This document discusses carcinoma of the nasopharynx, including its detection in early stages using MRI imaging, patterns of local and lymphatic spread, association with EBV, clinical features, staging according to AJCC guidelines, pathological classification, and treatment using radiotherapy techniques like three-dimensional conformal radiation therapy and intensity-modulated radiotherapy. Key points covered are detection of early lesions via MRI, common sites of local extension like the parapharyngeal space and skull base, routes of lymphatic spread to cervical lymph nodes, and role of plasma EBV DNA levels in diagnosis and prognosis.

1. Carcinoma
Nasopharynx
Moderator- Dr. Piyush Kumar
Presenter- Dr. Rashmi

2. Detection In Early Stage
 Appropriate examination, imaging and biopsy of nasopharyngeal mucosa are recommended
even if mucosal surface appears normal.
 Around 70% present with neck mass
 MRI imaging is superior to PET-CT for loco-regional invasion and RPLN metastasis. It is better for
detection of early lesions.
 EBV related serological testing for screening.

3. Loco-Regional Extensions

4. Loco-Regional Extensions

5. Anterior
 Nasal fossa
 Pterygoid plates
 Post ethmoid and
maxillary sinus
 If advance- orbital apex

6. Superior and Posterior
Superiorly
 Base of skull
 Sphenoid sinus
 Clivus
 F.Lacerum
Posterior
 Prevertebral muscle

7. Inferior
• Oropharynx
• Tonsillar pillars
• Tonsillar fossa
If Advance-
• C1 vertebra

8. Lateral
• Parapharyngeal space with
invasion of levator and tensor
veil palitini
If Advance
• Pterygoid muscle
• RPLN
• Cranial nerve compression
• Carotid artery

9. Lymphatic Spread

10.  Upper jugular-94%
 Middle juular-85%
 Retropharyngeal node- 80%
 Posterior cervical -46%
 Lower jugular-19%
 Supraclavicular -17%
 Submental-17%

11. Role of EBV
EBV is the first oncogenic virus identified in human cancer

14. EBV specific Serological tests:
• Association of EBV with NPC (non keratinizing type) provides basis for
serological test
• May enhance early detection of the primary disease/ relapses, supplement TNM
staging & improve prognostication
• For diagnosis: anti -VCA & anti EA Ab are both sensitive however IgA anti- VCA has
better specificity & may serve as screening test in high-riskpatients.
• For prognosis: prognostic effects of pre & post treatment Ab titre have been
controversial due to inconsistent results in variousstudies
• Titers remained persistently high even in patients who achieved remission.
• There was no reliable cut-off value for differentiating between recurrence and
remission.

15. 04/05/2018
EBV- <1000
29/08/2018
EBV not detected
20/02/2019
EBV not detected

16. • PCR based technique makes it possible to detect EBV DNAlevels
• Plasma EBV DNA is superior to serum anti-EBV Ab in prognostication
• Diagnosis: has high sensitivity (96%) & specificity (93%) for detecting NPC
• Levels correlated significantly with tumor load, TNM staging, recurrence rate,
and survival.
• Prognosis: study by Leung et al on 376 NPC pts. showed pretherapy DNA load was
an independent prognostic factor for OS
• Risk grouping: identify poor-risk among early-stage pts. & can complement TNM
staging and guide treatment decision.
Plasma Epstein Virus DNA Levels

17. CLINICAL FEATURES

18. Symptoms

19. Syndromes

20. Horner syndrome
Ptosis
Anhidrosis
Miosis

21. TROTTER’S TRIAD
Hearing
loss
Palatal
palsy
Facial
pain

22. Cranial Nerve Involvement
•Petro-sphenoidal syndrome (CN III-IV, VI):Oculomotor
signs/symptoms
•Villaret/ Retro-parotidian syndrome (CN IV-XII):
Enophthalmos, ptosis, miosis

23. Diagnostic Work-Up

24. STAGING

25. AJCC
TheAJCC 7th system
(T0)
• No evidence of primary
tumor
(T1)
• Tumor confined to the
nasopharynx, or tumor
extends to oropharynx
and/or nasal cavity
without parapharyngeal
extension.
TheAJCC 8th system
(T0)
• No tumor identified,
but EBV-positive
cervical node(s)
involvement
(T1)
• Tumor confined to
nasopharynx, or
extension to
oropharynx and/or
nasal cavity without
parapharyngeal
involvement

