PET/CT 顯像在頭頸部腫瘤中的臨床應(yīng)用進(jìn)展

鄭營(yíng)營(yíng) 綜述，楊忠毅 審校

復(fù)旦大學(xué)附屬腫瘤醫(yī)院核醫(yī)學(xué)科，復(fù)旦大學(xué)生物醫(yī)學(xué)影像研究中心，上海分子影像探針工程技術(shù)研究中心，復(fù)旦大學(xué)上海醫(yī)學(xué)院腫瘤學(xué)系，上海 200032

PET/CT 顯像在頭頸部腫瘤中的臨床應(yīng)用進(jìn)展

鄭營(yíng)營(yíng) 綜述，楊忠毅 審校

復(fù)旦大學(xué)附屬腫瘤醫(yī)院核醫(yī)學(xué)科，復(fù)旦大學(xué)生物醫(yī)學(xué)影像研究中心，上海分子影像探針工程技術(shù)研究中心，復(fù)旦大學(xué)上海醫(yī)學(xué)院腫瘤學(xué)系，上海 200032

楊忠毅，復(fù)旦大學(xué)附屬腫瘤醫(yī)院核醫(yī)學(xué)科副主任醫(yī)師。主要研究方向?yàn)镻ET/CT分子影像的基礎(chǔ)及臨床研究，尤其是乳腺癌18F-FES受體顯像及頭頸部腫瘤的分子影像診斷。熟悉PET/CT診斷，曾獲全國(guó)PET/CT讀片競(jìng)賽優(yōu)勝獎(jiǎng)第1名及上海市核醫(yī)學(xué)學(xué)術(shù)貢獻(xiàn)獎(jiǎng)等榮譽(yù)。主持國(guó)家自然科學(xué)基金、上海市自然科學(xué)基金和衛(wèi)生局課題多項(xiàng)；多次在美國(guó)和歐洲核醫(yī)學(xué)年會(huì)做口頭或壁報(bào)學(xué)術(shù)交流。近年來(lái)以第一作者或通訊作者發(fā)表SCI論文19篇，總影響因子近50分。

頭頸部腫瘤是常見(jiàn)的惡性腫瘤之一，由于其位置深在且復(fù)雜，臨床上主要采用根治性放療或同期放化療。早期療效評(píng)價(jià)對(duì)腫瘤治療決策的制定具有重要的指導(dǎo)意義。傳統(tǒng)的物理學(xué)技術(shù)已經(jīng)不能夠滿足對(duì)疾病早期做出診斷的需求。PET/CT作為一種無(wú)創(chuàng)的功能成像技術(shù)，能夠在解剖結(jié)構(gòu)改變之前探測(cè)到包括增殖、凋亡及乏氧等在內(nèi)的多種生物學(xué)信息的變化，在頭頸部腫瘤中的應(yīng)用日趨廣泛。該研究綜述了PET/CT顯像在頭頸部腫瘤中的臨床應(yīng)用進(jìn)展。

頭頸部腫瘤；PET/CT；臨床應(yīng)用進(jìn)展

［Key words］Head and neck carcinoma; PET/CT; The advances of clinical application

頭頸部腫瘤是臨床上常見(jiàn)的惡性腫瘤之一，乙醇、吸煙和人類乳頭瘤病毒感染是頭頸部腫瘤的主要誘發(fā)因素。常見(jiàn)的頭頸部腫瘤主要有甲狀腺癌(thyroid carcinoma，TC)、頭頸部鱗癌(head and neck squamous cell carcinoma，HNSCC)和鼻咽癌(nasopharyngeal carcinoma，NPC)等；頭頸部腫瘤位置多深在，周圍解剖結(jié)構(gòu)復(fù)雜，臨床上主要的治療方式是根治性放療或同期放化療。臨床常用的檢測(cè)手段，如內(nèi)鏡、CT及MRI等，均為物理學(xué)檢查手段，僅能反映解剖學(xué)的變化。PET/CT是一種功能成像的核醫(yī)學(xué)技術(shù)，與傳統(tǒng)成像技術(shù)相比，可以進(jìn)一步從分子水平反映腫瘤的生化和代謝，能夠?qū)υl(fā)和轉(zhuǎn)移病灶進(jìn)行定性、定量分析，評(píng)估治療療效，監(jiān)測(cè)預(yù)后和隨訪等。

