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Carcinoma Nasopharynx Moderator: Dr Sushmita Ghoshal

Carcinoma Nasopharynx

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Management of Carcinoma Nasopharynx

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Page 1: Carcinoma Nasopharynx

Carcinoma Nasopharynx

Moderator: Dr Sushmita Ghoshal

Page 2: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Anatomy

Page 3: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Anatomy

Foramen lacerum

Foramen spinosum

Foramen ovale

Foramen rotundum

Page 4: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Parapharyngeal Space

• The parapharyngeal space is located deep within the neck lateral to the pharynx and medial to the ramus of the mandible.

• Shape of an inverted pyramid with the floor at the skull base and it’s tip at the greater cornu of the hyoid bone

• Two compartments :– Prestyloid– Retrostyloid

Retrostyloid Space

Prestyloid Space

Page 5: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Lymphatic Drainage• Richest lymphatic plexus in the head

and neck region.• Submucosal lymphatics congregate at

the pretubal region – “pretubal plexus”.• These then pass on to the

retropharyngeal nodes as 8 -12 trunks which decussate in the midline.

• Lymphatic trunks pierce the level of the base of the skull and run between the pharyngobasilar fascia and the longus capitis.

• The lymphatic trunks drain in three directions:– To the retropharyngeal nodes.– To do the posterior cervical nodal and

the confluence of the 11th, cranial nerve and the jugular lymph node chains, situated at the tip of the mastoid.

– To the Jugulo-digastric nodes (Lederman )

Page 6: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Anatomy: RPLN• The retropharyngeal nodes are

present in two groups.– Median group.– Lateral group.

• The median group consists of 1 - 2 nodes interconnected in the midline.

• The lateral group consists of 1- 3 nodes located between the lateral aspect of the posterior pharyngeal wall and the carotid artery.

• These nodes are present from the vertebral levels C1- C3.

• The superior-most lymph node of the latter group is also known as the node of Rouviere.

• This node lies in front of the arch of the Atlas being separated from it by the longus colli muscle.

Page 7: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

CT anatomy

Page 8: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Incidence

Page 9: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Incidence: Sex

Page 10: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Clinical Features• Most common: Asymptomatic cervical

lymphadenopathy (87%)• MC node involved is the posterior deep cervical (direct

drainage from the lateral pharyngeal)• Other presenting symptoms:

– Nasal twang to speech– Unilateral serous otitis media ( in adults)– Cranial nerve palsy:

• U/L Cr nv. II to VI (petrosphenoidal syndrome of Jacod)

• U/L Cr nv. XI to XII ( Retroparotid syndrome of Villaret.)

• Cr nv V and VI most commonly involved. • Cr nv I, VII and VIII rarely involved.

– Sore throat : Oropharyngeal extension– Pain: Compression of Vth cranial nerve ( facial pain)– Trismus: Mandibular nerve involvement or pterygoid

muscle invasion.

Page 11: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Cranial Nerve involvement

0

5

10

15

20

25

30

35

40

45

50

I II III IV V VI VII VIII IX X XI XII

Lederman et al Leung et al

Page 12: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Local Spread

Nasal cavity & PNS

Orbital invasionBase of Skull, Clivus

Sphenoid sinus

Cavernous Sinus

Lateral Parapharyngeal space

Middle ear cavity

Oropharynx (tonsillar pillars)

C1 vertebrae

Page 13: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Nodal Spread

Page 14: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Etiology

Normal Epithelium

Low Grade Dysplasia

High Grade Dysplasia

Invasive Carcinoma

Metastatic Carcinoma

P53 Mutation

Gain Chromosome 12

Deletion 11 and 13

Deletion of Chromosomes 3p and 9p

Inactivation of Chromosome p14, 15 and 16

EBV infection

Page 15: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Investigations

• Staging:– CT– MRI– Endoscopy– PET scan– Chest Xray– USG Abdomen– Bone Scans

• Other Investigations– EBV Serology

Page 16: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Staging

• Several staging systems are in use:– Complex anatomy and spread patterns– Lack of international consensus:

• Separate Chinese, Hong Kong and American staging systems

• Systems available:– Fletcher (1967)– Ho’s staging (1978)– IUAC (1988)– Huaqing staging (1994)– AJCC (2002)

