放射物理學(xué)課件：Radiotherapy of Lung Cancer

1、Radiotherapy of Lung CancerWelcome to apply the Master Degree of the Oncology!Paper1. 第一作者論文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)

2、-S cell cycle transition in radioresistance of perinecrotic tumor cells, Oncogene. 2013;32(16):2058-25682. 通訊作者論文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-

3、7183.Paper3. 參與論文(1) Zhao T, Zhu Y, Morinibu A, Kobayashi M, Shinomiya K, Itasaka S, Yoshimura 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)

4、Zeng L, Morinibu A, Kobayashi M, Zhu Y, Wang X, Goto Y, Yeom CJ, Zhao T, Hirota K, Shinomiya K, Itasaka S, Yoshimura 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

5、; 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, Tanimoto 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

6、 deubiquitinating effect on HIF-1. Nat Commun. 2015;6:6153. doi: 10.1038/ncomms7153Paper3. 參與論文(4) Harada H, Inoue M, Itasaka S, Hirota K, Morinibu A, Shinomiya 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

7、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 M, Treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the effect of radiation therapy, Br J Cancer,

8、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 metalloproteinases-positive cells for in vivo imaging of invasive and metastatic activity of tumor cells, J Control Release

9、, 144(1):109-114, 2010ConferenceHiroshima：Tumor and hypoxiaNagoya：Annual oncologicmeetingForeign friendsIntroductionPrinciple of treatment of L CaThe status of RT in L Ca treatmentPrinciple of RT in L CaIndications for RT of lung cancerDelineation principles of tumor target Radiotherapy (RT) Primary

10、 Lung cancerMalignant 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 cancer (SCLC) Non small cell lung cancer (NSCLC) ：Squamous cell carcinoma, AdenocarcinomaMultidisciplinary

11、 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,toimprovethe prognosis, andthe life quality of the cancer patients.Radiotherapy WHO data: 45% cancer patients can be cured.22% surgery18% r

12、adiotherapy5% chemotherapy About 80% cancer patients may be treated with radiotherapy.Tabima M, Eur J Cancer 1997;28AInitial Outcome of Patients Treated with Conventional Radiotherapy for Localized Tumors GTV CTV ITV PTVTreated VolumeIrradiated Volume internal target volumevolume enclosed by an isod

13、ose surfaceVolume receives a dose considered significant in relation to normal tissue toleranceICRU 62#PTV is static, geometric concept 1.Dignosis2.Design the plan3.Fixation4.CT simulation6.Design Radiation fieldIMRT-process5.Delineation7. Evaluation and validation ofRT planning8. Setup errorverific

14、ation9.RTvarian23EX直線加速器10.Conclusion11. Follow upIMRT-processIntroductionPrinciple of treatment of L CaThe status of RT in L Ca treatmentPrinciple of RT in L CaIndications for RT of lung cancerDelineation principles of tumor target RadiotherapyPrinciple of treatment of L CaChina: Standard of diagno

15、sis and treatment ofprimarylung cancer 2015USA: National Comprehensive Cancer Network , NCCN 2015 Stage 0、:Surgery (nocontraindications) Stage AStrive to do radicaloperation if lesionsmay beresectedWhencompleteresectionis difficult,try to resecttumor,then RTforresiduallesion Stage BChemoradiotherapy

16、 Stage Given appropriatesystemic chemotherapyand palliative radiotherapy.The principle of Treatmentof NSCLCChinese Standard of diagnosis and treatment ofprimarylung cancer 2015 Thechemotherapy, RT, and operaion arepreferred.(1) Limited stage disease (LD) Chemotherapyafteroperation; Chemotherapy,oper

17、ation forresidual; Concurrent chemoradiotherapy; Sequential chemoradiotherapy(2) Extensive stage disease (ED)Given appropriatesystemic chemotherapyPalliative radiotherapyThe principle of treatmentof SCLCChinese Standard of diagnosis and treatment ofprimarylung cancer 2011IntroductionPrinciple of tre