1 PET/CT顯像在TC中的應(yīng)用進(jìn)展

TC近10年發(fā)病率有明顯上升趨勢(shì)，因此對(duì)該疾病的早期診斷和療效預(yù)測(cè)具有重大的臨床指導(dǎo)價(jià)值。

1.1 甲狀腺結(jié)節(jié)良、惡性的鑒別

除傳統(tǒng)的超聲檢查外，臨床上對(duì)于甲狀腺結(jié)節(jié)多采用穿刺的細(xì)胞學(xué)結(jié)果進(jìn)行良、惡性鑒別，但仍有部分患者無(wú)法獲得確定性診斷。Merten等［1］通過(guò)對(duì)細(xì)胞學(xué)上定義不確定的甲狀腺結(jié)節(jié)進(jìn)行系統(tǒng)性調(diào)查發(fā)現(xiàn)，甲狀腺結(jié)節(jié)PET顯像表現(xiàn)為陰性，即標(biāo)準(zhǔn)攝取值(standard uptake value，SUV)小于等于5，那么腫瘤為惡性的可能性較低，陰性預(yù)測(cè)值可達(dá)94%。PET/CT是一項(xiàng)非侵襲性的檢查，可以降低患者誤切甲狀腺的概率。Wang等［2］通過(guò)對(duì)5個(gè)數(shù)據(jù)庫(kù)7項(xiàng)研究的Meta分析發(fā)現(xiàn)，18F-FDG PET或PET/CT鑒別甲狀腺結(jié)節(jié)良、惡性的匯總靈敏度和特異度分別為89%和55%。Vriens等［3］的研究結(jié)果也顯示，18F-FDG PET對(duì)于細(xì)針穿刺細(xì)胞學(xué)檢查病理不能確診的甲狀腺結(jié)節(jié)鑒別的匯總靈敏度和特異度分別為95%和48%。由此可見(jiàn)，PET有望用于細(xì)胞學(xué)檢查無(wú)法確診患者進(jìn)一步治療決策的制定。

1.2 甲狀腺髄樣癌中的診斷價(jià)值

甲狀腺髓樣癌(m e d u l l a r y t h y r o i d carcinoma，MTC)起源于甲狀腺濾泡旁細(xì)胞，占所有TC比例不足10%，但是惡性程度比較高的一種TC類型。有回顧性研究對(duì)比分析了18F-FDG PET/CT與111In-Octreotide SPECT在轉(zhuǎn)移性MTC中的作用，發(fā)現(xiàn)18F-FDG PET/CT在診斷準(zhǔn)確率及發(fā)現(xiàn)淋巴結(jié)轉(zhuǎn)移病灶方面具有明顯優(yōu)勢(shì)，而111In-Octreotide SPECT在發(fā)現(xiàn)骨轉(zhuǎn)移方面價(jià)值更大［4］。此外，有研究提示，無(wú)論基于患者還是病灶的靈敏度，18F-FDG PET/CT都最高，99mTc-Octreotide次之，99mTc-MIBI最低［5］。

18F-DOPA PET/CT作為基于受體的成像技術(shù)，有望用于高度懷疑術(shù)后復(fù)發(fā)患者的診斷；在基于患者的分析中，其靈敏度可達(dá)75.6%［6］。近年來(lái)，關(guān)于MTC生長(zhǎng)抑素受體成像的研究逐漸增多， Treglia等［7］回顧性分析評(píng)價(jià)了18F-DOPA、18F-FDG和68Ga-生長(zhǎng)抑素受體類似物在檢測(cè)MTC復(fù)發(fā)方面的應(yīng)用，發(fā)現(xiàn)18F-DOPA PET/CT在三者之中最具優(yōu)勢(shì)。PET/ CT在復(fù)發(fā)、轉(zhuǎn)移MTC中診斷價(jià)值的Meta分析見(jiàn)表1［8-10］。

表1 PET/CT或PET在復(fù)發(fā)、轉(zhuǎn)移甲狀腺髓樣癌診斷中的Meta分析Tab. 1 The Meta-analysis of PET/CT or PET in diagnosis of recurrent/metastatic MTC

1.3 核素治療中的價(jià)值

如果18F-FDG PET/CT顯像表現(xiàn)為高攝取灶，那么一般表現(xiàn)為對(duì)放射性碘的攝取則較低，與轉(zhuǎn)移病灶無(wú)18F-FDG攝取的患者相比3年死亡率明顯升高［11］。只有少數(shù)文獻(xiàn)［12］報(bào)道甲狀腺癌轉(zhuǎn)移病灶對(duì)131I和18F-FDG同時(shí)有攝取的現(xiàn)象，表明轉(zhuǎn)移病灶呈現(xiàn)分化良好的與去分化的腫瘤細(xì)胞共同存在的狀態(tài)。