Page 17: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Comparison System Staging

T1 T2 T3 T4

Fletcher (1967)

< 1 cm diameter

> 1 cm but confined to

nasopharynx

Beyond nasopharynx

Involving skull base or cranial

nerves

Ho (1978)

Confined to

nasopharynx

Extending to nasal fossa or oropharynx

Bone/ Cranial nerve/ orbital / hypopharyngea

l / infratemporal

fossa involvement

NA

IUAC (1988)

Limited to one site in nasophary

nx

Extending to two sites in

nasopharynx

No bony destruction

Bony destruction including

eustachian tube

Huaqing (1994)

Limited to nasophary

nx

Involving the nasal cavity, oropharynx,

anterior cervical vertebrae, PPS before SO line

Pterygoid process / posterior

cranial nerve / posterior cervical

vertebrae / BOS / PPS beyond SO

line

Infratemporal fossa /

cavernous sinus / PNS /

direct invasion of C2 or C1 /

anterior cranial nerves

Page 18: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Ho’s vs AJCC

Page 19: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

AJCC system: T staging

• T1: – Tumor confined to the nasopharynx

• T2: – Tumor extends to soft tissues

• T2a : Extends to the oropharynx or the nasal fossa

• T2b : With parapharyngeal extension

• T3: – Tumor invades bony structures and/or paranasal

sinuses

• T4: – Tumor with intracranial extension and/or

involvement of cranial nerves, infratemporal fossa, hypopharynx, orbit, or masticator space

Page 20: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

AJCC system: N staging• N0:

– No regional lymph node metastasis

• N1: – Unilateral metastasis in lymph

node(s), < 6 cm in greatest dimension, above the supraclavicular fossa

• N2:– Bilateral metastasis in lymph

node(s), < 6 cm in greatest dimension, above the supraclavicular fossa

• N3:– N3a: Metastasis in a lymph

node(s) >6 cm – N3b: Extension to the

supraclavicular fossa

Ho’s Triangle

Page 21: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Staging: AJCC 2002

Stage I Stage IIA Stage IIB

Stage III Stage IVA Stage IVB

Page 22: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Pathology

• Some authors consider carcinomas to be of two types:– Keratinizing – Non keratinizing

• Others consider carcinomas to be of 4 types:– Keratinizing Squamous– Non Keratinizing Squamous– Lymphoepithelioma– Undifferentiated carcinomas

• WHO 3 types:– Type I : SCC– Type II : Non Keratinizing carcinoma– Type III : Undifferentiated carcinoma

Page 23: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Endemic NPC• Known to occur in China, Hong Kong, South Eastern

Asia, Greenland• Associated with EBV virus infection• In India similar pathology seen in Kashmiris.• Present a decade younger.• Not associated with smoking or alcohol consumption• Associated with undifferentiated carcinoma ( WHO II and

III)• Associated with more advanced disease at presentation• Nodal stage also more advanced and more frequently

involved.• Both chemo and radio sensitive

– Histologically more vascularized (Better Rx response)– Greater % of cell in the growth fraction.

• Better loco regional control and survival than sporadic variants.

• Several markers for predicting biological behavior

Page 24: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Prognostic factors• Most important stage.• Parapharyngeal extension is associated with a

poorer prognosis.• A Chinese series found that 4th cranial nerve

involvement – poor prognosis.• Nodal disease status:

– Bilateral cervical lymphadenopathy – Supraclavicular lymphadenopathy – Lymph node fixity

• Lymphoepithelioma histology: better prognosis• Undifferentiated histology: better prognosis• Molecular markers:

– Ki -67 over expression– P 53– E – cadherin expression

Page 25: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Treatment strategyStage

Early stage

Late stageExternal Radiation EBRT + ICBT

KPS > 70 KPS < 70

Concurrent Chemoradiation

Palliative Radiotherapy

Page 26: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Dose response

• Significant dose response relationship exists.

