Oropharynx

most common cancer in men. While oropharynx cancer usually occurs in people over the age of 45 years, there has been an increasing incidence of this type of malignancy in younger people (<45) in the past 20 to 30 years. This increase has been attributed to the rising rate of human papillomavirus (HPV) infected youth. HPV has been linked with an increased risk of developing oropharyngeal cancers in young non-smokers.[2] Twenty-five percent of oropharyngeal cancers occur in the tongue with another 10% to 15% occurring in the tonsillar region. || AJCC Grading Scale: G=Grade G1- __**Well differentiated**__ (low grade) G2- __**Moderately differentiated**__ (intermediate grade) G3- __**Poorly differentiated**__ (high grade) G4- __**Undifferentiated**__ (high grade) [8] ||  ||   || **Stage III** ** Stage III is either of the following: ** * The cancer is **__larger than 4 centimeters__** and has **__not spread outside the oropharynx.__** Stage IVA is either of the following: Stage IVB is either of the following: * The cancer is found in a lymph node that **__ is larger than 6 centimeters __** and may have **__ spread to other tissues __** around the oropharynx. T1: Greatest diameter of primary tumors** < or = 2 cm ** T2: > 2 cm or = 4 cm  T3: >4 cm  T4: massive tumor with deep invasion into maxilla, mandible, ptergoid muscles, deep tongue muscle, skin and soft tissue of neck. NX-regional lymph nodes can’t be assessed NO-no regional lymph node metastasis N1-Metastgasis in a single ipsilateral lymph node, <3 cm in greatest dimension N2-Mets in a single ipsilateral lymph node, >3 cm but <6 or multiple ipsilateral lymph nodes none >6 cm or bilateral contralateral lymph nodes none >6 cm N3 Mets in lymph node >6 cm in greatest dimension M- evaluates metastatic disease: MX- distant metastasis can’t be assessed MO- No distant metastasis M1- Distant metastasis [4] || **For T1-2N0;** Definitive RT. Alternative, surgery w/post-op RT as indicated **For III- IV;** Concurrent chemo-RT (preferred). Indications are extracapsular nodal spread & positive margin. Alternative, surgery with post-op (chemo-) RT. Indicators are close margins, multiple positive LNs, PNI, LVSI. For patients who aren't candidates for standard chemo-RT (cisplatin), consider RT & cetuximab. If unable to tolerate concurrent chemo, altered fractionation RT could be used.(12) -For T3-4 primaries, tonsillar lesions require radical tonsillectomy often with partial mandibulectomy; base of tongue lesions require partial or total glossectomy and myocutaneous flap reconstruction. Patients needing removal of more than 1/2 of tongue or elderly patients w/poor pulmonary function often require total laaryngectomy to prevent subsequent aspiration. __Preferred treatment for locally advanced oropharyngeal=primary organ preservation w/RT or chemo-RT (12)__ Types of Neck Dissection- 1) Radical Neck Dissection (RND); removal of levels I-V, sternocleidomastoid muscle, omohyoid muscle, internal & external jugulars, CN XI, and submandibular gland. 2) Modified RND; leaves >1 sternocleidomastoid muscle, internal jugular or CN XI. 3) Selective neck dissection; does not remove >1 level of levels I-V. 4) Supraomohyoid neck dissection; removes levels I-III. 4) Lateral neck dissection; removes levels II-IV (12) prescription doses, treatment fields, planning techniques  Stage T1-2N0 definitive conventional 200cgy/day to 7000cgy  Stage T1N1 & T2N0-1 6 fx week during weeks 2-6, 200cGy/day to 7000cGy  Or, concurrent boost 150cGy/day for GTV & 180cGy/day for CTV to 7200cGy  Or, hyperfractionation 120cGy/BID to 8160cGy  Stage III-IV 7000cGy total dose  Elective Neck 160 or 200cGy/day to 5000 or 5600cGy total dose  Post-op 200cGy/day to 6000 or 6600cGy total dose  IMRT 7000cGy total dose (12)  The patient is simulated supine with neck extended as much as possible. Dentures are removed and mouth is examined for dental work that may need shielding with wax.(7) All scars are wired before thermoplastic immobilization mask is created. Shoulders are pushed downward if possible with pulls or straps. CT simulation is then fused with either MRI, PET, or diagnostic CT with contrast for contouring. Important structures to contour and their dose tolerances are as follows: spinal cord <4500cGy brainstem <5000cGy parotids mean dose <2600cGy mandible <7000cGy larynx mean dose <4350cGy eyes <500cGy Conventional head & neck treatment plans include opposing laterals base of skull & mastoids matching an anterior supraclavicular field. After 4000cGy it is then necessary to go off-cord by decreasing lateral blocks and inserting electron fields in the posterior necks.(7) A conformal treatment plan would block according to the CTV+margin and set fields accordingly, suited to the shape of the CTV & GTV. For IMRT planning, typically seven nonopposing beam angles are used. || > > ==== ==== ||
