Rebecca Johnson

ONCOLOGY OF, AND RADIOTHERAPY

TECHNIQUE FOR PATIENTS WITH
MALIGNANCY OF THE LARYNX
TRT-5-003
November, 2014

Learning Outcomes
Learning Outcomes:
Identify the aetiological factors associated

with the development of tumours of the

larynx.
Describe the presenting symptoms of
laryngeal tumours
Identify the investigations that will enable
the correct diagnosis to be made.
Identify the TNM staging for such tumours.
Describe the oncological management of
patients with tumours of the larynx.
Describe in detail the radiotherapy
techniques that may be employed in the
management of these patients, explaining
the rationale for each selected.
Describe the possible side effects from
radiotherapy treatment and explain how
they may be minimized.
Describe the daily management of patients
undergoing radiotherapy for laryngeal
tumours.

Larynx anatomy review

Biological Function:
to act as a valve to prevent air from escaping the lungs,
to prevent foreign substances from entering the lungs,
trachea and glottis, e.g. while swallowing, the epiglottis
covers the opening to the larynx.
to forcefully expel foreign substances which threaten the
trachea, e.g. coughing
Non Biological Function:
The production of sound

Skeleton of the larynx

Hyoid Bone
The yellowish bone in the image, it is
horseshoe shaped and is the only
bone in the body that floats,
unconnected to another bone. It can
be felt by pressing a finger into the
crease where your chin becomes your
neck.
Cartilages
Thyroid - the "Adam's apple" on
men, this V shaped cartilage features
a notch in the front which can be felt
with the edge of your thumb.
Cricoid - a ring shaped cartilage
connected to the trachea, it is larger
in back where the arytenoid cartilages
sit (not visible in this image).
Trachea
Made up of a series of cartilaginous
rings, the trachea can stretch, much
like a vacuum cleaner hose. Compress
it by swallowing, stretch it by tipping
your head back.

Skeleton of the larynx

The Epiglottis
Functioning much like a "flap valve" on a
toilet, the epiglottis drops down in
swallowing to close off the entrance to the
larynx, thereby protecting the airway.
The Fat Pad
Sitting behind the Epiglottis is a pad of fat
(yellowish in the image above) which
cushions it as it rises.
The Arytenoid Cartilages
The arytenoids are pyramid shaped and sit
on top of the widest part of the cricoid
cartilage. The vocal folds are attached to
these cartilages and it is their movement
that opens and closes the glottis (the
space between the vocal folds).

Anatomy of the Larynx

This image shows the larynx

from the side, featuring the
vocal ligament, so that you
can visualize the placement of
the vocal folds within the
structure of the cartilages.

Anatomy of the Larynx

This image shows the cartilages of
the larynx from above, giving an
excellent reference point for future
images of the larynx as seen
through an endoscope, as they
really appear.

Anatomy of the Larynx

The "true" vocal folds - are made up of five
layers:
epithelium - the surface "skin" of the
larynx, which is continuous with the lining
of the mouth, pharynx and with the trachea
below the larynx.
lamina propria - three distinct layers, each
with a different consistency
superficial layer: a jelly-like
substance, close to the surface
intermediate layer: an elastic,
fibrous substance, like rubber
bands
deep layer: a thread-like
collagenous fibre layer
vocalis muscle: the main body of the vocal
fold, and very stiff

Vocal cords: Inhalation

This image shows the vocal folds abducted for inhalation. You can see the two bumps of the of
the arytenoid cartilages near the bottom corners of the picture, the vocal folds are making a V
pointing at the thyroid cartilage, and you can see the shiny epiglottis at the top of the image,
like a crescent moon. Looking inside the glottis, you can make out the rings of the trachea.

Vocal cords: Exhalation

In this image, the vocal folds are adducted for phonation on the exhaled breath.
You can see that the arytenoid cartilages have swung forwards and together to bring the
edges of the folds into contact. The folds are photographed in mid vibration; you can see the
degree to which the folds separate during each vibratory cycle (not much!). The folds appear
white in colour because there is very little blood flow to the fold tissue, and the arteries are
microscopic. However, if a blood vessel were to break, the results would be very dramatic, as
the tissue would quickly fill with blood, turning a deep red colour.

