Extranodal extension in head and neck squamous cell carcinomas as a risk factor for pulmonary metastases: a multicentre, prospective cohort study

Abstract

BACKGROUND: Head and neck malignancies rank sixth in incidence as a group of cancer. Within the histological types, squamous cell carcinoma is the most prevalent one, and it is associated with risk factors such as tobacco or alcohol. These tumours are characterized by their rapid lymphatic spread to regional lymph nodes, frequently having to associate a cervical lymphadenectomy as a part of the treatment. These neoplasms also have a high percentage of distant metastases after treatment of the primary tumour. The lung is the most affected organ, with a poor prognosis when pulmonary metastases develop. New clinical and pathological markers are considered when establishing the prognosis. The type of follow-up performed on patients affected by these neoplasms may be modified by these factors. Extranodal extension (ENE) is an upstaging factor as stated in the last TNM edition. Although TNM staging system suggests a division into major and minor ENE subtypes, studies are lacking to conclude ENE’s role in distant metastases. Moreover, none of them evaluate these subtyping implications. OBJECTIVES: To determine if there is a direct association between the HNSCC’s extranodal extension and the incidence of pulmonary metastases. Also, as a secondary objective, to determine if this association is maintained in both minor and major subtypes of extranodal extension. DESIGN: This study is designed as a multicentre observational prospective cohort study with three-year follow-up. SAMPLE: A non-probabilistic consecutive sampling method will be performed, and the patients will be recruited in six hospitals around Catalonia. The patients must have received a cervical lymphadenectomy as part of their HNSCC’s treatment and be older than 18 years. METHODS: We will recruit 200 patients in 15 months, with a follow-up of three years. Two groups will be created, one with extranodal extension stratified in ENEma and ENEmi, and another without extranodal extension. We will observe if pulmonary metastases are detected during the follow-up. We will use a Cox regression adjusted for the covariates with a CI of 95%