concise presentation on nasopharyngeal cancer management external beam radiotherapy and boost brachytherapy

1. Nasopharyngeal Cancer
Dr.Ali Azher MD Radiation Oncology
The Gujarat Cancer & Research Institute,
BJ Medical College, Ahmadabad

2. Introduction
• Cuboidal chamber – below skull base
• 4-5.5cm transverse, 2.5 to 3.5 AP diameter, 4cm
height
• Anteriorly nasal cavity via posterior choana
• Inferiorly oropharynx
• Roof sphenoid & occipital bones
• Floor soft palate
• Lateral walls Eustachian Tube
• Lateral walls & fossa of rosenmuller common
sites for malignancies

3. • Foramen lacerum – spread to middle
cranial fossa
• Close to cavernous sinus, CNs 2,3,4

4. Anatomy
Lateral
Eustachian tube,
torus tubarius,
fossa of Rosenmuller,
Superior pharyngeal
Constrictors
medial pterygoid
plate
Anterior Posterior nasal
septum/choanae
Posterior Clivus and C1–2
Superior Sphenoid bone/
sinus
Inferior Roof of soft
palate

5. Foramen rotundum - Maxillary division of trigeminal (V2)
nerve
Foramen ovale - Mandibular division of trigeminal (V3)
Nerve, Accessory meningeal artery, Lesser superficial
petrosal nerve
Foramen lacerum - Internal carotid, sympathetic carotid
plexus; vidian nerve,
meningeal branch of ascending pharyngeal artery,
emissary vein
Foramen spinosum - Recurrent branch of V3 nerve
Middle meningeal artery and vein

6. Lymphatic Drainage
• Rich lymphatic plexus – roof, posterior,
lateral walls
• Three lymph node collecting stations
1. RP node of Rouviere
2. Jugular chain – upper lateral JD nodes
3. Upper deep cervical node at the confluence
of Spinal accessory
• Lymphatic capillary plexus – lymphiod
aggregates in the pharyngeal tonsil &
tubal tonsil

7. • RP nodes – lateral parapharyngeal space
• RP nodes – proximity to 9,10,11,12
• Classic NP node – 3-4 high lateral jugular
nodes that lie deep into SCM and lateral to
IJV

8. • Lymph collectors
• Lateral side of the pharyngeal wall
• The lateral lymph collector empties into
multiple first-tier nodes (lateral pharyngeal
node, the jugulodigastric/subdigastric
nodes, 3,4,5 RP group
• The posterior lymph collector empties into
the first node (node of Rouviere) of RP

9. CT anatomy

13. Epidemiology
• Highest in china 3/100,000
• Bimodal age distribution 15-25 yrs & 50-59yrs
• Causation is multifactorial involving
environmental, genetic and familial and viral
factors
• Early lymphatic spread and notorious
predilection for distant metastases
• Anatomical proximity to critical structures
makes surgical extirpation difficult without
morbidity.
• RADIOSENSITIVE

14. Etiology
• Genetic
• Environmental
Salted fish in southern china
Dimethyl nitrosamine
Alcohol, cigarette, dust etc
• Viral – EBV
NPC non keratinising type
Tumorigenic potential – LMP 1, 2A, 2B
Nuclear antigens – EBNA1 & 2

15. Natural history
• Local extension
Anterior – nasal fossa → lateral walls of nasal
fossa → destruction of pterygoid plates
• Ethmoid, maxillary sinus less common
• Advanced disease orbital invasion
• Superior & Posterior
Base of skull, sphenoid sinus,clivus
Cavernous sinus,
• Inferiorly – tonsillar pillar, tonsillar
fossa, oropharyngeal wall

16. Border Spread Significance
Lateral Parapharyngeal
Space
Fossa of Rosenmuller is the most common
site for NPC. Retroparotidian syndrome =
involvement of CN IX–XII and cervical
sympathetics
Masticator space Trismus
anterior Pterygopalatie
fossa (PPF) via
sphenopalatine
foramen from nasal
cavity
Tumors can extend proximally along V2 from
PPF to cavernous sinus
Posterior Retropharyngeal
(RP) nodes and
prevertebral space
>75% patients - cN+, 90% - subclinical nodes,
40–50% b/l nodes. Level 2 & lateral RP nodes
are the first echelon
Superior Skull base Foramen ovale (CN V3) and foramen lacerum
commonly involved. True intracranial
extension is uncommon (<10%).
Petrosphenoidal syndrome = extension
through foramen lacerum to cavernous sinus
Inferior Hard palate
(oropharynx)
Infrequent

