Head and Neck Cancers
Kazumi Chino, M.D.
Radiation Oncology
Epidemiology
• 52,000 people diagnosed in the US annually
• 3% of all cancers in the US
• Men are twice as likely as women to develop a
head and neck cancer
• Dx is most common after age 50
Risk Factors
• Tobacco – approx. 85% of H&N Ca related to
tobacco
• Alcohol
• HPV in oropharyngeal cancers
• Epstein-Barr virus in nasopharyngeal cancers
• Poor dental/oral hygiene
• Poor nutrition – vit A and B deficiency
• GERD in pharyngeal cancers
Histology
• 90% of H&N cancers are squamous cell
carcinomas arising from the mucosal surfaces
• Salivary gland tumors are typically
adenocarcinomas
Anatomy
Anatomy: Nasopharynx
• Eustachian tube
• Torus Tubaris
• Fossa of Rosenmuller
Anatomy: Oro/Hypopharynx
•
•
•
•
From the uvula to hyoid bone
Palatine tonsils, tonsillar pillars
Base of tongue
Epiglottis and vallecula
Anatomy: Laryngopharynx
• From the epiglottis to the inferior cricoid
cartilage
• Vocal cords, piriform sinuses, arytenoid
cartilage and aryepiglottic folds
Anatomy: Laryngopharynx
Cervical Lymph Nodes
Presentation: Nasopharynx
Nasopharyngeal Cancer Sx’s
• Nasal obstruction, bleeding, discharge
• Hearing problems if eustachian tube
obstructed, otitis media
• Headaches
• Cranial nerve palsy with involvement of the
base of skull
• Neck mass, particularly at the mastoid tip
Staging: Nasopharynx
Primary tumor (T)
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
Tis
Carcinoma in situ
T1
Tumor confined to the nasopharynx, or
tumor extends to oropharynx and/or nasal
cavity without parapharyngeal extension
(eg, without posterolateral infiltration of
tumor)
T2
Tumor with parapharyngeal extension
(posterolateral infiltration of tumor)
T3
Tumor involves bony structures of skull
base and/or paranasal sinuses
T4
Tumor with intracranial extension and/or
involvement of cranial nerves,
hypopharynx, or orbit, or with extension to
the infratemporal fossa/masticator space
Staging: Nasopharynx
Regional lymph nodes (N)
NX
Regional nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Unilateral metastasis in cervical lymph
nodes ≤6cm in greatest dimension,
above the supraclavicular fossa, and/or
unilateral or bilateral retropharyngeal
lymph nodes ≤6 cm in greatest
dimension (midline nodes are considered
ipsilateral nodes)
N2
Bilateral metastasis in cervical lymph
nodes ≤6cm in greatest dimension,
above the supraclavicular fossa (midline
nodes are considered ipsilateral nodes)
N3
Metastasis in a lymph node >6cm and/or
to the supraclavicular fossa (midline
nodes are considered ipsilateral nodes)
N3a
>6cm in dimension
N3b
Extension to the supraclavicular fossa
Staging: Nasopharynx
Stage
T
N
M
0
Tis
N0
M0
I
T1
N0
M0
II
T1
N1
M0
T2
N0
M0
T2
N1
M0
T1
N2
M0
T2
N2
M0
T3
N0
M0
T3
N1
M0
T3
N2
M0
T4
N0
M0
T4
N1
M0
T4
N2
M0
IVB
T Any
N3
M0
IVC
T Any
N Any
M1
III
IVA
Tx & Prognosis: Nasopharynx
• Stage I/II tx’d RT alone: local control rates at 5
years for T1= 93%, T2 = 79%, T3 = 68% and T4 =
53%
• Intergroup 0099 compared RT alone vs cisplatin
100mg/ms day 1, 22, 43 + RT for Stage III/IV
• 3 yr progression free survival was 24% vs 69% in favor of
concurrent chemo/RT
• 3 yr overall survival was 47% compared to 78% in favor or
concurrent chemo/RT
– Similar trial JCO 2005 showed OS 65%  80% with
chemo
Nasopharynx NCCN Guidelines