• Several series demonstrate that an increased-dose leads to better survival– Doses of 90 Gy delivered by boost increase

the local control and the distant metastasis free rate significantly over doses > 70 Gy

– Price however paid in increased morbidity

• Local recurrence rate reduced with the use of larger fields (Field size more than 250 cm2 associated with a doubling of local control as compared to field size of 100 cm2)

Page 27: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Dose-response

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

50 - 60 Gy 60 - 67.5 Gy > 67.5 Gy

T1

T2

T3

T4

Page 28: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Doses used• Radical radiotherapy:

– 60 – 66 Gy in 2 Gy per fraction over 6 – 6 ½ weeks

– Higher dose can be given with more conformal techniques:

• ICBT• IMRT• 3 DCRT

– In our patients with poor nutrition, advanced disease and absence of individualized care split course radiotherapy is an alternative

• 35 Gy in 15 # • 25 – 30 Gy in 10 – 15 # after 2-3 weeks

• Palliative radiotherapy:– 30 Gy / 10#– 20 Gy / 5#– 800 -1000 cGy single fraction

Page 29: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Treatment volume• The nasopharynx.• Posterior 2 cm of nasal cavity.• Posterior ethmoid sinuses.• Entire sphenoid sinus and the basiocciput• Cavernous sinus.• Base of skull, including the foramen ovale,

carotid canal and foramen spinosum.• Pterygoid fossae• Posterior 1/3rd of maxillary sinus.• Lateral and posterior oropharyngeal wall to

the level of mid-tonsillar fossa? Posterior 1/4th of orbit ( Fletcher – YES,

Perez - NO )

Page 30: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Nodal volumes

• The entire neck is at high risk for microscopic spread of disease.

• The neck nodes that should be treated are:– Upper deep jugular– Submandibular– Jugulodigastric– Midjugular– Posterior cervical– Retropharyngeal

Page 31: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Treatment planning

• Positioning:– Supine position.– Head should be extended

• Immobilization– To ensure accuracy in setup patient should be

immobilized with a custom-made thermoplastic cast.

• Localization:– All nodes are delineated with the use of radio –

opaque lead wires.– The outer canthus the eye opposite to which

simulation film is taken is marked with a lead wire.– Tumor localization performed with the help of CT

and clinical details.

Page 32: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Techniques• Techniques

– Conventional technique– Three-dimensional conformal radiation therapy.– Intensity-modulated radiotherapy.– Image-guided radiotherapy.

• Energy selection:– Co60 : 1.25 MeV– LINAC : 4 – 6 MV– Higher-energies used in certain Western

centers during the boost phase to:• Reduce dose to the mandible,

temporomandibular joints, ears and subcutaneous tissue (lateral edge effect)

– Kutcher and associates however warn that use of these high energy beams may be associated with underdosage near the surface and near the paranasal sinus cavities.

Page 33: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Portal selection

• For Initial Phase:– Two parallel opposing fields– Three field approach

• For the boost phase:– Fletcher’s Technique ( 4 fields – antral

boost)– Anterolateral wedge pair technique– Ho’s technique ( with separate

parapharyngeal boost)

Page 34: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Two field technique

• Clinical field markings:– Superior border:

• 2.5 cm above the zygomatic arch• 5 cm above the zygomatic arch in case of

intracranial extension– Anterior border:

• 2 cm beyond the anterior most extent of the disease (usually placed just along the lateral canthus of the eye)

– Posterior border:• Along the tip of the mastoid or behind the

posterior most extent of cervical lymphadenopathy

– Inferior border:• Along the superior border of the clavicle

Page 35: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Two Field technique• Radiological boundaries:

– Superior border:• Splitting the pituitary fossa and extending

along the superior surface of the sphenoid sinus• In case of IC extension to include at least 1 cm

above the pituitary fossa.– Anterior border:

• At least 2 cm of the nasal cavity and maxillary antrum.

• At least 2 cm margin to the gross tumor extent– Posterior border:

• Kept open if gross cervical LAD• Else match with tips of spinous processes of the

cervical vertebrae.

Page 36: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Technique

Page 37: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Three field technique

• The superior, anterior and posterior boundaries are kept as same.

• Inferior boundary restricted to the level of the thyroid notch unless cervical LAD is present

• In latter case matching done more inferiorly.

• Dose prescription done usually at 3 cm depth.

• Several measures need to be taken to circumvent the problem of field matching

Page 38: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Field Matching• Without asymmetrical jaws:

– Using laryngeal block:• A laryngeal block is placed at the level of the larynx.• The block has a thickness such that it is located 1cm

medial to the lateral border of thyroid cartilage• The block extends from the superior border of the

lower field to 2 cm below the level of the cricoid cartilages.

