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Salivary Gland Malignancy
Dr Sasikumar Sambasivam
Dept. of Radiation Oncology
• Most Salivary Gland tumors are benign(Pleo. Aden)
• Major > Minor
• M C benign tumor of parotid in children-Hemangioma
• Malignancy varies inversely with size
• MC site of Minor SG tumor is Oralcavity(Hard palate)
• FNAC –IOC
• Excision not enucleation
•Superficial parotidectomy: Implies complete removal of
the parotid gland superficial to the plane of the facial
– minimum standard surgical procedure.
– “treatment of choice” for tumors in the superficial
lobe, which are not involving the facial nerve.
– avoid enucleation and excision biopsy because it
greatly increases the likelihood of recurrence (up to
80%) and nerve damage
• Adequate parotidectomy:
Implies removing the tumor completely, taking care to
avoid capsular rupture or nerve damage, with
approximately 0.5– 1-cm tumor-free margins.
– Requires very careful and stringent case selection
– Should be done only in benign tumors, limited to
superficial lobe, preferably small pleomorphic
adenomas in tail of parotid.
– In properly selected benign tumors, adequate
parotidectomy is as safe as and less morbid than
• Total Conservative parotidectomy:
Implies excision of entire parotid gland (superficial
and deep lobes), while preserving the facial nerve.
• Done for:
– tumors involving the deep lobe, with intact facial nerve
– high-grade malignant tumors with a high risk for
– any parotid malignancy with an indication of metastasis
to intraglandular or cervical lymph nodes
– any primary malignancy originating within the deep lobe
– Positive margin (base) after superficial parotidectomy
• Total Parotidectomy with the excision of facial
• Radical parotidectomy:
Implies excision of other structures than the parotid gland
and facial nerve.
Done when tumor involves:
– Infra-temporal fossa
– TM joint
– Petrous bone
• Node negative (N0) neck:
– No consensus regarding management of node negative neck.
• Some recommendations based on retrospective studies
for elective neck dissection are:
– T3, T4 tumors
– Size > 4 cm
– High grade
– Extraparenchymal spread
• Alternate approach: Routine sampling of level II nodes
• Frozen section if positive, Modified Neck Dissection is
• Large number of prospective and retrospective studies are the
guidelines for use of PORT
• Indications are as follows:
– 1. T3/T4 cancers
– 2. Close or positive margins
– 3. Lymph node metastasis
– 4. Adenoid cystic carcinoma
– 5. High or intermediate grade tumors
– 6. Deep lobe cancers
– 8. Peri-neural involvement
– 9. Recurrent tumors
Adjuvant RT -Bibliography
• Dutch Head–Neck Oncology Cooperative Group (NHNOCG), 2005 →
• Parotid gland in 59%, submandibular gland in 14%, oral cavity in
23%, and elsewhere in 5%.
• All with surgery and 78%(386) postoperative RT.
• Median RT dose: 62 Gy.
• Adjuvant RT significantly increased local control in T3–T4 tumors,
close surgical margins, incomplete resections, bone invasions and
• Postoperative radiotherapy improved 10-year local control
significantly compared with surgery alone in T(3-4) tumors (84% vs.
18%), in patients with close (95% vs. 55%) and incomplete
resection (82% vs. 44%), in bone invasion (86% vs. 54%), and
perineural invasion (88% vs. 60%). N+ neck 86% vs. 62% for surgery
– Terhaard CHJ et al (2005) The role of radiotherapy in the treatment of
Elective Nodal RT- Bibliography
• UCSF; 2007 → 251 N0 malignant salivary gland tumors. Adenocystic 33%,
mucoepidermoid 24%, adenocarcinoma 23%. Gross total resection R0 44%, R1
56%. No neck dissection. All with adjuvant RT. Median primary RT dose 63 Gy.
• Elective neck RT: ipsilateral 69%, bilateral 31%.
• Nodal relapse: T1 7%, T2 5%, T3 12%, T4 16%.
