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Salivary Gland Malignancy 
Dr Sasikumar Sambasivam 
DNB Resident 
Dept. of Radiation Oncology 
BMCHRC,Jaipur(www.bmchrc.org)
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) 
• FNAC –IOC 
• Excision not enucleation 
BMCHRC,Jaipur(www.bmchrc.org)
Staging 
BMCHRC,Jaipur(www.bmchrc.org)
BMCHRC,Jaipur(www.bmchrc.org)
BMCHRC,Jaipur(www.bmchrc.org)
SURGERY 
PAROTID GLAND: 
•Superficial parotidectomy: Implies complete removal of 
the 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 to 
80%) and nerve damage 
BMCHRC,Jaipur(www.bmchrc.org)
• 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 
superficial parotidectomy. 
BMCHRC,Jaipur(www.bmchrc.org)
• 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 parotidectomy 
BMCHRC,Jaipur(www.bmchrc.org)
• 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)
NECK DISSECTION 
• 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 
done. 
BMCHRC,Jaipur(www.bmchrc.org)
BMCHRC,Jaipur(www.bmchrc.org)
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)
Adjuvant RT -Bibliography 
• Dutch Head–Neck Oncology Cooperative Group (NHNOCG), 2005 → 
538 cases. 
• 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 
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. 
BMCHRC,Jaipur(www.bmchrc.org) 
– 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– 
994 
BMCHRC,Jaipur(www.bmchrc.org)
BMCHRC,Jaipur(www.bmchrc.org)
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 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)
BMCHRC,Jaipur(www.bmchrc.org)
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 T3–4 tumors and for RT doses 
<66 Gy. 
– 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 
BMCHRC,Jaipur(www.bmchrc.org)
Neutron therapy: 
•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 
photon/electron arm. 
– 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. 
BMCHRC,Jaipur(www.bmchrc.org)
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 
BMCHRC,Jaipur(www.bmchrc.org)
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 
BMCHRC,Jaipur(www.bmchrc.org)
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 / metastatic 
adenoid 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)
RT Planning & Delivery 
BMCHRC,Jaipur(www.bmchrc.org)
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 
BMCHRC,Jaipur(www.bmchrc.org)
• 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, the 
CTV60 should include the course of 
the facial nerve up to the stylomastoid 
foramen at the skull base 
BMCHRC,Jaipur(www.bmchrc.org)
• 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 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 
3–5 mm. 
BMCHRC,Jaipur(www.bmchrc.org)
Parotids 
• Single field technique with photon–electron 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. 
• Anterior–posterior 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)
BMCHRC,Jaipur(www.bmchrc.org)
Parotids 
• Electron portal margins should be 1 cm larger than those for 
photons because of the constriction of the electron isodose curves 
at depth 
• 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. 
BMCHRC,Jaipur(www.bmchrc.org)
Parotids 
• 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 
best approach 
• 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 
BMCHRC,Jaipur(www.bmchrc.org)
Submandibular glands 
• 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 
used. 
BMCHRC,Jaipur(www.bmchrc.org)
Sublingual Gland 
•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. 
BMCHRC,Jaipur(www.bmchrc.org)
Brachytherapy 
• 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 
I-125 . 
• Previously, radiation therapy had been administered to 15 of these 
patients. 
• 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)
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 
environment 
– 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 
BMCHRC,Jaipur(www.bmchrc.org)
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. 
BMCHRC,Jaipur(www.bmchrc.org)
Patient Care 
• Swallowing problems,mucositis—Symp 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 
• 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)
Thank you. 
BMCHRC,Jaipur(www.bmchrc.org)

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Salivary gland tumors

  • 1. Salivary Gland Malignancy Dr Sasikumar Sambasivam DNB Resident Dept. of Radiation Oncology BMCHRC,Jaipur(www.bmchrc.org)
  • 2. 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) • FNAC –IOC • Excision not enucleation BMCHRC,Jaipur(www.bmchrc.org)
  • 6. SURGERY PAROTID GLAND: •Superficial parotidectomy: Implies complete removal of the 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 to 80%) and nerve damage BMCHRC,Jaipur(www.bmchrc.org)
  • 7. • 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 superficial parotidectomy. BMCHRC,Jaipur(www.bmchrc.org)
  • 8. • 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 parotidectomy BMCHRC,Jaipur(www.bmchrc.org)
  • 9. • 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)
  • 10. NECK DISSECTION • 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 done. BMCHRC,Jaipur(www.bmchrc.org)
  • 12. 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)
  • 13. Adjuvant RT -Bibliography • Dutch Head–Neck Oncology Cooperative Group (NHNOCG), 2005 → 538 cases. • 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 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. BMCHRC,Jaipur(www.bmchrc.org) – Terhaard CHJ et al (2005) The role of radiotherapy in the treatment of
  • 14. 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– 994 BMCHRC,Jaipur(www.bmchrc.org)
  • 16. 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 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)
  • 18. 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 T3–4 tumors and for RT doses <66 Gy. – 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 BMCHRC,Jaipur(www.bmchrc.org)
  • 19. Neutron therapy: •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 photon/electron arm. – 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. BMCHRC,Jaipur(www.bmchrc.org)
  • 20. 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 BMCHRC,Jaipur(www.bmchrc.org)
  • 21. 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 BMCHRC,Jaipur(www.bmchrc.org)
  • 22. 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 / metastatic adenoid 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)
  • 23. RT Planning & Delivery BMCHRC,Jaipur(www.bmchrc.org)
  • 24. 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 BMCHRC,Jaipur(www.bmchrc.org)
  • 25. • 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, the CTV60 should include the course of the facial nerve up to the stylomastoid foramen at the skull base BMCHRC,Jaipur(www.bmchrc.org)
  • 26. • 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 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 3–5 mm. BMCHRC,Jaipur(www.bmchrc.org)
  • 27. Parotids • Single field technique with photon–electron 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. • Anterior–posterior 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)
  • 29. Parotids • Electron portal margins should be 1 cm larger than those for photons because of the constriction of the electron isodose curves at depth • 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. BMCHRC,Jaipur(www.bmchrc.org)
  • 30. Parotids • 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 best approach • 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 BMCHRC,Jaipur(www.bmchrc.org)
  • 31. Submandibular glands • 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 used. BMCHRC,Jaipur(www.bmchrc.org)
  • 32. Sublingual Gland •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. BMCHRC,Jaipur(www.bmchrc.org)
  • 33. Brachytherapy • 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 I-125 . • Previously, radiation therapy had been administered to 15 of these patients. • 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)
  • 34. 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 environment – 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 BMCHRC,Jaipur(www.bmchrc.org)
  • 35. 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
  • 36. 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. BMCHRC,Jaipur(www.bmchrc.org)
  • 37. Patient Care • Swallowing problems,mucositis—Symp 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)
  • 38. 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)