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NCI/PDQ^® Health professionals: Laryngeal Cancer Treatment (PDQ®)

National Cancer Institute
Ultima Vez Modificado: 23 de octubre del 2012

TABLE OF CONTENTS

• General Information About Laryngeal Cancer
  • Incidence and Mortality

• Cellular Classification of Laryngeal Cancer

• Stage Information for Laryngeal Cancer
  • Definitions of TNM

• Treatment Option Overview

• Stage I Laryngeal Cancer
  • Supraglottis
  • Glottis
  • Subglottis
  • Current Clinical Trials

• Stage II Laryngeal Cancer
  • Supraglottis
  • Glottis
  • Subglottis
  • Current Clinical Trials

• Stage III Laryngeal Cancer
  • Supraglottis
  • Glottis
  • Subglottis
  • Current Clinical Trials

• Stage IV Laryngeal Cancer
  • Supraglottis
  • Glottis
  • Subglottis
  • Current Clinical Trials

• Recurrent Laryngeal Cancer
  • Current Clinical Trials

• Changes to This Summary (10/23/2012)

• About This PDQ® Summary
  • Purpose of This Summary
  • Reviewers and Updates
  • Levels of Evidence
  • Permission to Use This Summary
  • Disclaimer
  • Contact Us

• Get More Information From NCI

General Information About Laryngeal Cancer

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Incidence and Mortality

Estimated new cases and deaths from laryngeal cancer in the United States in 2012: 1

• New cases: 12,360.
• Deaths: 3,650.

The larynx is divided into the following three anatomical regions:

• The supraglottic larynx includes the epiglottis, false vocal cords, ventricles, aryepiglottic folds, and arytenoids.
• The glottis includes the true vocal cords and the anterior and posterior commissures.
• The subglottic region begins about 1 cm below the true vocal cords and extends to the lower border of the cricoid cartilage or the first tracheal ring.

The supraglottic area is rich in lymphatic drainage. After penetrating the pre-epiglottic space and thyrohyoid membrane, lymphatic drainage is initially to the jugulodigastric and midjugular nodes. About 25% to 50% of patients present with involved lymph nodes. The precise figure depends on the T stage. The true vocal cords are devoid of lymphatics. As a result, vocal cord cancer confined to the true cords rarely, if ever, presents with involved lymph nodes. Extension above or below the cords may, however, lead to lymph node involvement. Primary subglottic cancers, which are quite rare, drain through the cricothyroid and cricotracheal membranes to the pretracheal, paratracheal, and inferior jugular nodes, and occasionally to mediastinal nodes. 2

A clear association has been made between smoking, excess alcohol ingestion, and the development of squamous cell cancers of the upper aerodigestive tract. 3 For smokers, the risk of the development of laryngeal cancer decreases after the cessation of smoking but remains elevated even years later when compared to that of nonsmokers. 4 If a patient who has had a single cancer continues to smoke and drink alcoholic beverages, the likelihood of a cure for the initial cancer, by any modality, is diminished, and the risk of second tumor is enhanced. Because of clinical problems related to smoking and alcohol use in this population, many patients succumb to intercurrent illness rather than to the primary cancer. (Refer to the PDQ® summary on Smoking in Cancer Care for more information.)

Second primary tumors, often in the aerodigestive tract, have been reported in as many as 25% of patients whose initial lesion is controlled. A study has shown that daily treatment of these patients with moderate doses of isotretinoin (i.e., 13-cis-retinoic acid) for 1 year can significantly reduce the incidence of second tumors. 5 No survival advantage has yet been demonstrated, however, in part because of recurrence and death from the primary malignancy.

Supraglottic cancers typically present with sore throat, painful swallowing, referred ear pain, change in voice quality, or enlarged neck nodes. Early vocal cord cancers are usually detected because of hoarseness. By the time they are detected, cancers arising in the subglottic area commonly involve the vocal cords; thus, symptoms usually relate to contiguous spread.

