Larynx

Laryngeal cancer, or cancer of the larynx, represents about 2% of the total cancer risk, and other than skin, is the most commonly occurring head and neck cancer. 1 Laryngeal cancer is caused by several things but primarily from cigarette smoking. By stopping smoking, the risk of developing tobacco related cancers of the upper alimentary and respiratory tracts decreases after 5 years without smoking and it decreases to the level of a non-smoker once the 10 year mark is reached. 1 Other causes are having a poor diet, extensive use of one’s voice, an increased amount of alcohol usage, long-term exposure to certain chemicals and fumes, and exposure to the human papillomavirus (HPV). 2 Laryngeal cancer is also more prevalent in the elderly and around the age of 70, it becomes more common in women than in men. || The following is a list of the common signs and symptoms, and clinical presentations of laryngeal cancer: Persistent sore throat and hoarseness that does not go away. 5 They’re a variety of different methods for detecting larynx abnormalities. - Laryngoscopy: This process involves either two types of examinations to the back of the throat. One, which uses mirrors to assess, and another, which utilizes a fiber optic camera inserted into the nose or mouth. 7 This process can assess for any type of visual abnormalities in the larynx or surrounding areas. - Panendoscopy: Although this process may sound like the normal laryngoscopy, it utilizes general anesthesia to further examine the larynx and surrounding structures that can include the throat, esophagus, trachea, and sometimes bronchi. 7 This procedure is sometimes used in conjunction with biopsies to remove a sample of suspected tumor for assessment. - Chest X-Ray: Sometimes a chest x-ray will be taken to assess on whether the cancer has spread to various areas. - MRI: Although not used very often, and MRI (Magnetic Resonance Imaging) scan will be done to obtain very detailed images of the larynx and surrounding structures. This scan is also helpful in determining if the cancer has spread outside of the larynx. 7 - CT: Many times a diagnostic CT (Computed Tomography) scan will be done to obtain information about the size, shape, and location of the cancer. It also helps in assessing whether or not any lymph nodes have changed as a result of the tumor. 7 - PET: Another form of diagnostic imaging within larynx cancer is Positron Emission Tomography (PET). This process allows physicians an adequate visualization on where the tumor originated, and also where and if it spread within the body. - Barium Swallow: This procedure, which is used very commonly for laryngeal cancers, involves drinking a barium-based solution that can be seen on an image, to assess if there is any type of blockage within the throat or esophagus. 7 This procedure will usually determine where the blockage is within the head and neck region (if there is something causing it). || Larynx cancers account for 2% of all malignancies reported and 75% of these cases are well differentiated squamous cell carcinomas. Other neoplasms less commonly seen affecting the larynx include adenocarcinomas, sarcomas, lypmphomas, true small cell or oat cell carcinomas and myelomas. Early tissue changes in the larynx include dysphasia, premalignant atypia, and carcinoma in situ. This last condition usually presents itself as a whitish, thickened irregular area of the mucosa.3 Common variants of squamous cell carcinoma include verrucous carcinoma, which is a slow growing tumor and squamous cell carcinoma with spindle cell features also known as pseudosarcoma. At the time of presentation, two thirds of laryngeal tumors are confined to the vocal cords and the anterior portion is the most commonly affected area.4 || Lymph node drainage is separated into 3 sections: Metastatic spread in laryngeal cancers depend heavily on the location of the tumor. Laryngeal cancers of the supraglottic larynx will metastasize in 50% of cases due to the abundance of lymphatic channels available through which the cancer can spread. 8 For cancers of the glottic larynx, metastasis only occurs in 10% of cases and will usually only metastasize in the late stages due to the much more limited lymphatic drainage of the glottis. 8 Metastasis from the subglottis more common, as there is significantly more lymphatic drainage. If metastasis does occur, spread to the thyroid gland, trachea, or esophagus is common along with jugular nodes. 