Description of anatomy, lymphatic drainage, pathway of spread, diagnosis and management of oropharyngeal tumours

1. BY Dr DEEPAK KUMAR DAS
MOD- Dr AMIT BAHL
PGIMER, CHANDIGARH

2. ANATOMY
Posterior continuation of oral cavity
which communicates with nasopharynx
above and laryngopharynx below
Extends from plane of hard palate
superiorly to plane of hyoid bone
inferiorly

3.  Subdivided into palatine (faucial
arch) and oropharynx proper
 Lateral walls of oropharynx
limited posteriorly by tonsillar
fossa & post tonsillar pillar
 With in oropharynx 4 main sites
– soft palate , tonsillar region ,
BOT , post & lateral pharyngeal
wall

4. EPIDEMIOLOGY
 Most common site: Tonsil and ant. Tonsillar pillar
 M: F- 4: 1
 Oropharyngeal cancers account for approximately 10% of annual
worldwide incidence of head and neck squamous cell carcinoma.

5. Relative proportion of pharyngeal cancer
Male Female
Tonsil 37% 33.3%
Other 27.7% 16.1%
Oropharynx
AGE GROUP
MALE FEMALE
0-14 YEAR 0.2% 0
15-34 1.4% 4.6%
35-64 69.3% 72.4%
65 AND ABOVE 29.1% 23%
HBCR, RCC, PGIMER, A 3 YEAR CONSOLIDATED REPORT

6. Stage at diagnosis: PGIMER
STAGE I 1.7%
STAGE II 10.7%
STAGE III 21.8%
STAGE IV 63.6%

7. ETIOLOGY
 80-90%: Due to tobacco exposure
:Cigarette smoking, cigar and pipe smoking, smokeless tobacco
 Alcohol: synetrgistic with alcohol
 Viral: HPV usually types 16 and 18
HPV
 Double standard DNA virus with >120 strains.
 HPV types 6, 11, 16 and 18 are high risk.
 HPV 16 is the most common HPV type identified in human tumors.

8. Etiology cont...
HPV 16
>90% of all HPV related oropharyngeal cancers
Confers 14 fold increase in risk for oropharyngeal
cancer
HPV genome encodes three oncoproteins E5, E6 and E7 in
addition to the regulatory genes E1 and E2 as well as
capsid proteins L1 and L2.

9. CRITICAL STEPS OF HPV INDUCED CARCINOGENESIS

10. PATHOLOGY
• Almost exclusively squamous cell carcinoma(95%)
60%- mod diff.
20%- well diff
20%- poorly diff
Variants;
Spindle cell- resembles sacoma
Basaloid- aggressive behaviour and poor clinical
outcome
• Lymphoma-10 to 15% tonsil
- 1 to 2% BOT

11. Pathology cont........
• Malignant melanoma
• Lymphoepithelioma
• Minor salivary gland tumors
• Sarcomas
• Plasmacytomas

12. ROUTES OF SPREAD
Primary routes of spread- direct extension
and lymphatic spread
Hematogenous- less common
Submucosal extension- visualised as
erythematous regions without distinct
borders or ulceration

13. Lymphatic spread of oropharyngeal tumors
The typical order of metastatic
progression is systemic:
Upper jugular chain(level I/II: first
echelon)
Mid cervical( level III)
 Lower cervical nodes(
level IV)
 Skip metastasis are rare(0.3%)
and level I or V involvement is
usually associated with
involvement of other nodes.
Most common location of LN metastasis
from oropharyngeal cancer is ipsilateral
level II

14. Percentage incidence of clinical LN mets and
stage
TONSILLAR
FOSSA
BOT SOFT
PALATE
OROPHARY-
NGEAL WALL
T1 <10% 70% 10-20% 25%
T2 30% 75% 35% 30%
T3& T4 65-70% 75-85% 60-65% 65-75%

15. LOCAL SPREAD
CA TONSIL
Initial lesions
-Tend to be exophytic with central ulceration with
infiltratative margins
- some develop submucosally neck nodes
with no obvious tonsillar lesion
Advanced lesion
- Penetrate to parapharyngeal space skull
base
- May involve mandible, nasopharynx and pyriform
sinus

16. SOFT PALATE
 Earliest tumor- red lesion with ill defined border
 Spread occurs first to tonsillar pillar and hard
palate
 Lateral spread may penetrate superior constrictor
muscle and skull base and may rarely extend to
cranian nerves in parapharyngeal space
 Involvement of lateral wall of nasopharynx in
advanced cases

