Laryngeal Cancer Treatment (PDQ®)–Health Professional Version

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General Information About Laryngeal Cancer

Incidence and Mortality

Estimated new cases and deaths from laryngeal cancer in the United States in 2016:[1]

  • New cases: 13,430.
  • Deaths: 3,620.

Anatomy

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]

Risk Factors

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.)

Clinical Features

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.

Prognostic Factors

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.[5]

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,[6] 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.[7]

Locally advanced lesions are treated with combined modality treatment involving radiation and chemotherapy with or without surgery, the aim of which is laryngeal preservation in appropriately selected candidates.[8] 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.

Follow-up and Survivorship

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.[9] No survival advantage has been demonstrated, partially because of recurrence and death from the primary malignancy.

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 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Last accessed June 23, 2016.
  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. Yilmaz T, Hoşal S, Gedikoglu G, et al.: Prognostic significance of depth of invasion in cancer of the larynx. Laryngoscope 108 (5): 764-8, 1998. [PUBMED Abstract]
  6. 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]
  7. 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]
  8. Forastiere AA, Zhang Q, Weber RS, et al.: Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 31 (7): 845-52, 2013. [PUBMED Abstract]
  9. 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]

Cellular Classification of Laryngeal Cancer

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] 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.

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.

Stage Information for Laryngeal Cancer

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 fiberoptic laryngoscopy. Panendoscopy under anesthesia ensures careful clinical examination to determine clinical extent of local disease. The tumor must be confirmed histologically, and any other pathological data obtained on biopsy may be included. Head and neck magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography should be done before 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, and/or 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 Nodesab
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
Stage T N M
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.
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.

Treatment Option Overview for Laryngeal Cancer

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 with concurrent chemotherapy for larynx preservation and total laryngectomy for bulky T4 disease or salvage.[1-3]

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.

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.[4,5]

Direct comparison of the results of radiation therapy versus endolaryngeal surgery (with or without laser) has not been made for patients with early stage laryngeal cancer. The evidence is insufficient to show a clear difference in the results between treatment options in regard to local control or OS. Retrospective data suggests that in comparison with surgery, radiation therapy might cause less perturbation of voice quality without a significant difference in patient perception.[6]

A direct comparison of chemotherapy followed by radiation therapy versus upfront surgery was made by The Department of Veterans Affairs (VA) Laryngeal Cancer Study Group in a trial in which 332 patients were randomly assigned to three cycles of chemotherapy (cisplatin and fluorouracil) and radiation therapy or surgery and radiation therapy.[7] After two cycles of chemotherapy, the clinical tumor response was complete in 31% of the patients, and there was a partial response in 54% of the patients. Survival was similar in both arms; however, larynx preservation was possible in 64% of the patients in the chemotherapy-followed-by-radiation therapy arm.

The VA study was followed up in a randomized study, RTOG 9111 (NCT00002496), in which the laryngeal preservation arm of the VA study was compared with the concomitant chemoradiation and radiation-alone arms, and the primary endpoint was laryngectomy-free survival (LFS).[3] The RTOG 9111 study evaluated 547 patients with locally advanced laryngeal cancer who were enrolled between August 1992 and May 2000, with a median follow-up for surviving patients of 10.8 years (range, 0.07–17 years). Three regimens were compared, including induction chemotherapy plus radiation therapy, concomitant chemoradiation, and radiation therapy alone. Both chemotherapy regimens improved LFS compared with radiation therapy alone (induction chemotherapy vs. radiation therapy alone, hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.59–0.95; P = .02; concomitant chemotherapy vs. radiation therapy alone, HR, 0.78; 95% CI, 0.78–0.98; P = .03).

Concurrent radiation therapy plus cisplatin resulted in a statistically significantly higher percentage of patients with an intact larynx at 10 years (67.5% for patients who had induction chemotherapy; 81.7% for patients who had concomitant chemotherapy; and 63.8% for patients who received radiation alone); 80% of laryngectomies were performed during the first 2 years (84 laryngectomies during year 1 and 35 laryngectomies during year 2).

