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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.

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Non-small cell lung cancer


Body mass index


Hazard ratio




Alanine aminotransferase


Aspartate aminotransferase


Alkaline phosphatase


Glutamyl aminotransferase


Total protein




Total bile acid


Total bilirubin


Direct bilirubin






Uric acid


Creatine kinase


Lactate dehydrogenase




Total cholesterol


Total triglyceride


Carcinoembryonic antigen




Carbohydrate antigen 125


Cytokeratin 19 fragment antigen


Neuron-specific enolase


Squamous cell carcinoma-associated antigen


Eastern Cooperative Oncology Group


Southwest Oncology Group


European lung Cancer Working Party


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The authors thank the staff in the Department of Clinical Biochemistry and the Department of Radiology at the Chinese PLA General Hospital for their support. The study was funded by the National Key Technology Support Program of China (2009BAI86B05 to Xinyu Wen) and by the National High-tech Technology Research and Development Program of China (2011AA 02A 111 to Yaping Tian).

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The authors declare that they have no conflict of interest.

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Correspondence to Yaping Tian.

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Wenjun Mou and Zhaoqi Liu contributed equally to this work.

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The fitted coefficients of the most accurate prognostic factors in the multivariate Cox proportional hazards model in all four studied subsets, including subset of patients with no metastasis(A), with one metastatic site(B), with two metastatic sites(C), with multiple sites(D). (JPEG 1628 kb)

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Mou, W., Liu, Z., Luo, Y. et al. Development and cross-validation of prognostic models to assess the treatment effect of cisplatin/pemetrexed chemotherapy in lung adenocarcinoma patients. Med Oncol 31, 59 (2014).

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