The Larynx - laryngeal cancers treatment

Because of the prominent role the larynx plays in communication, swallowing, respiration, protection of the lower airway, and therefore, quality of life, the treatment of cancer of the larynx presents formidable dilemmas regarding the functional consequences of treatment in addition to the intrinsic threat to life posed by these cancers. Unique to this particular site of head and neck cancer, quality-of-life issues have been incorporated into treatment decision making more extensively than for other cancer sites. Cancer of the larynx is generally diagnosed at an earlier stage than are other head and neck sites, primarily owing to the early manifestation of symptoms. As a result, cure rates are generally higher than for other sites.

The larynx is divided into three subsites that form the basis for classifying laryngeal cancers. These separations exist because each site is associated with different risks of local spread, lymphatic metastasis and control rates. These differences exist as a result of differences in embryologic development, and vascular and lymphatic anatomy. The TNM staging for these subsites is listed in

Table 90-13.

Considerable attention has been devoted to anatomic studies of the vascular and lymphatic compartments of the larynx. These studies have defined natural anatomic barriers to cancer spread within the larynx and have contributed to the development of select surgical procedures for partial laryngeal resections of certain cancers.

The true vocal cords present an effective boundary between supraglottic and subglottic lymphatic spread within the larynx. This separation breaks down with tumors involving the anterior or posterior commissures and with deeply invasive tumors that extend vertically across the true and false vocal cords (transglottic cancers). Normally, the internal perichondrium of the thyroid cartilage also presents an effective barrier to cancer spread. However, cancer involvement of the anterior commissure or transglottic extension is associated with invasion of the thyroid cartilage in 40% to 60% of cases.

Early diagnosis is critical for achieving high survival rates and larynx preservation. Most cancers that are diagnosed at an early stage of development arise in the glottic larynx. This is so because minimal changes in the mass of the vibrating vocal cord due to tumor growth result in changes in its vibrating characteristics and presents early as dysphonia or hoarseness. Supraglottic cancers are usually more advanced than glottic cancers at the time of diagnosis because they do not generally produce early symptoms of hoarseness. Rather, the earliest symptoms of a supraglottic cancer are usually sore throat, dysphagia, referred otalgia, or the development of a neck mass representing regional metastasis. Airway compromise may be an early symptom with subglottic cancer.

Modern clinical evaluation of laryngeal cancers includes fiberoptic laryngoscopy, direct laryngoscopy, CT, and MRI of the larynx and neck, as well as videostroboscopic analysis. The radiologic assessments are of value in assessing direct extension to the preepiglottic and paraglottic spaces of the larynx, detecting cartilage invasion and evaluating the soft tissues and lymph nodes of the neck. These studies have replaced conventional tomography and contrast laryngo-graphy. The precise evaluation of tumor extent still requires direct laryngoscopy under anesthesia. With large obstructive tumors, this may necessitate prior tracheostomy. In some patients with large obstructive lesions, debulking the tumor mass at the time of direct laryngoscopy can obviate the need for tracheostomy and thereby reduce the potential risk of tumor seeding of the tracheostomy site. Even with precise clinical evaluation, inaccurate estimation of tumor extent (usually underestimation) occurs in 30% to 40% of cases. Most often this involves failure to identify invasion of the laryngeal cartilage framework.

Supraglottic primary tumors account for 25% to 50% of all laryngeal cancers, A knowledge of the laryngeal compartments aids in understanding the spread and staging of supraglottic and glottic cancers. The staging of supraglottic cancers is based on the subsite or region of the supraglottis involved in the cancer. Subsites include the false vocal cords, arytenoids, lingual and laryngeal surfaces of the epiglottis, and aryepiglottic folds. The epiglottis itself is also subdivided into the region extending above the plane of the hyoid and that below the hyoid. Suprahyoid epiglottic tumors tend to have a better prognosis than infrahyoid cancers with the exception of those invading the aryepiglottic fold (marginal area) to involve the pyriform sinus. Early cancers (T1 and T2) can involve one or more subsites but have normal vocal cord motion. Those cancers that cause fixation of the vocal cord or involve the postcricoid region, medial wall of the pyriform sinus, or preepiglottic space are staged T3. Those that extend beyond the larynx or invade thyroid cartilage are staged T4.

Glottic carcinomas are also staged according to the subsites involved. Cancers limited to the true vocal cords are T1 (T1a - one vocal cord involved; T1b - both vocal cords involved), and those with extension to an adjacent site are staged T2. Vocal cord fixation is classified T3 whereas those with cartilage involvement or extension outside the larynx are T4.