The most important adverse prognostic factors for laryngeal cancers include increasing T stage and N stage. Other prognostic factors may include sex, age, performance status, and a variety of pathologic features of the tumor, including grade and depth of invasion. 6

Prognosis for small laryngeal cancers that have not spread to lymph nodes is very good with cure rates of 75% to 95% depending on the site, tumor bulk, 7 and degree of infiltration. Although most early lesions can be cured by either radiation therapy or surgery, radiation therapy may be reasonable to preserve the voice, leaving surgery for salvage. Patients with a preradiation hemoglobin level higher than 13 g/dL have higher local control and survival rates than patients who are anemic. 8

Locally advanced lesions, especially those with large clinically involved lymph nodes, are poorly controlled with surgery, radiation therapy, or combined modality treatment. Distant metastases are also common, even if the primary tumor is controlled.

Intermediate lesions have intermediate prognoses, depending on site, T stage, N stage, and performance status. Therapy recommendations for patients with these lesions are based on a variety of complex anatomic, clinical, and social factors, which should be individualized and discussed in multidisciplinary consultation (surgery, radiation therapy, and dental and oral surgery) prior to prescribing therapy.

Patients treated for laryngeal cancers are at the highest risk of recurrence in the first 2 to 3 years. Recurrences after 5 years are rare and usually represent new primary malignancies. Close, regular follow-up is crucial to maximize the chance for salvage. Careful clinical examination and repetition of any abnormal staging study are included in follow-up, along with attention to any treatment-related toxic effect or complication.

References:

1. American Cancer Society.: Cancer Facts and Figures 2012. Atlanta, Ga: American Cancer Society, 2012. Available online [PUBMED Abstract]
2. Spaulding CA, Hahn SS, Constable WC: The effectiveness of treatment of lymph nodes in cancers of the pyriform sinus and supraglottis. Int J Radiat Oncol Biol Phys 13 (7): 963-8, 1987. [PUBMED Abstract]
3. Spitz MR: Epidemiology and risk factors for head and neck cancer. Semin Oncol 21 (3): 281-8, 1994. [PUBMED Abstract]
4. Bosetti C, Garavello W, Gallus S, et al.: Effects of smoking cessation on the risk of laryngeal cancer: an overview of published studies. Oral Oncol 42 (9): 866-72, 2006. [PUBMED Abstract]
5. Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323 (12): 795-801, 1990. [PUBMED Abstract]
6. Yilmaz T, Hoal S, Gedikoglu G, et al.: Prognostic significance of depth of invasion in cancer of the larynx. Laryngoscope 108 (5): 764-8, 1998. [PUBMED Abstract]
7. Reddy SP, Mohideen N, Marra S, et al.: Effect of tumor bulk on local control and survival of patients with T1 glottic cancer. Radiother Oncol 47 (2): 161-6, 1998. [PUBMED Abstract]
8. Fein DA, Lee WR, Hanlon AL, et al.: Pretreatment hemoglobin level influences local control and survival of T1-T2 squamous cell carcinomas of the glottic larynx. J Clin Oncol 13 (8): 2077-83, 1995. [PUBMED Abstract]

Cellular Classification of Laryngeal Cancer

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The vast majority of laryngeal cancers are of squamous cell histology. Squamous cell subtypes include keratinizing and nonkeratinizing and well-differentiated to poorly differentiated grade. A variety of nonsquamous cell laryngeal cancers also occur. 1 2 These are not staged using the American Joint Cancer Committee staging system, and their management, which is not discussed here, can differ from that of squamous cell laryngeal cancers. In situ squamous cell carcinoma of the larynx is usually managed by a conservative surgical procedure such as mucosal stripping or superficial laser excision. Radiation therapy may also be appropriate treatment of selected patients with in situ carcinoma of the glottic larynx. 3

References:

1. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80. [PUBMED Abstract]
2. Chepeha DR, Haxer MJ, Lyden T: Rehabilitation after treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 781-8. [PUBMED Abstract]
3. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997. [PUBMED Abstract]

Stage Information for Laryngeal Cancer

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The staging system for laryngeal cancer is clinical and based on the best possible estimate of the extent of disease before treatment. The assessment of the primary tumor is based on inspection and palpation when possible and by both indirect mirror examination and direct endoscopy when necessary. The tumor must be confirmed histologically, and any other pathological data obtained on biopsy may be included. Head and neck magnetic resonance imaging or computed tomography should be done prior to therapy to supplement inspection and palpation. 1 Additional radiographic studies may be included. The appropriate nodal drainage areas in the neck should be examined by careful palpation.

