Laryngeal Carcinoma: An Overview

Ryan Eric Neilan MS IV For the Dept of Otolaryngology University of Texas Medical Branch July 20, 2007

Overview
11,000

new cases of laryngeal cancer per year in the U.S. Accounts for 25% of head and neck cancer and 1% of all cancers One-third of these patients eventually die of their disease Most prevalent in the 6th and 7th decades of life

Overview
4:1

male predilection Downward shift from 15:1 post WWII Due to increasing public acceptance of female smoking More prevalent among lower socioeconomic class, in which it is diagnosed at more advanced stages

Subtypes
Glottic

Cancer: 59% Cancer: 40%

Supraglottic Subglottic Most

Cancer: 1%

subglottic masses are extension from glottic carcinomas

History
The

first laryngectomy for cancer of the larynx was performed in 1883 by Billroth Patient was successfully fed by mouth and fitted with an artificial larynx In 1886 the Crown Prince Frederick of Germany developed hoarseness as he was due to ascend the throne.

Crown Prince Frederick of Germany

History
Was

evaluated by Sir Makenzie of London, the inventor of the direct laryngoscope Fredericks lesion was biopsied and thought to be cancer He refused laryngectomy and later died in 1888

History

Frederick was succeeded by Kaiser Wilhelm II, who along with Otto von Bismark militarized the German Empire and led them into WW I Could an Otolaryngologist have prevented WW I?

Risk Factors

Risk Factors
Prolonged

use of tobacco and excessive EtOH use primary risk factors The two substances together have a synergistic effect on laryngeal tissues 90% of patients with laryngeal cancer have a history of both

Risk Factors
Human

Papilloma Virus 16 &18 Chronic Gastric Reflux Occupational exposures Prior history of head and neck irradiation

Histological Types
85-95%

of laryngeal tumors are squamous cell carcinoma Histologic type linked to tobacco and alcohol abuse Characterized by epithelial nests surrounded by inflammatory stroma Keratin Pearls are pathognomonic

Histological Types
Verrucous

Carcinoma Fibrosarcoma Chondrosarcoma Minor salivary carcinoma Adenocarcinoma Oat cell carcinoma Giant cell and Spindle cell carcinoma

Anatomy

Anatomy

Anatomy

Anatomy

Anatomy

Anatomy

Anatomy

Anatomy

Natural History
Supraglottic

tumors more aggressive:

Direct extension into pre-epiglottic space Lymph node metastasis Direct extension into lateral hypopharnyx, glossoepiglottic fold, and tongue base

Natural History
Glottic

tumors grow slower and tend to metastasize late owing to a paucity of lymphatic drainage They tend to metastasize after they have invaded adjacent structures with better drainage Extend superiorly into ventricular walls or inferiorly into subglottic space Can cause vocal cord fixation

Natural History
True

subglottic tumors are uncommon Glottic spread to the subglottic space is a sign of poor prognosis Increases chance of bilateral disease and mediastinal extension Invasion of the subglottic space associated with high incidence of stomal reoccurrence following total laryngectomy (TL)

Presentation
Hoarseness

Most common symptom Small irregularities in the vocal fold result in voice changes Changes of voice in patients with chronic hoarseness from tobacco and alcohol can be difficult to appreciate

Presentation
Patients

presenting with hoarseness should undergo an indirect mirror exam and/or flexible laryngoscope evaluation Malignant lesions can appear as friable, fungating, ulcerative masses or be as subtle as changes in mucosal color Videostrobe laryngoscopy may be needed to follow up these subtler lesions

Presentation
Good

neck exam looking for cervical lymphadenopathy and broadening of the laryngeal prominence is required The base of the tongue should be palpated for masses as well Restricted laryngeal crepitus may be a sign of post cricoid or retropharyngeal invasion

Presentation
Other

symptoms include:

Dysphagia Hemoptysis Throat pain Ear pain Airway compromise Aspiration Neck mass

Work up
Biopsy

is required for diagnosis Performed in OR with patient under anesthesia Other benign possibilities for laryngeal lesions include: Vocal cord nodules or polyps, papillomatosis, granulomas, granular cell neoplasms, sarcoidosis, Wegners granulomatosis

Work up
Other

potential modalities:

Direct laryngoscopy Bronchoscopy Esophagoscopy Chest X-ray CT or MRI Liver function tests with or without US PET ?

