management protocols of laryngeal malignancy

1. MANAGEMENT
OF CARCINOMA
LARYNX
Dr. Satish Chandra T
Professor
Dept of ENT & Head and Neck surgery
Dr PSIMS&RF

5. ANATOMY

6. 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.

7. ANATOMY

8. PRE-EPIGLOTTIC SPACE & PARA-GLOTTIC 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
• Bilateral neck drainage
• Almost 50% of supraglottic
carcinomas have preepiglottic
space involvement… implication is
upstage to T3 tumor.

9. PARAGLOTTIC SPACE
 Paraglottic space:
 Superior border : quadrangular
membrane
 Inferior border: conus elasticus
 Lateral border: inner surface of the
thyroid cartilage
 Medial border: ventricle

10. 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

11. 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.

12. DIAGNOSIS
 Dysphagia
 Vocal changes
 Aspiration
 Otalgia
 Blood-tinged sputum
 Neck mass
 Cachexia
 Dyspnea
 Pain
 Halitosis

13. NATURAL HISTORY WITHOUT
TREATMENT
 Hemoptysis> supraglottic tumors
 Dysphonia> TVC/glottic lesions
 Airway Obstruction> insidious subglottic tumors
 Aspiration> supraglottic (also with incompetent
glottis)
 Otalgia> supraglottic (infiltration of musculature)
 Dysphagia: any location, muscle, sensory, motor, joint

14. 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

15. BIOPSY AND HISTOLOGY
 Direct laryngoscopy with biopsy
 Histologic subtypes
 Squamous cell carcinoma
 > 90% of cases
 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.

16.  The five categories of laryngeal squamous cell abnormality
(from benign to clearly malignant):
 hyperkeratosis
 hyperkeratosis with atypia
 carcinoma in situ (CIS)
 superficially invasive carcinoma
 invasive carcinoma

17. H, H+A, CIS
 hyperkeratosis +/- atypia and CIS
 conservative management: stripping of VC
 5%–30% with future invasive cancer
 follow-up and possible re-biopsy 6 - 12 weeks

18. BORDERS GRADING

19. SUPERFICIALLYINVASIVEVS.INVASIVESCC

20.  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.

21. 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

22. • 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

23. • 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

24. STAGE GROUPING
Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III
T3 N0 M0
T1-3 N1 M0
Stage IVA
T4a N0-1 M0
T1-4a N2 M0
Stage IVB
T4b any N M0
any T N3 M0
Stage IVC any T any N M1
Early
stage
Advanced
stage

25. MANAGEMENT OF PRECANCEROUS
LESIONS
 Radiotherapy …not so much!!!
 failure (10%)
 no future option for XRT T1 / T2
 Surgery
 Generous stripping
 Informed consent re: multiple treatments
 Good compliance (years)
 Supravital staining with toluidine blue
 Rapid or frequent recurrence

26.  Surgery
 Microlaryngeal surgery
 Hemilargyngectomy
 Supraglottic laryngectomy
 Near-total laryngectomy
 Total laryngectomy
 Photodynamic Therapy
 Radiation
 Chemothrapy
 Cisplatin + 5-fluorouracil
Treatments – Options

27. 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]
Open organ-preservation surgery
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)]
Open organ-preservation surgery
OR
Concurrent chemoradiation therapy (selected patients with
node-positive disease)
Radiation therapy
Endoscopic resection (selected patients)
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]
Open organ-preservation surgery
OR
Radiation Therapy
Endoscopic resection (selected patients)
T2 Cancer (Supraglottis, unfavorable)
[More locally advanced and invasive]
Open organ-preservation surgery
OR
Concurrent chemoradiation therapy (selected patients with
node-positive disease)
Radiation therapy
Endoscopic resection (selected patients)
T3 – T4 Cancers (Glottis or Supraglottis) Concurrent chemoradiation therapy
OR
Open organ-preservation surgery (in highly selected
patients)
Radiation therapy

