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1 Decision Making of Treatment Modality of Hepatocellular Carcinoma: Consideration of KLCSG- NCC Korea Guideline Bo Hyun Kim Center for Liver Cancer, National Cancer Center, Goyang, Korea 서론 간세포암종 (hepatocellular carcinoma, HCC) 의치료에는간절제, 간이식과같은수술적방법뿐아니라, 고주파열치료술 (radiofrequency ablation, RFA), 경동맥화학색전술 (transarterial chemoembolization, TACE) 등과같은국소치료요법, 체외방사선치료, 전신항암요법등의여러가지방법이있으나, 종양의 크기나개수, 위치, 나아가기저간기능등에따라선택할수있는치료법이달라진다. 본고에서 는 2014 년개정된대한간암학회 - 국립암센터간세포암종진료가이드라인에기반하여치료방법의 선택에대해가이드라인에서채택하고있는 modified UICC 병기체계 (Figure1, Table 1) 에따라기술하고자한다. 1 Figure 1. Modified UICC Stage, T stage 1-3

2 *Vp, portal vein; Vv, hepatic vein; B, bile duct ** Adopted from the reference 1. 1 Table 1. Modified UICC Stage 1-3 Stage T N M I T1 N0 M0 II T2 N0 M0 III T3 N0 M0 IV A T4 N0 M0 T1, T2, T3, T4 N1 M0 IV B T1, T2, T3, T4 N0, N1 M1 1. Modified UICC Stage I 본론 1) 2cm 이하의혈관침범이없는단일종괴 간경변증이없는간에국한된단일간세포암종환자에서 1 차치료법은간절제술이며, 4 있는경우에도간기능이잘보존되어있는경우우선적으로고려할수있다. 5,6 간경변증이 가이드라인에따르 면, 문맥압항진증과고빌리루빈혈증이모두없는 Child- Pugh 등급 A 의환자에서간에국한된단일 간세포암종에대하여간절제술을일차치료법으로권장 ( 권고등급 A2) 하고있으며, 경미한문맥압 항진증또는경미한고빌리루빈혈증을동반한 Child- Pugh 등급 A 및상위 B 등급의간세포암종에서도제한적간절제술을선택적으로시행할수있다고권고 (C1) 하였다. 1 또한, 고주파열치료술도 직경 3cm 이하의단일간세포암종에서간절제술과유사한생존율을기대할수있어권장 (A2) 되는

3 치료법이나, 1 간문주위나대장과같은주요장기가간세포암종에인접한경우시술합병증의위 험성이높아지고, 비교적큰혈관주위에종양이인접한경우열씻김현상 (heat sink effect) 으로인하여치료효과가떨어질수있어이러한경우간절제술이더유용할수있다. 7 혈관주위에종양 이위치해있는경우, 열씻김현상을극복하기위하여에탄올주입술을시행할수있으며, 특히 2cm 이하의간세포암종에서는두치료법의결과가유사하여고주파열치료술이어려운경우에탄 올주입술을시행할수있다 (A2). 하지만, 간기능이감소되어간절제술이불가능한경우에는간이 식을우선적으로고려해야한다. 또한최근 3cm 이하의단일간세포암종에서간절제술, 고주파열치료술또는 TACE 의생존율을비 교한후향연구에따르면, TACE 치료를받은환자에서생존율이가장낮았지만, 통계적인보정이후에는생존율의차이가소실되었다고보고된바있어, 8 환자가수술을거부하거나위험성이높은경우, 고주파열치료술이적용되기어려운경우등에경동맥화학색전술을고려해볼수있다 Modified UICC Stage II 1) 혈관침범이없는 2cm 초과의단일종괴 Modified UICC stage I 에서와같이간절제술과고주파열치료술을고려할수있다. 다만, 일반적으로고주파열치료술은단발성종양의경우 5cm 이하에서고려할수있고, 1 크기가 3cm 을초과하게되 면국소재발률이높아진다는점을염두에두어야한다. 최근일련의연구들에의하면종양의크 기가 3-5cm 인경우고주파열치료술과경동맥화학색전술을병행치료하면고주파열치료술단독치료에비해국소재발율과생존율면에서좀더우수한효과를보인다고보고된바있다 간절제 술이나고주파열치료술등의국소치료술이어려운경우, 경동맥화학색전술을시행할수있으며, 간기능이저하되어있는경우, 간이식을고려할수있다. 특히단일종괴로서 6.5cm 이하인경우 는 UCSF (University of California, San Francisco) criteria 에해당, 간이식후 5 년생존율 75% 로보고된바있다. 12 2) 혈관침범이없는 2cm 이하의다발성종괴 밀란척도 ( 단일결절로 5cm 이하이거나, 다발성인경우결절이 3 개이하각결절이 3cm 이하 ) 이 내에해당하는경우간이식이우선적으로권고된다. 밀란척도이내의간세포암종에서간이식을 하는경우무병생존율 83%, 4 년생존율 75% 로간세포암종이아닌적응증으로간이식을받은환자와비슷한 5 년생존율 (65~78%) 를보인다 간기능이보존되어있으면일반적으로경동맥화학색전술이추천되며, 3 개이하인경우고주파열치료술도고려할수있다. 1 3) 혈관침범을동반한 2cm 이하의단일종괴 혈관침범을동반하는경우, Barcelona Clinic Liver Cancer (BCLC) 병기법에따라진행성간세포암종으 로분류, 소라페닙을사용해볼수있다. 소라페닙의다기관 3 상무작위연구결과에의하면, 간문 맥침범이있거나간외전이가있는진행성간세포암종에서소라페닙치료를받은환자의중앙생존기간이 6.5~10.7 개월정도였지만, 17,18 국내연구결과에서는주문맥이나 1 차분지침습이있는경 우라도결절성형태의종양이거나그범위가국한되어있을때에경동맥화학색전술이비교적좋 은성적 ( 중앙생존기간 22~30 개월 ) 을보인바있어경동맥화학색전술또한치료법으로고려할수 있다 (B2). 1,19,20 또한, 체외방사선치료도고려할수있다 (Modified UICC stage III, 3-3 참조 )

