Individualized prediction of distant metastases risk in oral cavity carcinoma: A validated predictive-score model.
Authors: Id Said Badr , Alfaraj Fatimah , Marta Gustavo Nader , Kowalski Luiz Paulo , Huang Shao Hui , Su Jie , Xu Wei , Eng Lawson , Ynoe de Moraes Fabio , Hahn Ezra , Kim John , Ringash Jolie , Waldron John , Prisman Eitan , Irish Jonathan Crawford , Yao Christopher M.K.L , de Almeida John R , Goldstein David Paul , Hope Andrew , Hosni Ali 
Published: October 2024

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 >2), intermediate risk (sum=1-2), and standard risk (sum<1). In the discovery cohort, 5-yr DM for high vs intermediate vs standard risk groups was 33% vs 19% vs 6%, p<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<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<0.001), late (>2 yr) DM (11% vs 5% vs 3%; p<0.001), DM in patients treated with surgery only (26% vs 11% vs 6%, p<0.001), PORT (37% vs 23% vs 7%, p<0.001), and PO-CRT (42% vs 29% vs 9%, p<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<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
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* pT3-4 (p=0.04)* pN+ (p<0.001)* G3 (p< 0.001)* LVI (p<0.01)
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-

@
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.