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Oropharyngeal Carcinoma

  • Jeremy Setton
  • Ian Poon
  • Nadeem Riaz
  • Eli Scher
  • Nancy Lee
Chapter
Part of the Medical Radiology book series (MEDRAD)

Abstract

The oropharynx is contiguous with the oral cavity anteriorly, the larynx and hypopharynx inferiorly, and the nasopharynx superiorly. It is commonly divided into four subsites: the tonsillar region, base of the tongue, soft palate, and pharyngeal wall

Keywords

Soft Palate Posterior Pharyngeal Wall Retropharyngeal Lymph Node Target Volume Delineation Pharyngeal Constrictor Muscle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

1 Anatomy and Patterns of Spread

  • The oropharynx is contiguous with the oral cavity anteriorly, the larynx and hypopharynx inferiorly, and the nasopharynx superiorly. It is commonly divided into four subsites: the tonsillar region, base of the tongue, soft palate, and pharyngeal wall (Fig. 1).
    Fig. 1

    Subsites of the oropharynx: a tonsil, b base of the tongue, c soft palate, d pharyngeal wall

  • The anterior and posterior tonsillar pillars are mucosal folds produced by the underlying palatoglossal muscle and palatopharyngeal muscle, respectively. These pillars define the borders of the tonsillar fossa, which contains the palatine tonsil. Tonsillar cancers most commonly arise on the anterior pillar and may extend superiorly along this structure towards the soft palate or inferiorly towards the base of the tongue. Anterolateral spread along the pharyngeal constrictor muscle to the pterygomandibular raphe and retromolar trigone may occur. Superolateral spread to the infratemporal space can be seen in advanced cases.

  • The base of the tongue is bounded anteriorly by the circumvallate papillae. Inferiorly, the vallecula is considered part of the base of the tongue, while the epiglottis belongs to the supraglottic larynx. Cancers of the tongue base may spread anteriorly into the oral tongue and/or floor of the mouth or posteriorly/inferiorly via the vallecula into the preepiglottic space.

  • The inferior surface of the soft palate and uvula belong to the oropharynx, while the superior surface is a nasopharyngeal structure. Tumors of the soft palate may spread laterally/inferiorly to the tonsil via the anterior tonsillar pillar or superiorly towards the nasopharynx.

  • The superior pharyngeal constrictor muscle forms the posterior and lateral walls of the oropharynx. Cancers of the lateral and posterior pharyngeal walls may spread via the mucosa or submucosa towards the hypopharynx and/or nasopharynx. Skip lesions are not uncommon.
    Fig. 2

    Estimated risk of pathologic nodal involvement by level when negative by CT imaging for T1–T2 oropharyngeal primary tumors (Sanguineti et al. 2009) (Figure printed with permission from publisher- Elsevier)

  • Lymphatic spread is predictable. Ipsilateral level II is the most common location for lymph node metastasis. Next echelon lymphatic drainage includes levels III and IV and the retropharyngeal lymph nodes. Involvement levels I and V is uncommon (Fig. 2).

  • The incidence of retropharyngeal nodal involvement varies by subsite. Bussels et al. reported a significantly higher incidence in those with primary tumors of the posterior pharyngeal wall (38 %) and soft palate (44 %) than those with primary tumors of the base of the tongue (13 %) or tonsil (14 %) (Bussels et al. 2006).

2 Diagnostic Workup Relevant for Target Volume Delineation

  • Both physical examination and imaging should be used for delineation of the gross tumor volume.

  • Visual inspection, palpation, and fiber-optic examination are critical for accurate delineation of mucosal extension. The true extent of mucosal extension may be missed on imaging but appreciated on clinical examination (Fig. 3).
    Fig. 3

    Direct visualization of anterior mucosal spread to retromolar trigone

  • MRI has distinct advantages in soft tissue discrimination and reduced dental amalgam interference. It provides complementary information to CT and PET and may allow for improved GTV and normal tissue delineation.
    • T2-weighted with fat saturation: assessment of retropharyngeal lymph nodes, parapharyngeal space, and preepiglottic space

    • T1-weighted pre-contrast: used primarily for evaluation of fate planes, especially parapharyngeal fat space for asymmetry. Additional utility for assessment of bone marrow

    • T1-weighted post-contrast: assessment of perineural invasion

  • The use of MRI requires co-registration or fusion with the CT simulation scan. The use of immobilization mask during MRI allows for improved fusion accuracy but may preclude the use of a dedicated head and neck coil.

  • Diffusion-weighted (DWI) MRI provides apparent diffusion coefficients (ADC), which are inversely correlated with tissue cellularity. DW-MRI has a high negative predictive value for the assessment of lymph node metastases (Vandecaveye et al. 2009).