124I PET/CT在具有碘吸收功能的TC中具有評(píng)價(jià)預(yù)后的作用。Pont等［13］對(duì)20例患者在131I放射性消融治療前行124I PET/CT顯像，131I放射性消融治療后行131I SPECT/CT顯像。124I PET/ CT與131I平面和SPECT/CT顯像結(jié)果相比，其中15%的患者TNM分期提高，主要是由于SPECT/ CT的空間分辨率和靈敏度較低，即使注射較高的放射性劑量，假陽(yáng)性率依舊高于PET/CT。Ruhlmann等［14］則通過(guò)治療中的顯像取代治療后的131I顯像，其結(jié)果顯示，在以病灶為中心的分析中，共發(fā)現(xiàn)227處轉(zhuǎn)移灶，其中124I PET探測(cè)到98%的病灶，131I則為99%，一致率為97%(221/227)，并且發(fā)現(xiàn)1%的治療劑量用作診斷劑量一致率較高。有文獻(xiàn)支持在診斷方面，131I治療前124I PET顯像與治療后131I成像相比具有優(yōu)勢(shì)［13］，但也有報(bào)道不支持以上研究結(jié)果［15-16］，故目前對(duì)此仍存在較大爭(zhēng)議。

1.4 甲狀腺偶發(fā)瘤的檢出

Hagenimana等［17］回顧性分析了進(jìn)行18F-FDG PET/CT檢查的40 914例患者，其中探測(cè)到甲狀腺偶發(fā)瘤的發(fā)生率為0.74%。Yang等［18］對(duì)15 948例非甲狀腺疾病的患者進(jìn)行18F-FDG PET/CT的回顧性研究則提示偶發(fā)瘤的檢出率高達(dá)3.1%。當(dāng)表現(xiàn)為局灶性18F-FDG攝取，且SUVmax極高，或出現(xiàn)鈣化的現(xiàn)象時(shí)，那么很有可能是甲狀腺惡性腫瘤，需要進(jìn)一步的檢查。

2 PET/CT顯像在HNSCC中的應(yīng)用進(jìn)展

HNSCC在全球發(fā)病率和死亡率中占較大比例，對(duì)于手術(shù)不能切除的病灶，主要采取根治性放療伴或不伴化療，其中腫瘤對(duì)放療敏感與否是HNSCC重要的預(yù)后和預(yù)測(cè)因子。

2.1 診斷、分期、再分期

HNSCC是頭頸部腫瘤中最常見(jiàn)的病理類型，其發(fā)生遠(yuǎn)處臟器轉(zhuǎn)移的概率雖然僅4%～25%，但遠(yuǎn)處轉(zhuǎn)移是HNSCC的主要死因［19］，一旦探測(cè)到遠(yuǎn)處臟器轉(zhuǎn)移，期望存活率僅有4.4～7.3個(gè)月［20］。一系列的Meta分析提示，18F-FDG PET/CT在HNSCC中的匯總靈敏度為48.3%～89.3%，特異度為86.2%～98.0%(表2)，具有一定的診斷價(jià)值［21-24］。

2.2 療效預(yù)測(cè)

18F-FDG PET/CT通過(guò)對(duì)代謝活性進(jìn)行定量分析，能夠在評(píng)估HNSCC預(yù)后及療效預(yù)測(cè)方面提供有價(jià)值的信息。有研究對(duì)2 692例頭頸部腫瘤患者進(jìn)行了回顧性分析，發(fā)現(xiàn)轉(zhuǎn)移腫瘤的18F-FDG SUVmax與HNSCC患者的生存結(jié)果具有明顯相關(guān)性［20］。另有研究提示，18F-FDG SUVmax除可用于預(yù)后判斷外，其與臨床TNM分期亦具有很好的相關(guān)性［25］。此外，對(duì)64例咽癌患者的回顧性研究結(jié)果表明，治療前代謝腫瘤體積(metabolic tumor volume，MTV)大于13.6 mL是復(fù)發(fā)的唯一預(yù)測(cè)指標(biāo)［26］。

表2 PET/CT或PET在原發(fā)HNSCC中的Meta分析Tab. 2 The Meta-analysis of PET/CT or PET in primary head and neck squamous cell carcinoma

