The role of iA CCRT in HCC

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1 Radiation oncologist s perspective: Providing survival benefit Ik Jae Lee Gangnam Severance Hospital Yonsei University College of Medicine, Department of Radiation Oncology

2 간세포암종가이드라인세계현황 Guideline 2001 Barcelona-EASL consensus No 2002 US NCCN guideline EBRT 2003 KLCSG-NCC guideline Yes 2005 AASLD guideline No* 2005 Japan guideline for evidence-based clinical practice No 2007 JSH guideline: consensus-based clinical practice manual 2008 US NCCN guideline Yes 2009 KLCSG guideline Yes 2010 AASLD No 2012 EASL-EORTC 2012 Yes * Non-curative treatment: There are multiple other treatment modalities such as octreotide, interferon, external radiation, tamoxifen, or antiandrogenic therapy, but none have been shown to improve survival. For Child-Pugh C cases with vascular invasion or an extrahepatic lesion, palliative care is the basic treatment, including radiotherapy aimed at palliative pain removal. No

3 Ablation (RFA etc.) Emblization RTx

6 간세포암종가이드라인 (2003)

7 2003 간세포암종진료가이드라인 T6 방사선치료 1. 절대적비적응증 간기능 Child-Pugh C 이면서전간의다발성, 미만성종양이며수행상태 ECOG 활동도 3 이상 2. 상대적비적응증 간기능 Child-pugh A,B 이면서전간에걸친다발성, 미만성종양 제한적간외전이 주변장기, 외장간등의활동성염증이나궤양이동반된경우 3. 적응증 근치적목적 : 간기능 child-pugh A,B 이면서종양이전간의 2/3 이하이고간외전이가없는경우 완화목적 : 종양으로인한통증, 파열이예상되는종양, 간문맥종양혈전증, 종양으로인한담도폐색, 국소적간외전이등

8 Treatment plan for HCC (2009, KLCSG) 근치적치료 간절제술 간이식 고주파열치료 ( 경동맥화학색전술 ) 종양치료가능 선택검사 간세포암종 간암병기 Child-Pugh 등급 ECOG 수행능력 ICG 검사 뼈스캔 흉부 CT 혈관조영술 PET-CT 용적측정 위내시경 종양치료불가능 비근치적치료 경동맥화학색전술 방사선치료 (II-I) 힝앙화학요법 )* * Sorafenib (I) 세포독성화학요법 (III) 임상적시도 Drug eluting bead-tace 방사선색전술 HIFU 간동맥내주입항암요법 세포독성화학요법 전이병소절제술 종양병기진행 간기능저하 (Child-Pugh 등급 C)** 동반된전신질환 (ECOG >2) 동반된전신질환 보존적치료 ** 간이식고려 (I)

10 치료결정알고리즘 ; 방사선종양학과제시안 근치적치료 간절제술 간이식 고주파열치료 ( 경동맥화학색전술 ) 방사선치료 (II-1) ; 경동맥화학색전술후잔존병소 종양치료가능 선택검사 ICG 검사 뼈스캔 흉부 CT 혈관조영술 PET-CT 용적측정 위내시경 종양치료불가능 비근치적치료 종양병기진행 간기능저하 (Child-Pugh 등급 C)** 동반된전신질환 (ECOG >2) 동반된전신질환 경동맥화학색전술 방사선치료 (II-I) 항암화학요법 * * Sorafenib (I) 세포독성화학요법 (III) 보존적치료 임상적시도 Drug eluting bead-tace 방사선색전술 HIFU 간동맥내주입항암요법 세포독성화학요법 전이병소절제술 양성자치료 * 방사선치료 (II-3) * 간외전이 ( 뇌, 뼈, 복부임파절 ) * 방사선치료 (II-2) ** 간이식고려 (I)