Concomitant cisplatin with radiation therapy resulted in a 41% reduction in risk of locoregional failure compared with radiation therapy alone (HR, 0.59; 95% CI, 0.43–0.82; P = .0015) and a 34% reduction in risk compared with induction chemotherapy (HR, 0.66; 95% CI, 0.48–0.92; P = .004). Both chemotherapy regimens had a lower incidence of distant metastases, although this did not reach statistical significance compared with radiation therapy alone.

The 10-year cumulative rates of late toxicity (grades 3–5) were 30.6% for induction chemotherapy, 33.3% for concomitant chemotherapy, and 38% for radiation alone, and were not significantly different between the arms.

OS was not significantly different between the groups, although there was possibly a worse outcome in the concomitant groups compared with the induction chemotherapy group (HR, 1.25; 95% CI, 0.98–1.61; P = .08). The OS rates were 58% (5 year) and 39% (10 year) for induction chemotherapy, 55% (5 year) and 28% (10 year) for concomitant chemoradiation, and 54% (5 year) and 32% (10 year) for radiation alone. The number of deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy (30.8% vs. 20.8% with induction chemotherapy and 16.9% with radiation alone), because after approximately 4.5 years, the survival curves began to separate and favor induction, although the difference was not statistically significant.[3]

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. Elective neck radiation should be considered for T3 or T4 glottic tumors or T1 to T4 supraglottic tumors.[8]

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;[9] therefore, patients should be counseled on smoking cessation 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.[10,11]

References
  1. Silver CE, Ferlito A: Surgery for Cancer of the Larynx and Related Structures. 2nd ed. Philadelphia, Pa: Saunders, 1996.
  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.
  3. Forastiere AA, Zhang Q, Weber RS, et al.: Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 31 (7): 845-52, 2013. [PUBMED Abstract]
  4. 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]
  5. 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]
  6. Yoo J, Lacchetti C, Hammond JA, et al.: Role of endolaryngeal surgery (with or without laser) compared with radiotherapy in the management of early (T1) glottic cancer: a clinical practice guideline. Curr Oncol 20 (2): e132-5, 2013. [PUBMED Abstract]
  7. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med 324 (24): 1685-90, 1991. [PUBMED Abstract]
  8. 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]
  9. 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]
  10. 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]
  11. 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 Treatment

Selection of treatment should include an evaluation of voice function and quality after treatment. Endoscopic CO2 laser resections may also achieve similar results in terms of local control and function [1] compared with radiation therapy, although no randomized studies have been performed.[2] A meta-analysis of 22 consecutive case series to examine oncologic control demonstrated no clear differences between transoral CO2 laser excision and external beam radiation therapy in terms of local control (odds ratio [OR], 0.81; 95% confidence interval [CI], 0.51–1.3 and laryngectomy-free survival [OR, 0.84, 95% CI, 0.42–1.66]). There was a trend for improved posttreatment voice quality with radiation therapy. Transoral CO2 laser–excision surgery dominates radiotherapy from a cost-utility standpoint.[Level of Evidence: 2C]

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.

Glottis

Standard treatment options:

  1. Radiation therapy.[3-6]
  2. Cordectomy for very carefully selected patients with limited and superficial T1 lesions.[7,8]
  3. Partial or hemilaryngectomy or total laryngectomy, depending on anatomic considerations.
  4. Endoscopic CO2 laser excision.[9]

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 the list of NCI-supported 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 website.

References
  1. Agrawal A, Moon J, Davis RK, et al.: Transoral carbon dioxide laser supraglottic laryngectomy and irradiation in stage I, II, and III squamous cell carcinoma of the supraglottic larynx: report of Southwest Oncology Group Phase 2 Trial S9709. Arch Otolaryngol Head Neck Surg 133 (10): 1044-50, 2007. [PUBMED Abstract]
  2. Dey P, Arnold D, Wight R, et al.: Radiotherapy versus open surgery versus endolaryngeal surgery (with or without laser) for early laryngeal squamous cell cancer. Cochrane Database Syst Rev (2): CD002027, 2002. [PUBMED Abstract]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. Steiner W: Results of curative laser microsurgery of laryngeal carcinomas. Am J Otolaryngol 14 (2): 116-21, 1993 Mar-Apr. [PUBMED Abstract]
  8. 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]
  9. Higgins KM: What treatment for early-stage glottic carcinoma among adult patients: CO2 endolaryngeal laser excision versus standard fractionated external beam radiation is superior in terms of cost utility? Laryngoscope 121 (1): 116-34, 2011. [PUBMED Abstract]

