Impact of pretherapeutic neutrophil-to-lymphocyte ratio, serum albumin, body-mass index, and advanced lung cancer inflammation index on clinical outcome in sinonasal squamous cell carcinoma

Abstract

Background

Squamous cell carcinoma of the nasal cavity and paranasal sinuses is a rare and aggressive cancer entity with poor survival rates. Data on this group of head and neck tumors are scarce. Inflammation and cachexia-based markers and their impact on clinical outcome have been studied in several cancer groups. The aim of this study was to evaluate their prognostic potential in sinonasal squamous cell carcinoma.

Patients and methods

This retrospective analysis included all patients treated for sinonasal squamous cell carcinoma at a tertiary referral center between 2002 and 2015. Patients were divided into groups with low and high pretherapeutic values based on the values of serum albumin (ALB, median 41.6 g/l), neutrophil-to-lymphocyte ratio (NLR, median 3.5), body-mass index (BMI, median 24.7), or advanced lung cancer inflammation index (ALI, median 29.5). Main outcome measures were overall survival (OS) and disease-free survival (DFS). Statistical analysis included calculation of survival differences using log-rank tests, hazard ratios (HR), and respective 95% confidence intervals (CI).

Results

41 patients were included. Low ALB values did not influence OS (median OS not reached in both groups; p = 0.59, HR = 0.75, CI = 0.3–2.1) or DFS (median DFS 0.9 years vs 2.2 years; p = 0.6, HR = 0.8, CI = 0.4–1.8). High NLR was significantly associated with worse OS rates (median OS not reached vs 1.7 years, p = 0.02, HR = 3.4, CI = 1.0–108) but with no influence on DFS (median DFS 3.1 years vs 0.8 years; p = 0.15, HR = 1.8, CI = 0.8–4.2). Similar results were observed for patients with low ALI (median OS 1.7 years vs not reached; p = 0.03, HR = 0.3, CI = 0.1–0.9 and median DFS 0.8 years vs 2.2 years; p = 0.58, HR = 0.8, CI = 0.3–1.8). BMI was the strongest prognosticator in our study. Low pretherapeutic BMI was linked to significantly worse OS (median OS 1.4 years vs not reached; p = 0.003, HR = 0.2, CI = 0.0–0.6) and DFS (median DFS 0.8 years vs not reached; p = 0.02, HR = 0.4, CI = 0.2–0.8). In multivariate analysis BMI was revealed as an independent marker for OS (p = 0.015). No marker reached the level of significance in regard to DFS in multivariate analysis.

Conclusion

Pretherapeutic BMI had a superior prognostic value in patients with sinonasal squamous cell carcinoma in comparison with other tested variables. BMI may be a simple tool for estimating clinical outcome in SNSCC. However, larger studies are necessary to validate our results.

Introduction

Sinonasal carcinomas include cancers of the nasal cavity and paranasal sinuses. These carcinomas comprise less than 1% of all cancers among men and less than 0.5% among women (Curado et al., 2007). Most sinonasal cancers have an epithelial histology, with squamous cell carcinomas being the most frequent, followed by adenocarcinomas (Franchi et al., 2011). Survival of patients with this rare and aggressive malignancy is low, with a 5-year survival rate of less than 40% (Kuo et al., 2017).

A common therapy modality for sinonasal squamous cell carcinoma (SNSCC) is surgical resection, showing excellent results in small tumors with clear resection margins (Robbins et al., 2011). However, in many patients SNSCC is detected at a rather advanced stage, which makes surgical resection more difficult, especially because of the close proximity to the orbit and skull base. In large tumors and in resections with positive margins, postoperative radiotherapy is employed. However, survival of these patients remains poor. In locally advanced cases (T4b) primary chemoradiotherapy is utilized, although the benefit of this therapeutic approach remains questionable (Porceddu et al., 2004).

Systemic inflammation is known to be an important factor during carcinogenesis in many cancer types; it enhances angiogenesis, response to treatment, and metastasis development (Mantovani, 2009). The role of inflammation in sinonasal cancer was investigated by Turri-Zanoni et al. (2017). They reported that high pretherapeutic values of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with poor survival.

Pretherapeutic values of nutrition markers, namely body-mass index (BMI) and serum albumin (ALB), can also be used as survival predictors in malignant diseases. Gama et a.l (Gama et al., 2017) noted that high BMI prior to therapy is associated with better outcomes in head and neck cancer. Similar results were reported by Takenaka et al. (2015).

Pretreatment ALB was shown to be a significant prognosticator in head and neck squamous cell carcinoma Lim et al. (Lim et al., 2017). Head and neck cancer patients often present with a poor nutritional status and weight loss at the time of initial diagnosis (McRackan et al., 2008). Therefore, patients with a higher BMI might have greater nutritional reserves for enduring the side-effects of radio- and chemotherapy, including appetite loss, mucositis, and oral pain (Jafri et al., 2013).

Advanced lung cancer inflammation index (ALI) appears to be another useful tool for predicting patients outcome. It is calculated by multiplying the ALB value (g/l) and the BMI, and then dividing by the NLR. The importance of its predictive value has been shown with regard to lung cancer (Jafri et al., 2013). Feng et al. (2014) reported on the significant prognostic value of ALI in esophageal squamous cell carcinoma. Jank et al. (2019) noted that low pretherapeutic ALI was linked with significantly worse overall survival (OS) and disease-free survival (DFS) in patients with head and neck squamous cell carcinoma undergoing primary surgical resection with postoperative radiotherapy.

Generally, research into predictive markers in head and neck cancer focuses on tumors localized in the oral cavity, pharynx, or larynx. Studies investigating SNSCC are comparatively rare. Our study aimed to investigate the prognostic value of pretherapeutic inflammation and the nutritional markers NLR, ALB, BMI, and ALI in SNSCC patients.