Development and cross-validation of prognostic models to assess the treatment effect of cisplatin/pemetrexed chemotherapy in lung adenocarcinoma patients.

Better understanding of the treatment effect of cisplatin/pemetrexed chemotherapy on lung adenocarcinoma patients is needed to facilitate chemotherapy planning and patient care. In this retrospective study, we will develop prognostic models by the cross-validation method using clinical and serum factors to predict outcomes of cisplatin/pemetrexed chemotherapy in lung adenocarcinoma patients. Lung adenocarcinoma patients admitted between 2008 and 2013 were enrolled. 29 serum parameters of laboratory tests and 14 clinical factors were analyzed to develop the prognostic models. First, the stepwise selection and five-fold cross-validation were performed to identify candidate prognostic factors. Then a classification of all patients based on the number of metastatic sites resulted in four distinct subsets. In each subset, a prognostic model was fitted with the most accurate prognostic factors from the candidate prognostic factors. Categorical survival prediction was estimated using a log-rank test and visualized with Kaplan-Meier method. 227 lung adenocarcinoma patients were enrolled. Twenty candidate prognostic factors evaluated using the five-fold cross-validation method were total protein, total bilirubin, direct bilirubin, creatine kinase, age, smoking index, neuron-specific enolase, bone metastasis, total triglyceride, albumin, gender, uric acid, CYFRA21-1, lymph node metastasis, liver metastasis, lactate dehydrogenase, CA153, peritoneal metastasis, CA125, and CA199. From these 20 candidate prognostic factors, the multivariate Cox proportional hazard model with the highest prognostic accuracy in each subset was identified by the stepwise forward selection method, which generated significant prognostic stratifications in Kaplan-Meier survival analyses (all log-rank p < 0.01). Generally, the prognostic models using five-fold cross-validation achieve a good prediction performance. The prognostic models can be administered safely to lung adenocarcinoma patients treated with first-line cisplatin/pemetrexed chemotherapy, and a comprehensive assessment of clinical and serum factors helps predict the outcomes of cisplatin/pemetrexed chemotherapy.