20. Lymphatic Spread
• Vast avalvular lymph nodes
• Ipsilateral 85-90%
• Bilateral 50%

22. Hematogenous Spread
• DM in 3-6%
• Higher in advanced neck node mets
• Bone > Lung > Liver

23. Signs & Symptoms
• Neck masses – upper neck (upper posterior
neck, palpable beneath SCM)
• Nasopharynx Tumor Mass – epistaxis, nasal
obstruction discharge
• Skull base erosion – palsy of cranial nerves
(headache, diplopia, facial pain, numbness)
• Neck mass> nasal & aural symptoms
• CN – V& VI frequently involved

24. Neurological symptoms
• Advanced disease
• Petrosphenoidal syndrome of Jacob –
unilateral trigeminal neuralgia, unilateral ptosis,
complete ophthalmoplegia, and amaurosis –
CN II-VI by IC extension

25. Villaret Syndrome
• Retroparotidian syndrome
• dysphagia, alterted taste
• problems in salivation
• paralysis of trapezius & SCM
• Weakness of tongue & soft palate
• CN IX-XII involvement by RP node mets

26. Horners Syndrome
• Enophthalmos
• Ptosis
• Miosis

27. Work up & Evaluation
• Complete head & neck physical exam
Node – size, mobility, extent of enlarged node
Vision, hearing
Exclusion of gross signs of DM
• Nasopharyngoscopy + Biopsy of Primary / FNAC
• Labs – CBC, LFT , EBV titers (IgA anti VCA, IgG
anti EA)
• Chest X ray
• CT brain + PNS + Neck
• MRI with contrast include skull base,
nasopharynx, and neck to clavicles

28. • MRI better sensitivity than CT
• Detection rates of MRI and CT Scan compared
• IC Extension 57 % vs. 36 %
• Skull base involvement 60 % vs. 40 %
• Retropharyngeal node 58 % vs. 21 %
• Prevertebral muscle infiltration 51 % vs. 22 %
• MRI detected bone erosion in all cases, as seen on
CT
• Upstage of T stage in 22%, downstage in 4 %

29. • Metastatic work up
PET-CT (especially for non-keratinizing
histology, endemic phenotype, N2 or N3, and
stage III –IV)
CT chest & abdomen
Bone scan

30. Consultations
• Medical Oncology
• Dental Evaluation
• ENT – audiology
• Nutrition – swallowing

31. Differentials
• If small nasopharyngeal mass and confined to
the mucosa:
Prominent, but normal adenoidal tissue
Nasopharyngeal lymphoma
Early primary nasopharyngeal malignancy

32. • If larger nasopharyngeal mass +/-involvement of
the skull base:
 Primary nasopharyngeal malignancy
 Adenoid cystic carcinoma
 Papillary adenocarcinoma
 Melanoma
 Plasmacytoma
 Lymphoma
 Chordoma/Chondrosarcoma
 Meningioma
 Rhabdomyosarcoma/other sarcoma

33. Histopathology
• Poorly differentiated carcinoma
• Pleomorphic epithelioid cells in a background
of lymphocytes
• Presence of keratin – adverse prognostic factor

34. WHO classification
• Keratinizing Squamous cell carcinoma 20%
• Nonkeratinizing carcinoma - Most Common
 Differentiated subtype 30-40%
 Undifferentiated subtype 50-60% - most
favorable prognosis, EBV
• Basaloid Squamous cell carcinoma <0.2% -
agrressive clinical course – poor survival

35. AJCC 8th Edition
T Criteria
Tx Primary Tumor cannot be assessed
T0 Tumor identified, EBV + CERVICAL NODES
T1 Tumor Confined to NP or extension to oropharynx/nasal cavity
WITHOUT PARAPHARYNGEAL INVOLVEMENT
T2 Tumour with extension to PARAPHARYNGEAL SPACE and/or
adjacent soft tissue involvement (medial pterygoid, lateral
pterygoid, prevertebral muscles)
T3 Tumour invades BONY STRUCTURES of skull base cervical
vertebra, pterygoid structures, and/or PARANASAL SINUSES
T4 Tumour 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

