2016csco肺癌診療規(guī)范解讀

1、中國臨床腫瘤學(xué)會(huì)CSCO原發(fā)性肺癌診療指南解讀,2016.V1楊衿記廣東省肺癌研究所廣東省醫(yī)學(xué)科學(xué)院&廣東省人民醫(yī)院 華南理工大學(xué)醫(yī)學(xué)院&南方醫(yī)科大學(xué),1,指導(dǎo)原則特色,基于地區(qū)發(fā)展不平衡的指南,Resource stratified guidelines,基于資源可及性的指南,?能否應(yīng)用到,基于腫瘤治療價(jià)值的指南,英國NICE modelASCO和ESMO的Value,2,指導(dǎo)原則特色,基本策略,

2、可選策略,必須做到的最低要求 —— 縣級(jí)及縣級(jí)以上醫(yī)院能做 也應(yīng)該做到的最基本要求,對(duì)不同地區(qū)不同級(jí)別醫(yī)療單位的補(bǔ)充選擇,高證據(jù)級(jí)別和可及性,高級(jí)別證據(jù)，但在可及性或價(jià)值方面有所不足,3,主要內(nèi)容,影像和分期診斷,病理學(xué)診斷,分子分型,基于病理類型、分期和分子分型的綜合治療,隨訪,4,,影像和分期診斷總體推薦,5,*肺癌高危人群指的是年齡在55-74歲之間，既往或現(xiàn)在有超過30包年的吸煙史，且無肺癌證據(jù)的人群,與胸片相比，經(jīng)低劑量螺

3、旋CT篩查的具有高危因素的人群肺癌相關(guān)死亡率降低了20%,影像和分期診斷低劑量螺旋CT篩查的獲益,National Lung Screening Trial Research Team, et al. Radiology. 2011 Jan;258(1):243-53. National Lung Screening Trial Research Team, et al. N Engl J Med. 2011 Aug 4;365(5)

4、:395-409.National Lung Screening Trial Research Team, et al. J Natl Cancer Inst. 2010 Dec 1;102(23):1771-9.,6,主要內(nèi)容,影像和分期診斷,病理學(xué)診斷,分子分型,基于病理類型、分期和分子分型的綜合治療,隨訪,7,,病理學(xué)診斷總體推薦,上述證據(jù)級(jí)別全部為2A類證據(jù),8,,病理學(xué)診斷細(xì)胞學(xué)標(biāo)本診斷原則,9,病理學(xué)診斷組織標(biāo)本診斷

5、原則,10,病理學(xué)診斷組織標(biāo)本診斷原則（續(xù)）,11,主要內(nèi)容,影像和分期診斷,病理學(xué)診斷,分子分型,基于病理類型、分期和分子分型的綜合治療,隨訪,12,分子分型總體推薦,13,,主要內(nèi)容,影像和分期診斷,病理學(xué)診斷,分子分型,基于病理類型、分期和分子分型的綜合治療,隨訪,NSCLC的治療? 小細(xì)胞肺癌的治療,14,,1.IA、IB期原發(fā)性NSCLC的治療 2. IIA、IIB期原發(fā)性NSCLC的治療 3. 可

6、手術(shù)IIIA期原發(fā)性肺癌的治療 4. 不可手術(shù)IIIA、IIIB期原發(fā)性肺癌的治療 5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療 EGFR突變/ALK陽性 6. IV期無驅(qū)動(dòng)基因、非鱗癌NSCLC的治療 7.IV期無驅(qū)動(dòng)基因、鱗癌的治療 8. IV期孤立性轉(zhuǎn)移NSCLC的治療,15,NSCLC的治療,NSCLC的治療,16,,5.IV期驅(qū)動(dòng)基因陽性N

