Cavidad Oral Radioterapia

Head and Neck Cancers
5
Gokhan Ozyigit, Murat Beyzadeoglu, and Cuneyt Ebruli
Head and neck cancers constitute approximately 10% of all cancers [1]. They are
named according their location and subsite in the head or neck. Head and neck cancers
are essentially seen in older patients (50–70 years), but they can also be seen in chil-
dren, and they are more common in males than females. Certain types are more fre-
quently observed in certain geographic regions (e.g., nasopharyngeal cancer in Far East
Asia). Smoking and alcohol use have a very close association with head and neck can-
cers. Chewing tobacco and tobacco-like substances also increase the risk of oral cavity
cancers [2].
Genetic tendency is another important risk factor. A previous history of head or neck
cancer as well as a history of cancer in first-degree family members is also a risk factor.
Head and neck cancers can be seen simultaneously or metachronously in multiple loca-
tions in the same person. Exposure to radiation, as well as to sun (ultraviolet radiation), is
closely related to the risk of head and neck cancer [3]. Exposure to radiation can occur in
various ways, such as through previous radiotherapy in the head and neck region, or radio-
active contamination from nuclear reactor accidents (e.g., Chernobyl) or nuclear weapons
(e.g., Hiroshima and Nagasaki).
Nutritional disorders and vitamin deficiencies are other risk factors. Bad nutritional
habits and iron deficiency anemia in particularly women may cause these types of
cancers [4]. Poor oral hygiene, use of inappropriate prostheses, chronic infections,
gastroesophageal reflux, and particular viral infections (EBV, HPV) are additional risk
factors [5].
The head and neck region has a rich lymphatic network (Table 5.1). This network is
divided into sublevels for the purposes of neck dissection or neck radiotherapy
(Fig. 5.1). Each site-specific cancer has also its specific route for lymph node metasta-
sis (Fig. 5.2).
M. Beyzadeoglu et al. Basic Radiation Oncology, 205

DOI: 10.1007/978-3-642-11666-7_5, © Springer-Verlag Berlin Heidelberg 2010
206 5 Head and Neck Cancers
Table 5.1 Head and neck lymphatics

Level Lymphatics
Ia Submental lymphatics
Ib Submandibular lymphatics
II Upper jugular lymph nodes
III Mid-jugular lymph nodes
IV Lower jugular lymph nodes
(transverse cervical)
V Spinal accessory chain lymph nodes
(posterior triangle)
VI Prelaryngeal, pretracheal,
paratracheal lymph nodes
Fig. 5.1 Lymphatic levels of neck

for head and neck cancers
Head and Neck Cancers 207
Lower lip, floor of mouth,

lower gum 1a
Face, nose, paranasal
sinuses, oral cavity, 1b
Submandibular submandibular gland
Anterior scalp,
forehead, parotid
Jugulodigastric Oral cavity, oropharynx,
(upper jugular) nasopharynx,
2
hypopharynx,
supraglottic larynx
Delphian node (larynx) 6
Spinal
accessory chain Thyroid, larynx, hypopharynx,
cervical esophagus 3
Jugulo-omohyoid
(mid-jugular)
Nasopharynx, thyroid,
Transverse
esophagus, lung, breast 5
cervical
Supraclavicular
(lower jugular)
7
Tracheoesophageal Nasopharynx, thyroid,
groove esophagus, lung, breast 4
Fig. 5.2 Route of lymphatic involvement for head and neck cancers (from [6], p 18, Fig. 2.1, repro-
duced with the permission from Springer Science and Business Media)
Over 30% of all head–neck cancer cases show clinical lymph node positivity
(Table 5.2) [9]:
• Pharyngeal wall cancer: 50%

• Pyriform sinus cancer: 49%
• Supraglottic laryngeal cancer: 39%
Head–neck cancers with clinical neck lymph node (−) but pathological lymph node (+)
(Table 5.2) [9]:
• Pyriform sinus cancer: 59%

• Pharyngeal wall cancer: 37%
• Tongue cancer: 33%
• Supraglottic laryngeal cancer: 26%
• Floor of mouth cancer: 21%
• Glottic laryngeal cancer: 15%
Table 5.2 Lymphatic involvement ratios in various head–neck cancers (%) [8]

Region Level I Level II Level III Level IV Level V RPLN
N− N + N− N + N− N + N− N + N− N + N− N +
Nasopharynx 40 86
Tongue 14 39 19 73 16 27 3 11 0 0 – –
Base of tongue 4 19 30 89 22 22 7 10 0 18 0 6
Retromolar 25 38 19 84 6 25 5 10 1 4 – –
trigone
Tonsil 0 8 19 74 14 31 9 14 5 12 4 12
Pharyngeal wall 0 11 9 84 18 72 0 40 0 20 16 21
Pyriform sinus 0 2 15 77 8 57 0 23 0 22 0 9
Supraglottic 6 2 18 70 18 48 9 17 2 16 0 4
larynx
Glottic larynx 0 9 21 42 29 71 7 24 7 2 –
RPLN retropharyngeal lymph nodes
a b c d
Retropharyngeal Nodes Level Ib

Level V
Level II Level Ia
e f g
Level III Level VI Level IV
Fig. 5.3 Consensus guidelines for the delineation of N0 (elective) neck nodes [7]
h i
Level V Level VI
Fig. 5.3 (continued)
The RTOG/EORTC group has published a consensus document on the determination

and delineation of N0 neck nodes for conformal radiotherapy of head and neck cancers
(Fig. 5.3) [7].
Outer table
Frontal sinus Dipolë
Inner table
Anterior clinoid
process
Sphenoidal sinus
Vasal imprints
Floor of sella turcica
Lambdoid suture
Anterior nasal spine External occipital
protuberance
Hard palate
Posterior clinoid
process
Fig. 5.4 Bony markers useful for the determination of conventional radiotherapy portals
One anterior and two lateral fields are usually used in conventional radiotherapy of
head–neck cancers.
• orthogonal planning.
Several bony markers are used to determine the radiotherapy portal in conventional
planning (Fig. 5.4).
There is a risk of hot spots or cold spots in the abutment region between these fields.
Two main methods are used to decrease this probability:
1. Divergence adjustment technique. This is based on couch rotation or changing the
collimator angle.
(continued)
(continued)
• Divergence is prevented at the abutment of the lateral and anterior fields by modify-
ing the couch rotation angle and/or collimator angle as the lateral fields are planned.
• The couch and/or collimator angle usually varies between 2 and 4° (Fig. 5.5).
SCFfield length
Collimator angle = arctangent (5.1)
2 ´ SSD

SCF field length
Couch rotation angle = arctangent (5.2)
2 ´ SAD
a b
q
Couch
Couch
rotation (-)
rotation (+)
Collimator angle q
Couch rotation angle
Fig. 5.5 Collimator and couch angles
2. Half-block/asymmetrical collimator use (Fig. 5.6).
• An asymmetrical collimator is a component of a linac that allows secondary colli-

mators move independently of each other. Thus, asymmetrical fields can be created.
The beam divergence problem is totally eliminated with this simple and easy-to-use
technique.
• A half-block shuts out half of the beam from the center so that lateral beams and
anterior supraclavicular fields do not abut.
Symmetrical collimation Asymmetrical collimation
Half Block Half Block
Fig. 5.6 (a) Asymmetrical collimation technique; (b) half-beam cutter
Practically, a 3–5 mm gap is left between the anterior and supraclavicular fields to pre-
vent hot and cold spots. However, dose the distribution should be checked, since this
gap interval may change according to photon energy.
• The utilization of such a gap on involved lymph nodes or stoma is not

recommended.
5.1
Pharyngeal Cancers
The superior border of the pharynx is the cranial base (the base of the sphenoid sinus), and
it extends inferiorly to the cricopharyngeal sphincter, becoming thinner as it goes down. It
is located between the C1 and C6 vertebrae, and is 12–13 cm long in adults. It has a mus-
cular structure, and is covered with mucosa [10].
Soft Nasopharynx
palate Tonsillar fossa
Tonsil
Base of Tonsillar pillar
tongue Lateral wall of
oropharynx Oropharynx
Epiglottis
Hypopharynx
Fig. 5.7 Subsites of the pharyngeal region (from [11], p 28, Fig. 4.1, reproduced with the permis-
sion from the American Joint Committee on Cancer)
Subsites of the Pharyngeal Region (Fig. 5.7)
Superior part that is continuous with the nasal cavity: nasopharynx or epipharynx.
Middle part that is continuous with the oral cavity: oropharynx or mesopharynx.
Inferior part that is continuous with the larynx: laryngopharynx or hypopharynx.
5.1 Pharyngeal Cancers 213
5.1.1
Nasopharyngeal Cancer
The nasopharynx extends from the cranial base to the soft palate, and is continuous with
the nasal cavity via the choanae anteriorly (Fig. 5.8).
Sinus frontalis
Os nasale
Septum nasi Sinus sphenoidalis
Processus lateralis der Processus posterior der
Cartilago septi nasi
Cartilago septi nasi
Choane
Crus mediale der
Cartilago alaris major Pars nasalis pharyngis
= Epipharynx = Nasopharynx
Organon vomeronasale Lamina horizontalis des
= Jacobson’sches Organ Os palatinum
Canalis incisivus Processus palatinus
der Maxilla
Fig. 5.8 Nasopharyngeal anatomy
Normal Anatomical Structures in the Nasopharynx [10]
Base of sphenoid sinus and cranial base superiorly