Definitions of TNM

The American Joint Committee on Cancer has designated staging by TNM classification to define laryngeal cancer. 2

Table 1. Primary Tumor (T)^a

^aReprinted with permission from AJCC: Laryngeal. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 57-67.

TX	Primary tumor cannot be assessed.
T0	No evidence of primary tumor.
Tis	Carcinoma in situ.
Supraglottis
T1	Tumor limited to one subsite of supraglottis with normal vocal cord mobility.
T2	Tumor invades mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx.
T3	Tumor limited to larynx with vocal cord fixation and/or invades any of the following: postcricoid area, pre-epiglottic space, paraglottic space, and/or inner cortex of thyroid cartilage.
T4a	Moderately advanced local disease.
	Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus).
T4b	Very advanced local disease.
	Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures.
Glottis
T1	Tumor limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility.
T1a	Tumor limited to one vocal cord.
T1b	Tumor involves both vocal cords.
T2	Tumor extends to supraglottis and/or subglottis and/or with impaired vocal cord mobility.
T3	Tumor limited to the larynx with vocal cord fixation and/or invasion of paraglottic space and/or inner cortex of the thyroid cartilage.
T4a	Moderately advanced local disease.
	Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus).
T4b	Very advanced local disease.
	Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures.
Subglottis
T1	Tumor limited to the subglottis.
T2	Tumor extends to vocal cord(s) with normal or impaired mobility.
T3	Tumor limited to larynx with vocal cord fixation.
T4a	Moderately advanced local disease.
	Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus).
T4b	Very advanced local disease.
	Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures.

Table 2. Regional Lymph Nodes^ab

^aReprinted with permission from AJCC: Laryngeal. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 57-67.^bMetastases at level VII are considered regional lymph node metastases.

NX	Regional lymph nodes cannot be assessed.
N0	No regional lymph node metastasis.
N1	Metastasis in a single ipsilateral lymph node, 3 cm in greatest dimension.
N2	Metastasis in a single ipsilateral lymph node, >3 cm but 6 cm in greatest dimension.
	Metastases in multiple ipsilateral lymph nodes, none >6 cm in greatest dimension.
	Metastases in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension.
N2a	Metastasis in a single ipsilateral lymph node, >3 cm but 6 cm in greatest dimension.
N2b	Metastases in multiple ipsilateral lymph nodes, none >6 cm in greatest dimension.
N2c	Metastases in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension.
N3	Metastasis in a lymph node, >6 cm in greatest dimension.

Table 3. Distant Metastasis (M)^a

^aReprinted with permission from AJCC: Laryngeal. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 57-67.

M0	No distant metastasis.
M1	Distant metastasis.

Table 4. Anatomic Stage/Prognostic Groups

^aReprinted with permission from AJCC: Laryngeal. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 57-67.

