Laryngeal Anatomy and Patterns of Tumor Spread
Target volume delineation in larynx cancer demands precise understanding of the three-dimensional anatomy across the three laryngeal subsites — each carrying distinct risks for nodal spread. The larynx divides into the supraglottis, glottis, and subglottis, and overlooking this compartmentalization leads directly to either inadequate coverage or unnecessarily large fields.
The supraglottic larynx includes the ventricles, false vocal cords, arytenoids, aryepiglottic folds, and the epiglottis (suprahyoid, infrahyoid, and laryngeal surfaces). Given its rich bilateral lymphatic drainage, bilateral elective nodal irradiation is mandatory for all supraglottic tumors — no exceptions.
The glottic larynx encompasses the true vocal cords, anterior and posterior commissures, and the infraglottic space (extending 0.5 cm below the free margin of the true vocal cords). Early-stage glottic tumors (T1–T2 N0) do not require elective nodal irradiation. However, advanced disease (≥T3 or node-positive) demands bilateral coverage — small larynx-only fields are inappropriate in this setting.
The subglottic larynx extends from the inferior border of the glottis to the superior border of the trachea. Its propensity for nodal spread mandates bilateral elective nodal irradiation including level VI.
A frequently overlooked detail: the paraglottic and pre-epiglottic spaces are connected fat planes with no barriers between them. The paraglottic space is bounded laterally by the thyroid cartilage and medially by the vocal cords. The pre-epiglottic space communicates inferiorly with the paraglottic space — a spread pathway that dedicated CT and MRI must carefully evaluate.
True vocal cord mobility must be assessed on laryngoscopy (normal, hypomobile, or fixed). A medialized fixed cord suggests recurrent laryngeal nerve injury, while a lateralized fixed or hypomobile cord indicates intrinsic laryngeal muscle involvement. Thyroid cartilage invasion deserves special attention: inner cortex invasion signifies T3 disease, while extension through the outer cortex defines T4. For true T4 disease, total laryngectomy is preferred, although organ preservation may be considered in select cases.
For a comprehensive overview of all anatomical sites covered in this series, see our complete guide on target volume delineation and field setup.
Diagnostic Workup for Larynx Cancer Target Delineation
Beyond physical examination with laryngoscopy, imaging should include a dedicated, thin-slice (1–2 mm) high-resolution CT and/or MRI of the larynx with IV contrast. Careful attention should be directed toward evaluating pre-epiglottic and paraglottic space extension and thyroid cartilage invasion.
A dedicated CT and/or MRI is strongly recommended even for clinically staged T1–T2 glottic tumors, specifically to rule out paraglottic extension — which would upstage the tumor to T3. In practice, this is an avoidable staging error that completely changes the treatment strategy.
Contrast-enhanced MRI is particularly valuable for visualizing locoregional disease extent. Worth noting: more than 1 cm of base of tongue invasion was an exclusion criterion in the larynx preservation trials (RTOG 91-11). PET/CT complements the workup by identifying suspicious lymph nodes and metastatic disease.
Simulation and Daily Localization
The patient should be simulated supine with a head rest, neck extended, in a five-point customized Aquaplast mask immobilizing the head, neck, and shoulders. A shoulder pull board can lower the shoulders out of the beam angle path.
CT simulation should use ≤3 mm slices with IV contrast, covering the entire vertex through the carina. The isocenter is typically placed at the arytenoids when there is no subglottic or hypopharyngeal extension. If either is present, the isocenter shifts 1 cm inferiorly. For postoperative cases, placing a radiopaque marker on the scar helps guide delineation.
For IGRT, the ideal approach consists of daily cone beam CT aligned to the larynx. Daily kV imaging aligned to bone with weekly cone beam CTs is also adequate. Two practical points often overlooked: patients should be instructed not to swallow during simulation, IGRT, or treatment; and bolus placement is needed to ensure adequate anterior coverage, especially for tumors involving the anterior commissure. Patients with metal dental fillings benefit from a custom mouthguard to absorb electron scatter and mitigate treatment-related mucositis.
Target Volume Delineation and Treatment Planning
The GTV should be delineated using all relevant clinical information — laryngoscopy, CT, MRI, and PET. Positive lymph nodes are defined as those with central necrosis, extracapsular extension, and/or short axis diameter >1 cm. Borderline nodes with FDG avidity should be considered disease. Enlarged retropharyngeal nodes, although unusual in laryngeal cancer, should be considered positive even when small.
Target Volumes for Gross Disease
The table below summarizes suggested volumes for gross disease in locally advanced laryngeal cancers — glottic, supraglottic, or subglottic.
| Volume | Definition and Description |
|---|---|
| GTV 70 | Primary: all gross disease on physical examination and imaging. Neck nodes: all nodes ≥1 cm or PET-positive. Include borderline nodes in doubt as GTV to avoid undertreatment. |
| CTV 70 | Usually same as GTV70 (typically no need to add margin unless there is uncertainty about disease extent). An additional 0–0.5 cm margin may be added to GTV70. |
| PTV 70 | CTV70 + 3–5 mm, depending on daily positioning reproducibility and available IGRT. |
Source: Target Volume Delineation and Field Setup, 2nd Edition (Table 4.1)
Subclinical Volumes — Advanced Disease
For supraglottic, subglottic, or locally advanced glottic laryngeal cancers, subclinical coverage volumes are detailed below.
