Albumin-Alkalen Fosfataz Oranının (Aapr) Küçük Hücreli Dışı Akciğer Kanserinde Prognoza Etkisi

Abstract

Lung cancer is the most frequently diagnosed solid cancer worldwide, originating from the respiratory tract or lung parenchyma. Despite developing treatment modalities, investigation of factors related to disease prognosis and treatment response continues. Studies have shown that albumin-alkaline phosphatase ratio (AAPR), a new marker combining serum albumin and serum alkaline phosphatase, has an important prognostic value in various cancer types, especially hepatocellular carcinoma. The aim of our study is to investigate the effects of AAPR on prognostic parameters in patients diagnosed with non-small cell lung cancer (NSCLC). Adult patients followed up in our center with the diagnosis of NSCLC between January 2012 and May 2022 were included. Basic demographic and clinical data of the patients, laboratory results, radiological, histopathological and molecular-genetic findings of lung cancer and received treatments were retrospectively analyzed from the hospital electronic database. The predictive prognostic feature of AAPR for overall survival was analyzed by Receiver Operating Characteristics (ROC) analysis. Factors affecting overall (OS) and progression-free survival (PFS) were investigated by multiple regression analysis. The mean age of 306 patients [219 (71.6%) men and 87 (28.4%) women] included in the study was 64.7±10.2 years, and the mean age at diagnosis was 61±10.3 years. ROC analysis showed that AAPR had significant predictive properties for overall survival (AUC: 0.622; 95% CI: 0.558-0.687; p<0.001). When the cut-off value is ≤0.44, the sensitivity of the test in predicting mortality is 60.6%; specificity 60.2%; positive predictive value of 75%; negative predictive value was found to be 43.7%. AAPR at initial diagnosis was low in 164 (53.6%) patients. The frequency of advanced cancer (p=0.003) and median serum CRP levels (p<0.001) were higher in patients with low AAPR than in normal patients. During a median follow-up of 2.98 (0.1-10) years, the 5-year OS rate was 36.2% (95% CI: 30.5-41.9), and the 5-year PFS rate was 22.2% (95% CI: 17.5-26.9). In univariate analysis, low AAPR was found to have a significant effect on OS (p<0.001) and PFS (p=0.002). In the multivariate Cox regression model which including having symptoms at the time of diagnosis and the central tumors, age at diagnosis ≥65 (HR: 1.409, %95GA: 1.047-1.895, p=0.024), male gender (HR: 1.405, %95 GA: 1.013-1.950, p=0.042), ECOG 2-3 (HR: 3.955, %95 GA: 1.565-9.994, p=0.004), AAPR ≤0.44 (HR: 1.374, %95GA: 1.023-1.847, p=0.035), clinical stage 3-4 disease (HR: 2.771, %95 GA: 1.844-4.164, p<0.001) and unresponsiveness to first-line treatment (HR: 3.614, %95 GA: 2.630-4.966, p<0.001) were seen as independent risk factors for OS. On the other hand, ECOG 2-3 (HR: 2.697, %95 GA: 1.068-6.811, p=0.036), clinical stage 3-4 disease (HR: 2.584, %95 GA: 1.813-3.682, p<0.001) and unresponsiveness to first-line treatment (HR: 5.181, %95 GA: 3.694-7,264, p<0.001) were independent predictors of PFS. In our study, it was shown that AAPR was independent risk factor for predicting overall survival in patients with NSCLC in univariate analysis. In this group, low AAPR can be seen due to low serum albumin associated with advanced cancer and increased inflammation and high ALP due to distant metastases.

Keywords: Non-small cell lung cancer, albumin-alkaline phosphatase ratio, survival, progression free survival

Lung cancer is the most frequently diagnosed solid cancer worldwide, originating from the respiratory tract or lung parenchyma. Despite developing treatment modalities, investigation of factors related to disease prognosis and treatment response continues. Studies have shown that albumin-alkaline phosphatase ratio (AAPR), a new marker combining serum albumin and serum alkaline phosphatase, has an important prognostic value in various cancer types, especially hepatocellular carcinoma. The aim of our study is to investigate the effects of AAPR on prognostic parameters in patients diagnosed with non-small cell lung cancer (NSCLC). Adult patients followed up in our center with the diagnosis of NSCLC between January 2012 and May 2022 were included. Basic demographic and clinical data of the patients, laboratory results, radiological, histopathological and molecular-genetic findings of lung cancer and received treatments were retrospectively analyzed from the hospital electronic database. The predictive prognostic feature of AAPR for overall survival was analyzed by Receiver Operating Characteristics (ROC) analysis. Factors affecting overall (OS) and progression-free survival (PFS) were investigated by multiple regression analysis. The mean age of 306 patients [219 (71.6%) men and 87 (28.4%) women] included in the study was 64.7±10.2 years, and the mean age at diagnosis was 61±10.3 years. ROC analysis showed that AAPR had significant predictive properties for overall survival (AUC: 0.622; 95% CI: 0.558-0.687; p<0.001). When the cut-off value is ≤0.44, the sensitivity of the test in predicting mortality is 60.6%; specificity 60.2%; positive predictive value of 75%; negative predictive value was found to be 43.7%. AAPR at initial diagnosis was low in 164 (53.6%) patients. The frequency of advanced cancer (p=0.003) and median serum CRP levels (p<0.001) were higher in patients with low AAPR than in normal patients. During a median follow-up of 2.98 (0.1-10) years, the 5-year OS rate was 36.2% (95% CI: 30.5-41.9), and the 5-year PFS rate was 22.2% (95% CI: 17.5-26.9). In univariate analysis, low AAPR was found to have a significant effect on OS (p<0.001) and PFS (p=0.002). In the multivariate Cox regression model which including having symptoms at the time of diagnosis and the central tumors, age at diagnosis ≥65 (HR: 1.409, %95GA: 1.047-1.895, p=0.024), male gender (HR: 1.405, %95 GA: 1.013-1.950, p=0.042), ECOG 2-3 (HR: 3.955, %95 GA: 1.565-9.994, p=0.004), AAPR ≤0.44 (HR: 1.374, %95GA: 1.023-1.847, p=0.035), clinical stage 3-4 disease (HR: 2.771, %95 GA: 1.844-4.164, p<0.001) and unresponsiveness to first-line treatment (HR: 3.614, %95 GA: 2.630-4.966, p<0.001) were seen as independent risk factors for OS. On the other hand, ECOG 2-3 (HR: 2.697, %95 GA: 1.068-6.811, p=0.036), clinical stage 3-4 disease (HR: 2.584, %95 GA: 1.813-3.682, p<0.001) and unresponsiveness to first-line treatment (HR: 5.181, %95 GA: 3.694-7,264, p<0.001) were independent predictors of PFS. In our study, it was shown that AAPR was independent risk factor for predicting overall survival in patients with NSCLC in univariate analysis. In this group, low AAPR can be seen due to low serum albumin associated with advanced cancer and increased inflammation and high ALP due to distant metastases.

Keywords: Non-small cell lung cancer, albumin-alkaline phosphatase ratio, survival, progression free survival