| Summary: | 博士 === 國立臺灣大學 === 病理學研究所 === 105 === The behavior of hypopharyngeal cancer is different from those cancers arising from other head and neck subsites, despite their similar histological presentation. Frequent advanced stage at presentation, poor nutrition, common lymphatic and systemic spread, and predisposition to development of second malignancies are the main causes of its poor prognosis. Owing to the reality that most patients are diagnosed to have stage III or IV disease in spite of different size of primary lesions or even nodal classification, it is sometimes difficult to estimate treatment outcome in this heterogeneous combination. Therefore, this study aimed to investigate the clinicopathological prognostic predictors of resected T3-4 or stage IV hypopharyngeal squamous cell carcinomas (SCCs) and extend the traditional TNM classification system to advance its predictive ability.
We performed a case note review of T3-4 or stage IV hypopharyngeal SCC patients treated with pharyngolaryngectomy and neck dissection between January 2001 and December 2008 in one tertiary center. All patients had pathological T3-4 or stage IV disease and received planned adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) treatment. In the first part of our study, a total of 105 patients with pathologically T3-4 hypopharyngeal cancer were enrolled. The 5-year disease-free, disease-specific and overall survivals of all the patients were 47.2%, 50.6% and 44.8%, respectively. The pretreatment neutrophil-to-lymphocyte ratio (NLR; median, 3.22; range, 0.62-46.50) was associated with disease recurrence and patient survival. A difference in the 5-year cumulative disease recurrence rate between patients with high NLRs (≥ 3.22) and low NLRs (< 3.22) was significant (60.4% and 36.5%, respectively; p = 0.004). A multivariate analysis confirmed that an NLR ≥ 3.22 was an independent indicator of a poor prognosis for advanced hypopharyngeal SCC per the following parameters: overall survival [hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.48-4.30, p = 0.001], disease-specific survival (HR 2.45, 95% CI 1.38-4.34, p = 0.002), and disease-free survival (HR 2.18, 95% CI 1.24-3.83, p = 0.007). An NLR ≥ 3.22 is associated with a higher risk of disease recurrence and poor survival in patients with resected T3-4 hypopharyngeal SCCs.
In the second part of our study, a total of 120 patients with pathologically stage IV hypopharyngeal cancer were enrolled. The 5-year disease-free, disease-specific and overall survivals of all the patients were 48.0%, 51.6% and 44.6%, respectively. The lymph node ratio (mean, 0.113; range, 0-1) was associated with disease recurrence and patient survival. In multivariate analysis, lymph node (LN) ratio ≥ 0.113 was a significant poor prognostic factor for OS [hazard ratio (HR) 1.89, 95 % confidence interval (CI) 1.17-3.05, p = 0.009], DSS (HR 2.17, 95 % CI 1.29-3.64, p = 0.003), and DFS (HR 2.24, 95 % CI 1.12-4.52, p = 0.024) in stage IV hypopharyngeal cancer. Patients with LN ratio ≥ 0.113 had significantly ( all ps < 0.05) higher rates of local failure (25.0 % vs. 6.4 %), regional recurrence (25.0 % vs. 9.2 %) and distant metastases (50.0 % vs. 31.6 %) than those with LN ratio < 0.113. Furthermore, we found that patients with LN ratio ≥ 0.113 or < 0.113 had significantly difference in disease recurrence (68.2 % vs. 39.5 %, respectively; p = 0.002).
In conclusion, we found that pretreatment NLR ≥ 3.22, and LN ratio ≥ 0.113 had significant relation with disease control and treatment outcomes in patients with T3-4, and stage IV hypopharyngeal SCCs, respectively. We propose the use of an NLR and LN ratio to broaden the current TNM staging system to advance its predictive ability; the development of a more effective treatment protocol for patients with either high NLRs or high LN ratio will be essential and merits basic or clinical studies in the future.
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