title: Randomized trial comparing surgery and adjuvant radiotherapy versus concurrent chemoradiotherapy in patients with advanced, nonmetastatic squamous cell carcinoma of the head and neck: 10-year update and subset analysis.
abstract: BACKGROUND
  The current study was performed to report the long-term results of a trial comparing concurrent chemotherapy and radiotherapy (CCRT) with surgery and adjuvant radiotherapy (RT) in patients with stage III/IV nonmetastatic head and neck squamous cell carcinoma.
  
  
  METHODS
  Patients with stage III/IV resectable head and neck squamous cell carcinoma were randomized to surgery followed by RT or CCRT. The trial was halted prematurely due to poor accrual. Human papillomavirus status was tested on archival material using polymerase chain reaction sequencing.
  
  
  RESULTS
  Of the total of 119 patients, 60 patients were randomized to primary surgery (S arm) and 59 patients were randomized to CCRT (C arm). Human papillomavirus status was tested in 75 patients, and only 3 were found to be positive. The median follow-up for surviving patients was 13 years. Analysis of the entire cohort demonstrated no statistically significant difference in overall survival and disease-specific survival (DSS): 5-year rates were 45% versus 35% for overall survival (P = .262) and 56% versus 46% for DSS (P = .637) for the S arm and C arm, respectively. Analysis by subsites indicated that this difference favoring the S arm was mainly driven by survival data among patients with cancers of the oral cavity and maxillary sinus. For patients with oral cavity cancer, survival was significantly better in those who underwent primary surgery compared with CCRT; the 5-year DSS rate was 68% versus 12% for the S arm and C arm, respectively (P = .038). For patients with cancers of the maxillary sinus, the 5-year DSS rate was 71% for patients on the S arm and 0% for patients on the C arm (P = .05).
  
  
  CONCLUSIONS
  These long-term results demonstrate a significant advantage for primary surgery in patients with cancers of the oral cavity or maxillary sinus, providing strong support for primary surgery as the main modality of treatment for these subsites. In other subsites, CCRT and surgery with adjuvant RT were found to demonstrate similar efficacy for survival in patients with advanced resectable tumors.
authors: Department of Surgical Oncology, National Cancer Centre, Singapore; Cancer Therapeutics Research Laboratory, National Cancer Centre, Singapore.
authors: N Gopalakrishna
authors: NG
authors: Iyer
authors: Daniel S W
authors: DS
authors: Tan
authors: Veronique K M
authors: VK
authors: Tan
authors: Weining
authors: W
authors: Wang
authors: Jacqueline
authors: J
authors: Hwang
authors: Ngian-Chye
authors: NC
authors: Tan
authors: Ranjiv
authors: R
authors: Sivanandan
authors: Hiang-Khoon
authors: HK
authors: Tan
authors: Wan Teck
authors: WT
authors: Lim
authors: Mei-Kim
authors: MK
authors: Ang
authors: Joseph
authors: J
authors: Wee
authors: Khee-Chee
authors: KC
authors: Soo
authors: Eng Huat
authors: EH
authors: Tan
mesh_terms: D000328:Adult; D000368:Aged; D052685:Alphapapillomavirus / Q000302:isolation & purification; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy* / Q000821:virology; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D004279:DNA, Viral / Q000302:isolation & purification; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy* / Q000821:virology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000175:diagnosis; D016133:Polymerase Chain Reaction; D018714:Radiotherapy, Adjuvant; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
chemical_list: D004279:DNA, Viral; D002945:Cisplatin; D005472:Fluorouracil
keywords: head and neck cancer; head and neck squamous cell carcinoma; oral cancer; surgical arm