– Using collimator tilt:• A collimator rotation may be given for the lateral

fields to counteract the divergence of the lower anterior field – 5° for Co 60.

• May increase the dose to the supero-anterior portion of the field where the eyes are located

• With asymmetrical jaws: – Using an isocentric technique with half beam block for 3

fields overdosage at the field junction can be avoided.– Alternative is to use half beam block in the lower

anterior field only and use a small shield of 1 – 2 cm in midline to shield the spinal cord.

Page 39: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Additional modifications

• In both 3 field and 2 field techniques a higher dose can be given to the eye due to the beam divergence.

• Lateral fields need to angled – a “posterior” tilt needs to be given

• Magnitude by which the field edge shifts at the midline ( for Co60)– 5° – 0.5 cm– 10° – 1.2 cm

5° 10°

1.20.5

1.1

2.5

Page 40: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Actual Implementation

270°

275°

Lateral Canthus

Page 41: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Doses Prescribed

• 40 – 44 Gy in 2 Gy per fraction over 20 – 22 fractions ( 4 – 4½ weeks) for the entire field.

• Rest of the dose ( 20 – 26 Gy) to delivered with spine shielding:– Lateral fields:

• Posterior border drawn along the junction of the posterior 1/3rd and the anterior 2/3rd of the vertebral bodies ( Co60).

• In LINACs the posterior edge of the vertebrae may be choosen.

• Clinically marked straight along the lobule of ear.

– Anterior fields:• 2 cm wide midline shield is adequate.

Page 42: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Boosting neck nodes

• Photons only:– Antero-posterior glancing fields ( ± wedges)

– Medial border is 2 cm from midline.– Additional boost radiation may be delivered

by posterior fields to increase the dose to the posterior cervical nodes after the course of RT is completed.

• Electrons:– Direct abutting lateral fields used.– Energy selected 9 MeV– Prescribed at 85% isodose ( Usually 3 cm

depth)– 6 x 6 cm usually adequate– Treated at extended SSD of 110 cm

Page 43: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Nasopharynx Boost• A 4 field approach can be used to boost

the nasopharynx to additional 10 – 15 Gy.• Volume treated is roughly cuboidal and

has the dimensions of 7 cm x 6 cm.• The anterior fields are tilted “medially”

by 20° – 30° in order to – Increase the dose to the Posterior

nasopharynx– Spare the anterior nasal cavity and the

deeper brain-stem

• Opposing lateral fields also used with lower border at the level of angle of mandible.

Page 44: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Field marking

• The boundaries for the anterior facial fields are:– Superiorly – below the eyeball– Medially – 1 cm in either side of midline– Inferiorly – upto the commissure of lips– Laterally – Usually a distance of 6 cm – allow beam

fall-off.

• In order to ensure that the superior border of the anterior field matches the lateral fields the head position is adjusted (hyperextended) based upon the collimator lights.

• Beam weights are adjusted to ensure that the brain doesn't receive excess dose.– Anterior : Lateral = 33% : 66%

Page 45: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

4 field technique

Page 46: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Dose distribution

Page 47: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Nasopharynx Boost

• In case of gross anterior extension:– Three field, lateral wedge pair arrangement is

preferred – Anterior border of the lateral fields are extended

to cover the anterior disease adequately– Alternative technique is to use differential beam

weights– Electrons may be used to supplement the doses to

the anterior diseases with lateral photon fields.

• In lateralized anterior extension:– Anterior field may be “wedged” with thin end

towards side where disease is present.

• In inferior extension:– Boost fields are by necessity parallel opposing.

Page 48: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Ho’s Technique• Proponent: Prof John H C Ho • Developed: late 1960s• Extensive experience : 3 decades• Special features:

– Different CTV specification – Field arrangements and patient position are

different.– Arrangement of different shields specified based

upon bony anatomy – customized shields not necessary.

– Reproducible treatment plan.– Lack of CT planning facilities circumvented.– Ease of use in a busy radiotherapy department Cost

saving additional factor.• Over 10,000 patients have been treated in

Hong Kong – excellent long term results in early disease T1, T2 and T3.

