Modeling pathologic response of esophageal cancer to chemoradiation therapy using spatial-temporal 18F-FDG PET features, clinical parameters, and demographics.

PURPOSE To construct predictive models using comprehensive tumor features for the evaluation of tumor response to neoadjuvant chemoradiation therapy (CRT) in patients with esophageal cancer. METHODS AND MATERIALS This study included 20 patients who underwent trimodality therapy (CRT+surgery) and underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) both before and after CRT. Four groups of tumor features were examined: (1) conventional PET/CT response measures (eg, standardized uptake value [SUV]max, tumor diameter); (2) clinical parameters (eg, TNM stage, histology) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, cross-validations being used to avoid model overfitting. Prediction accuracy was assessed by area under the receiver operating characteristic curve (AUC), and precision was evaluated by confidence intervals (CIs) of AUC. RESULTS When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). With the use of spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications)-results that were significantly better than when conventional PET/CT measures or clinical parameters and demographics alone were used. For groups with many tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than did the LR model. CONCLUSIONS The SVM model that used all features including spatial-temporal PET features accurately and precisely predicted pathologic tumor response to CRT in esophageal cancer.

[1]  R. Munden,et al.  Utility of PET, CT, and EUS to identify pathologic responders in esophageal cancer. , 2004, The Annals of thoracic surgery.

[2]  R. Wahl,et al.  From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid Tumors , 2009, Journal of Nuclear Medicine.

[3]  B. Krause,et al.  18F-FDG PET and 18F-FDG PET/CT for Assessing Response to Therapy in Esophageal Cancer , 2009, Journal of Nuclear Medicine.

[4]  Otto S Hoekstra,et al.  Esophageal cancer: CT, endoscopic US, and FDG PET for assessment of response to neoadjuvant therapy--systematic review. , 2005, Radiology.

[5]  K. Polyak,et al.  Tumor heterogeneity: causes and consequences. , 2010, Biochimica et biophysica acta.

[6]  M. Suntharalingam,et al.  Outcomes After Trimodality Therapy for Esophageal Cancer: The Impact of Histology on Failure Patterns , 2011, American journal of clinical oncology.

[7]  K. Geisinger,et al.  Predictive Value of 18-Fluoro-Deoxy-Glucose-Positron Emission Tomography (18F-FDG-PET) in the Identification of Responders to Chemoradiation Therapy for the Treatment of Locally Advanced Esophageal Cancer , 2006, Annals of surgery.

[8]  K Kubota,et al.  From tumor biology to clinical PET: A review of positron emission tomography (PET) in oncology , 2001, Annals of nuclear medicine.

[9]  A. Ruol,et al.  Interval Between Neoadjuvant Chemoradiotherapy and Surgery for Squamous Cell Carcinoma of the Thoracic Esophagus: Does Delayed Surgery Have an Impact on Outcome? , 2010, Annals of surgery.

[10]  John L. Humm,et al.  Tumor Treatment Response Based on Visual and Quantitative Changes in Global Tumor Glycolysis Using PET-FDG Imaging. The Visual Response Score and the Change in Total Lesion Glycolysis. , 1999, Clinical positron imaging : official journal of the Institute for Clinical P.E.T.

[11]  Shan Tan,et al.  Spatial-temporal [¹⁸F]FDG-PET features for predicting pathologic response of esophageal cancer to neoadjuvant chemoradiation therapy. , 2013, International journal of radiation oncology, biology, physics.

[12]  M. Hatt,et al.  Intratumor Heterogeneity Characterized by Textural Features on Baseline 18F-FDG PET Images Predicts Response to Concomitant Radiochemotherapy in Esophageal Cancer , 2011, The Journal of Nuclear Medicine.

[13]  J. Bradley,et al.  Combined PET/CT image characteristics for radiotherapy tumor response in lung cancer. , 2012, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[14]  E. Halpern,et al.  CT tumor measurement for therapeutic response assessment: comparison of unidimensional, bidimensional, and volumetric techniques initial observations. , 2002, Radiology.

[15]  Nils Lehmann,et al.  Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  Jason Weston,et al.  Gene Selection for Cancer Classification using Support Vector Machines , 2002, Machine Learning.

[17]  C. Compton,et al.  AJCC Cancer Staging Manual , 2002, Springer New York.

[18]  Nagara Tamaki,et al.  Biologic correlates of intratumoral heterogeneity in 18F-FDG distribution with regional expression of glucose transporters and hexokinase-II in experimental tumor. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[19]  K. Geisinger,et al.  Outcomes of patients with esophageal cancer staged with [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET): can postchemoradiotherapy FDG-PET predict the utility of resection? , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  J. Ajani,et al.  Does the timing of esophagectomy after chemoradiation affect outcome? , 2012, The Annals of thoracic surgery.

[21]  R. M. Kwee Prediction of tumor response to neoadjuvant therapy in patients with esophageal cancer with use of 18F FDG PET: a systematic review. , 2010, Radiology.

[22]  C. Tseng,et al.  Interval Between Neoadjuvant Chemoradiotherapy and Surgery for Esophageal Squamous Cell Carcinoma: Does Delayed Surgery Impact Outcome? , 2013, Annals of Surgical Oncology.

[23]  Zixiang Xiong,et al.  Optimal number of features as a function of sample size for various classification rules , 2005, Bioinform..

[24]  J. Petiot,et al.  Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations , 1994, Cancer.

[25]  B. Loo,et al.  Postchemoradiotherapy positron emission tomography predicts pathologic response and survival in patients with esophageal cancer. , 2012, International journal of radiation oncology, biology, physics.

[26]  T. Conroy,et al.  Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  D. Sugarbaker,et al.  Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  F O'Sullivan,et al.  Incorporation of tumor shape into an assessment of spatial heterogeneity for human sarcomas imaged with FDG-PET. , 2005, Biostatistics.