Outcome and prognostic factors of palliative chemotherapy for non-small cell lung cancer patients at single institution: 2002-2011

Abstract

This study is related to general and clinicopathologic characteristics of non-small cell lung cancer patients who received palliative chemotherapy, overall survival, and factors that affect the survival rates. The study subjects were 402 non-small cell lung cancer patients who received palliative chemotherapy during 10 years from January 2002 to December 2011 at a university hospital. The data were processed using an SPSS 20.0 program and survival rates were analyzed using log rank tests and Cox's proportional hazards model. Major results are as follows. 1. The total number of study patients was 402, their median age was 59 years, and their ages were distributed between 30 years and 80 years. As for the patients' distribution among age groups, 431(84.8%) patients were younger than 70 years and 61(15.2) patients were 70 years old or older. With regard to gender distribution, 259(64.4%) patients were males and 143(35.6%) patients were females with a male/female ratio of 1.81:1 meaning that the number of males was larger by 1.81 times. As for smoking histories, the number of the smoking group was 236(58.7%) and number of the non-smoking group was 145(36.1%) meaning that the number of the smoking group was larger by 1.63 times. 2. As for the study patients' clinicopathologic characteristics, 300(74.6%) patients were in the ECOG performance status (PS) 0,1 groups, 31(7.7%) patients were in the ECOG PS 2,3 groups and 71(17.7%) patients had missing values indicating that palliative chemotherapy was mainly performed in groups with good ECOG PS. As for disease stages, 15(3.7%) patients were in stage IIIA, 48(11.9%) patients were in stage IIIB, 256(63.7%)patients were in stage IV, and 83(20.6%)patients had missing values. As for histologic types, 74(18.4%) patients were squamous cell carcinoma and 328(81.6%) patients were non-squamous cell carcinoma. 3. As for palliative chemotherapy-related characteristics, 296(73.6%) patients received combination chemotherapy as first line therapy and 106(26.4%) patients received single agent chemotherapy as first line therapy. The results of lines of chemotherapy indicated that 163(40.6%) patients received first line therapy only, 124(30.8%) patients received second line therapy, and 115(28.6%) patients received third or later line of therapy. 4. In survival analysis, the median survival period of all patients was 11 months, one year overall survival was 48.3%, two year overall survival was 22.1%, three year overall survival was 12%, and five year overall survival was 3.6%. Univariate analysis showed that variables with statistical significance were sex(p<0.0001), age(p=0.013), smoking history(p<0.0001), ECOG PS(p=0.004), histologic types(p=0.009), lines of chemotherapy(p<0.0001), and disease status(primary advanced or recurrent)(p=0.010). 5. Multivariate analysis showed that sex, the number of times of drug changes, and disease status had statistically significant effects on mortality risks. The analysis with sex showed that the mortality risk of males was higher by 1.4 times than females(p=0.006) and the analysis with the number of times of changes in chemotherapy showed that the mortality risk of second line therapy was 1.8 times higher than that of third or later line of therapy and the mortality risk of first line therapy was 2.3 times higher than that of third of later line of therapy(p<0.0001). The analysis of disease status demonstrated that the mortality risk of the primary advanced lung cancer group was 1.6 times higher than that of the postoperative recurrent lung cancer group(p=0.035) Because this study was conducted with only patients in a university hospital in Suwon, the results cannot represent the characteristics of lung cancer in the entire Korea. This study has a limitation that the quality of information obtained in this study may be a little lower compared to prospective studies because this study is a retrospective study and information bias may be involved. In conclusion, the significance prognostic factors of non-small cell lung cancer patients who received palliative chemotherapy were sex, the number of times of regimen changes, and primary advanced disease status. Mortality risks were shown to be higher among males compared to females, higher in patients who received first or second line of therapy compared with those who received third or later line of therapy, and higher in the primary advanced lung cancer group compared to the postoperative recurrent lung cancer group. In terms of public health, it is considered that studies are necessary to find and treat lung cancer patients earlier along with multilateral nonsmoking policies because the prognosis of lung cancer is very poor if the disease is diagnosed at advanced status and there is no special screening test. In terms of clinical aspects, it is considered that studies of female lung cancer patients with no smoking history and studies for outcome of patients who received first line, second line, third or later line of chemotherapy should be continuously conducted.

