Radiotherapy Characteristics and Outcomes for Head and Neck Carcinoma of Unknown Primary vs T1 Base-of-Tongue Carcinoma

JAMA Otolaryngol Head Neck Surg. 2016 Dec 1;142(12):1208-1215. doi: 10.1001/jamaoto.2016.3083.


Importance: Transoral robotic surgery- or transoral laser microsurgery-assisted lingual tonsillectomy may improve the identification rate of hidden base-of-tongue (BOT) carcinoma presenting as head or neck carcinoma of unknown primary (CUP) site.

Objective: To evaluate the potential impact of lingual tonsillectomy in CUP site by comparing differences in radiotherapy volumes, dosimetry, and clinical outcomes for CUP site and T1-category BOT carcinoma.

Design, setting, and participants: Retrospective study of 115 patients treated at a tertiary cancer center between January 1, 2005, and December 31, 2013, that included patients with BOT carcinoma (category T1N1-3M0) and CUP site (category T0N1-3M0) with known p16 status. Fifty-four patients with T1-category BOT carcinoma (50 [92.6%] p16-positive) were treated with definitive intensity-modulated radiotherapy (IMRT), including 34 (63%) who received concurrent chemotherapy. Sixty-one patients with CUP site (38 [62.3%] p16-positive) received definitive (42 [68.9%]) or postoperative (19 [31.1%]) IMRT, including 22 (36%) who received concurrent chemotherapy.

Interventions: Definitive or postoperative IMRT, with or without concurrent chemotherapy.

Main outcomes and measures: Characteristics of mucosal clinical target volume (CTV-T), nodal CTV, and organ-at-risk dosimetry; local, regional, and distant control; cause-specific and overall survival; and Radiation Therapy Oncology Group grade 3 or higher late toxic effects.

Results: Of 115 participants, 104 (90.4%) were male; mean (SD) age was 59 (10) years. High-dose CTV-T was prescribed in all 54 patients with BOT carcinoma and 23 (37.7%) with CUP site (effect size [Δ], 62%; 95% CI, 50%-74%). Low-dose CTV-T included mucosal pharyngeal sites outside the oropharynx in no patients with BOT carcinoma and 26 (42.6%) (95% CI, 30%-54%) with CUP site, with greater low-dose CTV-T volume in CUP site than BOT carcinoma (113 vs 84 cm3; Δ, 30 cm3; 95% CI, 10-49 cm3). Bilateral neck irradiation was used in 53 of 54 patients (98.1%) with BOT carcinoma and 46 of 61 (75.4%) with CUP site (Δ, 23%; 95% CI, 12% to 34%). Patients with BOT carcinoma received a higher maximum dose to the mandible (71 vs 67.2 Gy; Δ, 3.8 Gy; 95% CI, 1.6 to 6 Gy), with a nonsignificantly higher maximum dose (66.1 vs 62.8 Gy; 3.2 Gy; 95% CI, -0.1 to 6.5 Gy) and lower mean dose to the larynx (43.8 vs 47.1 Gy; 3.3 Gy; 95% CI, -0.3 to 6.9 Gy). There were no significant differences in local control, regional control, distant control, cause-specific survival, and overall survival between the BOT carcinoma and CUP site groups stratified by p16 status. Grade 3 Radiation Therapy Oncology Group late toxic effects occurred in 2 patients (3.3%) with CUP site (both neck fibrosis) and 5 (9.3%) with BOT carcinoma (2 neck fibrosis, 2 osteoradionecrosis, and 1 dysphagia).

Conclusions and relevance: Intensity-modulated radiotherapy for CUP site or T1-category BOT carcinoma had similar clinical outcomes. Identifying hidden BOT primary carcinoma with novel approaches (eg, transoral robotic surgery and transoral laser microsurgery) may lead to changes in the radiotherapy target volume and dose prescription. Studies are needed to investigate the effect of these differences on quality of life and functional outcomes.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Carcinoma / therapy*
  • Chemoradiotherapy
  • Cisplatin / therapeutic use
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Female
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / secondary
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Male
  • Middle Aged
  • Neoplasms, Unknown Primary / metabolism
  • Neoplasms, Unknown Primary / pathology
  • Neoplasms, Unknown Primary / therapy*
  • Radiotherapy Dosage
  • Radiotherapy, Intensity-Modulated* / adverse effects
  • Retrospective Studies
  • Tongue Neoplasms / metabolism
  • Tongue Neoplasms / pathology
  • Tongue Neoplasms / therapy*
  • Tonsillectomy


  • Antineoplastic Agents
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cisplatin