17. BOT
 Usually remains in tongue unless it begins at
peripheral margin
 May invade glossotonsillar sulcus and
eventually escape to neck
 Advanced lesions- spread to larynx, oral
tongue and parapharyngeal space

18. VALLECULA
 Posteriorly- to lingual surface of epiglottis
 Laterally- to lateral pharyngeal wall and
anterior wall PFS along pharyngoepiglottic
fold
 Inferiorly- to pre-epiglottic space via thin
hyoepiglottic ligament

19. CLINICAL PRESENTATION
• Most common symptom- pain either local or reffered,
local pain usually described as sore throat.
• Reffered pain: By cranial nerve IX and X
• CN IX involvement referred pain via tympanic nerve of
Jacobson localised to inner ear or temperomandibular
joint
• CN X involvement referred pain through auricular
nerve of Arnold to external auditory canal
• Asymptomati mass within upper neck
• Odynophagea

20. Cont........
• Dysphagea
• Dysarthria- hot potato voice caused by CN XII
involvement or narrowing of pharyngeal air lumen
• Trismus- involvement of pterygoid
• Deep ulceration and necrosis

21. DIAGNOSTIC WORK UP
History
General physical examination
LN Examination
 Neck should be turned to the side examined to relax
sternocleidomastoid muscle
Level, No. ,size, character, skin involvement
 INSPECTION
should be done under proper illumination and should
be systematic and reproducible
 Indirect mirror examination
Allows optimal inspection of BOT, tonsil, vallecula as
well as documenting spread to laryngeal and
pharyngeal subsites

22. Cont.......
Fibreoptic examination
more informative than IL
Palpation
Palpation of tonsillar fossa and BOT should be
performed because these location can harbour occult
primary tumors and should be performed at the
completion of examination owing to its propensity to
trigger gag reflex
Direct laryngoscopy
useful to evaluate large tonsillar or BOT lesions

23. CONT............
 Pan endoscopy
because of risk of second
primaries in upper digestive tract
 Biopsy of tumor and any
suspicious areas
 FNAC of LNs
LABOROTORY STUDIES
 Complete blood count
Radiographic studies
• Chest X-ray
• Plain radiograph of neck or
mandible
• CECT( BOS TO T4)
• MRI
• PET

24. RADIOGRAGHIC STUDIES
CECT BOS TO T4
 Extent of primary tumor
 Evaluation of LN status
 Evaluating involvement of
mandible or base of skull
 Extracapsular extension- with
irregular nodal margin without
clear distinction with
surrounding fat or when there is
thickening of surrounding
fibroadipose tissue or muscle
 Subcapsular spread is often
difficult to characterise with CT

25. CONT..........
MRI
 Superior to CT in specific
situations including delineating
orbital or skull base involvement
and defining intracranial
perineural tumor spread
 Better able to identify subtle soft
tissue involvement by tumor,
deep osseous invasion and
marrow replacement
 Perineural spread of the disease
 Extent of anterior spread of BOT
tumors

26. CONT....... PET
 Sensitivity-100%
 Specificity-60% for
pathologically proven
tumour
 Ability to detect clinically
and radiographically
occult pathologic cervical
LAP which is useful for
delineating radiotherapy
volume

27. TNM staging system for
oropharyngeal cancer
Endoscopic, radiographic and physical examination
findings should be included while determining staging
PRIMARY TUMOR(T)
Tx: primary tumor cannot be assessed
T0: no evidence of primary tumour
Tis: carcinoma in situ
T1: tumour size 2cm or less
T2: Tumour size > 2 cm but < 4cm in greatest dimension
T3: Tumour >4 cm in greatest dimension

28. Staging cont.......
T4a: Tumour invades larynx, deep/extrinsic muscle of
tongue, medial pterygoid, hard palate or mandible
T4b: Tumour invades lateral pterygoid muscle,
pterygoid plate, lateral nasopharynx or skull base or
encases carotid artery
REGIONAL LN
Nx: regional LN can not be assessed
N0: no regional LN mets
N1: metastasis in a single ipsilateral LN <3 cm in
greatest dimension