18、atment of L CaThe status of RT in L Ca treatmentPrinciple of RT in L CaIndications for RT of lung cancerDelineation principles of tumor target RadiotherapyThe status of RT in L Ca treatmentEvidence based medicine64.3%4.7% of NSCLC cases require RT45.9%4.3% in their initial treatment18.3%1.8% later i

19、n the couse of the illnessThe status of RT in L Ca treatmentIncidence 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 i

20、n L Ca treatmentIntroductionPrinciple of treatment of L CaThe status of RT in L Ca treatmentPrinciple of RT in L CaIndications for RT of lung cancerDelineation principles of tumor target RadiotherapyPrinciple of RT of L CaChina: Standard of diagnosis and treatment ofprimarylung cancer 2015USA: Natio

21、nal Comprehensive Cancer Network , NCCN 2016Principle of RT of L CaRadical RTPalliative RTAduvant RTProphylactic RTRadical RTKPS score70NSCLC: Medical or personal reason rufuse operationUnresectable local advanced NSCLCSCLC: LCPalliative RTAdvanced stage：reducesymptoms.NSCLC with single brain metast

22、asis: operation with RT or RT aloneAduvant RTNeoaduvant RT: decrease 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 syste

23、m treatments.The combination of chemo and RT depends on the stage, purpose, 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 l

24、ong time break is not acceptableRadiotherapy IntroductionPrinciple of treatment 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 eff

25、ective methodPost operation: Positive mediastinal lymph node （pN2）, chemo and 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 t

26、he treatment interruption, and decreasing doseIndications for NSCLCStage IV: palliative radiation for primary tumor and metastases.Indications for NSCLCLimited stage SCLC: after chemotherapy, some patients can achieve complete remission, but if not combined with radiotherapy, the risk of intrathorac

27、ic recurrence is very high, with RT can not only decrease the local recurrence rate, but also significantly reduced the risk of deathIndications for SCLCExtensive stage SCLC: chemotherapy combined with thoracic RT can improve the tumor control rate and prolong the survivalIndications for SCLCNote: I

28、f the condition permits, radiation treatment of SCLC should begin as soon as possibleSynchronized 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 SC

29、LCPatients with LD SCLC, the intrathoracic lesions were CR, recommended prophylactic cranial irradiation (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

30、both doctors and patients after weighing the pros and cons of each patientProphylactic RTIn patients 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 m

31、etastasis. Palliative RTConsider using hypofractionated irradiation technique, patient relieve symptoms more convenient, and more quicklyPalliative RTEvaluate the efficacy of RT with WHO response evaluation criteria in solid tumor (RECIST)Efficacy evaluationDuring RT, attention should be paid to the

32、 protection of the lung, heart, esophagus and spinal cord, to avoid severe radiation damage to the body organs. According to the RTOG criteria for acute radiation-induced lung injuryProtectionIntroductionPrinciple of treatment of L CaThe status of RT in L Ca treatmentPrinciple of RT in L CaIndicatio

33、ns for RT of lung cancerDelineation principles of tumor target RadiotherapyImprove the control rate of the 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.

34、PurposeDelineation principlesTarget definition and target delineation: according to ICRU50 and ICRU62 report, 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 met

35、astasis and other metastatic lesions.CTV (clinical target area): refers to the range of possible sub clinical invasion 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

36、 range of ITV = CTV+ movementPTV (planning target area): including CTV, ITV, setup error, position of target and target volume changes during RT. PTV = CTV + organ motion+setup errorMovement of Lung cancer: mainly refers torespiratory motion cardiovascular pulsation(respiratory movement is particula

37、rly important)PTV is the final target area of irradiation: PTV = ITV+1cmNSCLC:Stage, （T1-3N0-1M0） GTV：lung window-delineation of the lung lesions, including the edge of spiculation; mediastinal window-mediastinal lesions CTV：squamous GTV+6mm adeno GTV+8mm Not including lymphatic drainage area Deline

38、ation principlesNSCLC:PTV：CTV+ITV（respiratory）+setup error（meachine）10mm Dose：DT66Gy/33f if T5cm, try SBRT，5Gy*12f或6Gy*10fDelineation principles2.Local advanced：A, BGTV：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