RESUMO
Oral squamous cell carcinoma (OSCC) biomarker studies rarely employ multi-omic biomarker strategies and pertinent clinicopathologic characteristics to predict mortality. In this study we determine for the first time a combined epigenetic, gene expression, and histology signature that differentiates between patients with different tobacco use history (heavy tobacco use with ≥10 pack years vs. no tobacco use). Using The Cancer Genome Atlas (TCGA) cohort (n = 257) and an internal cohort (n = 40), we identify 3 epigenetic markers (GPR15, GNG12, GDNF) and 13 expression markers (IGHA2, SCG5, RPL3L, NTRK1, CD96, BMP6, TFPI2, EFEMP2, RYR3, DMTN, GPD2, BAALC, and FMO3), which are dysregulated in OSCC patients who were never smokers vs. those who have a ≥ 10 pack year history. While mortality risk prediction based on smoking status and clinicopathologic covariates alone is inaccurate (c-statistic = 0.57), the combined epigenetic/expression and histologic signature has a c-statistic = 0.9409 in predicting 5-year mortality in OSCC patients.
RESUMO
OBJECTIVE: To investigate adjuvant therapy indications, utilization, and associated survival disparities in major salivary gland cancer (MSGC). STUDY DESIGN: Retrospective cohort study. SETTING: The 2006 to 2017 National Cancer Database. METHODS: Patients with surgically resected MSGC were included (N = 11,398). pT3-4 classification, pN2-3 classification, lymphovascular invasion, pathologic extranodal extension (pENE), and positive surgical margin (PSM) were considered indications for adjuvant radiotherapy (aRT). pENE and PSM were considered possible indications for adjuvant chemotherapy. Multivariable logistic and Cox regression models were implemented. RESULTS: Among 6694 patients with ≥ $\ge $ 1 indication for aRT, 1906 (28.5%) received no further treatment and missed aRT. Age, race, comorbidity status, facility type, and distance to reporting facility were associated with missed aRT (P < .025). Among 4003 patients with ≥1 possible indication for adjuvant chemoradiotherapy (aCRT), 914 (22.8%) received aCRT. Patients with pENE only (38.5%) and both pENE and PSM (44.0%) received aCRT more frequently than those with PSM only (17.0%) (P < .001). Academic facility was associated with aCRT utilization (P < .05). aCRT utilization increased between 2006 and 2017 in both academic (14.8% vs 23.9%) and nonacademic (8.8% vs 13.5%) facilities (P < .05). Among 2691 patients with ≥1 indication for aRT alone, missed aRT portended poorer OS (hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.28-2.03, P < .001). Among 4003 patients with ≥1 possible indication for aCRT, aRT alone (HR: 1.02, 95% CI: 0.89-1.18, P = .780) and aCRT were associated with similar OS. CONCLUSION: Missed aRT in MSGC occurs frequently and portends poorer OS. Further studies clarifying indications for aCRT are required.