔn)確率高于CA125(35 U/mL)。
【關(guān)鍵詞】卵巢癌;18F-脫氧葡萄糖;正電子發(fā)射計(jì)算機(jī)斷層掃描;糖類抗原125
卵巢癌高死亡率的主要原因是病情隱蔽,早期難以發(fā)現(xiàn)和治療后易復(fù)發(fā)及轉(zhuǎn)移[1]。血清糖類抗原125(carbohydrate antigen 125,CA125)是臨床常用的卵巢癌術(shù)后監(jiān)測(cè)復(fù)發(fā)的腫瘤標(biāo)志物,其水平過高或增長速度過快,常提示卵巢癌復(fù)發(fā)[2],但需結(jié)合影像學(xué)所見來確診。目前卵巢癌術(shù)后常規(guī)影像學(xué)檢查方法有超聲、CT和MRI,在區(qū)分術(shù)后局部復(fù)發(fā)與瘢痕纖維化、腹膜隱蔽轉(zhuǎn)移灶、骨骼肌肉轉(zhuǎn)移灶中有一定的局限性,增強(qiáng)CT和MRI亦然[3]。而PET/CT實(shí)現(xiàn)了代謝與結(jié)構(gòu)成像的有機(jī)融合,其在卵巢癌術(shù)前分期、術(shù)后復(fù)發(fā)及療效評(píng)價(jià)上明顯優(yōu)于常規(guī)影像學(xué)手段。目前,PET/CT臨床應(yīng)用最廣泛的顯像劑為18F-脫氧葡萄糖(18F-fluorodeoxyglucose,18F-FDG),其最大標(biāo)準(zhǔn)化攝取值(maximum standardized uptake value,SUVmax)是判斷腫瘤組織代謝活性及生物學(xué)特征的指標(biāo),具有非侵入性和實(shí)時(shí)性。關(guān)于SUVmax與血清CA125值是否相關(guān)尚不確定。本研究收集101例卵巢癌術(shù)后患者行PET/CT檢查,同時(shí)監(jiān)測(cè)血清CA125值,探討18F-FDG PET/CT聯(lián)合血清CA125診斷卵巢癌術(shù)后復(fù)發(fā)和轉(zhuǎn)移的價(jià)值。
1.1 入組標(biāo)準(zhǔn)
收集2010年1月—2012年5月于哈爾濱醫(yī)科大學(xué)附屬腫瘤醫(yī)院行腫瘤細(xì)胞減滅術(shù)的101例卵巢癌患者,年齡(52±12.57)歲(30~69歲)。病理分型:漿液性乳頭狀囊腺癌70.3% (71/101)、透明細(xì)胞癌7.9% (8/101)、黏液性癌9.9% (10/101)和子宮內(nèi)膜樣腺癌11.9% (12/101)?;颊咝g(shù)后定期復(fù)查血清CA125且半年后因血清CA125異常增高出現(xiàn)相應(yīng)臨床癥狀在本中心行18F-FDG PET/ CT檢查。101例患者術(shù)前均未發(fā)現(xiàn)轉(zhuǎn)移。從初次手術(shù)到18F-FDG PET/CT檢查,間隔時(shí)間為6~24個(gè)月,同時(shí)定期檢測(cè)血清CA125水平。經(jīng)二次手術(shù)病理證實(shí)為惡性病變47例、良性病變6例;經(jīng)穿刺活檢病理證實(shí)惡性病變21例、良性病變5例;經(jīng)長時(shí)間隨訪證實(shí)惡性病變10例、良性病變12例。
1.2 PET/CT檢查
18F-FDG由回旋加速器和化學(xué)合成系統(tǒng)自動(dòng)合成,放化純度>95%。PET/CT掃描使用Discovery ST PET/CT掃描儀。患者先行全身(自顱骨頂部至股骨上段)螺旋CT掃描。掃描條件:掃描視野50 cm、電壓120 kV、管電流140 mAs、準(zhǔn)直5.00 mm、層厚3.75 mm、0.5 ms/轉(zhuǎn)、螺距1.25,掃描時(shí)間20~30 s。掃描時(shí)患者體位保持不變,在CT同一掃描范圍內(nèi),以3D模式行PET圖像采集,一般取6~7個(gè)床位,每個(gè)床位2.5 min。應(yīng)用CT數(shù)據(jù)對(duì)PET圖像進(jìn)行衰減校正,圖像重建采用內(nèi)迭代法,經(jīng)計(jì)算機(jī)軟件處理后獲得橫斷、矢狀、冠狀面圖像,并將數(shù)據(jù)傳至Xeleris工作站,進(jìn)行PET/CT融合圖像處理。
1.3 PET/CT圖像分析
