The Canary in the Coal Mine: The Growth of Patient-Derived Tumorgrafts in Mice Predicts Clinical Recurrence after Surgical Resection of Pancreatic Ductal Adenocarcinoma
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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.
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.
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).
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.
KeywordsOverall Survival National Comprehensive Cancer Network National Comprehensive Cancer Network Pancreatic Ductal Adenocarcinoma Preoperative Therapy
This study was supported by the Viragh Family Foundation, the Khalifa Bin Zayed Al Nahyan Foundation, various donors to the Pancreatic Research Fund at MD Anderson Cancer Center, and the National Institutes of Health through Training Grant NIH T32-CA9599 (RT) and MD Anderson’s Cancer Center Support Grant CA016672.
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