대한한방내과학회지제 37 권 2 호 (2016 년 5 월 ) J. Int. Korean Med. 2016:37(2)412-419 한방병원에입원한노인암환자의치료특성분석 오혜경, 이지영, 류한성, 윤성우강동경희대학교병원한방암센터한방내과 Analysis of Clinical Characteristics and Treatments among Geriatric Cancer Patients Hospitalized in a Traditional Korean Medical Hospital Hye-kyung Oh, Jee-young Lee, Han-sung Ryu, Seong-woo Yoon Dept. of Internal Medicine, Korean Medicine Cancer Center, Kyung Hee University Hospital at Gangdong ABSTRACT Objective: Because the number of geriatric cancer patients is on the rise but information on treatments for this population is limited, this study aimed to analyze clinical characteristics and the factors that influence treatment decisions among elderly cancer patients. Method: Data on elderly cancer patients ( 65 years of age) who were admitted to a traditional Korean medicine hospital from March 2014 to February 2016 were collected. We compared the clinical characteristics and overall survival rates of the chemotherapy group and the non-chemotherapy group. Results: Nineteen patients were included in this study. Nine people received chemotherapy, and ten people did not receive chemotherapy due to concerns about quality of life. Age, activities of daily living (ADL) score, and Eastern Cooperative Oncology Group (ECOG) performance status all showed differences between the two groups, although median survival times did not differ significantly between the two. Compared with chemotherapy alone, traditional Korean medicine combined with chemotherapy prolonged median survival times. Conclusion: Old age and low ECOG performance status and ADL scores appear to be influential factors for the decision to undergo chemotherapy. Further studies are needed to confirm that these factors influence decisions about cancer treatment methods among geriatric cancer patients. Key words: geriatric cancer patients, chemotherapy, Korean medicine hospital Ⅰ. 서론 미국의한연구에따르면 65세이상의노인층에서매년암발병률이 50% 씩증가하고있으며 50년후에는노인암환자가현재의 2배가될것이라고 투고일 : 2016.04.01, 심사일 : 2016.05.30, 게재확정일 : 2016.05.31 교신저자 : 윤성우서울시강동구동남로 892 강동경희대학교병원한방암센터한방내과 TEL: 02-440-7279 FAX: 02-440-7287 E-mail: stepano212@hanmail.net 한다 1. 우리나라의경우도 65세이상의노인의경우 11명당 1명 ( 전체노인인구대비 9.2%) 이암환자이고노인암환자가전체암환자의 40.7% 로 2 노인암환자에대한중요성이점점증가하고있으며이에따라사회적관심도증가하고있다. 그러나암환자를위한치료지침연구에이러한노인인구는배제되어있기때문에현행치료지침은노인암환자에게적합하다고할수없을것이다 3. 노인암환자에게성인암환자와동일한표준치료가생존기간연장에기여하는등동일한 412