由3名有經(jīng)驗(yàn)的PET/CT診斷醫(yī)師獨(dú)立閱片,在不知患者血清CA125值和結(jié)合血清CA125值的情況下分別閱片,并給出診斷(為便于對(duì)卵巢癌術(shù)后局部復(fù)發(fā)、遠(yuǎn)處轉(zhuǎn)移及非轉(zhuǎn)移病灶的論述,后文復(fù)發(fā)或轉(zhuǎn)移性疾病統(tǒng)稱為惡性病變,非轉(zhuǎn)移性疾病統(tǒng)稱為良性病變)。
以二次手術(shù)或穿刺病理為金標(biāo)準(zhǔn)。對(duì)于未行二次手術(shù)或穿刺的患者,則長時(shí)間(>6個(gè)月)隨訪,定期(1個(gè)月)行超聲、CT或MRI檢查。如果病灶體積逐漸增大(1~3個(gè)月體積增大1倍),則認(rèn)為是惡性病變,反之則認(rèn)為是良性病變。
1.4 CA125檢測(cè)
所有患者均定期在哈爾濱醫(yī)科大學(xué)附屬腫瘤醫(yī)院檢驗(yàn)中心進(jìn)行血清CA125檢測(cè)。血清CA125檢查:采用電化學(xué)發(fā)光法,使用Modular PE生化免疫分析系統(tǒng)(德國Roche公司)。血清CA125值<35 U/mL為陰性,≥35 U/mL為陽性。
1.5 統(tǒng)計(jì)學(xué)處理
應(yīng)用SPSS 18.0統(tǒng)計(jì)軟件進(jìn)行分析,P<0.05為有統(tǒng)計(jì)學(xué)意義。
18F-FDG PET/CT顯像和血清CA125診斷卵巢癌良惡性病變的靈敏度、特異度、陽性預(yù)測(cè)值、陰性預(yù)測(cè)值、準(zhǔn)確率分別為94.1%、81.8%、91.4%、87.1%、90.1%,以及97.1%、12.1%、69.5%、66.7%、69.3% (表1)。18F-FDG PET/CT顯像發(fā)現(xiàn)假陽性6例,假陰性4例;血清CA125測(cè)定發(fā)現(xiàn)假陽性29例,假陰性2例。
表118F-FDG PET/CT、CA125結(jié)果與病理結(jié)果的比較
卵巢癌術(shù)后復(fù)發(fā)和轉(zhuǎn)移的SUVmax及血清CA125平均值均高于良性病變,卡方檢驗(yàn)顯示差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。不同病理類型的卵巢腫瘤中,漿液性乳頭狀囊腺癌的平均SUVmax及血清CA125最高(圖1);黏液性癌的平均SUVmax及血清CA125值為中等(圖2);透明細(xì)胞癌的平均SUVmax及血清CA125最低(表2)。根據(jù)受試者工作特征(receiver operating characteristic,ROC)曲線計(jì)算得出SUVmax的截?cái)帱c(diǎn)為1.3,CA125值的截?cái)帱c(diǎn)為65 U/mL,曲線下面積(area under curve,AUC)分別為0.595和0.960(圖3)。
圖1 漿液性乳頭狀囊腺癌復(fù)發(fā)灶PET/CT及病理表現(xiàn)陰道殘端團(tuán)塊狀異常放射性濃聚,診斷為漿液性乳頭狀囊腺癌復(fù)發(fā)灶
圖2 黏液性癌轉(zhuǎn)移灶PET/CT及病理表現(xiàn)腹腔腸系膜內(nèi)見圓形不均勻異常放射性濃聚灶,診斷為黏液性癌轉(zhuǎn)移灶
表2 不同病理類型腫瘤的平均SUVmax和CA125值
圖3 SUVmax、血清CA125診斷卵巢癌的ROC曲線
Pearson相關(guān)分析顯示,SUVmax與血清CA125值之間存在明顯相關(guān)性(r=0.771,P=0.00)。線性回歸分析顯示,SUVmax與血清CA125之間具有線性關(guān)系,其決定系數(shù)R2=0.595。
對(duì)常規(guī)FDG顯像診斷腫瘤閾值(2.5)、常規(guī)血清CA125診斷腫瘤閾值(35 U/mL),以及經(jīng)ROC曲線計(jì)算出的SUVmax和CA125的截?cái)帱c(diǎn)1.3和65 U/mL為診斷閾值進(jìn)行比較,分析它們對(duì)卵巢癌復(fù)發(fā)或轉(zhuǎn)移的診斷效能(表3)。結(jié)果顯示,以SUVmax1.3為截?cái)帱c(diǎn)診斷卵巢癌復(fù)發(fā)和轉(zhuǎn)移的效能優(yōu)于以2.5為截?cái)帱c(diǎn),但卡方檢驗(yàn)顯示差異無統(tǒng)計(jì)學(xué)意義(P>0.05);以血清CA125值65 U/mL為閾值優(yōu)于以35 U/mL為閾值對(duì)卵巢癌術(shù)后良惡性病變的診斷效能,卡方檢驗(yàn)顯示差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。