30. yes No

32. GLOTTIC CARCINOMA
 T1, N0, M0
 CO2 laser cordectomy ± RxTh (if positive margin)
 T1a away from the ant. commissure and the arytenoid cartilage
 External RxTh: T1a reaching or slightly invading the ant commissure
T1b not originating from the ant. commissure
T1 invading the post. Commissure
T1a with inadequate exposure for laser cordectomy
 Partial laryngectomy
 Tumor of the ant. commissure
 Patients with poor compliance for follow-up

33.  T2, N0-N1, M0
 Partial laryngectomy (supracricoid laryngectomy) + bilateral ND ± RxTh
 “Moderately advanced” RxTh protocol + ND
-tumor not suitable for conservative surgery
-poor general health, poor pulmonary reserve
-patient’s wish to preserve excellent voice
 CO2 laser “extended” cordectomy
-only in very specific cases: T2a (normal V.C.mobility) easily exposed by endoscopy
-surgeon’s feeling to obtain free margins
 T2, N2a, M0
-“Locally advanced” RxTh protocol + ND
- Partial laryngectomy (supracricoid laryngectomy) + bilateral ND + RxTh

34. SUPRAGLOTTIC CARCINOMA
 T1-T2, N0-N1, M0
 External surgery: supraglottic laryngectomy or supracricoid laryngectomy
(T2 invading glottis) + bilateral ND ± RxTh
 adequate general health and pulmonary reserve
 Endoscopic laser supraglottic laryngectomy
 only for selected superficial and suprahyoid T1
 T2, N2a, M0
 “Locally advanced” RxTh protocol (T+N bilateral) + ND
 External surgery: supraglottic laryngectomy or supracricoid laryngectomy (T2
invading glottis) + bilateral ND + RxTh

35. 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

37. 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.”

38. 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

39. 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

40. ENDOSCOPIC LASER COEDECTOMY

41. 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

42.  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

44. 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

45. 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

46. • Oncologic contraindications for SCPL-CHEP
• Tumors of the glottis with subglottic extentension
• Tumors of the glottis invading the posterior commissure
• Tumors of the glottis invading the outer perichondrium of the thyroid cartilage or
manifesting with extralaryngeal spread of tumor
• Oncologic contraindications for SCPL-CHP
• Arytenoid cartilage fixation
• Infraglottic extension of tumor more than 10 mm anteriorly (cricothyroid membrane),
more than 5 mm posterolaterally,
• Major preepiglottic space invasion with clinical evidence of bulging beneath the vallecula
mucosa and/or extension through the thyrohyoid membranes
• Tumor abutting the hyoid bone, requiring resection of this structure
• Cricoid cartilage invasion

47. 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

48. TOTAL LARYNGECTOMY

49. 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

50. 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

51. COMPLICATIONS
 Infection
 Voice alterations
 Swallowing difficulties
 Loss of taste and smell
 Fistula
 Tracheostomy dependence
 Stroke or carotid “blowout”
 Hypothyroidism
 Radiation induced fibrosis

52. VOICE REHABILITATION
 Tracheoesophageal prosthesis
 Electrolarynx
 Pure esophageal speech

54. 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

55. 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

56. Induction Chemotherapy
Direct Laryngoscopy
>50% Response <50% Response
LaryngectomyChemoradiation
Adjuvant Chemotherapy Adjuvant Therapy

57. 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.

58.  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

60. P
F
Laryngectomy
PF: Cisplatin 100 D1 + 5-FU 1000 CI-D1-5 Q 3 weeks
Response? Radiation
No
Yes
Radiation
P
F
X 2

61. T
P
F
TPF: Docetaxel 75D1 + Cisplatin 75D1 + 5-FU 750 CI- D1-5 Q 3 weeks x3
Response
Laryngectomy
Radiation
No
Yes

62. 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

63. 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

64. 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.

65. 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

66. LINEAR ACCLERATOR
• Produces high energy electron
beams and Xray beams
• Patient positioning and targeting
systems are integrated into the
treatment machine

67. 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).

68.  Hypothyroidism
 Mucositis
 Dermatitis
 Xerostomia
 Fibrosis
 Fistulas
 Dysgeusia
Anticipated Toxicities