Nasal cavity and choanae superior–anteriorly
Pharyngeal side of soft palate inferior–anteriorly
Laterally: ostium of eustachian tubes, tubal tonsils (Gerlach tonsils)
5.1.1.1
Pathology
Recent studies have shown that the histological subtype of nasopharyngeal cancer is an
important prognostic factor. The WHO classification is the most widely used histopatho-
logical classification system. This system essentially differentiates between tumors that do
or do not produce keratin. Although the WHO classification is practical and simple, it does
not give detailed information on the cell type and degree of anaplasia. Therefore, this sys-
tem is considered inadequate to determine prognosis in regions where nasopharyngeal
cancer is endemic. The use of Hsu’s histopathological classification is recommended to
compensate for these inadequacies. Another system is the Cologne system, which divides
the nonkeratinized tumors into subgroups based on the presence of lymphoid infiltration,
which is frequently seen together with nasopharyngeal cancers [12].
WHO Classification, 1978 [12]

WHO Type 1: keratinized squamous cell cancer.
WHO Type 2: nonkeratinized carcinoma.
WHO Type 3: undifferentiated carcinoma.
Cologne system, 1981
Nonkeratinized carcinoma Lymphoid infiltration (+)
Lymphoid infiltration (−)
Undifferentiated carcinoma Lymphoid infiltration (+)
Lymphoid infiltration (−)
Keratinized squamous cell carcinoma – WHO Type I: seen in older patients, less fre-
quently associated with EBV, and has the best prognosis (represents 20% of all nasopha-
ryngeal cancer cases).
Nonkeratinized tumors: includes most nasopharyngeal cancers.
• Nonkeratinized carcinoma – WHO Type II (30–40%)

• Undifferentiated carcinoma – WHO Type III (40–50%)
Undifferentiated carcinoma = lymphoepithelioma
5.1.1.2
General Presentation
Symptoms appear to be related to the localization and extent of the tumor. These symp-
toms can be grouped into four classes [13]:
1. Nasal and nasopharyngeal symptoms are seen as a result of nasopharyngeal localization

and tumor extension into the nasal cavity anteriorly. These symptoms are nasal obstruc-
tion and nasal bleeding.
2. Otological symptoms are due to the entrance to an Eustachian tube becoming filled and
obstructed. These are the symptoms and findings of serous otitis media: hearing loss,
tinnitus, and otophonia.
3. Cervical symptoms are neck lymph node metastases that are the extension of the
nasopharyngeal cancer into first the parapharyngeal and retropharyngeal lymph nodes
and then the jugular and spinal accessory chain. Fifty percent of patients have bilateral
while 80–90% have bilateral neck metastases at presentation. Neck mass is the first sign
in 40% of cases.
4. Ophthalmoneurological symptoms are observed due to the extension of the tumor into
the cranial base and then into the foramen lacerum, various other foramens and fissures,
and the cranial nerves. Dry eye due to the invasion of the greater superficial petrosal
nerve; hypo- or hyperesthesia in the face due to the invasion of the trigeminal nerve;
and ophthalmoplegia and diplopia due to extension into the cavernous sinus and supe-
rior orbital fissure, resulting in III, IV, and VI cranial nerve invasion, are all important
findings. Parapharyngeal lymphatic involvement or extensive invasion of the lower cra-
nial nerves (IX, X, XI, and XII) causes nasolali, aspiration, stridor, shoulder pain, motor
weakness, and speaking disorders. Horner’s syndrome may develop as a result of inva-
sion of the cervical sympathetic chain located around large vessels.
5.1.1.3
Staging
T staging (Fig. 5.9) [14]
TX: Primary tumor cannot be assessed

T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1: Tumor confined to the nasopharynx, or extends to the oropharynx and/or nasal cav-
ity without parapharyngeal extension*
T2: Tumor with parapharyngeal extension*
T3: Tumor invades bony structures and/or paranasal sinuses
T4: Tumor with intracranial extension and/or involvement of cranial nerves, infratem-
poral fossa, hypopharynx, orbit, or masticator space
*Parapharyngeal extension denotes posterolateral infiltration of tumor
T1 T2 T2a T2b
Intracranial T4
T3 T4
extension
Cranial
nerves
Fig. 5.9 T staging for nasopharyngeal cancers (from [11], reproduced with the permission from the
American Joint Committee on Cancer)
N Staging (Fig. 5.10)
N0: No regional lymph node metastasis

N1: Unilateral metastasis in lymph node(s), not more than 6 cm in greatest dimen-
sion, above the supraclavicular fossa, retropharyngeal lymph nodes, 6 cm or less
in greatest dimension (Midline nodes are considered ipsilateral nodes)
N2: Bilateral metastasis in lymph node(s), not more than 6 cm in greatest dimension,
above the supraclavicular fossa
N3: Metastasis in a lymph node(s) larger than 6 cm and/or to supraclavicular fossa
N3a: Larger than 6 cm
N3b: Extension to the supraclavicular fossa
N1 N2 N3
N3a
>6 cm
≤6 cm ≤6 cm
N3b
Fig. 5.10 N staging for nasopharyngeal cancers (from [11], reproduced with the permission from
the American Joint Committee on Cancer)
AJCC Stage Groups
Stage 0: TisN0M0
Stage I: T1N0M0
Stage II: T1N1M0, T2N0M0 T2N1M0,
Stage III: T1N2M0, T2N2M0, T3N0M0, T3N1M0, T3N2M0
Stage IVA: T4N0M0, T4N1M0, T4N2M0
Stage IVB: Any T, N3M0
Stage IVC: Any T, Any N, M1
Gadolinium MRI is superior to CT in the differentiation of tumor and normal tissue. Its
disadvantage is its high artifact ratio.
The most important prognostic factor in nasopharyngeal cancer is nodal status (N)
followed by T stage (Fig. 5.11) [15]:
N0 → 17% distant metastasis (+).
N3 → 78% distant metastasis (+).
Distant metastasis is very rare, and the most frequent sites of distant metastasis are
the lungs, bones and liver.
I (17 %)
(17%) II (94 %)
III (85 %)
Va (46 %)
IV (19 %) Vb (17 %)
Fig. 5.11 Neck node metastasis

ratio for nasopharyngeal cancers Supraclavicular field
Five-year survival in nasopharyngeal cancer is 35–50%.

Stage I–II → 70–80%, relapse-free survival (RFS) 75–90%
Stage III–IV → 10–40%, RFS ~50%
5.1.1.4
Treatment Algorithm
The treatment algorithm for nasopharyngeal cancers is summarized in Fig. 5.12 [16].

T1N0 T1-2aN123
M1
T2aN0 T2b-4N0123
Cisplatin 100mg/m2
≥70 Gy (1,22,43.days) Chemotheraphy
(platinum-based)
(to primary tumor) +
≥70 Gy
(to primary tumor and
metastatic neck
lymphatics) Complete response
[50 Gy
(all neck lymphatics)]
Cisplatin 80 mg/m2,
5-FU 1000 mg/m2 (96-hr
infusion )
(q4w x 3 cycles)
(Neck: Complete response) (Neck: Partial response)
OBSERVATION NECK DISSECTION
Fig. 5.12 Treatment algorithm for nasopharyngeal cancers [16]
Surgery does not play a major role in the management of nasopharyngeal cancer, except
when diagnostic biopsies and neck dissections are performed in certain circumstances.
5.1.1.5
Radiotherapy
Conventional orthogonal irradiation (two lateral fields, one anterior supraclavicular

field) (Fig. 5.13).
Borders of lateral fields (primary tumor + upper neck).

Superior: cranial base including sphenoid sinus.
Inferior: true vocal cords (to spare larynx).
Posterior: spinous processes of vertebrae.
Anterior: 2–3 cm margin to tumor including pterygoid plate and posterior one-third
of maxillary sinus.
• If supraclavicular LN (+),the upper mediastinal lymph nodes are covered by the

anterior field by lowering the inferior border.
Fig. 5.13 Nasopharyngeal lateral RT field (from

[17], p 460, Fig. 18c, reproduced with the
permission from Springer Science and Business
Media)
Supraclavicular field (Fig. 5.14). Superior border; inferior border of lateral fields if

collimator or couch angle is given to lateral fields. 0.3–0.5 cm gap if no angle is given.
Inferior border: bottom of sternoclavicular joint; lateral border: includes two-thirds of
the clavicula.
Fig. 5.14 Simulation films for lateral and anterior SCF fields for nasopharyngeal cancer
Conformal RT Fields (Fig. 5.15) [18]
GTV: gross disease.

