Salivary gland ca

SALIVA
 Is a clear, slightly acidic,mucoserous secretion,which
provides chemical milieu of the teeth and oral soft
tissue.
 Composed of more than 99% water and less than 1%
solids , mostly electrolytes and proteins.
 Daily production : 0.5 to 1.0 litres

Salivary Gland Secretions
Gland type Saliva type
Parotid Serous
Submandibular Mixed, more serous than mucous
Sublingual Mixed, but mostly mucous
Most minor Mucous

SALIVARY FLOW RATE
 Stimulated flow -
 90% of average daily
saliva production
 At a rate of between 0.2
and 7 mL/min
 Parotid glands
contribute > 50% of
total salivary flow
 Unstimulated state –
 Normal flow > 0.1
mL/min
 Submandibular glands -
65% of total flow;
 Parotid glands - 20%
 Sublingual glands - 7%–
8%.

 3 major
 Parotid
 Submandibular
 Sublingual
 Many smaller, minor glands located throughout the
upper aerodigestive tract.
Perez and Brady’s Principles and Practice of Radiation Oncology (sixth edition)

PAROTID GLAND
 Largest Gland
 Located superficial to and partly behind the ramus of
the mandible and covers the masseter muscle
 Structures within gland
 External Carotid Artery
 Maxillary Artery
 Retromandibular vein
 Facial Nerve
 Parotid Lymph Nodes

LYMPHATICS
 Drain
 Temple
 Part of scalp
 Part of auricle
 External Acoustic Meatus
 Middle ear
 Parotid Gland
 Upper cheek
 Part of eyelid
 Orbit
 Drainage
 Parotid Glands
 Upper deep cervical

SUBMANDIBULAR GLAND
 Situated in Digastric triangle
 A rich lymphatic capillary network lies in the interstitial spaces
of the gland
 From the lateral and superior portions of the gland, lymph flows
to the prevascular or preglandular submandibular lymph nodes.
 The posterior portion of the gland gives rise to one or two
lymphatic trunks, which follow the facial artery and go directly
to the anterior subdigastric nodes of the internal jugular chain.
 The nodes overlying the submandibular gland, followed by the
subdigastric and high midjugular lymph nodes, are those
involved in nodal metastases.

SUBLINGUAL GLAND
 Smallest major gland
 Lies between the mucous membrane of the floor of the
mouth above and the mylohyoid muscle below
 Drains to :
 Submandibular lymph nodes
 Deep internal jugular chain
 Rarely - Submental node or supraomohyoid jugular
node.

MINOR SALIVARY GLANDS
 Widely distributed in the upper aerodigestive tract,
palate, buccal mucosa, base of tongue, pharynx,
trachea, cheek, lip, gingiva, floor of mouth, tonsil,
paranasal sinuses, nasal cavity, and nasopharynx.

EPIDEMIOLOGY
 0.4% of all cancers
 <5% of the annual incidence of head and neck
malignancies in the United States
Salivary Tumor Malignant Tumor
Parotid Gland 70% 25%
Submandibular Gland 8% 43%
Minor glands 22% 65%

 Preponderance of benign tumors in women
 Mean age
 Benign : 46 years
 Malignant : 54 years
 Etiologic factors- not clearly defined
 Nutrition : Low intake of Vitamin A and C
 Cigarette smoking : >80 pack years
 Irradiation : survivors of Hiroshima and Nagasaki
 Occupational : Hairdressers or working in beauty shops

NATURAL HISTORY
 Local Invasion : Initial route of spread
 Lymph Node metastasis
 Distant Metastasis
 3% of patients at presentation
 33% after 10 years
 Lung, bone, and occasionally liver

CLINICAL PRESENTATION
 Painless mass
 Depends on site
 Clinical features suggesting a malignant salivary gland
tumor
 Rapid growth rate
 Pain
 Facial nerve palsy
 Skin involvement
 Cervical adenopathy

DIAGNOSTIC WORK UP
 History and Physical Examination
 USG
 FNAC
 CT/MRI
 PET CT
 Biopsy

USG
 First Diagnostic Step
 Features
Malignant Benign
Ill-defined borders Well defined
Heterogonous architecture Hypoechoic
Internal necrosis
Cystic changes

FNAC
 Useful for differentiating between yes and no
neoplastic lesions
 Specificity of >95%
 Colella et al found concordant cytology in 80%, 96%,
and 94%, respectively, for patients with a histologic
diagnosis of a malignant tumor, a benign tumor, or a
non neoplastic lesion.