본 연구는 고식적 항암화학요법을 받은 비소세포폐암 환자의 일반적 특성, 임상 병리학적 특성, 치료 약제의 생존율과 이에 영향을 미치는 요인에 관한 연구이다. 연구대상은 2002년 1월부터 2011년 12월까지 10년 동안 일개 대학병원에서 비소세포폐암으로 진단받고 고식적 항암화학요법을 받은 환자 402명을 대상으로 분석하였다. 자료는 SPSS 20.0 프로그램을 이용하여 로그 순위 검정과 콕스의 비례위험모형에 의하여 생존율 분석을 하였으며 주요 결과는 다음과 같다. 1. 전체대상자는 402명이고 연구대상자의 중앙연령은 59세 이었고, 30세부터 80세까지 분포하였다. 연령대별 분포는 70세 미만이 431명(84.8%), 70세 이상이 61명(15.2%)으로 분포되어 있다. 성별분포는 남자가 259명(64.4%), 여자가 143명(35.6%)으로 남녀의 비는 1.81:1로 남자가 1.81배 많았다. 흡연력에 있어서는 흡연군 236명(58.7%), 비흡연군 145명(36.1%)으로 흡연군이 비흡연군에 비해 1.63배 많았다. 2. 연구대상자의 임상병리적 특성은 ECOG 활동도 0,1 군은 300명(74.6%), 2,3은 31명(7.7%), 결측치 71명(17.7%)로 ECOG 활동도가 좋은 군에서 고식적 항암화학요법이 주로 시행되는 것으로 나타났으며 병기에서는 IIIA 15명(3.7%), IIIB 48명(11.9%), IV 256명(63.7%), 결측치 83명(20.6%)이었다. 조직형은 편평세포암종 74명(18.4%), 비편평세포암종 328명(81.6%)이었다. 3. 고식적 항암화학요법의 치료관련 특성으로는 1차 요법 중 복합항암화학요법이 296명(73.6%), 단일항암화학요법 106명(26.4%)이었다. 항암화학요법 차수에 따른 조사결과 1차요법 163명(40.6%), 2차 요법 124명(30.8%), 3차 요법 이상은 115명(28.6%)이었다. 4. 생존기간에 따른 분석에서는 전체 중앙생존기간은 11개월, 1년 생존율은 48.3%, 2년 생존율은 22.1%, 3년 생존율은 12%, 5년 생존율은 3.6%이었으며, 단변량 분석에서 통계적으로 유의하게 차이가 있는 변수로는 성별(p<0.0001), 연령별 (p=0.013), 흡연력(p<0.0001), ECOG 활동도(p=0.004), 조직형(p=0.009), 항암화학요법 차수(p<0.0001), 재발여부(p=0.010) 등 이었다. 5. 사망위험률에 관한 다변량 분석에서는 사망에 위험을 미치는 변수로는 성별, 약제 변경 차수, 재발여부가 통계적으로 유의하였다. 여자를 기준으로 남자의 사망 위험도가 1.4배 높았으며(p=0.006), 항암화학요법 변경 차수에 따른 분석에서는 3차 요법 이상을 기준으로 2차 요법이 1.8배, 1차 요법이 2.3배 사망 위험도가 높았다(p<0.0001). 또한 재발여부에서는 수술 후 재발 폐암군에 비해 진행성 폐암군의 사망 위험도가 1.6배 높았다(p=0.035) 이 연구는 수원의 한 대학병원만의 조사 결과이므로 전체 한국 폐암의 특성을 대표하기는 어려우며, 후향적 연구로 정보 비뚤림이 개입되어 전향적 연구에 비하여 다소 정보의 질이 떨어질 수 있다는 한계점을 가지고 있다. 그러나 이 논문의 장점은 단일기관에서 단일질환, 단일치료에 대한 10년 동안의 장기데이터를 생존 추적 조사하였다는데 큰 의의가 있다. 결론적으로 고식적 항암화학요법을 받은 비소세포폐암 환자의 예후인자는 성별, 약제 변경 차수, 재발여부 등 이었다. 여자에 비해 남자가, 3차 요법 이상에 비해 2차 요법, 1차 요법이 수술 후 재발 폐암군에 비해 진행성 폐암군이 사망위험도가 높았다. 보건학적 측면에서는 특별한 선별검사가 없으며 진행된 상태에서 진단 시 예후가 매우 불량한 폐암 환자에 대한 조기발견, 조기치료에 대한 연구와 적극적인 예방 대책으로 금연 정책의 다각적인 대책이 필요하다고 생각된다. 임상적 측면에서는 흡연력이 없는 여성에서의 폐암 환자에 대한 연구와 1, 2차 요법과 3차 요법 이상의 생존율에 대한 연구도 지속적으로 이루어져야 할 것이다.