Page 49: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Ho’s technique: Planning

• Patient is immobilized in FLEXED head position in the initial phase.

• Similar to the planning technique for pituitary.

• Allows easier shielding of the brainstem and the oral cavity and reduces the field size requirements.

• Dose: 40 Gy in 20 #

Page 50: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Ho’s technique: Planning

• Three field arrangement:– Opposed lateral fields

irradiate the upper cervical lymphatics ( upto level III) en bloc.

– An anterior field irradiates the lower field.

– Shielding of the lateral fields is done to adjust for the beam overlap with the anterior field.

– In the lower anterior field a midline shield is placed throughout the treatment.

Below vocal cords C6

0.5 cm above the anterior clinoid process

Bisecting the maxillary antrum

Page 51: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Ho’s technique: Planning• Specialized arrangement of

shielding is done for all patients.– Brain Stem: Shielded with 5

HVL block placed in a manner such that it is 0.5 cm behind the upper edge of the clivus and 1 cm below the lower edge.

– Eye: 5 HVL shield placed 1.5 cm behind the lateral canthus.

– Posterior tongue also shielded with standard block.

– Pituitary and temporal lobes: upper half of the pituitary fossa shielded.

Page 52: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Ho’s technique: Planning• In the boost phase a 3 field

arrangement was used.• Patient was replanned in the

EXTENDED head position with oral stent.

• Anterior cervico-facial field was used in all patients

• Lower border of the later fields reduced down to level of angle of mandible.

• Allowed dose reduction to: TM joints, ear, parotids & pinnae.

• Dose prescribed: 22.5 Gy in 9 #

• Total tumor dose was 62.5 Gy in 29#

• Biologically equivalent to 66 Gy in 33#

Page 53: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Ho’s technique: Planning• In patients with

parapharyngeal disease a posterior oblique boost was given after the 2nd phase.

• Dose prescribed was 20 Gy /10#

• This field was usually 5.5 cm x 8 cm in size.

• Ascending ramus of the mandible was shielded in this phase.

Page 54: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Ho’s vs 3D CRT and IMRT

T1 NO MO

T4 N2 MO

Kam et al: IJROBP 2003

Page 55: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Results by Ho’s Technique

Page 56: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Conventional Radiation

Page 57: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Conventional Radiation

Page 58: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Altered fractionation

• Concomitant boost technique has been evaluated in a large series by Teo et al (IJROBP 2000).

• Study prematurely terminated as:– 40% incidence of temporal lobe neuropathy– 17% incidence of cranial nerve palsies– 50% patients had one or other form of

neurological complication– 2.6% treatment related mortality– Neural complications were more severe

and occurred earlier than conventional techniques.

– No difference in outcome

Page 59: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Conformal Radiation• Includes 3 D CRT , IMRT and IGRT• Potential:

– Dose escalation – Conformal avoidance

• Results are immature for IMRT• Largest series of IMRT by Kam et al:

– 63 patients – Median F/U 30 months– Only 4 had local failure ( None marginal miss)– OS was 90%– Distant metastasis primary cause of failure– Grade III mucositis: 41% patients– Late toxicity till 2 yrs : Xerostomia (21%)

Page 60: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Brachytherapy

• The following requirements should be fulfilled prior to taking up a patient for brachytherapy:– Tumor thickness less than 10 mm.– Absence of intracranial, paranasal sinus and

oropharyngeal involvement.– Absence of involvement of underlying bone or

infratemporal fossa.– Absence of metastatic disease.– Expertise in nasopharyngeal intracavitary

brachytherapy.

“In effect, nasopharyngeal brachytherapy is ineffective in tumors extending beyond the

nasopharynx” -Xiao-Kang Zheng

Page 61: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Techniques• Techniques:

– Temporary intracavitary application– Temporary interstitial implantation– Permanent interstitial implantation

• Dose-rates used:– Low dose rate (LDR).– High dose rate (HDR).

• Situations used:– Routine use as a boost after XRT ( Hong Kong,

China and Netherlands)– Use with documented residual disease ( USA)– Recurrence ( Hong Kong, USA - Syed and Chinese

Series)

Page 62: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

History of brachytherapy• In 1920s, Pierquin and Richard

were the first persons is to employ brachytherapy in the treatment of nasopharyngeal carcinomas.

