Laryngeal Cancer

Epidemiology

General

Risk Factors

Embriology of Larynx

  • Mesenchyme of the 3rd and 4th pharyngeal arches » hypobrachial eminence » Epiglottis
  • Rostal part of this eminence forms the posterior third of the tongue.
  • Endoderm of the cranial end of the laryngotracheal tube » epithelial lining of the larynx
  • Neurocrest cells » Arytenoid swellings » laryngeal inlet » larngeal ventricles » These recesses are bound by folds of mucous membrane that become the vocal cords and vestibular folds.

Presentation and Evaluation

Anatomy

  • Supraglottic larynx
  • Epiglottis, false vocal cord, ventricles, and aryepiglottic folds, including the arytenoids.
  • apex of the ventricle
  • Glottic larynx
  • True vocal cords and the anterior commissure
  • Vocal cord length, 2.2 cm in men and 1.8 cm in women
  • 5 mm below the free margin of the vocal cord
  • (AJCC 1 cm from lateral margin of the ventricle)
  • Subglottic larynx (below the vocal cord)
  • inferior border o the cricoid cartilage

Reinke’s space is the most superficial layer of the lamina propria under the free edge of the vocal cord where edema develops. Two deeper layers are the vocal ligament.
Quadrangular membrane is a thin, submucosal sheet of connective tissue that extends from the arytenoid cartilage to the epiglottis.
Paraglottic fat space is limited by the conus elasticus inferiorly; the thyoid ala, thyrohyoid membrane, and hyoid bone anerolaterally; the hyoepiglottic liament superiorly; and fascia of the intrinsic muscles on the medial side. Posteriorly it is in relationship to the anterior wall of the pyriform sinus.

Pathology

  • Most all are squamous cell or variants
    • CIS of the vocal cord (treat like cancer due to possible microinvasion)
    • SCC with spindle cell stromal reaction
    • Verrucous carcinoma
  • Mucoepidermoid
  • Adenoid cystic
  • Fibrosaroma/ rhabdomyosarcoma/ pseudosarcoma
  • Small Cell (neuroendocrine)
    • Rapid growth, early dissemination, and responsiveness to chemotherapy
  • Minor salivary gland tumors
  • Chemodectoma, carcinoid, lymphoma, plasmacytoma

Clinical Presentation

  • Sore throat; unilateral if confined to lateral pharyngeal wall or pyriform sinus. (can point to pain with one finger)
  • Dysphagia, sensation of foreign body, ear pain, blood-streaked saliva, aspiration, and voice changes occur later.
  • Weight loss with advanced lesion
  • Neck mass may be the only presenting symptom

Causes of vocal cord fixation

  • Invasion or destruction of vocal muscle
  • Invasion of the cricoarytenoid muscle/joint
  • Invasion of the recurrent laryngeal nerve
  • Infection or bulk of tumor

Routes of Spread

Supraglottic (55% nodal mets at diagnosis)
preeiglottic space and thyrohyoid membrane »> piriform sinus »> subdigastic lymph nodes
middle internal jugular chain lymph nodes
Glottic -> NO lymphatics, the the risk of LN spread for
* T1 lesions is 0%
* T2 is 2-5%.
Subglottic (poor lymphatics)
Posteriorly through the cricotracheal membrane, with some to paratrachal lymph nodes, while others pass to inferior jugular chain.

Diagnostic Studies

Staging

  • CT of head and neck with thin cuts through the larynx and volume study
  • Tumor volume > 3.5 cm3 is correlated with 50% local failure rate
  • MRI has not been proven to be better than CT
  • “Triple endoscopy”
  • Direct laryngoscopy, esophagoscopy and bronchoscopy (3% synchronous second tumor)
  • CXR
  • CT of the chest lacks specificity for the precise diagnosis o potential distant metastasis
  • Spirometry is not a staging study but pulmonary function has implications with regard to ability to tolerate aspiration for both surgical and nonsurgical treatments

Treatment

CIS Glottic

  • Stripping the cord
    • Controls the tumor
    • difficult to exclude microinvasion
    • recurrence is frequent » thickened cord with hoarseness with repeated stripping
  • Early radiation is a good choice for voice preservation
  • Transoral laser excision (T1b)
  • Open partial laryngectomy (Salvage or not available for radiation)
  • Voice quality
    • Laser excision = radiotherapy for T1a, otherwise radiotherapy > laser excision > partial laryngectomy
Treatment Glottic Larynx
Conventional radiation Tis
* 66 Gy in 33 fractions (as some may have invasive component) OR
* CO2 excision
T1, N0 (Positive nodes are rare in glottic cancer)
* 66 Gy in 33 fractions
T2 N0 (positive nodes are rare in glottic cancer)
* 70 Gy in 35 fractions
Concurrent Chemoradiation T3-4 ("Small") or N+ (Except as noted in post-operative section_
* 70 Gy in 2 Gy per fraction with Cisplatin 100 mg/m2 on days 1, 22, 43
T4a with thyroid desctruction laryngectomy + PORT
T4a with invasion into trachea, esophagus or base of tongue Chemoradiation
T4b with prevertibral space/facia, encasement of carotid artery or mediastinal involvement Unresectable and needs chemoRT

