Support vector machine-based prediction of local tumor control after stereotactic body radiation therapy for early-stage non-small cell lung cancer.

BACKGROUND Several prognostic factors for local tumor control probability (TCP) after stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) have been described, but no attempts have been undertaken to explore whether a nonlinear combination of potential factors might synergistically improve the prediction of local control. METHODS AND MATERIALS We investigated a support vector machine (SVM) for predicting TCP in a cohort of 399 patients treated at 13 German and Austrian institutions. Among 7 potential input features for the SVM we selected those most important on the basis of forward feature selection, thereby evaluating classifier performance by using 10-fold cross-validation and computing the area under the ROC curve (AUC). The final SVM classifier was built by repeating the feature selection 10 times with different splitting of the data for cross-validation and finally choosing only those features that were selected at least 5 out of 10 times. It was compared with a multivariate logistic model that was built by forward feature selection. RESULTS Local failure occurred in 12% of patients. Biologically effective dose (BED) at the isocenter (BED(ISO)) was the strongest predictor of TCP in the logistic model and also the most frequently selected input feature for the SVM. A bivariate logistic function of BED(ISO) and the pulmonary function indicator forced expiratory volume in 1 second (FEV1) yielded the best description of the data but resulted in a significantly smaller AUC than the final SVM classifier with the input features BED(ISO), age, baseline Karnofsky index, and FEV1 (0.696 ± 0.040 vs 0.789 ± 0.001, P<.03). The final SVM resulted in sensitivity and specificity of 67.0% ± 0.5% and 78.7% ± 0.3%, respectively. CONCLUSIONS These results confirm that machine learning techniques like SVMs can be successfully applied to predict treatment outcome after SBRT. Improvements over traditional TCP modeling are expected through a nonlinear combination of multiple features, eventually helping in the task of personalized treatment planning.

[1]  D. Hirst,et al.  Molecular biology: the key to personalised treatment in radiation oncology? , 2010, The British journal of radiology.

[2]  H. Rix,et al.  CLASSIFICATION OF FIELD DWARFS AND GIANTS IN RAVE AND ITS USE IN STELLAR STREAM DETECTION , 2010, 1010.3697.

[3]  T. Araki,et al.  Stereotactic hypofractionated high‐dose irradiation for stage I nonsmall cell lung carcinoma , 2004, Cancer.

[4]  J. Fowler,et al.  Stereotactic Body Radiation Therapy in Non–Small-Cell Lung Cancer: Linking Radiobiological Modeling and Clinical Outcome , 2011, American journal of clinical oncology.

[5]  Tom Fawcett,et al.  An introduction to ROC analysis , 2006, Pattern Recognit. Lett..

[6]  Issam El Naqa,et al.  Machine learning methods for predicting tumor response in lung cancer , 2012 .

[7]  U. Kämmerer,et al.  Is there a role for carbohydrate restriction in the treatment and prevention of cancer? , 2011, Nutrition & metabolism.

[8]  A. Fischman,et al.  Dose-response relationship between probability of pathologic tumor control and glucose metabolic rate measured with FDG PET after preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer. , 2002, International journal of radiation oncology, biology, physics.

[9]  Joseph O Deasy,et al.  A Bayesian network approach for modeling local failure in lung cancer , 2011, Physics in medicine and biology.

[10]  F. Sterzing,et al.  Safety and Efficacy of Stereotactic Body Radiotherapy for Stage I Non–Small-Cell Lung Cancer in Routine Clinical Practice: A Patterns-of-Care and Outcome Analysis , 2013, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[11]  E. DeLong,et al.  Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. , 1988, Biometrics.

[12]  Stephen Kwek,et al.  Applying Support Vector Machines to Imbalanced Datasets , 2004, ECML.

[13]  P Okunieff,et al.  Radiation dose-response of human tumors. , 1995, International journal of radiation oncology, biology, physics.

[14]  Xavier Robin,et al.  pROC: an open-source package for R and S+ to analyze and compare ROC curves , 2011, BMC Bioinformatics.

[15]  Chih-Jen Lin,et al.  LIBSVM: A library for support vector machines , 2011, TIST.

[16]  Nitesh V. Chawla,et al.  SMOTE: Synthetic Minority Over-sampling Technique , 2002, J. Artif. Intell. Res..

[17]  G Starkschall,et al.  Respiratory-driven lung tumor motion is independent of tumor size, tumor location, and pulmonary function. , 2001, International journal of radiation oncology, biology, physics.

[18]  Suresh Senan,et al.  Outcomes of stereotactic ablative radiotherapy for central lung tumours: a systematic review. , 2013, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[19]  Kurt Baier,et al.  Dose-response in stereotactic irradiation of lung tumors. , 2005, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[20]  P. Lambin,et al.  Predicting outcomes in radiation oncology—multifactorial decision support systems , 2013, Nature Reviews Clinical Oncology.

[21]  Angelika Hoess,et al.  Stereotactic single‐dose radiotherapy (radiosurgery) of early stage nonsmall‐cell lung cancer (NSCLC) , 2007, Cancer.

[22]  Pavel Stavrev,et al.  Computed 88% TCP dose for SBRT of NSCLC from tumour hypoxia modelling , 2012, Physics in medicine and biology.

[23]  J. Deasy,et al.  Datamining approaches for modeling tumor control probability , 2010, Acta oncologica.

[24]  Carsten Peterson,et al.  Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast-conservation surgery, with or without postoperative radiotherapy , 2008, Breast Cancer Research.

[25]  Yan Zhang,et al.  Molecular Prognostic Prediction for Locally Advanced Nasopharyngeal Carcinoma by Support Vector Machine Integrated Approach , 2012, PloS one.

[26]  Trevor Hastie,et al.  An Introduction to Statistical Learning , 2013, Springer Texts in Statistics.

[27]  M. Stuschke,et al.  Altered fractionation schemes in radiotherapy. , 2010, Frontiers of radiation therapy and oncology.

[28]  J. Deasy,et al.  Combining multiple models to generate consensus: application to radiation-induced pneumonitis prediction. , 2008, Medical physics.

[29]  Matthias Guckenberger,et al.  Dose-response relationship for image-guided stereotactic body radiotherapy of pulmonary tumors: relevance of 4D dose calculation. , 2009, International journal of radiation oncology, biology, physics.

[30]  Jan-Jakob Sonke,et al.  Modeling local control after hypofractionated stereotactic body radiation therapy for stage I non-small cell lung cancer: a report from the elekta collaborative lung research group. , 2012, International journal of radiation oncology, biology, physics.

[31]  Y. Onodera,et al.  Steep dose-response relationship for stage I non-small-cell lung cancer using hypofractionated high-dose irradiation by real-time tumor-tracking radiotherapy. , 2008, International journal of radiation oncology, biology, physics.

[32]  Sayan Mukherjee,et al.  Assessing the Radiation Response of Lung Cancer with Different Gene Mutations Using Genetically Engineered Mice , 2013, Front. Oncol..

[33]  K. Miles,et al.  Warburg revisited: imaging tumour blood flow and metabolism , 2008, Cancer imaging : the official publication of the International Cancer Imaging Society.

[34]  F. Yin,et al.  Investigation of the support vector machine algorithm to predict lung radiation-induced pneumonitis. , 2007, Medical physics.

[35]  Corinna Cortes,et al.  Support-Vector Networks , 1995, Machine Learning.