P2.02-003 Increased Circulating Cytokeratin-19 (Cyfra 21-1) is Predictive of Poor Outcome of Locally Advanced Squamous Cell Carcinoma in Lung

Abstract

Our goal was to evaluate the prognostic significance of circulating tumor markers in locally advanced squamous cell carcinoma of lung (LA-SCCL). Eligible patients included those with histologically proven LA-SCCL, available baseline tumor marker panel analysis (carcino-embryonic antigen [CEA], carcinoma antigen 125 [CA125], squamous cell carcinoma antigen [SCC], cytokeratin-19 [Cyfra 21-1] and neuron-specific enolase [NSE]) and receiving definitive radiotherapy. Age, gender, radiation dose, baseline KPS, smoking history, weightless, TNM stage, PET staging, RT technique and treatment modality (radiotherapy alone vs. sequential chemoradiotherapy vs. concurrent chemoradiotherapy) were also retrospectively collected. To dichotomize the continuous values of tumor markers into categorical variables, ROC analysis was adopted to identify the optimal cutoff values using the progression within 2 years after diagnosis as the endpoint. Cox regression based multivariate analyses were used to select independent factors correlated with various survival endpoints. Overall survival (OS), local regional progression free survival (LRPFS) and distant metastasis free survival (DMFS) were defined as the time from diagnosis until the first occurrence of specific event: death, local-regional recurrence or distant metastasis, respectively. Progression free survival (PFS) was defined as the duration between the cancer diagnosis and the date of any progression or cancer related death. A total of 216 patients with LA-SCCL were analyzed. The optimal discriminative values for CEA, CA125, SCC, Cyfra 21-1 and NSE in predicting 2-y progression were 5.3 ng/ml, 17.0 U/ml, 2.5 ng/ml, 5.2 ng/ml and 17.8 ng/ml, respectively. Univariate analyses showed that increased Cyfra 21-1 was associated with inferior OS, LRPFS, DMFS and PFS. Increased NSE was predictive of poor OS, DMFS and PFS. CEA also presented significant correlation with OS. Under multivariate analysis involving all clinical and tumor markers, IIIA stage, better performance status, CEA ≤ 5.3 ng/ml and Cyfra 21-1 ≤ 5.2 ng/ml were independently associated with improved OS. IMRT technique, RT dose ≥ 60Gy and Cyfra 21-1 ≤ 5.2 ng/ml were correlated with better LRPFS. None-smoker, IIIA stage, NES ≤ 17.8 ng/ml were favorable predictors for DMFS. IIIA stage, KPS ≥ 80 and Cyfra 21-1 ≤ 5.2 ng/ml were advantageous factors related with favorable PFS. Baseline tumor marker panel including Cyfra 21-1, NSE and CEA can be prognostic of OS, local and distant tumor control for LA-SCCL, and should be recommended for baseline evaluation of tumor burden.