  • CT remains superior to MRI for the assessment of cortical bone invasion. Administration of iodinated contrast is recommended for enhanced tumor discrimination.

  • FDG-PET provides metabolic information that is complementary to CT and MRI. It has been shown to reduce interobserver variability in tumor delineation and may aid in the identification of tumor extension missed by CT or MRI (Syed et al. 2005).

  • FDG-PET has been shown to provide metabolic information that is of prognostic value independent of tumor size and T-category (Romesser et al. 2012).

  • Limitations of FDG-PET include poor spatial resolution and low sensitivity for small-volume lymph node metastases. The absence of FDG uptake in an otherwise suspicious lymph node should not be considered reassuring.

3 Simulation and Daily Localization

  • The patient should be set up in the supine position with the neck extended. The immobilization device (Aquaplast mask) should provide adequate shoulder immobilization. Bite-block and/or mouth guard may be inserted.

  • CT simulation using 2.5–3 mm slice thickness with IV contrast. Isocenter is typically placed just above the arytenoid cartilages.

  • MRI and PET images, if available, may then be registered or fused to the CT simulation scan.

  • At MSKCC, image guidance is achieved with daily linear-accelerator-mounted 2D kV imaging and weekly kV conebeam CT. Alternative methods for image guidance include orthogonal kV imaging (“ExacTrac”) or linear-accelerator-mounted MV CT images (“TomoTherapy”).

  • CTV to PTV expansion of 3–5 mm, depending on the accuracy of daily patient positioning and image guidance.

4 Target Volume Delineation and Treatment Planning

4.1 Selected IMRT Dose Fractionation Schemes for Oropharyngeal Cancer

  • Standard fractionation (33 fractions) with integrated boost. Gross disease dose: 69.96 Gy in 33 fractions. High-risk subclinical disease dose: 59.4 Gy in 33 fractions. Low-risk subclinical disease dose: 54.12 Gy in 33 fractions. Single phase (simultaneous integrated boost), with 5 fractions weekly (Garden et al. 2013; Setton et al. 2012).

  • Standard fractionation (35 fractions) with cone-down. Gross disease dose: 70 Gy in 35 fractions. Subclinical disease dose: 54 Gy in 30 fractions. Initial phase (simultaneous integrated boost): 2 Gy per fraction to gross disease, 1.8 Gy per fraction to subclinical disease (30 fractions). Boost: 2 Gy per fraction to gross disease.

  • RTOG 00–22. Gross disease dose: 66 Gy in 30 fractions. Subclinical disease dose: 54 Gy in 30 fractions. Optional high-risk subclinical disease dose: 60 Gy in 30 fractions. Single phase with one plan (simultaneous integrated boost), with 5 fractions weekly (Eisbruch et al. 2010).

  • RTOG 10–16. Gross disease dose: 70 Gy in 35 fractions. High-risk subclinical disease dose: 56 Gy in 35 fractions. Low-risk subclinical disease dose: 50–52.5 Gy in 35 fractions. LAN field dose: 44 Gy in 22 fractions. Single phase with one plan (simultaneous integrated boost), six fractions weekly.

  • Concomitant boost (RTOG 90–03, 01–29): two phases, twice daily treatment for the last 12 days. Total duration of 6 weeks. 54 Gy in 30 fractions to gross and subclinical disease. For the last 12 fractions, a second daily fraction to gross disease of 1.5 Gy is delivered (at least 6-h interval) (Ang et al. 2010; Beitler et al. 2014).

4.2 Split-Field Versus Whole-Field IMRT

  • For patients without low neck disease, a low anterior AP field with larynx block is matched to the IMRT field at the isocenter just above the arytenoids. Dose is 45–50 Gy in 20–25 fractions, prescribed to 3 cm depth. In cases of gross involvement of the low neck or near the match-line, whole neck IMRT is preferred.