CTV1: nasopharynx, sphenoid sinus, cavernous sinus, cranial base, anterior half of
nasal cavity, posterior third of maxillary sinus, posterior of ethmoid sinus, pterygoid
fossa, side and lateral pharyngeal walls at midtonsillar fossa level, and retropharyngeal
lymph nodes.
CTV2: elective nodal regions (II, III, IV, V, and supraclavicular lymph nodes).
Radiotherapy Dose
• Parallel opposed fields 2 Gy/day 46 Gy, 6 MeV X-ray or Co-60, then give 50 Gy
after sparing spinal cord. Posterior neck dose is completed to 50 Gy with suitable
electron energy.
• After 50 Gy, remaining 20 Gy dose is given to (primary tumor + 2 cm) (total dose to
primary is 70 Gy).
• Elective neck dose (N0 neck) is 50 Gy.
• Lymph node <3 cm: total lymph dose is 66 Gy.
• Lymph node >6 cm: total lymph dose is 70 Gy.
• Anterior field (supraclavicular field) dose is 50 Gy.
a b
c
Fig. 5.15 Conformal radiotherapy fields for nasopharyngeal cancer
Table 5.3 TD5/5 doses to critical organs in head and neck radiotherapy

Organ Single fraction Conventional fractionation
Brain 15–25 60–70
Lens 2–10 6–12
Skin 15–20 50–60
Spinal cord 8–10 46–50
VCTS 10–20 50–60
Mucosa 5–20 65–77
Peripheral nerve 15–20 65–77
(continued)
Table 5.3 (continued)
Organ Single fraction Conventional fractionation
Muscle >30 >70
Bone–cartilage >30 >70
Thyroid – 30–40
Optic pathways 8–10 55–60
VCTS vascular connective tissue system
Modified from [54]
Side Effects Related to Radiotherapy (Table 5.3)
Skin → early period: hyperemia, dry desquamation, wet desquamation, and ulceration;
late period: telangiectasia, fibrosis, and tissue necrosis.
Hair → alopecia starts after seven days (temporary until 7 Gy, permanent >7 Gy).
Mucosa → erythema, edema, patchy mucositis, and confluent mucositis (mucositis
starts after >3 Gy).
Esophagus → early period: retrosternal pain due to esophagitis (10–12 days). This
heals in 1–2 weeks. Late effects: muscular and epithelial changes, fibrosis, ulceration,
and swallowing difficulty.
Salivary gland → decrease in saliva starts in 24 h, and its viscosity decreases. pH
becomes acidic, bicarbonate and IgA levels decrease. If irradiated volume of salivary
gland is more than 50%, marked xerostomia is seen.
5.1.1.6
Selected Publications
Radiotherapy alone
RTOG, 1980 → complete response 96% for T1, 88% for T2, 81% for T3, 74% for T4. N
(+) → 5-year survival 71–93%.
Marcial VA et al (1980) Split-course radiation therapy of carcinoma of the nasophar-
ynx: results of a national collaborative clinical trial of the Radiation Therapy Oncology
Group. Int J Radiat Oncol Biol Phys. 6(4):409–14
Yeh sa et al., 2005 → 849 cases. Five-year survival 59%, 5-year disease-free survival 52%.
Yeh SA et al (2005) Treatment outcomes and late complications of 849 patients with
nasopharyngeal carcinoma treated with radiotherapy alone. Int J Radiat Oncol Biol Phys.
62(3):672–9
Altered fractionation
Wang et al., 1989 → nonrandomized. Accelerated hyperfractionation (twice daily). Five-
year local control in T1–2 tumors: 89% in hyperfractionation arm, 55% in conventional
arm. Five-year local control in T3–4 tumors: 77% in hyperfractionation arm, 45% in con-
ventional arm.
Wang CC (1989) Accelerated hyperfractionation radiation therapy for carcinoma of the
nasopharynx. Techniques and results. Cancer. 63(12):2461–7
Chemoradiotherapy
VUMCA I trial—International Nasopharynx Cancer Study Group 1996 → randomized. 339
cases. N2–3 and undifferentiated (WHO II–III) histology (70 Gy RT alone) vs. neoadjuvant
three cycles CT + concurrent chemoradiotherapy (BEC in every 3 weeks). Two-year disease-
free survival: 60% in chemoradiotherapy arm vs. 40% in RT alone arm. No difference in OS.
International Nasopharynx Cancer Study Group: Vumca I. Trial. Preliminary results of
a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomy-
cin) plus radiotherapy vs. radiotherapy alone in stage IV (≥N2, M0) undifferentiated
nasopharyngeal carcinoma: A positive effect on progression-free survival. Int J Radiat
Oncol Biol Phys. 1996 Jun 1;35(3):463–9.
RTOG 88-17/Intergroup 0099 (Al Sarraf et al.) → The most important randomized trial
showing the survival benefit of chemoradiotherapy. 147 cases. Median follow-up 2.7 years.
Three-year progression-free survival: 69% (RT + cisplatin arm) vs. 24% (RT-alone arm).
Three-year overall survival: 78% (chemoradiotherapy arm) vs. 47% (RT-alone arm).
Al-Sarraf M et al (1998) Chemoradiotherapy versus radiotherapy in patients with
advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin
Oncol. 16(4):1310–1317
Meta-analysis 2002 → six trials. 1,528 cases. Chemotherapy was used concurrently in
only one trial (Al Sarraf et al.). Chemotherapy: 25–40% increase in disease- or progres-
sion-free survival and 20% increase in OS. Significant survival increase was only observed
in concomitant chemoradiotherapy.
Huncharek M et al (2002) Combined Chemoradiation Versus Radiation Therapy Alone
in Locally Advanced Nasopharyngeal Carcinoma: Results of a Meta-analysis of 1,528
Patients From Six Randomized Trials. Am J Clin Oncol. 25(3):219–223
IMRT
UCSF, 2002 → 67 patients with nasopharyngeal cancer. 65–70 Gy to GTV, 60 Gy to CTV,
50–60 Gy to negative neck RT. 1.8 Gy/fraction CTV and neck; 2.12–2.25 Gy/fraction
GTV. CTV = nasopharynx, posterior one-third of nasal cavity and maxillary sinus, retro-
pharyngeal lymph node, clivus, base of cranium, pterygoid fossa, parapharyngeal space,
and inferior sphenoid sinus. Median follow-up: 31 months.
• One local recurrence at the primary site. One patient failed in the neck. Seventeen
patients developed distant metastases; five of these patients have died.
• Four-year local progression-free, locoregional progression-free, and distant metastasis-free
rates were 97, 98, and 66%, respectively. The 4-year estimate for overall survival was 88%.
• Excellent locoregional control for NPC was achieved with IMRT.
Lee N et al (2002) Intensity-modulated radiotherapy in the treatment of nasopharyngeal
carcinoma: an update of the UCSF experience. Int J Radiat Oncol Biol Phys.
53(1):12–22
Hong Kong, 2007 → randomized. 60 cases of T1–2bN0 nasopharyngeal cancer. IMRT 66 Gy
(CTV = GTV + 1 cm; PTV = CTV + 3 mm)/lower neck LN (+) 66 Gy, LN (−) 54–60 Gy/intrac-
avitary brachytherapy boost vs. 66 Gy conventional RT + intracavitary brachytherapy boost.
Serious xerostomia: IMRT 39% vs. 2D-RT 82%. No difference in the feeling of xerostomia.
Wu SX et al Outcome of Fractionated Stereotactic Radiotherapy for 90 Patients With
Locally Persistent and Recurrent Nasopharyngeal Carcinoma. Int J Radiat Oncol Biol
Phys 69(3): 761–769
Reirradiation
Guangzhou et al. 2007 → retrospective. 90 cases [persistent (n = 34) or recurrent (n = 56)]
of stereotaxic RT. Three-year progression-free survival: 55%. Late complications: 19%;
fatal hemorrhage: two cases. Stereotaxic RT is more efficient and safe than stereotaxic
radiosurgery.
5.1.2
Oropharyngeal Cancer
The oropharynx starts from the soft palate and extends to the superior portion of the epi-
glottis (Fig. 5.16) [19].
Posterior Posterior
pharyngeal wall pharyngeal wall
Vallecula Epiglottis
Tonsillar pillar
Tonsillar fossa
Tonsil Base of tongue
Tonsillar fossa
Tonsillar pillar
Fig. 5.16 Normal anatomical

structures of the oropharnynx
(from [11], reproduced with
the permission from the
American Joint Committee
on Cancer)
Normal anatomical structures of the oropharynx (Fig. 5.17) [19]:

Anterior: oral cavity
Anterior–superior: front side of soft palate
Mid-anterior: isthmus faucium and oral cavity
Lower-anterior: base of tongue and vallecula
Lateral: palatine tonsils
Posterior: posterior pharyngeal wall and prevertebral fascia of C2–3 vertebrae
Regions of the oropharynx in which malignancies may develop [19]:
Posterior one-third of tongue (base of tongue)
Lingual site of epiglottis, vallecula
Soft palate and uvula
Tonsils and tonsil plicae
Mucosa of posterior oropharyngeal wall
Fig. 5.17 Normal anatomical structures of the

oropharynx
5.1.2.1
Pathology
Most oropharyngeal tumors are squamous cell cancers, although other types like lym-
phoma and minor salivary glands may also be observed.
Squamous cell cancer: 75%

