MANAGEMENT

OF CARCINOMA
LARYNX
Dr. Satish Chandra T

Associate Professor

Dept of ENT & Head and Neck surgery

Dr PSIMS&RF
ANATOMY
 ANATOMY AND CANCER
 Weak points for the spread of laryngeal cancer

 Broyle’s ligament has no perichondrium, providing carcinoma direct access to the

cartilage.

 Fenestrations within the infrahyoid epiglottis provide a route for invasion of the
preepiglottic space.

 Ossification at the anterior commissure and the posterior border of the thyroid ala of
the thyroid cartilage provide a route for cancer spread.

 Points of attachment of the cricothyroid ligament and the anterior origin of the
thyroarytenoid musculature provide a route for cancer spread.

 The tubuloalveolar glands of the subglottis and the anterior floor of the ventricle serve
as a route of cancer spread inferiorly beneath the mucosa and anteriorly to the thyroid
cartilage.
ANATOMY
 PRE-EPIGLOTTIC SPACE
• Pre-epiglottic space
– Anterior: thyrohyoid membrane &
thyroid cartilage
– Posterior: epiglottis elastic cartilage
– Inferior: Petiole attachment to thyroid
cartilage
• Conduit :
– elastic epiglottic cartilage has
perforations -direct extension
of infrahyoid supraglottic cancer
into this fascia-bound space
• - Bilateral neck drainage
• - Almost 50% of supraglottic
carcinomas have preepiglottic
space involvement… implication is
upstage to T3 tumor.
 PARAGLOTTIC SPACE

 Paraglottic space:
 Superior border : quadrangular
membrane
 Inferior border: conus elasticus
 Lateral border: inner surface of the
thyroid cartilage
 Medial border: ventricle
 TRANSGLOTTIC TUMORS

 Usually initiate as supraglottic or glottic

cancers
 McGravan (1961)
 must cross three regions: false
cords, ventricle, true cord
 alters prognosis
 Fail the compartmentalization
hypothesis
 direct mucosal extension
 paraglottic space
 LYMPH DRAINAGE

 Rule of thumb: Glottic and supraglottic

to levels 2-3, subglottic to level 4

 Very sparce lymphatics in TVC,

therefore glottic ca usually better
prognosis

 Delphian node = midline pretracheal

node

 Glottic and subglottic tumors have a 2%

to 5% risk of neck disease unless the
subglottic extension exceeds 10 mm.
 CLINICAL PRESENTATION
 Physical Exam
 Complete head and neck exam
 Palpation for nodes; restricted laryngeal crepitus.
 Quality of voice
 Breathy voice = cord paralysis
 Muffled voice = supraglottic lesion
 Laryngoscopy
 Laryngeal mirror
 Fiberoptic exam (lack depth perception)
 Note: contour, color, vibration, cord mobility, lesions.
 Stroboscopic video laryngoscopy
 Highlights subtle irregularities: vibration, periodicity, cord closure
 BIOPSY AND HISTOLOGY

 Direct laryngoscopy with biopsy

 Histologic subtypes
 Squamous cell carcinoma
 > 90% of causes
 Characterized by nl  hyperplasia  dysplasia  CIS  invasive CA
 Invasive CA characterized by: well, moderately, or poorly differentiated
 Linked to tobacco and excessive alcohol
 Variance: verrucous, spindle cell carcinoma, & basaloid.
 Laryngoscopy – direct and micro
 Points for assessment include the following:
 Degree of alteration of mobility of the true vocal cord
 Degree of alteration of mobility of the arytenoid cartilage
 Involvement of the anterior commissure
 Degree of invasion of the subglottis
 Status of the mucosa surrounding the primary site
 This posterolateral cricoid involvement is a major contraindication to any
organ preservation surgery techniques.
 This pseudofixation is unlikely to represent malignant invasion of the
cricoarytenoid joint and/or musculature, suggesting that laryngeal
preservation techniques may be employed.
 IMAGING
 Tumor extent (limitations of endoscopy)
 Pre-epiglottic space and paraglottic space involvement, cartilage erosion

 Ultrasound
 To identify cervical mets and laryngeal abn.

