Salivary Glands

Key points

Salivary neoplasms originate mostly from major salivary glands (parotid, submandibular, and sublingual glands) but can arise from thousands of minor glands spread throughout the mucosa of the head and neck.
The most common neoplasm is benign pleomorphic adenoma. Malignant tumors are uncommon but comprise a wide variety of histologic types, with mucoepidermoid carcinoma, adenoid cystic carcinoma (ACC), and salivary ductal carcinoma leading the list.
Histologic grade of differentiation is a strong prognostic factor. Distant metastases are more common in patients with high-grade tumors.
Surgery is the recommended frontline treatment for resectable salivary gland cancers. Many of these tumors are locally infiltrative with ill-defined borders. Surgical section margins are often close or positive.
Adjuvant radiation is often recommended. Indications for radiation include extraglandular extension, close or positive surgical margins, nodal involvement, highgrade histology, and perineural spread.
Due to perineural spread, particularly with ACC, radiation volumes often include the nerve pathways from the primary tumor to the skull base.
Primary radiotherapy is reserved for inoperable tumors. Neutron therapy may be advantageous in this situation, particularly for ACC.
The role of combination of chemotherapy and radiation for the treatment of high-risk salivary cancers is being investigated.

Despite the realization of the diverse natural history and variation of radiation technique by specific site of origin, the rarity of salivary cancers led many investigators to report treatment outcomes in aggregate. Therefore, this chapter begins by summarizing the general background outcome data before addressing individual subsites.

Background Data

Table 13.1 Histologic Distribution of Salivary Neoplasms by Site

Site	Benign	Mucoepidermoid	Adenoid Cystic	Adenocarcinoma	MMT	Acinic	Epidermoid	Anaplastic
Parotid	1,342	272	54	62	107	75	45	8
Submandibular	106	37	45	9	24	2	8	–
Palate	60	37	67	41	18	1	–	4
Lip/cheek	13	23	12	20	2	3	–	–
Antrum	–	13	31	23	3	1	–	1
Tongue	2	14	30	12	2	–	–	3
Nasal cavity	4	12	17	23	–	1	–	3
Gingiva	–	13	10	6	3	1	–	1
Floor of mouth	1	6	7	8	–	–	–	–
Larynx	–	3	3	7	–	–	–	8^a
Tonsil	–	4	3	3	1	–	–	2
Ethmoid	–	1	1	6	–	–	–	1
Nasopharynx	–	2	1	5	1	–	–	–
Pharyngeal wall	1	2	–	–	–	–	–	–
^aAll neuroendocrine carcinomas.
MMT, malignant mixed tumor.
From Spiro RH. Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 1986;8:177-184, with permission.

Table 13.2 Local Failure of Adenoid Cystic Carcinoma Treated with Surgery and Postoperative Irradiation Stratified by Positive Margins and Named Nerve Involvement

Site	No. of Failures/No. of Patients (%)	No. of Failures/No. of Patients with Positive Margins (%)	No. of Failures/No. of Patients with Named Nerve Involvement (%)
Minor salivary gland	16/122 (13)	10/54 (19)	5/31 (16)
Submandibular/sublingual gland	1/41 (2)	1/11 (9)	1/14 (7)
Parotid gland	4/30 (13)	3/15 (20)	4/10 (40)
All patients	21/193 (11)	14/80 (18)	10/55 (18)
Data from the M.D. Anderson Cancer Center.
Modified from Garden AS, Weber RS, Morrison WH, et al. The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation. Int J Radiat Oncol Biol Phys 1995;32:619.

Table 13.3 Five-Year Actuarial Local-Regional Control of Adenoid Cystic Carcinoma Treated with Neutron Therapy

Site	No. of Patients	Local-Regional Control (%)
Paranasal sinus	32	43
Oral cavity	26	68
Oropharynx	19	75
Nasopharynx	15	21
Submandibular-sublingual gland	15	59
Parotid	27	67
Modified from Douglas JG, Laramore GE, Austin-Seymour M, et al. Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 2000;46:551.

PAROTID

Treatment Strategy

Surgery is the preferred treatment for operable cases. Postoperative radiotherapy is indicated in the following clinical settings: high-grade tumors (mucoepidermoid carcinomas, malignant mixed tumors, adenocarcinomas, and squamous cell carcinomas); close or positive surgical margins (including incompletely resected recurrent pleomorphic adenoma); tumor adherence to or invasion of the facial nerve, or presence of histologic evidence of perineural spread; bone and/or connective tissue involvement; lymph node metastases (particularly with extracapsular extension); or after resection of recurrent disease even with negative margins.

Postoperative Radiotherapy

Target Volume

Initial Target Volume

The volume for benign and low-grade tumors without lymph node involvement is the parotid bed only. For high-grade tumors and tumors with lymph node involvement, the volume encompasses the parotid bed and ipsilateral neck nodes. For macroscopic invasion of the facial nerve, more generous coverage of facial canal to geniculate ganglion is desired.