Subglottic cancers that are limited to the subglottic region (T1) or to the subglottis and true vocal cords (T2) are early cancers. Fixation of the vocal cord (T3) and cartilage invasion or extension outside the larynx (T4) is associated with a worse prognosis. The nodal classification for staging is the same as for other HNSCC sites.

Although a great deal of controversy exists, at our institution, curative radiotherapy is generally the treatment of choice for early-stage laryngeal lesions. It is for the moderately advanced lesions that one must consider the trade-offs between definitive radiotherapy with salvage surgery held in reserve versus definitive surgery, or more recently, combined chemotherapy and radiation therapy approaches.

A treatment algorithm for premalignant and early glottic malignancies is shown in

Figure 90-3. Obviously, examination under anesthesia and biopsy make up the gold standard in the assessment of early lesions, with radiographic imaging reserved for assessment of the paraglottic space (when decreased cord mobility is noted) and thyroid cartilage (if an infiltrative lesion of the anterior commissure is noted). Radiation therapy remains the management of choice for early glottic cancers. Nevertheless, in some instances, patients may choose conservation laryngeal surgery, including endoscopic laser excision of localized lesions, or partial laryngeal surgery. Both require frozen-section analysis of margins if the patient and tumor factors support such an approach. Additionally, in many instances, conservation laryngeal surgical salvage is effective in those 10% to 20% of cases in which external beam therapy has been unsuccessful for stages I and II cancers.

The design of the radiation portals must be tailored to the individual patient, but some general comments can be made. In general, supraglottic tumors have access to a richer lymphatic drainage than do tumors of the glottic larynx and so radiation fields tend to be larger in order to treat the larger volume at risk for metastatic disease. Typically, one treats the primary tumor volume and regions at risk for subclinical metastatic disease to 5,000 cGy, and then reduces the field size to areas of gross disease and delivers an additional 2,000 to 2,400 cGy. The spinal cord is shielded at 4,500 cGy, and megavoltage electron beams are used to treat the posterior cervical nodes to higher doses as required. Because of the V shape of the anterior neck, wedge-compensating filters are often required to ensure uniform radiation dose distributions. If the anterior supraclavicular fossa is at risk for micrometastatic disease, it is treated to 5,000 cGy, using an anterior field suitably matched to the upper neck fields. Early-stage (T1-2, N0) glottic lesions are generally treated with relatively small fields localized to the primary tumor. Tumors of the subglottic larynx can spread to the upper paratracheal nodes as well as to the nodes in the cervical chain, and radiation fields for this disease must therefore include the upper mediastinum.

The treatment of more advanced laryngeal cancers (T3 and T4) has historically included surgery with or without radiation therapy. Prospective randomized studies have shown convincingly that chemotherapy and radiation therapy (including surgical salvage) are equally effective in the long-term survival of patients with T3 laryngeal cancers as compared with surgery with or without radiation therapy. It is important to note that approximately 60% of patients may preserve their larynx, and thus quality of life has significantly improved. Speech communication profiles are clearly better in the group of patients randomized to the larynx preservation arm, but there was no determination of swallowing function. However, local control was poorer for patients with T4 lesions. Current standard of care argues that laryngeal preservation protocols be considered in treating such patients. A treatment algorithm for advanced glottic cancers is shown in

Figure 90-4.

More recently, there has been increasing focus on the use of chemotherapy in the management of laryngeal cancers of all stages. Laccourreye and colleagues have published a series of articles that suggest that exclusive chemotherapy may be effective in select cases. Furthermore, when induction chemotherapy is combined with conservation laryngeal surgery, improved locoregional control rates have been achieved. In the United States, these approaches are being investigated. While there is promise, these regimens should only be used as part of IRB-reviewed protocols.

Many surgical procedures for laryngeal carcinoma involve the creation of a tracheal stoma. This area is sometimes at significant risk for tumor recurrence, which is most likely associated with peritracheal metastases that erode into the peristomal area. For this reason, bilateral peri- tracheal dissections should be performed in T4 glottic cancers and radiation therapy provided postoperatively if metastases to this echelon of nodes are found pathologically. Once a stomal recurrence has developed, the prognosis is grave regardless of whether it is treated with surgery or radiotherapy. Sisson and colleagues reported on a series of 28 patients with stomal recurrences treated with one or more surgical resections. The 5-year survival was only 17%. Schneider and colleagues reported on patients with tracheal recurrences treated with radiotherapy; good palliation of local pain and/or bleeding was achieved, but the 2-year survival rate was only 6%. Given the poor results with salvage therapy, it is clearly better to prevent stomal recurrence in the first place. If risk factors for stomal recurrence are present (

Table 90-14), then the tracheal stoma should be irradiated as part of the initial management.

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Revision date: July 9, 2011
Last revised: by Sebastian Scheller, MD, ScD