36. N Criteria
Nx Regional LN cannot be assessed
N0 No regional LN
N1 UNILATERAL metastasis, in cervical lymph node(s),
and/or unilateral or bilateral metastasis in
RETROPHARYNGEAL LN, 6 cm or less ,above the
caudal border of cricoid cartilage
N2 BILATERAL metastasis in cervical lymph node(s), 6
cm or less ABOVE the caudal border of cricoid
cartilage
N3 Metastasis in cervical lymph node(s) GREATER
THAN 6 CM in dimension and/or extension BELOW
the caudal border of cricoid cartilage

37. Staging
T1 T2 T3 T4
N0 I II III IVA
N1 II II III IVA
N2 III III III IVA
N3 IVA IVA IVA IVA
M1 IVB IVB IVB IVB

38. Prognostic factors
Younger age & female sex – better prognosis
Histology – non keratinizing & undifferentiated –
more radiosensitive – better prognosis
Advanced T stage – worse LC
Advanced N stage – increased risk of DM & worse
survival
EBV DNA load – higher recurrence
EGFR, VEGF over expression – poor

39. Treatment strategy
• Surgery difficult ; only role in:
Biopsy for pathologic diagnosis
Salvage for persistent / recurrent disease
• RT ALONE / IN COMBINATION WITH CT

40. Treatment Algorithm
Stage Treatment options
T1 N0 Definitive RT
T1 N+
T2-4 N0
T2-4 N+
Concurrent CRT
+/– Adj Chemo
Induction Chemo ► Concurrent CRT
M1 Chemotherapy
Concurrent CRT

41. Diagnosis of NPC
Staging of NPC
Stage IVA
T4 or N3 M0
Stage IVB
M1
Stage I
T1N0M0
Stage II/III
T1-3 N0-2, M0
Definitive
IMRT
CRT
IMRT +
Cisplatin
Adj CT
Cis+ 5FU
NACT
Cisplatin
CRT
IMRT +
Cisplatin
Adj CT
Cis+ 5FU
CT
Cisplatin
+/-
Pall RT

42. Chemo radiotherapy
ARM 3Yr SURVIVAL 5Yr SURVIVAL DM RATE
RT 56.38% 41.09% 38.71%
CRT 68.74% 51.91% 26.19%
The result demonstrated that
CRT increased overall survival by 12% at 3 years, and 11% at 5
years.
After CRT, the rate of distant metastasis was reduced by 12%.
Meta-analysis included 18 trials enrolling a total of 1993 patients from China.
Yank AK,Liu TR, Guo x, QI gl, Chen FJ.

43. Dose
Dose T stage Local Tumor Control
Rate(%)
>70Gy T1 T2 100
66-70 Gy T1 T2 80
>70GY T3 T4 <55
60 Gy T1 T2 76
TOTAL DOSE IMPORTANT
DOSE FRACTION NOT
70Gy/35#/7weeks to GTV
50-60 Gy for potential risk sites
FRACTIONAL DOSE OF > 2Gy SHOULD BE AVOIDED

44. Pediatric
• Per COG ARAR 0331 protocol
• Stage I: RT alone (61.2/1.8 Gy for Stage I;
66.6/1.8 Gy for StageII)
• Stage ≥ II: Cisplatin/5-FU × 3c → RT (CR/PR to
chemo 61.2/1.8 Gy, SD to chemo 70.2/1.8 Gy)
and concurrent cisplatin
• 36–46/2–3 Gy to unresectable metastases

45. Radiation Planning
• Conventional
• Conformal

46. Conventional set up
• Direct marking open field
• Simulator
• 3 fields; 2 lateral opposed for primary and
upper neck, matched to 1 anterior field for
lower neck.

47. Portals
B/L parallel opposed portals for primary & upper neck
• Superior : 2 to 2.5 cm above the zygomatic arch and
splits the pituitary fossa. In case of base of skull
involvement or intracranial extension it is taken 4.0
to 5.0 cm above the zygomatic arch or 1 cm above
the pituitary fossa.
• Inferior : at the thyroid notch
• Anterior : encompasses posterior ½ of nasal cavity
or moved forward to cover the extensions if any.
• Posterior : kept open to cover the posterior triangle

48. • Single anterior portal for lower neck
 Superior : matched to the inferior border of the lateral
fields.
 Inferior : extend below to cover the lower edge of
clavicles.
 Lateral : cover medial 2/3rd of the clavicle.