Lymphoma: 15%
Lymphoepithelioma: 5%
Others: 5% (minor salivary gland cancer, sarcoma)
Squamous cell cancer is particularly seen in older men. However, the male/female ratio
has decreased to 4:1. Smoking with the use of alcohol leads to a very high risk for oropha-
ryngeal cancers [20].
5.1.2.2
The first symptom is usually unilateral, progressive otalgia, and dysphagia with throat dis-
comfort. Most patients have a feeling of a mass in throat posteriorly. Lymph node metastasis
at presentation is frequent. Thus, neck mass may be the first symptom at presentation. The
risk of bilateral neck node metastases is very high, especially in base of tongue cancers. In
more advanced cases, dysfunctions in swallowing and speaking abilities, oral fetor, bleeding,
hemoptysis, fixed tongue, trismus, and weight loss may be seen. The tumor is usually ulcer-
ated in a routine physical exam, and unilateral tonsil enlargement may be observed. Therefore,
unilateral tonsil hypertrophy in older patients should be examined for possible malignancy.
Indirect laryngoscopy with a mirror should be performed to see the base of the tongue
and vallecula. A tumor in this region may easily invade the surrounding soft tissues and
present at more advanced stages. However, the actual size of the tumor is determined by
bimanual palpation and advanced imaging modalities (MRI, CT). Mandibular invasion is
also detected via radiological techniques. The risk of distant metastasis is a bit higher than
that for the oral cavity. Furthermore, the presence of a secondary malignancy or later devel-
opment in the upper or lower airways is also higher. Thus, the patient should be evaluated
and followed up for this possibility. The final and exact diagnosis is made via biopsy.
Etiology → cigarette smoking, alcohol, chronic irritation, and HPV 16 [21]
5.1.2.3
Staging
Primary Tumor (T) (Fig. 5.18) [14]

T1: Tumor 2 cm or smaller in greatest dimension
T2: Tumor larger than 2 cm but 4 cm or smaller in greatest dimension
T3: Tumor larger than 4 cm in greatest dimension or extension to lingual surface of
epiglottis
T4a: Moderately advanced local disease: Tumor invades the larynx, deep/extrinsic
muscle of tongue, medial pterygoid, hard palate, or mandible
T4b: Very advanced local disease: Tumor invades lateral pterygoid muscle, pterygoid
plates, lateral nasopharynx, or skull base or encases carotid artery
T1 T2 T3
£ 2 cm
>4 cm
2-4 cm
T4a T4b
Submucosal extension
to pterygoid fossa
Fig. 5.18 T staging in oropharyngeal cancer (from [11], reproduced with the permission from the
AJCC stage groups

Stage 0: TisN0M0
Stage I: T1N0M0
Stage II: T2N0M0
Stage III: T3N0M0, T1N1M0, T2N1M0, T3N1M0
Stage IVA: T4aN0M0, T4aN1M0, T1N2M0, T2N2M0, T3N2M0, T4aN2M0
Stage IVB: T4b, any N, M0; any T, N3M0
Stage IVC: any T, any N, M1
5.1.2.4
Treatment Algorithm
Treatment Algorithm for Oropharyngeal Cancer [16]
T1,2–N0,1 → three alternative approaches:

Definitive radiotherapy
In case of residual disease after RT → salvage surgery
Primary tumor excision + uni/bilateral neck dissection
One lymph node (+), poor prognostic factor (−) → RT
Poor prognostic factor (+):
One or two major risk factors or ³2 minor risk factors (+) → chemoradiotherapy
Less than two minor risk factors (+) → RT
T1–2 N1 tumors → RT + CT
T3,4a– N0 → three alternative approaches
Concurrent chemoradiotherapy
WPoor prognostic factor (+)
Induction chemotherapy followed by chemoradiotherapy
T3,4a– N or any T and N2,3 → three alternative approaches
Complete response in primary after chemo-RT → neck dissection
Residual disease in primary after chemo-RT
Salvage surgery + neck dissection
(continued)
(continued)
Residual disease in neck after chemo-RT

N1 → surveillance
N2, N3 → surveillance or neck dissection
Induction chemotherapy followed by chemoradiotherapy
Complete response in primary after chemo-RT → neck dissection
Residual disease in primary after chemo-RT
Residual disease in neck after chemo-RT
N1→ surveillance
N1, N2a, N2b, N2c. N3 → RT and/or CT
Poor prognostic factors
• Major risk factors (postoperative chemo-RT indications):

Surgical margin positivity and/or extracapsular nodal extension
• Minor risk factors (postoperative RT alone indications):
pT3, pT4
N2, N3
IV and V lymphatic involvement
Vascular embolism
5.1.2.5
Radiotherapy
Conventional Orthogonal Radiotherapy Fields (Fig. 5.19)
Two parallel–opposed lateral fields and supraclavicular anterior field

Borders of lateral fields (primary tumor + upper neck) (Fig. 5.20)
Superior: cranial base
Inferior: whole neck by pulling shoulders as far down as possible
Posterior: spinous processes of vertebrae
Anterior: 2–3 cm margin to tumor
• Anterior and superior borders should be modified by the clinician according to

tumor localization (e.g., base of tongue, tonsil, vallecula) and tumor size.
Fig. 5.19 Lateral RT fields for oropharyngeal cancer (from [17], p 459, 460, Figs. 18.6, 18.7, repro-
duced with the permission from Springer Science and Business Media)
Fig. 5.20 Conventional RT films for oropharyngeal cancer

Dose
Parallel–opposed fields until 46 Gy in 2 Gy/day by 6 MeV X-rays or Co-60. Then 4 Gy
with spinal cord sparing. Four grays to protected posterior neck using adequate electron
energies.
• After 50 Gy (primary tumor + 2 cm), 66–72 Gy.

• If N (−), elective neck dose is 50 Gy.
• Lymph node <3 cm, 60 Gy.
• Lymph node >6 cm, 66–72 Gy.
5.1.2.6
See also Sect. 5.8

Base of tongue
MDACC, 2004 → retrospective. 299 cases. T1–T2 oropharyngeal tumor, stage III–IV. RT
alone. Median follow-up: 82 months. Five-year local relapse 15%, OS 64%. Locoregional
control 95% for T1, 79% for T2.
Garden AS et al (2004) Is concurrent chemoradiation the treatment of choice for all
patients with Stage III or IV head and neck carcinoma? Cancer. 100(6):1171–1178
Interstitial brachytherapy
Mass General Hospital, 2005 → 40 cases. Primary or recurrent base of tongue. 54% T3/
T4 tumor. Median implant dose 17.4 and 61 Gy external RT (equivalent total dose 80 Gy).
Five-year OS: 62%. Local control: 78%. Ten-year local control: 70%. Organ preservation
rate: 78%. Grade III osteoradionecrosis in two patients (2%).
Foote RL et al (1990) Is interstitial implantation essential for successful radiothera-
peutic treatment of base of tongue carcinoma? Int J Radiat Oncol Biol Phys. 18(6):
1293–8
Neck control
MSKCC, 1997 → 68 base of tongue tumors. 54 Gy external RT + 20–30 Gy interstitial
implant. 50 Gy neck RT (clinically (+) lymph nodes 60 Gy). Neck dissection if palpable
lymph node after RT. Five-year neck control 95%, 10-year neck control 86%. Grade III
fibrosis (−).
Lee HJ et al (1997) Long-term regional control after radiation therapy and neck dissec-
tion for base of tongue carcinoma. Int J Radiat Oncol Biol Phys. 38(5):995–1000
Tonsil
University of Florida, 2000 → retrospective. 400 cases. T1–T4, N0–N3, tonsil cancer. RT
alone. Minimum 2 years of follow-up. Five-year local control: 83% in T1, 81% in T2, 74%
in T3, 60% in T4. Local relapse in 83 cases; 36 had salvage surgery and 17 were salvaged
(nearly 50%). Grade III–IV toxicity (−). Local control was similar to surgery, and had
lower rate of fatal complications than surgery.
Mendenhall WM eta al (2000) Radiation Therapy for Squamous Cell Carcinoma of the
Tonsillar Region: A Preferred Alternative to Surgery? J Clin Oncol. (11):2219–25
Ipsilateral RT
Princess Margaret, 2001 → retrospective. 228 cases. Ipsilateral RT only. T1–2 N0 tumors.
Recurrence in contralateral neck was 3.5%. Conclusion: ipsilateral neck RT is feasible in
selected cases with unilateral tonsil cancer.
Int J Radiat Oncol Biol Phys 2001; 51(2):332–343
Hyperfractionation
EORTC 22791 → 356 cases. T2–3, N0–1 oropharyngeal cancers except base of tongue.
Tumor size <3 cm. 70 Gy/7–8 weeks vs. 80.5 Gy hyperfractionated 7 weeks (1.15 Gy
BID). Increase in local control of T3 tumors receiving hyperfractionated schedule. No
increase in local control of T2 tumors. There was a trend for increased OS.
Horiot HJ et al (1992) Hyperfractionation versus conventional fractionation in oropha-
ryngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group
of radiotherapy. Radiother Oncol. 25(4):231–241
IMRT
Washington University, 2004 → 74 oropharyngeal cancer patients treated with IMRT. 31
patients received definitive IMRT; 17 also received platinum-based chemotherapy. 43
patients received combined surgery and postoperative IMRT. Median follow-up for all
patients was 33 months.
• Ten locoregional failures were observed. Six patients died of the disease and three died
of concurrent disease. Distant metastasis developed in six patients.
• Four-year estimate of overall survival was 87%, and the 4-year estimate of disease-
free survival was 81% (66% in the definitive vs. 92% in the postoperative RT
group).
• Four-year estimate of locoregional control was 87% (78% in the definitive vs. 95% in
the postoperative RT group); the 4-year estimate of distant metastasis-free survival was
90% (84% in the definitive vs. 94% in the postoperative group).
• Multivariate analysis showed that GTV and nGTV were independent risk factors deter-
mining locoregional control and disease-free survival for definitive oropharyngeal
IMRT patients.
• IMRT was found to be an effective treatment modality for locally advanced oropharyn-
geal carcinoma.
Chao KS, Ozyigit G, Blanco AI et al (2004) Intensity-modulated radiation therapy for oropha-
ryngeal carcinoma: impact of tumor volume. Int J Radiat Oncol Biol Phys 59(1):43–50
5.1.3
Hypopharyngeal Cancer
The hypopharynx is located between the epiglottis and the bottom of the cricoid cartilage
(cricopharyngeal sphincter) (Fig. 5.21) [10].
Fig. 5.21 Hypopharynx,
oropharynx and nasophar-
ynx (from [11], reproduced
Nasopharynx
with the permission from
American Joint Committee
on Cancer)
Oropharynx
Hypopharyngeal
aspect of aryepiglottic
fold
Hypopharynx Pyriform sinus
Posterior wall of
hypopharnyx
Postcricoid
Esophagus region
Normal Anatomical Structures of the Hypopharynx (Fig. 5.22) [10]
Anterior–superior: laryngeal entrance (aditus ad laryngeum), aryepiglottic folds, and

