Patient-Derived Xenograft Engraftment Predicts Oral Cavity Cancer Outcomes

Abstract

Listen

Translate article

Patient-derived xenografts (PDX) can help identify oral cavity squamous cell carcinoma (OSCC) patients at risk for disease recurrence and optimize clinical decision-making. In this study, we develop and validate a prediction score for locoregional failure (LRF) and distant metastases (DM) in OSCC that incorporates PDX engraftment in addition to known clinicopathological risk factors.PDX models were generated from OSCC patients. Patients were scored as a ''non-engrafter" if PDX formation did not occur within 6 months. Multivariable analysis (MVA) was used to identify predictors of LRF and DM. Factors retained in the final MVA were used to construct a prediction score and classify patients into risk groups using a 10-fold cross-validation approach.Overall 288 OSCC patients were analyzed. MVA identified pT3-4, pENE, and engraftment as predictors of LRF and DM. Patients whose tumors engrafted (n = 198) were more likely to develop LRF (HR 1.98, 95% CI: 1.24-3.18, P < 0.01), and DM (HR 2.64, 95% CI 1.21-5.75, P < 0.01) compared to non-engrafters. A prediction score based on the aforementioned variables identified patients at high-risk (defined as having at least two of the three high risk features i.e., engraftment, pT3-4, pENE) and low-risk for LRF (43.5% vs 26.5% at 5-years, P < 0.001), DM (38.2% vs 8.4% at 5-years, P < 0.001), and poorer 5-year OS (34% vs 66%, P < 0.001). The prediction model that included engraftment had the highest discriminatory capacity in the cross-validation analysis (AUC: 67.8 [63.5-72.9]), while removal of engraftment as a predictor resulted in a lower c-index (AUC: 62.7 [57.0-68.4]). In patients classified based on a clinical score only (i.e., presence or absence of pT3-4 and pENE), engraftment remained useful in identifying those with worse outcomes. Compared to non-engrafters, engraftment was associated with higher rates of DM (15.8% vs. 5.4%, P < 0.05) in clinically "high risk" patients as well as higher rates of LRF (31.9% vs. 13.8%, P < 0.05) in clinically "low risk" patients at 5-years. Finally, engraftment was associated with poorer 5-year OS in both clinically "high risk" (36% vs. 65%, P < 0.05), and "low risk" patients (57% vs. 78%, P < 0.01).A prediction score utilizing OSCC PDX engraftment, in conjunction with pT3-4 and pENE, improves the prognostic utility of existing clinical models and predicts patients at risk for LRF, DM and poor survival.