오혜경 이지영 류한성 윤성우 이득을보이고있다는긍정적인연구 4,5 결과도있으나, 노인암환자에게항암치료는생존기간연장의효과가적으며 6 오히려취약한계층에서심각한독성보고비율이높아부정적인결과를초래할수있다는상반된연구결과가있었다 7. 이에따라최근세계적으로노인암환자의건강상태평가및치료예후와관련한연구가활발히진행되고있다. 특히일상생활기능, 동반질환, 인지기능, 정서상태, 영양상태등을포함한 CGA(comprehensive geriatric assessment) 를통해노인인구중수술, 항암치료, 방사선치료와같은표준치료에취약한계층을구분하고계획된치료의득실을예측하여환자의상태에맞춰치료계획을세움으로써치료에대한심각한독성및부작용을예방하고치료의성과를높이고자하는노력이증가하고있다 8,9. 한편국내에서도노인암환자들의항암치료현황에대한연구가진행되어국내노인암환자들이성인암환자에비해완화적항암치료 (palliative chemotherapy) 시행률이낮으며 10 또한부작용과전신활동도저하등으로항암치료의중도포기율이높다는것이알려져있으나 11 이러한치료의결정에영향을미치는요인을분석한연구는드물었다. 따라서본연구에서는한방병원에입원한항암치료에적합한 65세이상의노인암환자를대상으로노인암환자의임상적인특성을이해하고자하였으며항암치료에적합한환자군중에서항암치료를받은군과받지않은군각각의특징을비교함으로써치료결정에영향을미치는인자를분석해보고자하였다. Ⅱ. 연구대상및방법 2014년 3월부터 2016년 2월까지강동경희대학교병원한방암센터한방내과에입원한 65세이상의암확진을받은환자를대상으로이중항암치료에적합하지않은환자를제외하였다. 이들중항암치료를받은군과항암치료를받지않은군의 성별, 나이, 병기, 일상생활수행능력, 인지능력, 영양지표, 기저질환, 신체질량지수 (body mass index, BMI), 혈중알부민, 전신활동도를의무기록을통해후향적으로비교및분석하여노인암환자에있어항암치료결정의차이가되는인자를살펴보고자하였다. 또한추가적으로두군간생존기간을분석하여치료의결과를평가해보고자하였다. 일상생활수행능력은 ADL(activities of daily living) 을기준으로평가하였는데이는세면, 식사, 의복의착탈, 용변, 입욕등의행위가가능한지평가하며낮을수록기능이떨어지는지표이다. 영양지표는강동경희대학교병원에서개발한 KNNRS(Kyung Hee neo nutrition risk screening) 12 을사용하였는데, 이지표는혈중 albumine, hemoglobin, lymphocyte count, 표준체중백분율, 연령, 진단명, 식이형태를포함한객관적지표와식욕부진, 구토, 메스꺼움, 설사등식사시문제점을평가하는주관적지표로구성되어있으며 0점에서 20점으로평가하여높을수록위험도가높다. 또한기저질환은 CCI(Charlson comorbidity index) 를통해평가하였는데이는기저질환의종류와중증도를반영한지표로 0~37점으로구성되어높을수록불량한상태를의미한다. 전신활동도는 ECOG(Eastern cooperative oncology group) 을기준으로하였는데 ECOG은 0~4로구성되어정상적활동도를가지면 0, 불량한활동도를가질수록 4로점수가높아진다. 통계는 SPSS 18.0 version 을사용하여두집단간의차이를독립표본 t 검정혹은카이제곱검정을통해비교하였고, Kaplan-Meier 생존함수를이용하여생존분석을시행하였다. Ⅲ. 결과 2014년 3월부터 2016년 2월까지입원한 65세이상의암환자는총 41명이있었다. 이중항암치료에적합한환자는기대여명 3개월미만의임종간호 (terminal care) 대상자 11명, 현재암이존재하 413
한방병원에입원한노인암환자의치료특성분석 지않는상태 (no evidence of disease) 인환자 3명, 지지요법 (best supportive care) 만을권유받은환자 6명, 수술을권유받은환자 2명을제외한 19명 이었다. 항암치료에적합한 19명의환자중 9명 (47.37%) 은항암치료를시행하였으나, 10명 (52.63%) 은항암치료를받지않았다 (Fig. 1). Fig. 1. Flow chart. 1. 환자군의일반적특징전체 19명의환자군의성비는남자 11명, 여자 8 명으로비슷하였고, 평균연령은 75.1세 (67-85) 였다. 원발암의경우소화기계 7명, 폐 6명, 간담도계 3명이었으며, 기타뇌종양, 두경부암, 흑색종환자가 1명씩있었다. 16명의환자들은 Ⅳ기에해당하였고, Ⅱ기환자가 2명, Ⅲ기환자가 1명있었다. 8 명의환자는수술, 항암치료, 방사선치료를기존에받지않았다. 그밖에수술을경험한환자는 8명, 항암치료를경험한환자는 5명, 방사선치료를경험한환자는 1명이있었다. 동반질환의경우혈압, 당뇨 등순환기계통의질환을가진환자가 16명으로가장많았고, 중풍과파킨슨을포함하는중추신경계문제를동반하는환자가 3명, 치매등의정신과적문제를가진환자가 2명, 호흡기질환을가진환자가 2명, 근골격계질환을가진환자는 3명이있었다. 환자들의전신활동도는다양하였는데, EOCG 을기준으로 1인환자는 4명, 2인환자는 9명, 3인환자는 4명, 4인환자는 2으로나타나 ECOG 3 이상인환자가 6명 (31.58%) 있었으며환자들의평균재원기간은 16.26±11.98일이었다 (Table 1). 414
오혜경 이지영 류한성 윤성우 Table 1. Demographic and Characteristics of Patients Total (n=19) n (%) or mean (range) Male 11 (57.89%) Gender Female 8 (42.11%) Age 75.1 (67-85) Tumor origin Stage Treatment history Comorbidity ECOG PS Gastrointestinal 7 (36.84%) Lung 6 (31.58%) Hepatobiliary 3 (15.79%) Neurological 1 (5.26%) Head and neck 1 (5.26%) Melanoma 1 (5.26%) Ⅰ 0 (0%) Ⅱ 2 (10.53%) Ⅲ 1 (5.26%) Ⅳ 16 (84.21%) Surgery 8 (42.11%) Chemotherapy 5 (26.32%) Radiotherapy 1 (5.26%) Treatment naive 8 (42.11%) Cardiovascular 16 (84.21%) Central nervous system 3 (15.79%) Psychiatry 2 (10.53%) Pulmonary 2 (10.53%) Musculoskelectal 3 (15.79%) 1 4 (21.05%) 2 9 (47.37%) 3 4 (21.05%) 4 2 (10.53%) ECOG PS : Eastern cooperative oncology group performance status 2. 