salivary gland malignancy

7/29/2019 Salivary Gland Malignancy

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Salivary Gland Malignancy

Dr Sasikumar Sambasivam

DNB Resident

Dept. of Radiation Oncology

BMCHRC,Jaipur(www.bmchrc.org)


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General Intro

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)

FNACIOC

Excision not enucleation



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Staging



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SURGERY

PAROTID GLAND:

Superficial parotidectomy: Implies complete removal ofthe parotid gland superficial to the plane of the facial

nerve

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 to80%) and nerve damage



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Adequate parotidectomy:

Implies removing the tumor completely, taking care toavoid capsular rupture or nerve damage, withapproximately 0.5 1-cm tumor-free margins.

Requires very careful and stringent case selection

Should be done only in benign tumors, limited tosuperficial lobe, preferably small pleomorphicadenomas in tail of parotid.

In properly selected benign tumors, adequateparotidectomy is as safe as and less morbid thansuperficial parotidectomy.



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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

functions

high-grade malignant tumors with a high risk for

metastasis

any parotid malignancy with an indication of metastasis to

intraglandular or cervical lymph nodes any primary malignancy originating within the deep lobe

itself

Positive margin (base) after superficial parotidectomyBMCHRC,Jaipur(www.bmchrc.org)


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Total Parotidectomy with the excision of facial

nerve

Radical parotidectomy:Implies excision of other structures than the parotid gland

and facial nerve.

Done when tumor involves: Skin

Infra-temporal fossa

Mandible

TM joint

Petrous bone



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NECK DISSECTION

Node negative (N0) neck:

No consensus regarding management of node negative neck.

Some recommendations based on retrospective studiesfor 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 isdone.



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ADJUVANT RADIOTHERAPY

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



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Adjuvant RT -Bibliography

Dutch HeadNeck Oncology Cooperative Group (NHNOCG), 2005

538 cases.

Parotid gland in 59%, submandibular gland in 14%, oral cavity in23%, and elsewhere in 5%.

All with surgery and 78%(386) postoperative RT.

Median RT dose: 62 Gy.

Adjuvant RT significantly increased local control in T3T4 tumors,

close surgical margins, incomplete resections, bone invasions and

perineural infiltrations.

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 alone.

Terhaard CHJ et al (2005) The role of radiotherapy in the treatment ofmalignant salivary gland tumors. Int J Radiat Oncol Biol Phys 61(1):103111



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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

994BMCHRC,Jaipur(www.bmchrc.org)


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RADICAL RT FOR UNRESECTABLE PRIMARY


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RADICAL RT FOR UNRESECTABLE PRIMARY:

Role of definitive radical RT is restricted to unresectable

tumors. This form of treatment is usually palliative in

intent.

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 fastneutron 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)


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Definitive RT- Bibliography

UCSF, 2006 45 malignant salivary gland tumors treated with RT

alone.

Median 66 Gy.

Five-year local control: 70%; 10-year local control: 57%.

Local recurrences are frequent in T34 tumors and for RT doses


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Neutron therapy: RTOG-MRC Neutron Trial, 1993 randomized. 32 inoperable or

recurrent major/minor salivary gland tumors, Neutrons (1722

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

photon/electron arm.

No difference in OS (2515%).

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 OncolBiolPhys 27(2):235

240

Caterall et al. -65patients -Locally advanced Recurrent malignantsalivary gland tumors, 89% of which were stage IV

Achieved a 72% local control rate;5-year survival rate was 50% Facialnerve was not damaged by fast neutron therapy.



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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):13651372



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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):11951204



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CHEMOTHERAPY

Chemotherapy has role only in palliative setting in

patients with recurrent unresectable disease or

distant metastases.

May have a palliative benefit for a small

proportion of patients with recurrent / metastaticadenoid cystic carcinomas after due consideration

of other therapies (palliative radiation,

metastatectomy of solitary lesions)

Recommendations: Single agent - Mitoxantrone

and/ or Vinorelbine Combination



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RT Planning & Delivery



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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

General Considerations & Volume definition:



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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

included

In adenoid cystic carcinomas, theCTV60 should include the course of

the facial nerve up to the stylomastoid

foramen at the skull base



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If Neck dissection is + the levels to be treated are included in the

CTV60.

