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1 대흉외지 2007;40: 임상연구 전이성폐암에대한폐절제술의성적 이영옥 * ㆍ이응배 * ㆍ류경민 * Clinical Outcome of Pulmonary Metastasectomy in Patients with Pulmonary Metastasis Young-Ok Lee, M.D.*, Eung-Bae Lee, M.D.*, Kyoung-Min Ryu, M.D.* Background: Surgical resection is accepted widely as the standard therapy for complete resectable pulmonary metastases. The number of cases of pulmonary metastasectomy and its survival rate is increasing due to the development of the therapeutic modalities. We attempted to analyze the survival rate and prognosis factors of pulmonary metastasectomy during the last 10 years. Material and Method: We retrospectively analyzed the data of 89 patients who underwent 96 procedures of pulmonary metastasectomy between January 1996 and December The factors that may influence the long term prognosis such as completeness of resection, the type of primary cancer, the disease-free interval, the number and size of metastasis and the laterality were investigated. Result: There was no operative mortality. The mean disease free interval (DFI) was 29.6±27.9 months and there were 3 cases of synchronous metastasis (3.4%). The overall 3, 5 and 10 year survival rate was 52.5%, 32.1% and 20.7%, respectively. The median survival time was 38 months. The 5-year survival rate according to the IRLM appraisal was 63.5%, 33.3%, 22.1% and 0% for stage I, II, III and IV, respectively. Univariate analysis showed a better prognosis for patients with a disease free interval of 36 months or more, unilateral metastasis and 4 or less metastases. Conclusion: The survival rate for completely resectable pulmonary metastasectomy was favorable. The disease free interval, laterality and the number of metastasis were the prognosis factors. Key words: 1. Metastasectomy 2. Neoplasm metastasis 3. Survival analysis 4. Risk analysis (Korean J Thorac Cardiovasc Surg 2007;40: ) 서론전이성폐암은폐에서발생하는종양중가장많으며폐암이외의암환자중 20 30% 에서발견되고이들중 15 20% 는폐이외의다른장기로의전이는발견되지않는다 [1]. 또한전이성폐암의수술적치료에대한병리생리학적당위성이밝혀지고수술로인한이환율과사 망률이낮으며, 수술후장기생존율의향상이증명됨에따라이미많은수술이이루어지고있다 [2]. 하지만장기생존에영향을미치는예후인자에대해서는아직명확하게정립되어있지않은상태이다. 전이성폐암에관한가장큰규모의연구는 1997년 International Registry of Lung Metastases (IRLM) 에의해이루어졌으며, 이들은유럽과북미 18개기관에서 5,206 * 경북대학교의과대학부속병원흉부외과학교실 Department of Thoracic and Cardiovascular Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine 본논문은대한흉부외과학회제 38 차추계학술대회에서포스터발표되었음. 논문접수일 :2007 년 4 월 16 일, 심사통과일 :2007 년 8 월 10 일책임저자 : 류경민 ( ) 대구중구삼덕동 2 가, 경북대학교병원흉부외과 (Tel) , (Fax) , cskmin@naver.com 본논문의저작권및전자매체의지적소유권은대한흉부외과학회에있다. 674

