Educational lecture for trainees at KOSRO

1. General Principles and Practical Points
in Target Delineation: Oropharynx Ca
Yong Chan Ahn, MD, PhD
Dept of Radiation Oncology
Samsung Medical Center
Sungkyunkwan University School of Medicine

3. Anatomy

4. Tonguebase (Vallecula)
Tonsil
Ant pilla
Fossa
Post pilla
Soft palate

5. Soft Palate
• Soft palate is thin, mobile muscle complex
separating nasopharynx from oropharynx.
• It is contiguous laterally with tonsillar pillars.
• Epithelium:
– Oral side is squamous
– Nasopharyngeal surface is respiratory

6. Tonsillar Fossa
• Boundaries:
– Ant -- ant tonsillar pillar (palatopharyngeal
muscle)
– Post -- post tonsillar pillar (palatopharyngeal
muscle)
– Inf -- glossotonsillar sulcus and
pharyngoepiglottic fold
– Lat -- pharyngeal constrictor muscle and its
fascia, mandible, and lateral pharyngeal space

7. Tonguebase
• Boundaries:
– Ant -- circumvallate papillae
– Lat -- glossotonsillar sulci
– Post -- epiglottis
• Vallecula:
– Ttransition from tonguebase to epiglottis
• Tonguebase musculature is contiguous
with oral tongue.

10. Natural History
& Patterns of Spread

11. Primary Lesion
 Spread is dictated by local anatomy, and each
anatomic site has its own peculiar patterns.
 Muscle invasion – common (may spread along
muscle or fascial planes)
 Bone and cartilage act as barrier to spread
 Parapharyngeal space invasion – sup~inf
spread from base of skull to low neck
 Perineural invasion
 Vascular space invasion

12. Ant Tonsillar Pillar -- Primary
• Usually diagnosed early when superficial
– Usually with indistinct margins
– May be red, white, or mixture
• May develop central ulcer with rolled
margin
– Sup/Med -- to soft palate, post hard palate, and
maxillary gingiva.
– Ant/Lat -- to retromolar trigone, post
gingivobuccal sulcus, buccal mucosa, adjacent
tongue.

13. Ant Tonsillar Pillar -- Primary
• Advance lesions:
– Mandible invasion
– Skullbase and nasopharynx occurs late
associated with medial pterygoid muscle and
plate invasion (trismus and temporal pain).

14. Tonsillar Fossa -- Primary
• Initial lesions:
– Tend to be exophytic with central ulceration
plus an iniltrative component.
– Some develop submucosally -- neck nodes
with no obvious tonsillar lesion.
• Extension to posterior tonsillar pillar and
oropharyngeal wall occurs early.
• Invasion into glossotonsillar sulcus and
tonguebase occurs in 25%.

15. Tonsillar Fossa -- Primary
• Advance lesions:
– Penetrate to parapharyngeal space  access
to skull base.
– Cranial nerve involvement is uncommon.
– May invade mandible, nasopharynx, and
pyriform sinus.

16. Post Tonsillar Pilla -- Primary
• Early lesions are uncommon.
• May spread inferiorly along
palatopharyngeal muscle to its insertions
into middle pharyngeal constrictor,
pharyngoepiglottic fold, and posterior
border of thyroid cartilage.
• Also, lymphatic trunks of posterior tonsillar
pillar are theoretically more likely to spread
to junctional (parapharyngeal) and level V
nodes.

17. Soft Palate -- Primary
• Nearly all lesions occur on oral side.
• Earliest tumors are red lesions with ill
defined borders.
• White lesions may be leukoplakia,
carcinoma in situ, or early invasive
carcinoma.
• Multiple sites involvement with normal-
appearing intervening mucosa may occur.
• Most carcinomas are diagnosed while still
confined to soft palate.

18. Soft Palate -- Primary
• Spread occurs first to tonsillar pillars and
hard palate.
• Lateral spread may penetrate superior
constrictor muscle and skull base and may
rarely extend to cranial nerves in
parapharyngeal space.
• Involvement of lateral wall(s) of
nasopharynx may occur in advanced
lesions.