• Elective nodal RT: 10-year nodal relapse risk decreased from 26% to 0% (decrease
in risk: squamous 67%, undifferentiated 50%, adenocarcinoma 34%).
• Whether or not elective nodal RT was given, no nodal relapse was observed in
adenocystic (0/84) and acinic cell (0/21) tumors.
• Conclusion: elective nodal RT is required for high-grade tumors, but not for
adenoid cystic and acinic cell tumors.
– Chen AM (2007) Patterns of nodal relapse after surgery and postoperative
radiation therapy for carcinomas of the major and minor salivary glands: what
is the role of elective neck irradiation? Int J Radiat Oncol Biol Phys 67(4):988–
RADICAL RT FOR UNRESECTABLE PRIMARY:
• Role of definitive radical RT is restricted to unresectable
tumors. This form of treatment is usually palliative in
• Fast neutron beam therapy has been shown to be
beneficial than standard photon therapy in a RCT.
However its use is limited by the extremely scarce
availability of fast neutron RT units.
RT indications in benign salivary gland tumors
• Inoperable or unresectable tumor
• Facial nerve involvement
• Recurrent tumor
• Subtotal excision BMCHRC,Jaipur(www.bmchrc.org)
Definitive RT- Bibliography
• UCSF, 2006 → 45 malignant salivary gland tumors treated with RT
• Median 66 Gy.
• Five-year local control: 70%; 10-year local control: 57%.
• Local recurrences are frequent in T3–4 tumors and for RT doses
– Chen AM et al (2006) Long-term outcome of patients treated
by radiation therapy alone for salivary gland carcinomas. Int J
Radiat Oncol Biol Phys 66(4):1044–1050
•RTOG-MRC Neutron Trial, 1993 → randomized. 32 inoperable or
recurrent major/minor salivary gland tumors, Neutrons (17–22 nGy)
vs. photons/electrons (55 Gy/4 weeks or 70 Gy/7 weeks).
– Ten-year locoregional control: 56% in neutron vs. 17%
photon/electron arm (p = 0.009).
– Median survival: 3 years in neutron vs. 1.2 years in
– No difference in OS (25–15%).
• Laramore G et al (1993) Neutron versus photon irradiation for
unresectable salivary glandtumors: final report of an RTOG-MRC
randomized clinical trial. Int J Radiat Oncol BiolPhys 27(2):235–240
•Caterall et al. -65patients -Locally advanced Recurrent malignant
salivary gland tumors, 89% of which were stage IV
– Achieved a 72% local control rate;5-year survival rate was 50% Facial
nerve was not damaged by fast neutron therapy.
Adenoid cystic carcinoma
•MSKCC, 2007 → 59 adenoid cystic carcinomas (oral cavity 28%,
paranasal sinus 22%, parotid 14%, submandibular gland 14%). T1–4
tumors. Treated with surgery + RT. Included cranial base in 90% of
cases. Median follow-up: 5.9 years.
•Five-year local control: 91%; OS: 87%.
•Ten-year local control: 81%; OS: 65%.
•Poor prognostic factors: T4 tumor, gross and/or clinical nerve
involvement, LN (+).
•Adjuvant RT after surgery had excellent local control rates.
– Gomez DR (2008) Outcomes and prognostic variables in adenoid cystic
carcinoma of the head and neck: a recent experience. Int J Radiat Oncol
Biol Phys 70(5):1365–1372
Minor salivary glands
•Netherland Cancer Institute, 2000 → retrospective. 55 minor
salivary gland tumors.
•Median follow-up: 11 years.
•Five-year disease-specific survival: 76%; 10-year: 74%.
•Prognostic factors: age, stage, lymph node status, vascular invasion,
nasopharynx/paranasal sinus localization.
