Evaluation of risk-tailored individualized selection of radiation therapy target volume for head and neck carcinoma of unknown primary

Radiother Oncol. 2022 Oct:175:56-64. doi: 10.1016/j.radonc.2022.07.016. Epub 2022 Jul 26.


Purpose: Intensity-modulated radiation therapy (IMRT) has enabled risk-tailored approach to elective mucosal and nodal clinical target volumes (CTVs) in treatment of head and neck carcinoma of unknown primary (HNCUP). This study report outcomes following such approach.

Methods: HNCUP patients treated with definitive IMRT between 2005 and 2018 were reviewed. Local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS) and grade ≥3 late toxicity (LT) were analyzed. Multivariable analysis (MVA) was used to identify OS predictors for entire cohort and cN2-3 subgroup.

Results: A total of 203 patients were eligible: cN1 (7%), cN2a (14%), cN2b (46%), cN2c (14%) and cN3 (19%). Among 118 patients with known HPV status (by p16 staining), 81 (68%) were positive. IMRT target volume spared contralateral tonsil (55%), bilateral or contralateral sides of hypopharynx (72%), nasopharynx (72%), larynx (87%) and contralateral uninvolved neck (21%). Median follow-up was 5 years. Five-year LF, RF, DM, OS, and LT were 3%, 14%, 10%, 79%, and 7% respectively. Four patients developed mucosal recurrence: 3 within and 1 at the margin of the elective mucosal CTV. None of ipsilateral neck irradiation patients failed in the contralateral uninvolved neck. MVA identified cN2c-N3, HPV-negative status and older age as predictors for inferior OS. Within cN2-3 subgroup (n = 189): cN2c-N3, HPV-negative status and older age predicted lower OS, while concurrent chemotherapy was associated with better OS.

Conclusion: Definitive IMRT with risk-adaptive radiation volume de-escalation for HNCUP resulted in high probability of tumor control with acceptable rate of late toxicity.

Keywords: Head and neck cancer; IMRT; Outcomes; Radiation therapy; Unknown primary; Volume de-escalation.

MeSH terms

  • Carcinoma*
  • Head and Neck Neoplasms* / etiology
  • Head and Neck Neoplasms* / radiotherapy
  • Humans
  • Neoplasms, Unknown Primary* / pathology
  • Neoplasms, Unknown Primary* / radiotherapy
  • Papillomavirus Infections*
  • Radiotherapy, Intensity-Modulated* / adverse effects
  • Radiotherapy, Intensity-Modulated* / methods