Carcinoma Nasopharynx

Moderator: Dr Sushmita Ghoshal

Anatomy

Department of Radiotherapy, PGIMER, Chandigarh

Anatomy

Foramen rotundum Foramen ovale Foramen spinosum Foramen lacerum

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 Space

Retrostyloid Space

– Prestyloid Department – Retrostyloid 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 atof Radiotherapy, PGIMER, Chandigarh Department the tip of the

Anatomy: RPLN
• The retropharyngeal nodes are present in two groups. • The median group consists of 1 - 2 nodes interconnected in the midline. • The lateral group consists of 13 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 separatedDepartment of Radiotherapy, PGIMER, Chandigarh from it by the longus
– Median group. – Lateral group.

CT anatomy

Department of Radiotherapy, PGIMER, Chandigarh

Incidence

Department of Radiotherapy, PGIMER, Chandigarh

Incidence: Sex

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 Department of Radiotherapy, PGIMER, Chandigarh muscle invasion.

Cranial Nerve involvement
50 45 40 35 30 25 20 15 10 5 0 I II III IV V VI VII VIII IX Leung et al X XI XII Lederman et al

Department of Radiotherapy, PGIMER, Chandigarh

Local Spread
Sphenoid sinus Cavernous Sinus

Base of Skull, Clivus

Nasal cavity & PNS Orbital invasion

Lateral Parapharyngeal space Middle ear cavity Oropharynx (tonsillar pillars) C1 vertebrae
Department of Radiotherapy, PGIMER, Chandigarh

Nodal Spread

Department of Radiotherapy, PGIMER, Chandigarh

Etiology
Normal Epithelium
Deletion of Chromosomes 3p and 9p

Low Grade Dysplasia
Inactivation of Chromosome p14, 15 and 16

High Grade Dysplasia
EBV infection

Gain Chromosome 12 Deletion 11 and 13

Invasive Carcinoma
P53 Mutation

Metastatic Carcinoma

Department of Radiotherapy, PGIMER, Chandigarh

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

• Other Investigations
– EBV Serology
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)
Department of Radiotherapy, PGIMER, Chandigarh

Comparison
Syste m Fletch er (1967) Ho (1978) Staging T1
< 1 cm diameter Confined to nasophary nx Limited to one site in nasophary nx Limited to

T2
> 1 cm but confined to nasopharynx Extending to nasal fossa or oropharynx

T3
Beyond nasopharynx Bone/ Cranial nerve/ orbital / hypopharyngea l/ infratemporal fossa No bony involvement destruction

T4
Involving skull base or cranial nerves NA

IUAC (1988) Huaqin g (1994)

Extending to two sites in nasopharynx Involving the nasal cavity, oropharynx, anterior cervical vertebrae, PPS before SO line

Pterygoid nasophary process / nx posterior cranial nerve / posterior cervical vertebrae / BOS / PPS Department of Radiotherapy, PGIMER, Chandigarh beyond SO

Bony destruction including eustachian Infratemporal tube fossa / cavernous sinus / PNS / direct invasion of C2 or C1 / anterior cranial nerves

Ho’s vs AJCC

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 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
Ho’s Triangle

• N3:
– N3a: Metastasis in a lymph node(s) >6 cm Department of – N3b: Extension toRadiotherapy, PGIMER, Chandigarh the

Staging: AJCC 2002

Stage I

Stage IIA

Stage IIB

Stage III

Stage IVA
Department of Radiotherapy, PGIMER, Chandigarh

Stage IVB

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 Department of Radiotherapy, PGIMER, Chandigarh – Type III : Undifferentiated carcinoma

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.
Department of Radiotherapy, PGIMER, Chandigarh

• Better loco regional control and survival than

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
Department of Radiotherapy, PGIMER, Chandigarh

Treatment strategy
Stage Early stage External Radiation Late stage

EBRT + ICBT

KPS > 70

KPS < 70

Concurrent Chemoradiation

Palliative Radiotherapy

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 useDepartment of Radiotherapy, PGIMER, Chandigarh size of larger fields (Field
2

Dose-response
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 50 - 60 Gy 60 - 67.5 Gy > 67.5 Gy T1 T2 T3 T4

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 – 30 Gy / 10# – 20 Gy / 5# – 800 -1000 cGy single fraction Department of Radiotherapy, PGIMER, Chandigarh

• Palliative radiotherapy:

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 )
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
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 Department of Radiotherapy, PGIMER, Chandigarh and clinical details.