Epidemiology
Cancer of the larynx is rare.
Around 2,300 people are diagnosed in the UK each year.
Fewer than 1 in every 100 cancers is a cancer of the

larynx.
Cancer of the larynx is more common in men than in
women. There are around 5 times as many men
diagnosed as women.
More common in older people than in younger. There are
very few cases in people under 40 years of age.

Aetiology
Smoking

Exposure to chemicals
Excessive drinking

Genetics
Poor diet

Immunosuppression &
HPV virus

Histology
85-95% of Laryngeal tumours are squamous cell

carcinoma
Others include:
Verrucous carcinoma
Fibrosarcoma
Chondosarcoma
Minor salivary carcinoma
Adenocarcinoma
Oat cell carcinoma
Giant and Spindle cell carcinoma

Signs & Symptoms

Hoarseness
Difficulty in swallowing food
The feeling of a lump in the throat
Cough or shortness of breath
Halitosis
Unexplained Weight Loss

These symptoms are common in conditions other than cancer and

most people with these symptoms will not have laryngeal cancer.

Clinical Investigations
Full body examination
Full medical history
Laryngoscopy / Transnasal oesophagostomy
Biopsy
Blood tests
Chest x-ray

MRI (magnetic resonance imaging) scan

CT (computerised tomography) scan
Isotope bone scan
PET/CT

Laryngoscopy
Carcinoma in-situ

T1 carcinoma of the larynx

T3 carcinoma of the larynx

PET/CT

Tumour NM
TX :Indicates the primary tumour cannot be evaluated.
T0: No evidence of a tumour is found.
Tis: Describes a stage called carcinoma (cancer) in situ. This is a very early
cancer where cancer cells are found only in one layer of tissue.

When describing a later stage tumour, the larynx is divided into three regions: the
glottis, the supraglottis, and the subglottis.

Tumour NM- glottis

T1: Describes a tumour that is limited to the vocal folds, but it does not affect
movement of the folds.
T1a: Describes a tumour in just the right or left vocal fold.
T1b: Describes a tumour in both vocal folds.
T2: Describes a tumour that has spread to the supraglottis and/or the subglottis. T2
also describes a tumour that affects the movement of the vocal fold, without paralyzing
the fold.
T3: Describes a tumour that is limited to the larynx and paralyzes at least one of the
vocal folds.
T4a: The tumour has spread to the thyroid cartilage and/or the tissue beyond the
larynx.
T4b: The tumour has spread to the area in front of the spine (prevertebral space), chest
area, or encases the arteries.

Tumour NM-supraglottis
T1: Describes a tumour located in a single area above the vocal folds that
doesnt affect movement of the vocal folds.

T2: Describes a tumour that started in the supraglottis, but has spread to the
mucus membranes that line other areas, such as the base of the tongue.
T3: Describes a tumour that is limited to the larynx with vocal fold involvement
and/or has spread to surrounding tissue.
T4a: The tumour has spread through the thyroid cartilage and/or the tissue
beyond the larynx.
T4b: The tumour has spread to the area in front of the spine (prevertebral
space), chest area, or encases the arteries.

Tumour NM-subglottis
T1: Describes a tumour that is limited to the subglottis.

T2: Describes a tumour that has spread to the vocal folds and may or may not
affect movement of the folds.
T3: Describes a tumour that is limited to the larynx and affects the vocal folds.
T4a: The tumour has spread to the cricoid or thyroid cartilage and/or the tissue
beyond the larynx.
T4b: The tumour has spread to the area in front of the spine (prevertebral
space), chest area, or encases the arteries.

T Nodes M
NX: Indicates that the regional lymph nodes cannot be evaluated.
N0: There is no evidence of cancer in the regional nodes.
N1: Indicates that cancer has spread to a single node on the same side as the primary tumor

and the cancer found in the node is 3 cm or smaller.

