臺北榮總肺癌診療共識V009

1、taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊v.1.0 2009臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊revised on 2009/04/13released on 2009/05/04taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊multidisciplinary teamtaipei vgh lung cancer panel memberstnm sta

2、ging taipei vgh supplement to tnm staging table of stage groupingevaluation and treatment stage o (tis) stage i (t1-2,n0) and stage ii (t1-2, n1) stage iib (t3,n0) and stage iiia (t3,n1) stage iiia (t1-3,n3) and stage iiib (t4, n0-1) stage iiib (t1-3,n3) stage iiib (t4,n2-3) (t4: pleural effusion or

3、 pericardial effusion) stage iv (m1: solitary site or disseminated)surveillancetherapy for recurrence and metastasesoccult (tx,n0,m0),evaluation and treatmentsecond lung primary, evaluation, and treatmentprinciples of surgical resectionprinciples of pathologyprinciples of radiation therapy - recomme

4、nded radiation doses - dose volume data for radiation pneumonitisprinciples of ccrtprinciples of chemotherapy - non-small cell lung cancer - small cell lung canceradjuvant chemotherapyneoadjuvant chemotherapyclinical trials for advanced/ metastatic nsclctracheal cancer references關(guān)於此臨床指引：關(guān)於此臨床指引：肺癌的診

5、療仍在發(fā)展階肺癌的診療仍在發(fā)展階段，本指引主要在呈現(xiàn)目前肺癌診療的進(jìn)段，本指引主要在呈現(xiàn)目前肺癌診療的進(jìn)展與共識，展與共識，醫(yī)師應(yīng)鼓勵病患參與臨床試驗醫(yī)師應(yīng)鼓勵病患參與臨床試驗 ，使其有機(jī)會得到最好的治療。在本指引，使其有機(jī)會得到最好的治療。在本指引中的化療用藥建議是基於現(xiàn)有的臨床證據(jù)，中的化療用藥建議是基於現(xiàn)有的臨床證據(jù)，和目前的衛(wèi)生署或健保局規(guī)定無關(guān)。和目前的衛(wèi)生署或健保局規(guī)定無關(guān)。taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊癌委會癌委會胸內(nèi)胸內(nèi)核心成員核心成員召集人：

6、蔡俊明、許文虎召集人：蔡俊明、許文虎副召集人：賴信良、吳玉琮副召集人：賴信良、吳玉琮肺癌委員會暨肺癌多專科團(tuán)隊肺癌委員會暨肺癌多?？茍F(tuán)隊非核心成員非核心成員胸外胸外放射放射病理病理骨科骨科核醫(yī)核醫(yī)社工社工營養(yǎng)營養(yǎng)放療放療藥劑部藥劑部個案管理師個案管理師：宋易珍宋易珍taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊胸腔胸腔內(nèi)科內(nèi)科陳育民陳育民賴信良賴信良李毓芹李毓芹蔡俊明蔡俊明胸外胸外吳玉琮吳玉琮許文虎許文虎放射放射吳美翰吳美翰許明輝許明輝病理病理林可瀚林可瀚周德盈周德盈放療放療

7、陳一瑋陳一瑋顏上惠顏上惠邱昭華邱昭華陳俊谷陳俊谷核醫(yī)核醫(yī)王世楨王世楨 taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nsclc tnm staginglababede, o. et al. chest 1999;115:233-235taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊clifton f. mountain, chest1997- extended

8、 mediastinoscopy- mediastinotomy- vats- eus-fna- vats- ebus-tbna- vats (limited to 10 and 11)- mediastinoscopy- eus-fna- ebus-tbna-vats- mediastinoscopy; eus-fna, ebus-tbnan1=ipisilateral hilar nodesn2=subcarinal, ipisilateral mediastinal nodesn3=contralateral hilar/ mediastinal, or supraclavicular

9、or scalene nodes how to approach eus: endoscopic ultrasound; ebus: endobronchoscopic ultrasound; fna: fine needle aspiration; tbna: transbronchoscopic needle aspiration; vats: video assisted thoracoscopic surgerytaipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊pft:

10、necessary for all operable stagespet (pet/ct) : recommend for all clinical stages, except wet iiib or stage iv with disseminate m1mediastinoscopy: recommend for all clinical stages, except peripheral t1n0 wet iiib or stage iv with disseminate m1p.s. n2 or n3 disease can be confirmed by other methods

11、 including mediastinotomy, thoracoscopy, ebus-fna, eus-fna, ct-guided-fna, supraclavicle ln biopsy brain mri: recommend for all clinical stages, except stage i wet iiib or stage iv with disseminate m1taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊 正子掃描（pet/ct scan

12、）：肺癌clinical stage 的pre-treament workup，至於安排時間點(diǎn)是在胸腔電腦斷層（chest-ct）後。 除非chest ct或pet scan都無縱膈腔異常發(fā)現(xiàn)且主要病灶在週邊(peripheral ia lesion)可以不做縱膈腔鏡外，否則縱膈腔鏡仍是評估縱膈腔淋巴結(jié)的gold standard brain mri取代brain ct建議在clinical stage ii及stage iii以上的病人安排。 術(shù)中病理檢查若有r1 (microscopic residual tumor) 或r2(macroscopic residual tumor)，應(yīng)視實(shí)

13、際情形考慮reresection /（+chemotherapy）或是chemoradiation /（+ chemotherapy）。 taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nscl-1from nccn guideline, v.2.2009taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nscl-2from nccn guideline, v.2

14、.2009taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nscl-3from nccn guideline, v.2.2009taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nscl-4from nccn guideline, v.2.2009taipei vgh practice guidelines:oncology guidelines indexlun

15、g cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nscl-5from nccn guideline, v.2.2009taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nscl-6from nccn guideline, v.2.2009taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nscl-7from nccn guideline, v.2.2009taipe

16、i vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nscl-8from nccn guideline, v.2.2009taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nscl-9from nccn guideline, v.2.2009taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北

17、榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nscl-10from nccn guideline, v.2.2009taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nscl-11from nccn guideline, v.2.2009taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nscl-12from nccn guideline, v.2.2009taipei vgh p

18、ractice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nscl-13gefitinib or erlotinib(if criteria met)z (2b)gefitinib or erlotinib(if criteria met)z (2b)(2b)(2b)z criteria for treatment with gefitinib (ipass trial): adenocarcinoma, non-smoker or light ex-smoker (quit 15yrs and 10 pack

19、-years or fewer) no pre-existing idiopathic pulmonary fibrosisby evidence on chest ct from nccn guideline, v.2.2009taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nscl-14from nccn guideline, v.2.2009taipei vgh practice guidelines:oncology guidelines indexlung cance

20、r臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊nscl-15orgefitiniborgefitinibgefitinib and erlotinib in 2nd-line therapy : adenocarcinomagefitnib in 3rd-line therapy: adenocarcinoma; erlotinib in 3rd-line therapy: nsclcfrom nccn guideline, v.2.2009taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊

21、principles of surgical resection非緊急狀況下，術(shù)前所需影像學(xué)檢查應(yīng)完備。是否可切除(resectablility)之決定建議應(yīng)由有經(jīng)驗之胸腔外科醫(yī)師來決定。如生理狀況許可(physiologically feasible) ，應(yīng)採取lobectomy或pneumonectomy。如生理狀況受限制(physiologically compromised) ，應(yīng)採局部切除(limited resection-segmentectomy or wedge resection) 。在不違背標(biāo)準(zhǔn)腫瘤手術(shù)原則下，可採用vats (video- assisted thorac

22、ic surgery) 。taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊principles of surgical resectionn1&n2 node resection and mapping (minimum of three n2 stations sampled or complete lymph node dissection)如內(nèi)科狀況無法開刀(medically inoperable) ，clinical stage i& ii病人應(yīng)接受p

