Increased Utilization of Chemotherapy for Early Stage Oropharyngeal Squamous Cell Carcinoma Despite Evidence for Benefit

Abstract

Definitive radiotherapy (RT) offers the potential for organ preservation in patients with early stage oropharyngeal squamous cell carcinoma (OPSCC). For locally advanced OPSCC, the addition of chemotherapy to RT improves overall survival (OS) at the expense of increased acute and late toxicity. However, ASTRO recently presented guidelines recommending against chemoradiotherapy (CRT) in early stage OPSCC given prospective and retrospective evidence of equivalent locoregional control with RT alone. We used the National Cancer Database (NCDB) to evaluate the trends in utilization of chemotherapy in conjunction with RT in early stage OPSCC. This study compared outcomes following definitive CRT or RT in T1N0-1 and T2N0 OPSCC patients diagnosed between 1998 and 2012. Chi squared analysis was used to compare CRT to RT for clinicopathologic factors and trends in use over time. Logistic regression (LR) was performed to determine the odds ratio (OR) for factors associated with receipt of CRT. HPV/p16 was not assessable due to limited reporting prior to 2010. Due to significant imbalances in patient characteristics, propensity-score matching was performed based on probability of receipt of CRT and quartile of patients most likely to receive CRT were evaluated with Kaplan Meier for OS. We identified 3,346 early stage OPSCC patients with median age of 61 years. Use of CRT increased significantly from 14.5% in 1998 to a peak of 57.8% in 2007 and remained elevated at 54.3% in 2012 (OR 1.16/year, 95% CI 1.147 – 1.189, p<0.01). Those patients who received CRT were younger (52.7 vs 42.1% < 60 years, p<0.01), had private insurance (58.0 vs 42.2%, p<0.01), with less tonsil primaries (35.8 vs 47.5%, p<0.01), had lower comorbidity scores (86.3 vs 82.5% Charlson/Deyo score 0, p<0.01), and more often had T2 (52.6 vs 41.4% T1, p<0.01) and N1 (43.7 vs 15.3%, p<0.01) disease. In propensity-score matching, 3-year OS for the quartile most likely to receive chemotherapy was not significantly different for CRT vs RT (91.1%, 95% CI 89.8 – 92.4; vs 87.6%, 95% CI 85.3 – 89.9, log rank p=0.37). There has been a remarkable increase in the utilization of chemotherapy for early stage OPSCC despite lack of evidence showing improvement in outcomes and at the expense of increased toxicity. Further work is needed to determine if the ASTRO consensus guidelines will impact the addition of chemotherapy to radiation in this patient population.