Recurrent or Persistent Dz
Prognosis: Nasopharnx
• Keratinizing squamous cell carcinoma has a
higher risk of local recurrence after tx than
non-keratinizing SCCa or undifferentiated
• High EBV DNA titers after tx are associated
with an increased risk of recurrence
Presentation: Oropharynx
•
•
•
•
•
Globus sensation
Difficultly swallowing
Slurred speech
Pain in throat or ear
Neck mass
Staging: Oropharynx
Primary tumor (T)
Oropharynx:
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
Tis
Carcinoma in situ
T1
Tumor ≤2cm in greatest dimension
T2
Tumor >2cm but ≤4cm in greatest
dimension
T3
Tumor >4cm in greatest dimension or
extension to lingual surface of the
epiglottis
T4a
•Moderately advanced, local disease
Tumor invades the larynx, deep/extrinsic
muscle of the 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 the carotid artery
Staging: Hypopharynx
Hypopharynx:
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
Tis
Carcinoma in situ
T1
Tumor limited to 1 subsite of the
hypopharynx and/or ≤2cm in greatest
dimension
T2
Tumor invades more than 1 subsite of
the hypopharynx or an adjacent site or
measures >2cm but ≤4cm in greatest
dimension, without fixation of the
hemilarynx
T3
Tumor >4cm in greatest dimension or
with fixation of the hemilarynx or
extension to the esophagus
T4a
•Moderately advanced, local disease
Tumor invades thyroid/cricoid cartilage,
hyoid bone, thyroid gland, esophagus, or
central compartment soft tissue
(including prelaryngeal strap muscles
and subcutaneous fat)
T4b
•Very advanced, local disease Tumor
invades prevertebral fascia, encases
carotid artery, or involves mediastinal
structures
Staging: Oro/Hypopharynx
Regional lymph nodes (N)
NX
Regional nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Metastasis in a single ipsilateral lymph
node ≤3cm in greatest dimension
N2
Metastasis in a single ipsilateral lymph
node >3cm but ≤6cm in greatest
dimension; or in multiple ipsilateral lymph
nodes, none >6cm in greatest dimension;
or in bilateral or contralateral lymph nodes,
none >6cm in greatest dimension
N2a
Metastasis in a single ipsilateral lymph
node >3cm but ≤6cm in greatest dimension
N2b
Metastasis in multiple ipsilateral lymph
nodes, none >6cm in greatest dimension
N2c
Metastasis in bilateral or contralateral
lymph nodes, none >6cm in greatest
dimension
N3
Metastasis in a lymph node >6cm in
greatest dimension
Staging: Oro/Hypopharynx
Stage
T
N
M
0
Tis
N0
M0
I
T1
N0
M0
II
T2
N0
M0
III
T3
N0
M0
T1
N1
M0
T2
N1
M0
T3
N1
M0
T4a
N0
M0
T4a
N1
M0
T1
N2
M0
T2
N2
M0
T3
N2
M0
T Any
N3
M0
T4b
N Any
M0
T Any
N Any
M1
IVA
IVB
IVC
Tx & Prognosis: Oro/Hypopharynx
• RTOG 73-03 randomized advanced
oropharyngeal tumors to surgery with or
without post-op RT
– Post-op RT better LRC (48 vs 65%) & OS (26% vs
38%)
• RTOG 90-03 and EORTC studies on locally
advanced H&N Ca’s (excluding NPX) showed
improved LC with concomitant boost with RT
Tx & Prognosis: Oro/Hypopharynx
• GORTEC 94-01 (JCO 2004) for Stage III/IV showed
benefit of 3 cycles carboplatin/5-FU + RT vs RT
alone
– Chemo-RT improved LC (25 vs 48%), DFS (15 vs 27%)
OS (16 vs 23%)
• Intergroup Trial (JCO 2003) and Duke trials (NEJM
1998) showed similar benefit for cisplatin +/- 5FU
• Bonner (NEJM 2006) showed benefit of
cetuximab with RT over RT alone
– Cetuximab increased 3 yr LRC (34 vs 47%) OS (45 vs
55%).