19. Tonguebase -- Primary
• Usually remains in tongue unless it begins
at peripheral margin.
• Vallecular lesions:
– Post -- to lingual surface of epiglottis.
– Lat -- to lateral pharyngeal wall and anterior
wall of pyriform sinus along pharyngoepiglottic
fold.
– Inf -- to preepiglottic space via thin
hyoepiglottic ligament.

20. Tonguebase -- Primary
• Lateral tonguebase lesions:
– May invade glossotonsillar sulcus and
eventually escape into neck (no effective
musculature barrier).
• Advanced lesions spread to larynx, oral
tongue, and parapharyngeal space.

21. Lymphatic Spread
 Predictors of LN meta:
 Histologic type
 Differentiation of tumor
 Primary lesion size
 Vascular space invasion
 Capillary lymphatics density
 Recurrence

22. Lymphatic Spread
 Subclinical disease in clinically (-) LN:
 Positive nodes by elective neck dissection
 Regional recurrence by F/U after no neck Tx

23. Subclinical Disease
 Defined as
 Disease statistically known to be present
 Cannot be seen or palpated in areas
accessible to physical examination
 Cannot be seen on highly efficient imaging
studies
 From barely detectable microscopic focus to
undetected 2 cm node completely replaced by
tumor

25. Incidence of Subclinical Disease

26. Lymphatic Spread
 Orderly progression
 Well-lateralized lesions  spread to
ipsilateral neck
 Lesions on or near midline and lateralized
tongue base and nasopharyngeal lesions 
may spread to both sides, and tend to spread
to bulky side

27. Incidence of Subclinical Disease (%)

28. Lymphatic Spread
 Contralateral disease in clinically (+) LN:
 Large or multiple LN
 Lymphatic pathways obstruction by surgery
or RT
 Shunting is mainly through submental space
 Level II LN is most commonly involved in
contralateral metastases from well-lateralized
lesions

30. Lymphatic Spread
 Skip metastasis can occur:
 If unusual LN site involvement (+) 
search for second primary
 Retrograde LN metastases in ipsilateral
axilla if lower neck LN involved

31. Lymphatic Spread
 Retropharyngeal LN involvement:
 Became easier with CT and MRI
 Risk of retropharyngeal adenopathy is
related to clinically involved LN and primary
site

33. Lymphatic Spread
(Oropharynx Cancer Summary)
Tonguebase Tonsillar fossa Ant pillar Soft palate
1st echelon II II Ib/II Ib/V
cN(+) 75% 75% 45% 55%
Contralateral 30% 10% 5% 15%
Occult 40~50% 50~60% 10~15% 20%

34. Distant Metastasis
 Same for stage for stage regardless of Tx modality
 Related more to cN and involved LN location than:
 <10% for cN0-1 disease
 30% for cN3 disease or cN1-2 nodes with low neck LN
involvement
 Lung is most common:
 About 1/2 of first metastatic sites
 50%, 80%, and 90% at 9 months, 2 years, and 3 years
 Risk doubles if recurrence above clavicles

35. Neck Management Issues

38. Management of N0 Neck
 Occult cervical LN metastases: 20~30%
 Influenced by multiple factors
 Size and location of primary cancer
 Depth of invasion
 Tumor differentiation
 Elective LN dissection or irradiation is
needed as part of standard management

39. Policy of Elective Neck Treatment
 Same modality of treating primary site
 RT + ENI  little additional morbidity
 Surgery + MND  modest additional
morbidity
 Survival advantage is small and usually
offset by Tx failures, second cancer, and
intercurrent disease

40. Surgical Management of Neck
 Radical neck dissection is the standard
 involves complete removal of the lymphatic
pathways within the neck
 SCM muscle, SAN, and JV are routinely
sacrificed
 More conservative surgical procedures
 sparing of specific anatomic structures (i.e.,
SAN and SCM muscle)

41. Selective Neck Dissection: Rationales
 Better understanding of disease
characteristics
 More clinical experience and data
 Better anatomic imaging tools (CT and MR)
 Functional and physiologic imaging tools
available
 Intra-operative therapeutic decision
 Systematic use of intraop frozen section
 Concept of sentinel lymph node

42. Types of Neck Dissections
Classification
Level of LN
Removed
Standard RND I, II, III, IV, V
Modified RND I, II, III, IV, V
Selective ND
Supraomohyoid I, II, III
Lateral II, III, IV
Posterlateral II, III, IV, V
Anterior compartment IV
Extended ND