 MRI:
 high-density tumor vs fat in the preepiglottic space
 Soft tissue invasion
 Nodal disease
 Extra capsular spread

 CT: thyroid cartilage destruction

 (presence mandates a total laryngectomy)
 Still undercalls cartilage invasion

 PET
 Role under investigation, currently not standard of care
 Specific application
 Identifying occult nodal mets
 Distinguish recurrence vs radionecrosis or other prior tx sequalae
 Staging

•• Subglottis
Supraglottis
Glottis
––
– Tis:
Tis:
Tis:CA
CAin-situ
CA in-situ
in-situ
–– T1:
T1:limited
limitedtotosubsite
cord; of supraglots
– T1: limited to subglottis
w/normal
T1a: onecord mobility
cord; T1b: two cords
– T2: extends to vocal cord with
–– T2:
T2:invade mucosa
extends of > 1 subsite
to supraglottis, of
and/or
normal or impaired
supraglottis, or mobility
glottis,w/impaired
outsidecord
of
subglottis, and/or
T3: limited
– supraglottis
mobility to larynx
w/out fixationw/vocal cord
of the larynx
–– T3:
T3:limited
limitedtotolarynx
fixation larynxw/vocal
w/vocalcord
cordfixation
and/or invades
fixation postcricoid
and/or area, pre-space,
invades paraglottic
– T4a: invades cricoid or thyroid
epiglottic tissues,
and/or minor paraglottic
thyroid space,
cartilage erosion
cartilage, and/or invades tissues
– and/or minor thyroid cartilage erosion
T4a: invades thyroid cartilage and/or
beyond the larynx
– T4a: invades
tissues thyroid
beyond cartilage and/or
larynx
– T4b:
– tissues
invades
beyond prevertebral space,
larynx
T4b: invades prevertebral space,
– encases
T4b:
encases carotid
invades
carotid artery,
prevertebral
artery, or invades
orspace,
invadesencases
carotid artery,
mediastinal
mediastinal or invades mediastinal
structures
structures
structures
 Staging

• Subglottis • Nodes
– Tis: CA in-situ – N0: no regional node mets
– T1: limited to subglottis – N1: single ipsilateral node, ≤ 3 cm
– T2: extends to vocal cord with – N2a: single ipsilateral node, > 3
normal or impaired mobility cm, ≤ 6 cm
– T3: limited to larynx w/vocal cord – N2b: multiple ipsilateral nodes, ≤ 6
fixation cm
– T4a: invades cricoid or thyroid – N2c: bilateral or contralateral
cartilage, and/or invades tissues nodes, ≤ 6 cm
beyond the larynx – N3: node > 6 cm
– T4b: invades prevertebral space, • Mets
encases carotid artery, or invades – Mx: unknown
mediastinal structures
– M0: no distant mets
– M1: distant mets
 STAGE GROUPING

Stage 0 Tis N0 M0
Early
Stage I T1 N0 M0
stage
Stage II T2 N0 M0
T3 N0 M0
Stage III
T1-3 N1 M0
T4a N0-1 M0
Stage IVA Advanced
T1-4a N2 M0
stage
T4b any N M0
Stage IVB
any T N3 M0
Stage IVC any T any N M1
 Treatments – Options
 Surgery
 Microlaryngeal surgery
 Hemilargyngectomy
 Supraglottic laryngectomy
 Near-total laryngectomy
 Total laryngectomy
 Photodynamic Therapy
 Radiation
 Chemothrapy
 Cisplatin + 5-fluorouracil
Type of Cancer Recommended Treatment Other Option

T1 Cancer (Glottis) Endoscopic Resection (selected patients) Open organ-preservation surgery

OR
Radiation Therapy

T2 Cancer (Glottis, favorable) Open organ-preservation surgery Endoscopic resection (selected patients)
[Superior tumor on radiographic imaging, OR
with normal cord mobility] Radiation Therapy

T2 Cancer (Glottis, unfavorable) Open organ-preservation surgery Radiation therapy

[Deeply invasive tumor on radiographic imaging, OR
with or without subglottic extension, with impaired Concurrent chemoradiation therapy (selected patients with Endoscopic resection (selected patients)
cord mobility (indicating deeper invasion)] node-positive disease)

T1 – T2 Cancer (Supraglottis, favorable) Open organ-preservation surgery Endoscopic resection (selected patients)
[Superficial invasion on radiographic imaging and OR
preserved cord mobility, and/or a tumor of the Radiation Therapy
aryepiglottic fold with minimal involvement of the
medical wall of the pyriform sinus]

T2 Cancer (Supraglottis, unfavorable) Open organ-preservation surgery Radiation therapy

OR
[More locally advanced and invasive]
Concurrent chemoradiation therapy (selected patients with Endoscopic resection (selected patients)
node-positive disease)