arytenoids
Anterior–inferior: postcricoid region
Posterior: prevertebral fascia of C3–6 vertebrae
Lateral: pyriform sinuses (food is transferred into the esophagus from these sinuses)
Inferior: cervical esophagus
Fig. 5.22 Hypopharyngeal anatomy

5.1.3.1
Pathology
Almost all hypopharyngeal malignancies are squamous cell cancers, and the most frequent
is the poorly differentiated type.
The frequencies of all hypopharyngeal cancers according to subsite:

Pyriform sinuses: 60%
Postcricoid region: 30%
Posterior wall: 10%
5.1.3.2
Primary hypopharyngeal cancer, particularly pyriform sinus cancer, frequently metasta-

sizes to neck lymph nodes. Postcricoid region tumors frequently bilaterally invade neck
nodes as well as mediastinal and paratracheal lymphatics.
The major clinical findings in hypopharyngeal neoplasms are otalgia, palpable neck
nodes, dysphagia, dysphonia, and weight loss.
Actual dysphagia is a late finding where the tumor has become very advanced until it
obstructs the upper airway and digestive passages. The first signs are usually odynophagia
(pain and discomfort during swallowing) and an irritating feeling during the movement of
nutrition from the pharyngoesophagus. Dysphagia is usually severe at presentation and
almost always associated with weight loss. Reflective pain (otalgia) in the ear is common.
Dysphonia is due to either the direct invasion of the larynx or vocal cord paralysis as a
result of recurrent laryngeal nerve involvement, and dyspnea may also be seen. Fetor oris
(foul smelling breath) and hemoptysis may also be observed. Aspiration of nutrition (par-
ticularly liquids) and related aspiration pneumonia may be seen, resulting from an obstruc-
tion at the level of the hypopharynx.
Unfortunately, most cases are at an advanced stage at presentation. The risk of distant
metastasis is approximately 10%, and the most frequent sites are lung, bone and liver,
respectively.
• Posterior pharyngeal wall tumors usually drain into level II, III and IV neck nodes [9].
• Surgical findings also show that they frequently drain into the retropharyngeal
lymph nodes (Rouviere’s lymph nodes).
5.1.3.3
Staging
Primary tumor (T) (Fig. 5.23) [14].

T1: Tumor limited to one subsite* of the hypopharynx and 2 cm or less in greatest
dimension
T2: Tumor invades more than one subsite* of the hypopharynx or an adjacent site, or
measures more than 2 cm but 4 cm or less in greatest diameter without fixation of
hemilarynx
T3: Tumor measures more than 4 cm in greatest dimension or with fixation of hemilarynx
or extension to esophagus
T4a: Moderately advanced local disease: Tumor invades thyroid/cricoid cartilage,
hyoid bone, thyroid gland, or central compartment soft tissue, which includes
prelaryngeal strap muscles and subcutaneous fat
T4b: Very advanced local disease: Tumor invades prevertebral fascia, encases carotid
artery, or involves mediastinal structures
*Subsites of the hypopharynx are as follows:
Pharyngoesophageal junction (i.e., the postcricoid area), extending from the level of the
arytenoid cartilages and connecting folds to the inferior border of the cricoid cartilage.
Pyriform sinus, extending from the pharyngoepiglottic fold to the upper end of the
esophagus, bounded laterally by the thyroid cartilage and medially by the surface of the
aryepiglottic fold and the arytenoid and cricoid cartilages.
Posterior pharyngeal wall, extending from the level of the floor of the vallecula to the
level of the cricoarytenoid joints.
T1 T2 T3
£ 2 cm > 4 cm
2-4 cm
T4a
T4b
Hyoid bone
Carotid
Thyroid cartilage artery
Vertebral
Thyroid gland body
Fig. 5.23 T staging in hypopharyngeal cancer (from [11], reproduced with the permission from the
5.1.3.4
Treatment Algorithm
Treatment Algorithm for Hypopharyngeal Cancer [16]
T1 N0–1; T2N0 → total laryngectomy is not always required.

Definitive radiotherapy
Residual disease after RT → salvage surgery ± neck dissection
Residual disease in neck after RT → surveillance
Surgery (partial laryngectomy + ipsilateral/bilateral neck dissection)
Poor prognostic factor after surgery (+)
One or two major risk factor(s) or ³2 minor risk factors (+) → chemoradiotherapy
T1N2, T2–3 any N → total laryngectomy may be required.
Induction chemotherapy (two cycles of neoadjuvant chemotherapy)
Complete response in primary → definitive RT
Residual disease in primary after RT → neck dissection
Neck node residual after RT
N1 → surveillance
Partial response in primary after induction (endoscopy (+))
One more cycle of chemotherapy is added
Complete response in primary after treatment → definitive RT
Residual disease in primary after RT → neck dissection
Neck node residual after RT
N1 → surveillance
Partial response in primary after treatment → salvage surgery
Poor prognostic factor after surgery (−) → RT
No response in primary after induction → surgery
Laryngopharyngectomy uni/bilateral neck dissection
Residual disease in primary after treatment
(continued)
(continued)

Residual disease in neck after treatment
N1 → surveillance
T4a, any N →
Surgery + bilateral neck dissection
After surgery → RT and/or chemotherapy
Residual disease in primary after treatment
Residual disease in neck after treatment
N1 → surveillance
Poor prognostic factors
• Major risk factors:

Positive surgical margin and/or extracapsular nodal involvement
• Minor risk factors:
pT3, pT4
N2, N3
Level IV and V lymph node involvement
Vascular embolism
5.1.3.5
Radiotherapy
Conventional Orthogonal RT Fields
Two parallel–opposed lateral fields and supraclavicular anterior field (Fig. 5.24)

Borders of lateral fields (primary tumor + upper neck)
Superior: mastoids and cranial base, including retropharyngeal lymph nodes

Inferior: whole neck, by pulling shoulders down as much as possible (at least 1 cm
below tumor)
Posterior: spinous processes of vertebrae
Anterior: 2–3 cm anterior to tumor (Ia and Ib lymphatics are left outside if not
involved)
Retropharyngeal
lymph nodes
(Rouviere)
Pyriform sinus
Posterior wall of hypopharynx
Fig. 5.24 Conventional RT fields for hypopharyngeal cancer (from [17], pp 457–458, Figs. 18.3,
18.4, reproduced with the permission from Springer Science and Business Media)
Conformal RT Fields (Fig. 5.25) [18]
CTV1: GTV + 1–2 cm and involved lymph nodes

CTV2: elective nodal regions (determined individually by clinician)
Fig. 5.25 Conformal RT fields
Radiation Dose
• Parallel opposed fields until 46 Gy in 2 Gy/day by 6 MeV X-rays or Co-60. Then
4 Gy with spinal cord sparing. Four grays to protected posterior neck using adequate
electron energies.
• After 50 Gy, (primary tumor + 2 cm) 66–72 Gy.
• If N (−), elective neck dose is 50 Gy.
• Lymph node <3 cm, 60 Gy.
• Lymph node >6 cm, 66–72 Gy.
• Anterior supraclavicular field: 46 Gy if not involved.
• Postoperative (adjuvant) total dose 60 Gy (if surgical margin (+), 66 Gy.
5.1.3.6
See Sect. 5.8
5.2 Laryngeal Cancer 239
5.2
Laryngeal Cancer
The larynx is located between the tip of the thyroid (bottom of the C3 vertebral corpus) and
the bottom of the cricoid cartilages (C6 vertebra) [22].
The larynx is divided into three compartments (Fig. 5.26) [22]:

Supraglottic region. Section above the vocal cords. This region includes epiglottis, aryepi-
glottic plica, arythenoids, ventricular bands (false vocal cords), and laryngeal ventricles.
Glottic region. Region of the vocal cords. It includes the vocal cords, rima glottidis,
anterior, and posterior commissure. The vocal cords consist of the vocal ligaments,
vocalis muscle, and mucosal layers. The vocal cords are 1.7 cm long in females and
2–2.4 cm long in males.
Subglottic region. This is the region inferior to the vocal cords until the first tracheal ring.
Suprahyoid
epiglottis
Aryepiglottic
fold Supraglottis
Infrahyoid
epiglottis
Ventricular Pyriform
band sinus
(false cord)
Glottis Glottis
Subglottis
Laryngeal
cartilage
Fig. 5.26 Anatomy of the larynx (from [11], reproduced with the permission from the American
Joint Committee on Cancer)
5.2.1
Pathology
Most (95–96%) malignant tumors of the larynx are squamous cell cancers of epithelial
origin. Other malignancies, such as verrucous, basocellular and fusiform cell carcinomas,
adenocarcinoma, adenoid cystic carcinoma, and mesenchymal malignancies such as sarco-
mas, are very rare [23].
The incidence of synchronous carcinoma in a patient with laryngeal cancer is

approximately 1%. The probability of a metachronous primary tumor is 5–10% [24].
• Laryngeal cancer is the most frequent tumor seen together with another type of
malignancy.
5.2.2
Hoarseness. This is the most common sign, particularly glottic lesions. Laryngeal cancer should
be ruled out if the hoarseness lasts for more than 2 weeks with a detailed ENT exam.
Dysphagia (difficulty swallowing). This is more common in supraglottic cancers.
Dyspnea and stridor. This symptom is seen when the tumor mass in the larynx obstructs
the airway. Supraglottic tumors must be larger than glottic and subglottic tumors to narrow
the airways.
Otalgia (ear pain). This is a referred pain that is particularly seen in supraglottic cancers
via Arnold’s nerve, a branch of the vagus nerve.
Cough. This is observed in cases with involvement of the superior laryngeal nerve
(sensory nerve of the larynx), causing swallowing dysfunctions and sensory disorders.
Hemoptysis associated with cough may be observed in ulcerated tumors.
Neck mass. Swelling or skin invasion seen in the laryngeal region or the bottom of the
hyoid is a sign of advanced disease, since it shows that the tumor has invaded the thyroid
cartilage and thyrohyoid membranous barrier. A mass combined with the larynx at the front
of the neck may be palpated. Sometimes lymph node metastasis (delphian node) in the front
of the larynx at the level of the cricothyroid or thyrohyoid membranes may be observed as
an anterior mass. Neck masses palpated at lateral sites are a sign of neck metastases.
5.2.3
Staging
Supraglottis (Fig. 5.27) [14]
T1: Tumor limited to one subsite* of supraglottis with normal vocal cord mobility
T2: T umor invades mucosa of more than one adjacent subsite* of supraglottis or glot-
tis or region outside the supraglottis (e.g., mucosa of base of tongue, vallecula, or
medial wall of pyriform sinus) without fixation of the larynx
T3: T umor limited to larynx with vocal cord fixation and/or invades any of the follow-
ing: postcricoid area, pre-epiglottic tissues, paraglottic space, and/or minor thy-
roid cartilage erosion (e.g., inner cortex)
T4a: Moderately advanced local disease: Tumor invades through the thyroid cartilage,
and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of the neck includ-
ing deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus)
T4b: V
ery advanced local disease: Tumor invades prevertebral space, encases carotid
artery, or invades mediastinal structures
Subsites include the following: Ventricular bands (false cords), Arytenoids, Suprahyoid
epiglottis, Infrahyoid epiglottis, Aryepiglottic folds (laryngeal aspect)
Supraglottic laryngeal cancer
T1
T1
Epiglottis False cord
T2 T2
T3 T3
T4b
T4a Pre-epiglottic
space
Epiglottis
Fig. 5.27 T staging for supraglottic laryngeal cancer (from [11], reproduced with the permission
from the American Joint Committee on Cancer)
Glottis (Fig. 5.28) [14]
T1: T umor limited to the vocal cord(s), which may involve anterior or posterior com-
missure, with normal mobility
T1a: Tumor limited to one vocal cord
T1b: Tumor involves both vocal cords
T2: T umor extends to supraglottis and/or subglottis and/or with impaired vocal cord
mobility
T3: T umor limited to the larynx with vocal cord fixation and/or invades paraglottic
space, and/or minor thyroid cartilage erosion (e.g., inner cortex)
T4a: Moderately Advanced Disease: (Midline nodes are considered ipsilateral nodes)
Tumor invades through the thyroid cartilage and/or invades tissues beyond the
larynx (e.g., trachea, soft tissues of neck, including deep extrinsic muscle of
the tongue, strap muscles, thyroid, or esophagus)
T4b: Very Advanced Local Disease: Tumor invades prevertebral space, encases carotid
Glottic laryngeal cancer
T1a
T2
T1
T1b
Fig. 5.28 T staging for glottic laryngeal cancer (from [11], reproduced with the permission from the
T3 T4a
T4b
Pre-epiglottic
space
Epiglottis
Subglottis (Fig. 5.29) [14]
T1: Tumor limited to the subglottis

T2: Tumor extends to vocal cord(s) with normal or impaired mobility
T3: Tumor limited to larynx with vocal cord fixation
T4a: Moderately Advanced Local Disease: Tumor invades cricoid or thyroid cartilage
and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck, includ-
ing deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus)
T4b: Very Advanced Local Disease: Tumor invades prevertebral space, encases carotid
subglottis laryngeal cancer
T1 T2 T3
T4a
Fig. 5.29 T staging for subglottic laryngeal cancer (from [11], reproduced with the permission from
the American Joint Committee on Cancer)
Supraglottic larnyngeal cancer generally metastasizes to level II, III and IV cervical
lymph nodes [25]
Clinical lymph node positivity: 55%
Bilaterality: 16%
The true vocal cords have no lymphatics, so lymphatic involvement is observed in
the presence of supraglottic or subglottic tumor extension.
Lymph node involvement in glottic cancers:
• T1: <2%
• T2: 5%
• T3: 15–20%
• T4: 20–40%
5.2.4
Treatment Algorithm
Treatment Algorithm for Laryngeal Cancer [26]
Tis
Endoscopic excision (stripping, laser) or definitive RT
T1–2, N0
Glottic definitive RT, or
Surgery (cordectomy, partial laryngectomy ± selective neck dissection)
T1–2, N0 supraglottic
Definitive RT, or
Surgery (partial laryngectomy ± selective neck dissection)
Resectable T1–2, N (+); T3N0; T3N (+)
Complete response in primary → surveillance
Residual in primary (+) → salvage surgery + neck dissection
Or surgery
N0–1 → laryngectomy + bilateral/ipsilateral neck dissection
N2–3 → laryngectomy + extended neck dissection
Resectable T4N0/(+)
Surgery
N0–1 → total laryngectomy + bilateral/ipsilateral neck dissection
N2–3 → total laryngectomy + extended neck dissection
Unresectable T4–N0/(+)
Concurrent chemoradiotherapy or definitive RT
Postoperative chemoradiotherapy indications

Surgical margin (+)
Extranodal capsular extension
Postoperative RT or chemoradiotherapy indications
Surgical margin (−)
Perineural invasion (+)
Lymphovascular space involvement (+)
Multiple lymph node involvement (+)
Less than or equal to 1 cm subglottic extension
T3–4 tumor
Cartilage invasion (+)
5.2.5
Radiotherapy
T1–2 Glottic Laryngeal Cancer (Fig. 5.30)
Superior: top of thyroid cartilage

Inferior: bottom of cricoid cartilage
Anterior: 0.5–1 cm fall-off to skin
Posterior: in front of vertebral bodies
C3 vertebra level → hyoid bone
C4 vertebra level → top of thyroid cartilage
C6 vertebra level → cricoid cartilage
Fig. 5.30 Conventional RT fields for T1–2 glottic

laryngeal cancers (from [17], p 455, Figs. 18.2,
18.4, reproduced with the permission from
Springer Science and Business Media)
T3–4 Glottic and Supraglottic Laryngeal Cancer (Fig. 5.31)
Superior: superior to mandibular angle

Inferior: bottom of cricoid cartilage
• Subglottic extension (+), shoulders should be pulled down as much as possible.