4.3 Suggested Target Volumes

Table 1

Suggested target volumes for gross disease

Target volumes

Definition and description

GTV70

Primary: all gross disease as defined by clinical examination (e.g., base of tongue tumors that are superficial and not apparent on imaging) and imaging

Neck nodes: all suspicious (>1 cm, necrotic, enhancing, or FDG avid) lymph nodes. Borderline suspicious lymph nodes may be treated to an intermediate dose (66 Gy in 33 fractions)

CTV70

Typically same as GTV70 (no added margin). Margin of 5 mm may be added if there is uncertainty in extent of gross tumor so that GTV70 + 5 mm = CTV70

PTV70

CTV70 + 3–5 mm, depending on accuracy of daily patient positioning and image guidance

Table 2

Suggested target volumes for subclinical disease: general guidelines

Target volumes

Definition and description

CTV59.4

Primary: generally the primary CTV59.4 should encompass GTV + minimum 1 cm margin while respecting anatomical barriers to spread, including bone, air, and skin

Neck nodes – should include the at-risk lymphatic areas in the node-positive neck:

 Levels II–IV

 Lateral retropharyngeal lymph nodes up to skull base/jugular foramen

 High level II/retrostyloid space (see Fig. 7)

Although sparing of ipsilateral IB is controversial, at MSKCC, it is routinely spared unless there is gross involvement or extension of the primary GTV into the oral cavity (Tam et al. 2013)

CTV54

Neck nodes – should include the at-risk lymphatic areas in the node-negative neck:

 Levels II–IV

 Lateral retropharyngeal lymph nodes up to C1

 High level II/retrostyloid space is excluded

Table 3

Suggested target volumes for subclinical disease: subsite-specific guidelines

Target volumes

Definition and description

Tonsil

Primary CTV59.4

Ipsilateral soft palate, ipsilateral base of the tongue, ipsilateral glossotonsillar sulcus. Superiorly, ipsilateral pharynx superiorly to pterygoid plate (Figs. 4 and 5). Inferiorly, at least 1 cm below GTV, down to level of the hyoid for advanced tumors. Consider coverage of ipsilateral retromolar trigone if anterolateral spread along pharyngeal constrictor to the pterygomandibular raphe is suspected

Nodal CTV59.4 or CTV54

In patients with well-lateralized T1-2, N0-1 primary tumors (at least 1cm from central structures) without base of tongue or soft palate involvement, treatment of the ipsilateral neck may be considered. In such cases, the nodal CTV can be limited to ipsilateral levels II–IV, ipsilateral lateral retropharyngeal lymph nodes (Figs. 4 and 5). In node-positive patients, treat level II–IV bilaterally and lateral retropharyngeal nodes. At MSKCC, we do not routinely treat level Ib or V, unless involved or considered at high risk

Base of the tongue

Primary CTV59.4

Glossotonsillar sulcus, vallecula, preepiglottic space (Figs. 6 and 7). Superiorly cover to level of the tip of the uvula. Consider inclusion of entire supraglottic larynx with epiglottic involvement (Fig. 7). Anteriorly, ensure the entire base of the tongue is covered; often this may require 1 cm of coverage of oral tongue (use signal differences in lymphoid tissue to help delineate as one cannot see circumvallate papillae)

Nodal CTV59.4 or CTV54

Bilateral levels II–IV, lateral retropharyngeal LN. IB only with significant extension of the primary GTV into the oral cavity. At MSKCC, we do not routinely treat level Ib or V, unless involved or considered at high risk

Soft palate

Primary CTV59.4

Entire soft palate, superior aspect of tonsillar pillars + fossa, adjacent nasopharynx superiorly to pterygoid plate. For advanced primaries, consider inclusion of pterygopalatine fossa. Ensure adequate coverage anteriorly, which may require coverage of portion of the hard palate. If pterygopalatine fossa is involved, assessment of the base of skull with MRI is required.

Nodal CTV59.4 or CTV54

Bilateral levels II–IV, lateral retropharyngeal LN to skull base given propensity for involvement (Fig. 9). At MSKCC, we do not routinely treat level Ib or V, unless involved or considered at high risk

Pharyngeal wall

Primary CTV59.4

Generous superior-inferior margins given the possibility of skip lesions. In patients with advanced primary tumors, consider extending CTV cranially to include nasopharynx and caudally to include hypopharynx (Fig. 8)

Nodal CTV59.4 or CTV54

Bilateral levels II–IV, lateral retropharyngeal LN. Consider inclusion of lateral retropharyngeal lymph nodes to skull base given propensity for involvement. At MSKCC, we do not routinely treat level Ib or V, unless involved or considered at high risk

Fig. 4

Representative slices of target delineation in a patient with cT4aN2b squamous cell carcinoma of the right tonsil. GTV70 (red), CTV59.4 (green), CTV54 (blue)

Fig. 5

Representative axial slices from registered MRI/CT simulation scan for a patient with cT3N2c squamous cell carcinoma of the right tonsil (GTV70: red, CTV59.4: green)

Fig. 6

Representative slices of target delineation in a patient with cT1N0 well-lateralized squamous cell carcinoma of the left tonsil. GTV70 (red), CTV54 (green)

