management of ca larynx

MANAGEMENT OF CARCINOMA

LARYNXDr. 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

• Supraglottis

– Tis: CA in-situ

– T1: limited to subsite of supraglots

w/normal cord mobility

– T2: invade mucosa of > 1 subsite of

supraglottis, glottis, or outside of

supraglottis w/out fixation of the larynx

– T3: limited to larynx w/vocal cord

fixation and/or invades postcricoid

area, pre-epiglottic tissues, paraglottic

space, and/or minor thyroid cartilage

erosion

– T4a: invades thyroid cartilage and/or

tissues beyond larynx

– T4b: invades prevertebral space,

encases carotid artery, or invades

mediastinal structures

• Glottis

– Tis: CA in-situ

– T1: limited to cord;

T1a: one cord; T1b: two cords

– T2: extends to supraglottis, and/or

subglottis, and/or w/impaired cord

mobility

– T3: limited to larynx w/vocal cord

fixation and/or invades paraglottic

space, and/or minor thyroid cartilage

erosion

– T4a: invades thyroid cartilage and/or

tissues beyond larynx

– T4b: invades prevertebral space,

encases carotid artery, or invades

mediastinal structures

• Subglottis

– Tis: CA in-situ

– T1: limited to subglottis

– T2: extends to vocal cord with

normal or impaired mobility

– T3: limited to larynx w/vocal

cord fixation

– T4a: invades cricoid or thyroid

cartilage, and/or invades tissues

beyond the larynx

– T4b: invades prevertebral

space, encases carotid artery, or

invades mediastinal structures

Staging

• Subglottis

– Tis: CA in-situ

– T1: limited to subglottis

– T2: extends to vocal cord with

normal or impaired mobility

– T3: limited to larynx w/vocal

cord fixation

– T4a: invades cricoid or thyroid

cartilage, and/or invades tissues

beyond the larynx

– T4b: invades prevertebral

space, encases carotid artery, or

invades mediastinal structures

Staging

• Nodes

– N0: no regional node mets

– N1: single ipsilateral node, ≤ 3

cm

– N2a: single ipsilateral node, > 3

cm, ≤ 6 cm

– N2b: multiple ipsilateral nodes,

≤ 6 cm

– N2c: bilateral or contralateral

nodes, ≤ 6 cm

– N3: node > 6 cm

• Mets

– Mx: unknown

– M0: no distant mets

– M1: distant mets

STAGE GROUPING

Stage 0 Tis N0 M0

Stage I T1 N0 M0

Stage II T2 N0 M0

Stage IIIT3 N0 M0

T1-3 N1 M0

Stage IVAT4a N0-1 M0

T1-4a N2 M0

Stage IVBT4b any N M0

any T N3 M0

Stage IVC any T any N M1

Earlystage

Advanced stage

Surgery

Microlaryngeal surgery

Hemilargyngectomy

Supraglottic laryngectomy

Near-total laryngectomy

Total laryngectomy

Photodynamic Therapy

Radiation

Chemothrapy

Cisplatin + 5-fluorouracil

Treatments – Options

Type of Cancer Recommended Treatment Other Option

T1 Cancer (Glottis) Endoscopic Resection (selected patients)

OR

Radiation Therapy

Open organ-preservation surgery

T2 Cancer (Glottis, favorable) [Superior tumor on radiographic imaging, with normal cord mobility]


OR

Radiation Therapy

Endoscopic resection (selected patients)

T2 Cancer (Glottis, unfavorable) [Deeply invasive tumor on radiographic imaging, with or without subglottic extension, with impaired cord mobility (indicating deeper invasion)]


OR

Concurrent chemoradiation therapy (selected patients with node-positive disease)

Radiation therapy


T1 – T2 Cancer (Supraglottis, favorable) [Superficial invasion on radiographic imaging and preserved cord mobility, and/or a tumor of the aryepiglottic fold with minimal involvement of the medical wall of the pyriform sinus]


OR

Radiation Therapy


T2 Cancer (Supraglottis, unfavorable)

[More locally advanced and invasive]


OR

Concurrent chemoradiation therapy (selected patients with node-positive disease)

Radiation therapy


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

OR

Open organ-preservation surgery (in highly selected patients)

Radiation therapy

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 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.

Supraglottic Laryngectomy

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 survival5 year survival

Stage IStage I >95%>95%

Stage IIStage II 85-90%85-90%

Stage IIIStage III 70-80%70-80%

Stage IVStage IV 50-60%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

LaryngectomyChemoradiation

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

P

F

Laryngectomy

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

Response? Radiation

No

Yes

Radiation

P

FX 2

T

P

F

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

Response

Laryngectomy

Radiation

No

Yes

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).

Hypothyroidism

Mucositis

Dermatitis

Xerostomia

Fibrosis

Fistulas

Dysgeusia

Anticipated Toxicities

management of ca larynx

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