23、otential curative radiotherapy。假如解剖位置適當(dāng)與邊緣可切除乾淨(jìng)(anatomically appropriate and margin-negative resection) ，採取肺葉保存術(shù)式比全肺切除好( lung sparing anatomic resection-sleeve lobectomy preferred over pneumonectomy) 。taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊principles of pa

24、thological review病理評估的目的包括: classify the lung cancer; determine the extent of invasion; establish the status of cancer involvement of surgical margins; determine the molecular abnormalities to predict for response to egfr- tki 。手術(shù)病理報告應(yīng)該有who肺癌組織分類。pure bronchioloalveolar carcinoma (bac)應(yīng)無stroma、pleur

25、a與lymphatic spaces之侵犯。免疫染色: non-mucinous bac = ttf-1 (+) / ck7 (+) / ck20 (-); mucinous bac = ttf-1 (-) / ck7 (+) / ck20 (+) 。免疫染色可幫助鑑別原發(fā)或轉(zhuǎn)移肺腺癌，區(qū)別腺癌及惡性間皮細(xì)胞癌，決定腫瘤之神經(jīng)內(nèi)分泌分化。egfr: epidermal growth factor receptortki: tyrosine kinase inhibitorttf-1: thyroid transcription factor-1taipei vgh practice guide

26、lines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊principles of pathological reviewttf-1對區(qū)分原發(fā)或轉(zhuǎn)移肺腺癌很重要。大部分原發(fā)肺腺癌ttf-1為陽性，轉(zhuǎn)移腺癌(甲狀腺癌除外)為陰性反應(yīng)。primary lung adenocarcinoma: ttf-1(+) / ck7(+) / ck20(-) / cdx-2 (-) metastatic colorectal carcinoma: ttf-1(-) / ck7(-) / ck20(+) / cdx-2 (+)egfr mutation

27、之有無與tki治療之反應(yīng)相關(guān)；如tki 對exon19 deletion之腫瘤治療效果良好。k-ras與吸煙相關(guān)；k-ras與egfr mutation為mutually exclusive；有k-ras mutation對tki治療效果不佳。 小細(xì)胞癌多數(shù)(95%)原發(fā)自肺，少數(shù)則來自肺外器官，二者有類似之臨床和生物特性，極易廣泛轉(zhuǎn)移。小細(xì)胞癌細(xì)胞通常keratin 及至少一種之neuroendocrine differentiation markers (cd56, synaptophysin或 chromogranin a)呈陽性免疫染色。taipei vgh practice guid

28、elines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊3d conformal techniquetaipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊 按2009年nccn guideline的精神，其所建議的放射治療已非傳統(tǒng)二次元定位的方式，而是因應(yīng)放射治療技術(shù)的進(jìn)步，以電腦斷層評估腫瘤的位置、體積和淋巴結(jié)引流的三次元定位方式，來決定照射的角度、劑量和範(fàn)圍。 美國nccn所建議的放射照射劑量並不完全適用於國人，本共識

29、以依國內(nèi)病人狀況要做適度的調(diào)整 。taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊treatment plantotal dosefraction sizepreoperative45-50 gy1.8 - 2 gypostoperative1.negative margin2.extracapsular nodal extension or microscopic positive margin3. gross residual tumor50 gy 54-60 gy 60-

30、66 gy up to 70 gy1.8 - 2 gy1.8 - 2 gy1.8 - 2 gy1.8 - 2 gydefinitive1.without concurrent chemotherapy2. with concurrent chemotherapy (mainly paclitaxel + carboplatin)up to 70 gy for volume 25% up to 60-66 gy for volume between 25-36% up to 60-66 gy1.8 - 2 gy1.8 - 2 gy1.8 - 2 gypalliative (for primary

31、 lung lesion; svc syndrome, obstructive pneumonitis, etc.)30-50gy2-2.5 gytaipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊rt +/- induction chemotherapyconcurrent chemotherapyparameterrange pneumonitis(%)range pneumonitis(%) mld 300-109-1624-2724-44 42338 lp(20) 20 (