Tx & Prognosis: Oro/Hypopharnx
• EORTC 22931 Stage III/IV operable H&N Ca’s (excluding
NPX) pT3-4 N0/+ Tl-2N2-3, or Tl-2 N0-1 with ECE, +
margin, or PNI randomized to post-op cisplatin
100mg/ms days 1, 11, 43 + RT vs RT alone
– ChemoRT improved 3/5 yr DFS (41/36 vs 59/47%) OS
(49/40 vs 65/53%) 5yr LRC (69 vs 82%)
• RTOG 95-01 operable H&N cancer who had > 2 LN, ECE,
or + margin randomized to RT vs RT + cisplatin
– Chemo-RT improved 2yr DFS (43 vs 54%), LRC (72 vs 82%)
& trend for improved OS (57 vs 63%)
– No difference in distant mets for either study
NCCN Guidelines Orophyarnx
NCCN Guidelines Oropharyx
NCCN Guidelines Oropharynx
NCCN Guidelines Hypophyarnx
NCCN Guidelines Hypophyarnx
NCCN Guidelines Hypophyarnx
NCCN Guidelines Hypopharynx
Presentation: Larynx
•
•
•
•
•
Hoarse voice
Stridor
Cough, hx of GERD
Trouble swallowing
For glottic tumors
– T1-2 5% LN involvement
– T3-4 20% LN involvement
Staging: Larynx
Supraglottis:
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
Tis
Carcinoma in situ
T1
Tumor limited to 1 subsite of the
supraglottis, with normal vocal cord
mobility
T2
Tumor invades mucosa of more than 1
adjacent subsite of the supraglottis or
glottis or region outside the supraglottis
(eg, mucosa of base of the tongue,
vallecula, medial wall of piriform sinus),
without fixation of the larynx
T3
Tumor limited to the larynx, with vocal
cord fixation, and/or invades any of the
following: postcricoid area, preepiglottic
space, paraglottic space, and/or inner
cortex of the thyroid cartilage
T4a
•Moderately advanced, local disease
Tumor invades through the thyroid
cartilage and/or invades tissues beyond the
larynx (eg, trachea, soft tissues of the neck,
including deep extrinsic muscle of the
tongue, strap muscles, thyroid, or
esophagus)
T4b
•Very advanced local disease Tumor
invades prevertebral space, encases carotid
artery, or invades mediastinal structures
Staging: Larynx
Glottis:
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
Tis
Carcinoma in situ
T1
Tumor limited to the vocal cord(s) (may
involve anterior or posterior
commissure), with normal mobility
T1a
Tumor limited to 1 vocal cord
T1b
Tumor involves both vocal cords
T2
Tumor extends to the supraglottis
and/or subglottis, and/or with impaired
vocal cord mobility
T3
Tumor limited to the larynx with vocal
cord fixation and/or invasion of the
paraglottic space and/or inner cortex of
the thyroid cartilage
T4a
•Moderately advanced, local disease
Tumor invades through the outer cortex
of the thyroid cartilage and/or invades
tissues beyond the larynx (eg, trachea,
soft tissues of the neck, including deep
extrinsic muscle of the tongue, strap
muscles, thyroid, or esophagus)
T4b
•Very advanced, local disease Tumor
invades prevertebral space, encases
carotid artery, or invades mediastinal
structures
Staging: Larynx
Subglottis:
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
Tis
Carcinoma in situ
T1
Tumor limited to the subglottis
T2
Tumor extends to vocal cord(s), with
normal or impaired mobility
T3
Tumor limited to the larynx, with vocal
cord fixation
T4a
•Moderately advanced, local disease
Tumor invades cricoids or thyroid
cartilage and/or invades tissues beyond
the larynx (eg, trachea, soft tissues of the
neck, including deep extrinsic muscle of
the tongue, strap muscles, thyroid, or
esophagus)
T4b
•Very advanced, local disease Tumor