Case Study 13-1

A 39-year-old woman presented with a 4-month history of a right parotid swelling. She underwent a surgical exploration, which revealed a large mass extending from the base of skull to the subdigastric muscle inferiorly. This lesion was dissected off the facial nerve and removed in two major pieces. Histologic examination showed a pleomorphic adenoma. Five months later, she presented with a recurrent nodule in the upper posterior cervical region. This was excised and was also found to contain pleomorphic adenoma. Four months after the second intervention, a small mass developed at the posterior auricular region. Fine-needle aspiration showed carcinoma. She was then referred to M.D. Anderson Cancer Center. Review of the slides revealed carcinoma ex-pleomorphic adenoma in the specimens of the first and second surgical procedures.

Physical examination upon referral revealed no palpable residual disease and an intact facial nerve. It was decided to deliver postoperative radiotherapy to the parotid bed and upper neck with a lateral appositional field (Fig. 13.1) using a combination of electrons and photons (20 MeV and 6 MV, respectively). An intraoral stent was used to protect the mucosa of the oral tongue and contralateral oral cavity. The mid and lower neck nodes on the ipsilateral side were treated with a separate electron field. The tumor bed received a dose of 60 Gy in 30 fractions prescribed to the 90% isodose line and the mid and lower neck prescribed a dose of 50 Gy in 25 fractions.

Off-cord reduction is made after reaching a dose of approximately 44 Gy, and the posterior strip is supplemented with lower energy electrons (usually 9 MeV).

Figure 13.1

The boost volume encompasses the tumor bed and the involved nodal bed.

Setup and Field Arrangement for Conventional Technique

Target volume 5 cm or less deep (superficial lobe and deep lobe in thin patients) (see Case Studies 13-1 and 13-2).

An intraoral stent containing cerrobend is used to shield the posterior oral tongue (see Chapter 3).

Marking of the surgical scar and lateral canthus of the ipsilateral orbit facilitates portal design.

The patient is immobilized in an open-neck position with a thermoplastic mask. Flattening of the ipsilateral ear against the mastoid process minimizes dose heterogeneity resulting from electron perturbation. For the same reason, the external auditory canal is filled with Domeboro fluid prior to each electron treatment.

Case Study 13-2

A 66-year-old man presented with a 2-cm left preauricular mass. Radiographic imaging revealed a mass in the superficial lobe of the left parotid gland. He underwent a superficial parotidectomy and upper neck dissection. Histologic examination revealed an ACC with positive anterior and deep margins but none of five lymph nodes harbored metastases. The patient received postoperative radiotherapy in the open-neck position.

Figure 13.2A,B

As shown in Figure 13.2, a tongue-displacing stent (S) was used and bolus material (B) applied to modulate the depth of the electron range. An initial 50 Gy was delivered to the parotid bed and upper neck (Fig. 13.2A) with a 4:1 mix of 16-MeV electrons and 6-MV photons. A boost of 16 Gy to the high-risk area was delivered with 12-MeV electrons. A representative axial isodose distribution is shown in Figure 13.2B.

Bolus is used to cover the superior aspect of the portal when it extends above the zygomatic arch to minimize the dose to the temporal lobe of the brain.

A lateral appositional field is used to cover the parotid bed and upper neck nodes. Radiation is delivered with a combination of electrons (12 to 20 MeV depending on the depth) and photons (6 MV) usually in the ratio of 4:1.

Portal borders are as follows:

Superior: zygomatic arch or higher as indicated by tumor extent or surgical scar.
Anterior: anterior edge of the masseter muscle.
Inferior: thyroid notch.
Posterior: just behind the mastoid process.

A 1.5- to 2-cm bevelled bolus or a computer-generated custom bolus is placed at the superior part of the portal (above the line connecting the orbital floor and the mastoid process) to reduce the dose to the temporal lobe. A lateral appositional electron field is used to treat the mid and lower neck nodes when indicated (for borders of neck field, see “General Principles”). Field reduction takes place after 50 to 54 Gy in 25 to 27 fractions to deliver the boost dose when indicated. If the anterior edge of the portal is close to the eye, skin collimation is applied and the beam maybe angled 5 to 10 degrees posteriorly to minimize the dose to the orbital content.

For more deep-seated tumors or when the facial canal is part of the target volume, a wedge-pair technique (see Case Studies 13-3 and 13-4) or intensity-modulated radiation therapy (IMRT) (see Case Studies 13-5, 13-6 and 13-7) with photon beams is often preferable.

With these techniques, the patient is immobilized in a supine position with the head hyperextended with thermoplastic mask. The axial plane of the fields is chosen so that the posterolateral portal does not exit through the contralateral eye. A relatively simple wedge-pair technique uses anterolateral and posterolateral oblique photon fields (the anterolateral oblique field is on the spinal cord and the posterolateral oblique field is off the cord). The simulation focuses on marking of the surgical scar and both inferior orbital rims and selection of provisional isocenter. The provisional isocenter is generally placed at the center of the square defined by the zygomatic arch, anterior edge of the masseter, thyroid notch, and mastoid, and halfway between the skin and the oropharyngeal wall.