表3 SUVmax、血清CA125不同截?cái)帱c(diǎn)對(duì)卵巢癌復(fù)發(fā)和轉(zhuǎn)移灶的診斷效能
卵巢癌的主要治療手段是腫瘤細(xì)胞減滅術(shù)和術(shù)后化療,腫瘤是否有殘余和復(fù)發(fā)對(duì)患者生存期具有重要影響。早期發(fā)現(xiàn)殘余灶和復(fù)發(fā)灶,盡早進(jìn)行二次手術(shù)或化療對(duì)提高患者生存期有重要作用[4-7]。目前,國內(nèi)監(jiān)測(cè)卵巢癌術(shù)后主要手段是超聲、CT、MRI和血清CA125。
血清CA125是監(jiān)測(cè)卵巢癌較好的腫瘤標(biāo)志物,對(duì)診斷、術(shù)后療效評(píng)估、復(fù)發(fā)和轉(zhuǎn)移監(jiān)測(cè)有重要意義[8-11]。本研究表明,血清CA125的假陽性率高于18F-FDG PET/CT顯像,即部分未發(fā)生轉(zhuǎn)移或復(fù)發(fā)的卵巢癌血清CA125仍異常升高,使血清CA125診斷的特異度較低。以血清CA125<35 U/mL (常規(guī)標(biāo)準(zhǔn))為診斷閾值,發(fā)現(xiàn)其對(duì)卵巢癌術(shù)后復(fù)發(fā)和轉(zhuǎn)移診斷的特異度和準(zhǔn)確率不高。而通過ROC曲線確定的以CA125=65 U/mL為復(fù)發(fā)和轉(zhuǎn)移診斷閾值時(shí),其對(duì)卵巢癌術(shù)后復(fù)發(fā)和轉(zhuǎn)移的診斷靈敏度、特異度、陽性預(yù)測(cè)值、陰性預(yù)測(cè)值、準(zhǔn)確率均高于以35 U/mL為截?cái)帱c(diǎn),提示可將CA125診斷腫瘤的閾值定為65 U/mL來提高良惡性診斷效能。
PET/CT顯像可反映腫瘤細(xì)胞代謝變化,能早期、準(zhǔn)確發(fā)現(xiàn)腫瘤的復(fù)發(fā)和轉(zhuǎn)移,特別是易發(fā)現(xiàn)超聲、CT與MRI不易發(fā)現(xiàn)的隱蔽部位或不易定性的軟組織影,如腹膜、腸系膜、盆腔組織等,并作出定性和定位診斷[12-17]。本研究顯示,18FFDG PET/CT顯像對(duì)卵巢癌復(fù)發(fā)和轉(zhuǎn)移定性診斷的靈敏度、特異度、陽性預(yù)測(cè)值、陰性預(yù)測(cè)值、準(zhǔn)確率分別為94.1%、81.8%、91.4%、87.1%、90.1%,與大多數(shù)研究[18-21]結(jié)果類似。
目前,國內(nèi)外對(duì)卵巢癌術(shù)后復(fù)發(fā)和轉(zhuǎn)移的FDG SUVmax與血清CA125之間關(guān)系的研究尚不多。本研究表明,F(xiàn)DG SUVmax與血清CA125之間有線性關(guān)系。18F-FDG PET/CT顯像與血清CA125聯(lián)合對(duì)卵巢癌術(shù)后病灶良惡性的診斷效能明顯高于單純18F-FDG PET/CT顯像,且以CA125 >65 U/mL為截?cái)帱c(diǎn)時(shí)診斷卵巢癌良惡性的效能最高。
綜上所述,對(duì)于卵巢癌術(shù)后復(fù)發(fā)和轉(zhuǎn)移的診斷,18F-FDG PET/CT診斷的特異度和準(zhǔn)確率較高。對(duì)于血清CA125異常升高而超聲、CT、MRI征象不典型者,18F-FDG PET/CT檢查可提高臨床對(duì)卵巢癌術(shù)后轉(zhuǎn)移和復(fù)發(fā)的診斷準(zhǔn)確率,為治療提供準(zhǔn)確的分子影像學(xué)客觀資料。
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Values of18F-fluorodeoxyglucose PET/CT and serum carbohydrate antigen 125 in diagnosis of recurrent and metastatic ovarian cancers
YU Lijuan, SUN Yanqin, XU Jiyou (PET/CT-MRI Center, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China))
Correspondence to: YU Lijuan E-mail: yulijuan2003@126.com