Stage	T	N	M
0	Tis	N0	M0
I	T1	N0	M0
II	T2	N0	M0
III	T3	N0	M0
	T1	N1	M0
	T2	N1	M0
	T3	N1	M0
IVA	T4a	N0	M0
	T4a	N1	M0
	T1	N2	M0
	T2	N2	M0
	T3	N2	M0
	T4a	N2	M0
IVB	T4b	Any N	M0
	Any T	N3	M0
IVC	Any T	Any N	M1

References:

1. Thabet HM, Sessions DG, Gado MH, et al.: Comparison of clinical evaluation and computed tomographic diagnostic accuracy for tumors of the larynx and hypopharynx. Laryngoscope 106 (5 Pt 1): 589-94, 1996. [PUBMED Abstract]
2. Larynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 57-62. [PUBMED Abstract]

Treatment Option Overview

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Small superficial cancers without laryngeal fixation or lymph node involvement are successfully treated by radiation therapy or surgery alone, including laser excision surgery. Radiation therapy may be selected to preserve the voice and to reserve surgery for salvaging failures. The radiation field and dose are determined by the location and size of the primary tumor. A variety of curative surgical procedures are also recommended for laryngeal cancers, some of which preserve vocal function. An appropriate surgical procedure must be considered for each patient, given the anatomic problem, performance status, and clinical expertise of the treatment team. Advanced laryngeal cancers are often treated by combining radiation and surgery. 1 2 3 4 5

Evaluation of treatment outcome can be reported in various ways: locoregional control, disease-free survival, determinate survival, and overall survival (OS) at 2 to 5 years. Preservation of voice is an important parameter to evaluate. Outcome should be reported after initial surgery, initial radiation, planned combined treatment, or surgical salvage of radiation failures. Primary source material should be consulted to review these differences.

Direct comparison of results of radiation versus surgery is complicated. Surgical studies can report outcome based on pathologic staging, whereas radiation studies must report on clinical staging, with the obvious problem of understaging in patients treated with radiation, particularly in the neck. In addition, radiation alone is often recommended for patients with poor performance status, which leads to less favorable results.

A review of published clinical results of radical radiation therapy for head and neck cancer suggests a significant loss of local control when the administration of radiation therapy was prolonged; therefore, lengthening of standard treatment schedules should be avoided whenever possible. 6 7 Because the cure rate for advanced lesions is low, clinical trials exploring chemotherapy, hyperfractionated radiation therapy, 8 radiation sensitizers, or particle-beam radiation therapy should be considered. 9 10 Although cure rates are not changed with chemoradiation administered in a neoadjuvant setting, organ preservation is increased. 11

A multi-institutional trial randomly assigned patients to induction cisplatin plus fluorouracil (5-FU) followed by radiation therapy, radiation therapy administered concurrently with cisplatin, or radiation therapy alone. 11 Concurrent radiation therapy plus cisplatin resulted in a statistically significantly higher percentage of patients with an intact larynx at 2 years (i.e., 88% vs. 75% and 70% for concurrent chemotherapy, induction chemotherapy, and radiation alone, respectively) and higher locoregional control (i.e., 78% vs. 61% and 56%, respectively) than the other two regimens. Both chemotherapy regimens had a lower incidence of distant metastases and better relapse-free survivals than radiation therapy alone, but they also had a higher rate of high-grade toxic effects. OS rates were not significantly different between the different groups. 11[Level of evidence: 1iiC]

The risk of lymph node metastases in patients with stage I glottic cancer ranges from 0% to 2%, and for more advanced disease, such as stage II and stage III glottic, the incidence is only 10% and 15%, respectively. Thus, there is no need to treat glottic cancer cervical lymph nodes electively in patients with stage I tumors and small stage II tumors. Consideration should be given to using elective neck radiation for larger or supraglottic tumors. 12

For patients with cancer of the subglottis, combined modality therapy is generally preferred for the uncommon small lesions (i.e., stage I or stage II); however, radiation therapy alone may be used.

Patients who smoke during radiation therapy appear to have lower response rates and shorter survival durations than those who do not; 13 therefore, patients should be counseled to stop smoking before beginning radiation therapy.