T3 – T4 Cancers (Glottis or Supraglottis) Concurrent chemoradiation therapy Radiation therapy

OR
Open organ-preservation surgery (in highly selected
patients)
yes No
 NECK NODES

 Modified or radical neck dissections are indicated in

the presence of nodal disease
 Neck dissections may be performed in patients with
supra or subglottic T2 tumors even in the absence of
nodal disease
 N0 necks can have a selective dissection sparing the
SCM, IJ, and XI
 N1 necks usually have a modified dissection of levels
II-IV
 ORGAN PRESERVING SURGERY

 Principles:
 Local control and accurate assesment of 3D extent of tumor
 The cricoarytenoid unit is the basic functional unit of the larynx.
 “It is the cricoarytenoid unit, not the vocal folds, that allows for
physiologic speech and swallowing without the permanent need for
a tracheostoma after supracricoid laryngectomy.”
 ORGAN SPARING SURGERY
 Mostly for early laryngeal cancers (T1 and T2)

 Absolute Contraindications:
 arytenoid fixation, thyroid cartilage invasion, interarytenoid invasion,
subglottic extension to involve the cricoid cartilage, lesions that extend
outside the larynx, and preepiglottic space invasion.
 (a relative contraindication is anterior commisure lesions… recurrance rates
are higher and speech results are variable)

 Preoperative evaluation
 “fixed vs. pseudofixed” TVC
 Pulmonary function testing:
 the real issue is how well pt will tolerate aspiration in early recovery period
 COPD is relative contraindication
 TRANS ORAL LASER MICROLARYNGEAL
SURGERY
 Minimal loss of healthy tissue

 Few surgical contraindications based on tumor - Carotid artery involvement

- Bilateral arytenoid involvement

 Avoidance of extensive reconstruction which would result in insensate anatomy

 Avoidance of tracheotomy !!

 No external incisions

 Early swallowing post-operatively

 ALL other therapy methods are still available

 Rarely a need for tracheotomy

 Usually able to remove NG feeding tube quickly

 Neck dissection if needed is done 2 - 3 weeks after TLM

ENDOSCOPIC LASER COEDECTOMY
Vertical partial laryngectomy.

• Vocal cord tumors that approach

or involve the anterior commissure
but do not cause vocal cord fixation

• The posterior extension is

sufficient to retain the arytenoid
cartilage
 Supraglottic Laryngectomy

 Supraglottic carcinomas with normal

vocal cord mobility and no ventricular
involvement

 Contraindications
 tumor extension into the glottis or
impairment of cord mobility;
 invasion of the thyroid cartilage,
cricoid cartilage, postcricoid area
 extension to the base of the tongue
 involvement of the apex of the
piriform sinus.
SUPRACRICOID LARYNGECTOMY WITH
CRICOHYOIDOPEXY

 Supraglottic carcinomas involving the

preepiglottic space, paraglottic space,
or thyroid cartilage

 Paraglottic, epiglottic, and preepiglottic

spaces and the entire thyroid cartilage
are resected.

 The resultant large laryngeal defect is

repaired by suturing the hyoid bone
tightly to the cricoid cartilage
SUPRACRICOID LARYNGECTOMY WITH
CRICOHYOIDOEPIGLOTTOPEXY
 early-stage carcinomas of the
anterior commissure,
 tumors involving both vocal
cords
 tumors of an entire vocal
cord with impaired mobility
 larynx is reconstructed by
suturing the hyoid bone and
the suprahyoid epiglottis
closely to the cricoid
cartilage
NEAR TOTAL LARYNGECTOMY

 A segment of the contralateral

(uninvolved) side of the larynx
is preserved
 Recurrent laryngeal nerve
 Part of the thyroid lamina
 The entire arytenoid cartilage,
and
 A portion of the
thyroarytenoid muscle
 Cricoid cartilage a part
TOTAL LARYNGECTOMY
 PROGNOSIS

5 year survival
Stage I >95%
Stage II 85-90%
Stage III 70-80%
Stage IV 50-60%
 After initial treatment patients are followed at 4-6 week
intervals. After first year decreases to every 2 months. Third
and fourth year every three months, with annual visits after that
 PROGNOSIS

 Patients considered cured after being disease

free for five years
 Most laryngeal cancers reoccur in the first two
years
 Despite advances in detection and treatment
options the five year survival has not improved
much over the last thirty years
 COMPLICATIONS
 Infection
 Voice alterations
 Swallowing difficulties
 Loss of taste and smell
 Fistula
 Tracheostomy dependence
 Stroke or carotid “blowout”
 Hypothyroidism
 Radiation induced fibrosis
 VOICE REHABILITATION