29. Staging cont......
N2: metastasis in a single ipsilateral LN> 3cm but not >
6cm in greatest dimension or in multiple ipsilateral
LNs none >6 cm in greatest dimension or in bilateral
or contralateral LNs , none >6cm in greatest
dimension
N2a: metastasis in a single ipsilateral LN > 3cm but not >
6cm in greatest dimension
N2b: multiple ipsilateral LNs, none >6cm in greatest
dimension
N2b: bilateral or contralateral LNs, none > 6cm in
greatest dimension
N3: LN > 6cm in greatest dimension

30. Staging cont.......
DISTANT METASTASIS
M0: no distant metastasis present
M1: distant metastasis present

31. Stage grouping
Stage 0- Tis N0 M0
Stage I- T1 N0 M0
Stage II- T2 N0 M0
Stage III- T3 N0 M0
T1-3 N1 M0
IVA- T4a N0-1 M0
T1-4a N2 M0
IVB- T4b any N M0
any T N3 M0
IVC- any T any N M1

32. AJCC sixth edition
T4a- resectable
T4b- unresectable
With the advancement of surgical techniques with free
flap and other reconstructive options that allow
previously unresectable primary lesion now to be
resected .
AJCC seventh edition
T4a- moderately advanced local disease
T4b- very advanced local disease

33. TREATMENT
OBJECTIVES
• Control of primary tumor and regional LNs
• Preservation of anatomy and function of the organ
• Minimal treatment sequelae
MODALITIES
Surgery
- for primary
- for neck disease
Radiotherapy
EBRT
- conventional
-3D CRT and IMRT
Brachytherapy
Chemotherapy
Combined modality

34. RADIOTHERAPY
 Used as definitive treatment in both early as well as late stage
disease as
 Cure rate high
 Functional outcome better
 Lesser morbidity

35. EBRT
 Prerequisite
 For optimal treatment planning thorough review of
diagnostic films, endoscopic finding and description of the
examination under anaesthesia essential to determine
target volume
 Preirradiation dental care hygiene - utmost imp
 All patients to be regularly seen by dental or oral surgeons
for dental evaluation and fluoride treatment
 Any potential surgical procedure and tooth extractions to be
performed before initiation of radiation therapy
 Hard toothbrushes to be avoided
 Artificial dentures to be avoided

36. Techniques
field technique
 Target Volume :
 Primary tumor and its local and regional extension with
1cm or 2cm margins.
 Nodal volume
 Upper , middle and lower deep cervical and
retropharyngeal and parapharyngeal LNS treated
bilaterally in all cases
u
 CONVENTIONAL
 Two lateral parallel opposed field parallel opposed fields
 Three field fieltechn

37. SIMULATION
 Supine position
 Orfit cast for immobilization
 Neck extended, shoulders pulled down to maximize exposure of
head & neck
 Tongue to be displaced from the palate by an individually
constructed tongue bite block
 Bite block – facilitate immobilization & ↓ amt of normal tissue in
field

38. Simulation cont........  Field margin :
 Superior border
 External land mark : zygomatic arch
 BOT- lower border of zygomatic
arch
 Tonsil and soft palate- upper border
of zygomatic arch
 Anterior border :
 Set up by clinical examination
(inspection and palpation of buccal
mucosa and BOT)
 With atleast 2cm margin beyond
any clinical evidence of disease
This margin should project 2-3 cm
forward of the anterior cortex of
ascending ramus of
mandible(depending on tumor
extent)

39. Simulation cont......
 Post border : to include post cervical l.n at tip of mastoid
 Inferior border : extends to thyroid notch (for 3 field technique) or
above clavicle (for 2 lateral fields)

40. BOT
Upper border kept
from ala of nose to tragus
In simulator planning,
kept at lower border of
zygomatic arch

41. 3 FIELD TECHNIQUE
 Isocentrically opposed
lateral fields matched to a
lower anterior neck field
 Primary tumor and both
sides of upper neck
irradiated through
opposing lateral field
 Both sides of lower neck
is irradiated through a
single AP field with a
midline block at junction
to shield larynx and spinal
cord

42. MATCHING OF
LATERAL AND
ANTERIOR FIELD
Collime
tre
rotation

43. Beam energy
 Optimal energy – CO60 ,4 or 6 MV photon

44. DOSE
 Standard daily dose – 200cGy/#
 5 fractions a week
 Dose to primary tumor & palpable lymph nodes range from 65-
74Gy in 6.5-7.5 wks depending on tumor stage
 For elective irradiation of subclinical microscopic lymphatic mets
should be atleast 50Gy
 After 40-45 Gy , spinal cord shielded along vertebral body
When indicated post cervical l.n boosted with 9 -12MeV electrons to
spare underlying spinal cord