2.3 第二原發(fā)腫瘤的檢出

16.3 %的頭頸部腫瘤具有發(fā)生第二原發(fā)腫瘤的傾向，故第二原發(fā)惡性腫瘤是一個(gè)重要的預(yù)后影響因子。一旦探測(cè)到第二原發(fā)腫瘤，患者預(yù)后多不佳，因此早期探測(cè)出該病灶尤為迫切。它是治療失敗及分期低的HNSCC患者死亡的主要原因，而且該腫瘤好發(fā)的部位多預(yù)后較差，如食管。18F-FDG PET/CT探測(cè)第二原發(fā)腫瘤的靈敏度和陽(yáng)性預(yù)測(cè)值分別為91%和69%［27］，故能在第二原發(fā)腫瘤早期探測(cè)到異常，為后續(xù)治療提供最佳機(jī)會(huì)。

2.4 個(gè)體化治療決策的制定

早期的報(bào)道［28-30］只研究了18F-FDG PET/ CT在HNSCC誘導(dǎo)化療1個(gè)療程后的治療效果，而沒(méi)有根據(jù)結(jié)果輔助個(gè)體化治療方案的制定。近些年，隨著個(gè)體化治療決策概念深入人心，有研究對(duì)比了功能MRI和18F-FDG PET/CT在HNSCC誘導(dǎo)化療1個(gè)療程后的早期療效評(píng)價(jià)的價(jià)值，結(jié)果表明MTV和病灶總糖代謝(total lesion glycolysis，TLG)可對(duì)誘導(dǎo)化療后進(jìn)行放化療的結(jié)果進(jìn)行早期預(yù)測(cè)，有望將患者進(jìn)行分層并進(jìn)行個(gè)體化治療［31］。

3 PET/CT顯像在NPC中的應(yīng)用進(jìn)展

3.1 診斷、分期和再分期

NPC是起源于鼻咽上皮細(xì)胞的惡性腫瘤，好發(fā)于中國(guó)南部，以未分化的病理類型居多。多數(shù)患者起病隱匿，確診時(shí)多已為局部晚期患者，90%的患者已發(fā)生淋巴結(jié)轉(zhuǎn)移，5%～10%的患者發(fā)生遠(yuǎn)處轉(zhuǎn)移［32］。雖然NPC對(duì)放化療非常敏感，但仍有7%～13%的患者治療后有殘余病灶持續(xù)存在。發(fā)生局部和遠(yuǎn)處復(fù)發(fā)后，患者預(yù)后顯著下降。因此，早期發(fā)現(xiàn)殘留和復(fù)發(fā)病灶對(duì)預(yù)后具有非常重要的意義。

18F-FDG PET/CT對(duì)NPC殘留或復(fù)發(fā)的診斷價(jià)值見(jiàn)表3［33-37］。此外，有Meta分析比較了18F-FDG PET/CT、201TI/99mTc-SPECT和MRI的診斷價(jià)值，SPECT的診斷靈敏度和特異度分別為85%和81%，MRI為77%和76%，而PET/CT可達(dá)90%和93%，故在早期探測(cè)殘余和復(fù)發(fā)病灶方面，18F-FDG PET/CT更具優(yōu)勢(shì)［33］。

3.2 療效預(yù)測(cè)

Yang等［38］利用局部晚期NPC患者治療前18F-FDG PET/CT顯像的異質(zhì)性數(shù)據(jù)評(píng)估患者的生存期，結(jié)果表明，腫瘤和淋巴結(jié)的異質(zhì)性指數(shù)越低，無(wú)進(jìn)展生存期越長(zhǎng)。Shi等［39］還對(duì)比了18F-FLT和18F-FDG PET/CT對(duì)NPC放化療療效的監(jiān)測(cè)價(jià)值，新輔助化療前后分別進(jìn)行兩種顯像劑顯像，治療后18F-FLT、18F-FDG PET∑SUVmax均較治療前有明顯下降，但18F-FLT與常規(guī)的18F-FDG顯像相比，并無(wú)明顯優(yōu)勢(shì)。Chen等［40］研究則發(fā)現(xiàn)，放療中18F-FDG SUVmean與局部病灶復(fù)發(fā)或引起死亡有顯著相關(guān)性。

由此可見(jiàn)，18F-FDG PET/CT有關(guān)的指標(biāo)SUVmean、SUVmax及MTV在NPC預(yù)后評(píng)估中可發(fā)揮重要作用。雖然TNM和CT都已用于評(píng)估預(yù)后，但是由于腫瘤的放射敏感性不同，單純依賴TNM和CT并不能精確反應(yīng)放療結(jié)果，而PET/ CT從分子水平反映腫瘤的功能改變，能夠更早期、更準(zhǔn)確地反映療效變化。