항암치료를받은군과받지않은군의의학적특징비교항암치료에적합한 19명의노인암환자중 9명은항암치료를받았고, 10명의환자는삶의질저하를우려하여항암치료를받지않았다. 항암치료를받은군과받지않은군은각각남자 5명대 6명, 여자 4명대 4명으로남녀비율에차이가없었고, 평균연령은항암치료를받은군 72.8세 (67-82), 항암치료를받지않은군 77.1세 (69-85) 로차이가있었다 (p=0.07). 항암치료를받은군과받지않은군은 IV기환자가각각 8명 (88.89%), 8명 (80%) 으로유사하였고, 일상생활수행능력의지표인 ADL의경우 4.67±1.83점, 2.87±1.99점으로항암치료를받지않은군이낮은것을알수있었다 (p=0.05). 인지와관련한문제가있는환자는항암치료를선택한군에서는없었으나항암치료를받지않는군에서는 2명 (20%) 이있었다. 영양상태지표인 KNNRS 의경우항암치료를받은군과받지않은군은각각 4.89±2.73점, 4.8±1.32점으로유사하였고, 동반질환지표인 CCI은각각 9.11±2.08점, 10.5±1.18점으로큰차이는없었다. 항암치료를받은군에서는저체중군이없었으나, 항암치료를받지않은군에서저체중군의비율이 2명 (20%) 으로대조적이며, 저알부민혈증환자의경우항암치료를받은군에서는 2명 (22.22%) 인반면항암치료를받지않은군에서는 5명 (50%) 이있었다. 두군간전신활동도는 ECOG 3 이상의환자의비율이항암치료를시행한군에서는 1명 (11.11%), 항암치료를받지않은군에서는 5명 (50%) 으로차이를보였다 (p=0.07) (Table 2). 415
한방병원에입원한노인암환자의치료특성분석 Table 2. Comparison of Characteristics between Chemotherapy Group and Non-Chemotherapy Group Chemotherapy group Non-chemotherapy group (n=9) (n=10) p value Gender Male 5 (55.56%) 6 (60%) Female 4 (44.44%) 4 (40%) 0.85* Age 72.8 (67-82) 77.1 (69-85) 0.07 I 0 (0%) 0 (0%) Stage Ⅱ 1 (11.11%) 1 (10%) Ⅲ 0 (0%) 1 (10%) 0.62* Ⅳ 8 (88.89%) 8 (80%) Functional status ADL 4.67±1.83 2.8±1.99 0.05 Cognitive disorder Yes 0 (0%) 2 (20%) No 9 (100%) 8 (80%) 0.16* Nutrition status KNNRS 4.89±2.73 4.8±1.32 0.93 Comorbidity CCI 9.11±2.08 10.5±1.18 0.10 BMI < 18.5 kg/m 2 0 (0%) 2 (20%) 0.16* Serum Albumin < 3.5 mg/dl 2 (22.22%) 5 (50%) 0.21* ECOG PS 0~2 8 (88.89%) 5 (50%) 3~4 1 (11.11%) 5 (50%) 0.07* * : p values for independent test for categorical variables were obtained by chi-square test. : p values for comparison of mean difference for continuous variables were obtained by independent t-test. ADL : activities of daily living, KNNRS : Kyung Hee neo nutrition risk screening, CCI : Charlson comorbidity index, BMI : Body Mass Index, ECOG PS : Eastern cooperative oncology group performance status 3. 생존분석결과논문작성을위해 2016년 3월을기점으로사망일을조사한결과항암치료를받은군은 9명중 5 명이사망하였고, 항암치료를받지않은군은 10명중 8명이사망하였다. 그룹간중앙생존기간은항암치료를받은군에서는 9.6개월 (4.4-14.9), 항암치료받지않은군에서는 4.1개월 (1.4-6.9) 로차이를보였으나, 통계학적으로의미는없었다 (p=0.55) (Fig. 2a). 항암치료를받은 9명의환자중 4명의환자는항암치료만을단독으로받았고 5명의환자는항암치료와더불어한방치료를병행하였다. 항암치료만을시행한환자의경우 4명중 4명이사망하였고중앙생존기간은 3.9개월 (2.8-5.0) 인반면, 한방치료와병행치료를시행한군의경우 5명중 3명이사망하였고, 중앙생존기간은 10.2개월 (9.3-11.1) 로통계학적으로유의한차이를보였다 (p=0.007)(fig. 2b). 416