| Volume | Definition and Description |
|---|---|
| CTV 54–60 (high risk) | Should encompass the entire GTV. Includes the entire larynx (bottom of hyoid or top of thyroid notch to bottom of cricoid, extending inferiorly when necessary). High-risk nodal regions: levels II–IV and retrostyloid space on the node-positive neck. Level II treated to skull base in node-positive neck. Level VI if subglottic extension or tracheostomy. |
| PTV 54–60 | CTV 54–60 + 3–5 mm. |
| CTV 54 (low risk) | Levels II–IV of the uninvolved neck. Superior border of level II: where the posterior belly of the digastric crosses the internal jugular vein (caudal edge of lateral process of C1). Levels IB and V not included unless gross involvement. Level VII recommended for subglottic extension or hypopharyngeal involvement. |
| PTV 54 | CTV 54 + 3–5 mm. |
Source: Target Volume Delineation and Field Setup, 2nd Edition (Table 4.2). High-risk subclinical dose: 1.8–2 Gy/fraction to 54–60 Gy. Low-risk subclinical dose: 1.54–1.8 Gy/fraction to 54 Gy.
Postoperative Volumes
| Volume | Definition and Description |
|---|---|
| CTV 60 | Entire operative bed, scar, stoma, and node-positive neck (levels II–IV, retrostyloid space, and involved nodal stations). |
| CTV 54 | Node-negative neck. Include levels VI and VII if subglottic extension or stoma present. |
| CTV 66 | Areas of positive margins, extracapsular extension, or stoma boost when indicated. May be delivered with sequential cone down or dose painting. |
| PTV | CTV + 3–5 mm, depending on immobilization and IGRT. |
Source: Target Volume Delineation and Field Setup, 2nd Edition (Table 4.3). Subclinical dose: 1.8–2 Gy/fraction to 54–60 Gy.
Stage-Based Approach: From Early to Advanced Disease
Early-Stage Disease (T1N0 and T2N0)
The CTV should encompass the entire larynx, including anterior and posterior commissures and arytenoids. For T1 tumors, coverage extends superiorly from the thyroid notch to the cricoid cartilage inferiorly. For T2 tumors, coverage extends down to the first tracheal ring. Inferior coverage is critical — most recurrences tend to be inferior.
For T1N0 glottic tumors, the recommended dose is 63 Gy in 28 fractions (2.25 Gy/fraction), supported by randomized evidence demonstrating a local control advantage with hypofractionation. For T2N0, local control improves with doses >65 Gy and dose per fraction ≥2.25 Gy — the recommended regimen is 65.25 Gy in 29 fractions (2.25 Gy/fraction). Carotid-sparing IMRT should be considered, though a CT-based opposed laterals technique is also acceptable.
Advanced Disease (≥T3 or Node-Positive)
Bilateral necks must be included. A sequential cone down approach is favored: an initial plan of 30 fractions with dose painting delivering 54 Gy (1.8 Gy/fraction) and 60 Gy (2 Gy/fraction) to the low- and high-risk subclinical regions, followed by a cone down of 5 fractions adding 10 Gy to gross disease only (total 70 Gy over 35 fractions).
A single dose-painted IMRT plan is also acceptable: over 35 days delivering 2 Gy/fraction, 1.8 Gy/fraction, and 1.54 Gy/fraction to achieve 70 Gy, 63 Gy, and 54 Gy for gross disease, high-risk subclinical disease, and low-risk subclinical disease, respectively.
Extended IMRT plans are favored over low anterior neck (LAN) fields, due to the risk of missing gross tumor or high-risk subclinical disease in the low-dose region of the match line.
Postoperative Radiation
Indications for postoperative radiation per NCCN v.2020 include positive margins, close margins, extranodal extension, pT4 primary, pN2–pN3 nodal disease, perineural invasion, vascular invasion, and lymphatic invasion. Concurrent chemotherapy should be added for extracapsular extension or positive margins.
The entire surgical bed, stoma, scar, and dissected node-positive neck comprise the high-risk CTV (60 Gy). Areas of positive margins or extracapsular extension may be boosted to 66 Gy. The undissected node-negative neck receives 54 Gy. The stoma may be boosted to 66 Gy for subglottic extension or if an emergent tracheostomy was performed — anatomically, a stomal recurrence is a tracheoesophageal node.
Radiation Following Induction Chemotherapy
In addition to post-chemotherapy targeting, pre-chemotherapy imaging should be fused for target delineation. The high-risk subclinical volume should include the pre-chemotherapy extent of disease and consider adjacent anatomical sites at risk for microscopic spread. The pre-chemotherapy CTV should be modified for anatomical differences after chemotherapy and exclude natural barriers to spread such as air and bone.
Planning Considerations
A PTV margin of 0.3–0.5 cm should be applied based on immobilization and laryngeal motion. For tumors involving the anterior commissure, flash and bolus are essential to ensure adequate coverage of the superficial extent of gross or subclinical disease. Dose heterogeneity should be limited to 105% of prescription when treating over the larynx.
For supraglottic and subglottic tumors, the elevated risk of occult nodal disease justifies bilateral elective irradiation of levels II–IV, and in many instances level VI. The superior limit of level II may stop where the posterior belly of the digastric muscle crosses the internal jugular vein.