32、%)20-31 320-2 (%)7-1513-48319185185 lp(30) 8 (%) 86 (%)24mld-mean lung dose, lp: percentage of lung that received radiation (gy)taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊同步化學(xué)併放射治療同步化學(xué)併放射治療(ccrt)原則原則 nsclc dose: up to 60-66gy/1.8-2gy/day limited sclc1.年齡小於等於年齡

33、小於等於70歲，歲，ps：01，接受，接受ccrt dose：5060 gy/1.8gy/day 排程：放療自開始持續(xù)做至排程：放療自開始持續(xù)做至5060 gy，而化學(xué)治療自開始先做三個療程後休，而化學(xué)治療自開始先做三個療程後休 息，須重新評估病患治療反應(yīng)，之後再依實(shí)際情形安排接續(xù)的治療。息，須重新評估病患治療反應(yīng)，之後再依實(shí)際情形安排接續(xù)的治療。 如有如有cr 加做預(yù)防性全腦放射治療加做預(yù)防性全腦放射治療 (prophylactic cranial irradiation, pci) dose： 30gy/ 2gy/ day x15 fractions(一天一次共十五次）一天一次共十五次）

34、如有如有pr 持續(xù)化學(xué)治療，但不做持續(xù)化學(xué)治療，但不做pci2.年齡大於年齡大於70歲，歲，ps：01，採用接續(xù)性化放療，採用接續(xù)性化放療(sequential chemoradiotherapy) dose：5060 gy/1.8gy/day 排程：連續(xù)的三個療程的化學(xué)治療後休息，在二週內(nèi)重新評估排程：連續(xù)的三個療程的化學(xué)治療後休息，在二週內(nèi)重新評估 如有如有cr 加做加做pci, dose： 30gy/ 2gy/ day x15 fractions(一天一次共十五次）一天一次共十五次） 如有如有pr 加做胸腔的放療及三個療程的化學(xué)治療，但不做加做胸腔的放療及三個療程的化學(xué)治療，但不做pci

35、3.如有如有pd 接受第二線化療。接受第二線化療。taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊肺癌化學(xué)治療用藥準(zhǔn)則肺癌化學(xué)治療用藥準(zhǔn)則 非小細(xì)胞肺癌非小細(xì)胞肺癌 第一線第一線 - gemcitabine (gc-g) g (1000-1250mg/m2) + cisplatin (60-75mg/m2), q3-4w. - vinorelbine (nc-n) vinorelbine (25-30 mg/m2 i.v. or 60-80 mg/m2 p.o.) + cisp

36、latin (60-75 mg/m2), q3-4w. - paclitaxel (tac or tac-ta-ta) 1. paclitaxel (160-175 mg/m2)-d1 + cisplatin (60- 75 mg/m2)-d1, q3w. 2. paclitaxel (60-80 mg/m2) -d1,8,15 + cisplatin (60-75 mg/m2) -d1, q4w. - docetaxel (tc or tc-t) 1. docetaxel (60-75 mg/m2)-d1 + cisplatin (60-75 mg/m2)-d1, q3w. 2. docet

37、axel (30-35 mg/m2)-d1,8 + cisplatin (60-75 mg/m2)- d1,q3w. 備註備註: 1. elderly or poor performance status：cisplatin omited 2. cisplatin 若改成 carboplatin, 劑量為 (ccr+25) x auc, auc = 4-6 3. bevacizumab 7.5 mg/kg 可與 gemcitabine/cisplatin或 paclitaxel/carboplatin可並用於第一線化學(xué)治療 (2b) 4. gefitinib可用於第一線治療, if adeno

38、carcinoma, non-smoker or light ex-smoker (quit 15yrs and 10 pack-years or fewer) and no pre-existing idiopathic pulmonary fibrosisby evidence on chest ct (2b) 5. pemetrexate/cisplatin可用於第一線化學(xué)治療 in non-squamous (2b) 第二線第二線 - docetaxel 1. docetaxel (60 - 75mg/m2)-d1, q3w. 2. docetaxel (30 - 35mg/m2)-d

