Total Mucosal Irradiation with Intensity-modulated Radiotherapy in Patients with Head and Neck Carcinoma of Unknown Primary: A Pooled Analysis of Two Prospective Studies

Clin Oncol (R Coll Radiol). 2016 Sep;28(9):e77-e84. doi: 10.1016/j.clon.2016.04.035. Epub 2016 May 11.


Aims: 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).

Materials and methods: 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.

Results: 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%.

Conclusions: 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.

Keywords: Head and neck; IMRT; occult-primary; prospective; radiotherapy; squamous cell carcinoma.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / radiotherapy*
  • Female
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Male
  • Middle Aged
  • Mucous Membrane / radiation effects
  • Neoplasms, Unknown Primary / radiotherapy*
  • Prospective Studies
  • Radiotherapy Dosage
  • Radiotherapy, Intensity-Modulated / methods*
  • Squamous Cell Carcinoma of Head and Neck
  • Tomography, X-Ray Computed
  • Xerostomia / etiology