 * Epidemiology: || Oropharyngeal cancer strikes approximately 8500 people a year in the United States with males outnumbering females by two to one.[1] It is the 8th
 * Etiology: || [[image:smoker.jpg width="130" height="87"]] Smoking, alcohol consumption and the use of smokeless tobacco are the main causes of oropharyngeal cancers, with combined usage causing a synergistic effect. In developing countries, the consumption of betal and areca nuts as well as chewing tobacco are risks factor for this disease. The roles of nutrition and diet in the development of oropharyngeal cancer has been debated with no firm conclusions. However, it has been noted that a diet high in vegetables and fruits does offer protection against the development of this disease in those people who consume alcohol and/or smoke. Poor diets and malnutrition also influence the risk of developing this cancer.[2] A rising incidence of HPV infected people has contributed to an increase in oropharyngeal cancer. Fanconi anemia which is associated with HPV positivity carries a 500-700 fold increase in the risk of head and neck SCC. Although oral cancers are not considered a familial cancer, a family history of head and neck SCC causes a two to four fold increase in the risk of developing a SCC oral cancer.[3] ||
 * Signs & Symptoms: || * The most common symptom of oropharyngeal cancer is a sore throat [4]
 * Painless, palpable mass
 * Hoarseness and/or change in voice
 * Otalgia, or ear pain, and numbness of the face, both based on nerve involvement [5]
 * Dysphagia, or difficulty swallowing
 * Poor fitting dentures
 * Trismus, also known as lock jaw, based on involvement of muscles - masseter or pterygoid [5]
 * Loss of appetite ||
 * Diagnostic Procedures: || Diagnostic procedures for the oropharynx include [5]:
 * General
 * Physical exam
 * General history with an importance on alcohol intake, smoking, and tobacco chewing
 * Head and neck examination
 * Palpation is very important in examining the head and neck
 * Panendoscopy (procedure of examining the upper gastrointestinal tract with a camera on a flexible tube)
 * Image of a flexible endoscope can be found at: [|F 7-3 Flexible endoscope.jpg]
 * Examination of lymph nodes
 * Biopsy of suspicious areas
 * Laboratory studies
 * Complete Blood Counts
 * Urinalysis
 * Radiographic studies
 * Chest x-ray
 * Radiographs of the neck or mandible
 * Computed tomography scans
 * Magnetic resonance scans
 * Radionuclide bone scans / Positron emission tomography scans ||
 * Histology: || * Squamous Cell cancer; often poorly differentiated; 90% of base of tongue cancers(7)
 * Lymphoepithelioma; poorly differentiated non-keratinizing Squamous Cell ca with profuse lymphoid infiltration; <1.5%(6)
 * Glandular cancer; includes mucoepidermoid, adenocarcinoma, and adenoid cystic carcinoma; low %(7)
 * Non-Hodgkin’s Lympoma; 10-15% tonsil ca, 1-2% base of tongue ca (6)
 * Malignant Melanoma; 6% of melanomas found in upper passages.(6) ||
 * Lymph Node Drainage: || [[image:Katie-LymphNodeLevels-Neck.jpg width="168" height="212" align="right" caption="Figure 1. Lymph node levels of the neck. 13"]]
 * Tonsillar fossa = Subdigastric, submaxillary (Node Level I), midjugular chain (Node Level III), posterior cervical (Node Level V) [5,10]
 * Tonsillar fossa node involvement = 60-70%; involvement increasing with stage of disease
 * Soft pallet, retromolar trigone, tonsillar pillar = Submaxillary (Node Level 1), jugulodigastric (Node Level II); 45% rate of nodal involvement
 * Base of tongue = retropharyngeal (Node Level II, III, IV)[11] ||
 * Metastatic Spread: || The route of spread varies based off site of disease:
 * Base of Tongue
 * Early stage base of tongue tumors tend to grow locally
 * As the tumor advances it spreads laterally to the tonsilar fossa and pharyngeal wall, along with nodal involvement
 * The jugular chain of lymph nodes are the main lymph nodes involved
 * Tonsilar Region
 * Spread anteriorly to the tonsillar pillar and retromolar trigone