• In the Christie hospital at Manchester, Peterson used a 15 mg radium tube inserted in a cork with a diameter of 15 to 20 mm.

• The dose prescribed was 80 rads in seven days to a depth of 0.5 cm.

Peterson described this technique as a useful alternative to small

field X-ray technique but not superior to the use of X-rays

Cork Ra226 tube

String at either end of the cork

Page 63: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Applicator Design• Several applicator

designs available:– Mould technique– Levendag’s– Forzhou (Chinese

district)– Simple catheter based

Page 64: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Mould Technique

• Customized mould prepared for each patient

• Uses a special quick setting silicone jel to take the nasopharyngeal impression.

• The source placement for an average nasopharynx are:– 2 sources for 1 wall– 3 sources for two adjoining

wall– 4 sources for 3 walls

• Intersource separation kept at 1 – 1.5 cm.

Page 65: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Technique of Insertion

Page 66: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Rotterdam Applicator• Designed by Levendag.• Designed so that the applicator could be worn

by the patient comfortably continuously throughout the fractionated course of treatment given.

• Made up of silicone which is flexible and closely conforms to the curvature of the nasopharynx.

• Applicator design based upon a 3 D model of the nasopharynx ( based on CT of two patients)

• Allows closer fit to the base of the skull and situated at a fixed distance from the soft palate.

• A silicone bridge and flange used to fix the applicator against the posterior nasal septum and the anterior one respectively.

Page 67: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Rotterdam Applicator• Tube diameter

– Outer diameter 15 F (5.5 mm)– Inner diameter 9 F ( 3.5 mm)

• Can accommodate the 6 F HDR source easily.

• Two tubes ensure catheter stability.

• The tubes are diverging at the base

Page 68: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Prescription and points• Several anatomical points defined by

Levendag to calculated dose to the tumor as well as critical normal tissues.

• Tumor points:– Na (Nasopharynx) – 2 – BOS (Base of Skull) - 2– R (Node of Rouviere) - 1

• Normal Tissue points:– OC ( Optic Chiasm) - 1– P (Pituitary gland) - 1 – C (Cord) – 1– Pa (Soft Palate) – 2– Re (Retina) - 2– No ( Nose) - 2

Page 69: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Prescription points

BOS

PaR

NaRe

POC

C

Pa Pa

CR

OC

Re Re

BOS BOS

Na Na

P

NoNo

No

Line 1

Line 2

Page 70: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Dose prescribed

• In case EBRT given in dose of 60 Gy:– 3 Gy x 2 fractions per day for 6 fractions

by HDR– Total dose ~ 78 Gy– Minimum interfraction gap of 6 hrs.

• In case of EBRT given in dose of 70 Gy:– 3 Gy x 2 fractions for 4 fractions by

HDR– Total dose ~ 82 Gy– Minimum interfraction gap of 6 hrs.

Page 71: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Advantages• Comfortable applicator – can be kept between

fractions• Optimization possible – Na, BOS and the R

points.• Can be reused after steam sterilization.• Reduced normal tissue dose – to the retina,

palate and the nasal cavity• In earlier work Levendag used to use two other

points:– FL point:

• corresponding to the BOS point• Approximates the position of the foramen lacerum

– FO point:• Situated at the foramen ovale• Taken 2 cm lateral to the midline in then same

plane as the BOS point.

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Department of Radiotherapy, PGIMER, Chandigarh

Disadvantages

• Nasal synechia have been observed in few patients.– Corresponds to the hyperdose sleeve of

200% isodose around the applicator.– Approximately occurs in a radius of 6 mm

around the source axis after standard prescription

– Reduced by use of nasal pack for 7 days after ICBT

• Optimization can result in increased dose to some points (especially the spinal point).

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Department of Radiotherapy, PGIMER, Chandigarh

Chemoradiation

• Sequence:– Induction– Concurrent– Adjuvant

• Concurrent regimen is best.• Principle:

– Local cooperation– Spatial cooperation

• We use Concurrent Cisplatin in doses of 50 mg/m2 D1 and D22.