2 이영옥외전이성폐암의수술 Table 1. Pathology of primary tumor Carcinomas 55 Colorectal carcinoma 35 Hepatocellular carcinoma 10 Renal cell carcinoma 4 Cervical carcinoma 2 Parotid gland carcinoma 2 Breast cancer 1 Tracheal cancer 1 Sarcoma 30 Osteosarcoma 22 Synovial sarcoma 4 Chondrosarcoma 1 Ewing's sarcoma 1 Rhabdomyosarcoma 1 Alveolar softpart sarcoma 1 Other 4 Schwanoma 2 Melanoma 1 Wilm's tumor 1 명을대상으로연구를시행하였다 [3]. 이연구에서는전이성폐암의예후인자가완전절제여부, 무병생존기간, 폐전이병소의개수라고하였으며이를토대로한새로운병기모델을제시하였다. 국내에서도여러기관에서전이성폐암의수술결과및예후인자에대한연구들을발표하였으나그결과는각발표마다차이가있었다. 이에저자들은최근 10년간시행한전이성폐암의수술적치료결과분석을통해생존에영향을미치는예후인자를밝히고, IRLM에서제시한병기모델에따른생존및예후분석의타당성을연구하고자하였다. 대상및방법 1996년 1월부터 2005년 12월까지전이성폐암으로수술받은 89명의환자를대상으로후향적분석을하였다. 전이성폐암의수술적응으로는완전절제가가능하며, 원발병소및폐이외의다른장기에재발의소견이없으며, 심폐기능이수술에적절한경우로하였다. 환자들의의무기록및추적관찰기록을통하여전이성폐암의유형, 원발종양의세포형, 무병생존기간, 전이성폐암의위치, 병소의크기및개수등에따른장기성적의분석과함께세포유형별에따른각각의장기생존에대해분석 Fig. 1. Cummulative overall survival rate of pulmonary metastasectomy. The 5-year and 10-year survival rate was 32.1%, 20.7% and the median survival time was 38 months. 하였다. 생존곡선은전이성폐암의수술시점을기준으로 Kaplan-Meier 방법을이용하였고, 생존율의비교는단변량분석의경우 log-rank test를통하여 p값이 0.05 미만인경우를유의하다고판정하였고다변량분석의경우는 Cox hazard model을통하여 p값이 0.05 미만인경우를유의하다고판정하였다. 통계의처리는 SPSS ver. 12.0을이용하였다. 결 89명의전이성폐암환자에대하여 96예의폐절제술을시행하였다. 환자의평균연령은 45.9세 (10 75세) 였고, 남성이 51명, 여성이 38명이었다. 추적기간은평균 38개월 (3 110개월) 이었으며모든환자에서추적이가능하였다. 원발종양은암종이 55예 (61.8%), 육종이 30예 (33.8%), 기타암이 4예 (4.4%) 였으며, 기타암에는흑색종이 2예, 윌름씨종양 1예, 신경초종이 1예였다. 암종중에는대장암이 35예 (63.6%) 로가장많았고육종중에는골육종이 22 예 (73.3%) 로가장많았다 (Table 1). 원발종양의진단당시폐전이가있어수술한경우가 3 예 (3.8%) 였으며, 병변의분포는일측성인경우가 59명 (66.3%), 양측성인경우가 30명 (33.7%) 이었다. 2회이상의폐절제술을시행한경우가 15예 (16.8%) 였다. 수술의방법은폐부분절제술 81예, 폐엽절제술 6예, 폐구역절제술 3 예, 전폐절제술 1예, 폐엽절제술과폐부분절제술을동시에시행한경우가 2예, 폐구역절제술과부분절제술을동시에시행한경우가 3예였다. 무병생존기간은평균 과 675

3 대흉외지 2007;40: Fig. 2. Survival between prognostic factor. Univariate and multivariate analysis showed a better prognosis for patients with unilateral metastasis, and 4 or less metastases. Table 2. Analysis of prognostic factors Parameter No. Cancer type Carcinoma 55 Sarcoma 30 Disease free interval <36 months months 29 Laterality Unilateral 55 Bilateral 30 No. of metastasis < Size of metastasis <3cm 52 3cm 33 Univariate p value Multivariate 분석에서는 36개월미만의무병생존기간을가지고있는경우, 양측폐전이로수술한경우, 5개이상의전이병소를가지고있는경우통계적으로의미있게예후가불량하였고, 다변량분석에서는양측폐전이로수술한경우와 5개이상의전이병소를가지고있는경우통계적으로의미있게예후가불량하였다 (Table 2, Fig. 2). 