오혜경 이지영 류한성 윤성우 Fig. 2. Survival analysis of geriatric cancer patients. (a) Overall survival for all patients. Median survival time in non-chemotherapy group and chemotherapy group was 4.1 months (1.4-6.9) and 9.6 months (4.4-14.9) respectively (p=0.55). (b) Overall survival for chemotherapy group. Median survival time in chemotherapy alone and chemotherapy combined with traditional Korean medicine was 3.9 months (2.8-5.0) and 10.2 months (9.3-11.1) respectively (p=0.007). CTx : chemotherapy, TKM : traditional Korean medicine Ⅳ. 고찰및결론노인암환자에게성인암환자에서와같은표준치료를적용하는것은논란의여지가있다. 70세이상의전이된대장암환자를대상으로한연구에서 Fluorouracil 을기반으로한항암치료결과성인암환자와유사하게생존기간이연장되었고 4, 초고령인 75세이상의환자를대상으로한연구에서도노인암환자와성인암환자간항암치료에의한생존기간연장및부작용발생은비슷했다 5. 그러나급성골수성백혈병노인암환자의항암치료에대한연구에서나이는독자적인위험인자이며 75 세이상의경우표준적인항암치료를통한기대여명증진이득이적을수있음을보여주고있었다 6. 또한다양한원발부위를포괄하는 65세이상의전이암환자를대상으로한연구에서항암치료시노인암환자의경우심각한부작용이유의미하게높게나타나노인암환자의항암치료시독성 에대한고려가필수적임을시사하고있었다 13. 이렇듯노인암환자의치료의결과에대한연구가상반된결론을도출하는것은노화의과정은개인별로상이하고생체학적기능의감소는이에따라개인별로큰차이를가질수있어노인이라는집단자체가이질성이크기때문이다 14. 본연구에서고령, 전신활동도저하, 일상수행능력이제한된노인암환자일수록항암치료를받지않는것으로나타났으며그들은전신활동도저하에대한우려및삶의질유지를위해항암치료를받지않은것으로나타나노인암환자들에게활동및기능의유지가중요한요소임을확인할수있었다. 또한암환자에게있어환자개인의전신활동도, 일상생활수행능력, 인지기능, 동반질환, 영양상태와같은기능적인지표는중요한생존예후인자로이런생체학적기능이불량한환자들은기대여명이짧은것으로알려져있다 15-17. 따라서노인암환자에있어서전신활동도, 일상생활수행 417
한방병원에입원한노인암환자의치료특성분석 능력과같은치료결정에영향을미치는인자가생존예후인자와도관련되어있음을확인할수있었다. 또한생존분석결과항암치료를받은군과항암치료를받지않은군간에생존기간에유의미한차이는없었으나항암치료를받은환자중한방치료를함께받은군이그렇지않은군에비해중앙생존기간이유의미하게길게나타났다. 기존의연구결과항암치료와병행한한방치료의경우항암치료의부작용을완화시켜주는효과가있고면역기능을향상시키며암과관련한증상을완화시킨다 18 는보고가있어관련한후속연구가필요할것으로사료된다. 노인암환자들은고령, 전신활동도, 일상생활수행능력이저하되어있을수록항암치료를받지않는것으로나타났으며항암치료를받는군에서한방치료와병행하였을때생존기간연장의이득이더큰것으로나타나노인암환자의치료계획에있어서예후인자와관련된평가를하여그에적합한치료방향을결정하는것은바람직할것이라고생각된다. 그러나여전히 ECOG 이 3 이상으로전신활동도가불량하거나인지장애가있는경우에도항암치료를권유받는환자가있었고항암치료를받은군과받지않은군간에생존과관련한다른예후인자로도알려진 15-17 동반질환지표나영양지표간에는큰차이가없어임상현장에서노인암환자에대한이해가더욱필요할것으로생각된다. 본연구는소규모의후향적인연구로대상자가한방병원의입원환자로제한적이고다양한원발암을포함하여이질성이크다는점에서그한계가있다. 추후노인암환자의치료결과에영향을끼칠수있는인자에대한분석및한방치료와의병행을통한생존연장, 삶의질증진과관련한대규모전향적연구가진행되어노인암환자의생존기간연장에기여할수있는치료지침이제시되기를기대한다. 참고문헌 1. United States Census: U.S. Census Bureau projections show a slower growing, older, more diverse nation a half century from now. Available form: http://www.census.gov/newsroom/releases/ archives/population/cb12-243.html 2. National Cancer Information Center. Available form: http://www.cancer.go.kr/mbs/cancer/subview. jsp?id=cancer_040401000000 3. Hutchins LF, Unger JM, Crowley JJ, Coltman Jr CA, Albain KS. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 1999;341(27):2061-7. 4. Folprecht G, Seymour MT, Saltz L, Douillard JY, Hecker H, Stephens RJ, et al. Irinotecan/ Fuorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials. J Clin Oncol 2008;26(9):1443-51. 5. Miguchi M, Shimomura M, Hinoi T, Egi H, Ohdan H. Chemotherapeutic outcomes for metastatic colorectal cancer in elderly patients aged 75 years: A single-institutional retrospective analysis. Asia Pac J Clin Oncol 2016;12(2):151-8. 6. Malfuson JV, Etienne A, Turlure P, de Revel T, Thomas X, Contentin N, et al. Risk factors and decision criteria for intensive chemotherapy in older patients with acute myeloid leukemia. Haematologica 2008;93(12):1806-13. 7. Hamaker ME, Seynaeve C, Wymenga AN, van Tinteren H, Nortier JW, Maartense E, et al. Baseline comprehensive geriatric assessment is associated with toxicity and survival in elderly metastatic breast cancer patients receiving single-agent chemotherapy: Results from the 418
