CancerMail from the National Cancer Institute ****************************************************************************** * This information is intended mainly for use by doctors and other health * * care professionals. If you have questions about this topic, you can ask * * your doctor, or call the Cancer Information Service at 1-800-4-CANCER * * (1-800-422-6237). * ****************************************************************************** Information from PDQ -- for Health Professionals Laryngeal cancer 208/01519 ** GENERAL INFORMATION ** The larynx is divided into 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 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%-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%-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 2-3 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 three 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 2-5 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 -- Treatment options: Standard: 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 -- Treatment options: Standard: 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 -- Treatment options: Standard: 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, Parsons JT, Million RR, et al.: T1-T2 squamous cell carcinoma of the glottic larynx treated with radiation therapy: relationship of dose-fractionation factors to local control and complications. International Journal of Radiation Oncology, Biology, Physics 15(6): 1267-1273, 1988. 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 -- Treatment options:[1,2] Standard: 1. External-beam radiation therapy alone for the smaller lesions. 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. 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 -- Treatment options:[1,2,6] Standard: 1. Radiation therapy.[7,8] 2. Partial or hemilaryngectomy or total laryngectomy, depending on anatomic considerations. Under certain circumstances, laser microsurgery may be appropriate.[9] 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 -- Treatment options:[1,2] Standard: 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 in whom follow-up is likely to be difficult. 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, Parsons JT, Million RR, et al.: T1-T2 squamous cell carcinoma of the glottic larynx treated with radiation therapy: relationship of dose-fractionation factors to local control and complications. International Journal of Radiation Oncology, Biology, Physics 15(6): 1267-1273, 1988. 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 -- Treatment options:[1,2] Standard: 1. Surgery with or without postoperative radiation therapy.[3-6] 2. Definitive radiation therapy with surgery for salvage of radiation failures. Under clinical evaluation: 1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[7,8] 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.[9-13] 3. Clinical trials exploring chemotherapy, radiosensitizers, or particle- beam radiation therapy.[14-17] 4. Isotretinoin (13-cis-retinoic acid) daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[18] -- Glottis -- Treatment options:[1,2,19] Standard: 1. Surgery with or without postoperative radiation therapy.[3-6] 2. Definitive radiation therapy with surgery for salvage of radiation failures.[20] Under clinical evaluation: 1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[7,8] 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.[9-13] 3. Clinical trials exploring chemotherapy, radiosensitizers, or particle beam radiation therapy.[14,15,17] 4. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[18] -- Subglottis -- Treatment options:[1,2] Standard: 1. Laryngectomy plus isolated thyroidectomy and tracheoesophageal node dissection usually followed by postoperative radiation therapy.[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. Under clinical evaluation: 1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[7,8] 2. Clinical trials exploring chemotherapy, radiosensitizers, or particle- beam radiation therapy.[14,15,17] 3. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[18] 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. Wang CC, Ed.: Radiation Therapy for Head and Neck Neoplasms: Indications, Techniques and Results. Littleton, MA: John Wright-PSG, Inc., 2nd ed., 1990. 8. 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. 9. Wolf GT, Fisher SG, Hong WK, et al.: Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. New England Journal of Medicine 324(24): 1685-1690, 1991. 10. 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. 11. 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. 12. 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. 13. 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. 14. 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. 15. 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. 16. 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. 17. 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. 18. 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. 19. Mittal BB, Marks JE, Ogura JH: Transglottic carcinoma. Cancer 53(1): 151-161, 1984. 20. 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 -- Treatment options:[1-3] Standard: 1. Total laryngectomy with postoperative radiation therapy.[4-7] Under clinical evaluation: 1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[2,8] 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.[9-13] 3. Clinical trials exploring chemotherapy, radiosensitizers, or particle- beam radiation therapy.[14-17] 4. Isotretinoin (13-cis-retinoic acid) daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[18] -- Glottis -- Treatment options:[1-3,19] Standard: 1. Total laryngectomy with postoperative radiation therapy.[4] Under clinical evaluation: 1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[2,8] 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.[9-13] 3. Clinical trials exploring chemotherapy, radiosensitizers, or particle- beam radiation therapy.[14,15,17] 4. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[18] -- Subglottis -- Treatment options:[1-3] Standard: 1. Laryngectomy plus total thyroidectomy and bilateral tracheoesophageal node dissection usually followed by postoperative radiation therapy.[4] 2. Treatment by radiation therapy alone is indicated for patients who are not candidates for surgery. Under clinical evaluation: 1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[2,8] 2. Simultaneous chemotherapy and hyperfractionated radiation therapy.[20] 3. Clinical trials exploring chemotherapy, radiosensitizers, or particle beam radiation therapy.[14,15,17] 4. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[18] 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. 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. 9. Wolf GT, Fisher SG, Hong WK, et al.: Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. New England Journal of Medicine 324(24): 1685-1690, 1991. 10. 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. 11. 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. 12. 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. 13. 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. 14. 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. 15. 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. 16. 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. 17. 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. 18. 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. 19. Mittal BB, Marks JE, Ogura JH: Transglottic carcinoma. Cancer 53(1): 151-161, 1984. 20. 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 options: Treatment of recurrent supraglottic, glottic, and subglottic cancer includes further surgery or clinical trials.[1-4] Standard: 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. 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: 02/1999