51. Dose prescription
• Phase I : 40 to 44 GY in 20 to 22 fractions @ 2GY/#.
• Phase II : fields are shrinked to avoid the spinal cord.
• Primary tumor is boosted to an additional 20 to 25
GY.
• T1 & T2 tumor : 60 to 65 GY
• T3 & T4 tumor : 70 to 75 GY.
• Dose to neck nodes : 45 to 50 GY to N0 neck.

52. Morbidity from RT
Acute Toxicity
Mucositis
Dermatitis
Pharyngitis
Otitis
Dose-limiting organs
– Brain stem
– Spinal cord
– Pituitary-hypothalamic axis
– Temporal lobes
– Eyes
– Middle/inner ears
– Parotid glands
Chronic Toxicity
Xerostomia
sub cutaneous
fibrosis
radiation myelitis
cranial neuropathy
endocrine
dysfunction
temporal lobe
necrosis
hearing loss
otitis media

53. Limitations of Conventional RT
• rectangular-shaped - suboptimal target
coverage and inclusion of large volumes of
normal tissues
• high rate of xerostomia
• Carotid stenosis
• Cranial nerve palsy
• Dose escalation difficult

54. Conformal
• Immobilisation device orfit making
• Neck extended, shoulder down
• Fiducial markers
• Laser matching
• Topogram
• IV contrast
• Upto the level of carina

55. • IMRT is preferred

56. Rationale for IMRT
• Anatomically complex H&N region
• Treat target volumes adjacent to critical or
sensitive normal tissues
• Lack of organ motion in the H&N region
• Allows for dose escalation , allows for
concomitant boost.

57. Better normal tissue sparing
Better conformality
Dose escalation

58. Inverse Planning
• Desired dosimetric & clinical objectives are
stated mathematically
• Appropriate specifications for normal tissue
dose constraints
• Overstringent dose constraints to normal
tisues – ensure adequate dose cover to target

59. Forward Planning
• From field definition to dose distribution
• T/t parameters
• Dose calculation
• Dose distribution
• Dose delivery with uniform radiation
intensity

60. Inverse Planning
• From dose distribution to field definition
• Dose delivery with nonuniform radiation
Intensity
• leaf sequence generation
• optimization
• Treatment goals ( objective function )

61. Steps of IMRT
 Clinical evaluation & assessment
 Simulation
 Planning CT/MRI/PET-CT scan
 Target volume Delineation: Gross target
volume,Clinical target volume, Planning target
volume.
 Dose prescription : PTV dose and Organ at risk
(OAR) constraint
 IMRT Planning, Dose Volume Histogram
 Quality Assurance
 Execution of IMRT

62. Import of Images
• Monaco system
• OAR contouring
• Dose constraints

63. OAR
• Critical normal structures
• Could suffer significant morbidities
• Might influence treatment planning & dose
prescription
• All non target tissues
• Depend on the location of ctv

64. Rhyme respecting cord & brainstem
• Brainstem – lower part of lateral ventricle
to odontiod apical
• Cord starts from odontoid apical upto 5cm
below PTV
• Check for missing slice – DON’T
INTERPOLATE
• Serial organs – maximum dose minimum
• Brain window
• PRV extra degree of freedom

65. • Optic nerve – delineating orbital part only
NOT IDEAL
• Draw till chiasm through optic canal

66. PTV
• Geometric concept for treatment planning
• Tool to shape absorbed dose distributions
• Ensure the delivery of dose to all parts of
ctv
• Despite organ motion & set up variations

67. Contouring guide lines
• GTV 70 = gross disease
• GTV N = all nodes ≥10mm

68. LN Metastasis
• Ellipsoid
• Size ≥ 10mm (5mm RP)
• Central necrosis
• Extra capsular spread
• Clustered nodes 3 or more

69. CTV70
• GTV 70 + 5 mm
• Around the brainstem and spinal cord, 1-mm margin
• entire nasopharynx, sphenoid sinus, cavernous
sinus, base of skull, posterior ½ of nasal cavity,
posterior 1/3 of maxillary sinuses, post. Ethmoid
sinus, pterygoid fossa, lateral & posterior
pharyngeal wall, retropharyngeal nodes, & b/L
cervical nodes including level V & SCF.