Accumulating evidence has demonstrated a high incidence (i.e., >30%40%) of hypothyroidism in patients who have received external-beam radiation to the entire thyroid gland or to the pituitary gland. Thyroid-junction testing of patients should be considered prior to therapy and as part of posttreatment follow-up. 14 15

References:

1. Silver CE, Ferlito A: Surgery for Cancer of the Larynx and Related Structures. 2nd ed. Philadelphia, Pa: Saunders, 1996. [PUBMED Abstract]
2. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997. [PUBMED Abstract]
3. Thawley SE, Panje WR, Batsakis JG, et al., eds.: Comprehensive Management of Head and Neck Tumors. 2nd ed. Philadelphia, Pa: WB Saunders, 1999. [PUBMED Abstract]
4. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80. [PUBMED Abstract]
5. Chepeha DR, Haxer MJ, Lyden T: Rehabilitation after treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 781-8. [PUBMED Abstract]
6. Fowler JF, Lindstrom MJ: Loss of local control with prolongation in radiotherapy. Int J Radiat Oncol Biol Phys 23 (2): 457-67, 1992. [PUBMED Abstract]
7. Hansen O, Overgaard J, Hansen HS, et al.: Importance of overall treatment time for the outcome of radiotherapy of advanced head and neck carcinoma: dependency on tumor differentiation. Radiother Oncol 43 (1): 47-51, 1997. [PUBMED Abstract]
8. Bourhis J, Wibault P, Lusinchi A, et al.: Status of accelerated fractionation radiotherapy in head and neck squamous cell carcinomas. Curr Opin Oncol 9 (3): 262-6, 1997. [PUBMED Abstract]
9. Taylor SG 4th: Integration of chemotherapy into the combined modality therapy of head and neck squamous cancer. Int J Radiat Oncol Biol Phys 13 (5): 779-83, 1987. [PUBMED Abstract]
10. Stupp R, Weichselbaum RR, Vokes EE: Combined modality therapy of head and neck cancer. Semin Oncol 21 (3): 349-58, 1994. [PUBMED Abstract]
11. Forastiere AA, Goepfert H, Maor M, et al.: Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 349 (22): 2091-8, 2003. [PUBMED Abstract]
12. Spaulding CA, Hahn SS, Constable WC: The effectiveness of treatment of lymph nodes in cancers of the pyriform sinus and supraglottis. Int J Radiat Oncol Biol Phys 13 (7): 963-8, 1987. [PUBMED Abstract]
13. Browman GP, Wong G, Hodson I, et al.: Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med 328 (3): 159-63, 1993. [PUBMED Abstract]
14. Turner SL, Tiver KW, Boyages SC: Thyroid dysfunction following radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys 31 (2): 279-83, 1995. [PUBMED Abstract]
15. Constine LS: What else don't we know about the late effects of radiation in patients treated for head and neck cancer? Int J Radiat Oncol Biol Phys 31 (2): 427-9, 1995. [PUBMED Abstract]

Stage I Laryngeal Cancer

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Supraglottis

Standard treatment options:

1. External-beam radiation therapy alone.
2. Supraglottic laryngectomy. Total laryngectomy may be reserved for patients unable to tolerate potential respiratory complications of surgery or the supraglottic laryngectomy.

Radiation should be preferred because of the good results, preservation of the voice, and the possibility of surgical salvage in patients whose disease recurs locally. 1

Glottis

Standard treatment options:

1. Radiation therapy. 2 3 4 5
2. Cordectomy for very carefully selected patients with limited and superficial T1 lesions. 6 7
3. Partial or hemilaryngectomy or total laryngectomy, depending on anatomic considerations.
4. Laser excision. 6

Subglottis

Standard treatment options:

1. Lesions can be treated successfully by radiation therapy alone with preservation of normal voice.
2. Surgery is reserved for failure of radiation therapy or for patients who cannot be easily assessed for radiation therapy.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I laryngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Ogura JH, Sessions DG, Spector GJ: Conservation surgery for epidermoid carcinoma of the supraglottic larynx. Laryngoscope 85 (11 pt 1): 1808-15, 1975. [PUBMED Abstract]
2. Mittal B, Rao DV, Marks JE, et al.: Role of radiation in the management of early vocal cord carcinoma. Int J Radiat Oncol Biol Phys 9 (7): 997-1002, 1983. [PUBMED Abstract]
3. Wang CC: Factors influencing the success of radiation therapy for T2 and T3 glottic carcinomas. Importance of cord mobility and sex. Am J Clin Oncol 9 (6): 517-20, 1986. [PUBMED Abstract]
4. Mendenhall WM, Amdur RJ, Morris CG, et al.: T1-T2N0 squamous cell carcinoma of the glottic larynx treated with radiation therapy. J Clin Oncol 19 (20): 4029-36, 2001. [PUBMED Abstract]
5. Foote RL, Olsen KD, Kunselman SJ, et al.: Early-stage squamous cell carcinoma of the glottic larynx managed with radiation therapy. Mayo Clin Proc 67 (7): 629-36, 1992. [PUBMED Abstract]
6. Steiner W: Results of curative laser microsurgery of laryngeal carcinomas. Am J Otolaryngol 14 (2): 116-21, 1993 Mar-Apr. [PUBMED Abstract]
7. Olsen KD, Thomas JV, DeSanto LW, et al.: Indications and results of cordectomy for early glottic carcinoma. Otolaryngol Head Neck Surg 108 (3): 277-82, 1993. [PUBMED Abstract]

Stage II Laryngeal Cancer

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Supraglottis

Standard treatment options:

1. External-beam radiation therapy alone for the smaller lesions. 1 2 3
2. Supraglottic laryngectomy or total laryngectomy, depending on location of the lesion, clinical status of the patient, and expertise of the treatment team. Careful selection must be made to ensure adequate pulmonary and swallowing function postoperatively.
3. Postoperative radiation therapy is indicated for positive or close surgical margins.

Radiation should be preferred because of the good results, preservation of the voice, and the possibility of surgical salvage in patients whose disease recurs locally. 4

Treatment options under clinical evaluation:

1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue. 3 5
2. Isotretinoin (i.e., 13-cis-retinoic acid) daily for 1 year to prevent development of second upper aerodigestive tract primary tumors. 6

Glottis

Standard treatment options:

1. Radiation therapy. 1 2 3 7 8 9
2. Partial or hemilaryngectomy or total laryngectomy, depending on anatomic considerations. Under certain circumstances, laser microsurgery may be appropriate. 10

Treatment options under clinical evaluation:

1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue. 3 5
2. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors. 6

Subglottis

Standard treatment options:

1. Lesions can be treated successfully by radiation therapy alone with preservation of normal voice. 1 2
2. Surgery is reserved for failure of radiation therapy or for patients in whom follow-up is likely to be difficult.

Treatment options under clinical evaluation:

1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue. 3 5
2. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors. 6

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II laryngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80. [PUBMED Abstract]
2. Chepeha DR, Haxer MJ, Lyden T: Rehabilitation after treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 781-8. [PUBMED Abstract]
3. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997. [PUBMED Abstract]
4. Ogura JH, Sessions DG, Spector GJ: Conservation surgery for epidermoid carcinoma of the supraglottic larynx. Laryngoscope 85 (11 pt 1): 1808-15, 1975. [PUBMED Abstract]
5. Parsons JT, Mendenhall WM, Cassisi NJ, et al.: Hyperfractionation for head and neck cancer. Int J Radiat Oncol Biol Phys 14 (4): 649-58, 1988. [PUBMED Abstract]
6. Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323 (12): 795-801, 1990. [PUBMED Abstract]
7. Mittal B, Marks JE, Ogura JH: Transglottic carcinoma. Cancer 53 (1): 151-61, 1984. [PUBMED Abstract]
8. Medini E, Medini I, Lee CK, et al.: Curative radiotherapy for stage II-III squamous cell carcinoma of the glottic larynx. Am J Clin Oncol 21 (3): 302-5, 1998. [PUBMED Abstract]
9. Mendenhall WM, Amdur RJ, Morris CG, et al.: T1-T2N0 squamous cell carcinoma of the glottic larynx treated with radiation therapy. J Clin Oncol 19 (20): 4029-36, 2001. [PUBMED Abstract]
10. Steiner W: Results of curative laser microsurgery of laryngeal carcinomas. Am J Otolaryngol 14 (2): 116-21, 1993 Mar-Apr. [PUBMED Abstract]