26. The AJCC 7th system
T2
• Tumor with
parapharyngeal
extension*
T3
• Tumor involves bony
structures of skull base
and/or paranasal
sinuses
The AJCC 8th system
T2
• Tumor with extension to
parapharyngeal space,
and/or adjacent soft
tissue involvement
(medial pterygoid,
lateral pterygoid,
prevertebral muscles)
T3
• Tumor with infiltration of
bony structures at skull
base, cervical vertebra,
pterygoid structures,
and/or paranasal
sinuses

27. The AJCC 7th system
T4
The AJCC 8th system
T4
• Tumor with
intracranial
extension and/or
involvement of
cranial nerves,
hypopharynx, orbit,
or with extension to
the infratemporal
fossa/masticator
space
• Tumor with intracranial
extension,
involvement of cranial
nerves, hypopharynx,
orbit, parotid gland,
and/or extensive soft
tissue infiltration
beyond the lateral
surface of the lateral
pterygoid muscle

28. The AJCC 8th system
N1
• Unilateral metastasis in cervical
lymph node(s) and/or unilateral
or bilateral metastasis in
retropharyngeal lymph node(s),
6 cm or smaller in greatest
dimension, above the caudal
border of cricoid cartilage
N2
• Bilateral metastasis in cervical
lymph node(s), 6 cm or smaller
in greatest dimension, above
the caudal border of cricoid
cartilage
• The AJCC 7th system
• N1
• Unilateral metastasis in cervical
lymph node(s), 6 cm or less in
greatest dimension, above the
supraclavicular fossa, and/or
unilateral or bilateral,
retropharyngeal lymph nodes, 6
cm or less, in greatest dimension*
• N2
• Bilateral metastasis in cervical
lymph node(s), 6 cm or less in
greatest dimension, above
the supraclavicular fossa*

29. The AJCC 8th system
N3
• Unilateral or bilateral metastasis in
cervical lymph node(s), larger than 6
cm in greatest dimension, and/or
extension below the caudal border
of cricoid cartilage
The AJCC 7th system
N3a
• Greater than 6 cm in dimension
N3b
• Extension to the supraclavicular
fossa

30. Stage grouping
Stage 0 Tis N0 M0
Stage I T1 N0
M0
Stage II T2 T1,T2 N0
N1
Stage III T3 T1,T2 N0-N2 N2
Stage IV A
T4 N0,N1,N2
Any T N3
Stage IV B Any T Any N M1
Changes from 7th edition: TNM stage
change
The previous Sub-Stages IV-A(T4N0- 2M0)
and IV-B (any T N3 M0) are now merged to
form IV-A.
The previous IV-C (any T any N M1) is
now upstaged to IVB.

32. Pathological classification
• Carcinoma 80-90%
• Lymphomas 5%
Who classification
1. Keratinising SCC
2. Non keratinising SCC
3. Basaloid SCC
• 5 year survival is ~ 65% for nonkeratinizing
differentiated and undifferentiated subtypes
• Keratinizing type has a poorer outcome, with frequent
nodal metastasis and high mortality

33. Treatment

34. RADIOTHERAPY TECHNIQUES
 Conventional technique.
 Three-dimensional conformal radiation therapy.
 Intensity-modulated radiotherapy.
 Image-guided radiotherapy.

35. 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

36. 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 Lymphadenopathy
• Else match with tips of spinous processes of the cervical vertebrae.

38. Treatment volume
1. The Nasopharynx.
2. Posterior 2 cm of nasal cavity.
3. Posterior ethmoid sinuses.
4. Entire sphenoid sinus and the basiocciput
5. Cavernous sinus.
6. Base of skull, including the foramen ovale, carotid canal and foramen spinosum.
7. Pterygoid fossae
8. Posterior 1/3rd of maxillary sinus.
9. Lateral and posterior oropharyngeal wall to the level of mid-tonsillar fossa.
10.? Posterior 1/4th of orbit ( Fletcher – YES, Perez - NO )

39. 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

40. 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.

