title: Total Mucosal Irradiation with Intensity-modulated Radiotherapy in Patients with Head and Neck Carcinoma of Unknown Primary: A Pooled Analysis of Two Prospective Studies.
abstract: To determine the clinical outcomes of an intensity-modulated radiotherapy technique for total mucosal irradiation (TM-IMRT) in patients with head and neck carcinoma of unknown primary (HNCUP).
  
  
  
  A single-centre prospective phase II trial design was used in two sequential studies to evaluate TM-IMRT for HNCUP. Patients were investigated for primary tumour site using examination under anaesthetic and biopsies, computed tomography ± magnetic resonance imaging (MRI) or 18-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT). Patients received IMRT to the potential primary tumour sites and elective cervical nodes. Concomitant chemotherapy was used in patients who received primary radiotherapy or those with nodal extracapsular extension.
  
  
  
  Thirty-six patients with HNCUP were recruited; 72% male. Twenty-five patients (69.4%) had p16-positive disease. Two year mucosal and local nodal control rates were 97.1% (95% confidence interval 91.4-100) and 89.8% (78.4-100), respectively. One mucosal primary was detected 7.3 months after TM-IMRT and three patients died from recurrent/metastatic squamous cell carcinoma of the head and neck. Twelve patients (33%) developed grade 3 (Late Effects in Normal Tissue-Subjective, Objective, Management and Analytical; LENT-SOMA) dysphagia with a 1 year enteric tube feeding rate of 2.7%. The high-grade subjective xerostomia rate (LENT-SOMA) at 24 months after IMRT was 15%.
  
  
  
  At a median follow-up of 36.1 months, the use of TM-IMRT was associated with good local control. Toxicity was comparable with previously reported TM-IMRT regimens encompassing similar mucosal volumes.
authors.affiliation: Head and Neck Unit, Royal Marsden Hospitals NHS Foundation Trust, London and Surrey, UK.
authors.forename: T M
authors.initials: TM
authors.lastname: Richards
authors.affiliation: Head and Neck Unit, Royal Marsden Hospitals NHS Foundation Trust, London and Surrey, UK; The Institute of Cancer Research, London, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Bhide
authors.affiliation: Head and Neck Unit, Royal Marsden Hospitals NHS Foundation Trust, London and Surrey, UK.
authors.forename: A B
authors.initials: AB
authors.lastname: Miah
authors.affiliation: Head and Neck Unit, Royal Marsden Hospitals NHS Foundation Trust, London and Surrey, UK.
authors.forename: L
authors.initials: L
authors.lastname: Del Rosario
authors.affiliation: Department of Statistics, Royal Marsden Hospitals NHS Foundation Trust, Sutton, UK.
authors.forename: S
authors.initials: S
authors.lastname: Bodla
authors.affiliation: Department of Pathology, Royal Marsden Hospitals NHS Foundation Trust, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Thway
authors.affiliation: Head and Neck Unit, Royal Marsden Hospitals NHS Foundation Trust, London and Surrey, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Gujral
authors.affiliation: Head and Neck Unit, Royal Marsden Hospitals NHS Foundation Trust, London and Surrey, UK.
authors.forename: K P
authors.initials: KP
authors.lastname: Rooney
authors.affiliation: Head and Neck Unit, Royal Marsden Hospitals NHS Foundation Trust, London and Surrey, UK.
authors.forename: U
authors.initials: U
authors.lastname: Schick
authors.affiliation: Head and Neck Unit, Royal Marsden Hospitals NHS Foundation Trust, London and Surrey, UK.
authors.forename: T
authors.initials: T
authors.lastname: McGovern
authors.affiliation: Head and Neck Unit, Royal Marsden Hospitals NHS Foundation Trust, London and Surrey, UK.
authors.forename: L
authors.initials: L
authors.lastname: Grove
authors.affiliation: Head and Neck Unit, Royal Marsden Hospitals NHS Foundation Trust, London and Surrey, UK.
authors.forename: K L
authors.initials: KL
authors.lastname: Newbold
authors.affiliation: Head and Neck Unit, Royal Marsden Hospitals NHS Foundation Trust, London and Surrey, UK; The Institute of Cancer Research, London, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Harrington
authors.affiliation: Head and Neck Unit, Royal Marsden Hospitals NHS Foundation Trust, London and Surrey, UK. Electronic address: Chris.Nutting@rmh.nhs.uk.
authors.forename: C M
authors.initials: CM
authors.lastname: Nutting
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000528:radiation effects; D009382:Neoplasms, Unknown Primary / Q000532:radiotherapy*; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014057:Tomography, X-Ray Computed; D014987:Xerostomia / Q000209:etiology
keywords: Head and neck; IMRT; occult-primary; prospective; radiotherapy; squamous cell carcinoma