8 Depending on the case, the presence of cervical lymph node metastasis may be an indicator for a modified or radical neck dissection. If the primary cancer is treated with surgery and the patient is not receiving adjuvant radiation therapy, the neck dissection is recommended. However, if the primary cancer is being treated with radiation therapy or is being treated with surgery and adjuvant radiation therapy, a neck dissection is not recommended. 8 || Determining the grade of cancer provides doctors with the best information to establish both a prognosis and the most effective treatment regimen. Unfortunately, due to their location, laryngeal cancers are often hard to grade until after surgery has been performed and the tumor excised. To determine the grade of laryngeal cancer, a biopsy of the area of concern must be performed so that the histology can be determined. Viewed from beneath a microscope the biopsied laryngeal tissue contains certain features that establish its grade. The common grading system used for cancer of the larynx is: 2 ||
 * **Epidemiolgy:** || Megan
 * **Etiology:** || Kevin Tsai
 * Cigarette smoking
 * Alcohol abuse
 * Age
 * Family History
 * Diet
 * Human Papilloma Virus (HPV)
 * Ratio of glottis to supraglottic carcinoma is approximately 3 to 1. 3 4 ||
 * **Signs & Symptoms:** || Erin
 * Ear Pain
 * Difficulty or painful swallowing
 * A lump in the neck or throat
 * Constant coughing
 * Trouble breathing
 * Weight loss
 * A lump or mass in the neck (due to spread of the cancer to nearby lymph nodes). 6 ||
 * **Diagnostic Procedures:** || Spencer
 * **Histology:** || Pablo
 * **Lymph node drainage:** || Becky
 * Supraglottic structures have a rich capillary lymphatic plexus, whereas the trunk passes through the pre-epiglottic space and the thyrohyoid membrane and leads to subdigastric lymph nodes.
 * The glottic (true vocal cords) basically has no capillary lymphatics, therefore, if lymphatic spread occurs from glottis cancer, then the tumor has extended into the supraglottic or subglottic area.
 * Subglottic have few capillary lymphatics and the lymphatic trunk passes through the cricothyroid membrane to the pretracheal lymph nodes. The subglottic region drains posterior through the cricotracheal membrane, with some going to the paratracheal lymph nodes and others going to the inferior jugular chain. 6 ||
 * **Metastatic spread:** || Adam
 * **Grading:** || Megan
 * Grade 1- or low grade- the cells look reasonably similar to normal cells of the larynx. The cancer cells are said to be well differentiated. The cancer cells tend to grow and multiply quite slowly and are not very aggressive
 * Grade 2 - or intermediate grade
 * Grade 3 - or high grade - the cells look very abnormal and poorly differentiated. The cancer cells tend to grow and multiply quickly and spread more aggressively ||
 * **Staging:** || Kevin Tsai
 * TNM **
 * 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 without fixation of the larynx.
 * T3 Tumor limited to larynx with vocal cord fixation and/or invades any of the following: post cricoid area, pre-epiglottic space, paraglottic space, and/or inner cortex of thyroid cartilage.
 * T4a Moderately advanced local disease. Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx.
 * T4b Very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures.
 * Glottis **
 * T1 Tumor limited to vocal cord(s)
 * T1a Tumor limited to one vocal cord
 * T1b Tumor involves both vocal cord
 * T2 Tumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility
 * T3 Tumor limited to the larynx with vocal cord fixation and/or invasion of paraglottic space, and/or inner cortex of the thyroid cartilage
 * T4a Moderately advanced local disease
 * T4b Very advanced local disease
 * Subglottis **
 * T1 Tumor limited to the subglottis
 * T2 Tumor extends to vocal cord(s) with normal or impaired mobility
 * T3 Tumor limited to larynx with vocal cord fixation
 * T4a Moderately advanced local disease
 * T4b Very advanced local disease
 * 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, >3 cm but ≤6 cm in greatest dimension. Metastases in multiple ipsilateral lymph nodes, none >6 cm in greatest dimension. Metastases in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension.
 * N2a Metastasis in a single ipsilateral lymph node, >3 cm but ≤6 cm in greatest dimension.
 * N2b Metastases in multiple ipsilateral lymph nodes, none >6 cm in greatest dimension.
 * N2c Metastases in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension.
 * N3 Metastasis in a lymph node, >6 cm in greatest dimension.
 * Distant Metastasis (M) **
 * M0 No distant metastasis.
 * M1 Distant metastasis.
 * Anatomic Stage / Prognostic Group ** 4