4 3. Modified UICC Stage III 1) 혈관침범이없는 2cm 초과의다발성종괴 전술한바 (Modified UICC stage II, 2-2) 와같이밀란척도 ( 단일결절로 5cm 이하이거나, 다발성인경우 결절이 3 개이하각결절이 3cm 이하 ) 이내에해당하는경우간이식이우선적으로권고된다. 간 기능이보존되어있으면일반적으로경동맥화학색전술이추천되며, 암종의크기가 3cm 이하, 3 개이하인경우고주파열치료술도고려할수있다. 1 2) 혈관침범이있는 2cm 이하의다발성종괴 전술한바 (Modified UICC stage II, 2-3) 와같이혈관침범을동반하는경우소라페닙을사용해볼수 있으나, 잔존간기능이좋고간내종양의분포가국소적인경우경동맥화학색전술을고려할수있다. 1 3) 혈관침범이있는 2cm 초과의단일종괴 전술한바와같이간문맥침범을동반한경우, 간기능이유지되어있고, 국소적인분포를보이면 경동맥화학색전술을고려할수있다 (B2). 경동맥화학색전술의국소적종양치료효과는암종의 크기등에영향을받는데, 경동맥화학색전술후불완전한치료반응을보이는경우추가적으로 체외방사선치료를시행하는것도고려할수있다. 21 경동맥화학색전술과체외방사선치료를 병행하는경우경동맥화학색전술단독군에비해 3 년생존율을 10~28% 정도증가시킨다는 메타분석연구결과도있다. 22 단독치료로서도체외방사선치료를고려할수있는데, 간절제술, 간이식, 고주파열치료술, 에탄올주입술및경동맥화학색전술이어려운간세포암종에서전산화 방사선치료계획시 30 Gy 가조사되는체적이전체간부피의 60% 이하인경우시행할수 있다 ( 간기능이 Child- Pugh 등급 A 또는상위 B 인경우 ). 23 정위절제방사선치료를포함한저분할 방사선치료는주로간기능이잘보존되어있으면서정상간용적이충분한경우에시행하는데, 2 년국소제어율은 70~100%, 2 년생존율은 50~75% 이라고보고된바있다 특히크기의합이 6 cm 이하이고개수가 3 개이하인암종에서는 90% 이상의국소제어율을보였다. 24,28-30 또한, 혈관침범을동반하는경우이므로소라페닙을사용해볼수있다. 4. Modified UICC Stage IVa 1) 혈관침범이있는 2cm 초과의다발성종괴 간혈관침범을동반하는경우소라페닙치료를고려할수있다 (Child- Pugh 등급 A, A2; Child- Pugh 등급 B, B1). 또한, 간문맥침범을동반한간세포암종에서잔존간기능이좋고간내종양이국소적이라면경동맥화학색전술도고려할수있다 (B2). 2) 임파선침범을동반하는경우 Modified UICC stage IVb 부분참조.

5 5. Modified UICC Stage IVb 1) 전이를동반하는경우 간외전이가있는진행성간세포암종에서는소라페닙을일차적으로고려할수있다 (Child- Pugh 등 급 A, A1; Child- Pugh 등급 B, B1). 소라페닙치료에실패한진행성간세포암종환자에서양호한간 기능과좋은전신상태를갖고있는경우세포독성화학요법을시행할수있으나, 권고등급은높지않다 (C1). 1 또한, 원발암및전이암으로인한증상완화목적을위해필요시체외방사선치료를시행을고려 할수있다 (B1). 1 복부림프절전이나, 뼈전이, 뇌전이, 40 척수신경압박을동반한척추 전이, 41 폐전이 31,42 등을동반한경우체외방사선치료를통해증상의호전을기대할수있다. 결론 2009년간세포암종진료가이드라인이개정을거친이후우리나라현실을반영할수있는치료법에관한많은연구들이발표되고지식이축적됨에따라다시한번의개정작업을거쳐 2014년간세포암종진료가이드라인이발표되었다. 하지만, 실제임상에서는아직까지도대답하기어려운경우들이많은것이현실이니만큼, 좀더많은연구들이진행되어해결되어가기를기대한다.

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김범수

김범수 Analysis of Outcomes after Resection of Sarcomatous Hepatocellular Carcinoma Purpose: Sarcomatous hepatocellular carcinoma (HCC) is rare. Therefore, the clinicopathologic characteristics and prognosis