The Canary in the Coal Mine: The Growth of Patient-Derived Tumorgrafts in Mice Predicts Clinical Recurrence after Surgical Resection of Pancreatic Ductal Adenocarcinoma

Ryan M. Thomas, Mark Truty, Michael Kim, Ya’an Kang, Ran Zhang, Deyali Chatterjee, Matthew H. Katz, Jason B. Fleming

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1884-1892
Number of pages9
JournalAnnals of Surgical Oncology
Volume22
Issue number6
DOIs
StatePublished - Jun 1 2015

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Canaries
Coal
Adenocarcinoma
Recurrence
Growth
Disease-Free Survival
Therapeutics
Inbred NOD Mouse
SCID Mice
Multivariate Analysis
Lymph Nodes
Neoplasm Metastasis
Survival

ASJC Scopus subject areas

  • Surgery
  • Oncology

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The Canary in the Coal Mine : The Growth of Patient-Derived Tumorgrafts in Mice Predicts Clinical Recurrence after Surgical Resection of Pancreatic Ductal Adenocarcinoma. / Thomas, Ryan M.; Truty, Mark; Kim, Michael; Kang, Ya’an; Zhang, Ran; Chatterjee, Deyali; Katz, Matthew H.; Fleming, Jason B.

In: Annals of Surgical Oncology, Vol. 22, No. 6, 01.06.2015, p. 1884-1892.

Research output: Contribution to journalArticle

Thomas, Ryan M. ; Truty, Mark ; Kim, Michael ; Kang, Ya’an ; Zhang, Ran ; Chatterjee, Deyali ; Katz, Matthew H. ; Fleming, Jason B. / The Canary in the Coal Mine : The Growth of Patient-Derived Tumorgrafts in Mice Predicts Clinical Recurrence after Surgical Resection of Pancreatic Ductal Adenocarcinoma. In: Annals of Surgical Oncology. 2015 ; Vol. 22, No. 6. pp. 1884-1892.
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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.",
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T2 - The Growth of Patient-Derived Tumorgrafts in Mice Predicts Clinical Recurrence after Surgical Resection of Pancreatic Ductal Adenocarcinoma

AU - Thomas, Ryan M.

AU - Truty, Mark

AU - Kim, Michael

AU - Kang, Ya’an

AU - Zhang, Ran

AU - Chatterjee, Deyali

AU - Katz, Matthew H.

AU - Fleming, Jason B.

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N2 - 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.

AB - 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.

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