Prognostic Impact of Matted Lymphadenopathy in Oropharynx Cancer Treated With Chemoradiotherapy

Abstract

<h3>Purpose/Objective(s)</h3> Identifying prognostic factors beyond p16 status and smoking history in patients with oropharyngeal squamous cell carcinoma (OPC) is an area of active research. Prior data have suggested that the relatively straightforward radiologic finding of matted lymphadenopathy (ML) was strongly associated with disease-specific survival after chemoradiotherapy (CRT), but these results have not been validated in larger datasets. In this analysis, we evaluated the impact of ML on oncologic outcomes in a large cohort of patients treated with CRT for OPC. We hypothesized that ML would be associated with poorer outcomes as measured by rates of regional recurrence, distant metastasis and overall survival. <h3>Materials/Methods</h3> All OPC patients treated with definitive CRT at our institution between 2005 and 2018 were eligible for this retrospective analysis. ML was defined by three adjacent nodes without an intervening fat plane. Each subject scan was evaluated manually for these characteristics. Patients were stratified into favorable OPC (p16-positive with ≤ 10 pack-years smoking history) or unfavorable OPC (p16-negative or 10+ pack-years). Overall survival (OS) and progression-free survival (PFS) were determined using Kaplan-Meier statistics, and Cox regression was performed for multivariable adjustment. The cumulative incidences of distant metastasis (DM) and regional recurrence (RR) were calculated with death as a competing risk. <h3>Results</h3> A total of 417 patients (220 favorable, 197 unfavorable) were included, with a median follow-up time for surviving patients of 49.9 months. For patients with favorable OPC, there were no associations between ML and OS, PFS, RR, or DM. In contrast, the presence of ML was significantly and independently associated with worsened OS in patients with unfavorable OPC; the 3-year OS without and with ML was 74% vs. 56% (<i>P</i> = 0.05). On multivariable regression, only ML (HR 1.65, 95% CI 1.03-2.65) and active smoking were significantly related to OS. Similarly, 3-year PFS was 67% vs 44% without vs. with ML (<i>P</i> < 0.01), and ML retained significance for decreased PFS on multivariable analysis (HR 1.94, 95% CI 1.28-2.93). Finally, ML predicted increased rates of DM on both univariable and multivariable analysis (31% with vs. 9% without, HR 3.3, 95% CI 1.71-6.48, <i>P</i> < 0.01) for patients with unfavorable OPC. <h3>Conclusion</h3> Matted lymphadenopathy carried no meaningful prognostic impact in patients with favorable oropharyngeal squamous cell carcinoma, arguing ML should not be a contraindication for treatment de-escalation. However, for patients with either a significant smoking history or HPV-negative disease, ML was associated with a markedly adverse outcome. This population of OPC may be particularly well-suited for treatment intensification.