45. For lateralised lesions of tonsil
 RT given via a wedged pair with anterior and lateral fields
 Used for T1-2 and N0-1 diseases
 Incorporates primary site and ipsilateral neck
 Upper neck treated in same portal as primary site
 Lower neck treated with a single AP field with larynx & spinal cord
shielded at field junction
 CT scan used to assist in treatment planning for lesions treated
unilaterally
 CTV of ipsilateral t/t – primary lesion + I/L jugular vein +
retropharyngeal + supraclav l.ns
 Attention given to outline C/L salivary gland

46.  In T1N0 tumor of tonsil not necessary to treat post cervical chain &
mid lower l.n
 Only ipsilateral subdigastric l.n included in field
 Risk for C/L l.n mets low unless there is tongue invasion , invasion of
soft palate within 1cm of midline or extensive clinically +ve nodes in
ipsilat neck

47. ATTEMPTS TO IMPROVE THERAPEUTIC RATIO
 Altered fractionation
 Hyper fractionation
 Pure
 Impure
 Accelerated hyperfractionation
 Pure
 Hybrid
 Concurrent chemoradiation
 Radiosensitizer

48. HYPERFRACTIONATION
 Rationale – use of small dose # allows higher total doses to be
administered within tolerance of late responding tissues
 Pure hyperfractionation – same total dose & overall t/t time but
treating twice per day
 Impure hyperfractionation - ↑ in total dose & sometimes ↑ OTT & no.
of #

49. EORTC 22791
Non base of tongue cancer patients
T2-3N0-1
arm A arm B
70 Gy(2 Gy/#) 80.5 Gy(1.15 Gy/#,
2#/day)
Locoreg-
Ional control 40% 59%
Trend towards increased overall survival in stage III
patients

50. Accelerated treatment
 Shortening of overall treatment duration without a comparable
reduction in total dose
 Aim – to minimize potential for tumor growth or regeneration
during therapy
 Used in head & neck cancers because exhibit accelerate
repopulation
 Pure accelerated t/t – same total dose in half overall time by
giving 2 or more #s/day
↑ acute effects
 Impure – dose is reduced or rest period interposed in middle of
treatment

51. Accelerated treatment v/s hyperfractionation
Meta-analysis of radiotherapy in carcinoma of the head
and neck(MARCH) collaborative group
 Pooled 15 randomised studies
 N= 6,515
 %Oropharyngeal cancer= 44%
 Compared conventionally fractionated radiotherapy to either
accelerated radiotherapy or hyperfractionated radiotherapy
 Altered fractionation radiotherapy regimens were associated with a
3.4% absolute improvement in 5 year overall survival
 Hyperfractionated patients had an absolute 8.2% improvement in
overaal survival at 5 yeatrs
 2% absolute benefit with accelerated radiotherapy
 Heterogeneity in patient inclusion obscure direct comparision between
accelerated and hyperfractionated radiotherapy.

52. RTOG 90-03
CONVENTIONA
L
FRACTIONATI
ON( 70 Gy/ 35#)
Accelerated
fractionation with
split course
(67.2 Gy, 1.6 Gy/#, 2#/
day with 2 week rest
after 38.4 Gy)
Accelerated fractionation with
concomitant boost
( 72 Gy ,1.8Gy/# for 14# followed
by 1.8 Gy in the morning and
1.5Gy afternoon boost to the
gross disease)
DFS 31.7% 37.6% 39.3%

53. CONCOMITANT BOOST
 Boost dose to a reduced volume given concomitantly with
treatment of initial large volume .
 CBRT 54Gy / 30 # / 6 wks & boost dose of 1.5 Gy / # in 12 #
(18Gy) with Inter # interval of 6 hr in last 12#
 large field gets 54 Gy & boost field 72 Gy in 6 wks time
 In PGI CBRT 45Gy/25#/5wks(1.8Gy/#) , followed by boost of
22.5Gy/15#/3wks (1.5Gy/#)
 Boost field gets 67.5Gy/5wks

54.  N=216
 Stage III-IVA oropharyngeal cancer

55. CRT( 66 Gy/33# with
cisplatin 100 mg/m2,
days 1, 22 and 43)
ART with CB( 67.5 Gy/40
#)
Compliance to RT Better
Grade ¾ mucositis 39% 55%
Grade 3 xerostomia 33% 18%
2 year DFS 56% 61%
Patients with nodal size >2 cm had better DFS with CRT
CONCLUSION- In selected cases of locally advanced oropharyngeal cancer,
concomitant boost offers better compliance, toxicity profile and quality of life
than chemoradiation.