41. 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)

42. Techniques
• 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.

43. 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 Lymphadenopathy 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

44. Field Matching
• Without asymmetrical jaws:
• Using laryngeal block:
• A laryngeal block is placed at the level of thelarynx.
• 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 fieldonly and use a small shield of 1 – 2
cm in midline to shield the spinal cord.

45. 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.

46. 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

47. 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.

48. 4 Field Technique

49. 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 #

50. 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

51. 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.

52. 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#

53. 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.

54. Target Volumes
• ■ GTV/PTV: as per general principles. MRI fusion can delineate intracranial OARs, locate tumor infiltration, and
visualize nerves that need to be included.
• ■ CTV1 = GTV + 5 mm
• ■ CTV2 (per RTOG 0615) =
1) The entire nasopharynx,
2) Anterior one-half to two-thirds of the clivus (entire clivus, if involved),
3) Skull base (foramen ovale and rotundum bilaterally must be included for all cases),
4) Pterygoid fossae,
5) Parapharyngeal space,
6) Inferior sphenoid sinus (in T3–T4 disease, the entire sphenoid sinus), and
7) Posterior third to half of the nasal cavity and maxillary sinuses (to ensure pterygopalatine fossae
coverage).
8) The cavernous sinus should be included in high-risk patients (t3, t4, bulky
disease involving the roof of the nasopharynx).
9) Posterior ethmoid sinuses
10)Include bilateral levels Ib to V and retropharyngeal/parapharyngeal nodes for all cases.

55. Benefit of IMRT for NPC
• Improve the local control especially for concave shape tumors
• Reduce the post-irradiation complications
• Reduce the rate of distant metastasis by improving the local control
• The intensity of the radiation beams can be modulated to deliver a high
dose to the tumor with a superior target volume coverage while
significantly limiting the dose to surrounding normal structures.

56. IMRT Planning Flowchart

57. Immobilization
Imaging acquisition and
contouring

58. CT MRI FUSION

60. Brachytherapy
• Intracavitary/ interstitial implants have been used inNPC
• Indications:
As a boost treatment following EBRT
 In the treatment of recurrent disease.

61. 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

62. 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)

63. 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.

64. • 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
Rotterdam Applicator

65. 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.

66. 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.

67. 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).

68. 275 patients with loco regionally advanced NPC disease (TNM stages III or M0
stage IV)
treated by induction chemotherapy followed by concurrent chemoradiotherapy to
70 Gy conventional planning
NACT :cisplatin: 100 mg/m2 and doxorubicin 50 mg/m2 or Epirubicin 75 mg/m2 3
weeks for 2 cycles followed by EBRT 70 Gy to primary & positive nodes & 46 Gy to
negative neck and concurrent weekly cisplatin 30 mg/m2 /week for 7 weeks
boost of 11-Gy LDR or three fractions of
3-Gy HDR.
then randomized into 2 arms
Arm A:standard arm
ArmB:brachytherapy boost arm:

69. • In T1–3 disease as a boost treatment following external beam
irradiation, and improves local control
• Boost dose of 10–12 Gy in 2 fractions separated by a week.

71. Role Of Surgery
• Due to deep location of nasopharynx, and anatomic proximity to critical
structures, radical surgery is typically not used
• Limited to
Biopsy for histological confirmation
Neck dissections for persistently enlarged lymph nodes
Nasopharyngectomy in persistent or recurrent disease

72. CHEMOTHERAPY
 Concurrent Chemo radiotherapy
 Neoadjuvant/induction Chemotherapy
 Adjuvant Chemotherapy

73. Chemotherapy
 Chemotherapy is believed to act as radiosensitizer.
 It helps to reduce the chance of distant metastasis.
 For locally advanced disease (stage III-IV ) chemotherapy
in addition to radiotherapy appears to improve overall results.
 Combination chemotherapy produces better responses
 combination cisplatin/5-flurouracil is the most widely used
 Indicates that concurrent chemoradiotherapy has a major role in
advanced stage NPC

75. Follow up
• Complete H&N physical exam
• Mirror/fiberoptic exam
• Q1-3 months for year 1
• Q2-6 months for year 2
• Q4-8 months for years 3 – 5
• Yearly for years > 5
• Imaging for signs/symptoms
• TSH yearly (if neck irradiated)
• Speech/swallowing/dental/hearing evaluations
• Consider EBV-DNA monitoring

76. Thank You