7、SCLC的治療EGFR突變患者一線治療：總體推薦,a. 驅(qū)動(dòng)基因陽性的鱗癌參照非鱗癌，本章節(jié)主要涉及多發(fā)轉(zhuǎn)移患者，單發(fā)轉(zhuǎn)移參考本指南其他相應(yīng)章節(jié)。b. 確診EGFR突變前由于各種原因接受了化療的患者，在確診EGFR突變后除推薦參考本指南選擇EGFR-TKI外，也可在 疾病進(jìn)展或不能耐受當(dāng)前治療后參考本指南一線治療。c. 部分患者確診晚期NSCLC后因?yàn)楦鞣N原因未能明確基因類型，一線接受化療的患者進(jìn)展后活檢明確診斷為EGFR突變，

8、治療參考本指南一線治療。d. III期臨床研究均入組為PS≤2，EGFR-TKI在一線EGFR突變且PS=3分患者僅有 II期臨床研究數(shù)據(jù)，具體請(qǐng)參考下述討 論部分。e. 基于經(jīng)濟(jì)原因或患者個(gè)人意愿，可參考本指南無驅(qū)動(dòng)基因、IV期NSCLC治療部分。*一代EGFR-TKI包括厄洛替尼、吉非替尼、?？颂婺帷＜翘婺岷桶？颂婺嵋勋@一線適應(yīng)癥，厄洛替尼的一線中國注冊(cè) 研究已完成，等待審批。目前二代EGFR-TKI阿法替尼已經(jīng)被FDA批準(zhǔn)

9、用于19外顯子缺失或21L858R EGFR突變的轉(zhuǎn)移性 NSCLC患者的一線治療。,17,EGFR突變患者一線治療：一代EGFR-TKI的地位,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療,多個(gè)隨機(jī)對(duì)照研究顯示，厄洛替尼或吉非替尼對(duì)比化療可顯著改善患者的PFS，且3級(jí)及以上不良反應(yīng)顯著低于化療，奠定了厄洛替尼和吉非替尼在EGFR突變晚期NSCLC一線治療的地位,Mok TS, et al. N Engl J Med. 2009 Sep 3;

10、361(10):947-57. 2. Han JY, et al. J Clin Oncol. 2012 Apr 1;30(10):1122-8.Maemondo M, et al. N Engl J Med. 2010 Jun 24;362(25):2380-8. 4. Mitsudomi T, et al. Lancet Oncol. 2010 Feb;11(2):121-8.5. Rosell R, et al. Lancet

11、 Oncol. 2012 Mar;13(3):239-46. 6. Zhou C, et al. Lancet Oncol. 2011 Aug;12(8):735-42. 7. Wu YL, et al. Ann Oncol. 2015 Sep;26(9):1883-9.,18,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療EGFR突變患者一線治療：二代EGFR-TKI VS.化療,Sequist LV, et al1. J Clin Onc

12、ol. 2013 Sep 20;31(27):3327-34.Wu YL, et al. Lancet Oncol. 2014 Feb;15(2):213-22.,LUX Lung3[1] 、LUX Lung6[2]研究顯示二代EGFR-TKI阿法替尼相對(duì)化療均顯著提高 了PFS(分別為11.1月vs.6.9月，P=0.001和11.0vs.5.6月，P<0.0001),LUX-LUNG7研究 PFS、TTF和ORR更新,*未作

13、多重比較校正,更新的阿法替尼對(duì)比吉非替尼的ORR為73% vs 56% (OR 2.12 [95% CI 1.32–3.40], p=0.002)阿法替尼對(duì)比吉非替尼中位 (95% CI) DoR為10.1 (8.2–11.1) vs 8.3 (7.3–10.2)月,PFS (獨(dú)立第三方審查),時(shí)間 (月),,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,27.3%,16.0%,15.7

14、%,7.3%,0,3,6,9,12,18,15,21,24,27,30,33,36,39,42,45,48,51,1.0,0.8,0.6,0.4,0.2,0,,,,,,,,,,,,,,,,,,,,,,Estimated PFS probability,,,,,,,,,160,142,113,94,67,47,34,26,20,13,10,8,4,3,0,0,0,0,159,132,105,82,51,21,15,10,7,5,5,3,3

