Individualized prediction of distant metastases risk in oral cavity carcinoma: A validated predictive-score model.
Authors: Badr Id Said, Fatimah Alfaraj, Gustavo Nader Marta, Luiz Paulo Kowalski, Shao Hui Huang, Jie Su, Wei Xu, Lawson Eng, Fabio Ynoe de Moraes, Ezra Hahn, John Kim, Jolie Ringash, John Waldron, Eitan Prisman, Jonathan Crawford Irish, Christopher M.K.L Yao, John R de Almeida, David Paul Goldstein, Andrew Hope, Ali Hosni
Journal: Journal of Clinical Oncology (2022)

6037 Background: We aimed to develop and validate a risk-scoring system for distant metastases (DM) in oral cavity carcinoma (OCC). Methods: In this IRB-approved retrospective study, OCC patients treated at 4 tertiary cancer institutions with curative surgery +/- postoperative radiation/chemo-radiation (PORT/PO-CRT) were divided into discovery and validation cohorts (randomly selected in 3:2 ratio). Staging was reviewed based on TNM 8 th edition. Predictors of DM identified on multivariable analysis in discovery cohort were used to develop DM risk-score model to classify patients into risk groups using Contal and O’Quigley method for cut-off optimization. The utility of risk classification was subsequently evaluated in validation cohort. C-index was used to assess predictive ability of the continuous risk score. Results: Overall 2749 patients were analyzed (Table). Predictors (risk score coefficient) of DM in discovery cohort were: pT3-4 (0.4), pN+ (N1:0.8; N2:1.0; N3:1.5), histologic grade 3 (G3, 0.7) and lymphovascular invasion (LVI, 0.4). The DM risk groups were defined by cumulative sum of risk score coefficients: high risk (sum &gt;2), intermediate risk (sum=1-2), and standard risk (sum&lt;1). In the discovery cohort, 5-yr DM for high vs intermediate vs standard risk groups was 33% vs 19% vs 6%, p&lt;0.001 (C-index=0.79). Similarly, in the validation cohort, 5-yr DM for high vs intermediate vs standard risk groups was 36% vs 23% vs 7%, p&lt;0.001 (C-index=0.77). When applied to entire study population, this predictive model showed excellent discriminative ability in predicting DM only without locoregional failure (29% vs 18% vs 3%, p&lt;0.001), late (&gt;2 yr) DM (11% vs 5% vs 3%; p&lt;0.001), DM in patients treated with surgery only (26% vs 11% vs 6%, p&lt;0.001), PORT (37% vs 23% vs 7%, p&lt;0.001), and PO-CRT (42% vs 29% vs 9%, p&lt;0.001). Finally, 5-yr OS for high vs intermediate vs standard risk groups in the overall cohort was 24% vs 38% vs 66%, p&lt;0.001. Conclusions: A predictive-score model for DM utilizing pT3-4, pN1/2/3, G3 and LVI demonstrated a validated utility in identifying patients at higher risk of DM who may be evaluated for individualized risk-adaptive treatment escalation and/or surveillance strategies. Study cohorts and predictors of distant metastases in discovery cohort. Discovery (n=1650)N (%) Validation (n=1099)N (%) p Median follow up 4.6 yr 4.5 yr 0.11 pT3-4 895 (54) 565 (51) 0.16 pN1/pN2/pN3 156(9)/ 258 (16)/ 280 (17) 99 (9)/ 159 (14)/ 196 (18) 0.78 G3 210 (13) 132 (12) 0.62 LVI 349 (22) 271 (25) 0.05 PORT/PO-CRT 873 (54)/ 220 (13) 567 (52)/ 150 (14) 0.48 5-yr DM (95% CI) 14% (12%-17%) 12% (11%-14%) 0.07 5-yr OS (95% CI) 55% (52%-59%) 53% (51%-56%) 0.38 Predictors of DM @ * pT3-4 (p=0.04)* pN+ (p&lt;0.001)* G3 (p&lt; 0.001)* LVI (p&lt;0.01) - - @ variables included in multivariable analysis: age, gender, smoking history, subsite, pT, pN, grade, LVI, PNI, margin status, pN+ at level IV/VB, PORT and PO-CRT.