表3 PET/CT或PET在診斷殘余/轉(zhuǎn)移鼻咽癌的Meta分析Tab. 3 The Meta-analysis of PET/CT or PET in diagnosis of residual/metastatic nasopharyngeal carcinoma

3.3 放療計(jì)劃的制定

傳統(tǒng)的預(yù)后因子能夠提供臨床信息，卻不能預(yù)測(cè)治療療效；新型的預(yù)后因子致力于將危險(xiǎn)組進(jìn)行分層，從而根據(jù)患者的實(shí)際情況制定個(gè)體化的治療方案。其中應(yīng)用比較廣泛的危險(xiǎn)因子有SUVmax、MTV、TLG、吸煙狀態(tài)、化療與否、腫瘤大小、腫瘤部位及轉(zhuǎn)移與否等［41］。

4 PET/CT在不明原因頭頸部腫瘤中的應(yīng)用進(jìn)展

臨床上患者有時(shí)以頸部不明原因腫塊就診［42］，該類型腫瘤占所有腫瘤的0.5%～10.0%，占頭頸部腫瘤的1.0%～4.0%，但隨著影像學(xué)技術(shù)的發(fā)展，這一比例在逐漸下降，其中2.0%～5.0%為鱗狀細(xì)胞癌頸部淋巴結(jié)轉(zhuǎn)移的患者。形態(tài)學(xué)檢查(超聲、CT、MRI)對(duì)頭頸部淋巴結(jié)轉(zhuǎn)移原發(fā)病灶檢出率僅9%～23%，對(duì)模棱兩可的放射學(xué)影像結(jié)果結(jié)合內(nèi)鏡活組織檢查檢出率也僅提高到60%。

傳統(tǒng)形態(tài)學(xué)的檢查對(duì)隱蔽性高和其他類型腫瘤(如淋巴瘤、黑色素瘤)不易探測(cè)出。如今18F-FDG PET/CT作為傳統(tǒng)影像學(xué)技術(shù)的補(bǔ)充，在尋找原發(fā)灶中發(fā)揮著不可替代的作用，其檢出率為27%～68%［43-44］。

5 PET/CT的局限性

18F-FDG PET/CT是核醫(yī)學(xué)上常規(guī)使用的檢查，但是其靈敏度(35%～71%)和陽(yáng)性預(yù)測(cè)值(38%～50%)有限［45］。18F-FDG與糖酵解有關(guān)，炎性反應(yīng)、感染病灶、近期接受病理檢查或發(fā)生壞死的淋巴結(jié)，放療病灶均易出現(xiàn)假陽(yáng)性［46］。其次，PET/CT價(jià)格昂貴。

隨著衛(wèi)生保健支出的大幅上升，醫(yī)務(wù)工作者迫切需要對(duì)衛(wèi)生保健資源進(jìn)行評(píng)估來(lái)提升資源的分配。PET/CT在頭頸部腫瘤治療中的經(jīng)濟(jì)效益已獲肯定，有望充分發(fā)揮其價(jià)值用以改善患者的預(yù)后。

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The advances of clinical application of PET/CT in head and neck carcinoma

ZHENG Yingying, YANG Zhongyi (Department of Nuclear Medicine, Fudan University Shanghai Cancer Center; Center for Biomedical Imaging, Fudan University; Shanghai Engineering Research Center of Molecular Imaging Probes; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China)

YANG Zhongyi E-mail: yangzhongyi21@163.com

Head and neck carcinoma (HNC) is one of the common malignancies in the world. Because of its deep location and complicated surroundings, patients usually

efinitive radiotherapy or concurrent chemoradiotherapy. Early prediction has significant importance to guide physicians in making treatment decisions. Traditional imaging techniques have obvious limitations. However, positron emission tomography (PET), as a non-invasive functional imaging, allows quantitative assessment of many biologic processes before the anatomic changes, such as proliferation, apoptosis and hypoxia. PET/CT is more and more widely used in HNC nowadays. This article reviewed the advances of clinical application of PET/CT in HNC in this paper

10.19401/j.cnki.1007-3639.2017.06.005

R739.91

A

1007-3639(2017)06-0425-07

2017-03-20）

楊忠毅 E-mail: yangzhongyi21@163.com