15、,3,0,0,0,0,No. at risk:,阿法替尼,吉非替尼,,,,,,,,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療EGFR突變患者一線治療：二代EGFR-TKI VS.一代,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,LUX-LUNG7總患者人群和各亞組的OS,中位隨訪時(shí)間42.6月(截至2016/04/08),,156,153,148,139,125,111,

16、104,94,81,74,61,50,36,30,12,2,0,153,148,142,133,119,105,90,80,71,62,56,48,44,27,7,0,0,No. at risk:,,Afatinib,Gefitinib,,1.0,0.8,0.6,0.4,0.2,,,,,,Estimated OS probability,時(shí)間 (月),0,3,6,9,12,18,15,21,24,27,30,33,36,39,42,45

17、,48,51,,,,,,,,,,,,,,,,,,,,0,160,159,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療EGFR突變患者一線治療：二代EGFR-TKI VS.一代,LUX-LUNG7不同EGFR突變亞型的OS,Del19,時(shí)間 (月),1.0,0.8,0.6,0.4,0.2,0,,,,,,,Estimated OS probability,,No. at risk:,0,6,12,18,24,30,36,42,48,,,,,,,

18、,,,93,88,82,68,61,50,35,20,1,93,86,79,66,52,39,29,17,0,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,阿法替尼,吉非替尼,L858R,1.0,0.8,0.6,0.4,0.2,0,,,,,,,Estimated OS probability,,No. at risk:,阿法替尼,吉非替尼,67,65,57,43,33,24

19、,15,10,1,66,62,54,39,28,23,19,10,0,0,6,12,18,24,30,36,42,48,,,,,,,,,,時(shí)間 (月),,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療EGFR突變患者一線治療：二代EGFR-TKI VS.一代,Wu YL, et al. Lancet Oncol. 2013 Jul;14(8):777-86,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療EGFR突變患者一線治療：TKI 基礎(chǔ)上聯(lián)合化

20、療,EGFR突變患者中化療聯(lián)合交替厄洛替尼治療組中位PFS和OS均顯著優(yōu)于單純化療(中位PFS：16.8月vs.6.9月，P<0.001；中位OS：31.4月vs.20.6， P=0.0092)[11] 聯(lián)合治療組的中位PFS和OS也較單藥EGFR-TKI歷史數(shù)據(jù)有提高,23,CTONG1509研究,貝伐珠單抗聯(lián)合厄洛替尼對(duì)比單藥厄洛替尼治療伴有EGFR突變的晚期非鱗NSCLC的III期隨機(jī)對(duì)照研究,5.IV期驅(qū)動(dòng)基因

21、陽性NSCLC的治療EGFR突變患者一線治療：TKI 基礎(chǔ)上聯(lián)合貝伐珠單抗,http://clinicaltrials.gov/ct2/show/NCT02759614?term=CTONG+1509&rank=1,24,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療EGFR突變患者一線治療：耐藥后治療推薦,f：臨床進(jìn)展模式評(píng)估標(biāo)準(zhǔn)參考具體如下：ü 局部進(jìn)展型：疾病控制≥3月、顱外孤立進(jìn)展或顱內(nèi)進(jìn)展、癥狀評(píng)分≤1；&#

22、252; 緩慢進(jìn)展型：疾病控制 ≥6月、與以前相比，腫瘤負(fù)荷輕微增加、癥狀評(píng)分≤1；ü 快速進(jìn)展型：疾病控制 ≥3月、與以前相比，腫瘤負(fù)荷快速增加、癥狀評(píng)分2； 臨床癥狀評(píng)分基于：5項(xiàng)與肺癌相關(guān)的臨床表現(xiàn)(咳嗽、咳血、胸痛、發(fā)熱和呼吸困難)；1項(xiàng)轉(zhuǎn)移灶相關(guān)的臨床表現(xiàn)(如骨 轉(zhuǎn)移疼痛)組成；無癥狀為0分，穩(wěn)定為1分，任一癥狀惡化或新發(fā)均為2分 d：III期臨床研究均入組為PS≤2，EGFR-TKI在一線EGFR突變

23、且PS=3分患者僅有 II期臨床研究數(shù)據(jù)，具體請(qǐng)參考下述討 論部分,25,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療突變患者耐藥后單個(gè)或少量局部進(jìn)展：局部治療+繼續(xù)TKI,多個(gè)回顧性分析顯示EGFR突變患者單個(gè)或少量局部進(jìn)展后，繼續(xù)EGFR-TKI 治療聯(lián)合局部治療可繼續(xù)延長PFS或TTP時(shí)間 [1-6],1. Weickhardt AJ, et al. J Thorac Oncol. 2012 Dec;7(12):1807-14. 2.