Page 74: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Results: NACT

Page 75: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Results: Adjuvant CT

• Adjuvant Chemotherapy:– Of no benefit even if CDDP based.– Chi et al reported results of a phase III

randomized trial (2002) N = 157– Adjuvant chemotherapy with 24 hr

infusional Cisplatin 20 mg/m2, 5-fluorouracil 2,200 mg/m2, and leucovorin 120 mg/m2 x 9 cycles after 70 Gy XRT• 5-year overall survival 60.5% vs. 54.5%

(p = 0.5) • 5 yr relapse-free survival rates 49.5% vs.

54.4% (p = 0.38)

Page 76: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Results: Concurrent CT• Huncharek et al performed a meta-analysis in 2002.• 6 RCTs included• Statistically significant increase in the disease free

survival by approximately 20% to 40% • OS improved by ~ 20% (Statistically NS)• Better results with Cisplatin + 5 FU based regimen

( Al Sarraf)

Page 77: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Results : Metastatic disease

Page 78: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

NPC in Children• Problem of long term toxicity:

– Skull deformities– Neurological deficits– Pituitary dysfunction– Hearing impairment– TM joint ankylosis– Visual defects

• RT is the treatment modality of choice:– Dose 50 -60 Gy– Boost only after skull growth is complete (15yrs)– Lower neck usually not treated if clinically –ve.

• Outcome: – DFS is 70 – 80% in T1 and T2 tumors– DFS is 40 – 50% in T3 – T 4 tumors

Page 79: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Recurrence

• 2 types described (Wang et al)– Persistent disease– Relapse: Appearing 1 yr after treatment.

• Detecting recurrence:– Tc99m SPECT– MRI – High signal intensity on T1

weighted spin echo images

• Options:– Palliative treatment– Radiation therapy– Surgery

Page 80: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Surgery

• Usually indicated in situations like isolated nodal recurrence

• Local recurrences have been salvaged by extensive craniofacial surgery

Page 81: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Radiotherapy• EBRT• Brachytherapy

– Both temporary and permanent implants used.– Best results from Gold grain implantation.

• IMRT and 3 DCRT– Investigational

• Sterotactic Radiosurgery• Chemotherapy

– Cisplatin or taxane based– Mainstay in:

• Distant spread• Early recurrence• Extensive disease

Page 82: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Radiotherapy

• External radiotherapy:– High energy beams are better choosen– Small 6 x 6 field used to treat site of local

recurrence– Doses in range of 20 – 30 Gy.– Indications:

• Limited tumour size, • a relatively long period since previous

irradiation (minimal time period ~ 1 year)• Good performance status and • Lack of evidence of skin or soft tissue

damage (skin fibrosis, atrophy or telangiectasis) from the previous irradiation course

Page 83: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Results of RT

Page 84: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Results

Page 85: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Neurological Sequelae• Hypothalamo-Pituitary dysfunction

– Median incidence of clinical dysfunction is 3%. – Cumulative incidence of endocrine dysfunction

higher at 67% at 2 yrs. – Most common disturbance seen in GH secretion. – Thyroid hormone production affected the least.

• Hearing defects:– Almost 7% patients become deaf with standard

therapy.– Otitis media seen in 14% patients– Prolonged tinnitus may be seen in 30% patients

• Temporal lobe injury:– Incidence as high as 3% after 2 yrs.– Toxicity more in altered fractionation regimens

• Cranial nerve injury:– The incidence is as high as 6%.

Page 86: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Other Sequelae

• Significant xerostomia can be seen in as high as 80 %

• Some degree of xerostomia is seen all patients.

• Fibrosis of the subcutaneous tissue is seen when doses exceeding 50 Gy are used in almost 16% patients.

• Significant trismus, can occur in 5 to 10% patients.

• This particular complication can be reduced by using a three-field approach for boosting the nasopharynx.

Page 87: Carcinoma Nasopharynx

Department of Radiotherapy, PGIMER, Chandigarh

Conclusions

• Nasopharyngeal malignancies make up a different population of head and neck malignancies.

• These are eminently radio sensitive and curable.

• Treatment planning is by necessity complicated and time consuming.

• Brachytherapy can be used for boosting the local activities.

• Chemoradiation is standard treatment in locally advanced tumors

Page 88: Carcinoma Nasopharynx

Thank You