70. SCOPE
• S – Sinus (Sphenoid, Max post 1/3), skull
base, soft palate
• C- Clivus, cavity nasal post 1/3, cavernous
sinus, cave meckels
• O – ovale foramen
• P – Pterygopalatine fossa, pterygoid fossa,
parapharyngeal space, proper nasopharynx,
• E- ethmoid posterior

71. PTV70
• CTV 70 + 3–5 mm
• Around the brainstem
and spinal cord 1-mm

72. PTV2 (59.4 Gy)
High risk subclinical disease:
 Sphenoid sinus
 Cavernous sinus
 Skull base
 Clivus
 Posterior 1/3 of maxillary
sinus
 Posterior 1/3 of nasal cavity
 Pterygopalatine fossae
 Parapharyngeal space
 Retropharyngeal space
 Soft palate

73. High risk nodal levels
• Include all bilaterally
• Upper deep jugular
• Level I submandibular
• Level II JD
• Level III mid jugular
• Level IV Low jugular & supraclavicular
• Level V Posterior cervical
• Retropharyngeal

75. PTV3 (54 Gy)
Elective nodal coverage: Low risk sub
clinical disease
 Retrostyloidspace
 Bilateral IB –V (can omit IB, if N0)

76. Isodose distributions

77. Two different approaches
• Extended whole field EWF
Total target volume in the IMRT plan
• Split field SF
Target volume superior to vocal cord – IMRT
Lower neck – conventional anterior neck field
Dose to vocal cords minimum

78. Dose prescription
• PTV High Risk 70Gy
• PTV Intermediate risk 59.4Gy
• PTV Low risk 54Gy

79. OAR dose constraints
• Critical normal structures (higher priority):
• Brain stem D Max <54
• Optic Nerves <54
• Optic Chiasma <54
• Spinal Cord <45
• Mandible & TMJ < 70
• Temporal Lobes < 60
• Pituitary Dmax < 50Gy

80. • Other normal structures (lower priority):
• Parotids
• Dmean < 26 (atleast one gland)
• at least 20 cc of the combined volume of both parotid
glands to receive < 20 Gy,
• at least 50% of one gland to receive < 30 Gy
• TongueMax < 55 Gy
• Inner/middle ears Mean < 50 Gy
• (especially with concurrent Cisplatin)
• EyesMean < 35 Gy
• GlotticlarynxMean < 45 Gy
• Lens < 6

81. Delineating Parotid as OAR
• Identify the gland
• Mid aspect of the gland
• Then proceed cranially and caudally
• Boundaries
Cranial – EAC & Mastoid
Caudal – submandbular space
Anterior – masseteric muscle
Posterior - SCM

82. Simultaneous integrated boost SIB
• Simultaneously treat two or more volumes
• Different fraction sizes
• Use of same plan – less error
• Dose painting

83. Plan Evaluation
• DVH
• 95% isodose to 100% target volume
• Dose constraints to OAR

84. Treatment delivery
• IMRT
• Exact position
• Fiducial matching
• Isocentre
• SSD

85. Chemotherapy
• Induction
• Concurrent
• Adjuvant

86. NACT
• Ongoing trail
• Excellent outcomes & tolerability
• NCCN Category 3

87. 480 patients, Stage III, IV
Docetaxel, cisplatin, and fluorouracil (TPF)+CRT Vs CRT

88. Arm Distatnt FFS Locoregional
FFS
NACT+CRT 90 92
CRT 83 89

89. Trial No Description DFS
International
NPC study
339 RT vs NACT+RT 54 vs 40
Me et al 456 RT vs NACT+RT
Cis+bleo+5FU
63 vs56
AOCOA 334 RT vs NACT +RT
Cis
48 vs 42

90. CRT
• CDDP (Cis diammine dichlorido platinum)
100mg/m2
• Weekly monitoring of CBC, RFT
• Adequate hydration of patient
• Weekly oxaliplatin 70mg/m2
• Carboplatin
• Cetuximab EGFR target
• Bevacizumab VEGF

91. CDDP
• Pencillin of cancer
• Peyrone’s chloride
• Use with caution in altered RFT
• Hydrated before, after and post chemo
• Higher the dose more aggressive hydration (2L)
• Furosemide diuresis every 2L
• anti emetis (ondan, dexona, aprepitant)
• Nephrotoxic, ototoxic, neurotoxic
• Azoopermia, alopecia

92. CRT – key trials
Trial No Method DFS LRC Toxicity
NPC
9901
348 Conc
Cis+RT
No Adj CT
72 vs 62 92 vs 82 > CRT
arm
SQNP01 221 Al Sarraf
regimen
72 vs 53 > CRT
Taiwan 284 Cis/5Fu+RT
vs RT
72 vs 53 96.8 vs
92.1