MRI
 Excellent to assess the margins, extension into the
deep tissues, and patterns of infiltration
 Benign tumors are hyperintensive, and malignant
tumors show intermediate or low intensity at T2-W
MR images
 Early contrast enhancement and slow washout are
signs of malignancy on dynamic MRI

Imaging of salivary gland tumours Harriet C. Thoeny

PET CT
 FDG uptake in salivary glands is quite unpredictable,
resulting in a low sensitivity of FDG-positron emission
tomography
 Combined FDG PET/MRI scans could be a valuable
extension of the diagnostic imaging modalities in
salivary gland cancer

Biopsy
 Definitive diagnostic : Excisional biopsy (for minor
salivary glands)
 Unplanned incisional biopsies should be avoided

Histology Frequency Salivary Gland Prognosis
Adenoid Cystic
Carcinoma
27% Minor Salivary
Submandibular
Tubular : Good
Cribriform : Intermediate
Solid : Worst
*Perineural invasion is
common
Mucoepidermoid
Carcinoma
16% Parotid Low grade
High grade
Acinic Cell
Carcinoma
14% Parotid Ki 67
Carcinoma ex
pleomorphic
adenoma
8% All glands Poor prognosis
*High risk of distant
metastasis

Histology Frequency Salivary Gland Prognosis
Undifferentiated 7% Parotid Behave as head and
neck cancers
Salivary duct cancers 6% Highly aggressive
Polymorph low grade
adenocarcinoma
5% Palate Good prognosis
Squamous cell
carcinoma
5% Parotid Behave as head and
neck cancers

General Management
 Surgical excision
 Radiotherapy
 Chemotherapy

Prognostic Factors
 T and N stages
 Histologic subtype
 Grade of tumor
 Post Surgical residual disease
 Cranial Nerve Involvement
Perez and Brady’s Principles and Practice of
Radiation Oncology (sixth edition)

Major Salivary Glands
 Parotid Gland
Superficial lobe : Superficial Parotidectomy
Deep lobe : Total Parotidectomy
Adjacent soft tissue : Radical Parotidectomy
 Submandibular Gland
Small lesion : Excision
Extracapsular extension : en bloc resection
 Sublingual Gland
En bloc resection

Minor Salivary Glands
 Varies with location
 Usually involves an attempt at adequate surgical
excision first.
 Irradiation has been used in surgically inaccessible
sites or combined with surgery because of locally
aggressive tumor behavior and the occurrence of
incomplete resection.

Postoperative radiotherapy
 T3–4 tumors
 Close or incomplete resection
 Lymphovascular invasion
 Perineural invasion
 High-grade cancer
 Nodal metastasis
 Recurrent cancer

Results
 Postoperative radiotherapy improved 10-year local
control significantly compared with surgery alone in
 T3–4 tumors (84% vs. 18%)
 Close margins (95% vs. 55%)
 Incomplete resection (82% vs. 44%)
 Bone invasion (86% vs. 54%)
 Perineural invasion (88% vs. 60%)
 pN+ neck (86% vs. 62%)

Conclusion
 Postoperative radiotherapy with a dose of at least 60
Gy is indicated for patients with T3–4 tumors,
incomplete or close resection, bone invasion,
perineural invasion, and pN+.
 In unresectable tumors, a dose of at least 66 Gy is
advisable.

Results
 Nodal Relapse
 5 –year : 11%
 10-year : 13%
 The 10-year rates of nodal failure
 T1 : 5%
 T2 : 7%
 T3 : 12%
 T4 : 16%
 The use of ENI reduced the 10-year nodal failure rate from
26% to 0%

Results
 The highest crude rates of nodal relapse among those
treated without ENI were found in patients with
 Squamous cell carcinoma (67%)
 Undifferentiated carcinoma (50%)
 Adenocarcinoma (34%)
 Mucoepidermoid carcinoma (29%)
 There were no nodal failures observed among patients
with adenoid cystic or acinic cell histology.

CONCLUSION
 ENI effectively prevents nodal relapses and should be
used for select patients at high risk for regional failure

PAROTID GLAND : CONVENTIONAL
 Superior : lower orbital
margin
 Inferior : lower part of
gland and upper deep
cervical nodes.
 Anterior : cover the
masseter muscle
 Posterior : passes
through mastoid process

Field Arrangements
 Unilateral anterior and posterior wedged pair fields
using 60Co or 4- to 6-MV photons
Unilateral wedge arrangement and isodose distribution using wedged
pair

 Homolateral fields with 12- to 16-MeV electrons in
combination with photons.
 Usually, 80% of the dose is delivered with electrons
and 20% with 60Co or 4- to 6-MV photons to spare the
opposite salivary gland, reduce mucositis, and
decrease the skin reaction produced by electrons

Ipsilateral 16-MeV electrons plus 60Co (4:1) electron beam field

CONCLUSION
 The single photon lateral field [1] and the mixed electron-photon
beams [8] and [9] are not recommended treatment techniques
for unilateral parotid irradiation because of high doses delivered
to the contralateral parotid gland and high exit doses which are
associated with Xerostomia.
 The en face electron beam technique [2] and the mixed electron-
photon beam technique [6] are unacceptable due to the excessive
dose heterogeneity to the contiguous normal structures.
 In spite of optimal dose fall-off achieved using the en face
technique [3], most patients cannot tolerate the resulting high
skin doses.