invades prevertebral space, encases
carotid artery, or invades mediastinal
structures
Staging: Larynx
Regional lymph nodes (N)
NX
Regional nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Metastasis in a single ipsilateral lymph
node ≤3cm in greatest dimension
N2
Metastasis in a single ipsilateral lymph
node >3cm but ≤6cm in greatest
dimension; or in multiple ipsilateral lymph
nodes, none >6cm in greatest dimension;
or in bilateral or contralateral lymph nodes,
none >6cm in greatest dimension
N2a
Metastasis in a single ipsilateral lymph
node >3cm but ≤6cm in greatest dimension
N2b
Metastasis in multiple ipsilateral lymph
nodes, none >6cm in greatest dimension
N2c
Metastasis in bilateral or contralateral
lymph nodes, none >6cm in greatest
dimension
N3
Metastasis in a lymph node >6cm in
greatest dimension
Staging: Larynx
Stage
T
N
M
0
Tis
N0
M0
I
T1
N0
M0
II
T2
N0
M0
III
T3
N0
M0
T1
N1
M0
T2
N1
M0
T3
N1
M0
T4a
N0
M0
T4a
N1
M0
T1
N2
M0
T2
N2
M0
T3
N2
M0
T4a
N2
M0
T Any
N3
M0
T4b
N Any
M0
T Any
N Any
M1
IVA
IVB
IVC
Tx & Prognosis: Larynx
• Stage I tx’d with RT with salvage surgery if
needed: 5 yr OS 80-98%
• Stage II tx’d with RT with salvage surgery: 5 yr OS
68-93%
• VA Laryngeal Trial: Stage III/IV laryngeal tumors
randomized to surgery + post-op RT vs induction
chemo with cisplatin/5FU followed by RT
– 2 yr OS was 68% for both groups
– Laryngeal preservation rate was 64% (36% in the
chemo/RT group required salvage laryngectomy)
Tx & Prognosis: Larynx
• RTOG 91-11 compared RT alone vs sequential
chemo/RT vs concurrent chemo + RT
– LRC 56% RT alone, 61% sequential, 78% concurrent
– Decreased distant mets with chemo
• Bonner trial for cetuximab included laryngeal
tumors as well
• RTOG 95-01 and EORTC 22931 for post-op
chemoRT included laryngeal tumors
– Benefit for > 2LN, T3-4, + ECE, + margins
NCCN Guidelines Supraglottic Larynx
NCCN Guidelines Supraglottic Larynx
NCCN Guidelines Supraglottic Larynx
NCCN Guidelines Supraglottic Larynx
NCCN Guidelines Supraglottic Larynx
NCCN Guidelines Supraglottic Larynx
NCCN Guidelines Glottic Larynx
NCCN Guidelines Glottic Larynx
NCCN Guidelines Glottic Larynx
NCCN Guidelines Glottic Larynx
NCCN Guidelines Glottic Larynx
Overview of Treatment
• Surgery: First choice when possible, but often limited by
disfigurement and preservation of organ function such as
speech and swallowing
• Radiation: Most head and neck cancer is sensitive to
radiation while preserving organ function
– Side effects can be severe; Mucositis, permanent xerostomia,
osteoradionecrosis of the mandible, altered taste, weight loss,
and tooth decay
• Chemotherapy: Can have dramatic response to treatment,
but is often not a durable response
– Side effects can also be severe; decreased blood counts,
anemia, infections, weight loss, nausea, vomiting, and hair loss
– Newer targeted therapies have lower side effects
IMRT
Recent Advances and Future
Directions
• PET imaging may allow detection of occult LN
metastasis negating the need for post-RT neck
dissection
• Sentinel LN bx in the neck is showing use especially in
oral cancers
• IMRT improves SE’s from radiation therapy
• Taxanes are showing some promise with cisplatin
• Targeted therapies: phase III trials with zalutumumab
and panitumumab, sorafenib (an inhibitor of the
intracellular domain of VEGFR, PDGFR and c-Kit) and
afatinib (an irreversible inhibitor of pan-HER tyrosine
kinase)