 * Spread medially to the soft palate and across the glossopalatine sulcus into the base of tongue
 * Spread laterally to the pterygoid muscles and pharyingeal walls
 * Spread superiorly to the nasopharynx and inferiorly to the pyriform sinus
 * Soft Palate
 * Common routes of spread include the tonsillar pillars, tonsillar fossa, pharyngeal wall, and the hard palate
 * Nodal involvement upon diagnosis is seen in approximately 40% of cases [8]
 * Oropharyngeal Wall
 * Commonly spread into pharyngeal cavity and the pre-vertebral mucle
 * Spread to the vertebral bodies is rare
 * Nodal involvement for squamous cell carcinomas is seen in approximately 55% of cases [8] ||
 * Grading: || The **grade** of a tumor provides information about its **biological aggressiveness** and is based on the **degree of cell differentiation** . For some tumors it is one of the most important prognostic indicators. Differentiation is how much the tumor cells resemble normal cells of the same tissue type and is based on microscopic appearance of cancer cells. There is usually 4 grade classifications Grades 1, 2, 3, and 4. The cells of **Grade 1 tumors resemble normal cells**, and tend to grow and multiply slowly. **Grade 1 tumors are generally considered the least aggressive ** and **4 being most aggressive** .[9]
 * Staging: || **Staging** tells us the anatomic extent of the disease. The American Joint Committee on Cancer **(AJCC)** has established a staging system for cancer of the oral cavity. Head and neck cancer staging is based on **diagnostic information** that determines the ** size, extent, presence of positive nodes**.
 * Stage 0** Cancer is found only in **__cells lining the oropharynx__** . Stage 0 cancer is also called carcinoma in situ
 * Stage I** The cancer **__is 2 centimeters__** (about ¾ inch) or smaller and **__has not spread outside the oropharynx.__**
 * Stage II** The cancer is **__larger than 2 centimeters, but not larger than 4 centimeters__** (about 1½ inches), and has not spread outside the oropharynx.
 * Staging: || **Staging** tells us the anatomic extent of the disease. The American Joint Committee on Cancer **(AJCC)** has established a staging system for cancer of the oral cavity. Head and neck cancer staging is based on **diagnostic information** that determines the ** size, extent, presence of positive nodes**.
 * Stage 0** Cancer is found only in **__cells lining the oropharynx__** . Stage 0 cancer is also called carcinoma in situ
 * Stage I** The cancer **__is 2 centimeters__** (about ¾ inch) or smaller and **__has not spread outside the oropharynx.__**
 * Stage II** The cancer is **__larger than 2 centimeters, but not larger than 4 centimeters__** (about 1½ inches), and has not spread outside the oropharynx.
 * The cancer is **__any size__** and has spread **__to only one lymph node on the same side of the neck__** as the cancer. (Lymph nodes are small, bean-shaped structures found throughout the body. They help fight infection and disease.) The lymph node that contains cancer is 3 centimeters (just over one inch) or smaller
 * Stage IVA**
 * The cancer has **__spread to tissues near the oropharynx__**, including the voice box, roof of the mouth, lower jaw, muscle of the tongue, or central muscles of the jaw. Cancer may have spread to one or more nearby lymph nodes, **__none larger than 6 centimeters (almost 2½ inches).__**
 * The **__cancer is any size, is only in the oropharynx__**, and has spread to one lymph node that is **__larger than 3 centimeters but no larger than 6 centimeters__** , or to more than one lymph node, none larger than 6 centimeters.
 * Stage IVB**
 * Cancer surrounds the **__ main artery in the neck or has spread to bones in the jaw or skull __**, to muscle in the side of the jaw, or to the upper part of the throat behind the nose; the cancer may have spread to nearby lymph nodes.
 * Stage IVC ** In stage IVC, cancer has spread to **__ other parts of the body __** ; the tumor may be any size and may have spread to lymph nodes.(3)
 * __ Summary of Staging of Oral cavity and Oropharynx: __**
 * Radiation Side Effects: || Side effects resulting from radiation treatment of oropharyngeal cancers include erythema, xerostomia, mucositis, dysphagia, laryngeal edema, hearing loss, trismus, osteonecrosis, and carotid artery rupture. ** 2 **
 * ** Erythema ** has an approximate dose tissue response of 2000cGy.**1** Erythema can occur anytime within the first few weeks of treatment.