Fig. 7

Representative slices of target delineation in a patient with cT2N0 squamous cell carcinoma of the right base of the tongue and vallecula. GTV70 (red), CTV59.4 (green), CTV54 (blue)

Fig. 8

Representative slices of target delineation in a patient with cT3N2c squamous cell carcinoma of the base of the tongue. GTV70 (red), CTV59.4 (green)

Fig. 9

Representative slices of target delineation in a patient with cT3N2c squamous cell carcinoma arising from posterior pharyngeal wall. GTV70 (red), CTV59.4 (green)

Fig. 10

Representative slices of target delineation in a patient with cT3N0 squamous cell carcinoma of the soft palate. GTV70 (red), CTV54 (blue)

Fig. 11

Representative axial slices from postoperative CT simulation scan of patient with pT2N2b squamous cell carcinoma of the left tonsil treated with transoral robotic radical tonsillectomy and left modified radical neck dissection yielding negative surgical margins and no evidence of extracapsular extension (CTV60: green, CTV54: blue)

5 Plan Assessment

  • Prioritization for IMRT planning is as follows: critical structures > planning target volumes > other normal structures.

  • PTV coverage and dose homogeneity criteria are listed in Table 4. A 3-D isodose surface display is reviewed to ensure that hot spots are located inside the PTV.

Table 4

Intensity-modulated radiation therapy: target criteria

PTV coverage

D95 ≥ prescription dose

Dose homogeneity

D05 PTV70 ≤ 108 % of prescription dose (75.6 Gy)

 

D05 of PTV59.4 and PTV54 ≤ prescription of next higher-dose volume (70 Gy)

Based on guidelines presently used at Memorial Sloan-Kettering Cancer Center

PTV planning target volume

Table 5

Intensity-modulated radiation therapy: normal tissue dose constraints

Critical structures

Constraints

Brain stem

Max < 54 Gy (guideline), <60 Gy (limit)

Optic nerves

Max < 54 Gy (limit)

Optic chiasm

Max < 54 Gy (guideline), <60 Gy (limit)

Spinal cord

Max < 45 Gy (guideline), <50 Gy (limit)

Brachial plexus

Max < 65 Gy (limit)

Other normal structures

Constraints

Oral cavity

Mean < 40 Gy

Submandibular gland

Mean < 39 Gy

Parotid gland

(a) Mean ≤ 26 Gy in one gland

(b) Or at least 20 cc of the combined volume of both parotid glands will receive < 20 Gy

(c) Or at least 50 % of one gland will receive < 30 Gy

Cochlea

Mean < 45 Gy, V55 < 5%

Eyes

Mean < 35 Gy, Max < 50 Gy

Lens

Max < 25 Gy

Glottic larynx

Mean < 45 Gy

Mandible not PTV

Max < 70 Gy

Mandible

No hot spots

Esophagus

Mean < 45 Gy

Based on guidelines presently used at Memorial Sloan-Kettering Cancer Center

PTV planning target volume

References

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Further Reading

  1. Adelstein DJ, Ridge JA, Brizel DM et al (2012) Transoral resection of pharyngeal cancer: summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6–7, 2011, Arlington, Virginia. Head Neck 34:1681–1703CrossRefPubMedGoogle Scholar
  2. Denis F, Garaud P, Bardet E et al (2004) Final results of the 94–01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 22:69–76CrossRefPubMedGoogle Scholar
  3. Eisbruch A, Kim HM, Feng FY et al (2011) Chemo-IMRT of oropharyngeal cancer aiming to reduce dysphagia: swallowing organs late complication probabilities and dosimetric correlates. Int J Radiat Oncol Biol Phys 81:e93–e99CrossRefPubMedPubMedCentralGoogle Scholar
  4. O’Sullivan B, Warde P, Grice B et al (2001) The benefits and pitfalls of ipsilateral radiotherapy in carcinoma of the tonsillar region. Int J Radiat Oncol Biol Phys 51:332–343CrossRefPubMedGoogle Scholar
  5. O’Sullivan B, Huang SH, Siu LL et al (2013) Deintensification candidate subgroups in human papillomavirus related oropharyngeal cancer according to minimal risk of distant metastasis. J Clin Oncol 31:543–550CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Jeremy Setton
    • 1
  • Ian Poon
    • 2
  • Nadeem Riaz
    • 1
  • Eli Scher
    • 1
  • Nancy Lee
    • 1
  1. 1.Department of Radiation OncologyMemorial Sloan Kettering Cancer CenterNew YorkUSA
  2. 2.Department of Radiation OncologyUniversity of Toronto/Sunnybrook Health Sciences CentreTorontoCanada

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