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Target Delineation in Oropharynx Cancer
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
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.
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
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
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
29.
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
32.
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
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
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.
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.
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
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
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%
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
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?
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.