There are a number of side effects that a patient may experience during and after the course of radiation therapy treatment:
 * **Radiation side effects:** || Erin
 * Painful sores in the mouth and throat that may make eating and drinking difficult. This can lead to weight loss and malnutrition.
 * Skin irritation (similar to a sunburn)
 * Dry mouth (If the salivary glands such as the parotid glands exceed tolerance)
 * Worsening of hoarseness
 * Trouble swallowing
 * Possible breathing trouble from swelling of the larynx
 * Tiredness

Most of these side effects go away a short while after treatment is complete. 6 || Much of the prognosis of laryngeal cancers depends on a few different factors: -Stage -Location -Spread -Grade
 * **Prognosis:** || Spencer

Some of the general prognostic indicators can also include: - Age - Sex - Performance Status - Pathological Features of Tumor

Estimated new cases and deaths from laryngeal cancer in the United States in 2013. ⁷ New Cases – 12,260 Deaths – 3,630

For small laryngeal cancers that have not progressed to the lymph system, the prognosis is relatively good with a cure rate of about 75% to 95%. ⁷ || The primary goal in the treatment of laryngeal cancer is to maximize the cure rate for patients. Factors affecting the choice of treatment include the preservation of speech, the ability to swallow as well as the stage and extent of the disease.4 For early stages T1 and T2 laryngeal cancers, the combination of radiation therapy and surgery have been and continues to be the traditional choice of treatment. Limited surgery, laser excision, and cordectomy have been very successful in treating early stage cancer of the larynx. Radiation therapy has also proven useful for treating this disease at an early stage because the volume of tissue needed to be irradiated is fairly small, therefore diminishing the side effects caused by treatments. When the disease is considered advanced as in stage 3 and 4, a combination of therapies is usually recommended. Often chemotherapy, radiation and or surgery are used to control and fight the disease. For advanced cancers a total laryngectomy has been the standard of care for patients with bulky tumors. A combination of high dose Cisplatin and radiation therapy are the most common treatment approach. When patients receive radiation therapy, it is usually in the form of 6MV photons. Conventional treatment fields include lateral opposed and a 3-field technique. The latest technologies available allow for the use of intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT).3
 * **Treatments:** || Pablo



Radiation doses range from 60 to 70 Gray (Gy) at 2Gy per fraction. 60Gy is given to patients with no clinical disease after stripping, 66Gy to patients with bulky T1 tumors and 68 to 70Gy for patients with T2 tumors. It has been demonstrated that giving 2Gy per fraction yields better results than a more conventional dose of 1.8Gy per fraction. Patients are also treated twice per day (BID) in some centers. Doses when treating patient BID are typically 1.2Gy per fraction for a total of 74.4 to 79Gy. The latest trend however, has been to treat patients with what is called an intergrated boost. In this case the dose to the bulky tumor is 2.5Gy per fraction while the lymph nodes involved receive 2Gy per fraction for a total of 25 fractions.3 || Predicted tolerance doses of Emanmi et al. (1991):
 * **TD 5/5:** || Becky


 * Ear: 3000cGy—Acute serous otitis
 * Optic chiasma: 4500cGy—blindness
 * Eye lens: 1000cGy—cataracts
 * Optic nerve: 5000cGy—blindness
 * Salivary gland: 5000cGy—Xerostomia
 * Spinal cord: 4500cGy--Myelitis
 * Oral cavity: 6000cGy--ulceration.
 * Larynx**:** 7000cGy--necrosis 9 ||
 * **References:** || Adam


 * 1) Chao KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002:265
 * 2) Patient.CO.UK. Laryngeal (Throat) Cancer. http://www.patient.co.uk/health/laryngeal-throat-cancer. Aug 14, 2012. Accessed May 29, 2013.
 * 3) Chao C, Perez C, Brady L. Radiation Oncology Management Decisions. 3rd ed. PA: Lippincott Williams and Wilkins; 2011:285-297.
 * 4) National Cancer Institute. National Cancer Institute Web Site. []. Accessed May 27, 13.
 * CM, Leaver D. Principles and Practice of Radiation Therapy. St. Louis, MO: Mosby Inc; 2010:692-733.
 * 1) American Cancer Society. Laryngeal and Hypopharyngeal Cancer. American Cancer Society. []. Revised January 18, 2013. Accessed May 29, 2013.
 * 2) Laryngeal Cancer Diagnosis and Detection. Cancer Treatment Centers of America. http://www.cancercenter.com/laryngeal-cancer/laryngeal-cancer-diagnosis.cfm. Accessed May 29, 2013.
 * 3) Laryngeal Cancer. American Medical Network.http://www.health.am/cr/laryngeal-cancer/. Accessed May 29, 2013.
 * 4) Gunderson, L, L, Tepper, J, E. Clinical Radiation Oncology. 2nd Ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007. ||

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