43. Sentinel Lymph Node (SLN)
 The 1st LN to receive lymphatic drainage
from a primary tumor.
 If it contains metastatic tumor, this indicates
that other LN may contain tumor.
 If it dose not contains metastatic tumor,
other LN are not likely to contain tumor.
 Initially investigated for LN staging in
cutaneous melanoma
 Increasing clinical application in breast
cancer and H/N cancer

44. Neck Irradiation
Everyone knows that elective neck
irradiation is an essential component of
radical RT for almost all H/N cancers
Usually 45~50 Gy/5 weeks
Usually (but not always) to entire neck
Usually regarded ‘less morbid’ than surgery

45. Factors to be Considered in ENI
 Primary site
 Histologic grade, vascular space invasion
 Depth of invasion, size of primary lesion
 Risk for bilateral subclinical disease
 Difficulty of neck examination
 Relative morbidity of extending ENI vs risk of
subclinical disease
 Patients’ compliance to follow-up evaluations
 Patients’ suitability for RND in case of
recurrence after RT

47. Target Delineation Issues:
From 2D era to 3D era

48. Simulation films of 2 cases (T3N0 supraglottic larynx, T2N0 mobile tongue)
were sent to 16 experienced HN radiation oncologists in 11 departments in The
Netherlands.
Q1. To delineate treatment portals covering neck (and primary tumor).
Q2. To indicate neck LN regions for elective RT.

50. 2 Ports (I)
3 Ports (II)

53. Rotterdam and Brussels have independently published guidelines for
definition and delineation of CT-based neck nodal Levels I–VI.
Rotterdam and Brussels differed slightly in translating original surgical
level definitions proposed by 2002 AAO-HNS to CT guidelines.
Taking surgical 2002 AAO-HNS classification as a reference,
adjustments are proposed for Rotterdam and Brussels delineation
protocols to arrive at unified CT-based neck nodal classification.

60. Practical Points

61. ’04 Radiology

62. ’04 Radiology

63. ’04 Radiology

69. ’09 JKMS

75. Plan Parameters

76. DVH (Case 2)

77. Ipsilateral Parotid Contralateral Parotid
DVH (Case 2)

78. Institute
1 2 3 4 5
Case 1 Gross Lesion (Primary) 99 99 95 96 97
Gross Lesion (LN) 100 100 100 100 100
Case 2 Gross Lesion (Primary) 100 100 100 100 100
Gross Lesion (LN) 96 93 89 93 88
Case 1 Ipsilateral Parotid 52 51 24 23 11
Contralateral Parotid 2 10 2 1 2
Case 2 Ipsilateral Parotid 100 98 16 90 15
Contralateral Parotid 70 33 1 24 8
TCP and NTCP (Case 2)

79. Problems with GTV Delineation
• GTV is poorly appreciated by imaging and
FNABx.
– (+) and close resection margin at surgery
– Evidenced by partial organ surgery studies
• Causes of uncertainty:
– Submucosal spread, perineural invasion, non-cohesive
margins
– Poor sensitivity/specificity of GTV by CT, MR, PET
– Non-geometric tumor spread through tissue
E-Contouring @ ASTRO 2012

80. E-Contouring @ ASTRO 2012

81. E-Contouring @ ASTRO 2012

82. E-Contouring @ ASTRO 2012

83. E-Contouring @ ASTRO 2012

84. E-Contouring @ ASTRO 2012

85. How I Do?

86. Definition Description
GTV Palpable or visible
disease
Physical examination, radiographs
CTV GTV + expansion for
microscopic spread
Knowledge of patterns of spread (onco-
anatomy)
PTV CTV + expansion for
setup error and organ
motion
Imaging studies (fluoroscopy or 4D CT to
define degree of motion) and reproducibility/
stability of mobilization/localization systems

87. ICRU Nomenclature for Volumes

88. Why 45~50 Gy for ENI?
First documented by Gilbert Fletcher in 1972
(Cancer, 29:1450~1454)
45~50 Gy/5 weeks to initially uninvolved areas
Elective RT Partial neck Whole neck
# of patients 185 284
# with N3 disease 12 (6.5%) 100 (35.2%)
New neck disease 22 (12.0%) 5 (1.7%)