24、 Conforti F, et al. Lung Cancer. 2013 Sep;81(3):440-4.3. Shukuya T, et al. Lung Cancer. 2011 Dec;74(3):457-61. 4. Yu HA, et al. J Thorac Oncol. 2013 Mar;8(3):346-51.5. Hong SH, et al. Lung Cancer 2013; 80(Suppl 1):S35. 6

25、. Parra HJS, et al. J Thorac Oncol 2011; 6(6 Suppl 2):S1254.,26,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療突變患者耐藥后緩慢進(jìn)展：繼續(xù)使用TKI仍獲益,ASPIRATION：進(jìn)展后繼續(xù)厄洛替尼可延長PFS?接受進(jìn)展后厄洛替尼治療的患者(n=93)–PFS1為11.0月；PFS2較PFS1延長3.1月,RECIST PD后持續(xù)厄洛替尼治療 可將PFS延長3.1月，沒有出

26、現(xiàn)新的不良事件,Park K, et al. JAMA Oncol. 2016 Mar;2(3):305-12.,27,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療突變患者耐藥后緩慢進(jìn)展：化療基礎(chǔ)上繼續(xù)使用EGFR-TKI,對(duì)于EGFR-TKI耐藥的患者，化療目前仍為經(jīng)典治療選擇。?在化療的基礎(chǔ)上繼續(xù)使用EGFR-TKI是否能為進(jìn)一步獲益尚有爭議，IMPRESS研究[1,2] 在EGFR突變患者一線吉非替尼耐藥后的患者中對(duì)比了化療和化療

27、聯(lián)合吉非替尼的療效， 全組患者PFS并無顯著差異,Soria JC, et al. Lancet Oncol. 2015 Aug;16(8):990-8.Soria JC, et al. 2015 WCLC Oral17.08.,28,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療突變患者耐藥后治療：三代EGFR-TKI 奧希替尼,— AURA劑量擴(kuò)展研究 (N=201): ORR (by BICR) ：62%, mPFS 12.3 m，

28、mDoR 15.2 m— AURA2 (N=210): ORR (by BICR) ：70%, mPFS：9.9 m，mDoR：11.4 m,AURA3是第一個(gè)對(duì)比三代EGFR-TKI（奧希替尼）和鉑類雙藥化療治療一線EGFR-TKI耐藥后伴EGFR-T790M陽性的NSCLC 隨機(jī)III期臨床研究。,,奧希替尼是一種口服，不可逆，對(duì)中樞神經(jīng)系統(tǒng)有效，同時(shí)對(duì)EGFR敏感突變 和EGFRT790M耐藥突變高選擇性藥物1-2。前期

29、全球II期試驗(yàn)證實(shí)奧希替尼80mg QD 對(duì)EGFR-TKI 治療后耐藥伴EGFR T790M陽性NSCLC有很強(qiáng)的臨床療效和較少的不良反應(yīng)3,4,1. Cross et al. Cancer Discov2014;4:1046–61; 2. Ballard et al. ClinCancer Res 2016;22:5130–40; 3. Yang et al. AURA extension manuscript in prepara

30、tion; 4. Goss et al. Lancet Oncol2016 [ePubahead of print]AURA extension: NCT01802632; AURA2: NCT02094261; AURA3: NCT02151981BICR, Blinded Independent Central Review; CNS, central nervous system; DoR, duration of respo

31、nse; EGFR, epidermal growth factor receptor; ORR, objective response rate; NSCLC, non-small cell lung cancer; PFS, progression-free survival; QD, once daily; TKI, tyrosine kinase inhibitor,29,入組標(biāo)準(zhǔn)≥18歲（日本≥ 20歲）局部進(jìn)展或轉(zhuǎn)移性