39、1,8, q3w. - pemetrexed (500mg/m2)-d1,q3w. - gefitinib 250 mg, qd. (if adeno) - erlotinib 150 mg, qd. (if adeno) 第三線第三線 - gefitinib 250 mg, qd. (if adeno) - erlotinib 150 mg, qd (if nsclc)* 病患若參加本院病患若參加本院 irb 同意之同意之臨床試驗臨床試驗，則依該臨床試驗之則依該臨床試驗之治療計畫進(jìn)行治療計畫進(jìn)行taipei vgh practice guidelines:oncology guideline

40、s indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊肺癌化學(xué)治療用藥準(zhǔn)則肺癌化學(xué)治療用藥準(zhǔn)則 小細(xì)胞肺癌小細(xì)胞肺癌 （ 臨床試驗病例除外臨床試驗病例除外 ） standard regimens (pvp): 1. cisplatin (60-75 mg/m2) + vp-16 (60-80 mg/m2) d1,2,3/ q3w 2. carboplatin (auc=5)d1 + vp-16 (60-80 mg/m2) d1,2,3/ q3w relapsed regimens: 1. ifosfamide 1000 mg/m2 d1-3 + oral vp16 50 mg d

41、1-10/ q3w 2. topotecan 1.5 mg/m2 d1-3 + epirubicin 30 mg/m2 d1/ q3w taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊chemotherapy regimens for adjuvant therapy-cisplatin basepublished chemotherapy regimensschedulesnc-nvinorelbine (25-30 mg/m2 i.v. or 60-80 mg/m2 p.o

42、.)-d1,8 + cisplatin (60-75 mg/m2)-d1q3w for 4 cyclesother acceptable chemotherapy regimensschedulesgc-gg (1000-1250mg/m2)-d1,8 + cisplatin (60-75mg/m2)-d1q3w for 4 cyclestcdocetaxel (60-75 mg/m2)-d1 + cisplatin (60-75 mg/m2)-d1q3w for 4 cyclestac*paclitaxel (160-175 mg/m2)-d1 + cisplatin (60- 75 mg/

43、m2)-d1q3w for 4 cycleschemotherapy regimens for adjuvant therapy- alternativecisplatin 若改成若改成 carboplatin, 劑量為劑量為 (ccr+25) x auc, auc = 4-6*palitaxel+carboplatin regimen showed no survival benefit in stage ib patientstaipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊

44、stagingproposed tnm classification and staging for primary tracheal carcinoma*primary tracheal cancer*ref: paolo macchiarini, lancet oncol 2006; 7: 8391taipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊h&pcbc, plateletchemistry profilesmoking cessation counseling

45、pftchest ct scanbronchoscopy brain mristage i-iii, ivastage ivbmetastatic cancer multidisciplinary evaluation is encouragedpet/ct scanconsider 3d-ct reconstruction (multi-planar reconstruction, volume rendering technique, minimal intensity projector)medical fit for surgery, resectablemedical unfit f

46、or surgery, or unresectable, or surgery not elected and patient medically able to tolerate chemotherapy medical unfit for surgery and patient unable to tolerate chemotherapy see primary treatment (trach-1 ) see primary treatment (trach-2 ) see primary treatment (trach-2 ) see primary treatment (trac

47、h-3) workupclinical stageadditional evaluation (as clinically indicated)primary tracheal canceraa medically able to tolerate major thoracic surgery b unresctable tumor: greater than 50% of tracheal length involved by tumor, “frozen”mediastinum, poor general condition of patient, distant metastases i

48、n squamous cell carcinoma; oncologist 1997;2;245-253btaipei vgh practice guidelines:oncology guidelines indexlung cancer臺北榮總肺癌團(tuán)隊臺北榮總肺癌團(tuán)隊primary tracheal cancermedically fit for surgery, resectableprimary treatmentsurgeryadjunctive/adjuvant treatmentradiation complete resection (r0): 50gy over tumor bed and adjacent mediastinum incomplete resection with residual margin r1: r2: 60gy over tumor bed and 50gy over adjacent mediastinumaa medically able to tolerate major thoracic surgery c r0=no cancer at resection margins, r1=microscopic resid