UNKNOWN PRIMARY HEAD AND NECK-TARGET VOLUME DELINEATION

Squamous Cell Carcinoma of Unknown Primary

General Principles of Planning and Target Delineation

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  • A thorough workup is mandatory before diagnosing an unknown primary. Minimum evaluation must include:
    • Complete physical exam including cranial nerve testing.
    • Fiberoptic examination visualizing nasopharynx, oropharynx, larynx, and hypopharynx.
    • Cross‑sectional imaging with at least a high‑resolution contrast‑enhanced CT scan.
    • Detailed skin and scalp examination.
  • Careful patient history is essential to determine risk factors and to evaluate potential infraclavicular primary sources (thoracic, gynecologic, gastrointestinal).
  • PET/CT may detect additional primaries not found by other methods; performing PET/CT before biopsy reduces false‑positive findings.
  • Panendoscopy may be useful for identifying subtle or occult mucosal disease.
  • HPV and EBV testing should be performed to help identify possible primary sites:
    • HPV‑associated nodes are classified as T0 oropharynx.
    • EBV‑associated nodes are classified as T0 nasopharynx (AJCC 8th edition).
  • Directed biopsies of all suspicious lesions in the pharyngeal axis are mandatory. Blind biopsies of normal‑appearing mucosa are occasionally helpful but not routinely recommended.
  • Transoral tongue base mucosectomy (lingual tonsillectomy) and at least ipsilateral palatine tonsillectomy can detect ~80% of unknown primaries, especially HPV‑related cases. Some centers perform bilateral palatine tonsillectomies and may omit lingual tonsillectomy.
  • Patients with a single ipsilateral lymph node ≤3 cm without extranodal extension may be eligible for single‑modality therapy (surgery or RT).
  • Contrast‑enhanced CT simulation is required to guide nodal delineation.
  • For extended‑field IMRT, a thermoplastic mask immobilizing the head, neck, and shoulders is preferred over head‑and‑neck‑only immobilization.
  • Treatment generally includes bilateral neck and pharyngeal mucosa at risk for harboring the primary. Unilateral treatment has higher neck relapse and distant metastasis risk compared to comprehensive treatment.
  • Traditionally, the entire pharynx was irradiated. IMRT now allows targeted mucosal coverage, sparing normal tissues and reducing toxicity.
  • The extent of pharyngeal mucosa to treat must be individualized:
    • HPV‑positive patients may require oropharynx alone.
    • EBV‑positive patients (especially Asian ethnicity) may require only nasopharyngeal coverage.
    • When uncertain, treat the entire pharynx.
  • Patients who have undergone complete TORS evaluation may be spared pharyngeal axis irradiation, though more prospective validation is required.
  • Nodal irradiation:
    • Ipsilateral neck: Levels Ib–V + retropharyngeal nodes.
    • Contralateral neck: Levels II–IV + retropharyngeal nodes (prophylactic dose).
  • Concurrent chemotherapy:
    • Postoperative: indicated when extranodal extension (ECE) is present.
    • Definitive: recommended for advanced nodal disease.

Suggested Target Volumes

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Target VolumeDefinition and Description
GTV70n0
  • All lymph nodes ≥1 cm short axis, FDG‑avid, or positive on biopsy.
  • Contour any lymph node in doubt as GTV.
  • GTVn₀ = CTVn₀.
PTV70
  • GTVn₀ + 3–5 mm expansion depending on daily setup accuracy.
CTVnasopharynx
  • Extends from skull base to soft palate inferiorly.
  • Anterior: posterior choana → posterior pharyngeal wall.
  • Lateral: ensure adequate coverage of fossa of Rosenmüller.
CTVoropharynx
  • Superior: soft palate surface → vallecula (hyoid bone).
  • Anterior: base of tongue should be covered; oral tongue margin not required.
  • Lateral: tonsillar region.
  • Posterior: entire pharyngeal wall.
CTVlarynx+hypopharynx
  • Extends superior from hyoid → bottom of cricoid cartilage.
PTVmucosa
  • 3–5 mm expansion on mucosal surface CTVs depending on institutional accuracy.
  • Suggested dose: 54–60 Gy to mucosal surfaces at risk.
If postoperative: dissected neck should receive 60–66 Gy in 2 Gy fractions. Suggested dose to gross disease is 70 Gy in 33–35 fractions.