Staging- Primary Tumor (T)

TX T0 Tis Minimum requirements to assess primary tumor cannot be met No evidence of primary tumor Carcinoma in situ

Staging- Supraglottis
T1 Tumor limited to one subsite of supraglottis with normal vocal cord mobility Tumor involves mucosa of more than one adjacent subsite of supraglottis or glottis, or region outside the supraglottis (e.g. mucosa of base of the tongue, vallecula, medial wall of piriform sinus) without fixation Tumor limited to larynx with vocal cord fixation and or invades any of the following: postcricoid area, preepiglottic tissue, paraglottic space, and/or minor thyroid cartilage erosion (e.g. inner cortex) T2

T3

T4a Tumor invades through the thyroid cartilage and/or invades tissue beyond the larynx (e.g. trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus) T4b Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

Staging- Glottis
T1 T1a T1b T2 T3 Tumor limited to the vocal cord (s) (may involve anterior or posterior commissure) with normal mobilty Tumor limited to one vocal cord Tumor involves both vocal cords Tumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility Tumor limited to the larynx with vocal cord fixation and/or invades paraglottic space, and/or minor thyroid cartilage erosion (e.g. inner cortex) Tumor invades through the thyroid cartilage, and/or invades tissues beyond the larynx (e.g. trachea, soft tissues of the neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

T4a

T4b

Staging- Subglottis
T1 T2 T3 T4a Tumor limited to the subglottis Tumor extends to vocal cord (s) with normal or impaired mobility Tumor limited the larynx with vocal cord fixation Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond larynx (e.g. trachea, soft tissues of the neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus) Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

T4b

Staging- Nodes
N0 N1 N2a N2b N2c N3 No cervical lymph nodes positive Single ipsilateral lymph node 3cm Single ipsilateral node > 3cm and 6cm Multiple ipsilateral lymph nodes, each 6cm Bilateral or contralateral lymph nodes, each 6cm Single or multiple lymph nodes > 6cm

Staging- Metastasis
M0 No distant metastases M1 Distant metastases present

Stage Groupings
0 I II III IVA IVB IVC Tis T1 T2 T3 T1-3 T4a T1-4a T4b Any T Any T N0 N0 N0 N0 N1 N0-2 N2 Any N N3 Any N M0 M0 M0 M0 M0 M0 M0 M0 M0 M1

Treatment
Premalignant

lesions or Carcinoma in situ can be treated by surgical stripping of the entire lesion CO2 laser can be used to accomplish this but makes accurate review of margins difficult

Treatment
Early

stage (T1 and T2) can be treated with radiotherapy or surgery alone, both offer the 85-95% cure rate. Surgery has a shorter treatment period, saves radiation for recurrence, but may have worse voice outcomes Radiotherapy is given for 6-7 weeks, avoids surgical risks but has own complications

Treatment
XRT

complications include:

Mucositis Odynophagia Laryngeal edema Xerostomia Stricture and fibrosis Radionecrosis Hypothyroidism

Treatment
Advanced

stage lesions often receive surgery with adjuvant radiation Most T3 and T4 lesions require a total laryngectomy Some small T3 and lesser sized tumors can be treated with partial larygectomy

Treatment

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.

Treatment
Chemotherapy

can be used in addition to irradiation in advanced stage cancers Two agents used are Cisplatinum and 5flourouracil Cisplatin thought to sensitize cancer cells to XRT enhancing its effectiveness when used concurrently.

