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Information from PDQ -- for Health Professionals
Laryngeal cancer
208/01519
** GENERAL INFORMATION **
The larynx is divided into 3 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 centimeter 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 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.[1]
A clear association has been made between smoking, excess alcohol ingestion,
and the development of squamous cell cancers of the upper aerodigestive
tract.[2] If a patient with 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. Second
primary tumors, often in the aerodigestive tract, have been reported in up to
25% of patients whose initial lesion is controlled. A study has shown that
daily treatment of these patients with moderate doses of isotretinoin
(13-cis-retinoic acid) for 1 year can significantly reduce the incidence of
second tumors.[3] No survival advantage has yet been demonstrated, however, in
part because of recurrence and death from the primary malignancy. Additional
trials are ongoing.
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.[4]
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,[5]
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 greater than 13 grams per deciliter have higher local control
and survival rates than patients who are anemic.[6] This observation is being
evaluated in a randomized clinical trial.
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 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. Spaulding CA, Hahn SS, Constable WC: The effectiveness of treatment of
lymph nodes in cancers of the pyriform sinus and supraglottis.
International Journal of Radiation Oncology, Biology, Physics 13(7):
963-968, 1987.
2. Spitz MR: Epidemiology and risk factors for head and neck cancer.
Seminars in Oncology 21(3): 281-288, 1994.
3. Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors
with isotretinoin in squamous-cell carcinoma of the head and neck. New
England Journal of Medicine 323(12): 795-801, 1990.
4. Yilmaz T, Hosal AS, Gedikoglu G, et al.: Prognostic significance of depth
of invasion in cancer of the larynx. Laryngoscope 108(5): 764-768,
1998.
5. Reddy SP, Mohideen N, Marra S, et al.: Effect of tumor bulk on local
control and survival of patients with T1 glottic cancer. Radiotherapy
and Oncology 47(2): 161-166, 1997.
6. 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. Journal of Clinical Oncology 13(8): 2077-2083,
1995.
** CELLULAR CLASSIFICATION **
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 (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.[2]
References:
1. Sessions RB, Harrison LB, Forastiere AA: Tumors of the larynx and
hypopharynx. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer:
Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven
Publishers, 5th ed., 1997, pp 802-829.
2. Wang CC, Ed.: Radiation Therapy for Head and Neck Neoplasms:
Indications, Techniques and Results. Littleton, MA: John Wright-PSG,
Inc., 2nd ed., 1990.
** STAGE INFORMATION **
The staging system is clinical, 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 are examined by careful palpation.
The American Joint Committee on Cancer (AJCC) has designated staging by TNM
classification.[2]
-- TNM definitions --
Primary tumor (T)
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 tissues
T4: Tumor invades through the thyroid cartilage, and/or extends into soft
tissues of the neck, thyroid, and/or esophagus
*Subsites include the following:
ventricular bands (false cords)
arytenoids
suprahyoid epiglottis
infrahyoid epiglottis
aryepiglottic folds (laryngeal aspect)
Glottis
T1: Tumor limited to 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
T4: Tumor invades through the thyroid cartilage and/or to other tissues
beyond the larynx (e.g., trachea, soft tissues of neck, including
thyroid, pharynx)
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
T4: Tumor invades through cricoid or thyroid cartilage and/or extends to
other tissues beyond the larynx (e.g., trachea, soft tissues of neck,
including thyroid, esophagus)
Regional lymph nodes (N)
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest
dimension
N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not
more than 6 cm in greatest dimension, or in multiple ipsilateral lymph
nodes, none more than 6 cm in greatest dimension, or in bilateral or
contralateral lymph nodes, none more than 6 cm in greatest dimension
N2a: Metastasis in a single ipsilateral lymph node more than 3 cm
but not more than 6 cm in greatest dimension
N2b: Metastasis in multiple ipsilateral lymph nodes, none more than
6 cm in greatest dimension
N2c: Metastasis in bilateral or contralateral lymph nodes, none more
than 6 cm in greatest dimension
N3: Metastasis in a lymph node more than 6 cm in greatest dimension
In clinical evaluation, the actual size of the nodal mass should be measured,
and allowance should be made for intervening soft tissues. Most masses larger
than 3 centimeters in diameter are not single nodes but confluent nodes or
tumors in soft tissues of the neck. There are 3 stages of clinically positive
nodes: N1, N2, and N3. The use of subgroups a, b, and c is not required but
recommended. Midline nodes are considered homolateral nodes.
Distant metastasis (M)
MX: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis
Supraglottis involves many individual subsites. Relapse-free survival may
differ by subsite and by T and N groupings within stage.
Glottic presentation may vary by volume of tumor, anatomic region involved, and
the presence or absence of normal cord mobility. Relapse-free survival may
differ by these and other factors in addition to T and N subgroupings within
stage.
-- AJCC stage groupings --
-- Stage 0 --
Tis, N0, M0
-- Stage I --
T1, N0, M0
-- Stage II --
T2, N0, M0
-- Stage III --
T3, N0, M0
T1, N1, M0
T2, N1, M0
T3, N1, M0
-- Stage IVA --
T4, N0, M0
T4, N1, M0
Any T, N2, M0
-- Stage IVB --
Any T, N3, M0
-- Stage IVC --
Any T, Any N, M1
Evaluation of treatment outcome can be reported in various ways: locoregional
control, disease-free survival, determinate survival, and overall survival 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.
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.
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, leading to less favorable results.
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): 589-594, 1996.
2. Larynx. In: American Joint Committee on Cancer: AJCC Cancer Staging
Manual. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp
41-46.
** TREATMENT OPTION OVERVIEW **
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,
reserving 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.[1-4] Because the cure rate
for advanced lesions is low, clinical trials exploring chemotherapy,
hyperfractionated radiation therapy,[5] radiation sensitizers, or particle-beam
radiation therapy should be considered.[6,7] 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.[8,9]
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 irradiation for larger or supraglottic tumors.[10]
For patients with cancer of the subglottis, combined modality therapy is
generally preferred although for the uncommon small lesions (stage I or stage
II), 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;[11] therefore, patients
should be counseled to stop smoking before beginning radiation therapy.
Accumulating evidence has demonstrated a high incidence (>30%-40%) of
hypothyroidism in patients who have received external-beam irradiation to the
entire thyroid gland or to the pituitary gland. Thyroid-function testing of
patients should be considered prior to therapy and as part of post-treatment
follow-up.[12,13]
The designations in PDQ that treatments are "standard" or "under clinical
evaluation" are not to be used as a basis for reimbursement determinations.
References:
1. Silver CE: Surgery for Cancer of the Larynx and Related Structures. New
York: Churchill Livingstone, 1981.
2. Wang CC, Ed.: Radiation Therapy for Head and Neck Neoplasms:
Indications, Techniques and Results. Littleton, MA: John Wright-PSG,
Inc., 2nd ed., 1990.
3. Thawley SE, Panje WR, Batsakis JG, et al.: Comprehensive Management of
Head and Neck Tumors. New York: W.B. Saunders Company, 1986.
4. Sessions RB, Harrison LB, Forastiere AA: Tumors of the larynx and
hypopharynx. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer:
Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven
Publishers, 5th ed., 1997, pp 802-829.
5. Bourhis J, Wibault P, Lusinchi A, et al.: Status of accelerated
fractionation radiotherapy in head and neck squamous cell carcinomas.
Current Opinion in Oncology 9(3): 262-266, 1997.
6. Taylor SG: Integration of chemotherapy into the combined modality therapy
of head and neck squamous cancer. International Journal of Radiation
Oncology, Biology, Physics 13(5): 779-783, 1987.
7. Stupp R, Weichselbaum RR, Vokes EE: Combined modality therapy of head and
neck cancer. Seminars in Oncology 21(3): 349-358, 1994.
8. Fowler JF, Lindstrom MJ: Loss of local control with prolongation in
radiotherapy. International Journal of Radiation Oncology, Biology,
Physics 23(2): 457-467, 1992.
9. 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. Radiotherapy and
Oncology 43(1): 47-51, 1997.
10. Spaulding CA, Hahn SS, Constable WC: The effectiveness of treatment of
lymph nodes in cancers of the pyriform sinus and supraglottis.
International Journal of Radiation Oncology, Biology, Physics 13(7):
963-968, 1987.
11. Browman GP, Wong G, Hodson I, et al.: Influence of cigarette smoking on
the efficacy of radiation therapy in head and neck cancer. New England
Journal of Medicine 328(3): 159-163, 1993.
12. Turner SL, Tiver KW, Boyages SC: Thyroid dysfunction following
radiotherapy for head and neck cancer. International Journal of
Radiation Oncology, Biology, Physics 31(2): 279-283, 1995.
13. Constine LS: What else don't we know about the late effects of radiation
in patients treated for head and neck cancer? International Journal of
Radiation Oncology, Biology, Physics 31(2): 427-429, 1995.
** STAGE I LARYNGEAL CANCER **
-- 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. However, irradiation should be preferred because of
good results, preservation of voice, and possibility of surgical salvage in
patients whose disease recurs locally.[1]
-- Glottis --
Standard treatment options:
1. Radiation therapy.[2-5]
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:
Lesions can be treated successfully by radiation therapy alone with
preservation of normal voice. Surgery is reserved for failure of radiation
therapy or for patients who cannot be easily assessed for radiation therapy.
References:
1. Ogura JH, Sessions DG, Spector GJ: Conservation surgery for epidermoid
carcinoma of the supraglottic larynx. Laryngoscope 85(11): 1808-1815,
1975.
2. Mittal BB, Rao DV, Marks JE, et al.: Role of radiation in the management
of early vocal cord carcinoma. International Journal of Radiation
Oncology, Biology, Physics 9(7): 997-1002, 1983.
3. Wang CC: Factors influencing the success of radiation therapy for T2 and
T3 glottic carcinomas: importance of cord mobility and sex. American
Journal of Clinical Oncology 9(6): 517-520, 1986.
4. Mendenhall WM, Amdur RJ, Morris CG, et al.: T1-T2N0 squamous cell
carcinoma of the glottic larynx treated with radiation therapy. Journal
of Clinical Oncology 19(20): 4029-4036, 2001.
5. Foote RL, Olsen KD, Kunselman SJ, et al.: Early-stage squamous cell
carcinoma of the glottic larynx managed with radiation therapy. Mayo
Clinic Proceedings 67(7): 629-636, 1992.
6. Steiner W: Results of curative laser microsurgery of laryngeal
carcinomas. American Journal of Otolaryngology 14(2): 116-121, 1993.
7. Olsen KD, Thomas JV, DeSanto LW, et al.: Indications and results of
cordectomy for early glottic carcinoma. Otolaryngology and Head and
Neck Surgery 108(3): 277-282, 1993.
** STAGE II LARYNGEAL CANCER **
-- Supraglottis --
Standard treatment options:
1. External-beam radiation therapy alone for the smaller lesions.[1,2]
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. Irradiation should be preferred because
of good results, preservation of voice, and possibility of surgical salvage in
patients whose disease recurs locally.[3]
3. Postoperative radiation therapy is indicated for positive or "close"
surgical margins.
Treatment options under clinical evaluation:
1. Hyperfractionated radiation therapy to improve tumor control rates and
diminish late toxicity to normal tissue.[2,4]
2. Isotretinoin (13-cis-retinoic acid) daily for 1 year to prevent development
of second upper aerodigestive tract primary tumors.[5]
-- Glottis --
Standard treatment options:
1. Radiation therapy.[1,2,6-8]
2. Partial or hemilaryngectomy or total laryngectomy, depending on anatomic
considerations. Under certain circumstances, laser microsurgery may be
appropriate.[9]
Treatment options under clinical evaluation:
1. Hyperfractionated radiation therapy to improve tumor control rates and
diminish late toxicity to normal tissue.[2,4]
2. Isotretinoin daily for 1 year to prevent development of second upper
aerodigestive tract primary tumors.[5]
-- Subglottis --
Standard treatment options:
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.
Treatment options under clinical evaluation:
1. Hyperfractionated radiation therapy to improve tumor control rates and
diminish late toxicity to normal tissue.[2,4]
2. Isotretinoin daily for 1 year to prevent development of second upper
aerodigestive tract primary tumors.[5]
References:
1. Sessions RB, Harrison LB, Forastiere AA: Tumors of the larynx and
hypopharynx. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer:
Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven
Publishers, 5th ed., 1997, pp 802-829.
2. Wang CC, Ed.: Radiation Therapy for Head and Neck Neoplasms:
Indications, Techniques and Results. Littleton, MA: John Wright-PSG,
Inc., 2nd ed., 1990.
3. Ogura JH, Sessions DG, Spector GJ: Conservation surgery for epidermoid
carcinoma of the supraglottic larynx. Laryngoscope 85(11): 1808-1815,
1975.
4. Parsons JT, Mendenhall WM, Cassisi NJ, et al.: Hyperfractionation for
head and neck cancer. International Journal of Radiation Oncology,
Biology, Physics 14(4): 649-658, 1988.
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. New
England Journal of Medicine 323(12): 795-801, 1990.
6. Mittal BB, Marks JE, Ogura JH: Transglottic carcinoma. Cancer 53(1):
151-161, 1984.
7. Medini E, Medini I, Lee CK, et al.: Curative radiotherapy for stage
II-III squamous cell carcinoma of the glottic larynx. American Journal
of Clinical Oncology 21(3): 302-305, 1998.
8. Mendenhall WM, Amdur RJ, Morris CG, et al.: T1-T2N0 squamous cell
carcinoma of the glottic larynx treated with radiation therapy. Journal
of Clinical Oncology 19(20): 4029-4036, 2001.
9. Steiner W: Results of curative laser microsurgery of laryngeal
carcinomas. American Journal of Otolaryngology 14(2): 116-121, 1993.
** STAGE III LARYNGEAL CANCER **
-- Supraglottis --
Standard treatment options:
1. Surgery with or without postoperative radiation therapy.[1-6]
2. Definitive radiation therapy with surgery for salvage of radiation
failures.[7]
Treatment options under clinical evaluation:
1. Hyperfractionated radiation therapy to improve tumor control rates and
diminish late toxicity to normal tissue.[8,9]
2. In patients who would require total laryngectomy for control of disease,
either induction with combination chemotherapy followed by definitive radiation
therapy or chemotherapy administered concomitantly with radiation therapy can
be considered. Laryngectomy would be reserved for patients with less than 50%
response to chemotherapy or who have persistent disease following
radiation.[10-15]
3. Clinical trials exploring chemotherapy, radiosensitizers, or particle- beam
radiation therapy.[16-20]
A meta-analysis of 3 trials of patients with locally advanced laryngeal
carcinomas compared patients who received standard radical surgery plus
radiation therapy to patients who received neoadjuvant cisplatin and
fluorouracil, followed by radiation therapy alone in responders or radical
surgery plus radiation therapy in nonresponders.[21] The meta-analysis
demonstrated a nonsignificant trend in favor of the control group who received
standard radical surgery plus radiation therapy with an absolute negative
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
of the larynx in those patients whose disease was controlled.
4. Isotretinoin (13-cis-retinoic acid) daily for 1 year to prevent development
of second upper aerodigestive tract primary tumors.[22]
-- Glottis --
Standard treatment options:
1. Surgery with or without postoperative radiation therapy.[1-6,23]
2. Definitive radiation therapy with surgery for salvage of radiation
failures.[7,24]
Treatment options under clinical evaluation:
1. Hyperfractionated radiation therapy to improve tumor control rates and
diminish late toxicity to normal tissue.[8,9]
2. In patients who would require total laryngectomy for control of disease,
either induction with combination chemotherapy followed by definitive radiation
therapy or chemotherapy administered concomitantly with radiation therapy can
be considered. Laryngectomy would be reserved for patients with less than 50%
response to chemotherapy or who have persistent disease following
radiation.[10-15]
3. Clinical trials exploring chemotherapy, radiosensitizers, or particle beam
radiation therapy.[16,17,19,20]
A meta-analysis of 3 trials of patients with locally advanced laryngeal
carcinomas compared patients who received standard radical surgery plus
radiation therapy to patients who received neoadjuvant cisplatin and
fluorouracil, followed by radiation therapy alone in responders or radical
surgery plus radiation therapy in nonresponders.[21] The meta-analysis
demonstrated a nonsignificant trend in favor of the control group who received
standard radical surgery plus radiation therapy with an absolute negative
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
of the larynx in those patients whose disease was controlled.
4. Isotretinoin daily for 1 year to prevent development of second upper
aerodigestive tract primary tumors.[22]
-- Subglottis --
Standard treatment options:
1. Laryngectomy plus isolated thyroidectomy and tracheoesophageal node
dissection usually followed by postoperative radiation therapy.[1-3]
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.[8,9]
2. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam
radiation therapy.[16,17,19,20]
A meta-analysis of 3 trials of patients with locally advanced laryngeal
carcinomas compared patients who received standard radical surgery plus
radiation therapy to patients who received neoadjuvant cisplatin and
fluorouracil, followed by radiation therapy alone in responders or radical
surgery plus radiation therapy in nonresponders.[21] The meta-analysis
demonstrated a nonsignificant trend in favor of the control group who received
standard radical surgery plus radiation therapy with an absolute negative
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
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.[22]
References:
1. Thawley SE, Panje WR, Batsakis JG, et al.: Comprehensive Management of
Head and Neck Tumors. New York: W.B. Saunders Company, 1986.
2. Sessions RB, Harrison LB, Forastiere AA: Tumors of the larynx and
hypopharynx. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer:
Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven
Publishers, 5th ed., 1997, pp 802-829.
3. 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): 1819-1825, 1983.
4. Spaulding CA, Krochak RJ, Hahn SS, et al.: Radiotherapeutic management of
cancer of the supraglottis. Cancer 57(7): 1292-1298, 1986.
5. Ogura JH, Sessions DG, Spector GJ: Conservation surgery for epidermoid
carcinoma of the supraglottic larynx. Laryngoscope 85(11): 1808-1815,
1975.
6. Tupchong L, Phil D, Scott CB, 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. International
Journal of Radiation Oncology, Biology, Physics 20(1): 21-28, 1991.
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. International
Journal of Radiation Oncology, Biology, Physics 47(1): 65-71, 2000.
8. Wang CC, Ed.: Radiation Therapy for Head and Neck Neoplasms:
Indications, Techniques and Results. Littleton, MA: John Wright-PSG,
Inc., 2nd ed., 1990.
9. Parsons JT, Mendenhall WM, Cassisi NJ, et al.: Hyperfractionation for
head and neck cancer. International Journal of Radiation Oncology,
Biology, Physics 14(4): 649-658, 1988.
10. Induction chemotherapy plus radiation compared with surgery plus
radiation in patients with advanced laryngeal cancer. The Department of
Veterans Affairs Laryngeal Cancer Study Group. New England Journal of
Medicine 324(24): 1685-1690, 1991.
11. Urba SG, Forastiere AA, Wolf GT, et al.: Intensive induction chemotherapy
and radiation for organ preservation in patients with advanced
resectable head and neck carcinoma. Journal of Clinical Oncology 12(5):
946-953, 1994.
12. Spaulding MB, Fischer SG, Wolf GT, et al.: Tumor response, toxicity, and
survival after neoadjuvant organ-preserving chemotherapy for advanced
laryngeal carcinoma. Journal of Clinical Oncology 12(8): 1592-1599,
1994.
13. Merlano M, Benasso M, Corvo 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. Journal of the National Cancer Institute 88(9):
583-589, 1996.
14. 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 and Neck 19(7): 567-575, 1997.
15. 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. Journal of Clinical Oncology 18(7): 1458-1464, 2000.
16. Bachaud J, David J, 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
trial. International Journal of Radiation Oncology, Biology, Physics
20(2): 243-246, 1991.
17. Merlano M, Corvo R, Margarino G, et al.: Combined chemotherapy and
radiation therapy in advanced inoperable squamous cell carcinoma of the
head and neck: the final report of a randomized trial. Cancer 67(4):
915-921, 1991.
18. Wang CC, Suit HD, Blitzer PH, et al.: Twice-a-day radiation therapy for
supraglottic carcinoma. International Journal of Radiation Oncology,
Biology, Physics 12(1): 3-7, 1986.
19. Browman GP, Cripps C, Hodson DI, et al.: Placebo-controlled randomized
trial of infusional fluorouracil during standard radiotherapy in locally
advanced head and neck cancer. Journal of Clinical Oncology 12(12):
2648-2653, 1994.
20. 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): 876-883, 2000.
21. Pignon JP, Bourhis J, et al., on behalf of the MACH-NC Collaborative
Group: Chemotherapy added to locoregional treatment for head and neck
squamous-cell carcinoma: three meta-analyses of updated individual data.
Lancet 355(9208): 949-955, 2000.
22. Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors
with isotretinoin in squamous-cell carcinoma of the head and neck. New
England Journal of Medicine 323(12): 795-801, 1990.
23. Mittal BB, Marks JE, Ogura JH: Transglottic carcinoma. Cancer 53(1):
151-161, 1984.
24. Medini E, Medini I, Lee CK, et al.: Curative radiotherapy for stage
II-III squamous cell carcinoma of the glottic larynx. American Journal
of Clinical Oncology 21(3): 302-305, 1998.
** STAGE IV LARYNGEAL CANCER **
-- Supraglottis --
Standard treatment options:
1. Total laryngectomy with postoperative radiation therapy.[1-7]
2. Definitive radiation therapy with surgery for salvage of radiation
failures.[8]
Treatment options under clinical evaluation:
1. Hyperfractionated radiation therapy to improve tumor control rates and
diminish late toxicity to normal tissue.[2,9]
2. In patients who would require total laryngectomy for control of disease,
either induction with combination chemotherapy followed by definitive radiation
therapy or chemotherapy administered concomitantly with radiation therapy can
be considered. Laryngectomy would be reserved for patients with less than 50%
response to chemotherapy or who have persistent disease following
radiation.[10-15]
3. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam
radiation therapy.[16-20]
A meta-analysis of 3 trials of patients with locally advanced laryngeal
carcinomas compared patients who received standard radical surgery plus
radiation therapy to patients who received neoadjuvant cisplatin and
fluorouracil, followed by radiation therapy alone in responders or radical
surgery plus radiation therapy in nonresponders.[21] The meta-analysis
demonstrated a nonsignificant trend in favor of the control group who received
standard radical surgery plus radiation therapy with an absolute negative
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
of the larynx in those patients whose disease was controlled.
4. Isotretinoin (13-cis-retinoic acid) daily for 1 year to prevent development
of second upper aerodigestive tract primary tumors.[22]
-- Glottis --
Standard treatment options:
1. Total laryngectomy with postoperative radiation therapy.[1-4,23]
2. Definitive radiation therapy with surgery for salvage of radiation
failures.[8]
Treatment options under clinical evaluation:
1. Hyperfractionated radiation therapy to improve tumor control rates and
diminish late toxicity to normal tissue.[2,9]
2. In patients who would require total laryngectomy for control of disease,
either induction with combination chemotherapy followed by definitive radiation
therapy or chemotherapy administered concomitantly with radiation therapy can
be considered. Laryngectomy would be reserved for patients with less than 50%
response to chemotherapy or who have persistent disease following
radiation.[10-15]
3. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam
radiation therapy.[16,17,19,20]
A meta-analysis of 3 trials of patients with locally advanced laryngeal
carcinomas compared patients who received standard radical surgery plus
radiation therapy to patients who received neoadjuvant cisplatin and
fluorouracil, followed by radiation therapy alone in responders or radical
surgery plus radiation therapy in nonresponders.[21] The meta-analysis
demonstrated a nonsignificant trend in favor of the control group who received
standard radical surgery plus radiation therapy with an absolute negative
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
of the larynx in those patients whose disease was controlled.
4. Isotretinoin daily for 1 year to prevent development of second upper
aerodigestive tract primary tumors.[22]
-- Subglottis --
Standard treatment options:
1. Laryngectomy plus total thyroidectomy and bilateral tracheoesophageal node
dissection usually followed by postoperative radiation therapy.[1-4]
2. Treatment by radiation therapy alone is indicated for patients who are not
candidates for surgery.
Treatment options under clinical evaluation:
1. Hyperfractionated radiation therapy to improve tumor control rates and
diminish late toxicity to normal tissue.[2,9]
2. Simultaneous chemotherapy and hyperfractionated radiation therapy.[24]
3. Clinical trials exploring chemotherapy, radiosensitizers, or particle beam
radiation therapy.[16,17,19,20]
A meta-analysis of 3 trials of patients with locally advanced laryngeal
carcinomas compared patients who received standard radical surgery plus
radiation therapy to patients who received neoadjuvant cisplatin and
fluorouracil, followed by radiation therapy alone in responders or radical
surgery plus radiation therapy in nonresponders.[21] The meta-analysis
demonstrated a nonsignificant trend in favor of the control group who received
standard radical surgery plus radiation therapy with an absolute negative
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
of the larynx in those patients whose disease was controlled.
4. Isotretinoin daily for 1 year to prevent development of second upper
aerodigestive tract primary tumors.[22]
References:
1. Sessions RB, Harrison LB, Forastiere AA: Tumors of the larynx and
hypopharynx. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer:
Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven
Publishers, 5th ed., 1997, pp 802-829.
2. Wang CC, Ed.: Radiation Therapy for Head and Neck Neoplasms:
Indications, Techniques and Results. Littleton, MA: John Wright-PSG,
Inc., 2nd ed., 1990.
3. Thawley SE, Panje WR, Batsakis JG, et al.: Comprehensive Management of
Head and Neck Tumors. New York: W.B. Saunders Company, 1986.
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): 1819-1825, 1983.
5. Spaulding CA, Krochak RJ, Hahn SS, et al.: Radiotherapeutic management of
cancer of the supraglottis. Cancer 57(7): 1292-1298, 1986.
6. Ogura JH, Sessions DG, Spector GJ: Conservation surgery for epidermoid
carcinoma of the supraglottic larynx. Laryngoscope 85(11): 1808-1815,
1975.
7. Tupchong L, Phil D, Scott CB, 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. International
Journal of Radiation Oncology, Biology, Physics 20(1): 21-28, 1991.
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. International
Journal of Radiation Oncology, Biology, Physics 47(1): 65-71, 2000.
9. Parsons JT, Mendenhall WM, Cassisi NJ, et al.: Hyperfractionation for
head and neck cancer. International Journal of Radiation Oncology,
Biology, Physics 14(4): 649-658, 1988.
10. Induction chemotherapy plus radiation compared with surgery plus
radiation in patients with advanced laryngeal cancer. The Department of
Veterans Affairs Laryngeal Cancer Study Group. New England Journal of
Medicine 324(24): 1685-1690, 1991.
11. Urba SG, Forastiere AA, Wolf GT, et al.: Intensive induction chemotherapy
and radiation for organ preservation in patients with advanced
resectable head and neck carcinoma. Journal of Clinical Oncology 12(5):
946-953, 1994.
12. Spaulding MB, Fischer SG, Wolf GT, et al.: Tumor response, toxicity, and
survival after neoadjuvant organ-preserving chemotherapy for advanced
laryngeal carcinoma. Journal of Clinical Oncology 12(8): 1592-1599,
1994.
13. Merlano M, Benasso M, Corvo 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. Journal of the National Cancer Institute 88(9):
583-589, 1996.
14. 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 and Neck 19(7): 567-575, 1997.
15. 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. Journal of Clinical Oncology 18(7): 1458-1464, 2000.
16. Bachaud J, David J, 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
trial. International Journal of Radiation Oncology, Biology, Physics
20(2): 243-246, 1991.
17. Merlano M, Corvo R, Margarino G, et al.: Combined chemotherapy and
radiation therapy in advanced inoperable squamous cell carcinoma of the
head and neck: the final report of a randomized trial. Cancer 67(4):
915-921, 1991.
18. Wang CC, Suit HD, Blitzer PH, et al.: Twice-a-day radiation therapy for
supraglottic carcinoma. International Journal of Radiation Oncology,
Biology, Physics 12(1): 3-7, 1986.
19. Browman GP, Cripps C, Hodson DI, et al.: Placebo-controlled randomized
trial of infusional fluorouracil during standard radiotherapy in locally
advanced head and neck cancer. Journal of Clinical Oncology 12(12):
2648-2653, 1994.
20. 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): 876-883, 2000.
21. Pignon JP, Bourhis J, et al., on behalf of the MACH-NC Collaborative
Group: Chemotherapy added to locoregional treatment for head and neck
squamous-cell carcinoma: three meta-analyses of updated individual data.
Lancet 355(9208): 949-955, 2000.
22. Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors
with isotretinoin in squamous-cell carcinoma of the head and neck. New
England Journal of Medicine 323(12): 795-801, 1990.
23. Mittal BB, Marks JE, Ogura JH: Transglottic carcinoma. Cancer 53(1):
151-161, 1984.
24. Weissler MC, Melin S, Sailer SL, et al.: Simultaneous chemoradiation in
the treatment of advanced head and neck cancer. Archives of
Otolaryngology, Head and Neck Surgery 118(8): 806-810, 1992.
** RECURRENT LARYNGEAL CANCER **
Treatment of recurrent supraglottic, glottic, and subglottic cancer includes
further surgery or clinical trials.[1-4]
Standard treatment options:
Salvage is possible for failures of surgery alone or of radiation therapy alone
and further surgery 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] 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] 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.
References:
1. Million RR, Cassisi NJ, Eds.: Management of Head and Neck Cancer: a
Multidisciplinary Approach. Philadelphia: Lippincott, 1984.
2. Wang CC, Ed.: Radiation Therapy for Head and Neck Neoplasms:
Indications, Techniques and Results. Littleton, MA: John Wright-PSG,
Inc., 2nd ed., 1990.
3. Vikram B, Strong EW, Shah JP, et al.: Intraoperative radiotherapy in
patients with recurrent head and neck cancer. American Journal of
Surgery 150(4): 485-487, 1985.
4. Jacobs C, Lyman G, Velez-Garcia 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. Journal of
Clinical Oncology 10(2): 257-263, 1992.
5. Lavey RS, Calcaterra TC.: Partial laryngectomy for glottic cancer after
high-dose radiotherapy. American Journal of Surgery 162(4): 341-344,
1991.
6. Wang CC, McIntyre J: Re-irradiation of laryngeal carcinoma--techniques
and results. International Journal of Radiation Oncology, Biology,
Physics 26(5): 783-785, 1993.
7. Al-Sarraf M: Head and neck cancer: chemotherapy concepts. Seminars in
Oncology 15(1): 70-85, 1988.
Date Last Modified: 07/2002
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