《甲状腺髓样癌的分子分型及治疗精选PPT.ppt》由会员分享，可在线阅读，更多相关《甲状腺髓样癌的分子分型及治疗精选PPT.ppt（37页珍藏版）》请在taowenge.com淘文阁网|工程机械CAD图纸|机械工程制图|CAD装配图下载|SolidWorks_CaTia_CAD_UG_PROE_设计图分享下载上搜索。
1、关于甲状腺髓样癌的分子分型及治疗第1页，讲稿共37张，创作于星期二概况概况oHistologic subtypes of thyroid cancer Papillary:approximately 80%of all thyroid malignancies;Follicular and Hrthle:approximately 11%;Medullary:less than 5%-8%;Anaplastic:less than 2%.第2页，讲稿共37张，创作于星期二Introduction oMedullary thyroid cancer(MTC)Sporadic MTC:approx
2、imately 75%;50%somatic RET mutations(p.M918T)-predict a poor prognosis Hereditary MTC:approximately 25%;98%Germline RET mutations,MEN 2A(95%)and MEN 2B(5%)Arises from the neural crest-derived,calcitonin-secreting,parafollicular C cells of the thyroid gland 第3页，讲稿共37张，创作于星期二Introduction Sporadic MTC:
3、a solitary and unilateral or a palpable cervical lymph node Hereditary MTC:multicentric and bilateral the upper to middle parts of the thyroid lobes 第4页，讲稿共37张，创作于星期二Introduction oInvolvement of cervical lymph nodes is an early and common manifestation in the clinical course of the disease,with 35%t
4、o 50%or more,another 10%to 15%may have distant metastases at the time of initial presentation;oDistant metastatic spread of MTC frequently involves the mediastinal nodes,lung,liver(90%),and bones.第5页，讲稿共37张，创作于星期二p.C611YMEN2A第6页，讲稿共37张，创作于星期二Molecular Aberrations(overexpression)RET mutations VEGFR-2
5、 MET EGFR FGFR RAS (sMTC-56%KRAS+;12%HRAS)(Mutations in RAS appear to be mutually exclusive of RET abnormalities)Somatic RET mutations第7页，讲稿共37张，创作于星期二Molecular pathways PI3K/Akt/mTOR MAPK JNK RAS/ERKPlay critical roles in regulating cell proliferation,differentiation,motility,apoptosis,and survival
6、 第8页，讲稿共37张，创作于星期二Diagnosis and Monitoring FNA,US and CT,MRI or ECT(Ct 500 pg/mL);DNA analysis for the RET germline mutation ATA-2015,ETA-2013,NCCN-2017 Guidelines recommend The MTC specimen is positively stained for Ct,chromogranin A,and CEA or Congo Red.第9页，讲稿共37张，创作于星期二Diagnosis and Monitoring Se
7、rum-based biomarkers:calcitonin and CEA(50%)Preoperative:CEA(),Ct(-)-poorly differentiated tumors,Rare;Ct 100 pg/mL-predictive MTC;Ct 150 pg/mL,CEA 30 ng/L-regional spread;Ct 3000 pg/mL,CEA 100 ng/L-distant spread.Predictors of MTC progress,including recurrence and survival 第10页，讲稿共37张，创作于星期二Diagnos
8、is and MonitoringSerum-based biomarkers:calcitonin and CEAPostoperative:Ct()-the first sign of tumor recurrence;Ct(-)and sCt(-)-10-year survival rates(SR)of 100%;yearly Ct measurements;Ct doubling times(DT)1 yr(2yr)-5-and 10-yr SR of 98%and 95%;CEA DT 1 yr-5-and 10-yr SR of 100%；Ct DT 1 yr(6mon)-5-a
9、nd 10-yr SR of 36%and 18%（25%and 8%）;CEA 1 cm)(TT+Bi+UniLND)TT with bilateral lateral compartment neck dissection.(Bilateral tumors or extensive LN+on the contralateral side)(TT+Bi+BiLND)第19页，讲稿共37张，创作于星期二第20页，讲稿共37张，创作于星期二Surgical Management of MTC*Current recommendations for the timing of prophyla