N2: Describes any of the following conditions:
N2a: Cancer has spread to a single lymph node on the same side as the primary tumor, and

is larger than 3 cm, but not larger than 6 cm.

N2b: Cancer has spread to more than one lymph node on the same side as the primary

tumor, and none measure larger than 6 cm.

N2c: Cancer has spread to more than one lymph node on either side of the body, and none

measure larger than 6 cm.

N3: Indicates that the cancer found in the lymph nodes is larger than 6 cm.
Distant metastasis (for both larynx and hypolarynx). The M in the TNM system indicates

whether the cancer has spread to other parts of the body.

TN Metastasis
MX: Indicates that distant metastasis cannot be

evaluated.
M0: Indicates that the cancer has not spread to other

parts of the body.

M1: Describes cancer that has spread to other parts of the

body

Stage 0

Describes a carcinoma in situ (Tis), with no spread to

lymph nodes (N0) or distant metastasis (M0).

Stage I

Describes a small tumour (T1), with no spread to lymph

nodes (N0) and no distant metastasis (M0).

Stage II

Describes a tumour with some spread to nearby areas (T2), but has
not spread to lymph nodes (N0) or to distant parts of the body (M0).

Stage III

Describes any larger tumour (T3), with no spread to regional lymph nodes (N0) or
metastasis (M0), or a smaller tumour (T1, T2) that has spread to regional lymph
nodes (N1) but has no sign of distant metastasis (M0).

Stage IVa

Describes any invasive tumour (T4a), with either no lymph node involvement (N0) or
spread to only a single same-sided lymph node (N1), but no metastasis (M0). It is also
used for any tumour (any T) with more significant spread to the lymph nodes (N2), but no
metastasis (M0).

Stage IVb

Describes any cancer (any T) with extensive spread to lymph nodes (N3), but no
metastasis (M0). For laryngeal cancer, it is also used for a very advanced localized
tumour (T4b). with or without lymph node involvement (any N), but no metastasis (M0).

Stage IVc

Indicates there is evidence of distant spread (any T, any N,

M1).

Grading
GX: Indicates the grade cannot be evaluated.
G1: Indicates the cells look more like normal tissue (well

differentiated).
G2: The cells are only moderately differentiated.
G3: The cells dont resemble normal tissue (poorly

differentiated).

Oncological Management
Standard treatments for patients with laryngeal cancer
include the following:
Radiation therapy alone.
Surgery
Concurrent chemoradiation.

Laser surgery.
Biological therapy.
(National Cancer Institute, 2012)

Surgery- early stage

The most common surgical procedures used to treat early laryngeal cancer
include:
Partial laryngectomy. The removal of part of the larynx, preserving the voice.

The following are some of the different types of partial laryngectomies:

Supraglottic laryngectomy. The removal of the area above the vocal folds. If

part of the hypopharynx is to be removed with the cancer, this is called a

partial pharyngectomy.
Cordectomy. The removal of a vocal fold.
Vertical hemilaryngectomy. The removal of one side of the larynx.
Supracricoid partial laryngectomy. The removal of the vocal folds and the

area surrounding them.

Surgery- late stage

Total laryngectomy. The removal of the entire larynx. During this operation, a

hole called a stoma is made in the front of the neck through the windpipe to
allow the person to breathe. This is called a tracheostomy (see below).
Because the vocal folds have been removed, people can no longer speak
using their vocal folds after a total laryngectomy. However, a speech
pathologist can teach people to speak in a different way after the surgery.
Laryngopharyngectomy. A laryngopharyngectomy is the removal of the entire

larynx, including the vocal folds, and part or all of the pharynx. After this
surgery, doctors must reconstruct the pharynx using flaps of skin from the
forearm, other parts of the body, or a segment of the intestine. Like a total
laryngectomy, people can no longer speak using the vocal folds and they may
also have difficulty swallowing after laryngopharyngectomy. However, speech
pathologists can help people learn to speak and swallow afterwards.
Tracheostomy. In both partial and total laryngectomies, the surgeon makes a

hole called a stoma in the front of the neck into the windpipe or trachea. A
tube is often inserted to keep the hole open. Air enters and leaves the
windpipe (trachea) and lungs through the stoma, allowing the person to
breathe.

