title: Surgery with complete resection improves survival in radiooncologically treated patients with cervical lymph node metastases from cancer of unknown primary.
abstract: OBJECTIVE
  To assess long-term toxicity, outcome and prognostic factors after multimodal treatment of cervical lymph node metastases from cancer of unknown primary (CUP).
  
  
  METHODS
  In a retrospective study, the treatment results of 84 patients with CUP (median age 63 years, N1 n = 0, N2 n = 44, N3 n = 39, Nx n = 1), treated between 1971 and 2002 with radiotherapy (n = 84, median dose 60 Gy), platinum-based chemotherapy (n = 23) and surgery (n = 69, tonsillectomy [n = 40], neck dissection [n = 52], suprahyoid dissection [n = 18], lymph node excision [n = 14]), were analyzed.
  
  
  RESULTS
  After a mean follow-up time of 25 months (ranging from 0.1 to 260 months), the 3- and 5-year overall (disease-free) survival rates were 30% (39%) and 27% (34%), respectively. 75% of individuals achieved remission, whereas 23% showed no change or progression after treatment. The 3-, 5- and 10-year local control rates were 58%, 58% and 46%, respectively. 40% of patients suffered grade 3/4 late toxicity: severe skin contracture/induration (n = 2) and severe xerostomia (n = 32). Tonsillectomy (p = 0.003) and neck dissection (p = 0.037) performed before radiotherapy significantly improved outcome. Other prognostic factors were age (p = 0.0235), extracapsular spread (n = 63; p = 0.0045), incomplete resection (n = 24; p = 0.0026), nodal disease (p = 0.0034), and distant metastases (n = 17; p = 0.0002). After multivariate analysis only extracapsular spread (p = 0.004) and tonsillectomy (p = 0.01) showed impact on survival.
  
  
  CONCLUSIONS
  Irradiation of cervical lymph node metastases from CUP is an effective treatment option with acceptable late toxicity. Complete tonsillectomy and neck dissection significantly improved survival in N2/N3 disease. Extracapsular spread was the best predictor for survival and local control. Prospective studies defining a standard treatment are needed.
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Germany. Henrik.Hauswald@med.uni-heidelberg.de
authors.forename: Henrik
authors.initials: H
authors.lastname: Hauswald
authors.forename: Katja
authors.initials: K
authors.lastname: Lindel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rochet
authors.forename: Juergen
authors.initials: J
authors.lastname: Debus
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Harms
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D037981:Neck Dissection; D009367:Neoplasm Staging; D009382:Neoplasms, Unknown Primary / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012074:Remission Induction; D012189:Retrospective Studies; D013997:Time Factors; D014068:Tonsillectomy