환자가가장많은대장암, 골육종, 간암의폐전이환자에대한생존율에대한분석에서대장암의 3, 5년생존율은 76.6%, 32.4% 였고, 골육종은 74.4%, 45.6%, 간암은 47.4%, 23.1% 였다. IRLM에서제시한병기그룹에따른분류로는 1그룹 14예, 2그룹 26예, 3그룹 41예, 4그룹 4 예였고, 특히 4그룹은수술후병리검사에서절제연에종양이남아있다고보고된경우였다. 5년생존율은 1그룹 63.4%, 2그룹 33.3%, 3그룹 22.1%, 4그룹 0% 로, 그룹간의생존율은차이를보였으나통계학적인의미는없었다 (Table 3, Fig. 3). 고찰 29±27.9개월 (0 110개월) 이었다. 병리학적으로확진된전이성폐종양의개수는평균 4.8개 (1 33개) 였고절제된폐종양의크기는평균 2.9 cm ( cm) 였다. 기타암으로분류한 4예를제외한암종과육종환자 85 명을대상으로하여생존율및예후에대한분석을시행하였다. 이들환자의 3, 5, 10년생존율은 52.5%, 32.1%, 20.7% 였고, 중앙생존기간은 38개월이었다 (Fig. 1). 성별, 원발종양의병리소견, 무병생존기간, 병변의분포, 병소의개수및크기등에따른생존율의분석결과단변량 전이성폐암은병소의완전절제가가능하다면수술로서장기생존율을높일수있다는사실은이미여러연구를통하여입증된상태이다. 이에대한이론적근거로는첫째, 최근항암화학요법의진보에도불구하고고형종의일차적치료는절제라는점이며둘째, 인체를순환하는모든혈액은폐의모세혈관을통과하므로순환하는종양세포는폐의모세혈관에서여과되기때문에종양의더이상확산을예방할수있고셋째, 고형종은혼합세포군으로구성되어있어항암화학요법후에남아있 676

4 이영옥외전이성폐암의수술 Table 3. Survival between IRLM appraisal group Mean Group (n) 3YSR (%) 5YSR (%) survival (month) I (n=14) (DFI 36 months and single metastasis) II (n=26) (DFI<36 months or multiple metastasis) III (n=41) (DFI<36 months and multiple metastasis) IV (n=4) (Unresectable) IRLM=International registry of lung metastases; DFI=Disease free interval; 3YSR=3-year survival rate; 5YSR=5-year survival rate. 는종양세포는항암제에효과가없는것으로알려져있기때문에이러한종양은절제되어야하며넷째, 병변의조직학적인확진을위해서도외과적절제술이필요하다는것이다 [3,4]. 그러나전이성폐암환자의수술여부를결정하는기준이나수술후장기생존에미치는예후인자등에관해서는아직까지여러가지이견이있으며정립되어있지않은상태이다. 1958년 Ehrenhaft 등이전이성폐암의수술적치료에관한기준을처음기술하였는데점점그기준이확대되어현재통용되고있는기준은첫째, 원발종양이완치된상태이고둘째, 폐이외다른장기로의전이가없거나전이가있더라도치유가가능해야하며셋째, 전이성폐암이절제가능한종양이고넷째, 병변의절제후에도회복가능한폐기능을갖고있어야하고, 다섯째, 환자의전반적인건강상태가수술을견딜수있을만한상태이어야한다 [5-7]. 본원에서도수술적응증의기준을확대하여원발종양을수술적으로제거하지않고도약물치료와방사선치료후에방사선검사상원발부위에재발의소견이없어완전관해에해당한다고판단되는경우도위의기준에합당하다면수술을시행하였다 [3,7]. 전이성폐암의절제범위는전이된병소의완전절제를원칙으로하면서도그범위에있어서는저자마다약간의차이가있는데본원에서는정상폐조직을가능한한많이남김으로써술후환자의폐기능을최대한유지시키려하였으며환자의약 84% 에서폐부분절제술을시행하였다. 전폐절제술을 1예에서시행하였는데이환자의경우는대장암전이로인하여좌폐문부를포함한좌 Fig. 3. Survival between IRLM subgroup. There was no statistical significance. IRLM=International registry of lung metastases. 측폐에다발성으로전이암이발견된경우로폐엽절제술및폐쐐기절제술을계획하였으나종양의위치가좌측주기관지를침범하였고, 환자의전신상태가양호하여시행한경우였다. 5,206명의전이성폐암환자를대상으로한 IRLM의연구 [3] 에서는수술후예후인자로무병생존기간, 완전절제여부, 폐전이병소의개수를들었으며이와같은예후인자를통해새로운병기모델을제시하였다. 무병생존기간은원발종양의치료시기부터폐전이가확인된시점까지의기간을말하며 IRLM의연구에서 36개월을기준으로나누어비교하였을때생존율에유의한차이가있음을보고하였으며 Rena 등 [8] 의연구에서도비슷한결과를보고하였다. 그러나 Okumura 등 [9] 과 Yano 등 [10] 은직장-대장암에서폐로전이된병소의수술후예후에관한연구에서무병생존기간에따른수술후예후의차이를발견하지못했다. 본원의경우단변량분석에서는의미가있었으나 (p=0.03) 다변량분석에서는통계적으로유의하지않았다 (p=0.08). 이는강정한등 [11] 이생존율의감소는보이나통계적으로유의하지않았다고보고한것과비슷한결과이며, 아마도환자의수가적어통계적인검정력이떨어진것으로생각되어, 환자의수가늘면통계적인의미가있을것으로생각된다. 전이성폐암의개수에따른수술후예후에관해서도저자마다다른결과를나타내고있다. IRLM의연구 [3] 와 Rena 등 [8] 의연구에서는고립성일경우가다발성일경우보다예후가더좋은것으로보고하였으며 Okumura 등 [9] 은직장-대장암환자에서전이성폐암의병소가두개이하인경우가세개이상인경우보다수술후장기성적이의 677