Laryngectomy
Partial Laryngectomy
In a partial laryngectomy,

the stoma is usually

temporary. After recovery
from the partial
laryngectomy, the tube is
removed, the hole heals
closed, and the person can
then breathe and talk in the
same way as before the
surgery. In some cases, the
voice may be hoarse or
weak.

Total Laryngectomy

In a total laryngectomy,

the stoma is permanent,

and the person breathes
through the stoma and
must learn to speak in a
new way.

Surgery- neck dissection

If cancer has spread to the lymph nodes in the neck, a

neck dissection may be necessary.

There are several types of neck dissections, depending
on the stage and location of the cancer.
Some or all the lymph nodes in the neck may have to be
removed (partial neck dissection, modified neck
dissection, selective neck dissection). A
A patient may have varying degrees of stiffness in the
shoulder and the neck and loss of sensation in the neck
after this surgery.

Laser surgery

Watch the following clip to observe laser surgery for laryngeal carcinoma
patients

http://www.youtube.com/watch?v=-_rNvLW1iX4

Targeted therapy
Targeted therapies refer to a group of medicines that are designed to target and disrupt one

or more of the biological processes that cancerous cells use to grow and reproduce.
A targeted therapy called cetuximab can be used to treat cases of stage three or stage four

laryngeal cancer where it's not possible to use chemotherapy.

Cetuximab targets special proteins called epidermal growth factor receptors (EGFRs), which

are found on the surface of cancerous cells. EGFRs help the cancer to grow, so by targeting
them cetuximab can prevent the cancer from spreading.
Cetuximab is given intravenously which slowly delivers the first dose over the course of a few

hours. Further doses should take about an hour and are given weekly.
Most infusion reactions occur within 24 hours of treatment starting, so you'll be closely

monitored once your treatment begins. If you have symptoms of an infusion reaction, such as
a rapid heartbeat or breathing problems, anti-allergy medicines can be used to relieve them
for example, corticosteroids.
These measures mean that deaths resulting from infusion reactions in people taking

cetuximab are very rare, occurring in less than 1 out of every 1,000 cases.
NHS Choices (2011)

Targeted therapy
The side effects of cetuximab are usually mild and include:
skin rashes
feeling sick
diarrhoea
breathlessness
eye inflammation (conjunctivitis)

Cetuximab can trigger allergic reactions in some people, such as

a swollen tongue or throat.
Occasionally, the allergic reaction can be severe and lifethreatening. This is known as an infusion reaction and it occurs
in about 1 in 35 people who take cetuximab.
NHS Choices (2011)

Radiotherapy recommendations
Stage T1-2, N0 (Glottic & Supraglottic only):
Surgery/RT equivalent cure rate
RT alone offers 5 year local control rates of 75-90%in T1
tumours
RT preferable
Stages T3-4, N+:
Surgery plus adjuvant RT in selected cases
Nodal disease:
RT to neck for N2-3 disease or N1 with extra -capsular
disease

Recurrent Disease
Standard treatment options:
1.Selected patients with local recurrence may be retreated with moderate-dose
external-beam radiation therapy using intensity-modulated radiation therapy,
stereotactic radiation therapy, or intracavity or interstitial radiation to the site of
recurrence.
2.In highly selected patients, surgical resection of locally recurrent lesions may be
considered.
3.If a patient has metastatic disease or local recurrence that is no longer amenable
to surgery or radiation therapy, chemotherapy should be considered.
Treatment options under clinical evaluation:
Clinical trials evaluating chemotherapy should be considered.
Stereotactic radiation for locally recurrent disease or persistence

Radiotherapy Techniques
3D conformal treatment:
2/3 beams, PTV + 1cm margin
ant neck
Glottic Tumours:
55Gy/20 #/4 weeks
64Gy/32# /6.5 weeks
50Gy/16#/3 weeks
Other tumours:
66-70Gy/33-35#/7 weeks to
macroscopic disease
44-50Gy/22-25#/5 weeks to
microscopic disease

Radiotherapy Techniques

IMRT
Stereotactic
Arc therapy

NRAG Report (2007):

All Head neck patients must be treated using 4D
conformal radiotherapy by 2017.

