title: Quantitative Analysis of (18)F-Fluorodeoxyglucose Positron Emission Tomography Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated With Stereotactic Body Radiation Therapy.
abstract: To identify prognostic biomarkers in pancreatic cancer using high-throughput quantitative image analysis.
  
  
  
  In this institutional review board-approved study, we retrospectively analyzed images and outcomes for 139 locally advanced pancreatic cancer patients treated with stereotactic body radiation therapy (SBRT). The overall population was split into a training cohort (n=90) and a validation cohort (n=49) according to the time of treatment. We extracted quantitative imaging characteristics from pre-SBRT (18)F-fluorodeoxyglucose positron emission tomography, including statistical, morphologic, and texture features. A Cox proportional hazard regression model was built to predict overall survival (OS) in the training cohort using 162 robust image features. To avoid over-fitting, we applied the elastic net to obtain a sparse set of image features, whose linear combination constitutes a prognostic imaging signature. Univariate and multivariate Cox regression analyses were used to evaluate the association with OS, and concordance index (CI) was used to evaluate the survival prediction accuracy.
  
  
  
  The prognostic imaging signature included 7 features characterizing different tumor phenotypes, including shape, intensity, and texture. On the validation cohort, univariate analysis showed that this prognostic signature was significantly associated with OS (P=.002, hazard ratio 2.74), which improved upon conventional imaging predictors including tumor volume, maximum standardized uptake value, and total legion glycolysis (P=.018-.028, hazard ratio 1.51-1.57). On multivariate analysis, the proposed signature was the only significant prognostic index (P=.037, hazard ratio 3.72) when adjusted for conventional imaging and clinical factors (P=.123-.870, hazard ratio 0.53-1.30). In terms of CI, the proposed signature scored 0.66 and was significantly better than competing prognostic indices (CI 0.48-0.64, Wilcoxon rank sum test P<1e-6).
  
  
  
  Quantitative analysis identified novel (18)F-fluorodeoxyglucose positron emission tomography image features that showed improved prognostic value over conventional imaging metrics. If validated in large, prospective cohorts, the new prognostic signature might be used to identify patients for individualized risk-adaptive therapy.
authors: Department of Radiation Oncology, Stanford University, Palo Alto, California; Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo, Japan.
authors: Yi
authors: Y
authors: Cui
authors: Department of Radiation Oncology, Stanford University, Palo Alto, California.
authors: Jie
authors: J
authors: Song
authors: Department of Radiation Oncology, Stanford University, Palo Alto, California.
authors: Erqi
authors: E
authors: Pollom
authors: Department of Radiation Oncology, Stanford University, Palo Alto, California.
authors: Muthuraman
authors: M
authors: Alagappan
authors: Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo, Japan.
authors: Hiroki
authors: H
authors: Shirato
authors: Department of Radiation Oncology, Stanford University, Palo Alto, California; Stanford Cancer Institute, Stanford, California.
authors: Daniel T
authors: DT
authors: Chang
authors: Department of Radiation Oncology, Stanford University, Palo Alto, California; Stanford Cancer Institute, Stanford, California.
authors: Albert C
authors: AC
authors: Koong
authors: Department of Radiation Oncology, Stanford University, Palo Alto, California; Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo, Japan; Stanford Cancer Institute, Stanford, California. Electronic address: rli2@stanford.edu.
authors: Ruijiang
authors: R
authors: Li
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality* / Q000532:radiotherapy*; D049268:Positron-Emission Tomography / Q000379:methods / Q000706:statistics & numerical data*; D011379:Prognosis; D016016:Proportional Hazards Models; D019275:Radiopharmaceuticals; D016634:Radiosurgery / Q000706:statistics & numerical data*; D011879:Radiotherapy Dosage; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18