5 대흉외지 2007;40: 미있게좋은결과를나타냄으로써전이성폐암의개수가수술후예후와상관관계가있다고하였다. 반면에 Robert 등 [12] 은 276예의다양한세포형의전이성폐암의연구를통해서고립성일경우와다발성일경우수술후장기성적에차이가없다고하였고 Jablons 등 [13] 은전이성폐암의완전절제가가능하다면전이병소의개수는중요하지않다고하였다. 본원의경우전이암병소의개수가네개이하인경우가다섯개이상인경우보다통계적으로의미있게예후가좋은것으로나타났다 (p=0.001). 양측성전이여부에대해서는 Inoue 등 [14] 은 128명의전이성폐암환자의연구에서일측성병소보다양측성병소인경우가유의하게예후가더좋지않다고보고하면서양측성전이여부가중요한예후인자가될수있다고주장하였다. 그러나 Takita 등 [4] 과 Jablons 등 [13] 은전이된병소의완전절제가이루어질경우수술후예후에는차이가없다고보고하였다. 본원에서는일측성과양측성전이사이에유의한생존율의차이가있었다 (p=0.005). 전이된폐결절의크기는많은연구결과 [9,10,14] 에서예후와영향이없다고보고되었으며본연구에서도크기가 3 cm 이상인경우와그미만인경우통계학적으로유의한생존율의차이를보이지않았다. 원발성종양의세포형에따른예후의변화는크게암종과육종으로나누어비교할수있다. Thomford 등 [6] 은암종이육종에비해장기성적이우수하다고발표하였으나 Takita 등 [4] 과 Rena 등 [8] 은암종과육종사이에예후의차이가없다고하였으며본연구결과에서도예후와관련이없었다. 전이성폐암의수술접근법에있어서개흉술과비디오흉강경수술 (VATS) 의차이에대해서도여러이견이있다. Landreneau 등 [15] 은 VATS가개흉술보다술후유착이적게생기고비침습적이므로술전 CT 소견을정확하게비교분석하여크기와위치가적합한경우에비디오흉강경절제술을시행하면효과적인치료가가능하다고주장하였다. 그러나 McCormack 등 [16] 은술전 CT 검사에나타난전이성폐암을 VATS로절제한후개흉술로확인한결과정확도가 22% 임을발표하면서개흉술과수술시촉진에의한절제가전이성폐암의표준수술법이라고주장했다. 전이성폐암의수술적절제후예후에가장큰영향을미치는것이완전절제이며일반적으로 CT 검사상의병소의개수와수술시촉진에의한병소의개수가다를수있기때문에본원에서도개흉술을통한수술을원칙으로하고있으며말초성단일병소 인 5명의환자들에서만제한적으로비디오흉강경수술을시행하였는데, 5명의환자에서재발은없었으나, 향후추가적인연구를통해 VATS로수술한환자들에대한재발및예후에대한평가가이루어져야된다고생각한다. 결 전이성폐암의수술적치료는안전하면서도완전절제가가능할경우높은장기생존율을기대할수있다. 본연구에서는 36개월미만의무병생존기간을가지고있는경우, 양측폐전이로수술한경우, 5개이상의전이병소를가지고있는경우통계학적으로예후가불량하였으나전이성폐암의수술후예후에미치는인자에대해서는연구결과마다다르므로이에대한결정하기위해서는보다많은경험과장기적인관찰이필요할것으로생각한다. 론 참고문헌 1. Hammar SP. Common neoplasm. In: Dail DH, Hammar SP. Pulmonary pathology. 1st ed. New York. Springer Verlag. 1988; Mountain CF, McMurtrey MJ, Hermes KE. Surgery for pulmonary metastasis: a 20-year experience. Ann Thorac Surg 1984;38: Pastorino U, Buyse M, Friedel G, et al. Long-term reselts of lung metastasectomy: prognostic analyses based on 5,206 cases. J Thorac Cardiovasc Surg 1997;113: Takita H, Edgerton F, Karakousis C, Douglass HO, Vincent RG, Beckley S. Surgical management of metastases to the lung. Surg Gynecol Obstet 1981;152: Ehrenhaft JL, Lawrence MS, Sensenig DM. Pulmonary resection for metastatic lesions. Arch Surg 1958;77: Thomford NR, Woolner LB, Clagett OT. The surgical treatment of metastatic tumors in the lungs. J Thorac Cardiovasc Surg 1965;49: Kondo H, Okumura T, Ohde Y, Nakagawa K. Surgical treatment for metastatic malignancies. Pulmonary metastasis: indications and outcomes. Int J Clin Oncol 2005;10: Rena O, Papalia E, Oliaro A, et al. Pulmonary metastases from epithelial tumors: late results of surgical treatment. Eur J Cardiothorac Surg 2006;30: Okumura S, Kondo H, Tsuboi M, et al. Pulmonary resection for metastatic colorectal cancer: experiences with 159 patients. J Thorac Cardiovasc Surg 1996;112:

