OTOLARYNGOLOGY HEAD AND NECK SURGERY ANZJSurg.com

Contralateral neck failure in lateralized oral squamous cell carcinoma Miriam Habib,* Jothi Murgasen,* Kan Gao,† Bruce Ashford,*‡ Kerwin Shannon,† Ardalan Ebrahimi*§¶ and Jonathan R. Clark*†¶** *Department of Head and Neck Surgery, Liverpool Hospital, Sydney, New South Wales, Australia †Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia ‡Department of Head and Neck Surgery, Wollongong Hospital, Wollongong, New South Wales, Australia §Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia ¶South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia and **Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia

Key words contralateral neck metastasis, lymph nodes, neck dissection, oral cancer. Correspondence Dr Miriam Habib, Level 5 East 06, D-17 Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia. Email: [email protected] M. Habib MBChB, MS; J. Murgasen MBBS; K. Gao BEng; B. Ashford BDSc, MBBS, FRACS; K. Shannon MBBS, FRACS; A. Ebrahimi MBBS, MPH, FRACS; J. R. Clark BSc, MBBS, MBiostat, FRACS. This study was presented at the 5th World Congress of the International Federation of Head and Neck Oncologic Societies, New York City, NY, USA, 28 July 2014. Accepted for publication 3 May 2015. doi: 10.1111/ans.13206

Abstract Background: Elective treatment of the contralateral clinically node-negative (cN0) neck is not routinely recommended for lateralized oral cavity squamous cell carcinoma (SCC). We sought to determine the failure rate in the untreated contralateral neck in patients with lateralized oral SCC undergoing treatment of the primary and ipsilateral neck and to identify any features placing patients at sufficient risk of contralateral regional failure to justify elective treatment. Methods: We identified 688 patients with oral SCC undergoing curative surgery ± adjuvant therapy between 1985 and 2012 from a prospectively collected database. Patients with midline primaries and those undergoing bilateral neck treatment were excluded. The primary endpoint was isolated contralateral neck failure. Results: Of 481 patients, 14 (2.9%) developed isolated contralateral neck recurrence, with median time to recurrence of 8 months. Patients with poorly differentiated tumours or pathologically proven ipsilateral nodal metastases were at significantly higher risk of contralateral failure (hazard ratio (HR) 3.6, 95% confidence interval (CI) 1.1–11.9, P = 0.037 and HR 4.6, 95% CI 1.5–13.8, P = 0.006 respectively). Presence of both of these factors conferred a 10% risk of contralateral failure. Conclusion: Patients with lateralized oral SCC undergoing treatment of the primary tumour and ipsilateral neck have a low rate of isolated contralateral neck failure. Although poorly differentiated primaries and ipsilateral nodal metastases were predictors of contralateral recurrence, the risk remains relatively modest in this subset of patients suggesting close observation may be more appropriate than elective treatment. Our results support current recommendations for observation of the cN0 contralateral neck in lateralized oral SCC.

Introduction The presence of lymph node metastases is widely accepted as the most critical prognostic factor in patients with oral cavity squamous cell carcinoma (SCC).1–3 With the exception of thin early-stage tumours in the context of clinically and radiologically node negative necks (cN0), most patients with oral SCC undergo neck dissection.4 This has the benefit of treating occult metastatic disease and providing pathological staging information to direct adjuvant therapy.5–7 Although elective treatment of the contralateral neck is accepted for oral cancers approaching or crossing the midline, this is not © 2015 Royal College of Surgeons ANZ J Surg 86Australasian (2016) 188–192

routinely performed in lateralized cases. Contralateral neck recurrence rates in oral SCC are reported to be between 0 and 20%.8–13 However, most studies include oropharyngeal cancers and patients with cN+ contralateral neck disease, making it difficult to draw conclusions about the true rate of occult contralateral metastases in lateralized oral SCC. The rich lymphatic network in the head and neck renders oral cavity malignancies susceptible to spread across the midline via crossing vessels or aberrant drainage of the tumour bed secondary to lymphatic obstruction by tumour mass.14 Presence of disease in the contralateral neck confers a poorer prognosis and results in upstaging of patients to N2c in the American Joint Committee on Cancer staging system.15 ANZ J Surg •• (2015) ••–•• © 2015 Royal Australasian College of Surgeons

2Contralateral neck failure

The purpose of this study was to determine the rate of failure in the observed contralateral neck in patients with lateralized oral SCC undergoing surgical treatment of the primary and ipsilateral neck with curative intent. We also sought to define factors predictive of contralateral neck failure in order to identify a subset of patients that are at sufficient risk of contralateral regional failure to justify elective treatment.

Methods Study population The Sydney Head and Neck Cancer Institute at Royal Prince Alfred Hospital, Australia, maintains a prospective clinicopathological database. A retrospective search identified 688 consecutive patients with oral SCC undergoing surgery ± adjuvant therapy with curative intent between May 1985 and December 2012. Exclusion criteria were midline primaries (defined as tumours lying within 1 cm of the midline), patients undergoing contralateral neck dissection and/or irradiation and those who had previously undergone treatment for head and neck malignancy. Elective treatment of the contralateral neck, whether by surgery or radiotherapy, was instituted in selected cases with advanced primary disease or extensive ipsilateral nodal metastases on a case-by-case basis determined by the multidisciplinary team during the study period. The final study population consisted of 481 patients. Demographic data, tumour characteristics and treatment modalities were recorded, as well as follow-up time and outcomes. Salvage outcomes were recorded for patients who failed. All patients were assessed for neck disease by clinical examination which was supplemented with cross-sectional imaging ± positron emission tomography scans as the study period progressed. Ipsilateral neck dissection was performed therapeutically in the presence of clinically or radiologically suspicious lymph nodes and electively in patients at significant risk of occult nodal metastases which generally included all patients except those with small (T1) thin tumours.

Statistics Statistical analysis was performed using Stata version 12.0 SE (StataCorp LP, College Station, TX, USA). All statistics were twosided and a value of P < 0.05 was considered statistically significant. The primary endpoint of interest was isolated contralateral neck failure, that is in the absence of local failure or distant metastasis. This was calculated from the date of surgery to the date of pathologically proven contralateral neck recurrence. Patients not experiencing this endpoint were censored at last follow-up or date of death. Differences in survival were determined using univariate Cox regression analysis and cumulative failure curves were generated using the Kaplan–Meier method when appropriate. The following factors were analysed: age, gender, primary tumour location (oral tongue versus other), T category, N category (pathologically node-positive versus node-negative), tumour grade (poor versus well-moderately differentiated), surgical margins (clear (≥5 mm) versus close or involved (

Contralateral neck failure in lateralized oral squamous cell carcinoma.

Elective treatment of the contralateral clinically node-negative (cN0) neck is not routinely recommended for lateralized oral cavity squamous cell car...
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