1、Paper1.第一作者论文第一作者论文Zhu Y,Zhao T,Itasaka S,Zeng L,Yeom CJ,Hirota K,Suzuki K,Morinibu A,Shinomiya K,Ou G,Yoshimura M,Hiraoka M,Harada H*,Involvement of decreased hypoxia-inducible factor 1 activity and resultant G(1)-S cell cycle transition in radioresistance of perinecrotic tumor cells,Oncogene.2013;
2、32(16):2058-25682.通讯作者通讯作者论文论文Wang Y,Zhu YD,Gui Q,Wang XD,Zhu YX.Glucagon-induced angiogenesis and tumor growth through the HIF-1-VEGF-dependent pathway in hyperglycemic nude mice.Genet Mol Res.2014;13(3):7173-7183.Paper3.参与论文参与论文(1)Zhao T,Zhu Y,Morinibu A,Kobayashi M,Shinomiya K,Itasaka S,Yoshimura
3、 M,Guo G,Hiraoka M,Harada H*.HIF-1-mediated metabolic reprogramming reduces ROS levels and facilitates the metastatic colonization of cancers in lungs.Sci Rep.2014;4:3793.doi:10.1038/srep03793.(2)Zeng L,Morinibu A,Kobayashi M,Zhu Y,Wang X,Goto Y,Yeom CJ,Zhao T,Hirota K,Shinomiya K,Itasaka S,Yoshimur
4、a M,Guo G,Hammond EM,Hiraoka M,Harada H.Aberrant IDH3 expression promotes malignant tumor growth by inducing HIF-1-mediated metabolic reprogramming and angiogenesis.Oncogene.2015;34(36):4758-4766.(3)Goto Y,Zeng L,Yeom CJ,Zhu Y,Morinibu A,Shinomiya K,Kobayashi M,Hirota K,Itasaka S,Yoshimura M,Tanimot
5、o K,Torii M,Sowa T,Menju T,Sonobe M,Kakeya H,Toi M,Date H,Hammond EM,Hiraoka M,Harada H.UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1.Nat Commun.2015;6:6153.doi:10.1038/ncomms7153Paper3.参与论文参与论文(4)Harada H,Inoue M,Itasaka S,Hirota K,Morinibu A,Sh
6、inomiya K,Zeng L,Ou G,Zhu Y,Yoshimura M,McKenna WG,Muschel RJ,Hiraoka M,Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards tumour blood vessels,Nat Commun,3:783.doi:10.1038/ncomms1786,2012(5)Harada H,Itasaka S,Zhu Y,Zeng L,Xie X,Morinibu A,Shinomiya K,Hiraoka
7、M,Treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the effect of radiation therapy,Br J Cancer,100(5):747-757,2009(6)Zhao T,Harada H,Teramura Y,Tanaka S,Itasaka S,Morinibu A,Shinomiya K,Zhu Y,Hanaoka H,Iwata H,Saji H,Hiraoka M,A novel strategy to tag matrix metalloprotein
8、ases-positive cells for in vivo imaging of invasive and metastatic activity of tumor cells,J Control Release,144(1):109-114,2010ConferenceHiroshima：Tumor and hypoxiaNagoya：Annual oncologicmeetingForeign friends Introduction Principle of treatment of L Ca The status of RT in L Ca treatment Principle
9、of RT in L Ca Indications for RT of lung cancer Delineation principles of tumor target Radiotherapy(RT)Primary Lung cancer Malignant tumor of the Lung:Originated in the bronchial mucosa,gland or alveolar epithelial In the clinical application,L Ca is often divided into two categories：Small cell lung
10、 cancer(SCLC)Non small cell lung cancer(NSCLC)：Squamous cell carcinoma,AdenocarcinomaMultidisciplinary Therapy（MDT）Definition：According to the status of patients,tumor type,and the extent,make a reasonable treating plan by utlizing the existing treatment method,to improve the prognosis,and the life
11、quality of the cancer patients.Tabima M,Eur J Cancer 1997;28A internal target volumevolume enclosed by an isodose surfaceVolume receives a dose considered significant in relation to normal tissue toleranceICRU 62#PTV is static,geometric concept 1.Dignosis1.Dignosis2.Design the plan2.Design the plan3