OAR

Brachial Plexus < 60Gy

Brainstem < 54Gy (60Gy point dose)
Eye < 35Gy
Inner/Middle Ears < 50Gy
Lacrimal Gland < 30Gy
Lens < 10Gy
Mandible < 70Gy
Optic Chiasm < 50Gy
Optic NN < 54Gy
Parotid V24 < 50% (mean dose <
26Gy)
Spinal Cord < 45Gy
Temporal Lobe < 60Gy
TMJ < 70Gy
Tongue Max Dose < 55Gy
Tracheostomy (uninvolved) < 50Gy

Class interaction

On a post-it note write down at two acute side effects:

Stick the notes on the white board

Daily management- acute side effects

erythema
mouth ulcers
sore mouth and throat - pain
xerostomia
hypogeusia/ageusia
Dysgeusia- refers to the presence of a
metallic, rancid, or foul taste in the
mouth
anorexia
tiredness
nausea

Radiographer review daily-fit for treatment

MDT weekly review- consultant, registrar, Macmillan radiographer/nurse

specialist, dietician, speech and language therapist, pain management,

counsellor, chemotherapy nurses etc.
Regular blood counts

Chronic Side Effects

Possible long-term or late effects after treatment for laryngeal cancer include:
Problems swallowing (dysphagia) - This can be caused by fibrosis of the
wall of the oesophagus, by narrowing of the oesophagus (stricture), and by a
loss of sensation when swallowing. A speech and language therapist can
provide help and advice with swallowing problems.
Low levels of the thyroid hormone Thyroxine (hypothyroidism) - This
happens when radiotherapy treatment affects the nearby thyroid gland.
Lymphoedema - This is an abnormal collection of fluid called lymph that can
cause swelling in the neck. Its a rare side effect that can happen when
lymph nodes have been removed by surgery and/or damaged by
radiotherapy.
(MacMillan, 2011)

Prognosis

(NICE 2004)

Class interaction

Case Study Review: Your views

Questions?

References
American Joint Committee on Cancer (AJCC) (2010) AJCC Cancer Staging Manual, Seventh Edition (2010), SpringerVerlag: New York. [Online] Available at:, www.cancerstaging.net. (Accessed 15 November 2012).

Cancer Network (2012) Head and Neck Tumors. [Online]. Available from:
http://www.cancernetwork.com/image/image_gallery?img_id=1169527&t=1216996415170 (Accessed 15 November
2012).
NHS Choices (2011) Treating Laryngeal Cancer. [Online.] Available from:
http://www.nhs.uk/Conditions/Cancer-of-the-larynx/Pages/Treatment.aspx (Accessed 15 November 2012)
NICE (2004) Improving outcomes in head and neck cancers - The Manual. [Online] Available from:
http://guidance.nice.org.uk/CSGHN/Guidance/pdf/English (Accessed 15 November 2012).

MacMillan (2011) Follow-up after treatment for laryngeal cancer . [Online]. Available from:
http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Larynx/Livingwithlaryngealcancer/Followup.aspx
(Accessed 16 November 2012)

NRAG (2007) Radiotherapy: developing a world class service for England. Report to Ministers from National
Radiotherapy Advisory Group. London. [Online] Available from:
http://www.axrem.org.uk/radiotheraphy_papers/DH_Radiotheraphy_developing_first_class_service_NRAG.pdf

Suggested Reading
Gomez, D., Cahlon, O., Mechalakos, J and Lee, N. (2010) An investigation of intensity-modulated radiation therapy
versus conventional two-dimensional and 3D-conformal radiation therapy for early stage larynx cancer, Radiation
Oncology, Vol. 5. pp. 74. [Online] Available from:
http://www.biomedcentral.com/content/pdf/1748-717X-5-74.pdf (Accessed 20 November, 2012)