 Tracheoesophageal prosthesis

 Electrolarynx

 Pure esophageal speech

CHEMORADIATION ADVANTAGES

Theoretical Benefits of Chemoradiation

• Inhibiting repair of lethal and sublethal damage
induced by radiotherapy
• Radiosensitizing hypoxic cells
• Reducing tumor burden, leading to an improved
blood supply
• Redistributing tumor cells to a more
radiosensitive cell cycle phase
• Inducing apoptosis
 CHEMOTHERAPY

 Neoadjuvant – prior to surgery or radiotherapy

 Concomitant – simultaneously with radiotherapy

 Adjuvant – after local treatment (surgery or Rt or Chemoradiation)

 Alternating or split course - alternating chemo and rt, to

reduce tissue toxicity

 Chemotherapy alone – palliative for recurrent or metastatic

 Induction Chemotherapy

Direct Laryngoscopy

>50% Response <50% Response

Chemoradiation Laryngectomy

Adjuvant Chemotherapy Adjuvant Therapy

 INDUCTION CHEMOTHERAPY

 It is thought that chemotherapy will treat micrometastatic

disease.

 It is thought that chemotherapy will be better delivered in

tumors that are untreated.

 The patients are in better physical condition prior to

definitive therapy and therefore more likely to tolerate
full dose chemotherapy.

 There is an opportunity to shrink the tumor prior to

definitive therapy giving a better chance of cure.
 The most frequent and successful (until
recently) was cisplatin 100 mg/m2 on D1 and 5-
FU 1000 mg/m2 D1-5
 2 cycles of chemo (cisplatin and 5 FU)
 PR or CR assessed
 PR or CR had 3rd cycle of chemo followed by radiotherapy
 Non-responders went on to TL+PORT
 Yes P
P X2 Response? Radiation
F
F

No

Laryngectomy Radiation

PF: Cisplatin 100 D1 + 5-FU 1000 CI-D1-5 Q 3 weeks

 Radiation
T
Yes
P
Response
F
No

Laryngectomy
TPF: Docetaxel 75D1 + Cisplatin 75D1 + 5-FU 750 CI- D1-5 Q 3 weeks x3
 TARGETED CHEMOTHERAPY

• A specific receptor on the surface of

common head and neck cancer cells is
called Epidermal Growth Factor Receptor
(EGFR)
• EGFR levels increase in in advanced
stage tumors and in poorly
differentiated tumors.
• Cetuximab is an antibody against the
EGFR receptor which can stop cell cycle
progression and induce cell death
 RADIOTHERAPY

 Five fractions/week of 2 Gy, to a total dose of

60-70 Gy became an international standard, and
is recommended in the guidelines
 RADIOTHERAPY
 Adjuvant radiation is started within 6 weeks of surgery and with
once daily protocols lasts 6-7 weeks
 Indications for post-op radiation include:
 T4 primary, bone/cartilage invasion,
 extension into neck soft tissue,
 perineural invasion,
 vascular invasion,
 multiple positive nodes, nodal extracapsular extension,
 margins<5mm, positive margins, CIS margins,
 subglottic extension of primary tumor.
HOW RADIATION WORKS

• X-ray photons interact with matter,

knocking electrons from the orbitals of
atoms
• These high energy electrons can either
directly damage DNA chemical bonds, or
interact with water molecules forming free
radicals that then cause DNA damage
• Damage to DNA may result in single or
double strand breaks which can cause cell
death
• DNA repair enzymes are more readily
activated in healthy cells than in cancer
cells
LINEAR ACCLERATOR

• Produces high energy electron

beams and Xray beams
• Patient positioning and targeting
systems are integrated into the
treatment machine
 IMRT – INTENSITY MODULATED
RADIATION THERAPY

Intensity Modulated Radiation Therapy - means that the

intensity of the radiation beam in a given treatment field is
varied via multiple multileaf blocking arrangements called
segments.

• Intensity modulation combined with multiple fields (radiation

beam angles) or arcs allows for conformal radiotherapy (ie high
radiation isodose lines conform to the target volume and spare
normal tissues).
 Anticipated Toxicities

 Hypothyroidism
 Mucositis
 Dermatitis
 Xerostomia
 Fibrosis
 Fistulas
 Dysgeusia