12、.Fixation3.Fixation4.CT simulation4.CT simulation6.Design Radiation 6.Design Radiation fieldfieldIMRT-process5.Delineation5.Delineation7.7.Evaluation and Evaluation and validation ofvalidation of RT RT planningplanning8.8.Setup Setup errorerror verificationverification9.RT9.RTvarian23EX直线加速器10.Concl
13、usion10.Conclusion11.Follow up11.Follow upIMRT-process Introduction Principle of treatment of L Ca The status of RT in L Ca treatment Principle of RT in L Ca Indications for RT of lung cancer Delineation principles of tumor target RadiotherapyPrinciple of treatment of L CaStandard of diagnosis and t
14、reatment of primary lung cancer Stage 0、:Surgery(no contraindications)Stage A Strive to do radical operation if lesions may be resected When complete resection is difficult,try to resect tumor,then RT for residual lesion Stage B Chemoradiotherapy Stage Given appropriate systemic chemotherapy and pal
15、liative radiotherapy.The principle of Treatment of NSCLCChinese Standard of diagnosis and treatment ofprimarylung cancer The chemotherapy,RT,and operaion are preferred.(1)Limited stage disease(LD)Chemotherapy after operation;Chemotherapy,operation for residual;Concurrent chemoradiotherapy;Sequential
16、 chemoradiotherapy(2)Extensive stage disease(ED)Given appropriate systemic chemotherapyPalliative radiotherapyThe principle of treatment of SCLCChinese Standard of diagnosis and treatment ofprimarylung cancer Introduction Principle of treatment of L Ca The status of RT in L Ca treatment Principle of
17、 RT in L Ca Indications for RT of lung cancer Delineation principles of tumor target RadiotherapyThe status of RT in L Ca treatment Evidence based medicine64.3%4.7%of NSCLC cases require RT45.9%4.3%in their initial treatment18.3%1.8%later in the couse of the illnessThe status of RT in L Ca treatment
18、Incidence of RT for NSCLC-Stage DependentStage I:41.0%5.5%Stage II:54.5%6.5%Stage III:83.5%10.6%Stage IV:65.7%7.6%53.6%3.3%：SCLC need RT45.4%4.3%：in the initial treatment8.2%1.5%：later for recurrence or progressionThe status of RT in L Ca treatment Introduction Principle of treatment of L Ca The sta
19、tus of RT in L Ca treatment Principle of RT in L Ca Indications for RT of lung cancer Delineation principles of tumor target RadiotherapyPrinciple of RT of L CaChina:Standard of diagnosis and treatment of primary lung cancer 2015USA:National Comprehensive Cancer Network,NCCN 2016Principle of RT of L
20、 Ca Radical RT Palliative RT Aduvant RT Prophylactic RTRadical RTKPS score70NSCLC:Medical or personal reason rufuse operationUnresectable local advanced NSCLCSCLC:LCPalliative RTAdvanced stage：reduce symptoms.NSCLC with single brain metastasis:operation with RT or RT aloneAduvant RTNeoaduvant RT:dec
21、rease the size of tumor Aduvant RT:for positive surgical margin，as for pN2 positive,it is better to give RTNote:plan should be based on pathology and operation recordProphylactic RTSCLC:the RT of the whole brain after effective system treatments.The combination of chemo and RT depends on the stage,p
22、urpose,and the status of patients:concurrent or sequentialChemotherapy Regimens:EP or TPNote:combination of chemo and RTNote:combination of chemo and RTThe potential toxicity will increase,inform patients before treatmentThe long time break is not acceptableRadiotherapy IntroductionPrinciple of trea
