title: Influence of integrated molecular pathology test results on real-world management decisions for patients with pancreatic cysts: analysis of data from a national registry cohort.
abstract: BACKGROUND
  Integrated molecular pathology (IMP) approaches based on DNA mutational profiling accurately determine pancreatic cyst malignancy risk in patients lacking definitive diagnoses following endoscopic ultrasound imaging with fine-needle aspiration of fluid for cytology. In such cases, IMP 'low-risk' and 'high-risk' diagnoses reliably predict benign and malignant disease, respectively, and provide improved risk stratification for malignancy than a model of the 2012 International Consensus Guideline (ICG) recommendations. Our objective was to determine if initial adjunctive IMP testing influenced future real-world pancreatic cyst management decisions for intervention or surveillance relative to ICG recommendations, and if this benefitted patient outcomes.
  
  
  METHODS
  Analysis of data from the previously described National Pancreatic Cyst Registry. Associations between real-world decisions (intervention vs. surveillance), ICG model recommendations (surgery vs. surveillance) and IMP diagnoses (high-risk vs. low-risk) were evaluated using 2 × 2 tables. Kaplan Meier and hazard ratio analyses were used to assess time to malignancy. Odds ratios (OR) for surgery decision were determined using logistic regression.
  
  
  RESULTS
  Of 491 patients, 206 received clinical intervention at follow-up (183 surgery, 4 chemotherapy, 19 presumed by malignant cytology). Overall, 13 % (66/491) of patients had a malignant outcome and 87 % (425/491) had a benign outcome at 2.9 years' follow-up. When ICG and IMP were concordant for surveillance/surgery recommendations, 83 % and 88 % actually underwent surveillance or surgery, respectively. However, when discordant, IMP diagnoses were predictive of real-world decisions, with 88 % of patients having an intervention when ICG recommended surveillance but IMP indicated high risk, and 55 % undergoing surveillance when ICG recommended surgery but IMP indicated low risk. These IMP-associated management decisions benefitted patient outcomes in these subgroups, as 57 % had malignant and 99 % had benign outcomes at a median 2.9 years' follow-up. IMP was also more predictive of real-world decisions than ICG by multivariate analysis: OR 11.4 (95 % CI 6.0 - 23.7) versus 3.7 (2.4 - 5.8), respectively.
  
  
  CONCLUSIONS
  DNA-based IMP diagnoses were predictive of real-world management decisions. Importantly, when ICG and IMP were discordant, IMP influence benefitted patients by increasing confidence in surveillance and surgery decisions and reducing the number of unnecessary surgeries in patients with benign disease.
authors.affiliation: Department of Medicine, Jefferson Digestive Disease Institute, Thomas Jefferson University, Philadelphia, PA, USA. david.loren@jefferson.edu.
authors.forename: David
authors.initials: D
authors.lastname: Loren
authors.affiliation: Department of Medicine, Jefferson Digestive Disease Institute, Thomas Jefferson University, Philadelphia, PA, USA. tkowalmd@gmail.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kowalski
authors.affiliation: Department of Medicine, Jefferson Digestive Disease Institute, Thomas Jefferson University, Philadelphia, PA, USA. aas138@jefferson.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Siddiqui
authors.affiliation: Interpace Diagnostics Corporation, 2515 Liberty Avenue, Pittsburgh, PA, 15222, USA. sjackson@interpacedx.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Jackson
authors.affiliation: Interpace Diagnostics Corporation, 2515 Liberty Avenue, Pittsburgh, PA, 15222, USA. ntoney@interpacedx.com.
authors.forename: Nicole
authors.initials: N
authors.lastname: Toney
authors.affiliation: Division of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC, USA. nidhi6484@gmail.com.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Malhotra
authors.affiliation: Division of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC, USA. NGH3@gunet.georgetown.edu.
authors.forename: Nadim
authors.initials: N
authors.lastname: Haddad
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D004252:DNA Mutational Analysis; D003661:Decision Support Techniques; D019983:Guideline Adherence; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D010181:Pancreatic Cyst / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D057089:Pathology, Molecular / Q000379:methods*; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D010818:Practice Patterns, Physicians'; D011237:Predictive Value of Tests; D012042:Registries; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D019564:Unnecessary Procedures
chemical_list: D014408:Biomarkers, Tumor