10、ctic thyroidectomy depends on the risk level of the RET mutation in hereditary MTC(MEN 2).第21页，讲稿共37张，创作于星期二ATA-2015 Guidelines recommended第22页，讲稿共37张，创作于星期二第23页，讲稿共37张，创作于星期二Surgical Management of MTC ATA-D(HST)-MEN 2B 1yr,TT+Bi LND;ATA-AC(MODH)-MEN 2A basal Ct 40 pg/mL,TT without Bi LND is adequat
11、e.(Ct 60 ng/L,Elisei R,et al;Ct 70 ng/L,Qi XP,et al)第24页，讲稿共37张，创作于星期二Female,5.5yr;p.C634Y;bilateral MTC;DFS 6yr第25页，讲稿共37张，创作于星期二Residual and Recurrent Disease Residual and Recurrent:approximately 50%-80%,postoperationCt 150 pg/ml,higher probability of distant metastatic disease;US,CT/MRI;第26页，讲稿共3
12、7张，创作于星期二Residual and Recurrent DiseaseCytoreductive(Salvage)surgery Reduced Ct levels in many patients;Normalization of the Ct levels in up to about 1/3 of patients;The risk of surgical complications 第27页，讲稿共37张，创作于星期二Medical Management of Advanced Metastatic Disease Cytotoxic chemotherapy in limit
13、ed patients with rapidly progressive disease minimal benefit Radionuclide therapy I-131 responses only about 30%to 35%,Somatostatin analogs octreotide 第28页，讲稿共37张，创作于星期二Medical Management of Advanced Metastatic DiseaseTargeted therapy第29页，讲稿共37张，创作于星期二Tyrosine kinase receptors and downstream effecto
14、rs 第30页，讲稿共37张，创作于星期二Medical Management of Advanced Metastatic DiseaseTargeted therapy Tyrosine kinase inhibitors(TKIs)-RET,EGFR,VEGFR,and FGFR,MET Two small-molecule TKIs,vandetanib(Apr 2011)and cabozantinib(Nov 2012),are currently available as approved agents for the treatment of advanced or progr
15、essive MTC and provide significant increases in progression-free survival(PFS).第31页，讲稿共37张，创作于星期二Medical Management of Advanced Metastatic DiseaseVandetanib-RET,EGFR,VEGFR and EGFRtwo phase 2(hereditary only)dose daily 300 mg 100 mgPR 20%16%stable disease 53%53%median PFS 27.9 months 24 weeksphase 3
16、 in 331 patients(H-S-MTC)300mg/d;objective response rate(ORR)45%;median PFS 30.5 months.QT prolongation(14%),diarrhea(56%),rash(45%),hypertension(32%),headache(26%).第32页，讲稿共37张，创作于星期二Medical Management of Advanced Metastatic DiseaseCabozantinib-RET,VEGFR and c-MET less suitable for elderly patients
17、for whom the prevalence of cardiovascular risk factors The estimated median PFS with vandetanib is numerically longer than with cabozantinib Choice:The patients comorbid conditions and the toxicity profile that the patient is willing to bear 第33页，讲稿共37张，创作于星期二Medical Management of Advanced Metastati
18、c Diseaseother small-molecule kinase inhibitors sunitinib,sorafenib,and pazopanib Other targeted treatments mammalian target of rapamycin(mTOR)inhibitor-everolimus 第34页，讲稿共37张，创作于星期二Prevention-PD/PGDPreimplantation genetic diagnosis of multiple endocrine neoplasia type 2A using informative markers identified by targeted sequencingJ,Thyroid,2017.(UR)第35页，讲稿共37张，创作于星期二Acknowledgement 第36页，讲稿共37张，创作于星期二感感谢谢大大家家观观看看第37页，讲稿共37张，创作于星期二