Post on 04-Apr-2018
7/29/2019 Salivary Gland Malignancy
1/39
Salivary Gland Malignancy
Dr Sasikumar Sambasivam
DNB Resident
Dept. of Radiation Oncology
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
2/39
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
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
3/39
Staging
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
4/39
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
5/39
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
6/39
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
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
7/39
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.
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
8/39
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)
7/29/2019 Salivary Gland Malignancy
9/39
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
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
10/39
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.
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
11/39
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
12/39
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
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
13/39
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
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
14/39
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)
7/29/2019 Salivary Gland Malignancy
15/39
BMCHRC,Jaipur(www.bmchrc.org)
RADICAL RT FOR UNRESECTABLE PRIMARY
7/29/2019 Salivary Gland Malignancy
16/39
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)
7/29/2019 Salivary Gland Malignancy
17/39
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
18/39
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
7/29/2019 Salivary Gland Malignancy
19/39
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.
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
20/39
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
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
21/39
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
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
22/39
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
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
23/39
RT Planning & Delivery
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
24/39
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:
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
25/39
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
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
26/39
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.
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
27/39
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.
BMCHRC,Jaipur(www.bmchrc.org)
7/29/2019 Salivary Gland Malignancy
28/39
BMCHRC,Jaipur(www.bmchrc.org)
P tid
7/29/2019 Salivary Gland Malignancy
29/39
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.
BMCHRC,Jaipur(www.bmchrc.org)
P tid
7/29/2019 Salivary Gland Malignancy
30/39
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
BMCHRC,Jaipur(www.bmchrc.org)
b d b l l d
7/29/2019 Salivary Gland Malignancy
31/39
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.
BMCHRC,Jaipur(www.bmchrc.org)
S bli l Gl d
7/29/2019 Salivary Gland Malignancy
32/39
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.
BMCHRC,Jaipur(www.bmchrc.org)
Brachytherapy
7/29/2019 Salivary Gland Malignancy
33/39
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%.
BMCHRC,Jaipur(www.bmchrc.org)
F t N t Th
7/29/2019 Salivary Gland Malignancy
34/39
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
BMCHRC,Jaipur(www.bmchrc.org)
Dosing Definitive Setting (66 74 Gy)
7/29/2019 Salivary Gland Malignancy
35/39
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
7/29/2019 Salivary Gland Malignancy
36/39
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.
BMCHRC,Jaipur(www.bmchrc.org)
Patient Care
7/29/2019 Salivary Gland Malignancy
37/39
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.
BMCHRC,Jaipur(www.bmchrc.org)
Prognosticators
7/29/2019 Salivary Gland Malignancy
38/39
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)
7/29/2019 Salivary Gland Malignancy
39/39
Thank you.
BMCHRC J i ( b h )