56. SPLIT COURSE
 Gap in between treatment
 For pts with poor general condition, old age
 Disadvantages: impaired tumor control due to gap & prolonged
T/T time (Repopulation)
 In PGI 35Gy/15#/3wks followed by gap of 2 wks
25Gy/10#/2wks

57. Study Institution year No of
patients
T1 T2 T3 T4 Overall
Perez Washington university 1959-
91
154 76
%
63
%
59
%
33% 56%
Jackson Vacouver centre, British
columbia
1975-
93
271 94
%
79
%
58
%
56% 75%
Mende-
nhall
University of Florida 1964-
2003
503 88
%
84
%
78
%
61% 79%
Batani Institute Curie 1958-
83
465 90
%
84
%
64
%
47% 64%
Wang Massachusetts general
hospital
1970-
93
102 91
%
91
%
80
%
ND ND
LOCAL CONTROL RATES FOR TREATMENT OF SQ. CELL CA OF
TONSILLAR FOSSA

58. Study Institution year No. Of
patients
T1 T2 T3 T4 overall
Mendenh
all
University of
florida
1964-
2003
333 98% 92% 82% 53% 82%
Harrison MSKCC 1981-95 68 87% 93% 82% 89%
Wang MGH 1970-93 90 85% 85% 54% ND
LOCAL CONTROL RATE FOR TREATMENT OF SQ. CELL CA OF BOT

59. Local control rate with tumours of soft palate
study Institution year No of
patients
T1 T2 T3 T4 Overall
Chera
et al
University of
Florida
1963-
2004
145 90% 90% 67
%
57% 44%

60. LOCOREGIONAL ADVANCED OROPHARYNGEAL CANCER
Concurrent chemoradiation is the standard treatment
and established by:
Meta-Analysis of Chemotherapy on Head and Neck
Cancer( MACH-NC)
 Published in 2000 and updated in in 2007 , 2009 and 2011
 Includes 87 randomised trials
 N= 16485
 No of patients of oropharynx-5878
 Result: 6.2% absolute improvement in overall survival at 5 years from
the use of concurrent chemoradiotherapy compared to radiotherapy
alone
 Oropharynx- 8.1%

62. SEQUENTIAL CHEMORADIATION
 Administration of induction chemotherapy followed by concurrent
chemoradiation
Randomised trials comparing triplet( taxane, platin, 5 FU) v/s doublet(
platin, 5 FU) induction chemotherapy followed by concurrent
chemoradiation
Both Madrid trial and TAX 324 trial demonstrated that triplet therapy was
associated with higher rates of complete response, improve-
ment in time to failure, PFS and OS compared with doublet therapy
To date there is no comparative data between sequential chemoradiation
and concurrent chemoradiation

63. INDICATION OF POST OPERATIVE RADIATION
 Close , inadequate or (+) margins
 Larger lesions (T3-4)
 Poorly differentiated lesions
 Perineural spread
 Lymphovascular invasion
 Soft tissue extension
 Desmoplastic stromal invasion
 Multiple LNS involvement

64. ADJUVANT RADIATION OR CHEMORADIATION
 Two trials: EORTC 22931 and RTOG 9501
 EBRT: 60-66 Gy in 30- 33# concomitantly on days 1, 22 and 43 with
cisplatin
RTOG 9501 EORTC 22931
SAMPLE SIZE 416 334
Oropharynx 43% 30%
Hypopharynx 10% 20%
Inclusion criteria Positive margin
2 or more LN involved
Extracapsular extension
Positve margin, extra capsular
extension, perineural
involvement, LVE, oral cavity or
oropharyngeal tumours with
involvement of level IV OR V
HIGH RISK
Positive resection
margin
6% 13%