11 수정전권고사항 ( 방사선종양학과제시안 ) 간세포암에서의근치적방사선치료의적응증 1. 간기능이 Child-Pugh A 또는 B 이면서종양이전체간부피의 2/3이하이고, 간외전이가 없는경우근치적목적의방사선치료를시행할수있다. (II-3). 2. 간문맥혈전증은방사선치료가효과적이다. (II-1). 3. 경동맥화학색전술단독보다는방사선치료와의병합요법이보다효과적이다. (II-1) 간세포암에서의고식적방사선치료의적응증 1. 경동맥화학색전술후재발성간암에대한구제치료로서고식적목적의방사선치료를 시행할수있다. (II-2) 2. 간암으로인한복부통증등증상완화를목적으로방사선치료를시행할수있다. (III) 3. 황달증상을보이는간암에방사선치료를시행할수있다. (II-2) 4. 종양으로인한동정맥단락에서일차치료로방사선치료를시행하여향후 TACE 등을 가능하게할수있다. (III) 5. 복부림프절전이에대해서방사선치료의시행으로생존율의향상을기대할수있다. (II-2) 6. 뼈전이에의한통증이있는경우방사선치료로증상완화를이룰수있다. (II-3) 7. 뇌전이로인한신경학적증상을완화하기위해전뇌방사선치료가효과적이다. (II-3) 8. 간암의척수압박으로인한신경학적증상을완화하기위해방사선치료는효과적이다. (III)

13 Lee et al. Gut & Liver 6(2); ; 2012

14 Lee et al. Gut & Liver 6(2); ; 2012

15 Early stage M/59, T2N0 Initial

$x 4 fractions) 1 month 2$ months 6 months 6000 4000 2000

17 M/59, T2N0 Initial SBRT (9 Gy x 4 fractions) 1 month 2 months 6 months AFP (ng/ml)

18 Phase II trial Cancer Nov 1;118(21):

19 Intermediate stage

20 TACE in combination with RT for unresectable HCC: A systematic review and meta-analysis Meng et al. (2009) Radiotherapy and Oncology

21 TACE RTx How many TACE?? Consensus-Based Clinical Practice Guidelines Proposed by the Japan Society of Hepatology (JSH) 2010, Kudo et al. For patients who show no response of the treated tumour after at least two sessions of TACE, other therapies, including systemic therapy with a targeted agent, could be considered as an alternative to further TACE cycles. Raoul et al. Cancer Tret Rev, 2011

Advanced stage # HCC (non-b, non-c), ct3n1m0,

definitive CCRT 50Gy/ 25 fx (2011.02.05-2011.

22 Advanced stage # HCC (non-b, non-c), ct3n1m0, stage IVA Huge marginal enhancing mass in Rt lobe of liver, Rt PVT (+) aortocaval, retrocaval space, porta LNE s/p IA FL based definitive CCRT 50Gy/ 25 fx ( ) s/p IA FP #2 ( ) Initial AFP

23 비근치적치료 경동맥화학색전술 방사선치료 (II-I) 항암화학요법 )* * Sorafenib (I) 세포독성화학요법 (III) 임상적시도 Drug eluting bead-tace 방사선색전술 HIFU 간동맥내주입항암요법 세포독성화학요법 전이병소절제술 양성자선치료

24 Initial Tx? Salvage Tx? 내과 외과 방사선종양학과 영상의학과

25 TACE + Ext. RTx Role of Salvage Tx.

27 Clinical factors related to treatment failure after hepatic arterial concurrent chemoradiotherapy for locally advanced HCC Cha et al. Yonsei Univ. submitted. Local failure Distant failure Infield Intrahepatic-outfield Extrahepatic HR 95% CI p HR 95% CI p HR 95% CI p Age, Stage III-IV Portal vein thrombosis, Yes Pre-CCRT treatment history, Yes Pre-CCRT AFP (IU/mL), Pre-CCRT PIVKA-II (mau/ml), Pre-CCRT AFP & PIVKA-II

28 대한간암연구학회 39 차집담회

29 Stage D

30 Factors we have to consider for Radiotherapy Radiotherapy is locoregional Tx. Location Tumor volume Extrahepatic disease (Lymph node, portal vein thrombosis etc.) Normal liver volume Adjacent normal organ (stomach, duodenum, kidney.) Liver function (Child-Pugh s class etc.) Tumor markers Biologic behavior (CTx response, indolent vs. rapid progression) Available radiotherapy modalities (SBRT, 3D-CRT, IMRT, gated RTx, Immobilization device etc.)

