Inflammatory markers as prognostic factors of recurrence in advanced stage squamous cell carcinoma of the head and neck
BACKGROUND. Multiple immunologic parameters have provided useful prognostic and assessment significance in different cancers, including head and neck squamous cell carcinoma. We sought to identify whether pre-treatment inflammatory markers could prognosticate recurrence in patients with advanced (stage III or IV) head and neck squamous cell carcinomas that underwent therapy with curative intent in a tertiary care center between January 2010 and December 2012.
METHODS. We registered patient demographics, primary tumor characteristics, Human papillomavirus (HPV) status, pre-therapeutic inflammatory markers including body mass index (BMI), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and serum albumin; therapy received, date of relapse, death or last follow up. The main outcome was relapse free survival (RFS). Overall survival (OS) was a secondary outcome.
RESULTS. 235 charts were reviewed, 118 were included. Of these, 86 were oropharyngeal (50 HPV related, 18 were non-HPV related, 17 not available) and 32 non-oropharyngeal (19 HPV related, 7 non-HPV related, and 6 not available). Median follow-up was 2.45 years (IQR, 1.65-3.3). With regards to RFS, HPV positive status had an adjusted HR of 0.357 (95% CI 0.173-0.776, p=0.0087) and for NLR >=5, the raw HR was 1.637 (95% CI 0.673-3.983, p=0.2771). For OS, the raw HR for NLR >=5 was 2.997 (95% CI 1.280-7.018-, p=0.0114), and for HPV positive status, the raw HR was 0.514 (95% CI 0.226-1.169, p=0.1125). Only 54 patients had CRP available for analysis. For RFS, CRP >=8 had a raw HR of 2.350 (95% CI 1.1062-5.198, p=0.0349) and a raw HR of 1.455 (95% CI 0.497-4.260, p=0.4940) for OS. When adjusting NLR for age, gender and p16 positive status, NLR had a decreased hazard ratio of 2.352 (95% CI= 0.945-5.853, p=0.0659) for overall survival.
CONCLUSIONS. NLR>=5 at presentation is not associated with a higher risk of relapse but is associated with a higher risk of death in patients with squamous cell carcinoma of the head and neck. CRP >=8 was associated with a higher risk of relapse but not death. Lastly, HPV positive status was protective with a lower risk of relapse but not death. Interestingly, we found that when adjusting NLR for age, gender and HPV positive status, NLR had a decreased hazard ratio and therefore potentially protective status for overall survival.