Thin-slice computed tomography (CT) scan is obtained in the treatment position for outlining the target volume and planning the portal sizes, hinge angle, and thickness of wedges using treatment planning system. No off-spinal cord reduction is required with a wedged-pair technique because the posterolateral field is off the cord from the beginning. Field reduction for boost dose, when indicated, occurs after 50 to 54 Gy.

Case Study 13-3

A 46-year-old woman presented with a 1-year history of intermittent left facial swelling and left parietal headache. Physical examination of the parotid region and other head and neck areas was unremarkable. The facial nerve was intact. A CT scan, however, showed a soft-tissue mass in the deep lobe of the parotid (Fig. 13.3). The patient underwent a total parotidectomy with sparing of the facial nerve. The tumor was removed from beneath the facial nerve with some difficulty. Histologic examination revealed pleomorphic adenoma measuring 3.5 × 3 × 2.5 cm. The deep margin of resection was positive. Two intraparotid lymph nodes and 16 periparotid nodes, removed to gain access to the parotid, were all free of tumor. It was decided to treat this patient with postoperative radiotherapy because of difficult and incomplete resection. The target volume extended to 6 cm from the surface, which was too deep for the highest available electron energy (20 MeV). Therefore, it was elected to treat with wedge-pair fields. A total dose of 50 Gy was delivered to the 95%-isodose line in 25 fractions.

Figure 13.3A,B

Intensity-Modulated Radiation Therapy

With IMRT, the patient is immobilized with an extended head and shoulder thermoplastic mask in a supine position. Thin-slice CT scan is obtained for delineation of target volumes (see Case Studies 13-6 and 13-7).

Case Study 13-4

A 46-year-old man presented with a left parotid mass associated with facial pain and facial palsy. Magnetic resonance imaging (MRI) showed a mass occupying most of the superficial lobe and extending into the deep lobe, measuring 5 cm in greatest dimension. He underwent a resection of the mass consisting of left total parotidectomy, left parapharyngeal space dissection, left upper neck dissection, and left segmental mandibulectomy. Histopathologic evaluation of resected tumor showed cribriform, grade 2, ACC, 5.5 × 4.0 × 3.0 cm, extending to the surgical margin. None of 11 lymph nodes contained metastatic deposits. The patient received postoperative radiotherapy with a left anterior oblique and left posterior oblique pair of portals with 60-degree wedges. This was chosen because of the disease deep in the dissected parapharyngeal space. A field reduction was made at 50 Gy. The total dose was 66 Gy in 33 fractions. Figure 13.4 shows axial (Fig. 13.4A) and coronal (Fig. 13.4B) isodose distributions. The patient remains free of disease 30 months from diagnosis.

Figure 13.4A,B

Virtual Gross Target Volume

There is no actual gross target volume (GTV) after complete surgical tumor resection. However, it can be useful to formulate a virtual GTV (vGTV) to facilitate target volume definition. The vGTV is a best approximation of the
tissues having high likelihood of harboring microscopic tumor reconstructed based on findings of preoperative clinical examination, imaging studies, and surgical-pathologic assessment.

Case Study 13-5

A 31-year-old man presented with a slowgrowing right parotid mass. A MRI revealed the right parotid mass, involving the deep lobe and abutting the mastoid (Fig. 13.5A). He underwent a total parotidectomy with facial nerve sparing, partial mastoidectomy, and lateral skull base dissection. Histologic examination revealed acinic cell carcinoma, with tumor present at the margins. He received postoperative radiotherapy using IMRT to conform better to the postoperative bed, including the resected temporal bone. Figure 13.5B shows an axial isodose distribution at approximately the same level as the preoperative MRI image (Fig. 13.5A). Postoperative changes including the partial mastoidectomy are evident. A total dose of 60 Gy was delivered in 30 fractions. Note the oral cavity has a tongue-displacing stent, and the high-dose isodose lines encompass the stent rather than the tongue.

Figure 13.5A,B

Case Study 13-6

A 53-year-old man presented with an enlarging right parotid mass for which he underwent a total parotidectomy and selective neck dissection. Histologic examination revealed highgrade carcinoma ex-pleomorphic adenoma. The tumor abutted the surgical margin and there was extraglandular and perineural invasion. Ten dissected nodes were negative. He was treated with postoperative IMRT delivered in 30 fractions. As the location of the margin was unclear, a dose of 66 Gy was prescribed to tumor bed, 60 Gy to an additional 1-cm margin, and 57 Gy to the remaining operative bed including the negative upper neck. The right lower neck fields were treated with a matched pair of oblique photon beams. The lower neck was treated to 50 Gy in 25 fractions followed by an addition 6 Gy in three fractions.