23、tment of L CaThe status of RT in L Ca treatmentPrinciple of RT in L CaIndications for RT of lung cancerDelineation principles of tumor target Indications for NSCLCStage I:unable to receive operation NSCLC patients，RT is a effective methodPost operation:Positive mediastinal lymph node（pN2）,chemo and
24、RTPost operation:positive margin,pN2，concurrent chemoradiotherapy as soon as possibleII-III NSCLC:unsuitable for operation,conformal RTNote:in the hope of cure,carefully planning and better support treatment,avoid the treatment interruption,and decreasing doseIndications for NSCLC Stage IV:palliativ
25、e radiation for primary tumor and metastases.Indications for NSCLC Limited stage SCLC:after chemotherapy,some patients can achieve complete remission,but if not combined with radiotherapy,the risk of intrathoracic recurrence is very high,with RT can not only decrease the local recurrence rate,but al
26、so significantly reduced the risk of deathIndications for SCLC Extensive stage SCLC:chemotherapy combined with thoracic RT can improve the tumor control rate and prolong the survivalIndications for SCLCNote:If the condition permits,radiation treatment of SCLC should begin as soon as possible Synchro
27、nized with the chemotherapyIndications for SCLCNote:If the lesion is huge,resulting in the risk of lung injury,consider using 2-3 cycles of chemotherapy,then start RT as soon as possibleIndications for SCLCPatients with LD SCLC,the intrathoracic lesions were CR,recommended prophylactic cranial irrad
28、iation(PCI).In the case of ED SCLC,chemotherapy and RT are effective,combined with PCI may reduce the risk of brain metastasis.Prophylactic RTNSCLC:decision of PCI should be fully discussed between both doctors and patients after weighing the pros and cons of each patientProphylactic RT In patients
29、with advanced lung cancer.The main purpose is to solve the local compression symptoms,caused by primary or metastatic lesion,pain caused by bone metastasis,neurological symptoms caused by brain metastasis.Palliative RT Consider using hypofractionated irradiation technique,patient relieve symptoms mo
30、re convenient,and more quicklyPalliative RT Evaluate the efficacy of RT with WHO response evaluation criteria in solid tumor(RECIST)Efficacy evaluationDuring RT,attention should be paid to the protection of the lung,heart,esophagus and spinal cord,to avoid severe radiation damage to the body organs.
31、According to the RTOG criteria for acute radiation-induced lung injuryProtection Introduction Principle of treatment of L Ca The status of RT in L Ca treatment Principle of RT in L Ca Indications for RT of lung cancer Delineation principles of tumor target RadiotherapyImprove the control rate of the
32、 tumorImprove the accuracy of the RTIncrease the dose of target areaEnsure uniform dose distribution in the target areaReduce the radiation to normal tissue thereby reducing complications of RT.PurposeDelineation principles Target definition and target delineation:according to ICRU50 and ICRU62 repo
33、rt,the target area of lung cancer is defined as GTV,CTV,ITV,PTVGTV（Gross tumor volume）：）：A malignant lesion,visible,with a certain shape and size,including the primary tumor,lymph node metastasis and other metastatic lesions.CTV(clinical target area):refers to the range of possible sub clinical inva