• If patient is operated, 1.5 cm superior to stoma (stoma is treated in supraclavicular field).
Anterior: 0.5–1 cm skin fall-off to neck and one-third of mandible
Posterior: usually spinous processes
• Lymph node (+); lymph node should be included.
Fig. 5.31 Conventional RT fields for T3–4 glottic–

supraglottic laryngeal cancer (from [17], p 455,
Figs. 18.2, 18.4, reproduced with the permission from
Springer Science and Business Media)
Subglottic Laryngeal Cancer

Superior: level II (upper jugular) lymph nodes are included.
Inferior: 2 cm below primary tumor
Anterior and posterior: same as supraglottic field
• Lower neck lymphatics and upper mediastinal lymph nodes are treated in anterior
supraclavicular field.
5.2.6
See also Sect. 5.8

Supraglottic laryngeal cancer
Italy, 1997 → retrospective. 166 supraglottic patients. Larynx-preserving surgery vs.
definitive RT.
• DFS: 88% in surgery vs. 76% in RT.

• Local control: 92% in RT.
• Larynx preservation: 95% in surgery vs. 72% in RT.
Spriano G et al (1997) Conservative management of T1–T2N0 supraglottic cancer: a ret-
rospective study. Am J Otolaryngol 18(5):299–305
Rotterdam, 1990 → 203 supraglottic cancer 193 cases with RT. Reevaluation after
40 Gy: 60–70 Gy boost or surgery (33 patients).
• RFS in T2: 53%, T4: 39%.

Hoekstra CJ et al (1990) Squamous cell carcinoma of the supraglottic larynx without clini-
cally detectable lymph node metastases: problem of local relapse and influence of overall
treatment time. Int J Radiat Oncol Biol Phys 18(1):13–21
MDACC, 1989 → 41 supraglottic cancer cases. 1.2 Gy/fractions two times a day;
72–79 Gy (76.8 median) definitive RT.
• Local control: 87% in hyperfractionated arm vs. 76% in conventional arm.

Wendt CD, Peters LJ, Ang KK, Morrison WH, Maor MH, Goepfert H, Oswald MJ (1989)
Hyperfractionated radiotherapy in the treatment of squamous cell carcinomas of the supra-
glottic larynx. Int J Radiat Oncol Biol Phys 17(5):1057–1062
Glottic laryngeal cancer
RTOG 95-12/EORTC 22992 → randomized. 250 cases of T2a–bN0 glottic cancer.
Randomization: standard fractionation (SFX) 70 Gy (2 Gy/fractions) vs. hyperfraction-
ation (HFX) 79.2 Gy (1.2 Gy BID).
• Five-year local control: 79% in HFX vs. 70% in SFX (no significance).
• Five-year DFS: 51% in HFX vs. 37% in SFX (no significance).
• Five-year OS: 73 vs. 62% (no significance).
Trotti A (2006) A randomized trial of hyperfractionation vs. standard fractionation in T2
squamous cell carcinoma of the vocal cord. IJRBOP 66(3 Suppl 1):S15
Italy, 2005 → retrospective. 831 T1 cases.
• Five-year OS 77%, local control 84%, organ preservation 95%.

• Ten-year OS 57%, local control 83%, organ preservation 93%.
• Twenty-year secondary malignancy 23%.
• Field size 39–49 cm : >65 Gy may be used.
2
Cellai E (2005) Radical radiotherapy for early glottic cancer: results in a series of 1087
patients from two Italian radiation oncology centers. I. The case of T1N0 disease. Int J
Radiat Oncol Biol Phys 63(5):1378–1386
New Zealand, 2006 → retrospective. 145 T1–T2 cases. Median follow-up: 4.9 years.
• 6 MV standard fractionation (SFX) 60–66 Gy, 30–33 fractions (2 Gy/fractions), >6–6.5

weeks vs. accelerated hyperfractionation (AHFX) 52.5–55 Gy, 20 fractions (2.75 Gy/
fractions), >4 weeks.
• T1N0: locoregional control, 95% in AHFX vs. 75% in SFX (p < 0.05).
• T2N0: locoregional control, 81% in AHFX vs. 80% in SFX (p > 0.05).
• AHFX can be used in T1 glottic tumors.
Short S (2006) T1/T2 glottic carcinoma: a comparison of two fractionation schedules.
Australas Radiol 50(2):152–157
Subglottic laryngeal cancer
Ocshner clinic, 2006 → retrospective. 15 cases, >25 years. RT alone.
• Three-year OS : 25%.

• Recommendations: stage I–II → RT (including lower neck and upper mediastinal lym-
phatics); stage III–IV → surgery + RT.
Garas J (2006) Squamous cell carcinoma of the subglottis. Am J Otolaryngol 27(1):1–4

Toronto, 2002 → retrospective, 43 cases. Definitive RT + salvage surgery.
• Local control: 56% (82% salvage surgery).

• Five-year OS: 50%.
5.3 Oral Cavity Cancers 249
Paisley S (2002) Results of radiotherapy for primary subglottic squamous cell carcinoma.
Int J Radiat Oncol Biol Phys 52(5):1245–1250
5.3
Oral Cavity Cancers
The oral cavity is located between the vermillion line (the mucosa–skin boundary of the
upper and lower lips) anteriorly and the isthmus faucium posteriorly. It is an anatomical
space that is bounded by the floor of the mouth inferiorly, the hard palate superiorly, and
the buccal mucosa laterally. Although the oral cavity is a space, it is not a homogeneous
region, and it includes various subsites [27].
Normal Anatomical Structures of the Oral Cavity (Fig. 5.32) [27]
Upper and lower lips

Buccal mucosa
Gingiva and teeth (arches of the upper and lower teeth)
Hard palate
Part of the soft palate
Anterior two-thirds of tongue
Floor of mouth
Retromolar trigone
The oral cavity is divided into two parts via the arches of the upper and lower teeth
when the mouth is closed [27]:
• Anterior part: vestibulum oris (entrance to the oral cavity)

• Posterior part: cavum oris proprium (true oral cavity)
Retromolar trigone. This is located between the ramus of the mandible and the last
molar tooth, connecting these two spaces when the mouth is closed. This region is impor-
tant due to the fact that patients with maxillofacial trauma or maxillary fixation may feed
via the retromolar trigone [27].
250
Fig. 5.32 Normal anatomical structures of the oral cavity (from [11], reproduced with the permission from the American Joint Committee on
Cancer)
5 Head and Neck Cancers
Oral cavity cancers are the second most common head–neck cancers after laryngeal
cancers.
5.3.1
Pathology
Premalignant lesions of the oral cavity: some epithelial lesions have the potential for
malign transformation (Fig. 5.33) [28]. These are as follows [28]:
• Leukoplakia. This is the most common premalignant lesion in the head–neck region.
The white macules may have several histological features, from simple hyperkeratosis,
dysplasia and carcinoma in situ to invasive carcinoma. They are most commonly
observed in the oral cavity and laryngeal mucosa. The risk of malignant transformation
in these lesions is higher in smokers and in women.
• Erythroplakia. This is less common than leukoplakia. The oral cavity is the most fre-
quent localization. The risk of malignant transformation is much higher, and biopsy is
essential for histological evaluation.
• Lichen planus. Erosive lichen planus in the oral cavity may transform into malignancy.
These are benign lesions and are frequently localized in the buccal mucosa and tongue
symmetrically. The erosive type is seen in the floor of the mouth. Biopsy is essential to
determine lichen type and for differential diagnosis from leukoplakia.
• In addition, pemphigus, papilloma, chronic fungal infections, and Plummer–Vinson
syndrome are also followed for possible malignant transformations.
Fig. 5.33 Leukoplakia, erythroplakia, and lichen planus (from left to right)
Most oral cavity malignancies are squamous cell cancers (epidermoid cancers) [29].
Other malignant tumors of the oral cavity:
Epithelial origin: basal cell carcinoma, malignant melanoma
Glandular origin: adenocarcinoma, adenoid cystic carcinoma
Lymphoid origin: lymphoma
Soft tissue origin: sarcoma
5.3.2
The most prominent symptoms are a scar that does not heal and swelling or masses. The
swelling or mass may be located in the primary region as well as the neck, since they have
the potential to metastasize to cervical lymph nodes. In addition, pain (e.g., during chew-
ing, swallowing, throat pain, ear pain), bleeding, speaking disorders, swallowing dysfunc-
tions and dyspnea may also be seen.
5.3.3
Staging
Primary tumor (T) (Fig. 5.34) [14]
T1: Tumor no larger than 2 cm in greatest dimension

T2: Tumor larger than 2 cm but no larger than 4 cm in greatest dimension
T3: Tumor larger than 4 cm in greatest dimension
T4: Moderately Advanced Local Disease: (lip) Tumor invades through cortical bone,
inferior alveolar nerve, floor of mouth, or skin of face, i.e., chin or nose
T4a: Moderately Advanced Local Disease: (oral cavity) Tumor invades adjacent
structures (e.g., through cortical bone (mandible or maxilla), into deep [extrinsic]
muscle of tongue [genioglossus, hyoglossus, palatoglossus, and styloglossus],
maxillary sinus, and skin of face)
T4b: Very Advanced Local Disease: Tumor invades masticator space, pterygoid
plates, or skull base and/or encases internal carotid artery (superficial erosion
alone of bone/tooth socket by gingival primary is not sufficient to classify a
tumor as T4).
N staging is similar to those of other head–neck cancers, except nasopharynx cancer.
T1 T3
T1
> 4 cm
≤ 2 cm
≤ 2 cm
Fig. 5.34 T staging for oral cavity cancer (from [11], reproduced with the permission from the
a b c
T3
T2
T2
> 4 cm
2-4 cm
2-4 cm
d e f T3
T4 > 4 cm
Lip
h
g T4b
T4a
Pterygoid plate
Masticator
space
Approximately 50% of all oral cavity malignancies are located in the lower lip or
tongue, 10% in the buccal mucosa, and 10% in the mandible (teeth arches) or maxilla
(hard palate) [31].
Five-year survival is nearly 90% in lip cancers smaller than 2 cm in size, but
decreases to 40% in advanced cases [31].
Five-year survival is nearly 90% in stage I tongue cancers, but decreases to 10% in
stage IV cases [32].
Oral cavity cancer frequently involves the submandibular (level Ib), upper jugular
(level II) and mid-jugular lymph nodes (level III) [30].
When clinical N (−) tongue cancers are examined histopathologically after neck dissec-
tion, pathological lymph node positivity is nearly 33% [30].
5.3.4
Treatment Algorithm
Stage I–II [16]