Stage III Laryngeal Cancer

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Supraglottis

Standard treatment options:

1. Surgery with or without postoperative radiation therapy, as evidenced in RTOG-7303, for example. 1 2 3 4 5 6 7
2. Definitive radiation therapy with surgery for salvage of radiation failures. 8
3. Chemotherapy administered concomitantly with radiation therapy can be considered for patients who would require total laryngectomy for control of disease. Laryngectomy would be reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation. 9 10 11 12 13 14

Treatment options under clinical evaluation:

1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue. 15 16
2. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy. 17 18 19 20 21

   A meta-analysis of three trials of patients with locally advanced laryngeal carcinomas compared patients who received standard radical surgery plus radiation therapy with patients who received neoadjuvant cisplatin and fluorouracil (5-FU), followed by radiation therapy alone in responders or radical surgery plus radiation therapy in nonresponders. 22 The meta-analysis The meta-analysis demonstrated a nonsignificant trend in favor of the control group who received demonstrated a nonsignificant trend in favor of the control group who received standard radical surgery plus radiation therapy with an absolute negative standard radical surgery plus radiation therapy with an absolute negative effect in the chemotherapy arm that reduced survival at 5 years by 6%. The effect in the chemotherapy arm that reduced survival at 5 years by 6%. The possibility of a slightly decreased survival must be balanced by the retention possibility of a slightly decreased survival must be balanced by the retention of the larynx in those patients whose disease was controlled. of the larynx in those patients whose disease was controlled.

3. Isotretinoin (i.e., 13-cis-retinoic acid) daily for 1 year to prevent development of second upper aerodigestive tract primary tumors. 23

Glottis

Standard treatment options:

1. Surgery with or without postoperative radiation therapy, as evidenced in RTOG-7303, for example. 1 2 3 4 5 6 7 24
2. Definitive radiation therapy with surgery for salvage of radiation failures. 8 25
3. Chemotherapy administered concomitantly with radiation therapy can be considered for patients who would require total laryngectomy for control of disease. Laryngectomy would be reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation. 9 10 11 12 13 14

Treatment options under clinical evaluation:

1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue. 15 16
2. Clinical trials exploring chemotherapy, radiosensitizers, or particle beam radiation therapy. 17 18 20 21

   A meta-analysis of three trials of patients with locally advanced laryngeal carcinomas compared patients who received standard radical surgery plus radiation therapy with patients who received neoadjuvant cisplatin and fluorouracil, followed by radiation therapy alone in responders or radical surgery plus radiation therapy in nonresponders. 22 The meta-analysis The meta-analysis demonstrated a nonsignificant trend in favor of the control group who received demonstrated a nonsignificant trend in favor of the control group who received standard radical surgery plus radiation therapy with an absolute negative standard radical surgery plus radiation therapy with an absolute negative effect in the chemotherapy arm that reduced survival at 5 years by 6%. The effect in the chemotherapy arm that reduced survival at 5 years by 6%. The possibility of a slightly decreased survival must be balanced by the retention possibility of a slightly decreased survival must be balanced by the retention of the larynx in those patients whose disease was controlled. of the larynx in those patients whose disease was controlled.

3. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors. 23

Subglottis

Standard treatment options:

1. Laryngectomy plus isolated thyroidectomy and tracheoesophageal node dissection usually followed by postoperative radiation therapy. 1 2 3 4
2. Treatment by radiation therapy alone is indicated for patients who are not candidates for surgery. Patients should be closely followed, and surgical salvage should be planned for recurrences that are local or in the neck.