– Vander Poorten VL (2000) Stage as major long term outcome predictor in
minor salivary gland carcinoma. Cancer 89(6):1195–1204
• Chemotherapy has role only in palliative setting in
patients with recurrent unresectable disease or
• May have a palliative benefit for a small
proportion of patients with recurrent / metastatic
adenoid cystic carcinomas after due consideration
of other therapies (palliative radiation,
metastatectomy of solitary lesions)
• Recommendations: Single agent - Mitoxantrone
and/ or Vinorelbine Combination
General Considerations & Volume definition:
• Parotid gland contains several intraparotid lymph nodes-can
spread via the intraparotid nodes to the subparotid nodes in
the retrostyloid space and thence to the retropharyngeal
nodes, or directly to level II nodes
• Tumours of the submandibular salivary gland can invade locally
or perineurally in
– the marginal branch of the facial nerve,
– the lingual nerve, nerve to mylohyoid and hypoglossal nerve.
– Pathway : Lymphatic drainage is to level Ib nodes lying adjacent to(but
rarely within) the salivary gland and then to ipsilateral level II nodes
• The CTV60
• Particular attention is given to the
deep excision margin which is likely to
be close or involved if the facial nerve
has been preserved.
• As a minimum, the medial extent of
the CTV60 should be to the lateral
surface of the internal jugular vein,
but if the deep lobe of the parotid is
thought to contain tumour, the
parapharyngeal space should be
• In adenoid cystic carcinomas, the
CTV60 should include the course of
the facial nerve up to the stylomastoid
foramen at the skull base
• If Neck dissection is + the levels to be treated are included in the
• Retropharyngeal LN to be included for deep lobe tumors of
• For prophylactic neck radiotherapy,(High Grade) the ipsilateral
level Ib, II and III nodes should be included in the treated volume.
• A separate CTV44 can be defined to give these sites a
prophylactic dose; the proximity of the nodes to the parotid bed
are so that including them in the CTV60 and treating the whole
volume in one phase can be done.
• Sites where resection margins are involved, or where there was
extracapsular nodal extension, should be defined in a CTV66
• CTV is expanded isotropically to form the PTV by a margin usually
• Single field technique with photon–electron combination:
– Used to deliver a homogeneous dose distribution sparing the contralateral
– Superior: above zygomatic bone, including parotid and scar
– Inferior: above thyroid cartilage
– Anterior: anterior edge of masseter muscle
– Posterior: posterior to mastoid
– Lymph node (+) or neck irradiation is required: posterior to spinous process
– However, if the accessory parotid gland is involved with tumor, an
additional 2-cm margin must be added anteriorly because this is the
location of this parotid gland by anatomic variation.
• Anterior–posterior oblique double wedge technique
– This technique allows dose homogeneity and the contralateral parotid
– However, this technique may cause set-up errors.
• Electron portal margins should be 1 cm larger than those for
photons because of the constriction of the electron isodose curves
• The energy of the electron that has to be chosen depends on the
anatomic distance from the skin of the ipsilateral cheek to the oral
mucosa and generally ranges between 12 and 16 MeV
• When a combination of electrons and photons are used, either
modality can start first.
• There is a weighting between 50% and 80% with electrons.
• By mixing the two different beams, one can decrease the
irradiation of the contralateral parotid gland, acute radiation skin
reaction, and mucositis.
• For majority of cases, 3D-CRT using either a two- or three-field
approach including wedges is appropriate
• If adenoid cystic carcinoma, with the increased risk of perineural
invasion and travel along the pathways of the adjacent cranial
nerves require the treatment volume to include the neural
pathways to the base of the skull--IMRT treatment plans give the
• Sparing the contralateral parotid gland is a very important
consideration during the complex treatment planning process for
3D-CRT and IMRT
• Dose contraints to the contralateral parotid gland-
– Mean dose to the gland should be limited to less than or
equal to 26 Gy
– Dose to at least 50% of the gland should be limited to less
than 30 Gy
• Single field is enough.
• Possible regions that should be included in RT portal:
submandibular angle, neighboring 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.
