title: External validation of a publicly available computer assisted diagnostic tool for mammographic mass lesions with two high prevalence research datasets.
abstract: OBJECTIVE
  Lesions detected at mammography are described with a highly standardized terminology: the breast imaging-reporting and data system (BI-RADS) lexicon. Up to now, no validated semantic computer assisted classification algorithm exists to interactively link combinations of morphological descriptors from the lexicon to a probabilistic risk estimate of malignancy. The authors therefore aim at the external validation of the mammographic mass diagnosis (MMassDx) algorithm. A classification algorithm like MMassDx must perform well in a variety of clinical circumstances and in datasets that were not used to generate the algorithm in order to ultimately become accepted in clinical routine.
  
  
  METHODS
  The MMassDx algorithm uses a naïve Bayes network and calculates post-test probabilities of malignancy based on two distinct sets of variables, (a) BI-RADS descriptors and age ("descriptor model") and (b) BI-RADS descriptors, age, and BI-RADS assessment categories ("inclusive model"). The authors evaluate both the MMassDx (descriptor) and MMassDx (inclusive) models using two large publicly available datasets of mammographic mass lesions: the digital database for screening mammography (DDSM) dataset, which contains two subsets from the same examinations-a medio-lateral oblique (MLO) view and cranio-caudal (CC) view dataset-and the mammographic mass (MM) dataset. The DDSM contains 1220 mass lesions and the MM dataset contains 961 mass lesions. The authors evaluate discriminative performance using area under the receiver-operating-characteristic curve (AUC) and compare this to the BI-RADS assessment categories alone (i.e., the clinical performance) using the DeLong method. The authors also evaluate whether assigned probabilistic risk estimates reflect the lesions' true risk of malignancy using calibration curves.
  
  
  RESULTS
  The authors demonstrate that the MMassDx algorithms show good discriminatory performance. AUC for the MMassDx (descriptor) model in the DDSM data is 0.876/0.895 (MLO/CC view) and AUC for the MMassDx (inclusive) model in the DDSM data is 0.891/0.900 (MLO/CC view). AUC for the MMassDx (descriptor) model in the MM data is 0.862 and AUC for the MMassDx (inclusive) model in the MM data is 0.900. In all scenarios, MMassDx performs significantly better than clinical performance, P < 0.05 each. The authors furthermore demonstrate that the MMassDx algorithm systematically underestimates the risk of malignancy in the DDSM and MM datasets, especially when low probabilities of malignancy are assigned.
  
  
  CONCLUSIONS
  The authors' results reveal that the MMassDx algorithms have good discriminatory performance but less accurate calibration when tested on two independent validation datasets. Improvement in calibration and testing in a prospective clinical population will be important steps in the pursuit of translation of these algorithms to the clinic.
authors.affiliation: Department of Radiology, University Hospital Freiburg, Hugstetter Straße 55, Freiburg 79106, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Benndorf
authors.affiliation: Department of Radiology, University of Wisconsin-Madison School of Medicine and Public Health, 600 Highland Avenue, Madison, Wisconsin 53792.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Burnside
authors.affiliation: Kantonsspital Graubünden, Loesstraße 170, Chur 7000, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Herda
authors.affiliation: Department of Radiology, University Hospital Freiburg, Hugstetter Straße 55, Freiburg 79106, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Langer
authors.affiliation: Department of Radiology, University Hospital Freiburg, Hugstetter Straße 55, Freiburg 79106, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Kotter
mesh_terms: D022126:Access to Information; D000465:Algorithms; D019540:Area Under Curve; D001499:Bayes Theorem; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging*; D002138:Calibration; D016208:Databases, Factual; D003937:Diagnosis, Differential; D006801:Humans; D008327:Mammography / Q000379:methods*; D012372:ROC Curve; D011857:Radiographic Image Interpretation, Computer-Assisted / Q000379:methods*