65. Cont......
Extracapsular
extension
49% 41%
Both 4% 16%
Total 59% 70%
Outcome endpoint
CRT v/s RT
3 yr estimate 5 yr estimate
Locoregional recurrence 22% v/s 33% 18% v/s 31%
DFS 47% v/s 36% 47% v/s 36%
OS 56%v/s 47% 53 v/s 40%
Median follow up 45.9 month 60 month
Patients with involved resection margin and extracapsular spread of the disease
appear to gain the most benefit from concurrent chemoradiation

66. BRACHYRHERAPY
Used in ca BOT, soft palate, tonsil
INDICATION
 Used as a boost after EBRT
 Used alone in purely exophytic early tumors( T1 or T2)
 Recurrent carcinoma
C/I
 Large tumour > 5 cm
 Associated with bulky cervical nodes
 Extends to RMT, nasopharynx, larynx, hypopharynx
 Fixed to underlying structures or bone
Clinical target volume
Palpable and visible tumor including extension visible on CT or MRI with a safety margin of
at least 1 cm

67. ABS RECOMMENDATION
The dose by EBRT ranges from
50-60 Gy depending on the stage
of the disease and the dose of
brachytherapy ranges from 16-30
Gy
 HDR brachytherapy fraction
size should not exceed 4.5 Gy

68. RESULTS

69. RESULTS

70. IMRT
Increased dose gradient between target volumes and
surrounding normal tissue
Decreased acute and late side effects
DISADVANTAGE
- Potential for marginal misses and local failure from overly
restrictive radiation deposition in regions that received
comprehensive radiation with conventional techniques.
Benefits from IMRT requires:
- Appropriate patient selection
- Accurate delineation of organ at risk and treatment volumes
- Meticulous quality control in radiation planning and delivery
- Limiting interfraction and intrafraction variability

71. Target Volumes

72. Cont.....

73. CTV
59.4
GTV

74. CTV 54
CTV 59.4
GTV
CTV 59.4GTV

75. IMRT PLANNING AVOIDANCE STRUCTURES
HIGH PRIORITY COMPLICATION
SPINAL CORD TRANSVERSE MYELITIS
BRAIN STEM NEURAL DEFICIT
INTERMEDIATE PRIORITY
PAROTID GLAND( contralateral)
XEROSTOMIA
ADD. STRUCTURES
ORAL CAVITY ACUTE MUCOSITIS
LARYNX VOICE CHANGE
MANDIBLE OSTEORADIONECROSIS

76. CONSTRAINTS
PAROTID GLAND (RTOG 0022)
 Mean dose of either gland < 26 Gy
 At least 50% of either parotid gland receieves less than 30 Gy
 At least 20 ml of combined volume of both the parotid gland receives <
20 Gy
SUBMANDIBULAR GLAND
Mean dose < 39 Gy
CONSTRICTORS
Mean dose < 60 Gy
LARYNX
Mean dose < 45 Gy

77. RESULTS
Chao et al. Radiother Oncol 2001;61:275-80

78. RESULTS OF IMRT

79. BIOLOGIC THERAPY
 EGFR inhibitors – cetuximab
 IgG1 chimeric monoclonal Ab
MOA
 Abrogation of radiation induced
phosphorylation of EGFR
receptors ( mechanism underlying
accelerated repopulation)
 Enhanced radiation induced
apoptosis.
 Attenuate radiation induced
expression of DNA repair proteins

80. CETUXIMAB
 Specifically targets EGFR with high affinity & blocks ligand binding
 Enhances antitumor activity of cisplatin
 Enhances antitumor activity of radiotherapy
 Showed activity in pts with SCCHN & documented platinum
resistance
 EGFR inhibition is a promising new approach for radiosensitization
 Need to drive predictive biomarkers to assess response to molecular
therapies
 Optimize radiotherapy fractionation schemes to complement targeted
agents

81. DOSE, SCHEDULE AND TOXICITY
 Intravenous cetuximab given one week before radiotherapy
 Loading dose of 400 mg per square meter of BSA over a period of
120 minutes, followed by weekly 60-minute infusions of 250 mg per
square meter for the duration of radiotherapy
 Premedication to be given
 Before the initial dose , a test dose of 20 mg should be infused over
a 10-minute period, followed by a 30-minute observation period
Side effects
 Infusion reaction -angioedema, urticaria, hypotension
,bronchospasm
 Hypersenstivity reactions, acniform rash