【Abstract】Objective: To evaluate the values of18F-fluorodeoxyglucose (18F-FDG) PET/CT and serum carbohydrate antigen 125 (CA125) in the diagnosis of recurrent and metastatic ovarian cancers. Methods: A total of 101 consecutive patients with ovarian cancer who underwent18F-FDG PET/CT after cytoreductive surgery were chosen. The serum CA125 level was detected within one week before or after PET/CT examination. The gold standard of recurrence or metastasis was based on pathological results acquired from reoperation or biopsy. For the patients without pathological results, the long-term follow-up (at least 6 months) results were set as standard. All the data analyses were carried out by software package SPSS 18.0, and P<0.05 was established as the threshold for significance. Results: The sensitivity, specificity, positive predicted value (PPV), negative predicted value (NPV) and accuracyof PET/CT and serum CA125 for recurrence and metastasis was 94.1%, 81.8%, 91.4%, 87.1%, 90.1%, and 97.1%, 12.1%, 69.5%,66.7 %, 69.3%, respectively. When the maximum standardized uptake value (SUVmax) thresholds were set as ≥2.5 and ≥1.3, the corresponding diagnostic values were 94.1%, 81.8%, 91.4%, 87.1%, 90.1%, and 95.6%, 84.8%, 92.9%, 90.3%, 92.1%, respectively. When the thresholds were CA125 ≥35 U/ml and CA125 ≥65 U/ml, the corresponding values were 97.1%, 12.1%, 69.5%, 66.7%,69.3%, and 88.2%, 72.7%, 87.0%, 75.0%, 83.2%, respectively. There was a linear relationship between SUVmaxand serum CA125 value (R2= 0.595). Conclusion: Compared to serum CA125,18F-FDG PET/CT is a useful technique to detect recurrent and metastatic ovarian cancer in terms of specificity and accuracy.
【Key words】Ovarian carcinoma;18F-fluorodeoxyglucose; Positron emission tomography-computed tomography;Carbohydrate antigen 125
中圖分類號(hào):R445.5
文獻(xiàn)標(biāo)志碼:A
文章編號(hào):1008-617X(2015)01-0050-06
基金項(xiàng)目:黑龍江省自然基金重點(diǎn)項(xiàng)目(No:ZD2015017)。
通信作者:于麗娟 E-mail:yulijuan2003@126.com
收稿日期:(2016-03-01)