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Anatomy
Anatomy
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 its tip at the greater cornu of the hyoid bone Two compartments :
Prestyloid Space
Retrostyloid Space
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
Incidence
Incidence: Sex
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.
Local Spread
Sphenoid sinus Cavernous Sinus
Lateral Parapharyngeal space Middle ear cavity Oropharynx (tonsillar pillars) C1 vertebrae
Department of Radiotherapy, PGIMER, Chandigarh
Nodal Spread
Etiology
Normal Epithelium
Deletion of Chromosomes 3p and 9p
Invasive Carcinoma
P53 Mutation
Metastatic Carcinoma
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) Hos 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
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
Hos vs AJCC
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
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
Hos Triangle
N3:
N3a: Metastasis in a lymph node(s) >6 cm Department of N3b: Extension toRadiotherapy, PGIMER, Chandigarh the
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
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
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
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
Doses used
Radical radiotherapy:
60 66 Gy in 2 Gy per fraction over 6 6 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
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
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
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
Actual Implementation
Lateral Canthus
2 75 5 2 70
Doses Prescribed
40 44 Gy in 2 Gy per fraction over 20 22 fractions ( 4 4 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
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
Dose distribution
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 inferior extension:
Boost fields are by necessity parallel opposing.
Department of Radiotherapy, PGIMER, Chandigarh
Hos 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.
T1 NO MO
T4 N2 MO
Conventional Radiation
Conventional Radiation
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
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 Levendags Forzhou (Chinese district) Simple catheter based
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
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
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
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.
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
Results: NACT
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)
NPC in Children
Problem of long term toxicity:
Skull deformities Neurological deficits Pituitary dysfunction Hearing impairment TM joint ankylosis Visual defects
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
Radiotherapy
EBRT Brachytherapy
Both temporary and permanent implants used. Best results from Gold grain implantation.
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
Results
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 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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