Treatment
Induction

chemotherapy with definitive radiation therapy for advanced stage cancer is another option Studies have shown similar survival rates as compared to total laryngectomy with adjuvant radiation but with voice preservation. Role in treatment still under investigation

Treatment

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

Surgical Options

Hemilaryngectomy

No more than 1cm subglottic extension anteriorly or 5mm posteriorly Mobile affected cord Minimal anterior contralateral cord involvement No cartilage invasion No neck soft tissue invasion

Supraglottic laryngectomy

T1,2, or 3 if only by preepiglottic space invasion Mobile cords No anterior commissure involvement FEV1 >50% No tongue base disease past circumvallate papillae Apex of pyriform sinus not invloved

Supracricoid Laryngectomy

Resection of true vocal cords, supraglottis, thyroid cartilage Leave arytenoids and cricoid ring intact Half of patients remain dependent on tracheostomy

Total Larygectomy
Indications:

T3 or T4 unfit for partial Extensive involvement of thyroid and cricoid cartilages Invasion of neck soft tissues Tongue base involvement beyond circumvallate papillae

Total Laryngectomy

Total Laryngectomy

Total Laryngectomy

Total Laryngectomy

Voice Rehabilitation
Tracheostomal Electrolarynx Pure

prosthesis

esophageal speech

Complications

Inaccurate staging Infection Voice alterations Swallowing difficulties Loss of taste and smell Fistula Tracheostomy dependence Injury to cranial nerves: VII, IX, X, XI, XII Stroke or carotid blowout Hypothyroidism Radiation induced fibrosis

Prognosis
5 year survival Stage I Stage II Stage III Stage IV

>95% 85-90% 70-80% 50-60%

After initial treatment patients are followed at 46 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

References

Malignant Tumors of the Larynx and Hypopharynx. Hypopharynx. CummingsCummings- OtolaryngologyOtolaryngology- Head and Neck Surgery. 4th ed., Mosby, 2005. Malignant Laryngeal Lesions. LawaniLawani- Current Diagnosis and Treatment in OtolaryngologyOtolaryngology- Head and Neck Surgery. McGrawMcGraw-Hill and Lange, 2004. Neck. MooreMoore- Essential Clinical Anatomy. 2nd ed., Lippincott, 2002. Head and Neck. RohenRohen- Color Atlas of Anatomy. 5th ed., Lippincott, 2002. Surgery for Supraglottic Cancer. Cancer. MyersMyers- Operative Otolaryngology Head and Neck Surgery Vol. 1. 1st ed., Saunders, 1997. Surgery for Glottic Carcinoma. Carcinoma. MyersMyers- Operative Otolaryngology Head and Neck Surgery Vol. 1. 1st ed., Saunders, 1997. The Larynx. Larynx. Lore and MedinaMedina- An Atlas of Head and Neck Surgery. 4th ed., Elsevier, 2005. Hinerman, Hinerman, R, Morris, C, et al. Surgery and Postoperative Radiotherapy for for Squamous Cell Carcinoma of the Larynx and Pharynx. Am J Clin Oncol. Oncol. 2006; 29(6): 613613-621. Huang, D, Johnson, C, et al. Postoperative Radiotherapy in Head and Neck Carcinoma with Extracapsular Lymph Node extension and/or Positive Resection Margins: a Comparative Study. Int J Radiat Oncol Biol Phy. Phy. 1992; 23:73723:737-742. Bernier, J, Domenge, Domenge, C, et al. Postoperative Irradiation with or without Concomitant Concomitant Chemotherapy for Locally Advanced Head and Neck Cancer. N Engl J Med. 2004; 350: 19451945-1952. Sessions, D, Lenox, J, et al. Supraglottic Laryngeal Cancer: Analysis of Treatment Results. Laryngoscope. 2005; 115: 14021402-1410. Wolf, GT. The Department of Veterans Affairs Laryngeal Cancer Study Study Group. Induction Chemotherapy Plus Radiation Compared with Surgery Plus Radiation in Patients with Advanced Laryngeal Cancer. New England Journal of Medicine. 1991; 324: 16851685-90. Lefebre J, Chevalier D, Luboinski B, Kirkpatrick A, Collette L, Sahmoud T. Larynx Preservation in Pyriform Sinus Cancer: Preliminary Results of a European Organization for Research Research and Treatment of Cancer Phase III Trial. Journal of the National Cancer Institute. Jul 1996. 88(13): 890890-899. Grant Grants Atlas 10th ed. CDCD-ROM