Abstract
BackgroundThis study investigated the prognostic role of nuclear expression of p65 in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) receiving post-operative radio(chemo)therapy.MethodsNuclear p65-expression (H-score ≤50 versus >50) plus twelve characteristics were analyzed in 151 patients for overall survival (OS), metastases-free survival (MFS) and loco-regional control (LRC). Additional characteristics included age, gender, Karnofsky performance score (KPS), pre-radiotherapy hemoglobin levels, tumor site, histological grading, human papilloma virus (HPV)-status, T-classification, N-classification, American Joint Committee on Cancer (AJCC)-stage, extent of resection and concurrent chemotherapy. Univariate analyses were performed with Kaplan-Meier method and log-rank test, multivariate analyses with Cox proportional hazards model.ResultsOn univariate analyses, p65-expression had a significant impact on OS (p < 0.001) and LRC (p < 0.001) but not on MFS (p = 0.29). On multivariate analysis, KPS ≥80 (risk ratio [RR] 2.23; p = 0.012), HPV-positivity (RR 5.83; p = 0.020), T1-T2 (RR 1.38; p = 0.048), N0-N2a (RR 2.72; p = 0.005) and complete resection (RR 2.02; p = 0.049) were positively associated with OS; p65-negativity achieved borderline significance (RR 3.02; p = 0.052). Better MFS was associated with KPS ≥80 (RR 2.49; p = 0.015), T1-T2 (RR: 1.74; p = 0.005), N0-N2a (RR: 6.22; p < 0.001) and complete resection (RR 3.43; p = 0.003). Positive associations with LRC were found for p65-negativity (RR 5.06; p = 0.008), T1-T2 (RR: 1.49; p = 0.022), N0-N2a (RR: 2.97; p = 0.004) and favorable tumor site (RR 1.28; p = 0.025).ConclusionsP65-negativity was significantly associated with improved LRC and achieved borderline significance with respect to improved OS. Thus, p65-expression may be an additional target for novel agents in the treatment of locally advanced SCCHN.
Highlights
This study investigated the prognostic role of nuclear expression of p65 in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) receiving post-operative radio(chemo) therapy
Better metastases-free survival (MFS) was associated with Karnofsky performance score (KPS) ≥80 (RR 2.49; p = 0.015), T1-T2 (RR: 1.74; p = 0.005), N0-N2a (RR: 6.22; p < 0.001) and complete resection (RR 3.43; p = 0.003)
P65-negativity was significantly associated with improved loco-regional control (LRC) and achieved borderline significance with respect to improved overall survival (OS)
Summary
This study investigated the prognostic role of nuclear expression of p65 in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) receiving post-operative radio(chemo) therapy. Many patients with squamous cell carcinoma of the head and neck (SCCHN) present with locally advanced disease, which is often associated with unsatisfactory outcomes despite innovative treatment approaches [1,2,3]. The prognostic role of nuclear factor kappa B (NF-ĸB) has been suggested in a retrospective study of 101 SCCHN patients treated with definitive radio-chemotherapy [8]. In that study based on material from biopsies, nuclear expression of p65 (RelA), a transcription factor belonging to the NF-ĸB family, was associated with worse overall survival (OS) and metastases-free survival (MFS) in addition to a trend towards worse loco-regional control (LRC). Nakayama et al found in their series of 36 untreated biopsy specimens from patients with SCC and 15 specimens with epithelial dysplasia of the oral cavity that high expression of p65 was associated with malignant behavior [9]
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