Stage II Laryngeal Cancer Treatment

Supraglottis

Standard treatment options:

  1. External-beam radiation therapy alone for the smaller lesions encompassing the primary disease and regional elective nodes.[1]
  2. Supraglottic laryngectomy or total laryngectomy with bilateral neck dissections, 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 (PORT) is indicated for positive or close surgical margins or other adverse pathological risk factors.

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.

Glottis

Standard treatment options:

  1. Radiation therapy.[1-4]
  2. Partial or hemilaryngectomy or total laryngectomy, depending on anatomic considerations. Under certain circumstances, laser microsurgery may be appropriate.[5]

Subglottis

Standard treatment options:

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

PORT With or Without Chemotherapy

Depending on pathological findings after primary surgery, PORT or postoperative chemoradiation is used in the adjuvant setting for the following histological findings:

  • T4 disease.
  • Perineural invasion.
  • Lymphovascular invasion.
  • Positive margins or margins less than 5 mm.
  • Extracapsular extension of a lymph node.
  • Two or more involved lymph nodes.

An overall survival (OS) benefit was found for patients with positive margins and extracapsular extensions based on a pooled analysis of the European Organization for the Research and Treatment of Cancer (EORTC) 22931 [NCT00002555] and RTOG-9501 studies.[6-9][Level of evidence: 1iiA] The addition of chemotherapy to radiation therapy for other pathological risk factors is unclear. A postoperative randomized trial (RTOG-0920) is evaluating the use of cetuximab with adjuvant radiation therapy in the postoperative setting.[6-9][Level of evidence: 1iiA]

Current Clinical Trials

Check the list of NCI-supported 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 website.

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.
  2. Mittal B, Marks JE, Ogura JH: Transglottic carcinoma. Cancer 53 (1): 151-61, 1984. [PUBMED Abstract]
  3. 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]
  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. Steiner W: Results of curative laser microsurgery of laryngeal carcinomas. Am J Otolaryngol 14 (2): 116-21, 1993 Mar-Apr. [PUBMED Abstract]
  6. Bernier J, Cooper JS, Pajak TF, et al.: Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 27 (10): 843-50, 2005. [PUBMED Abstract]
  7. Cooper JS, Zhang Q, Pajak TF, et al.: Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 84 (5): 1198-205, 2012. [PUBMED Abstract]
  8. Cooper JS, Pajak TF, Forastiere AA, et al.: Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350 (19): 1937-44, 2004. [PUBMED Abstract]
  9. 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]

Stage III Laryngeal Cancer Treatment

Supraglottis

Standard treatment options:

  1. Chemotherapy administered concomitantly with radiation therapy can be considered for patients who would require total laryngectomy for control of disease.[1]
  2. Induction chemotherapy followed by concomitant chemotherapy and radiation. Laryngectomy is reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[1-6][Level of evidence: 1iiC]
  3. Definitive radiation therapy alone with altered fractionation in patients who are not candidates for concomitant chemotherapy and surgery (total laryngectomy) for salvage of radiation failures.[7]
  4. Surgery with or without postoperative radiation therapy (PORT).[8]

Glottis

Standard treatment options:

  1. Chemotherapy administered concomitantly with radiation therapy can be considered for patients who would require total laryngectomy for control of disease.[1]
  2. Induction chemotherapy followed by concomitant chemotherapy and radiation. Laryngectomy is reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[1-6]
  3. Definitive radiation therapy alone with altered fractionation in patients who are not candidates for concomitant chemotherapy and surgery (total laryngectomy) for salvage of radiation failures.[7]
  4. Surgery with or without PORT.[8]