Retropharyngeal LN to be included for deep lobe tumors of

parotid

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 thatincluding 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

35 mm.



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Parotids

Single field technique with photonelectron combination:

Used to deliver a homogeneous dose distribution sparing the contralateral

parotid gland

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.

Anteriorposterior oblique double wedge technique

This technique allows dose homogeneity and the contralateral parotid

gland sparing.

However, this technique may cause set-up errors.



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P tid


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Parotids Electron portal margins should be 1 cm larger than those for

photons because of the constriction of the electron isodose curvesat depth

The energy of the electron that has to be chosen depends on theanatomic distance from the skin of the ipsilateral cheek to the oralmucosa and generally ranges between 12 and 16 MeV

When a combination of electrons and photons are used, eithermodality can start first.

There is a weighting between 50% and 80% with electrons.

By mixing the two different beams, one can decrease theirradiation of the contralateral parotid gland, acute radiation skinreaction, and mucositis.


P tid


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For majority of cases, 3D-CRT using either a two- or three-fieldapproach including wedges is appropriate

If adenoid cystic carcinoma, with the increased risk of perineuralinvasion and travel along the pathways of the adjacent cranialnerves require the treatment volume to include the neuralpathways to the base of the skull--IMRT treatment plans give thebest approach

Sparing the contralateral parotid gland is a very importantconsideration during the complex treatment planning process for3D-CRT and IMRT

Dose contraints to the contralateral parotid gland-

Mean dose to the gland should be limited to less than orequal to 26 Gy

Dose to at least 50% of the gland should be limited to lessthan 30 Gy

Parotids


b d b l l d


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Submandibular glands

Single field is enough.

Possible regions that should be included in RT portal:

submandibular angle, neighboring oral cavity, pterygomaxillaryfossa, 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 areused.


S bli l Gl d


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Sublingual Gland

General portal margins that encompass the planning target volume

are as follows:

Superior1 cm above the upper border of the tongue

Inferiorhyoid bonethyroid notch interspace

Anterioranterior aspect of the mental symphysis

Posteriorposterior aspect of the ascending mandibular ramus Lateral2-cm flash of ipsilateral mandible

Medial2 cm past midline (however, the entire floor ofmouthsubmental region usually requires treatment)

Right and left opposed lateral portals are needed to completelyencompass this treatment volume, particularly when the regionallymph nodes are included.


Brachytherapy


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Brachytherapy

For technically implantable lesions, brachytherapy +/- EBRTforunresectable malignant parotid tumors or recurrence.

Armstrong et al. reported on 20 patients with recurrent oradvanced disease treated with brachytherapy alone using Ir-192 orI-125 .

Previously, radiation therapy had been administered to 15 of thesepatients.

Implant was to gross disease in 15 of the 20 patients.

Actuarial local control rate at 5 years was 60%.


F t N t Th


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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 hypoxicenvironment

Lethal effects of fast neutrons are less dependent on the cell cycle phasecompared 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 acutedermal reaction than photons


Dosing Definitive Setting (66 74 Gy)


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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 treatmentvolume and scheme for phase I for the remaining 2 weeks (10fractions) to a total of 54 Gy

Afternoon fraction is given 6 hours after the morning dose at afraction size of 1.6 Gy to a cone-down treatment volume that

consists of the primary gross tumor area and adenopathy. This iscontinued for 2 weeks (10 fractions) to a dosage of 16 Gy.

Ultimately, the total cumulative dosage from phase I and II tothe gross tumor areas is 70 Gy and to the electively irradiatedareas is 54 Gy

The spinal cord dosage is kept to a maximum dosage of 45 GyBMCHRC,Jaipur(www.bmchrc.org)

D i i Adj S i


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Dosing in AdjuvantSetting 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.


Patient Care


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Patient Care Swallowing problems,mucositisSymp Care

Advice on jaw exercises can reduce the risk of trismus and TMJ

dysfunction.

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

indicated.


Prognosticators


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Prognosticators 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

duct carcinoma

High Ki-67 and low p27expression: associated with shorter

disease-freesurvival in adenoid cystic andmucoepidermoid

carcinoma. BMCHRC,Jaipur(www.bmchrc.org)


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Thank you.

BMCHRC J i ( b h )

salivary gland malignancy

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