32、NSCLC一線EGFR-TKI治療后進(jìn)展進(jìn)展后組織活檢并中心確認(rèn)T790M突變（采用cobas® EGFR突變檢測(cè)）WHO 評(píng)分0或1進(jìn)展后沒有接受其他治療一線EGFR-TKI治療前6個(gè)月內(nèi)沒有接受輔助或新輔助化療允許穩(wěn)定的無癥狀腦轉(zhuǎn)移,根據(jù)種族：亞洲、非亞洲隨機(jī)分層每6周用RECIST v1.1評(píng)估直到進(jìn)展假設(shè)統(tǒng)計(jì)學(xué)顯著性界值設(shè)α為雙側(cè)5％時(shí)HR=0.67，總計(jì)出現(xiàn)221例進(jìn)展或死亡事件時(shí)，有80％的powe

33、r拒絕兩治療組間沒有顯著性差異的假設(shè),R2:1,奧希替尼（n=279)80mg po.QD,鉑類-培美曲塞（n=140）培美曲塞 500mg/m2+ 卡鉑 AUC 5或 順鉑 75mg/m2 q3w 最多6個(gè)周期可選培美曲塞維持治療,主要終點(diǎn)：PFS （研究者評(píng)估RECISTv 1.1)次要終點(diǎn)OSORRDORDCR腫瘤縮小獨(dú)立評(píng)估委員會(huì)（BICR）評(píng)估 PFS安全和毒性,選擇交叉補(bǔ)充：允許化療組在BIC

34、R確診進(jìn)展后揭盲到奧希替尼組接受治療,AURA3研究,,*Defined as not requiring corticosteroids for 4 weeks prior to study treatment; #For patients whose disease had not progressed after 4 cycles of platinum-pemetrexedHR, hazard ratio; Q3W, ever

35、y 3 weeks; R, randomisation; RECIST, Response Evaluation Criteria In Solid Tumors; WHO, World Health Organization,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療突變患者耐藥后治療：三代EGFR-TKI 奧希替尼,奧希替尼鉑類-培美曲塞,BICR的評(píng)估和研究者評(píng)估一致： HR 0.28 (95% CI 0.20, 0.38), p

36、<0.001; median PFS 11.0 vs 4.2 months.,Population: intent-to-treatProgression-free survival defined as time from randomisation until date of objective disease progression or death; calculated using the Kaplan-Meier a

37、pproach. Progression included deaths in the absence of RECIST progression.Tick marks indicate censored data; CI, confidence interval,AURA3 主要終點(diǎn):PFS （研究者評(píng)估）,1.0,0.8,0.6,0.4,0.2,0,0,3,6,9,12,15,18,Probability ofprogressi

38、on-free survival,No. at risk奧希替尼鉑類-培美曲塞,Months,,,,,,,,,,,,,,,,279140,24093,16244,8817,507,131,00,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療突變患者耐藥后治療：三代EGFR-TKI 奧希替尼,31,AURA3：治療緩解持續(xù)時(shí)間,,Population: intent-to-treatDoR defined as time f

39、rom date of first documented response until date of documented disease progression or last evaluable RECIST assessment for patients that did not progress.*Analysis performed using logistic regression adjusted for ethnic

40、ity (Asian/non-Asian). An odds ratio >1 favours osimertinib 80 mg. The p-value was calculated based on the likelihood ratio test which compared two models (one model with ethnicity covariate only and the other model w

41、ith both treatment factor and ethnicity covariate). #Calculated using Kaplan-Meier approach.,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療突變患者耐藥后治療：三代EGFR-TKI 奧希替尼,,SubgroupOverall (n=419)Cox proportional hazardsLog rank (primary)Ethnicity

42、 Asian (n=274) Non-Asian (n=145)SexMale (n=150)Female (n=269)Age at screening<65 (n=242)≥65 (n=177)EGFR-TKI sensitising mutation status prior to start of study Exon 19 deletion (n=279) L858R (n=128