89. Is ENI without Morbidity?
Aerodigestive track: swallowing discomfort,
pain, voice change, dyspnea, cough, sputum
Skin and soft tissue: dermatitis, lymphedema,
fibrosis, joint stiffness, soft tissue necrosis
Glandular structures: dry mouth (dental caries),
dry eye
Skeletal system: osteonecrosis, chondronecrosis
Others: fatigue, anorexia, nausea, second
cancer

90. ENI vs Observation?
Risk-benefit ratio should be considered
Assumptions
Same local control rate regardless of ENI
Efficiency of regional control by ENI = 90%
Salvage rate of surgery (if no ENI) = 60%
Risk of severe morbidity by ENI = 3%

91. Risk of Subclinical Disease
ENI 30% 20% 10%
No
Yes

92. Give-up Old Concept!
More accurate imaging
for treatment planning
High precision RT
Multimodal imaging
CT, MRI, PET, etc
3D-CRT, IMRT, SRT, IGRT
Paradigm shift:
36~40 Gy
Selective neck
Clinical evidences

94. Strategies for shrinking tumor:
• Shrinking field by 3D-CRT
• Dose painting by IMRT
• Both

95. Case 27**1: Lt Tonsil ca, Sq, cT2N1 (F/46)
• Definitive CCRT (3D shrinking field):
– ’09/5/8 ~ 6/25: 70 Gy/35 Fx’s
(36 Gy/18 Fx’s + 18 Gy/9 fx’s + 16 Gy/8 Fx’s)
– Concurrent CDDP #3 (100 mg/m2)

96. Case 27**1: 1st Plan upto 36 Gy/18 Fx’s

97. Case 27**1: 1st Plan upto 36 Gy/18 Fx’s
26 Gy/13 Fx’s

98. Case 27**1: 2nd Plan upto 54 Gy/27 Fx’s

99. Case 27**1: 2nd Plan upto 54 Gy/27 Fx’s
46 Gy/23 Fx’s

100. Case 27**1: 3rd Plan upto 70 Gy/35 Fx’s

101. Case 27**1: 3rd Plan upto 70 Gy/35 Fx’s
60 Gy/30 Fx’s

102. ’09-Apr ’10-Jan ’12-Oct
Pre-RT 8M 3Y 7M

103. ’09-Apr ’10-Jan ’12-Oct
Pre-RT 8M 3Y 7M

104. ’09-Apr ’10-Jan ’12-Oct
Pre-RT 8M 3Y 7M
Q: Dry mouth?
A: “Negligible!”

105. Case 28**6: Tonguebase ca, Sq, cT2N2 (M/59)
• Definitive CCRT (SIB using Tomotherapy):
– ’09/8/18 ~ 9/29: 66 Gy/30 Fx’s (39.6 Gy/18 Fx’s +
26.4 Gy/12 fx’s)
– Concurrent CDDP #3 (100 mg/m2)

106. Case 28**6: 1st Plan upto 39.6 Gy/18 Fx’s

107. Case 28**6: 1st Plan upto 39.6 Gy/18 Fx’s
28.6 Gy/13 Fx’s

108. Case 28**6: 2nd Plan upto 66 Gy/30 Fx’s

109. Case 28**6: 2nd Plan upto 66 Gy/30 Fx’s

110. Case 28**6: 1st vs 2nd Target Volumes

111. ’09-Aug ’09-Dec ’13-Fev
Pre-RT 4M 3Y 6M

112. ’09-Aug ’09-Dec ’13-Fev
Pre-RT 4M 3Y 6M
Q: How R U doing?
A: “Doing fine!”

113. Comparison of Dose Schedules at SMC
3D RT TomoTherapy
Main concept Serial shrinking field Dose painting
Subclinical
disease
36 Gy/18 Fx’s 36 Gy/18 Fx’s 36 Gy/18 Fx’s
Equivocal lesion 54 Gy/27 Fx’s
60~63.6 Gy/Fx’s
(2*30 or 2.2*18 + 2*12)
Definite lesion 70 Gy/35 Fx’s
66 Gy/30 Fx’s
(2.2*30)
69.4 Gy/30 Fx’s
(2.2*18 + 2.4*12)
Number plans 3 times 2 times
Duration 7 weeks 6 weeks