6 이영옥외전이성폐암의수술 10. Yano T, Hara N, Ichinose Y, et al. Results of pulmonary resection of metastatic colorectal cancer and its application. J Thorac Cardiovasc Surg 1993;106: Kang JH, Paik HC, Lee JG, Chung KY. Analysis of pulmonary metastases according to a new staging proposal. Korean J Thorac Cardiovasc Surg 2001;34: Robert DG, Lepore V, Cardillo G, et al. Long-term follow-up of operative treatment for pulmonary metastases. Eur J Cardiothorac Surg 1989;3: Jablons D, Steinberg DM, Roth JA, Pittaluga S, Rosenberg SA, Pass HI. Metastasectomy for soft tissue sarcomas. J Thorac Cardiovasc Surg 1989;97: Inoue M, Ohta M, Iuchi K, et al. Benefits of surgery for patients with pulmonary metastases from colorectal carcinoma. Ann Thorac Surg 2004;78: Landreneau RJ, De Giacomo T, Mark MJ, et al. Therapeutic video-assisted thoracoscopic surgical resection of colorectal pulmonary metastases. Eur J Cardiothorac Surg 2000;18: McCormack PM, Bains MS, Beqq CB, et al. Role of video-assisted thoracic surgery in the treatment of pulmonary metastases: results of a prospective trial. Ann Thorac Surg 1996;62: = 국문초록 = 배경 : 완전절제가가능한고형암의폐전이에대한절제술은이미표준화된치료방법이며, 1997 년 International Resistry of Lung Metastases (IRLM) 에서대규모의연구를통해전이성폐암에대한병기설정및예후인자에관하여제시한바있다. 국내에서도전이성폐암에대한수술이꾸준히증가하고있으며, 치료방법의개선에따른생존율역시좋아지는추세이다. 이에경북대학교병원흉부외과에서는지난 10 년간전이성폐암으로수술을받은환자들의치료결과에대해서조사하였다. 대상및방법 : 1996 년 1 월부터 2005 년 12 월까지전이성폐암환자 89 명에대해서 96 예의폐절제술을시행하였다. 이들의의무기록을토대로생존율및예후에영향을미치는임상적, 병리학적요인에대하여분석하였다. 결과 : 환자의평균나이는 45.9±17.4 세 (10 75 세 ) 였으며, 남성이 51 명, 여성이 38 명이었다. 이중암종의폐전이가 55 예, 육종인경우가 30 예, 기타 4 예였다. 암종중에서는대장암이 35 예 (64%), 육종중에서는골육종이 22 예 (73%) 로가장많았다. 원발암치료후부터폐절제술까지의종양자유기간은평균 29.6±27.9 개월 (0 180 개월 ) 이었으며, 원발암과동시에발견된경우는 3 예 (3.4%) 였다. 전체환자들의 3, 5, 10 년생존율은각각 52.5%, 32.1%, 20.7% 였고중앙생존기간은 38 개월이었다. 재수술은 15 예 (16.8%) 에서시행하였다. IRLM 제시에따른병기별 5 년생존율은 1 기 63.5%, 2 기 33.3%, 3 기 22.1%, 4 기 0% 였다. 36 개월미만의종양자유기간, 양측폐전이, 5 개이상의전이병소를가진경우예후가좋지않았다 (p<0.05). 결론 : 완전절제가가능한전이성폐암에대한폐절제술은만족할만한생존율을보였으며, 특히양측의다발성전이가있는경우예후가불량함을보였다. 하지만각종양별로의치료성적및예후에관한보다많은경험과추적관찰이필요하겠다. 중심단어 :1. 전이절제술 2. 종양전이 3. 생존분석 4. 위험인자분석 679

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