34、sion area based on GTV,including the lymphatic drainage area.ITV(internal target area):The range of CTV volume and shape changes caused by the movement of internal organs.Namely:the range of ITV=CTV+movementPTV(planning target area):including CTV,ITV,setup error,position of target and target volume
35、changes during RT.PTV=CTV+organ motion+setup errorMovement of Lung cancer:mainly refers torespiratory motion cardiovascular pulsation(respiratory movement is particularly important)PTV is the final target area of irradiation:PTV=ITV+1cmNSCLC:1.Stage,（T1-3N0-1M0）GTV：lung window-delineation of the lun
36、g lesions,including the edge of spiculation;mediastinal window-mediastinal lesions CTV：squamous GTV+6mm adeno GTV+8mm Not including lymphatic drainage area Delineation principlesNSCLC:1.PTV：CTV+ITV（respiratory）+setup error（meachine）10mm Dose：DT66Gy/33f if T5cm,try SBRT，5Gy*12f或或6Gy*10fDelineation pr
37、inciples2.Local advanced：A,B GTV：The primary tumor(not including atelectasis)+positive lymph nodes(short diameter 10mm or the same site 3)CTV：squamous GTV+6mm adeno GTV+8mm +ipsilateral hilar metastasis +adjacent lymphatic drainage areaDelineation principles2.Local advanced：A,B PTV：CTV+ITV+setup err
38、or（7-10mm）Dose：DT60-70Gy/30-35f,decrease the dose when combined with chemotherapyDelineation principlesSCLC:（(chemotherapy radiotherapy)GTV：lung window delineation of visible lesions(after chemo)+positive lymph node(before chemo)CTV：GTV+8mm+positive lymphatic drainage area PTV：CTV+ITV+setup error（7-
39、10mm）Dose：chemo-CR:DT50Gy/25f，residual lesions DT54-60Gy/27-30fDelineation principlesTypeTypeDoseDoseFractionFractionDuration(W)Duration(W)Pre operationPre operation45-5045-501.8-2Gy1.8-2Gy4-54-5After operationAfter operationNegative marginNegative margin50501.8-2Gy1.8-2Gy4-54-5Positive marginPositi
40、ve margin54-6054-601.8-21.8-25-65-6ResidualResidual残余残余60-7060-701.8-21.8-26-76-7根治性根治性单纯放疗或序贯化放疗单纯放疗或序贯化放疗60-7460-742 26-7.56-7.5同步化放疗同步化放疗60-7060-702 26-76-7姑息性姑息性梗阻性疾病（上腔静脉综合征）梗阻性疾病（上腔静脉综合征）30-4530-453 32-32-3骨转移伴软组织肿块骨转移伴软组织肿块30303 32 2骨转移不伴软组织肿块骨转移不伴软组织肿块8 88 81 1脑转移脑转移肺癌放射治疗的副反应及并发症肺癌放射治疗的副反应及
41、并发症 有全身反应、皮肤反应、放射性食管炎及放射性肺炎。有全身反应、皮肤反应、放射性食管炎及放射性肺炎。放射性肺炎是肺癌放疗中多见并且危害性较大的并发症。放射性肺炎是肺癌放疗中多见并且危害性较大的并发症。急性期表现为照射部位的肺组织急性渗出性炎症，临床表现为咳急性期表现为照射部位的肺组织急性渗出性炎症，临床表现为咳嗽嗽、咳痰及发热、胸背疼痛、气急、肺部听诊有湿罗音等，、咳痰及发热、胸背疼痛、气急、肺部听诊有湿罗音等，X线线片显示肺炎范围与照射野一致。用抗生素、肾上腺皮质激素、支片显示肺炎范围与照射野一致。用抗生素、肾上腺皮质激素、支气管扩张剂治疗，必要时吸氧治疗。气管扩张剂治疗，必要时吸氧治疗
42、。放射性肺炎的发生与肺受照射的容积量密切相关，与照射剂量、放射性肺炎的发生与肺受照射的容积量密切相关，与照射剂量、分割方式以及个体差异也有关系。分割方式以及个体差异也有关系。肺癌预后及影响预后的因素肺癌预后及影响预后的因素 肺癌的预后较差。早期病例（肺癌的预后较差。早期病例（III期）根治性手术切除期）根治性手术切除的的5-y-SR约为约为30%50%，中晚期病例放射治疗的，中晚期病例放射治疗的5-y-SR约为约为10%15%，而单纯化疗者仅有少数病人能得到，而单纯化疗者仅有少数病人能得到根治。根治。影响肺癌预后的主要因素：病期早晚、病理类型和分影响肺癌预后的主要因素：病期早晚、病理类型和分化
43、程度、治疗前患者的行为状态（化程度、治疗前患者的行为状态（KPS评分）和有无体重评分）和有无体重下降、治疗方式的选择和机体的免疫功能状态等。下降、治疗方式的选择和机体的免疫功能状态等。我们期望通过提高肺癌的早期诊断率、改进放射治疗我们期望通过提高肺癌的早期诊断率、改进放射治疗技术、合理应用综合治疗手段，来改善肺癌的治疗效果。技术、合理应用综合治疗手段，来改善肺癌的治疗效果。总总 结结 原发性肺癌的治疗应该严格按照卫生部的原发性肺癌的治疗应该严格按照卫生部的诊疗规范进行诊疗规范进行-患者及家属的维权意识增患者及家属的维权意识增强强 晚期难治性病期可以进行临床研究晚期难治性病期可以进行临床研究-伦理伦理 治疗期间注意观察患者的病情变化及不良治疗期间注意观察患者的病情变化及不良反应，及时处理，预防严重的并发症反应，及时处理，预防严重的并发症 谢谢 谢！谢！