114. Has It Worked Well?

115. Finished proof reading a week ago.
And will show up on Head and Neck soon!

116. Radiation Therapy
• 3D-CRT (7 weeks):
– 70 Gy/35 Fx’s in 35 patients
• Helical Tomotherapy (6 weeks):
– 66 Gy/30 Fx’s (2.2 Gy*30 Fx’s) in 14 patients
– 68.4 Gy/30 Fx’s (2.2 Gy*18 Fx’s + 2.4 Gy*12 Fx’s)
in 10 patients
• Routine adaptive re-plan during RT:
– 2nd CT simulation after median 15 (12–17) Fx’s

117. Treatment Outcomes
• Median F/U = 41.3 (9.3–73.5) months
• Response rate = 96.6%:
– CR 32 (54.2%)/PR in 25 (42.4%)/SD in 1 (1.7%)/PD in 1 (1.7%)
• 6 deaths (including 1 intercurrent death)
• 10 treatment failures
5
3 2
Regional
Local
Distant
At 1 year At 3 years
PFS 89.8% 82.7%
LC 91.5% 86.2%
OS 92.7%

118. LRRFS PFS vs TVRR

119. Clinical Implications
• TVRR during adaptive RT has prognostic value!
• It may serve as predictor that enable individualized
therapeutic modification during RT:
– Escalation of total radiation dose
– Intensification of chemotherapy during and/or after
planned RT
– Early implementation of surgical salvage

120. Summary?
or
Confusion?

121. Definition of Anatomic Subsites
• Neither clear demarcation line nor landmark
structure is used:
– No septum, capsule, fascia, mesothelial lining.
– Anatomic boudaries are mostly arbitrarily chosen
visual landmarks for physicians’ convenience.
• Overriding and/or skipped lesions are very
frequent.

122. Extent of Local Treatment
• One should understand Dx modality:
– Principles of image acquisition and interpretation
– Image resolution
– False (+)/(-), (+)/(-) predictive value, overall accuracy
• Extent of local Tx should depend on integrated
information:
– Physical findings: inspection, palpation, function test
– Imaging findings: CT, MR, PET/CT, USG

123. Understand Various Uncertainties!
• Simulation:
– Posture, mouth opening, neck extension
– Immobilization device
– Contrast enhancement
– Slice interval, thickness, region of interest
– Available reference images (CT, MR, PET, USG)
– Image co-registration (MR, PET)
• Q: Are Dx CT and sim CT images are the same?
• A: Never!

124. Understand Various Uncertainties!
• All that is yellow is not always gold!
– Too many noises interfering contrast enhancement
– SUV = specific uptake value or silly useless value?
• Great degree of variations:
– Inter-personal (사람마다 달라요~~~)
– Intra-personal (그때 그때 달라요~~~)
• Why & how to put margins?

125. Motion Monitoring During Tomotherapy
왜 이러는 걸까요?
Motion overlap

126. Develop Your Own Protocol
• Target delineation is game of probability:
– P of oncologist (range) vs P of patient (all or none).
– Everything is possible!
– Nothing is impossible!
• First refer to existing guidelines, protocols,
policies, experienced seniors, expert opinions…
• Practice game of trade-off:
– Local cure vs complication, cost, time.
• Develop reasonable and consistent protocol!

127. 論語 爲政 15章
• 學而不思則罔 (학이불사즉망)
– 학문을 닦아도 마음에 생각하는 바가 없으면
사물의 이치를 환히 깨닫지 못함.
• 思而不學則殆 (사이불학즉태)
– 생각만 하고 더 배우지 않으면 독단에 빠져 위
태롭게 됨.
• 배우면 생각하고, 생각하며 일하라.

128. Baseline understanding
Principle development
Exercise & Practice
Re-evaluation
Study Think

129. Study Think
Baseline understanding
Exercise & Practice
Re-evaluation
Principle development
Updated understanding
Principle modification
Evidence-based Evidence-making

133. Therapeutic Ratio
% tumor control by therapy A vs therapy B
Therapeutic Gain Factor (TGF) =
% complications by therapy A vs therapy B

134. Often times, it is very difficult to tell
where the seashore exactly is…

135. Any Questions?
Feel free to e-mail me at
ahnyc@skku.edu
ycahn.ahn@samsung.com
yber55@naver.com
yber55@gmail.com