오혜경 이지영 류한성 윤성우 OMEGA study of the Dutch Breast Cancer Trialists Group. Breast 2014;23(1):81-7. 8. Presley C, Lilenbaum R. The Treatment of Advanced Lung Cancer in the Elderly : The Role of a Comprehensive Geriatric Assessment and Doublet Chemotherapy. Cancer J 2015;21(5): 392-7. 9. Hurria A. Management of elderly patients with cancer. J Natl Compr Canc Netw 2013;11:698-701. 10. Park SY. Safety and efficacy of adjuvant therapy after surgery of elderly colon cancer patients 70 years of age or older. Master's thesis, Dept. of Medicine, Chung-Ang University 2015. 11. Shin GY. Study on current use of chemotherapy in elderly patients with colorectal cancer. Master's thesis, Dept. of Clinical Health Science, Ewha Womans University 2012. 12. Lee JS, Cho MR, Lee GJ. Validation of the developed nutritional screening tool for hospital patients. Korean J Nutr 2010;43(2):189-96. 13. Jatoi A, Foster NR, Egner JR, Burch PA, Stella PJ, Rubin J, et al. Older versus younger patients with metastatic adenocarcinoma of the esophagus, gastroesophagealjunction, and stomach : a pooled analysis of eight consecutive North Central Cancer Treatment Group(NCCTG) trials. Int J Oncol 2010;36:601-6. 14. Saif MW, Lichtman SM. Chemotherapy options and outcomes in older adult patients with colorectal cancer. Crit Rev Oncol Hematol 2009;72:155-69. 15. de Kock I, Mirhosseini M, Lau F, Thai V, Downing M, Quan H, et al. Conversion of Karnofsky Performance Status(KPS) and Eastern Cooperative Oncology Group Performance Status(ECOG) to Palliative Performance Scale(PPS), and the interchangeability of PPS and KPS in prognostic tools. J Palliat Care 2013;29(3):163-9. 16. Ommundsen N, Wyller TB, Nesbakken A, Jordhøy MS, Bakka A, Skovlund E, et al. Frailty is an independent predictor of survival in older patients with colorectal cancer. Oncologist 2014;19(12): 1268-75. 17. Maltoni M, Caraceni A, Brunelli C, Broeckaert B, Christakis N, Eychmueller S, et al. Prognostic factors in advanced cancer patients: evidence-based clinical recommendations-a study by the Steering Committee of the European Association for Palliative Care. J Clin Oncol 2005;23:6240-8. 18. Qi F, Zhao L, Zhou A, Zhang B, Li A, Wang Z, et al. The advantages of using traditional Chinese medicine as an adjunctive therapy in the whole course of cancer treatment instead of only terminal stage of cancer. Biosci Trends 2015;9(1):16-34. 419