Outcome

  • Local control is 90% for T1 and 70-80% for T2 lesions for both surgical and radiation

Studies

Yamakazi 2006 (Dose fractionation)
Eligibility

  • T1 N0 Glottic Cancer
60 or 66 Gy in 2 Gy fractions 56.25 or 63 Gy in 2.25 Gy fractions
5-year local control 77% 92%
Cause specific survival 97% 100%
  • lower doses were used if the tumor was less then 2/3 of the vocal cords

Results

  • Suboptimal doses for "small" tumors
  • local control in the 2 Gy arm is low compared to U.S. historical control
  • both regiment is acceptable.

RTOG 91-11
Eligibility

  • SCCA of the glottic or supraglottic larynx
  • Stage III or IV (ie. N+ or T3+)
  • T1 and “bulky” T4 are excluded (ie. Penetrating the cartilage).
  • KPS > 60

Treatment
Chemotherapy

  • Cisplatin 100 mg per square meter
  • 5-FU 1000 mg per square meter

Radiation

  • 70 Gy in 35 fractions
  • Cover entire neck, including supraclavicular areas and posterior neck with minimum of 50 Gy
  • Adjuvant RT to 50 or 70 Gy depending on the status of the margins on pathological reviews.
RT C → RT CRT
Laryngectomy Free
Survival at 5 years
53% 59%* 66%*
Overall Survival 75% 75% 75%
% of patients with intact larynx 70% 75% 88%

Conclusions

  • in recent reports time to laryngectomy improved with CRT compared to sequential
  • No difference in overall survival
  • swallowing at 1 year was worse for CRT but no difference at 2 years (15% of patients had difficulty at 2 years)
  • speech was same for all arms with 3-8% of patients having moderate difficulty at 2 years
  • 43% absolute reduction in laryngectomy with concurrent over RT alone.
  • Chemotherapy suppressed distant metastasis
  • Consider CRT for advanced laryngeal cancers without cartilage invasion or deep BOT invasion
  • Note meta-analysis confirms that patients over 70 years-old have not benefited from concurrent chemoradiation or altered fractionation

Complications

Laryngeal Edema

  • Post-RT Laryngeal edema usually subsides within 1-2 months.
  • Persistence of edema makes careful inspection & evaluation of larynx difficult.
  • Edema can be due to: recurrence, faulty treatment techniques, surgical trauma, or injudicious voice use.
  • Issue is when to biopsy or continue symptomatic tx?
  • Laryngeal edema increased significantly with (Fu Cancer 1982; 49: 655.)
    • Dose >6999 cGy
    • Increase field size 5.5 x 5.5 vs. 6x6
  • If laryngeal edema persists >6 months, re-biopsy to rule-out malignancy

Chrondritis

  • Soft tissue necrosis leading to chondritis is rare, <1%
  • usually in pts who continue to smoke. Give dexamethasone.
Bibliography
1. Cox J, Ang K. Radiation Oncology: rationale Technique Results. 8th ed. New York: Mosby, 2003.
2. Gunderson L, Tepper J: Clinical Radiation Oncology. 2nd ed. China: Elsevier 2007.
3. Devita V, Hellman S, Rsenberg S: Cancer: Principles and practice of Oncology. 7th ed. Philadelphia: Lippincott, 2005.
4. Yamazaki H, Nishiyama K, Tanaka E, Koizumi M, Chatani M. Radiotherapy for early glottic carcinoma (T1N0M0): results of prospective randomized study of radiation fraction size and overall treatment time. Int J Radiat Oncol Biol Phys. 2006 Jan 1;64(1): 77-82. 16169681 PubMed - indexed for MEDLINE
5. Langendijk JA, Slotman BJ, van der Waal I, Doornaert P, Berkof J, Leemans CR.
Risk-group definition by recursive partitioning analysis of patients with squamous cell head and neck carcinoma treated with surgery and postoperative radiotherapy. Cancer. 2005 Oct 1;104(7):1408-17.
Unless otherwise stated, the content of this page is licensed under Creative Commons Attribution-Share Alike 2.5 License.