MethodsRetrospective observational study
Participants and CountryN=56 including 50 males. Median age: 56 years (range: 33 to 81 years). Levels of nodal metastases were: I = 14, II = 39, III = 19, IV = 8, V = 9. Nodal staging was: N1 = 6, N2 = 37 and N3 = 13.
Country: Slovenia
InterventionsAll patients underwent surgery and post-operative RT. Neck dissection was performed in 48 patients and extended to neighbouring structures (parotid gland, mandible and external carotid artery) in 6 patients. The surgery was classified as:
  • Radical neck dissection (n=29)
  • Modified radical neck dissection only (n=7)
  • Selective neck dissection (n=6)
  • Extended neck dissection (n=6)
These procedures were assessed to have been complete in 45 cases but, in 11 patients, residual tumour was detected in histological samples.
Post-operative RT was given to 48 patients at a dose of 18 to 62Gy (median 50Gy) in 1.8 to 2Gy daily fractions applied five times weekly, although 6 patients received a lower dose of <50Gy. Five patients refused treatment and 1 patient died before receiving RT. The field of treatment depended on the level of nodal involvement and patient lifestyle i.e. history of smoking and/or drinking.
OutcomesOverall survival (OS) disease specific survival (DSS) regional (ipsilateral & contralateral neck) control, mucosal control and distant metastases. Adverse events
inclusion exclusion criteriaInclusion criteria: Patients with metastatic squamous cell carcinoma of cervical lymph nodes from an unknown primary tumour.
Exclusion criteria: None stated.
ResultsOverall survival:
5 year OS rate for all patients: 52% (95%CI: 38–65%)
10 year OS rate for all patients: 22% (95%CI: 5–38%)
Disease-specific survival:
5 year DSS rate for all patients: 66% (95%CI: 52–79%)
10 year DSS rate for all patients: 52% (95%CI: 31–72%)
Prognostic factors: extracapsular spread (ECS, +ve vs ?ve) and the extent of the irradiation field (unilateral neck vs neck and potential primary tumour sites) were significant predictors of a poorer 5 year DSS (P = 0.01 and P = 0.04 respectively).
Neck control:
Neck failure occurred in 10 patients, 9 of whom failed a median of 4 months after treatment (38 months for 1 patient). All but one of the patients experienced failure in the RT field, at the site of pre-existent nodal disease (n=7) and/or outside of it (n=2).
Prognostic factors: neck failure was correlated significantly with the extent of the RT field (P = 0.03) since when the neck alone received RT the failure rate was 50% compared with RT of potential primary sites (12%).
Mucosal control:
A primary lesion was detected in 5 patients after a median interval of 21 months (range: 16 to 98 months). None of the primary tumours occurred below the clavicles: oropharynx (n=2) maxillary sinus (n=1) nasopharynx (n=1) larynx (n=1). After further surgical or RT treatment, these patients survived between 29 and 108 months. One patient died of unrelated causes, 3 died of disease and 1 patient had no evidence of disease at last follow-up.
Distant failure:
Recurrence at distant sites was experienced by 6 patients within a median time after treatment of 7 months (range: 2 to 39 months). Metastases occurred in: liver (n=3) bone (n=2) lung (n=3) and other lymph nodes (n=1). All patients had ECS and were of stages N2 (n=4) or N3 (n=2). There
Prognostic factors: there were no prognostic factors for this outcome.
Adverse events:
Thirty-three patients, all of whom had received radical, or extended radical, neck dissection experienced surgical morbidity to some extent, including pain and reduced mobility. In patients irradiated by a large field technique, 27 patients reported mucositis (grade 3 in 23 patients and grade 4 in 4 patients) and 3 patients had grade 3 dermatitis. Late adverse effects included xerostomia (n=35) subcutaneous and/or muscular fibrosis (n=22) and trismus (n=2).
Follow-upFollow-up: The median follow-up time was 8.6 years (range: 1.6 to 17.8 years) and 79% of patients were followed for a minimum of 5 years.
NotesThis study describes a retrospective case file review of 56 patients treated for cervical lymph node metastases with surgery and post-operative RT between 1975 and 1994 at one Slovenian university oncology institute.
Data were analysed by the Kaplan Meier method, univariate and multivariate (Cox’s proportional hazard ratio). Prognostic factors affecting the treatment outcomes were reported but multivariate analysis was not performed due to the low patient number.
The authors concluded that the combined therapy resulted in acceptable toxicity, good local disease control and favourable survival results but that patients with a poorer prognosis may benefit from a more aggressive approach, perhaps employing the use of chemotherapy.

From: Guideline chapter 4, Specific Presentations

Cover of Diagnosis and Management of Metastatic Malignant Disease of Unknown Primary Origin
Diagnosis and Management of Metastatic Malignant Disease of Unknown Primary Origin.
NICE Clinical Guidelines, No. 104.
National Collaborating Centre for Cancer (UK).
Copyright © 2010, National Collaborating Centre for Cancer.

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