The Effect of Package Time on Locally Advanced Oral Cavity Cancer Outcomes

Abstract

Oral cavity cancer (OCC) with adverse pathologic features is treated with adjuvant radiation (RT) following definitive surgical resection. The 5-year overall survival (OS) in locally advanced OCC patients receiving adjuvant RT has remained stagnant at 60% for over 30 years. Although pathologic risk factors are well-established, the effect of clinical variables such as treatment package time (TPT) in the modern era of radiation and systemic agents is unclear. Examining a large, homogenous cohort of OCC patients, we hypothesized that TPT can predict OS and event free survival (EFS). A retrospective review of 359 adult patients with OCC treated with surgery and adjuvant RT with or without concurrent chemotherapy from 2012-2022 was performed at a single, high-volume center. Those without definitive surgery, treated to <50 Gy, or with a history of prior RT were excluded. TPT was defined as time from surgery to completion of RT. Other variables considered were sex, race, smoking status, AJCC 8 pathologic stage, perineural invasion (PNI), lymphovascular invasion (LVI), margin positivity, extranodal extension (ENE), and hospitalization between surgery and RT. Log rank tests were performed for OS and EFS where TPT was dichotomized into short (<97.5 days) and long (>97.5 days) groups based on the median TPT of the cohort. Univariate (UVA) and multivariate (MVA) cox regression analyses were performed for OS and EFS. A total of 234 patients met inclusion criteria. Median OS was 81.6 months. Median EFS was 50.0 months. Median OS was 51.1 months in the longer TPT group and was not reached in the shorter TPT group. Median EFS was greater with shorter TPT (72.6 vs 31.3 months). The longer TPT group had worse OS and EFS probabilities than the shorter TPT group (p = 0.006 and p = 0.059, respectively). On UVA, factors significantly associated with OS were TPT (p = 0.006), former/current smoker status (p = 0.003 and p = 0.011, respectively), pathologic stage IV (p<0.001), positive PNI (p<0.001) or LVI (p = 0.005), and ENE (p<0.001). On MVA for OS, shorter TPT (p = 0.026), former smoker status (p = 0.009), pathologic stage IV (p = 0.026), positive PNI (p = 0.009), and ENE (p = 0.05), remained significant. On UVA, factors significantly associated with EFS were former/current smoker status (p = 0.01/p = 0.04), pathologic stage IV (p<0.001), pT1/T2 (p = 0.018), positive PNI (p = 0.011) or ENE (p<0.001), and concurrent chemotherapy (p = 0.001). On MVA, former smoker status (p = 0.035) and positive PNI (p = 0.018) remained significant. Notably, of the 130 patients requiring hospitalization between surgery and radiation, 101 (78%) were prior/current smokers. In this large cohort of locally advanced OCC patients, TPT <97.5 days is associated with improved OS and EFS. Smoking history should be further explored for its potential contribution to treatment delay. Multidisciplinary coordination should be encouraged to minimize TPT.