Laryngeal Cancer: Changes in Demographics, Patterns of Care, and Survival, Exercises of Radiotherapy

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Malignant Lesions of the Larynx

Renee Penn M.D.

Head & Neck Oncology Fellow

Division of Head and Neck Surgery

University of California, Los Angeles

Incidence

• 10K new cases of laryngeal cancer in U.S. annually
  • 3,900 deaths annually
• Gender
  • Since 1950‐ M:F ratio 15:1 5:1 in 2004
  • women have equal place in the toxic work environment
  • cigarette smoking
• Risk factors:
  • Tobacco
    • 13‐fold risk for laryngeal cancer for smokers
    • risk increases with increasing tobacco use
  • Alcohol
    • 34‐fold risk for laryngeal cancer if consume >1.5 L wine/day
  • Tea time?
    • mate in Latin America and chimarra in Brazil

Gene<cs/ Risk factors

 Aneuploidy  Tumor suppressor gene inactivation  Gene locus 17p13 : mutant p53 ………………………….DNA repair, apoptosis  Gene locus 9p21 : mutant p16 …………………………. Cell cycle regulation  Proto‐oncogene activation  Proto‐oncogene (11q13) ampli`ies cyclin D1………. Cell cycle regulation  Mutagen‐induced chromosome breaks  HPV  Types 16 and 18: E6 and E7 viral protein‐mediated degradation of p  Oropharyngeal malignancy  GERD  Koufman: n=31 with glottic SCC, GERD documented in 84%; only 58% were smokers

Embryology

• Frazer (1909)
  • supraglottis originates from the buccopharyngeal primordium
    • high risk of bilateral neck disease vs. glottic tumors ‐ metastasize ipsilaterally
• Pressman (1956)
  • separate derivation from glottis‐ supraglottic tumors of substantial bulk do not spread across the laryngeal ventricle to the vocal cord
• Tucker and Smith (1982)
  • Dye studies anatomically based con`irmation re: elastic tissue barriers
    • Formed basis of partial laryngeal surgery
      • Already advocated by Biller Cummings: otolaryngology, 4 th ed‐ 2005 ‐ Mosby, Inc.

Pre‐epigloNc space & Para‐gloNc 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
• Paraglottic space
  • quadrangular membrane inferiorly
  • conus elasticus anteriorly and medially
  • thyroid cartilage laterally Myers: Laryngoscope, Volume 106(5).May 1996.559‐ Cummings: otolaryngology, 4th^ ed‐ 2005 ‐ Mosby, Inc.

TransgloNc 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 McGavran et al. Cancer 1961.

Natural History WITHOUT Treatment

• Hemoptysis> supraglottic tumors
• Dysphonia> TVC/glottic lesions
• Airway Obstruction> insidious subglottic tumors
• Aspiration> supraglottic (also with incompetent glottis)
• Otalgia> supraglottic (in`iltration of musculature)
• Dysphagia: any location, muscle, sensory, motor, joint

Histology

• 95% SCC - Variations : - verrucous carcinoma, spindle cell carcinoma, basaloid SCC, and papillary SCC

• Other types of carcinoma:
  • neuroendocrine carcinoma
  • lymphepitheliomatous carcinoma
  • adenocarcinoma
  • others (sarcomas, lymphomas)
  • adenoid cystic (trachea more than subglottis)
• Underlying:
  • hyperplasia, dysplasia, CIS
• Overlying:
  • surface keratinization may be present.

Whatcha got???

• Patients with glottic tumors are seen early because of hoarseness….
  • Biopsy !!!!!
• Oops!
  • fungal laryngitis, sarcoidosis, tuberculosis, or Wegener's granulomatosis , pseudoepitheliomatous hyperplasia (granular cell myoblastoma)
• The ive categories of laryngeal squamous cell _abnormality_ (from benign to clearly malignant): - hyperkeratosis - hyperkeratosis with atypia - carcinoma in situ (CIS) - supericially invasive carcinoma - invasive carcinoma

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

Superficial vs. Invasive GloNc SCC

• Super`icial invasive carcinoma vs. CIS

– It is all about the SLP!!!!!

• “The central third”

– early symptoms of voice change

• Sampling error:

– Slaughter's hypothesis of `ield cancerization

as described originally for the oral cavity

Management of precancerous lesions

• Radiotherapy …not so much!!!
  • failure (10%)
  • no future option for XRT T 1 / T 2
• Surgery
  • Generous stripping
  • Informed consent re: multiple treatments
  • Good compliance (years)
  • Supravital staining with toluidine blue
  • Rapid or frequent recurrence
• Smoking cessation program must be part of management!!!!

Radiology

• Tumor extent (limitations of endoscopy)

• Pre‐epiglottic space and paraglottic space involvement, cartilage erosion

• MRI:

• high‐density tumor vs fat in the preepiglottic space
• Soft tissue invasion
• Nodal disease
  • ECS

• CT: thyroid cartilage destruction

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

Early GloNc Cancer (T1/T2)

• Less biologically aggressive than supraglottic or hypopharyngeal
  • well to moderately differentiated
  • remains localized to the glottic compartment longer
  • without neck or distant metastases: sparse submucosal lymphatics
• Symptoms present early
  • most tumors originate on the free surface of the true vocal fold
  • anterior two‐thirds ‐ hoarseness invites medical evaluation
• Treatment
  • radiotherapy or conservation surgery
  • no need for elective ND
  • surgery offers 90% to 95% cure rates for T 1 lesions*****
  • surgical salvagetotal laryngectomy
    • equal long‐term cure but with different morbidities ***superstar status material