43、)Duration of prior EGFR-TKI<6 months (n=24)≥6 months (n=395)CNS metastasesYes (n=144)No (n=275)Smoking historyEver (n=136)Never (n=283),各亞組的PFS奧希替尼更獲益,Population: intent-to-treatHR <1 implies a lowe

44、r risk of progression on osimertinib 80 mg. Cox proportional hazards model includes randomised treatment, the subgroup covariate of interest, and the treatment by subgroup interaction. Size of circle is proportional to t

45、he number of events. Overall population analysis was performed using a Cox proportional hazards model and the primary analysis (U and V statistics) from stratified log-rank test. If there were <20 events in a subgroup

46、 then the analysis was not performed; NC, non-calculable,Hazard ratio (95% CI)0.37 (0.29, 0.48)0.30 (0.23, 0.41)0.32 (0.24, 0.44)0.48 (0.32, 0.75)0.43 (0.28, 0.65)0.34 (0.25, 0.47)0.38 (0.28, 0.54)0.34 (0.23,

47、 0.50)0.34 (0.24, 0.46)0.46 (0.30, 0.71)NC0.39 (0.30, 0.51)0.32 (0.21, 0.49)0.40 (0.29, 0.55)0.40 (0.27, 0.62)0.36 (0.26, 0.49),,,,,,,,,,,,,,,0.1,0.2,0.3,0.4,0.5,0.7,0.9,1.0,,,0.6,0.8,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療突變患

48、者耐藥后治療：三代EGFR-TKI 奧希替尼,33,基線伴/不伴腦轉(zhuǎn)移患者的PFS獲益,Population: intent-to-treatProgression-free survival defined as time from randomisation until date of objective disease progression or death. Progression included deaths in th

49、e absence of RECIST progression.Tick marks indicate censored data. CNS metastases determined programmatically from baseline data of CNS lesion site, medical history, and/or surgery, and/or radiotherapy.,5.IV期驅(qū)動(dòng)基因陽性NSCLC

50、的治療突變患者耐藥后治療：三代EGFR-TKI 奧希替尼,34,AURA3：安全性,Population: safety analysis set (all patients who received at least one dose of study drug and for whom post-dose data were available)*Patients with multiple events in the same

51、 category counted only once in that category. Patients with events in more than one category counted once in each of those categories; #As assessed by the investigator. Includes AEs with an onset date on or after the dat

52、e of first dose and up to and including 28 days following the date of last dose of study medication; AE, adverse event,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療突變患者耐藥后治療：三代EGFR-TKI 奧希替尼,35,5.IV期驅(qū)動(dòng)基因陽性NSCLC的治療 EGFR突變患者：三線治療推薦,d：III期臨床研究均入組為

53、PS≤2，EGFR-TKI在一線EGFR突變且PS=3分患者僅有 II期臨床研究數(shù)據(jù),36,8. IV期孤立性轉(zhuǎn)移NSCLC的治療孤立腦或腎上腺轉(zhuǎn)移：總體推薦,TNM分期參照UICC第七版SRS(Stereotactic Radiosurgery)：立體定向放射外科 WBRT(Whole Brain Radiotherapy)：全腦放射治療 SBRT(StereotacticBody Radiation Therapy)：體部立體定

54、向放療,主要內(nèi)容,影像和分期診斷,病理學(xué)診斷,分子分型,基于病理類型、分期和分子分型的綜合治療,隨訪,37,38,,隨訪：IV期NSCLC全身治療結(jié)束后隨訪推薦,注：I-IIIA期 NSCLC 局部治療后隨訪，常規(guī)不進(jìn)行頭顱CT或MRI、骨掃描或全身PET/CT檢查，僅當(dāng)患者出現(xiàn)相應(yīng)部位癥狀時(shí)才進(jìn)行；IIIB-IV期 NSCLC不建議患者采用PET/CT檢查作為常規(guī)復(fù)查手段。,總結(jié),影像和分期診斷,病理學(xué)診斷,分子分型,基于病理類型