Development and Validation of an Oral Cavity Cancer Outcomes Prediction Score Incorporating Patient-Derived Xenograft Engraftment

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Abstract
Question What is the prognostic value of patient-derived xenograft (PDX) engraftment in predicting locoregional failure and distant metastases in oral squamous cell carcinoma (OSCC)? Findings In this cohort study of 288 patients with OSCC, a prediction model was developed to identify patients at risk for locoregional failure and distant metastases using PDX engraftment data in conjunction with well-established clinical and pathologic predictors. Patients with engraftable tumors, rapid engrafters in particular, were at a higher risk for relapse and poor survival compared with nonengrafters. Meaning In this cohort study, PDX engraftment success was a predictor of poor cancer outcomes in OSCC. Importance Patient-derived xenografts (PDXs) offer the opportunity to identify patients with oral cavity squamous cell carcinoma (OSCC) who are at risk for recurrence and optimize clinical decision-making. Objective To 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. Design, Setting, and Participants In this retrospective cohort study, PDX models were generated from patients with OSCC treated with curative intent at Princess Margaret Cancer Centre (Toronto, Canada) between 2006 and 2018. The cohort included 288 patients (aged ≥18 years) with a new diagnosis of nonmetastatic (M0) OSCC whose tumor samples were available for engraftment under the skin of xenograft mice. Patients were scored as a nonengrafter if PDX formation did not occur within 6 months. Data analysis was performed between August 2006 and May 2018. Interventions All patients received up-front curative-intent surgery followed by either observation or postoperative radiation with or without concurrent chemotherapy based on institutional guidelines. Main Outcomes and Measures Main outcomes were LRF, DM, and overall survival (OS). 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. Results Overall, 288 patients (mean [SD] age at diagnosis, 63.3 [12.3] years; 112 [39%] women and 176 [61%] men) with OSCC were analyzed. The MVA identified pT3-4, pathologic extranodal extension, and engraftment as predictors of LRF and DM. Patients whose tumors engrafted (n = 198) were more likely to develop LRF (hazard ratio [HR], 1.98; 95% CI, 1.24-3.18) and DM (HR, 2.64; 95% CI, 1.21-5.75) compared with nonengrafters. A prediction score based on the aforementioned variables identified patients at high risk and low risk for LRF (43.5% vs 26.5%), DM (38.2% vs 8.4%), and inferior OS (34% vs 66%) at 5 years. Additionally, rapid engraftment was shown to be similarly prognostic, with rapid engrafters demonstrating higher rates of relapse and poor OS. Conclusions In this cohort study, a prediction score using OSCC PDX engraftment, in conjunction with pT3-4 and pathologic extranodal extension, was associated with improved prognostic utility of existing clinical models and predicted patients at risk for LRF, DM, and poor survival. Identify all potential conflicts of interest that might be relevant to your comment. Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. Err on the side of full disclosure. If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response. Not all submitted comments are published. Please see our commenting policy for details.

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