• Four to six megavolt X-rays, Co-60 or 6–18 MeV electrons are
•General portal margins that encompass the planning target volume
are as follows:
– Superior—1 cm 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 ascending mandibular ramus
– Lateral—2-cm flash of ipsilateral mandible
– Medial—2 cm past midline (however, the entire floor of
mouth–submental region usually requires treatment)
•Right and left opposed lateral portals are needed to completely
encompass this treatment volume, particularly when the regional
lymph nodes are included.
• For technically implantable lesions, brachytherapy +/- EBRTfor
unresectable malignant parotid tumors or recurrence.
• Armstrong et al. reported on 20 patients with recurrent or
advanced disease treated with brachytherapy alone using Ir-192 or
• Previously, radiation therapy had been administered to 15 of these
• Implant was to gross disease in 15 of the 20 patients.
• Actuarial local control rate at 5 years was 60%.
Fast Neutron Therapy
• Fast neutrons are a densely ionizing, high LET type of particulate radiation
• They are contrasted with photons in the following fashion
– Biologic effectiveness of fast neutrons is much less affected by a hypoxic
– Lethal effects of fast neutrons are less dependent on the cell cycle phase
compared with photons
– Repair of sublethal damage in malignant cells matters less
– Fast neutrons are biologically more effective (relative biologic effectiveness
[RBE] > 2.6)
– Fast neutrons lack skin sparing and thus can cause a more prominent acute
dermal reaction than photons
Dosing Definitive Setting (66-74 Gy)
• Phase I
– 1.8 Gy is administered per fraction @ 1fr/day
– 5 days per week for 4 weeks
– Total dosage of 36 Gy
• Phase II
– Begins with twice-a-day treatment separated by at least 6 hours
– Morning fraction is a continuation of the initial treatment
volume and scheme for phase I for the remaining 2 weeks (10
fractions) to a total of 54 Gy
– Afternoon fraction is given 6 hours after the morning dose at a
fraction size of 1.6 Gy to a cone-down treatment volume that
consists of the primary gross tumor area and adenopathy. This
is continued for 2 weeks (10 fractions) to a dosage of 16 Gy.
– Ultimately, the total cumulative dosage from phase I and II to
the gross tumor areas is 70 Gy and to the electively irradiated
areas is 54 Gy
– The spinal cord dosage is kept to BMCHRC,Jaipur(www.b mach rmc.orag)ximum dosage of 45 Gy
Dosing in Adjuvant Setting
• A dosage of 1.8 to 2.0 Gy per fraction, one fraction per day, 5 days per week
is administered to a total cumulative dosage as follows-
– High-risk areas for microscopic disease in surgically violated regions: 60 Gy
(2.0 Gy/fraction) to 63 Gy (1.8 Gy/fraction)
– Small volume of known microscopic disease: 66 Gy
– Elective irradiation of areas at risk for microscopic disease: 50 Gy
(2.0 Gy/fraction) to 54 Gy (1.8 Gy/fraction)
– Gross residual disease: 70 Gy.
• Swallowing problems,mucositis—Symp Care
• Advice on jaw exercises can reduce the risk of trismus and TMJ
• Conductive hearing loss due to middle ear effusions can occur and
take several months to improve after treatment has finished.
• If subjective hearing loss persists 2 months after treatment, an
audiogram should be performed.
• If there is evidence of conductive hearing loss, a grommet may be
• The 10 year disease free survival of salivary gland tumors
ranges from 47 to 74%; and 10 year overall survival was 50% in
one large study.
• Some prognostic factors associated with poor outcomes are:
– Extent of disease (Advanced T & N-status)
– Positive or close resection margins
– Nerve involvement
– Perineural invasion
– Grade: high-grade mucoepidermoid carcinoma, high grade
adenoid cystic carcinoma, undifferentiated carcinoma,
squamous cell carcinoma,adenocarcinoma NOS, salivary
– High Ki-67 and low p27expression: associated with shorter
disease-freesurvival in adenoid cystic andmucoepidermoid