 We conclude that the ipsilateral wedge pair [4], the 3-
field [5], and the mixed electron-photon beam [7]
techniques are optimal techniques in providing
relatively homogeneous dose distributions within the
target area and for minimizing dose to the relevant
normal structures

NECK IRRADIATION
 The ipsilateral neck is treated after a neck dissection
has been performed for positive nodes; levels I to V
should be Included.
 Elective irradiation should be considered for advanced
T stage, certain histologic subtypes, facial nerve
dysfunction at presentation, and recurrent disease.
 The intraparotideal nodes should be included.

 In early high-risk parotid cancer, levels II and III
should be included.
 In elective treatment the number of possible positive
nodes is unknown, most authors advise treatment of
levels Ib to IV prophylactically.
 There is no indication for bilateral elective neck
treatment.

For parotid tumors, the decision to treat the neck nodes will depend on the T
stage and the histologic type, and will be indicated by a score of at least 4

Boundaries
 Superior- matched with inferior border of parotid field
 Inferior- level of clavicle
 Anterior - Anterior Border of masseter/ buccinator
 Posterior - post to surgical limit or behind mastoid process

DOSE
 Post op : 60 Gy (@2Gy/#) post excision and 66 Gy for
high-risk patients with positive margins (<1 mm)
 Post Nodal Resection :60 Gy to positive nodes and 66
Gy for extranodal disease
 ENI : 46 to 50 Gy

Pleomorphic Adenoma
 Standard therapy : conservative (superficial)
parotidectomy
 Recurrence rates of about 0% to 5%
 Indications for postoperative irradiation
 recurrent disease
 microscopically positive margins after surgical resection
 large, deep-seated lesions that may not allow complete
surgical excision with adequate margins or would
require sacrificing the facial nerve

Submandibular glands
 Single field is enough
 Possible regions that should be included in portal:
submandibular angle , neighbouring oral cavity,
pterygomaxillary fossa, cranial base, ipsilateral neck
 Superior border : hard palate
 Inferior border: hyoid bone
 Anterior border: anterior to mentum
 Posterior border: posterior to mandibular angle

 Node Irradiation : Except for small acinic cell and
adenoid cystic cancers, the neck node levels I to IV
should be irradiated electively
 Dose : If there is perineural invasion of a major nerve,
a tumor dose of 60 to 66 Gy in 6 to 6.5 weeks is
recommended, and the nerve path to the base of skull
should be treated,

Sublingual gland
 Field Boundaries
 Superior: 1cm above the upper border of the tongue
 Inferior: hyoid bone- thyroid notch interspace
 Anterior : anterior aspect of the mental symphysis
 Posterior: posterior aspect of the mandibular ramus
 Right and left opposed lateral portals are needed to
completely encompass this treatment volume,
particularly when the regional lymph nodes are
included

MINOR SALIVARY GLANDS
 Depends on the area involved and is similar to the
treatment for squamous cell carcinomas in these areas
 Two significant exceptions :
 First, when a named branch of a cranial nerve is
involved by adenoid cystic carcinoma, the nerve
pathways to the base of the skull should be electively
treated.
 Second, for tumors of the palate or paranasal sinuses,
the base of the skull is included because of its proximity
to the tumor bed.

NODAL IRRADIATION
 Incidence of lymph node metastases is usually lower than that
for squamous cell carcinomas of similar size
 Elective treatment of the neck nodes depend on the scoring
system.
 T3/T4 N0 pharyngeal-site tumor neck nodes should be treated
prophylactically.
 In minor salivary gland cancers of the oral cavity elective
radiation of the neck nodes is seldom indicated.
 Postoperative radiotherapy is indicated after resection of
metastatic neck lymphadenopathy.

IMRT
 Five- to seven coplanar isocentric beams with 6
MV photon
 Advantages :
 Excellent coverage of the tumor
 Sparing of C/L parotid, mucosa,
temporal lobes, lenses
 Best approach for adenoid cystic
carcinomas (risk of perineural invasion &
treatment volume require to include neural
pathways to base of skull)

 N = 32 inoperable primary or recurrent major or minor
salivary gland tumors
 Statistically significant improvement in local/regional
control for the neutron group (56% vs. 17%, p = 0.009)
 No improvement in overall survival
 Patterns of failure : Distant metastases account for the
majority of failures in the neutron arm and local/regional
failures in the photon arm.
 Treatment-related morbidity : Incidence of morbidity
graded “severe” was greater on the neutron arm, there was
no significant difference in “life-threatening” complications

CONCLUSION
 Fast neutron radiotherapy appears to be the
treatment-of-choice for patients with inoperable
primary or recurrent malignant salivary gland tumors.

Biological Basis
Neutron Photon
LET High Low
DNA damage Single hit ds DNA damage Ss DNA damage
OER 1.6 2.5-3
RBE 8

SYSTEMIC THERAPY
 In the palliative setting cisplatin as monotherapy
showed a 20% response rate for locoregional disease
and 7% for distant failures
 A combination of 5-fluorouacil, cyclophosphamide,
cisplatin, and doxorubicin gave a response rate of 50%.
 Palliative chemotherapy may be beneficial in patients
who have progressive, symptomatic disease with no
other treatment options

Salivary gland ca

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