Definitive RT (66–72 Gy), or
Alternative → Surgery ± postoperative RT
Stage III–IV [16]
Concurrent chemoradiotherapy, or
Alternative → Surgery + postoperative chemoradiotherapy
Postoperative chemoradiotherapy indications (major risk factors):
• Extracapsular nodal involvement

• Surgical margin (+)
Postoperative radiotherapy indications (minor risk factors):
• Multiple lymph node (+)

• Perineural invasion
• Lymphovascular space invasion
5.3.5
Radiotherapy
Conventional RT Fields (Fig. 5.35).

Superior: 2 cm above primary tumor.
Inferior: below hyoid bone.
• Lymph node (+): level III is included

• Anterior: 2 cm in front of primary tumor (usually in front of mandible).
• Posterior: Back of vertebral corpuses.
• Lymph node (+): back of vertebral spinous processes.
• Two lateral parallel–opposed fields are used.
• Lymph node (+): neck and supraclavicular field is also treated.
(Two lateral and one anterior field.)
Interstitial brachytherapy can be used alone or in combination with external RT in
the management of floor of mouth, tongue, lip and buccal mucosa cancers.
c d
N0 Floor of the mouth N0 Floor of the mouth

(Tongue extension −) (Tongue extension +)
Fig. 5.35 Conventional RT fields for oral cavity cancers (from [17], p 459, 467, Figs. 18.11, 18.12,
18.16a, reproduced with the permission from Springer Science and Business Media)
Supraclavicular field
T4N0
Retromolar Trigone
(Postoperative)
Reasons for tongue depressor or cork use:
• To spare upper teeth, upper gingiva and soft palate and to stabilize the tongue in floor
of mouth, lower lip, retromolar trigone and tongue tumors
• Tongue stabilization in other oral cavity tumors
Conformal RT Fields [33]:

CTV1: GTV + 1 cm
CTV2: level Ib, II, III lymphatics
PTV: CTV + 0.5–1 cm
5.3.6
See also Sect. 5.8

Tongue
MDACC, 1990 → retrospective. 103 patients with T1–2 N0 tongue SCC (18 T1, 85 T2).
RT: interstitial brachytherapy (BRT) + hypofractionated RT (16–37 Gy, 2.4–4.0 Gy/frac-
tions or 40–50 Gy), interstitial BRT alone (38–55 or 40–50 Gy), normofractionated RT
(45–82 Gy).
5.4 Sinonasal Cancers 257
• RT alone: local recurrence in 5/8 patients.

• BRT alone: local recurrence in 6/18.
• BRT dose >40 Gy: two-year local control 92%.
• BRT dose <40 Gy: two-year local control 65%.
• Neck recurrence in patients with no neck RT: 44%.
Wendt CD et al (1990) Primary radiotherapy in the treatment of stage I and II oral tongue
cancers: importance of the proportion of therapy delivered with interstitial therapy. Int J
Radiat Oncol Biol Phys 18(6):1287–1292
Buccal mucosa
Indian Randomized Trial, 1996 → randomized. Stage III–IV buccal mucosa SCC. Surgery
vs. surgery + postoperative RT.
• Disease-free survival: 38% in surgery-alone arm vs. 68% in combined arm.

Mishra RC et al (1996) Post-operative radiotherapy in carcinoma of buccal mucosa, a
prospective randomized trial. Eur J Surg Oncol 22(5):502–504
Floor of mouth
Institute Gustave-Roussy, 2002 → retrospective. 160 cases: T1N1 49%, T2N1 51%; inter-
stitial BRT in all cases.
• Two-year survival: 89%; 5-year survival: 75%.

• Serious necrosis <10%.
• Bone necrosis 18%.
Marsiglia H et al (2002) Brachytherapy for T1–T2 floor-of-the-mouth cancers: the Gustave-
Roussy Institute experience. Int J Radiat Oncol Biol Phys 52(5):1257–1263
Retromolar trigone
Gainesville, 2005 → retrospective. 99 patients: RT alone in 35, surgery + RT in 64.
• Five-year locoregional control for stage I–III: 51% in RT alone vs. 87% in surgery + RT.
• Five-year locoregional control for stage IV: 42% in RT alone vs. 62% in surgery + RT.
• Multivariate analysis: RT + surgery was better than RT alone.
Mendenhall WM et al (2005) Retromolar trigone squamous cell carcinoma treated with
radiotherapy alone or combined with surgery. Cancer 103(11):2320–2325
5.4
Sinonasal Cancers
Sinonasal cancers include malignancies of the nasal cavity and paranasal sinuses (maxil-
lary sinus, frontal sinus, ethmoid sinuses, and sphenoid sinus) (Fig. 5.36).

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Head and Neck Cancers

M. Beyzadeoglu et al. Basic Radiation Oncology, 205

Table 5.1 Head and neck lymphatics

Fig. 5.1 Lymphatic levels of neck

Lower lip, floor of mouth,

• Pharyngeal wall cancer: 50%

• Pyriform sinus cancer: 59%

Table 5.2 Lymphatic involvement ratios in various head–neck cancers (%) [8]

Retropharyngeal Nodes Level Ib

Level III Level VI Level IV

The RTOG/EORTC group has published a consensus document on the determination

Frontal sinus Dipolë

Couch rotation angle

Fig. 5.5 Collimator and couch angles

2. Half-block/asymmetrical collimator use (Fig. 5.6).

• An asymmetrical collimator is a component of a linac that allows secondary colli-

Symmetrical collimation Asymmetrical collimation

Half Block Half Block

Fig. 5.6 (a) Asymmetrical collimation technique; (b) half-beam cutter

• The utilization of such a gap on involved lymph nodes or stoma is not

Subsites of the Pharyngeal Region (Fig. 5.7)

Fig. 5.8 Nasopharyngeal anatomy

Normal Anatomical Structures in the Nasopharynx [10]

Base of sphenoid sinus and cranial base superiorly

WHO Classification, 1978 [12]

• Nonkeratinized carcinoma – WHO Type II (30–40%)

1. Nasal and nasopharyngeal symptoms are seen as a result of nasopharyngeal localization

T staging (Fig. 5.9) [14]

TX: Primary tumor cannot be assessed

N0: No regional lymph node metastasis

AJCC Stage Groups

Fig. 5.11 Neck node metastasis

Five-year survival in nasopharyngeal cancer is 35–50%.

The treatment algorithm for nasopharyngeal cancers is summarized in Fig. 5.12 [16].

(Neck: Complete response) (Neck: Partial response)

OBSERVATION NECK DISSECTION

Fig. 5.12 Treatment algorithm for nasopharyngeal cancers [16]

Conventional orthogonal irradiation (two lateral fields, one anterior supraclavicular

Borders of lateral fields (primary tumor + upper neck).

• If supraclavicular LN (+),the upper mediastinal lymph nodes are covered by the

Fig. 5.13 Nasopharyngeal lateral RT field (from

Supraclavicular field (Fig. 5.14). Superior border; inferior border of lateral fields if

Conformal RT Fields (Fig. 5.15) [18]

GTV: gross disease.

Table 5.3 TD5/5 doses to critical organs in head and neck radiotherapy

Side Effects Related to Radiotherapy (Table 5.3)

Fig. 5.16 Normal anatomical

Normal anatomical structures of the oropharynx (Fig. 5.17) [19]:

Fig. 5.17 Normal anatomical structures of the

Squamous cell cancer: 75%

Etiology → cigarette smoking, alcohol, chronic irritation, and HPV 16 [21]

Primary Tumor (T) (Fig. 5.18) [14]

AJCC stage groups

Treatment Algorithm for Oropharyngeal Cancer [16]

T1,2–N0,1 → three alternative approaches:

Residual disease in neck after chemo-RT

Poor prognostic factors

• Major risk factors (postoperative chemo-RT indications):

Conventional Orthogonal Radiotherapy Fields (Fig. 5.19)

Two parallel–opposed lateral fields and supraclavicular anterior field

• Anterior and superior borders should be modified by the clinician according to

Fig. 5.20 Conventional RT films for oropharyngeal cancer

• After 50 Gy (primary tumor + 2 cm), 66–72 Gy.