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Medical Oncology

, 31:59 | Cite as

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

  • Wenjun Mou
  • Zhaoqi Liu
  • Yuan Luo
  • Meng Zou
  • Chao Ren
  • Chunyan Zhang
  • Xinyu Wen
  • Yong Wang
  • Yaping TianEmail author
Original Paper

Abstract

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.

Keywords

Prognostic models Five-fold cross-validation The stepwise forward selection Lung adenocarcinoma Chemotherapy 

Abbreviations

NSCLC

Non-small cell lung cancer

BMI

Body mass index

HR

Hazard ratio

KM

Kaplan–Meier

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

ALP

Alkaline phosphatase

GGT

Glutamyl aminotransferase

TP

Total protein

ALB

Albumin

TBA

Total bile acid

TB

Total bilirubin

DB

Direct bilirubin

UR

Urea

CR

Creatinine

UA

Uric acid

CK

Creatine kinase

LDH

Lactate dehydrogenase

GLU

Glucose

TC

Total cholesterol

TG

Total triglyceride

CEA

Carcinoembryonic antigen

AFP

a-Fetoprotein

CA125

Carbohydrate antigen 125

CYFRA21-1

Cytokeratin 19 fragment antigen

NSE

Neuron-specific enolase

SCC

Squamous cell carcinoma-associated antigen

ECOG

Eastern Cooperative Oncology Group

SWOG

Southwest Oncology Group

ELCWP

European lung Cancer Working Party

Notes

Acknowledgments

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).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

12032_2014_59_MOESM1_ESM.docx (22 kb)
Supplementary material 1 (DOCX 22 kb)
12032_2014_59_MOESM2_ESM.jpg (1.6 mb)
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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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Wenjun Mou
    • 1
    • 2
  • Zhaoqi Liu
    • 3
  • Yuan Luo
    • 1
  • Meng Zou
    • 3
  • Chao Ren
    • 4
  • Chunyan Zhang
    • 1
    • 2
  • Xinyu Wen
    • 1
  • Yong Wang
    • 3
  • Yaping Tian
    • 1
    Email author
  1. 1.Department of Clinical BiochemistryChinese PLA General HospitalBeijingChina
  2. 2.School of MedicineNankai UniversityTianjinChina
  3. 3.National Center for Mathematics and Interdisciplinary Sciences, Academy of Mathematics and Systems ScienceChinese Academy of SciencesBeijingChina
  4. 4.Department of RadiologyChinese PLA General HospitalBeijingChina

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