33 Predictive Index for PVTT in Patients with HCC treated with RTx (PITH) Performance status (ECOG), Child-Pugh classification B or C, 10 cm or more of tumor size, multiplicity of the tumor main PVTT involvement, complete occlusion of portal flow lymph node metastasis. Yu et al. JKMS 2011

34 저는어떤치료를받는것이가장좋을까요? 양성자치료 3 차원입체조형방사선치료 방사선수술, 사이버나이프 세기조절방사선치료, 래피드아크, 트루빔, 노발리스, 토모테라피

35 No. of Fraction Conventional RT IMRT Elekta Synergy, Varian Trilogy, Siemens Artiste, Helical Tomotherapy etc. 5 1 SRS FSRT Cyberknife, Novalis IGRT Tumor dose (Gy)

36 위치에따라다양한방사선치료계획이세워짐.

38 Spectrum of in-room image-guidance technologies

39 Spectrum of in-room image-guidance technologies

40 간암등록사업자료활용연구 - 대한간암연구학회 간세포암환자에서의방사선치료의효과에대한짝을이룬관찰치비교분석 (Matched-pair analysis)

41 Trial design strategies and control groups RTx ± Sorafenib Sorafenib + RTx CCRT ± Sorafenib

$radiotherapy (SBRT) doses will be 60 Gy in 3 fractionations. Patients receive 3 fractionations separated by >48 hours.$

42 Phase II multicenter study of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma (KROG 12-02) Radiation : Total stereotactic Body radiotherapy (SBRT) doses will be 60 Gy in 3 fractionations. Patients receive 3 fractionations separated by >48 hours. Target sample size: 71 7 institutes PI: Kim, MS

43 RTOG 1112: Randomized Phase III Study of Sorafenib versus SBRT followed by Sorafenib in HCC S T R A T I F Y Vascular involvement (IVC, main portal vein/right or left main branch portal vein vs. other vascular involvement vs. none) Hepatitis B vs. C vs. other North American site vs. Non-North American site HCC volume/liver volume (<10% vs vs. >40%) R A N D O M I Z E Arm 1 Daily sorafenib Arm 2 SBRT alone (27.5 Gy 50 Gy in 5 fractions) Followed by Sorafenib alone daily Patients Unsuitable for resection or transplant or radiofrequency ablation (RFA) Unsuitable for TACE or refractory to TACE Barcelona Clinic Liver Cancer Stage (BCLC) Intermediate (B) or Advanced (C) LINAC-based, Cyberknife, or protons RTOG Affiliated members in Korea: NCC, Severance hospital

44 In Evidence Based Medicine..

45 Summary and Conclusions RT can be a useful therapy for tumors in various stages according to the BCLC system. Stage 0 or A serve as a nonsurgical curative therapy. Stage B combined with other treatments such as TACE Stage C RT in combination treatment can prolong the survival time in selected patients who present locally advanced HCC associated with portal vein invasion but not distant metastasis. Stage D RT can provide effective palliation. A variety of new RT machines are currently available. Although 3D-CRT has been the standard mode, it is highly recommended to use a precision RT technology involving intensity modulation as well as image-guided one. Further clinical study in the radiation treatment of HCC is necessary to confirm its role in multidisciplinary management of HCC.

46 내이름을경외하는너희에게는의로운해가떠올라서치료하는광선을발하리니너희가나가서외양간에서나온송아지같이뛰리라말라기 4 장 2 절 Thank You!

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( )Jkstro011.hwp 비인강암의방사선치료결과및생존율에관한예후인자분석 2005 2 1 2005 3 28. :, Tel: 053)250-7665, Fax: 053)250-7984 E-mail: jhkim@dsmc.or.kr 정영연외 2 인 : 비인강암의예후인자분석 정영연외 2 인 : 비인강암의예후인자분석 Carcinoma of the nasopharynx treated by radiotherapy