Treatment options under clinical evaluation:

  • Clinical trials exploring chemotherapy, radiosensitizers, or particle beam radiation therapy.[9]

Subglottis

Standard treatment options:

  1. Laryngectomy plus isolated thyroidectomy and tracheoesophageal node dissection usually followed by postoperative radiation therapy.[10]
  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.
  3. Definitive radiation therapy alone with altered fractionation in patients who are not candidates for concomitant chemotherapy and surgery (total laryngectomy) for salvage of radiation failures.[6,7]
  4. Induction chemotherapy followed by concomitant chemotherapy and radiation. Laryngectomy is reserved for patients with less than a 50% response to chemotherapy or who have persistent disease after radiation.[6]

Treatment options under clinical evaluation:

  • Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy.[9]

Concomitant Chemoradiation Therapy

Concomitant chemoradiation therapy is a standard treatment option for locally advanced (stage III and stage IV) head and neck cancer. A meta-analysis of 93 randomized, prospective head and neck cancer trials published between 1965 and 2000 showed a 4.5% absolute survival advantage in the subset of patients receiving chemotherapy and radiation therapy.[11][Level of evidence: 2A] Patients receiving concomitant chemotherapy had a greater survival benefit than those receiving induction chemotherapy.

Induction Chemoradiation Therapy Followed by Concomitant Chemoradiation Therapy

Two published randomized trials that compared concomitant chemoradiation therapy with induction chemotherapy followed by concomitant chemoradiation therapy for locally advanced head and neck cancer failed to show a survival advantage for induction chemotherapy regimens. The role of induction chemotherapy remains unclear.[12,13][Level of evidence: 1iA]

Altered Fractionation

Radiation therapy alone with altered fractionation may be used for patients with locally advanced head and neck cancer who are not candidates for chemotherapy. Altered fractionation radiation therapy yields a higher locoregional control rate than standard fractionated radiation therapy for patients with stage III and stage IV head and neck cancer. A long-term analysis of randomized trial RTOG-9003 included the following four radiation therapy treatment arms:

  1. Standard fractionated radiation therapy (SFX) to 70 Gy in 35 daily fractions for 7 weeks.
  2. Hyperfractionated radiation therapy (HFX) to 81.6 Gy in 68 twice-daily fractions for 7 weeks.
  3. Accelerated fractionated radiation therapy (AFX-S) to 67.2 Gy in 42 fractions for 6 weeks with a 2-week rest after 38.4 Gy.
  4. Accelerated continuous fractionated radiation therapy (AFX-C) to 72 Gy in 42 fractions for 6 weeks.

The three experimental arms were to be compared with SFX. Only the HFX arm showed superior locoregional control and survival at 5 years compared with the SFX arm (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.62–1.00; P = .05). AFX-C was associated with increased late toxicity compared with SFX.[14-19][Level of evidence: 1iiA]

In a meta-analysis of 15 randomized trials with a total of 6,515 patients and a median follow-up of 6 years involving the assessment of HFX or AFX-S for patients with stage III and stage IV head and neck cancer, there was a significant survival benefit with altered fractionated radiation therapy and a 3.4% absolute benefit at 5 years (HR, 0.92; 95% CI, 0.86–0.97; P = .003). Altered fractionation improves locoregional control, and the benefit is higher in younger patients. HFX demonstrated a greater survival benefit (8% at 5 years) than AFX-S (2% with AFX-S without total dose-reduction and 1.7% with total dose-reduction at 5 years, P = .02).[20][Level of evidence: 1iiA]

Surgery Followed by PORT or Chemoradiation Therapy

Postoperative chemoradiation therapy for head and neck cancer squamous cell carcinoma demonstrates a locoregional control and survival benefit compared with radiation therapy alone in patients who have extracapsular extension (ECE) of a lymph node or positive margins.[5,21-23][Level of evidence: 1iiA]

For patients with T3 and T4 disease (or stage III and stage IV disease), perineural infiltration, vascular embolisms, and clinically enlarged level IV–V lymph nodes secondary to tumors arising in the oral cavity or oropharynx; two or more histopathologically involved lymph nodes without ECE, and close margins less than 5 mm, the addition of cisplatin chemotherapy given concurrently with PORT is unclear. The addition of cetuximab with radiation therapy in the postoperative setting for these risk factors is being tested in a randomized trial (RTOG-0920).

Current Clinical Trials

Check the list of NCI-supported 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 website.

References
  1. Forastiere AA, Zhang Q, Weber RS, et al.: Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 31 (7): 845-52, 2013. [PUBMED Abstract]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. Lefebvre JL, Pointreau Y, Rolland F, et al.: Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol 31 (7): 853-9, 2013. [PUBMED Abstract]
  7. 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]
  8. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med 324 (24): 1685-90, 1991. [PUBMED Abstract]
  9. Adelstein DJ, Lavertu P, Saxton JP, et al.: Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck. Cancer 88 (4): 876-83, 2000. [PUBMED Abstract]
  10. 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.
  11. Pignon JP, le Maître A, Maillard E, et al.: Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 92 (1): 4-14, 2009. [PUBMED Abstract]
  12. Haddad R, O'Neill A, Rabinowits G, et al.: Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol 14 (3): 257-64, 2013. [PUBMED Abstract]
  13. Hitt R, Grau JJ, López-Pousa A, et al.: A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer. Ann Oncol 25 (1): 216-25, 2014. [PUBMED Abstract]
  14. Fu KK, Pajak TF, Trotti A, et al.: A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys 48 (1): 7-16, 2000. [PUBMED Abstract]
  15. Overgaard J, Hansen HS, Specht L, et al.: Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet 362 (9388): 933-40, 2003. [PUBMED Abstract]
  16. Overgaard J, Mohanti BK, Begum N, et al.: Five versus six fractions of radiotherapy per week for squamous-cell carcinoma of the head and neck (IAEA-ACC study): a randomised, multicentre trial. Lancet Oncol 11 (6): 553-60, 2010. [PUBMED Abstract]
  17. Horiot JC, Le Fur R, N'Guyen T, et al.: Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy. Radiother Oncol 25 (4): 231-41, 1992. [PUBMED Abstract]
  18. Bourhis J, Lapeyre M, Tortochaux J, et al.: Phase III randomized trial of very accelerated radiation therapy compared with conventional radiation therapy in squamous cell head and neck cancer: a GORTEC trial. J Clin Oncol 24 (18): 2873-8, 2006. [PUBMED Abstract]
  19. Beitler JJ, Zhang Q, Fu KK, et al.: Final results of local-regional control and late toxicity of RTOG 9003: a randomized trial of altered fractionation radiation for locally advanced head and neck cancer. Int J Radiat Oncol Biol Phys 89 (1): 13-20, 2014. [PUBMED Abstract]
  20. Baujat B, Bourhis J, Blanchard P, et al.: Hyperfractionated or accelerated radiotherapy for head and neck cancer. Cochrane Database Syst Rev (12): CD002026, 2010. [PUBMED Abstract]
  21. Cooper JS, Pajak TF, Forastiere AA, et al.: Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350 (19): 1937-44, 2004. [PUBMED Abstract]
  22. Bernier J, Cooper JS, Pajak TF, et al.: Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 27 (10): 843-50, 2005. [PUBMED Abstract]
  23. Cooper JS, Zhang Q, Pajak TF, et al.: Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 84 (5): 1198-205, 2012. [PUBMED Abstract]

Stage IV Laryngeal Cancer Treatment

Supraglottis

Standard treatment options:

  1. Chemotherapy administered concomitantly with radiation therapy can be considered for patients who would require total laryngectomy for control of disease, including those with nonbulky T4a disease.[1]
  2. Induction chemotherapy followed by concomitant chemotherapy and radiation. Laryngectomy is reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[1-6]
  3. Definitive radiation therapy alone in patients who are not candidates for concomitant chemotherapy and surgery (total laryngectomy) for salvage of radiation failures.[7]
  4. For patients with bulky T4 disease, surgery with PORT with or without concomitant chemotherapy based on pathological risk factors for large volume T4 disease.[8]

Treatment options under clinical evaluation:

  • Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy.[9]

Glottis

Standard treatment options:

  1. Chemotherapy administered concomitantly with radiation therapy can be considered for patients who would require total laryngectomy for control of disease, including those with nonbulky T4a disease.[1]
  2. Induction chemotherapy followed by concomitant chemotherapy and radiation. Laryngectomy is reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[1-6]
  3. Definitive radiation therapy alone in patients who are not candidates for concomitant chemotherapy and surgery (total laryngectomy) for salvage of radiation failures.[7]
  4. For patients with bulky T4 disease, total laryngectomy with postoperative radiation therapy (PORT) with or without concomitant chemotherapy based on pathological risk factors for large volume T4 disease.[8]

Treatment options under clinical evaluation:

  • Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy.[9]

Subglottis

Standard treatment options:

  1. Laryngectomy plus total thyroidectomy and bilateral tracheoesophageal node dissection usually followed by postoperative radiation therapy.[10]
  2. Treatment by radiation therapy alone is indicated for patients who are not candidates for surgery.

Treatment options under clinical evaluation:

  1. Simultaneous chemotherapy and hyperfractionated radiation therapy.[11]
  2. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy.[9]

Concomitant Chemoradiation Therapy

Concomitant chemoradiation therapy is a standard treatment option for locally advanced (stage III and stage IV) head and neck cancer. A meta-analysis of 93 randomized, prospective head and neck cancer trials published between 1965 and 2000 showed a 4.5% absolute survival advantage in the subset of patients receiving chemotherapy and radiation therapy.[12][Level of evidence: 2A] Patients receiving concomitant chemotherapy had a greater survival benefit than those receiving induction chemotherapy.

Induction Chemoradiation Therapy Followed by Concomitant Chemoradiation Therapy

Two published randomized trials that compared concomitant chemoradiation therapy with induction chemotherapy followed by concomitant chemoradiation therapy for locally advanced head and neck failed to show a survival advantage for induction chemotherapy regimens. The role of induction chemotherapy remains unclear.[13,14][Level of evidence: 1iA]

Surgery Followed by PORT or Chemoradiation Therapy

Postoperative chemoradiation therapy for head and neck cancer squamous cell carcinoma demonstrates a locoregional control and survival benefit compared with radiation therapy alone in patients who have extracapsular extension (ECE) of a lymph node or positive margins.[5,15-17][Level of evidence: 1iiA]

For patients with T3 and T4 disease (or stage III and stage IV disease), perineural infiltration, vascular embolisms, and clinically enlarged level IV–V lymph nodes secondary to tumors arising in the oral cavity or oropharynx; two or more histopathologically involved lymph nodes without ECE, and close margins less than 5 mm, the addition of cisplatin chemotherapy given concurrently with PORT is unclear. The addition of cetuximab with radiation therapy in the postoperative setting for these risk factors is being tested in a randomized trial (RTOG-0920).

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage IV 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 website.

References
  1. Forastiere AA, Zhang Q, Weber RS, et al.: Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 31 (7): 845-52, 2013. [PUBMED Abstract]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. Lefebvre JL, Pointreau Y, Rolland F, et al.: Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol 31 (7): 853-9, 2013. [PUBMED Abstract]
  7. 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]
  8. Bernier J, Cooper JS: Chemoradiation after surgery for high-risk head and neck cancer patients: how strong is the evidence? Oncologist 10 (3): 215-24, 2005. [PUBMED Abstract]
  9. Adelstein DJ, Lavertu P, Saxton JP, et al.: Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck. Cancer 88 (4): 876-83, 2000. [PUBMED Abstract]
  10. 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.
  11. Weissler MC, Melin S, Sailer SL, et al.: Simultaneous chemoradiation in the treatment of advanced head and neck cancer. Arch Otolaryngol Head Neck Surg 118 (8): 806-10, 1992. [PUBMED Abstract]
  12. Pignon JP, le Maître A, Maillard E, et al.: Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 92 (1): 4-14, 2009. [PUBMED Abstract]
  13. Haddad R, O'Neill A, Rabinowits G, et al.: Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol 14 (3): 257-64, 2013. [PUBMED Abstract]
  14. Hitt R, Grau JJ, López-Pousa A, et al.: A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer. Ann Oncol 25 (1): 216-25, 2014. [PUBMED Abstract]
  15. Cooper JS, Pajak TF, Forastiere AA, et al.: Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350 (19): 1937-44, 2004. [PUBMED Abstract]
  16. Bernier J, Cooper JS, Pajak TF, et al.: Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 27 (10): 843-50, 2005. [PUBMED Abstract]
  17. Cooper JS, Zhang Q, Pajak TF, et al.: Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 84 (5): 1198-205, 2012. [PUBMED Abstract]

Recurrent Laryngeal Cancer

Treatment of recurrent supraglottic, glottic, and subglottic cancer includes further surgery or clinical trials.[1-3]

Standard treatment options:

  1. Surgery [4] and/or radiation therapy. Salvage is possible for failures of surgery alone or of radiation therapy alone, and further surgery [4] and/or radiation therapy should be attempted, as indicated. Selected patients may be candidates for partial laryngectomy after high-dose radiation therapy has failed.[5]
  2. Radiation therapy. Re-irradiation for laryngeal salvage following radiation therapy failure has resulted in long-term survival in a small number of patients; it may be considered for small recurrences after radiation therapy, especially in patients who refuse or are not candidates for laryngectomy.[6]
  3. Chemotherapy. A response of variable duration may be achieved after systemic chemotherapy.[7]

Salvage after previous combined total laryngectomy and radiation therapy is poor.

Treatment options under clinical evaluation:

  • Patients whose disease does not respond to combined radiation therapy and surgery probably are best treated by palliative chemotherapy in clinical trials.

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with recurrent 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 website.

References
  1. Million RR, Cassisi NJ, eds.: Management of Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott, 1994.
  2. Vikram B, Strong EW, Shah JP, et al.: Intraoperative radiotherapy in patients with recurrent head and neck cancer. Am J Surg 150 (4): 485-7, 1985. [PUBMED Abstract]
  3. Jacobs C, Lyman G, Velez-García E, et al.: A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol 10 (2): 257-63, 1992. [PUBMED Abstract]
  4. Wong LY, Wei WI, Lam LK, et al.: Salvage of recurrent head and neck squamous cell carcinoma after primary curative surgery. Head Neck 25 (11): 953-9, 2003. [PUBMED Abstract]
  5. Paleri V, Thomas L, Basavaiah N, et al.: Oncologic outcomes of open conservation laryngectomy for radiorecurrent laryngeal carcinoma: a systematic review and meta-analysis of English-language literature. Cancer 117 (12): 2668-76, 2011. [PUBMED Abstract]
  6. Wang CC, McIntyre J: Re-irradiation of laryngeal carcinoma--techniques and results. Int J Radiat Oncol Biol Phys 26 (5): 783-5, 1993. [PUBMED Abstract]
  7. Al-Sarraf M: Head and neck cancer: chemotherapy concepts. Semin Oncol 15 (1): 70-85, 1988. [PUBMED Abstract]

Changes to This Summary (05/20/2016)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information About Laryngeal Cancer

Updated statistics with estimated new cases and deaths for 2016 (cited American Cancer Society as reference 1).

Stage Information for Laryngeal Cancer

Revised text to state that the assessment of the primary tumor is based on inspection and palpation when possible and by fiberoptic laryngoscopy; also added that panendoscopy under anesthesia ensures careful clinical examination to determine the clinical extent of local disease. An additional revision states that head and neck magnetic resonance imaging, computed tomography, or positron emission tomography/computed tomography should be done before therapy to supplement inspection and palpation.

Treatment Option Overview for Laryngeal Cancer

Added text to state that elective neck radiation should be considered for T3 or T4 glottic tumors or T1 to T4 supraglottic tumors.

Stage I Laryngeal Cancer Treatment

Added text to state that selection of treatment should include an evaluation of voice function and quality after treatment; added that endoscopic CO2 laser resections may also achieve similar results in terms of local control and function (cited Agrawal et al. as reference 1) compared with radiation therapy, although no randomized studies have been performed (cited Dey et al. as reference 2). Also added that a meta-analysis of 22 consecutive case series to examine oncologic control demonstrated no clear differences between transoral CO2 laser excision and external beam radiation therapy (EBRT) in terms of local control; there was a trend for improved posttreatment voice quality with radiation therapy. Transoral CO2 laser–excision surgery dominates radiotherapy from a cost-utility standpoint (added level of evidence 2C).

Added option to list of glottis standard treatments to include endoscopic CO2 laser excision (cited Higgins as reference 11).

Stage II Laryngeal Cancer Treatment

Added option to list of supraglottis standard treatments to include EBRT alone for the smaller lesions encompassing the primary disease and regional elective nodes.

Revised option in list of supraglottis standard treatments to state supraglottic laryngectomy with bilateral neck dissections, depending on location of the lesion, clinical status of the patient, and expertise of the treatment team.

Revised option in list of supraglottis standard treatments to state postoperative radiation therapy (PORT) is indicated for positive or close surgical margins or other adverse pathological risk factors.

Added PORT With or Without Chemotherapy as a new subsection.

Stage III Laryngeal Cancer Treatment

Added Forastiere et al. as reference 1.

Added Lefebvre et al. as reference 6 and level of evidence 1iiC.

Revised option in list of supraglottis standard treatments to state definitive radiation therapy alone with altered fractionation in patients who are not candidates for concomitant chemotherapy and surgery for salvage of radiation failures.

Added option to list of supraglottis standard treatments to include surgery with or without PORT (cited The Department of Veterans Affairs Laryngeal Cancer Study Group as reference 8).

Revised option in list of glottis standard treatments to state definitive radiation therapy alone with altered fractionation in patients who are not candidates for concomitant chemotherapy and surgery for salvage of radiation failures.

Added option to list of glottis standard treatments to include surgery with or without PORT.

Added option to list of subglottis standard treatments to include definitive radiation therapy alone with altered fractionation in patients who are not candidates for concomitant chemotherapy and surgery (total laryngectomy) for salvage of radiation failures.

Added option to list of subglottis standard treatments to include induction chemotherapy followed by concomitant chemotherapy and radiation. Also added that laryngectomy is reserved for patients with less than a 50% response to chemotherapy or who have persistent disease after radiation.

Added Concomitant Chemoradiation Therapy as a new subsection.

Added Induction Chemoradiation Therapy Followed by Concomitant Chemoradiation Therapy as a new subsection.

Added Altered Fractionation as a new subsection.

Added Surgery Followed by PORT or Chemoradiation Therapy as a new subsection.

Stage IV Laryngeal Cancer Treatment

Added Forastiere et al. as reference 1.

Added Lefebvre et al. as reference 6.

Revised option in list of supraglottis standard treatments to state for patients with bulky T4 disease, surgery with PORT with or without concomitant chemotherapy based on pathological risk factors for large volume T4 disease.

Revised option in list of glottis standard treatments to state for patients with bulky T4 disease, total laryngectomy with PORT with or without concomitant chemotherapy based on pathological risk factors for large volume T4 disease.

Added Concomitant Chemoradiation Therapy as a new subsection.

Added Induction Chemoradiation Therapy Followed by Concomitant Chemoradiation Therapy as a new subsection.

Added Surgery Followed by PORT or Chemoradiation Therapy as a new subsection.

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of laryngeal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Laryngeal Cancer Treatment are:

  • Scharukh Jalisi, MD, FACS (Boston University Medical Center)
  • Minh Tam Truong, MD (Boston University Medical Center)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

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The preferred citation for this PDQ summary is:

PDQ® Adult Treatment Editorial Board. PDQ Laryngeal Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: http://www.cancer.gov/types/head-and-neck/hp/laryngeal-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389189]

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  • Updated: May 20, 2016

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