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.
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)
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: Department of Radiotherapy, PGIMER, Chandigarh • Along the superior border of the clavicle

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 Department of Radiotherapy, PGIMER, Chandigarh •

Technique

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 circumventRadiotherapy, PGIMER, Chandigarh field the problem of Department of

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 – Using an isocentric technique with half beam block for 3 fields overdosage at the field junction can be avoided. Department – Alternative is to of Radiotherapy, PGIMER, Chandigarh lower use half beam block in the

• With asymmetrical jaws:

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° 0. 1.2 5

1. 1

2. 5

Department of Radiotherapy, PGIMER, Chandigarh

Actual Implementation
Lateral Canthus

Department of Radiotherapy, PGIMER, Chandigarh

2 75° 5° 2 70°

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: 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) Department of Radiotherapy, PGIMER, Chandigarh – 6 x 6 cm usually adequate

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
Department of Radiotherapy, PGIMER, Chandigarh • Opposing lateral fields also used with

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 Department of Radiotherapy, PGIMER, Chandigarh the brain doesn't receive excess dose.

4 field technique

Department of Radiotherapy, PGIMER, Chandigarh

Dose distribution

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.
Department of Radiotherapy, PGIMER, Chandigarh

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

• Over 10,000 patients have been treated in Hong Kong – excellent long term results in Department of Radiotherapy, PGIMER, Chandigarh early disease T1, T2 and T3.

– 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.

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 #

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.
0.5 cm above the anterior clinoid process

Bisecting the maxillary antrum Below vocal cords C6

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. Department of Radiotherapy, PGIMER, Chandigarh – Pituitary and temporal

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#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

Department of Radiotherapy, PGIMER, Chandigarh

Ho’s vs 3D CRT and IMRT

T1 NO MO

T4 N2 MO

Kam et al: IJROBP 2003

Department of Radiotherapy, PGIMER, Chandigarh

Results by Ho’s Technique

Department of Radiotherapy, PGIMER, Chandigarh

Conventional Radiation

Department of Radiotherapy, PGIMER, Chandigarh

Conventional Radiation

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.
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%)
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 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) Radiotherapy, PGIMER, Chandigarh Department of

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.
Ra226 tube Cork

String at either end of the cork

Peterson described this technique as a useful alternative to small field XDepartment not superior ray technique butof Radiotherapy, PGIMER, Chandigarh

Applicator Design
• Several applicator designs available:
– Mould technique – Levendag’s – Forzhou (Chinese district) – Simple catheter based

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
Department of Radiotherapy, • Intersource separation PGIMER, Chandigarh kept

Technique of Insertion

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. Department of Radiotherapy, PGIMER, • A silicone bridge and flangeChandigarh to fix the used

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

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 – – – – – – OC ( Optic Chiasm) - 1 P (Pituitary gland) - 1 C (Cord) – 1 Pa (Soft Palate) – 2 Re (Retina) - 2 No ( Nose) - 2
Department of Radiotherapy, PGIMER, Chandigarh

• Normal Tissue points:

Prescription points
OC P BOS Na BOS Re Na No R Pa C Pa OC P BOS Na Re

Line 1
Re

2 ne Li

No Pa R C

No

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.
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: Department • Situated at of Radiotherapy, PGIMER, Chandigarh the foramen ovale

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). Radiotherapy, PGIMER, Chandigarh Department of

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.
Department of Radiotherapy, PGIMER, Chandigarh

Results: NACT

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, 5fluorouracil 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)
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)

Department of Radiotherapy, PGIMER, Chandigarh

Results : Metastatic disease

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:

• Outcome:

– Dose 50 -60 Gy – Boost only after skull growth is complete (15yrs) – Lower neck usually not treated if clinically –ve. – DFS is 70 – 80% in T1 and T2 tumors – DFS is 40 – 50% in T3 – T 4 tumors
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
Department of Radiotherapy, PGIMER, Chandigarh

Surgery
• Usually indicated in situations like isolated nodal recurrence • Local recurrences have been salvaged by extensive craniofacial surgery

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
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 of Radiotherapy, PGIMER, Chandigarh course Department

Results of RT

Department of Radiotherapy, PGIMER, Chandigarh

Results

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:

• Temporal lobe injury: • Cranial nerve injury:

– Almost 7% patients become deaf with standard therapy. – Otitis media seen in 14% patients – Prolonged tinnitus may be seen in 30% patients – Incidence as high as 3% after 2 yrs. – Toxicity more in altered fractionation regimens – The incidence is as high as 6%.
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 Department of Radiotherapy, PGIMER, Chandigarh nasopharynx.

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 oflocally PGIMER, Chandigarh tumors advanced Department Radiotherapy,

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