93. Al Sarraf Trial
• 193 patients
Trial 5 yr
PFS
5 yr
OS
RT 29 37
Chemo RT + Adj RT 58 67
Adjuvant CT
Cisplatin / 5FU
Concurrent CRT (Cisplatin)

94. MAC-NPC meta-analysis (Blanchard,
Lancet Oncol 2015)
• 19 trials with 4806 pts.
• 5-yr OS benefit for concurrent and adjuvant
chemo (12.4%) or concurrent chemo alone
(9.4%)

95. NPC 9901

96. Dose escalation
• Improvement in local tumor control rates
• External Beam RT
• Brachytherapy boost
• Stereotactic RT boost

97. Brachytherapy
• Suitable Candidate
Tumors restricted to Nasopharynx as BOOST
Thickness of CTV <10 mm - well circumscribed,
superficial local recurrences.
• Local control upto 90 – 95 % for T1-T2 tumours with
acceptable late toxicities
• Dose delivered through brachytherapy is adequate
only for superficial non-bulky tumours
• Outcome depends on accurate placement of the
catheters, which largely depends on patient anatomy
and clinician’s skill

98. • Boost minimal, local,residual local disease
• Salvage therapy well circumscribed
superficial local recurrences

99. Techniques
• Customised mould
• Rotterdam nasopharyngeal applicator
• Massachusetts general hospital technique
• Transnasal permanent interstitial implants

100. RN Apllicator
• Made of soft silicone
• Endocavitary
• Well tolerated by patient
• The two silicone tubes, can accommodate
standard 6 French afterloading catheters.
• The legs of the applicator sort through the
nostrils and are fixed with a silicone bridge,
pushed against the nasal septum

104. Nasopharynx Implant points
• Tumor tissue points
Node of Rouviere (R)
Nasopharynx (Na)
• Normal tissue points
Spinal cord, soft palate, base of skull, pituitary
gland, optic chiasm, and retina

105. Nasopharynx
RPN

106. Dose Prescription
• 5-10mm from mucosal surface
• Doses of 18Gy/6# [EBRT 60 Gy/30#]—T1
• 12Gy/4#[EBRT 70Gy/35#]—T2-T4 lesions

107. Boost with electrons
• Lateral field
• 9MeV
• 90% Isodose line
• 6x6cm field

108. 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

109. • 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

110. Complications
• Radiation induced
• Mucositis
• Xerostomia
• Chemo induced

111. Complications
• Temporal lobe necrosis
• Cranial neuropathy
• Oral complications
• Aural toxicity
• Carotid stenosis
• Endocrine dysfunction
• Second malignancies

112. Temporal Lobe Necrosis
• Sequelae of treatment
• Conventional 2D RT
• 65%
• > 2 Gy
• Hallucination, absence seizures, déjà vu (31%)
• Headache, convulsions, confusion,
hemiparesis (14%)
• Asymptomatic (16%)
• IMRT 3-4%

113. Cranial neuropathy
• IX, XII
• Slurring of speech, twitching of neck muscles,
dysphagia – fatal aspiration pneumonia
• VI

114. Oral complications
• Xerostomia
• Salivary flow dropped by half 7.2Gy
• Nadir after 36Gy
• For 2 years no recovery
• Parotid sparing IMRT
• Osteoradionecrosis – maxilla (2.7%),
mandible (1.7%)

115. Aural toxicity
• Hearing loss - SNHL
• Cisplatin increased the risk

116. Carotid stenosis
• High risk patients - >60yrs, smoking, HTN,
HCH, CVA

117. Endocrine dysfunction
• Hypothalamic pituitary dysfunction
• Amenorrhea, galactorrhea –
hyperprolactinemia
• Hypothyroidism
• Hypoadrenalism

118. Second malignancies
• Rare (0.04%)
• Latency period > 10yr
• Maxillary osteosarcoma
• Soft tissue sarcome

119. Follow up
 H&P + complete H&N physical exam +/-
mirror/fiberopticexam
 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 irradiated)
 Speech/swallowing/dental/hearing evaluations
 Consider EBV-DNA monitoring

120. Clinical Pearls
• Complex anatomy, radiosensitive & curable
• IMRT with SIB
• Dose 70Gy
• Concurrent cisplatin-based chemo + RT has been
shown to improve OS
• Brachytherapy for boost