title: The canary in the coal mine: the growth of patient-derived tumorgrafts in mice predicts clinical recurrence after surgical resection of pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  Recurrence after resection of pancreatic ductal adenocarcinoma (PDAC) is common, thus postoperative surveillance is critical for detection and treatment of recurrent disease. The development of biologically based techniques for early recurrence detection may enable more timely and effective treatment of such recurrences.
  
  
  METHODS
  Tumor fragments derived from patients who underwent potentially curative resection of PDAC were heterotopically implanted into NOD/SCID mice. Engraftment success rates and growth parameters were matched to clinicopathologic data, preoperative treatment status, and oncologic outcomes to correlate disease-free survival (DFS) and overall survival.
  
  
  RESULTS
  Seventy patients consented to participate with 56 (80 %) developing a mouse PDAC tumorgraft. Patients with successful engraftment had a shorter median DFS compared with patients whose tumorgrafts failed to engraft (9.8 vs. 40.9 mo, respectively; p < 0.01). Fifty patients received preoperative therapy with 36 (72 %) successful tumorgrafts from this cohort. On multivariate analysis, lymph node metastasis (hazard ratio [HR] 3, 95 % CI 1.4-6.7, p < 0.01) and successful engraftment (HR 5.8, 95 % CI 2-16.9, p < 0.01) were predictive of a shorter DFS in the preoperative therapy cohort. In patients who recurred, tumorgraft formation was identified at a median of 134.5 days before standard methods of radiographic recurrence detection (p < 0.01).
  
  
  CONCLUSIONS
  Patient-derived tumorgrafts from resected PDAC may potentially predict recurrence months before currently available surveillance modalities. This lead-time advantage may allow for earlier implementation or changes in therapy as successful engraftment, particularly in those having undergone preoperative therapy, may indicate a more biologically aggressive disease.
authors.affiliation: Department of Surgery, NF/SG VA Medical Center, Gainesville, FL, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Thomas
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Truty
authors.forename: Michael
authors.initials: M
authors.lastname: Kim
authors.forename: Ya'an
authors.initials: Y
authors.lastname: Kang
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.forename: Deyali
authors.initials: D
authors.lastname: Chatterjee
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Katz
authors.forename: Jason B
authors.initials: JB
authors.lastname: Fleming
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D009367:Neoplasm Staging; D010180:Pancreatectomy / Q000401:mortality*; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays