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Anatomy

The larynx is divided into the supraglottic, glottic, and subglottic regions. The supraglottic larynx consists of the epiglottis, the false vocal cords, the ventricles, and the aryepiglottic folds, including the arytenoids. The glottis includes the true vocal cords and the anterior commissure. The subglottis is located below the vocal cords (Fig. 42-1, Fig. 42-2A, and Fig. 42-2B). [ref: 12]













The lateral line of demarcation between the glottis and supraglottic larynx is considered clinically as the apex of the ventricle. The demarcation between the glottis and subglottis is ill defined, but the subglottis is considered to begin 5 mm below the free margin of the vocal cord and to end at the inferior border of the cricoid cartilage and the beginning of the trachea.

The vocal cords vary from 3 to 5 mm in thickness. Technically, the vocal cords terminate posteriorly with their attachment to the vocal process. The mucosa between the arytenoids is called the posterior commissure.

The outside shell of the larynx is formed by the hyoid bone, thyroid cartilage, and cricoid cartilage; the cricoid cartilage is the only complete ring. The more mobile interior framework is composed of the heart-shaped epiglottis and the arytenoid, corniculate, and cuneiform cartilages. The corniculate and cuneiform cartilages produce small, rounded bulges at the posterior end of each aryepiglottic fold.

The thyroid and the cricoid cartilages and a portion of the arytenoid cartilage are hyaline cartilage and may partially ossify with age, particularly in men. The epiglottis is elastic cartilage; ossification does not occur, and even focal calcification is rare. [ref: 39]

The external laryngeal framework is linked together by the thyrohyoid, the cricothyroid, and the cricotracheal ligaments or membranes (Fig. 42-3 and Fig. 42-4). [ref: 12]









The epiglottis is joined superiorly to the hyoid bone by the hyoepiglottic ligament. The epiglottis is joined to the thyroid cartilage by the thyroepiglottic ligament at a point just below the thyroid notch and above the anterior commissure. The arrangement of the ligaments that connect the cricoid and arytenoid cartilages and form the vocal ligaments, which are part of the true vocal cords, is shown in Fig. 42-2B. The conus elasticus (cricovocal ligament) is the lower portion of the elastic membrane that connects the inferior framework. It connects the upper surface of the cricoid, the vocal process of the arytenoid, and the lower thyroid cartilage; its free border is thickened into the vocal ligament.

The vocal ligaments and muscles attach to the vocal process of the arytenoid posteriorly and the thyroid cartilage anteriorly. The intrinsic muscles of the larynx, which primarily control the movement of the cords, are presented in Fig. 42-2A, Fig. 42-2B, and Fig. 42-3. The extrinsic muscles are concerned primarily with swallowing. The cricothyroid muscle produces tension and elongation of the vocal cords and is innervated by the superior laryngeal nerve (Fig. 42-4).

The preepiglottic and paraglottic fat spaces are, for practical purposes, one continuous space lying between the external framework of the thyroid cartilage and hyoid bone and the inner framework of the epiglottis and intrinsic muscles. Lam and Wong [ref: 33] showed that there are thin membranous septae between the paraglottic and preepiglottic space that are capable of holding tumor in check to a limited degree. The space is traversed by blood and lymphatic vessels and nerves. Because few capillary lymphatics arise in this area, invasion of the fat space should only indirectly be associated with lymph node metastases. The fat space is limited by the conus elasticus inferiorly; the thyroid ala, thyrohyoid membrane, and the hyoid bone anterolaterally; the hyoepiglottic ligament superiorly; and the fascia of the intrinsic muscles on the medial side. Posteriorly, it is adjacent to the anterior wall of the pyriform sinus.

The laryngeal surface of the epiglottis and the free margin of the vocal cords are squamous epithelium, and the remainder is usually pseudostratified ciliated columnar epithelium. Beneath the epithelium of the free edge of the vocal cord is the lamina propria, which can be divided into three layers. There is no true submucosal layer along the free margin of the vocal fold. [ref: 28]

The laryngeal arteries are branches of the superior and inferior thyroid arteries.

The intrinsic muscles of the larynx are innervated by the recurrent laryngeal nerve. The cricothyroid muscle, an intrinsic muscle responsible for tensing the vocal cords, is supplied by a branch of the superior laryngeal nerve; isolated damage to this nerve causes a bowing of the true vocal cord, which continues to be mobile, but the voice may become hoarse.

The supraglottic structures have a rich capillary lymphatic plexus; the trunks pass through the preepiglottic space and the thyrohyoid membrane and terminate mainly in the subdigastric lymph nodes; a few drain to the middle internal jugular chain lymph nodes.

There are essentially no capillary lymphatics of the true vocal cords; as a result, lymphatic spread from glottic cancer occurs only if tumor extends to supraglottic or subglottic areas.

The subglottic area has relatively few capillary lymphatics. The lymphatic trunks pass through the cricothyroid membrane to the pretracheal (Delphian) lymph nodes in the region of the thyroid isthmus. The subglottic area also drains posteriorly through the cricotracheal membrane, with some trunks going to the paratracheal lymph nodes and others continuing to the inferior jugular chain.

Epidemiology and Risk Factors

Cancer of the larynx represents about 2% of the total cancer risk and is the most common head and neck cancer (skin excluded). In 1997 in the United States, there were approximately 10,900 new cases of cancer of the larynx (8900 men and 2000 women) and about 4230 deaths from laryngeal cancer. [ref: 96] At diagnosis, about 62% of the cases remain localized, 26% have regional spread, and 8% have distant metastases. [ref: 80] The ratio of glottic to supraglottic carcinoma is approximately 3:1.

Cancer of the larynx is strongly related to cigarette smoking. The risk of tobacco-related cancers of the upper alimentary and respiratory tracts declines among ex-smokers after 5 years and is said to approach the risk of nonsmokers after 10 years of abstention. [ref: 98] The role of alcohol in provoking laryngeal cancer remains unclear. [ref: 92] Some evidence exists that heavy marijuana smoking may be associated with laryngeal cancer in young patients.

Patterns of Spread

Local Spread Although supraglottic and glottic lesions tend to remain confined to their original compartments, there is no anatomic barrier to growth from one area to the next. Glottic lesions tend to be slow growing, but after they increase in size, they quickly extend to the supraglottic and subglottic areas. Supraglottic lesions do not often start near the vocal cords. Involvement of the cords on their external epithelial surface is a late phenomenon, but submucosal extension by way of the paraglottic area occurs earlier.

The fat space is an important avenue of submucosal tumor spread for infrahyoid epiglottis, false cord, and true vocal cord lesions. As the false cord and the true vocal cord lesions penetrate anteriorly and laterally, they quickly encounter the tough perichondrium of the thyroid cartilage and may eventually be shunted by the conus elasticus (lateral cricothyroid membrane) out of the larynx via the cricothyroid space. Thyroid cartilage invasion usually occurs in the ossified section of the cartilage, commonly in the region of the anterior commissure tendon or the junction of the anterior one fourth and the posterior three fourths of the thyroid lamina. [ref: 4]

Fixation of the vocal cord from laryngeal cancer is usually caused by invasion or destruction of the vocal cord muscle, invasion of the cricoarytenoid muscle or joint, or, rarely, invasion of the recurrent laryngeal nerve.

Perineural spread is uncommon in laryngeal malignancies.

Supraglottic Larynx Suprahyoid Epiglottis A lesion of the suprahyoid epiglottis may produce a huge exophytic mass with little tendency to destroy cartilage or spread to adjacent structures. Other lesions may infiltrate the tip and destroy cartilage. The destructive lesions tend to invade the vallecula and preepiglottic space, the lateral pharyngeal walls, and the remainder of the supraglottic larynx.

Infrahyoid Epiglottis Lesions of the infrahyoid epiglottis tend to produce irregular tumor nodules and simultaneously invade the porous epiglottic cartilage and thyroepiglottic ligament into the preepiglottic fat space and extend toward the vallecula and base of the tongue. The thick hyoepiglottic ligament is an effective tumor barrier. However, the tumor may present in the vallecula and base of tongue without involving the suprahyoid epiglottis.

Lesions of the infrahyoid epiglottis grow circumferentially to involve the false cords, aryepiglottic folds, medial wall of the pyriform sinus, and the pharyngoepiglottic fold. Invasion of the anterior commissure and cords and anterior subglottic extension usually occur only in advanced lesions. Infrahyoid epiglottic lesions that extend onto or below the vocal cords are at a high risk for thyroid cartilage invasion, even if the cords are mobile. [ref: 73]

False Cord Early false cord carcinomas, which are usually submucosal with little exophytic component, are difficult to delineate accurately. They involve the paraglottic fat space early in their development and may spread a considerable distance beneath the mucosa without producing physical signs. These carcinomas extend to the perichondrium of the thyroid cartilage quite early, but cartilage invasion is a late phenomenon. Extension to the lower portion of the infrahyoid epiglottis and invasion of the preepiglottic space are common. Submucosal extension involves the true vocal cord, which may appear normal. Vocal cord invasion is often associated with thyroid cartilage invasion. Submucosal extension to the medial wall of the pyriform sinus occurs early.

Aryepiglottic Fold/Arytenoid Early lesions of the aryepiglottic fold/arytenoid are usually exophytic. It may be difficult to decide whether the lesion started on the medial wall of the pyriform sinus or on the aryepiglottic fold. As the lesions enlarge, they extend to adjacent sites and eventually cause fixation of the larynx, which is usually a result of involvement of the cricoarytenoid muscle of joint or, rarely, invasion of the recurrent laryngeal nerve. Computed tomography (CT) may distinguish the cause of fixation. Advanced lesions invade the thyroid, epiglottic, and cricoid cartilages and eventually invade the pyriform sinus and postcricoid area.

Glottic Larynx Most lesions of the true vocal cord begin on the free margin and upper surface of the cord. When diagnosed, about two thirds are confined to the cords, usually one cord. The anterior portion of the cord is the most common site. Anterior commissure involvement, which is common, is said to occur when no tumor-free cord can be seen anteriorly; if the lesion crosses to the opposite cord, anterior commissure invasion is certain. Small lesions isolated to the anterior commissure account for only 1% to 2% of cases. Extension to the posterior commissure area is uncommon, occurring only in advanced lesions.

Tumors at the anterior commissure may extend anteriorly via the anterior commissure tendon (Broyles' ligament), [ref: 10] into the thyroid cartilage. Kirchner, [ref: 32] using whole organ sections, showed that such extension is unusual unless the tumor extends off the vocal cord onto the base of the infrahyoid epiglottis and suggested that the tendon serves as more of a barrier than an avenue of tumor spread. Early subglottic extension is also associated with involvement of the anterior commissure, and tumor may grow through the cricothyroid membrane.

Lesions that arise on the posterior half of the vocal cord tend to extend along the submucosa toward the medial side of the vocal process and invade the cricoarytenoid joint and posterior commissure; this spread is difficult to appreciate by clinical examination.

Subglottic extension may occur by simple mucosal surface growth, but it more commonly occurs by submucosal penetration beneath the conus elasticus. One centimeter of subglottic extension anteriorly or 4 to 5 mm of subglottic extension posteriorly brings the border of the tumor to the upper margin of the cricoid exceeding the anatomic limits for conventional hemilaryngectomy. Lesions may spread beneath the epithelium along the length of the vocal cord within Reinke's space. [ref: 62]

As vocal cord lesions enlarge, they extend to the false cord, vocal process of the arytenoid, and subglottic region. Infiltrative lesions invade the vocal ligament and muscle and eventually reach the paraglottic space and the perichondrium of the thyroid cartilage. Advanced glottic lesions eventually penetrate through the thyroid cartilage or via the cricothyroid space to enter the neck, where they may invade the thyroid gland. Lesions involving the anterior commissure often exit the larynx via the cricothyroid space after they extend subglottically. [ref: 62]

A fixed cord that is associated with a lesion having less than 1 cm of subglottic extension and no false cord involvement does not ordinarily indicate invasion of the thyroid cartilage. [ref: 32] If the false cord is also involved, cartilage invasion is likely.

Subglottic Larynx Subglottic cancers are rare. Most involve the inferior surface of the vocal cords by the time they are diagnosed, so it is difficult to know whether the tumor started on the undersurface of the vocal cord or in the true subglottic larynx. Because early diagnosis is uncommon, most lesions are bilateral or circumferential at discovery. They involve the cricoid cartilages early because there is no intervening muscle layer. Partial or complete fixation of one or both cords is common; misdiagnosis or diagnostic delay is frequent.

Lymphatic Spread The location and stage of neck nodes detected on admission for previously untreated patients with squamous cell carcinoma of the supraglottic larynx are given in Fig. 42-5. [ref: 38]




The disease spreads mainly to the subdigastric nodes. The submandibular area is rarely involved, and there is only a small risk of spinal accessory lymph node involvement. The incidence of clinically positive nodes is 55% at the time of diagnosis; 16% are bilateral. [ref: 38] Elective neck dissection shows pathologically positive nodes in 16% of cases; observation of initially node-negative necks eventually identifies the appearance of positive nodes in 33% of cases. [ref: 17,58] Spread to the pyriform sinus, vallecula, and base of the tongue increases the risk of lymph node metastases. The risk of late-appearing contralateral lymph node metastasis is 37% if the ipsilateral neck is pathologically positive, but the risk is unrelated to whether the nodes in the ipsilateral neck were palpable before neck dissection.

In carcinoma of the vocal cord, the incidence of clinically positive lymph nodes at diagnosis approaches zero for T1 lesions and 1.7% for T2 lesions. [ref: 48] The incidence of neck metastases increases to 20% to 30% for T3 and T4 lesions. Supraglottic spread is associated with metastasis to the jugulodigastric nodes. Anterior commissure and anterior subglottic invasion are associated with involvement of the mid-line pretracheal lymph node (Delphian node).

Lederman [ref: 34] reported a 10% incidence of positive lymph nodes in 73 patients with subglottic carcinoma.

Clinical Presentation

Carcinoma arising on the true vocal cords produces hoarseness at a very early stage. Sore throat, ear pain, pain localized to the thyroid cartilage, and airway obstruction are features of advanced lesions.

Hoarseness is not a prominent symptom of cancer of the supraglottic larynx until the lesion becomes quite extensive. Pain on swallowing, usually mild, is the most frequent initial symptom, often described as a sore throat. Some patients report a sensation of a "lump in the throat." Pain is referred to the ear by way of the vagus nerve and auricular nerve of Arnold. A mass in the neck may be the first sign of a supraglottic cancer. Late symptoms include weight loss, foul breath, dysphagia, and aspiration.

Diagnostic Workup

Physical Examination Rigid and flexible fiberoptic illuminated endoscopes are now used routinely as a complement to the laryngeal mirror examination. The Hopkins rod with a right-angled lens gives excellent visualization of the infrahyoid epiglottis and anterior commissure, areas that may be difficult or impossible to see with a laryngeal mirror. The mirror gives a larger image of the larynx or hypopharynx than that obtained by direct laryngoscopy or fiberoptic endoscopy. The mirror often provides the best view of the posterior pharyngeal wall. The flexible fiberoptic laryngoscope is inserted through the nose and is useful in more difficult cases.

Determination of the mobility of the vocal cords frequently requires multiple examinations because the subtle distinctions between mobile, partially fixed, and fixed cords are often challenging, apparently changing from examination to examination. A cord that appeared mobile to the surgeon before direct laryngoscopy may exhibit impaired motion or even fixation after biopsy.

Ulceration of the infrahyoid epiglottis or fullness of the vallecula is an indirect sign of preepiglottic space invasion. Palpation of diffuse, firm fullness above the thyroid notch with widening of the space between the hyoid and the thyroid cartilages signifies invasion of the preepiglottic space. Lateral soft tissue roentgenograms of the neck may show irregular air cavities inferior to the vallecula in patients with lesions of the suprahyoid epiglottis invading into the preepiglottic space by way of the vallecula. The preepiglottic fat space is a low-density area on the CT scan, and changes resulting from tumor invasion are easily seen.

Postcricoid extension may be suspected when the laryngeal click disappears on physical examination. Postcricoid tumor may cause the thyroid cartilage to protrude anteriorly, producing a fullness of the neck.

Invasion of the thyroid cartilage remains a difficult clinical diagnosis. Localized pain or tenderness to palpation or a small bulge over one ala of the thyroid cartilage is suggestive.

Radiographic Studies CT scan with contrast enhancement is the method of choice for studying the larynx (Fig. 42-6).



The CT scan should be performed before biopsy so that abnormalities that may be caused by the biopsy are not confused with tumor. CT is preferred to magnetic resonance imaging (MRI) because the longer scanning time for MRI results in motion artifact. [ref: 54] CT slices 3-mm thick are obtained at 3-mm intervals through the larynx and at 5-mm intervals for the remainder of the study. The gantry is angled so that the scan slices are parallel to the plane of the true vocal cords. It is also necessary to obtain a CT scan of the entire neck to detect positive, nonpalpable lymph nodes. Positive retropharyngeal nodes may be present at diagnosis in patients with laryngeal cancer who have advanced neck disease. [ref: 41] Retropharyngeal adenopathy is often not apparent on physical examination but is usually apparent on CT scan.

Contrast enhancement helps to outline the blood vessels and thyroid gland. Tumor is often enhanced, probably because of reactive inflammatory changes. In addition to CT, MRI may be obtained to define subtle exolaryngeal spread or early cartilage destruction. The value of MRI for detecting early cartilage destruction is open to speculation. Sagittal MRI may be useful in detecting early invasion of the base of the tongue.

Vocal Cord Carcinoma The CT scan does not show minimal mucosal lesions and is generally not indicated for well-defined, easily visualized T1 or early T2 vocal cord carcinomas. CT is excellent for determining subglottic extension and is often used in selected T1 and most T2 lesions for this reason alone. CT scanning is useful in the diagnosis of moderately advanced and advanced lesions; it is excellent for demonstrating extension outside the larynx into the soft tissues of the neck and has potential for determining thyroid or cricoid cartilage invasion, which tends to occur at the edges of the cartilage rather than on the faces. Early cartilage involvement is difficult to detect with axial scans, but it may be demonstrated by coronal or sagittal scanning techniques. If the low-density plane of the paraglottic space is intact, cartilage is probably not invaded by tumor.

Archer and associates [ref: 5] correlated CT findings with the incidence of cartilage or bone invasion on whole-organ sections. For 12 of 14 patients with pathologic evidence of cartilage invasion, the average diameter of the tumor in two dimensions was more than 16 mm, and the lesion was located below the top of the arytenoid. Lesions in which the maximum diameter lay above the top of the arytenoid had a low incidence of cartilage invasion. [ref: 5,53]

Supraglottic Carcinoma The CT scan provides an excellent means for viewing the preepiglottic and paraglottic fat spaces. Soft tissue extension into the neck or base of the tongue also can be seen. The CT scan is also useful for determining extension to the subglottic areas. [ref: 39]

Diagnostic procedures for laryngeal cancer at the University of Florida are summarized in Table 42-1. A CT scan is not usually performed for T1 or early T2 vocal cord cancers, but it is almost always performed for the remainder of laryngeal lesions. Direct laryngoscopy and biopsy with frozen section are usually performed with the patient under general anesthesia. The ventricles, subglottic area, apex of the pyriform sinus, and postcricoid area must be carefully examined because these areas are not consistently seen by indirect examinations. Fiberoptic telescopes (0 and 30 degrees) are introduced through the laryngoscope for inspection of these areas. A generous biopsy specimen is taken from the obvious lesion; additional biopsy specimens may be obtained from suspicious areas and from areas grossly involved. The mucosa of the margin of the cord may be stripped to provide adequate tissue if the lesion is distributed superficially along the cord and is not obviously a carcinoma.

Staging

The 1992 American Joint Committee on Cancer (AJCC) staging system for laryngeal primary cancer is listed in Table 42-2. [ref: 2] T2 glottic cancers are stratified into those with normal (T2A) and impaired (T2B) vocal cord mobility. For lesions arising in the supraglottis, the sites of origin include false cords, aryepiglottic folds, suprahyoid epiglottis, infrahyoid epiglottis, pharyngoepiglottic folds, and arytenoids. Only in the early T stages can one identify the specific site of origin with certainty. As the lesion enlarges, the site of origin is an educated guess based on the location of the greatest bulk of tumor.

Pathologic Classification

Nearly all malignant tumors of the larynx arise from the surface epithelium and therefore are squamous cell carcinoma or one of its variants.

Carcinoma in situ occurs frequently on the vocal cords. Differentiating among dysplasia, carcinoma in situ, squamous cell carcinoma with microinvasion, and true invasive carcinoma is a problem that the pathologist and the clinician frequently confront.

Most vocal cord carcinomas are well differentiated or moderately well differentiated. In a few cases, an apparent carcinoma and sarcoma occur together, but most of these are actually a spindle-cell carcinoma or so-called pseudosarcoma (i.e., squamous cell carcinoma with a spindle-cell stromal reaction).

Verrucous carcinoma occurs in 1% to 2% of patients with carcinoma of the vocal cord. The histologic diagnosis is difficult and must correlate with the gross appearance of the lesion.

Small cell neuroendocrine carcinoma is rarely diagnosed in the supraglottic larynx, but it should be recognized because of its biologic potential for rapid growth, early dissemination, and responsiveness to chemotherapy.

Minor salivary gland tumors arise from the mucous glands in the supraglottic and subglottic larynx, but they are rare. [ref: 22]

Even rarer are chemodectoma, carcinoid, soft tissue sarcoma, malignant lymphoma, or plasmacytoma. Benign chondromas and osteochondromas are reported, but their malignant counterparts are rare.

Prognostic Factors

The extent of the primary lesion and neck disease are the major determinants of prognosis. The likelihood of local control is determined primarily by T stage; there are conflicting data pertaining to a possible inverse relationship between N stage and local control. The likelihood of locoregional control is impacted primarily by the overall AJCC stage, which accounts for both T stage and N stage. AJCC stage and N stage are the major determinants of cause-specific survival. Additionally, within each N stage, patients with positive nodes in the low neck below the level of the thyroid notch tend to have a lower cause-specific survival rate compared with those with disease confined to the upper neck. In general, women tend to have a better prognosis than men.

Treatment Selection and Technique

Vocal Cord Carcinoma Selection of Treatment Modality In treating vocal cord carcinoma, the goal is cure with the best functional result and the least risk of a serious complication. Patients may be considered to be in an early group if the chance of cure with larynx preservation is high, a moderately advanced group if the likelihood of local control is 60% to 70% but the chance of cure is still good, and an advanced group if the chance of cure is moderate and the likelihood of laryngeal preservation is relatively low. The early group may be treated initially by radiation therapy or, in selected cases, by partial laryngectomy. The moderately advanced group may be treated with either irradiation with laryngectomy reserved for relapse or by total laryngectomy with or without adjuvant postoperative irradiation. The obvious advantage of the former strategy, which we use at the University of Florida, is that there is a fairly good chance that the larynx will be preserved. The advanced group is usually treated with total laryngectomy and neck dissection, with or without adjuvant radiation therapy. Recent data suggest that if patients whose tumors show a partial or complete response to two to three cycles of neoadjuvant chemotherapy are then given high-dose radiation therapy, the cure rates are comparable with those obtained with initial total laryngectomy. [ref: 74,88]

Carcinoma In Situ Lesions diagnosed as carcinoma in situ may sometimes be controlled by stripping the cord. However, it is difficult to exclude the possibility of microinvasion on these specimens. Recurrence is frequent, and the cord may become thickened and the voice hoarse with repeated stripping.

We now recommend early radiation therapy for carcinoma in situ, realizing that most patients with this diagnosis eventually receive this treatment and that earlier use of irradiation means a better chance of preserving a good voice.

Many patients with a diagnosis of carcinoma in situ have obvious lesions that probably contain invasive carcinoma. We have often proceeded with radiation therapy rather than put the patient through a repeated biopsy procedure.

Early Vocal Cord Carcinoma In most centers, irradiation is the initial treatment prescribed for T1 and T2 lesions, with surgery reserved for salvage after radiation therapy failure. [ref: 14,48,52] Although hemilaryngectomy or cordectomy produces comparable cure rates for selected T1 and T2 vocal cord lesions, irradiation is generally preferred. [ref: 63] Transoral laser excision also may provide high cure rates for select patients with small, well-defined lesions limited to the mid-third of one true cord. [ref: 40,84,90] The major advantage of irradiation compared with hemilaryngectomy or cordectomy is better quality of the voice. Hemilaryngectomy finds its major use as salvage surgery in suitable cases after irradiation failure. [ref: 47,48] Even if the patient has a local recurrence after salvage hemilaryngectomy, there is a third chance with total laryngectomy, which may still be successful. [ref: 8]

Verrucous lesions have the reputation of being unresponsive to radiation therapy and, in some instances, converting into invasive, often anaplastic, metastasizing lesions. Hemilaryngectomy is recommended for early verrucous carcinoma of the glottis, but irradiation is recommended if the alternative is total laryngectomy. [ref: 11] We have observed typical verrucous lesions that have disappeared with radiation therapy and not recurred. O'Sullivan and associates [ref: 64] also have made this observation. Additionally, a variety of tumors that recur after unsuccessful treatment (with surgery, radiation therapy, and/or chemotherapy) are more likely to exhibit more aggressive behavior.

Moderately Advanced Vocal Cord Cancer Fixed-cord lesions (T3) may be subdivided into relatively favorable or unfavorable lesions. Patients with unfavorable lesions usually have extensive bilateral disease with a compromised airway and are considered to be in the advanced group. Patients with favorable T3 lesions have disease confined mostly to one side of the larynx, have a good airway, and are reliable for follow-up. Some degree of supraglottic and subglottic extension usually exists. The extent of disease and tumor volume, in particular, are related to the likelihood of control after radiation therapy. [ref: 37,51]

The patient with a favorable lesion is advised of the alternatives of irradiation with surgical salvage or immediate total laryngectomy. [ref: 69] The patient must be willing to return for follow-up examinations every 4 to 6 weeks for the first year, every 6 to 8 weeks for the second year, every 3 months for the third year, every 6 months for the fourth and fifth years, and annually thereafter. The patient must understand that total laryngectomy may be recommended purely on clinical grounds without biopsy-proven recurrence and that the risk of laryngeal osteochondronecrosis is about 5%.

Evaluation of cord mobility after 50.4 Gy or at the end of radiation therapy has not been helpful in predicting local control. [ref: 51] Some patients in whom the vocal cord remained fixed have had local tumor control of the disease for 2 years or longer after radiation therapy.

The major difficulty in using irradiation for the more advanced lesions is differentiating radiation edema and local recurrence during follow-up examinations. [ref: 71] Progressive laryngeal edema, persistent throat pain, or fixation of a previously mobile vocal cord frequently signify recurrent disease in the larynx, although a few patients with these findings remain disease-free with long-term follow-up.

Extended hemilaryngectomy has been used by a few surgeons in the treatment of well-lateralized fixed-cord lesions. A permanent tracheostomy is usually required because a portion of the cricoid is resected, but a useful voice may be retained. [ref: 72]

Advanced Vocal Cord Carcinoma Advanced lesions usually show extensive subglottic and supraglottic extension, bilateral glottic involvement, and invasion of the thyroid, cricoid, or arytenoid cartilage, or frequently all three. [ref: 4,5] The airway is compromised, necessitating a tracheostomy at the time of direct laryngoscopy in approximately 30% of patients. Clinically positive lymph nodes are found in about 25% to 30% of patients.

The mainstay of treatment is total laryngectomy, with or without adjuvant radiation therapy. The most frequent sites of local failure after total laryngectomy are around the tracheal stoma, in the base of tongue, and in the neck lymph nodes or soft tissues of the neck. If the neck is clinically negative before surgery and if postoperative irradiation is planned, neck dissection may be withheld, and radiation therapy may be used to treat both sides of the neck. However, in practice, some surgeons perform an elective neck dissection in conjunction with a total laryngectomy for T3N0 or T4N0 laryngeal cancer, even if postoperative irradiation is planned. If the lymph nodes are clinically positive, a neck dissection is performed at the time of laryngectomy.

The indications for postoperative radiation therapy include close or positive margins, significant subglottic extension (>/= 1 cm), cartilage invasion, perineural invasion, extension of the primary tumor into the soft tissues of the neck, multiple positive neck nodes, extracapsular extension, and control of subclinical disease in the opposite neck. [ref: 1,29,45] Preoperative irradiation is indicated for patients who have fixed neck nodes, have had an emergency tracheotomy through tumor, or have direct extension of tumor involving the skin.

Definitive irradiation is prescribed for the patient who refuses total laryngectomy or is medically unsuitable for major surgery.

As previously stated, there is evidence that two to three cycles of neoadjuvant chemotherapy followed by radiation therapy in patients obtaining at least a partial response may provide a moderate likelihood of larynx preservation without compromising cure. [ref: 74,85,88]

Surgical Treatment Thyrotomy with cordectomy is an excision of the vocal cord. Its use is usually confined to small lesions of the middle third of the cord. After cordectomy, a pseudocord is formed, and the patient has a useful, if somewhat harsh voice. A portion of the adjacent thyroid cartilage may be removed with the cord.

Vertical partial laryngectomy (i.e., hemilaryngectomy) allows removal of limited cord lesions with preservation of voice. One entire cord and as much as a third of the opposite cord is the maximum cordal involvement suitable for surgery in men; women have a smaller larynx, and usually only one vocal cord may be removed without compromising the airway. Partial fixation of one cord is not a contraindication to hemilaryngectomy, but only a few surgeons have attempted hemilaryngectomy for selected fixed-cord lesions. The maximum subglottic extension suitable for hemilaryngectomy is 8 to 9 mm anteriorly and 5 mm posteriorly; this limit is necessary to preserve the integrity of the cricoid. Tumor extension to the epiglottis, false cord, or both arytenoids is a contraindication to hemilaryngectomy.

Total laryngectomy with or without neck dissection is the operation of choice for advanced lesions and as a salvage procedure for radiation therapy failures in lesions that are not suited for conservation surgery. The entire larynx is removed, and the pharynx is reconstituted. A permanent tracheostomy is required. Speech may be reconstituted with a prosthesis, such as the Singer-Blom prosthesis or the Panje button, or with an electrolarynx.

Radiation Therapy Technique Irradiation for T1 or T2 vocal cord cancer is delivered by small portals covering only the primary lesion. The cervical lymph node chain is not electively treated. For T1 lesions, radiation therapy portals extend from the thyroid notch superiorly to the inferior border of the cricoid and fall off anteriorly. The posterior border depends on the posterior extension of the tumor. [ref: 54] For T2 tumors, the field is extended depending on the anatomic distribution of the tumor. The field size ranges from 4 cm x 4 cm to 5 cm x 5 cm (plus an additional 1.0 cm of "flash" anteriorly) and is occasionally 6 x 6 cm for a large T2 lesion. Portals larger than this increase the risk of edema without improving the cure rate.

A commonly used dose-fractionation schedule at many institutions is 66 Gy for T1 lesions and 70 Gy for T2 cancers given in 2-Gy fractions. Evidence suggests that increasing the dose per fraction may improve the likelihood of local control. [ref: 3,18,26,27,31,77,97] Ample data suggest that 1.8 Gy once daily results in significantly lower local control rates compared with 2 Gy once daily. [ref: 31] Patients with
T1 or T2 vocal cord cancer treated with once-a-day fractionation at the University of Florida are irradiated with 2.25-Gy fractions; the dose-fractionation schemes used are shown in Table 42-3. [ref: 55,65] Since December 1986, twice-a-day fractionation using 1.2-Gy fractions to deliver a total dose of 74.4 Gy has been used to treat most T2 glottic cancers.

At the University of Florida, patients are treated in the lateral decubitus ("chicken-wing") position with the arm flexed at the elbow and tucked under the thorax (Fig. 42-7A and Fig. 42-7B). [ref: 47]







The field is set up by the physician at the treatment machine each day according to palpable anatomic landmarks, and new lines are drawn on the patient each day. This allows the treatment volume to be kept at a minimum and reduces the risk of geographic miss. The lateral decubitus position is chosen because identification of the posterior border of the thyroid cartilage is easier than when the patient is supine, and the maximum lateral thickness of the patient is reduced. The technique requires no simulation, and portal films are unnecessary. [ref: 67] Freehand "stacked blocks" are used for secondary beam collimation; patients receiving an anterior boost dose are supine (Fig. 42-7A and Fig. 42-7B). [ref: 47] A three-field technique, using **60Co, is used to deliver approximately 95% of the dose through opposed lateral wedged fields weighted to the side of the lesion; the remaining dose is delivered by an anterior field shifted 0.5 cm toward the side of the lesion (Fig. 42-8). [ref: 54]



The tumor dose is usually specified at the 95% normalized isodose line.

At many institutions, patients are treated in the supine position with 4-MV x-rays or 6-MV x-rays using equally weighted parallel opposed fields. The portals are positioned by the therapist, and the field sizes are often somewhat larger (usually 5 cm x 5 cm or 6 cm x 6 cm) than those used at our institution.

Irradiation of T3 and T4 lesions requires larger portals, which include the jugulodigastric and middle jugular lymph nodes (Fig. 42-9). [ref: 43]



The inferior jugular lymph nodes are included in a separate low-neck portal. Patients are treated with continuous-course twice-daily radiation therapy at 1.2 Gy per fraction to total doses of 74.4 to 76.8 Gy. [ref: 68,69] The portals are reduced after 45.6 Gy in 38 fractions; the reduced portals cover only the primary lesion.

The treatment technique used for postoperative irradiation after total laryngectomy is depicted in Fig. 42-10A and Fig. 42-10B. [ref: 1]







The treatment technique for preoperative irradiation is essentially the same as that used for irradiation alone.

Treatment of Recurrence Most recurrences appear within 18 months, but late recurrences may appear after 5 years. [ref: 21] The risk of metastatic disease in lymph nodes increases with local recurrence. [ref: 44]

Recurrence After Radiation Therapy With careful follow-up, recurrence is sometimes detected before the patient notices a return of hoarseness. There is often minimal lymphedema for 1 to 2 months after irradiation, which usually subsides or stabilizes. An increase in edema, particularly if associated with hoarseness or pain, suggests recurrence, even if there is no obvious tumor. Fixation of a previously mobile vocal cord usually implies local recurrence, but we have occasionally observed a patient who has experienced a fixed cord with an otherwise normal-appearing larynx and who has not shown evidence of recurrence.

It may be difficult to diagnose recurrence if the tumor is submucosal. Generous, deep biopsies are required. If recurrence is strongly suspected, laryngectomy may rarely be advised without biopsy-confirmed evidence of recurrence.

Radiation therapy failures may be salvaged by cordectomy, hemilaryngectomy, or total laryngectomy. Biller and associates [ref: 7] reported a 78% salvage rate by hemilaryngectomy for 18 selected patients in whom irradiation failed; total laryngectomy was eventually required in two patients. Only two patients died of cancer. These investigators offered guidelines for using hemilaryngectomy: contralateral vocal cord is normal, arytenoid is not involved, subglottic extension does not exceed 5 mm, and vocal cord is not fixed. In our experience, six to 10 patients irradiated for T1 or T2 vocal cord cancers were successfully salvaged by surgery after radiation therapy failed. [ref: 48]

Recurrence After Surgery The rate of salvage by irradiation for recurrences or new tumors that appear after initial treatment by hemilaryngectomy is about 50%. Lee and associates [ref: 35] reported seven successes among 12 patients; one lesion was later controlled by total laryngectomy. Total laryngectomy can be used successfully to treat hemilaryngectomy failures not suitable for radiation therapy. Irradiation rarely cures patients with recurrence in the neck or stoma after total laryngectomy.

Supraglottic Larynx Carcinoma Selection of Treatment Modality Patients with supraglottic larynx carcinoma may be considered to be in an early or favorable group suitable for radiation therapy or supraglottic laryngectomy or an unfavorable group often requiring total laryngectomy.

Early and Moderately Advanced Supraglottic Lesions Treatment of the primary lesion for the early group is by external-beam irradiation or supraglottic laryngectomy, with or without adjuvant irradiation. [ref: 16,49,61] Total laryngectomy is rarely indicated as the initial treatment for this group of patients and is reserved for treatment failures.

Radiation therapy and supraglottic laryngectomy are highly successful modes of therapy for early lesions. Approximately 50% of supraglottic laryngectomies performed at the University of Florida have been followed by postoperative irradiation because of positive margins or for neck disease.

The decision to use radiation therapy or supraglottic laryngectomy depends on several factors including the anatomic extent of the tumor, medical condition of the patient, philosophy of the attending physician(s), and the inclination of the patient and family. Overall, about 80% of patients are treated initially by irradiation. Approximately half of the patients seen in our clinic whose lesions are technically suitable for a supraglottic laryngectomy are not suitable for medical reasons (e.g., inadequate pulmonary status or other major medical problems); these patients are treated by radiation therapy.

Analysis of local control by anatomic site within the supraglottic larynx shows no obvious differences in local control by irradiation for similarly staged lesions. An exception may be T3 false vocal cord primary tumors that appear to have a lower local control rate compared with T3 lesions arising from other supraglottic sites. [ref: 46] Invasion of the preepiglottic space is not a contraindication to supraglottic laryngectomy or irradiation. Primary tumor volume based on pretreatment CT is inversely related to local tumor control after radiation therapy. [ref: 46] A large, bulky infiltrative lesion, especially one with extensive preepiglottic space invasion, is a common reason to select supraglottic laryngectomy.

The status of the neck often determines the selection of treatment of the primary lesion. Patients with clinically negative neck nodes have a high risk for occult neck disease and may be treated by radiation therapy or supraglottic laryngectomy and bilateral conservation neck dissections.

If a patient has an early-stage primary lesion but advanced neck disease (N2b or N3), combined treatment is frequently necessary to control the neck disease. [ref: 45,50] In these cases, the primary lesion is usually treated by irradiation alone, with surgery added to the treatment of the involved neck site(s). If the same patient were treated with supraglottic laryngectomy, neck dissection, and postoperative irradiation, the portals would unnecessarily cover the primary site and the neck. If the patient has early, resectable neck disease (N1 or N2a) and surgery is elected for the primary site, postoperative irradiation is added only because of unexpected findings (e.g., positive margins, multiple positive nodes, or extracapsular extension). We prefer to avoid routine high-dose preoperative or postoperative irradiation in conjunction with a supraglottic laryngectomy because the lymphedema of the remaining larynx may be considerable, although it eventually subsides. However, Lee and co-workers [ref: 36] from M.D. Anderson Cancer Center reported good results with combined supraglottic laryngectomy and postoperative irradiation for moderately advanced lesions.

Advanced Supraglottic Lesions The surgical alternative for these lesions is total laryngectomy. Selected advanced lesions, especially those that are mainly exophytic, may be treated by radiation therapy, and total laryngectomy is reserved for irradiation failures. Borderline lesions are given a trial of irradiation (45 to 50 Gy), and if the response is good, irradiation is continued for cure. If the response is unsatisfactory, radiation therapy is stopped, and total laryngectomy is performed 4 to 6 weeks later.

Lesions unsuitable for irradiation are treated by total laryngectomy. If the neck disease is resectable, surgery is the initial treatment, and postoperative irradiation is added if needed. If the neck disease is unresectable, preoperative radiation therapy is used. The indications for preoperative and postoperative irradiation have been previously outlined.

Neoadjuvant chemotherapy followed by radiation therapy for responders is a reasonable alternative for selected patients.

Surgical Treatment Supraglottic Laryngectomy Supraglottic laryngectomy is voice-sparing surgery that can be used successfully for selected lesions involving the epiglottis, a single arytenoid, the aryepiglottic fold, or the false vocal cord. Extension of the tumor to the true vocal cord, the anterior commissure, or both arytenoids; fixation of the vocal cord; or thyroid or cricoid cartilage invasion preclude supraglottic laryngectomy. The supraglottic laryngectomy may be extended to include the base of the tongue if one lingual artery is preserved.

All patients have difficulty swallowing with a tendency to aspirate immediately after surgery, but almost all learn to swallow again in a short time; motivation and the amount of tissue removed are key factors in learning to swallow again. Preoperatively, adequate pulmonary reserve is evaluated by blood gas determinations, function tests, chest roentgenography, and a work test involving walking the patient up two flights of stairs to determine tolerance to pulmonary stress. The voice quality is generally normal after supraglottic laryngectomy.

Wide-Field Total Laryngectomy Total laryngectomy is performed as previously described.

Radiation Therapy Technique The primary lesion and both sides of the neck are treated with opposed lateral portals; wedges are used to compensate for the contour of the neck. The anterior mid-line skin is shielded if possible (Fig. 42-11). [ref: 42]




Most patients treated at the University of Florida are currently irradiated at 1.2 Gy per fraction, continuous course, with a minimum 6-hour interfraction interval. The dose for T1 and T2 lesions is 74.4 Gy, and the dose for T3 lesions is 74.4 to 76.8 Gy. The total doses for patients irradiated once daily at 2 Gy per fraction is as follows: T1, 60 Gy; T2, 64 to 66 Gy; and T3-4, 70 Gy. All patients are treated with the continuous-course technique. [ref: 66] The lower neck nodes are irradiated through a separate anterior portal (Fig. 42-12). [ref: 42]




In the case of clinically positive nodes, an electron-beam portal may be used to increase the dose to the posterior cervical nodes after the fields are reduced to avoid the spinal cord at 45 Gy. [ref: 42] The addition of a neck dissection usually increases the risk of temporary lymphedema; however, neck dissection is preferable in terms of tumor control and complications to the higher doses of irradiation required to control large neck nodes. [ref: 50]

Patients experience a sore throat, loss of taste, and moderate dryness during irradiation. Edema of the arytenoids may occur and give a sensation of a lump in the throat. Tracheostomy is rarely necessary, even for bulky lesions.

Edema of the larynx may persist for several months to a year. Patients who continue to smoke heighten the side effects of dryness, dysphagia, and hoarseness.

Preoperative and Postoperative Treatment Technique If total laryngectomy is required and the lesion is resectable, postoperative radiation therapy is preferred because there is no evidence that preoperative irradiation produces any better local-regional control or survival rates than surgery and postoperative radiation therapy. Irradiation is added for close or positive margins, invasion of soft tissues of the neck, significant subglottic extension (>/= 1 cm), thyroid cartilage invasion, multiple positive nodes, and extracapsular extension. The high-risk areas are usually the base of the tongue and the neck. The stomal area is at risk mainly if there is subglottic extension; otherwise, it may be shielded.

The dose for postoperative irradiation as a function of known residual disease is as follows: negative margins, 60 Gy in 30 fractions; microscopically positive margins, 66 Gy in 33 fractions; and gross residual disease, 70 Gy in 35 fractions. All patients are treated with continuous-course, one fraction per day, 5 days per week. If the daily dose is lowered to 1.8 Gy, 5 Gy is added to the total dose in each category. The lower neck is treated with doses to 50 Gy in 25 fractions at D(max). If there is subglottic extension, the dose to the stoma is boosted with electrons (usually 10 to 14 MeV) for an additional 10 Gy in five fractions. The treatment technique is outlined in Fig. 42-10A and Fig. 42-10B. If postoperative irradiation is added after a supraglottic laryngectomy, the dose is lowered to 55 Gy given in 1.8-Gy fractions. This dose produces acceptable rates of local control and laryngeal edema. [ref: 76]

The treatment technique used for preoperative radiation therapy is essentially the same as that used for patients treated with irradiation alone, using doses of 45 to 50 Gy at 1.8 to 2.0 Gy per fraction.

Treatment of Recurrence Failures after supraglottic laryngectomy or radiation therapy can frequently be controlled by further treatment; therefore, recognition of recurrence should be vigorously pursued. [ref: 71] Salvage of patients with recurrence after combined total laryngectomy and irradiation is uncommon. Stomal recurrences are occasionally controlled by radiation therapy or surgery.

Results of Treatment

Vocal Cord Cancer Surgical Results Neel and associates [ref: 57] reported results for 182 patients with early vocal cord carcinoma who were suitable for cordectomy; 177 had lesions that were confined to one cord. The lesions were 2 to 25 mm long. The follow-up was less than 3 years in 18% of the cases. Laryngeal recurrence developed in four patients, and neck recurrence developed in three patients. Only three patients (2%) died of vocal cord cancer.

Thomas and colleagues [ref: 89] reported on 159 patients who underwent open partial laryngectomy for T1 glottic cancers at the Mayo Clinic between 1976 and 1986. Seventeen of 159 patients had in situ lesions; the remainder were invasive. Local recurrence developed in 11 patients (7%), and nine eventually required laryngectomy. Ten patients experienced disease recurrence in the neck, and distant metastases were noted in 10 patients.

Ogura and co-workers [ref: 60] described a 3-year disease-free survival rate of 91% for 281 patients treated by hemilaryngectomy. The local recurrence rate was 4%, and the neck recurrence rate was 1.5%; 74% of the treatment failures were controlled by salvage therapy.

A review of 61 patients with involvement of the anterior commissure treated by hemilaryngectomy at Washington University showed an absolute survival rate of 74%. [ref: 78] There were three (9%) local recurrences and three (9%) neck recurrences.

Hemilaryngectomy including the ipsilateral arytenoid was reported by Som [ref: 83] for 130 cases of vocal cord carcinoma extending posteriorly to the vocal process and face of the arytenoid. The cure rate was 74% for 104 patients with T2 lesions, and 58% for 26 patients with T3 lesions.

Bauer and associates [ref: 6] analyzed the significance of the surgical margins in 111 hemilaryngectomy specimens. Thirty-nine patients (35%) had involved margins (usually the anterior margin). The local recurrence rate was 10% with 5-year minimum follow-up. Only seven of 39 patients (18%) with an involved margin experienced recurrence, compared with 6% with uninvolved margins. Another 5% had recurrence evident in the cervical lymph nodes. Four patients eventually died of cancer.

Ogura and colleagues [ref: 60] found that the 3-year cause-specific disease-free survival rate for patients treated by total laryngectomy with or without radical neck dissection was 80%. The local and regional recurrence rate was 21%; approximately 46% of treatment failures were successfully treated by surgery or radiation therapy, alone or combined.

Foote and co-workers [ref: 20] reported on 81 patients who underwent laryngectomy for T3 cancers at the Mayo Clinic between 1970 and 1981. Seventy-five patients underwent a total laryngectomy and six underwent a near-total laryngectomy; 53 patients received a neck dissection. No patient underwent adjuvant irradiation or chemotherapy. The 5-year rates of local-regional control, cause-specific survival, and absolute survival were 74%, 74%, and 54%, respectively.

The results of treatment of T4 vocal cord carcinoma from four surgical series and two radiation therapy series are summarized in Table 42-4. [ref: 25] The University of Florida results for total laryngectomy in T3 lesions are presented in the following section.

Radiation Therapy Results Pene and Fletcher [ref: 73] described the results for 79 patients with carcinoma in situ and seven patients with dysplasia. The local failure rate was 11% for lesions with a T1 anatomic distribution and 26% for T2 lesions. Elman and associates [ref: 13] reported similar results. Nineteen patients with carcinoma in situ were treated at the University of Florida, and the disease was locally controlled in 18 (95%), with a minimum follow-up of 2 years. [ref: 15]

The current local tumor control rates reported from several institutions for invasive squamous cell carcinoma are in the range of 90% for T1, 70% for T2, and 50% to 60% for T3 or T4 disease. The surgical salvage rate is 90% to 95% for patients with T1 or T2 lesions that recur after irradiation (Table 42-5 and Table 42-6). [ref: 25,47,69]

The local tumor control rates for 247 patients with squamous cell carcinoma of the vocal cord, according to stage and surgical alternative, who were treated by radiation therapy at the University of Florida are given in Table 42-7 and Table 42-8. [ref: 14] All patients with T1 lesions were irradiated once daily at 2.25 Gy per fraction; those with T2 cancers received 2.25 Gy per fraction once daily or 1.2 Gy per fraction twice daily. The results of a multivariate analysis of local control after irradiation are shown in Table 42-9; vocal cord mobility and surgical alternative significantly influenced this end point.

Based on our data and the literature, there is a direct relationship between the rate of local tumor control and dose per fraction, with poor results obtained particularly in the T2 lesions at 1.8 to 1.9 Gy per fraction at similar or higher total doses. This is consistent with data presented in Table 42-5 and Table 42-6. At the M.D. Anderson Cancer Center, the University of Maryland, and Princess Margaret Hospital, patients were usually treated at >/= 2.1 Gy or higher per fraction, compared with the regimen at the University of California at San Francisco, where most patients were treated with 1.8-Gy fractions. Schwaibold and associates [ref: 77] reported on 56 evaluable patients treated with irradiation for T1N0 glottic carcinoma. Twenty-eight patients were treated at 1.8 Gy per fraction with a local tumor control rate of 75%, which was compared with 100% local control for 28 patients treated at >/= 2 Gy or higher per fraction. Kim and co-workers [ref: 31] also noted a relationship between local control and dose per fraction.

There was a correlation between the rate of disease control in the neck for 268 patients with T1N0 or T2N0 vocal cord carcinoma treated with radiation therapy to the primary lesion alone and primary tumor control; if the primary lesion was controlled, 0% to 3% of patients experienced recurrent disease in the neck, but 20% to 22% of the patients experienced recurrent neck disease if the primary lesion recurred.

The absolute and cause-specific (excluding patients who died of intercurrent disease within 5 years of treatment) survival rates for T1N0 or T2N0 vocal cord cancers treated at the University of Florida are shown in Table 42-10. [ref: 48]

The survival and control rates of patients with T3 fixed-cord lesions treated at the University of Florida are presented in Table 42-11. [ref: 51] Forty-five patients treated with irradiation alone were evaluable for local control rates; eight patients were excluded who died less than 2 years after radiation therapy continuously free of disease at the primary site. The rate of local control after once-daily irradiation was nine of 17 (53%) compared with 20 of 28 (71%) after twice-daily irradiation. There was no relationship between subsequent local control and whether the vocal cord remained fixed or became mobile during irradiation. Lee and associates [ref: 37] noted an inverse relationship between primary tumor volume and local control rate after irradiation alone in a subset of these patients. The incidence of severe complications, including those after the initial treatment and any later salvage procedures was 15% after radiation therapy alone and 15% after surgery alone or combined with adjuvant irradiation. The vocal quality varied from fair to nearly normal.

Seven patients with T4 lesions of the glottic larynx were irradiated with twice-a-day fractionation at the University of Florida, and three had local control with 2 years or more of follow-up. [ref: 70]

Supraglottic Larynx Cancer Surgical Results The 3-year cause-specific survival rates for 134 N0 patients with supraglottic carcinoma treated by supraglottic laryngectomy at Washington University were as follows: T1N0, 64 of 78 (82%); T2N0, 23 of 34 (68%); T3N0, seven of 10 (70%); and T4N0, nine of 12 (75%). [ref: 61] The 3-year cause-specific survival rates for 42 N+ patients were as follows: T1, eight of 14 (57%); T2, eight of 12 (67%); T3, two of three (67%); and T4, eight of 13 (62%). [ref: 61] Low-dose preoperative irradiation was given to 109 of 176 patients. Local recurrence developed in only 11 patients (6%); in five, salvage by total laryngectomy or irradiation proved successful. Seventeen had treatment failures in the neck, and salvage was achieved in nine. For patients with advanced lesions treated with preoperative irradiation followed by total laryngectomy and radical neck dissection, the 3- and 5-year survival rates were 70% and 67%, respectively.

Ogura and associates [ref: 59] reported on 59 patients with supraglottic carcinoma with extension to one arytenoid treated by supraglottic laryngectomy; 56 had preoperative irradiation. Local recurrences developed in five patients, and neck recurrences developed in six patients. Salvage by total laryngectomy or radiation therapy was obtained in four.

Bocca [ref: 9] reported 250 cases of T1 and T2 supraglottic carcinoma treated by supraglottic laryngectomy and bilateral elective or therapeutic neck dissection. The local recurrence rate was 11%, and the neck recurrence rate was 5%; in nine patients, salvage was achieved by further therapy. The 5-year survival rate was 80%.

Lee and colleagues [ref: 36] reported 60 patients treated with supraglottic laryngectomy combined with adjuvant postoperative irradiation in 83% of the cases at the M.D. Anderson Cancer Center. All of the primary tumors were locally controlled.

Radiation Therapy Results A recent analysis of the results of treatment by irradiation alone at the University of Florida for 209 patients with 211 primary lesions is outlined in Table 42-12. [ref: 46] There was no difference in local control rates as a function of site within the supraglottic larynx, with the exception of T3 false cord tumors, which had a lower local control rate compared with T3 tumors arising elsewhere in the supraglottis. Local tumor control rates after radiation therapy versus CT-calculated primary tumor volume for T3 lesions were 11 of 13 (85%) for those less than 6 cm**3 compared with nine of 19 (47%) for those 6 cm**3 or more (P = 0.04). There was a modest improvement in the local tumor control rate for T2, T3, and T4 lesions irradiated twice a day. Local-regional control and 5-year survival rates are given in Table 42-13 and Table 42-14.

Combined-Therapy Results In patients with resectable stage IV supraglottic carcinomas, Fletcher and Goepfert [ref: 18] reported a 5-year survival rate of 24% (19 of 78 patients) with surgery alone and a rate of 42% (16 of 38) with combined surgery and irradiation. In a similar group of patients, Goepfert and associates [ref: 23] found a rate for failure above the clavicle of 24% (28 of 116 patients) with surgery alone and a rate of 13% (seven of 53) with surgery and postoperative irradiation. The data clearly support the use of combined-modality treatment in these patients.

Comparison of Surgery and Radiation Therapy Weems and colleagues [ref: 95] analyzed the University of Florida series of 195 patients treated with curative intent by irradiation, surgery, or both. Patients treated with surgery alone were grouped with those treated with preoperative or postoperative irradiation. [ref: 27,30,42] The rates of initial and ultimate local control, local control with voice preservation, and initial and ultimate control above the clavicles are shown in Table 42-15 and Table 42-16. Radiation therapy or surgery with selected use of adjuvant irradiation offered similar results (90% to 100% 5-year cause-specific survival) for early-stage lesions, but surgery offered better results than irradiation for stage IV disease (27% and 50%, respectively).

Follow-Up Policy

Follow-up of patients with early lesions is planned for every 4 to 8 weeks for 2 years, every 3 months for the third year, and every 6 months for years 4 and 5, and then annually for life.

Follow-up of patients with vocal cord or supraglottic larynx lesions treated by radiation therapy or conservative surgery is almost more important than the treatment itself because early detection of recurrence usually results in salvage that may include cure with voice preservation. [ref: 71]

If recurrence is suspected but the biopsy is negative, patients are reexamined at 2- to 4-week intervals until the matter is settled. The value of follow-up CT scans for detecting early local recurrence is investigational.

Wagenfeld and associates [ref: 93] studied 740 cases of glottic larynx cancer treated from 1965 to 1974 to determine the incidence of second respiratory tract malignancies. There was a minimum follow-up of 5 years. There were 48 second respiratory tract malignancies, although only 14 were expected. Twenty-five were in the lung, and 23 were scattered among other head and neck sites. Only seven of the 23 second head and neck primary lesions resulted in death; these second lesions were frequently diagnosed in an early stage during routine follow-up for the glottic lesion.

Because the risk of a lethal lung primary lesion is nearly as great as that of dying of an early glottic carcinoma, it makes sense to obtain annual chest roentgenograms.

Sequelae of Treatment

Surgical Sequelae Neel and co-workers [ref: 57] reported a 26% incidence of nonfatal complications for cordectomy. Immediate postoperative complications included atelectasis and pneumonia, severe subcutaneous emphysema in the neck, bleeding from the tracheotomy site or larynx, wound complications, and airway obstruction requiring tracheotomy. Late complications included granulation tissue that had to be removed by direct laryngoscopy to exclude recurrences, extrusion of cartilage, laryngeal stenosis, and obstructing laryngeal web.

The postoperative complications and sequelae of hemilaryngectomy include chondritis, wound slough, inadequate glottic closure, and anterior commissure webs. [ref: 21] The complications associated with supraglottic laryngectomy and total laryngectomy for supraglottic carcinomas include fistula (8%), carotid artery exposure or blowout (3% to 5%), infection or wound sloughing (3% to 7%), and fatal complications (3%). [ref: 21] The risk of complication increased if tumor margins were involved by tumor; there was no change in risk associated with age, sex, race, laryngeal site, stage of primary tumor, size of primary tumor, use of low-dose preoperative irradiation, or status of the positive nodes.

The risk of severe complications for a series of 195 patients with squamous cell carcinomas of the supraglottic larynx treated at the University of Florida is shown in Table 42-17. [ref: 95] A severe complication was defined as one that necessitated surgical intervention or resulted in death. Five percent of patients treated with radiation therapy with or without neck dissection experienced a severe complication, compared with 17% to 23% of those treated with a surgery alone or combined with adjuvant irradiation.


Radiation Therapy Sequelae The acute reactions from the treatment of early vocal cord cancer using a tumor dose of 2.25 Gy per day to administer a total dose of 56.25 to 63 Gy of **60Co in five fractions per week are relatively mild. During the first 2 to 3 weeks, the voice may improve as the tumor regresses. The voice generally becomes hoarse again because of irradiation-induced changes, even though the tumor continues to regress. A mild sore throat develops beginning at the end of the second week, but medication is usually not required. The voice begins to improve approximately 3 weeks after completion of treatment, usually reaching a plateau in 2 to 3 months. Patients with extensive lesions often recover a normal voice, although not as frequently as those with small tumors.

Edema of the larynx is the most common sequela after irradiation for glottic or supraglottic lesions. The rate of clearance of the edema is related to the irradiation dose, volume of tissue irradiated, addition of a neck dissection, continued use of alcohol and tobacco, and size and extent of the original lesion. Edema may be accentuated by a radical neck dissection and may require 6 to 12 months to subside.

Soft tissue necrosis leading to chondritis occurs in fewer than 1% of patients, usually in those who continue to smoke. Soft tissue and cartilage necroses mimic recurrence, with hoarseness, pain, and edema; a laryngectomy may be recommended as a last resort for fear of recurrent cancer, even though biopsy specimens show only necrosis.

Corticosteroids such as dexamethasone (Decadron) have been used to reduce irradiation-induced edema after recurrence has been ruled out by biopsy. If ulceration and pain occur, administration of an antibiotic such as tetracycline may help.

Of 304 patients with T1 or T2 vocal cord cancer treated at the University of Florida, five experienced significant complications; these included subcutaneous fat necrosis, one case of osteochondronecrosis (which healed with conservative management), and three cases of severe laryngeal edema, necessitating tracheostomy. One patient with edema was thought to have recurrent cancer, underwent a laryngectomy, and was found to have no tumor in the specimen. The incidence of significant complications as a function of T stage, total dose, and dose per fraction is shown in Table 42-18. [ref: 47]

In patients irradiated for supraglottic carcinoma, sore throat persists until 3 to 4 weeks after completion of treatment. There is an associated dry mouth from irradiation of the salivary and parotid glands, a loss of taste, and a sensation of a lump in the throat if the entire glottic area is included.

It is unusual for patients to require a tracheotomy before irradiation unless severe lymphedema develops at the time of direct laryngoscopy and biopsy. However, in patients who have recovered from the direct laryngoscopy and biopsy without obstruction, a tracheotomy has rarely been required during a fractionated course of radiation therapy.

Patients treated twice a day with 1.2-Gy fractions (continuous-course technique) to total doses of 74 to 76.8 Gy usually have more brisk acute reactions than those treated once a day with 2-Gy fractions. Approximately 10% treated with twice-a-day irradiation require nasogastric feeding tubes because they have difficulty in swallowing.

Examples of acute chondritis requiring discontinuation of treatment have not been seen, although most epiglottic lesions exhibit cartilage invasion.

The epiglottis, both suprahyoid and infrahyoid portions, remains thicker than normal for long periods of time, but this is not often associated with difficulty in swallowing, respiratory obstruction, or aspiration. The patient is cautioned to eat and drink slowly until the edema resolves. The false cord and arytenoids may develop some edema.

Lesions of the suprahyoid epiglottis frequently destroy the tip of the epiglottis, and it may require some time for the exposed cartilage to heal. Successful irradiation of infrahyoid epiglottis tumors is not associated with a high rate of necrosis, even though most of these lesions penetrate the porous epiglottic cartilage.

Shukovsky [ref: 79] analyzed the risk of severe complications for 114 patients with squamous cell carcinoma of the supraglottic larynx. Necrosis developed in five patients, and severe edema developed in seven patients. All but one of these complications appeared with doses in excess of 70 Gy delivered over 7 weeks or with larger treatment volumes. The incidence of severe complications in 209 patients treated
with radiation therapy alone or combined with neck dissection at the University of Florida was as follows: T1, zero of 18 (0%); T2, four of 81 (5%); T3, three of 89 (3%); and T4, five of 21 (24%). [ref: 46]