82. BONNER STUDY
EBRT( SFX: 70 Gy/ 35#, HFX:72-
76.8 Gy/ 60-64#, AFX with CB: 72
Gy/ 42#)
EBRT PLUS
CETUXIMAB
Median duration
of locoregional
control
14.9 month 24.4 month
2 year PFS 37% 46%
5 year OS 36.4% 45.6%
Median
survival
29.3 month 49 month

83. Cont.....
When compared by disease site, oropharyngeal tumors
derived most benefit with the addition of Cetuximab with
radiotherapy than the tumors of larynx and hypopharynx
Possible explanation may be
 The addition of anti EFGR antibody preferentially benefits
locally advanced squamous cell carcinoma of head and
neck based on tumors primary anatomic location favouring
oropharyngeal tumors.
 Findings is related to the fact that HPV is associated
primarily with oropharyngeal tumors
 Current study RTOG 1016 is comparing concurrent
chemoradiation to the same radiotherapy with cetuximab
in HPV associated oropharyngeal cancer

84. SURGERY
 Limited role in carcinoma oropharynx as because
 Surgically inaccessible
 Increased post operative and functional morbidities
INDICATION
 As definitive treatment for small lesion ( T1/T2)
 As a part of combined approach for advanced stage tumors (with RT)
 For residual ds in neck after RT
 As salvage for persistent or recurrent ds

85. ADVANTAGE
 One time procedure - But most pts will require postop RT
 Limited amount of tissue exposed to treatment
 Late sequelae minimal
 RT reserved for subsequent tumor which may be unsuitable for surgery
 Cosmetic defects
 Functional defects
 Greater amount of disability
 Complex reconstructive procedures
 Expertise required – not available everywhere
DISADVANTAGES

86. Surgical procedures
BOT
 Midline mandibulotomy-splitting the lip,mandible, oral tongue
midline
 Lateral mandibulotomy-dividing the mandible near the angle and
approaching the BOT from the side
 Floor drop procedure
TONSIL
 Tumour < 1 cm- wide local excision
 Tumour involving palatine tonsil- radical tonsillectomy
SOFT PALATE
Surgery is rarely recommended as initial therapy because of significant
nasopharyngeal reflux during swallowing

87. RESULTS
Parsons et el reviewed the radiation oncology and
surgical literature from 1970 to 2000 and compared
outcome between surgery with and without radiation
and definitive radiation with or without LN dissection
Surgery with or without
RT
RT with or without LN
dissection
Local control 79% 76%
5 year OS 49% 52%
5 year CSS 62% 63%
Severe complication 32% 3.8%
Fatal complication 3.5% o.4%

88. LOCOREGIONAL RECURRENT DISEASE
 Locoregional failure patients udergo salvage surgery if
feasible.
 Re-irradiation is performed in
- surgically unresectable
- high performance status
- patient understands the high potential of
significant treatment related morbidity and modest
likelihood of long term survival.
 These patients usually have limited volume well
circumscribed recurrent disease and a prolonged time from
initial treatment.
 All attempts are made to limit the volume of retreatment
with the use of IMRT.

89. Stage I & II: Surgery or RT( EBRT or brachytherapy) gives
similar locoregional control
Stage III & IV: Concurrent chemoradiation

90. OBJECTIVE: To review NCCN and ESMO clinical practice guidelines and to
suggest revisions to account for potential difference in demographic and
resources, to better reflect current clinical management of head and neck
cancer within Asean region

91. GUIDELINES
Stage I & II: only RT
Stage III, IVA & IVB: Concurrent chemoradiation
Sequential chemoradiation is preferred in N2-3
tumours in patients having good performance status

92. SEQUELAE OF TREATMENT
ACUTE TOXICITY LATE TOXICITY
- mucositis - xerostomia
-dermatitis - dental caries
- Dysphagea - osteoradionecrosis
-Sore throat - prolonged dysphagea
- Odynophagea - trismus
- In field alopecia - hypothyroidism
- Xerostomia - cervical fibrosis
- Taste distrubance - neck lymphedema
- Dehydration - hearing loss
-Compromised nutrition

93. CONCLUSION
 Primary radiotherapy is preferred treatment in early stage tumors
 Altered fractionation schedules produce better results but with increased toxicity
 No improvement in LRC or survival for pts treated with surgery +RT as compared
to RT alone
 Surgery preferred in case of residual or recurrent disease.
 Brachytherapy plays a limited role because of technical difficulty due to
anatomical location
 Concurrent chemoradiation is the treatment of choice for locoregionally
advanced tumors.

94. THANK YOU