Radiotherapy Versus Chemoradiation in Elderly Head-and-Neck Squamous Cell Carcinoma Patients – A Retrospective International Multicenter Study

Abstract

<h3>Purpose/Objective(s)</h3> While the proportion of elderly head-and-neck squamous cell carcinoma (HNSCC) patients is increasing, the evidence regarding the ideal treatment for this patient cohort is limited. The benefit of concomitant chemotherapy (CT) has been reported to decrease in elderly HNSCC patients; however, it remains unknown whether modern supportive treatments, state-of-the art radiotherapy (RT) techniques and the generally improved performance status of elderly patients nowadays may have altered this observation. <h3>Materials/Methods</h3> Elderly (≥65 years) patients with locoregionally advanced HNSCCs of the oral cavity, oropharynx, hypopharynx or larynx (cT3-4 and/or cN+) receiving definitive RT, with or without concomitant CT, between 2005 and 2019 were eligible for this analysis. Exclusion criteria were recurrent HNSCCs, distant metastases at the time of RT, or HNSCCs from the nasopharynx, salivary glands or the skin. <h3>Results</h3> A total of 824 elderly HNSCC patients from nine tertiary cancer centers met the inclusion criteria and were analyzed. The median age amounted to 72 years (range 65-96 years), and 568 patients (80% of the patients with known ECOG status, n=708) exhibited an ECOG performance status of 0 or 1. The median age-adjusted Charlson Comorbidity Index (CCI) ranged at 4 points (IQR 3-5). Only a minority of HNSCCs (n=140, 17%) exhibited p16 positivity. About half of the cohort suffered from oropharyngeal carcinomas (n=418, 51%), followed by cancers of the hypopharynx (n=151, 18%), oral cavity (n=124, 15%), larynx (n=102, 12%) and multi-level carcinomas (n=29, 4%). A positive smoking history was present in 473 patients (70% of the patients with known smoking status, n=674). Seven hundred thirty-six (89%) of the analyzed patients completed the pre-specified RT dose. OS/PFS amounted to 71%/56% at 1 year, 56%/45% at 2 years, and 46%/38% at 3 years, respectively. Chemoradiation (CRT) resulted in significantly improved OS (HR=0.49, <i>p</i><0.05) and PFS (HR=0.53, <i>p</i><0.05) compared to RT. Even for patients aged ≥75 years (n=329), CRT was associated with superior OS (HR=0.57, <i>p</i><0.05) and PFS (HR=0.61, <i>p</i><0.05). However, patients receiving concomitant CT were significantly younger (<i>p</i><0.05), exhibited a better ECOG performance status (<i>p</i><0.05) and fewer comorbidities (<i>p</i><0.05). In order to control for these disparities, a matched-pair analysis with the matching variables ECOG, CCI and age was conducted, resulting in 98 matching pairs (n=196): Here, both OS (HR=0.44, <i>p</i><0.05) and PFS (HR=0.45, <i>p</i><0.05) remained superior in the CRT compared to the RT group. <h3>Conclusion</h3> This analysis suggests a benefit of concomitant CT in elderly HNSCC patients receiving RT and does not support the usage of a strict age cut-off for CT. Structured assessment of patient performance and comorbidities may help to guide treatment decisions regarding CRT in elderly HNSCC patients.