Treatment options under clinical evaluation:

1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue. 15 16
2. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy. 17 18 20 21

   A meta-analysis of three trials of patients with locally advanced laryngeal carcinomas compared patients who received standard radical surgery plus radiation therapy with patients who received neoadjuvant cisplatin and fluorouracil, followed by radiation therapy alone in responders or radical surgery plus radiation therapy in nonresponders. 22 The meta-analysis The meta-analysis demonstrated a nonsignificant trend in favor of the control group who received demonstrated a nonsignificant trend in favor of the control group who received standard radical surgery plus radiation therapy with an absolute negative standard radical surgery plus radiation therapy with an absolute negative effect in the chemotherapy arm that reduced survival at 5 years by 6%. The effect in the chemotherapy arm that reduced survival at 5 years by 6%. The possibility of a slightly decreased survival must be balanced by the retention possibility of a slightly decreased survival must be balanced by the retention of the larynx in those patients whose disease was controlled. of the larynx in those patients whose disease was controlled.

3. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors. 23

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III laryngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Thawley SE, Panje WR, Batsakis JG, et al., eds.: Comprehensive Management of Head and Neck Tumors. 2nd ed. Philadelphia, Pa: WB Saunders, 1999. [PUBMED Abstract]
2. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80. [PUBMED Abstract]
3. Chepeha DR, Haxer MJ, Lyden T: Rehabilitation after treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 781-8. [PUBMED Abstract]
4. Arriagada R, Eschwege F, Cachin Y, et al.: The value of combining radiotherapy with surgery in the treatment of hypopharyngeal and laryngeal cancers. Cancer 51 (10): 1819-25, 1983. [PUBMED Abstract]
5. Spaulding CA, Krochak RJ, Hahn SS, et al.: Radiotherapeutic management of cancer of the supraglottis. Cancer 57 (7): 1292-8, 1986. [PUBMED Abstract]
6. Ogura JH, Sessions DG, Spector GJ: Conservation surgery for epidermoid carcinoma of the supraglottic larynx. Laryngoscope 85 (11 pt 1): 1808-15, 1975. [PUBMED Abstract]
7. Tupchong L, Scott CB, Blitzer PH, et al.: Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03. Int J Radiat Oncol Biol Phys 20 (1): 21-8, 1991. [PUBMED Abstract]
8. MacKenzie RG, Franssen E, Balogh JM, et al.: Comparing treatment outcomes of radiotherapy and surgery in locally advanced carcinoma of the larynx: a comparison limited to patients eligible for surgery. Int J Radiat Oncol Biol Phys 47 (1): 65-71, 2000. [PUBMED Abstract]
9. Spaulding MB, Fischer SG, Wolf GT: Tumor response, toxicity, and survival after neoadjuvant organ-preserving chemotherapy for advanced laryngeal carcinoma. The Department of Veterans Affairs Cooperative Laryngeal Cancer Study Group. J Clin Oncol 12 (8): 1592-9, 1994. [PUBMED Abstract]
10. Merlano M, Benasso M, Corví R, et al.: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. J Natl Cancer Inst 88 (9): 583-9, 1996. [PUBMED Abstract]
11. Adelstein DJ, Saxton JP, Lavertu P, et al.: A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer: preliminary results. Head Neck 19 (7): 567-75, 1997. [PUBMED Abstract]
12. Jeremic B, Shibamoto Y, Milicic B, et al.: Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol 18 (7): 1458-64, 2000. [PUBMED Abstract]
13. Forastiere AA, Goepfert H, Maor M, et al.: Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 349 (22): 2091-8, 2003. [PUBMED Abstract]
14. Bernier J, Domenge C, Ozsahin M, et al.: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350 (19): 1945-52, 2004. [PUBMED Abstract]
15. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997. [PUBMED Abstract]
16. Parsons JT, Mendenhall WM, Cassisi NJ, et al.: Hyperfractionation for head and neck cancer. Int J Radiat Oncol Biol Phys 14 (4): 649-58, 1988. [PUBMED Abstract]
17. Bachaud JM, David JM, Boussin G, et al.: Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized tri