 * ** Xerostomia ** has an approximate dose tissue response of 2000cGy. **1** Moderate to severe cases of xerostomia is reported in approximately 75% patients who have received a conventional radiation beam arrangement. IMRT can reduce this side effect exponentially by 4% per cGy. **2**
 * ** Mucositis & Dysphagia ** has an approximate dose tissue response of 3000cGy.**1** Mucositis and dysphagia can be moderate to sever and are the most common radiation side effects reported. **2**
 * ** Laryngeal Edema, Hearing Loss, & Trismus ** are less common side effects. Approximate dose tissue responses are 5000cGy, 4000cGy, & 6000cGy respectively. **1**
 * ** Osteonecrosis ** has an approximate dose tissue response of 5000cGy-6000cGy. Radiation side effects are dependent on many factors. These factors include stage of tumor, dose delivered, use of oral hygiene, trauma, and radiation technique.**2**
 * ** Carotid Artery Rupture ** can occur in up to 3% of patients needing surgery following a radiation failure.**2** ||
 * Prognosis: || Gender, tumor extension and stage are all prognostic factors.
 * Primary tumor stage and cervical lymph node metastasis has a significant influence on 5 year survival.
 * Decreased survival is associated with tumor extension into the base of tongue.
 * According to Chao, et al. some studies suggest that age does not effect survival.**2** ||
 * Treatments: || **__2002 Stage__ __Recommendation__**
 * Surgery **
 * Radiation Therapy **
 * Simulation and Treatment Planning **
 * TD5/5: || Below is a list of TD 5/5 doses to volumes of organs at risk in the oropharynx region. At these doses, 1 in 20 patients will exhibit the listed outcomes within 5 years of dose administration.
 * Parotid = 3200 cGy to 2/3 or 3/3 volume; outcome = xerostomia [12]
 * Larynx = 7900 cGy to 1/3, 7000 cGy to 2/3 or 3/3; outcome = cartilage necrosis
 * Larynx = 4500 to 2/3 or 3/3; outcome = laryngeal edema
 * Thyroid = 4500 cGy to 3/3; outcome = hypothyroidism
 * Middle ear = 3000 cGy to 1/3, 2/3, or 3/3; outcome = acute serous otitis
 * Middle ear = 5500 cGy to 1/3, 2/3, or 3/3; outcome = chronic serous otitis
 * Oral mucosa = 6000 cGy to 50 cubic centimeters (cm); outcome = ulcer/fibrosis
 * Spinal cord = 5000 cGy to 5 or 10 cm, 4700 cGy to 20 cm; outcome = myelitis/necrosis
 * Mandible = 4000-5000 cGy; outcome = osteoradionecrosis [14]

> Radiation Oncology Training in Australia. http://ozradonc.wikidot.com/late-bone-reactions. Accessed May 28, 2011. > > Principles and Practice of Radiation Therapy. Radiation Oncology Management Decisions.// 2nd ed. Phidelphia, PA: Lippincott, Williams & Wilkins; 2002:237 & 244.
 * 1) Huang K, Quivey J M. Oropharyngeal cancer. In: Hansen EK, Roach M III, eds.  Handbook of Evidence-based Radiation Oncology.  New York, NY: Springer Science + Business Media, LLC; 2007:86-92.
 * 2) Cohan D M, Popat S, Kaplan S E, Rigual N, Loree T. Oropharyngeal cancer: current understanding and management.  Otolaryngology & Head and Neck Surgery.  2009; 17:88-94.
 * 3) Oropharyngeal cancer. Best Practice Web site .  __[]__ . Accessed May 24, 2011.
 * 4) Washington C, Leaver D. //Principles and Practice of Radiation Therapy//. 3rd ed. Mosby Inc. St. Louis, MO. 2004: p. 723.
 * 5) Chao C, Perez C, Brandy L. Radiation Oncology Management Decisions. 2nd ed. Lippincott Williams & Wilkins, Philadelphia, PA. 2002:223-245.
 * 6) Perez, Brady, Halperin, Schmidt-Ullrich; //Principles and Practice of Radiation Therapy// //4th Edition//; Philadelphia PA; Lippincott Williams and Wilkins; 2004; 1030
 * 7) Fletcher; //Textbook of Radiotherapy;// Philadelphia PA. Lea & Febiger; 1980
 * 8) Hansen, Roach; //Handbook of Evidence-Based Radiation Oncology;// New York NY. Springer; 2010:121-127
 * 9) 1. Gunderson L, Tepper J. Clinical Radiation Oncology. Churchill Livingstone. Philadelphia PA. 2000: 456-457
 * 10) Perez, Brady, Halperin, Schmidt-Ulrich, //Principles & Practice of Radiation Oncology 5th edition//; Philadelphia PA; Lippincott, Williams & Wilkins; 2008: 891-957
 * 11) American Academy of Otolaryngology – Head and Neck Surgery Website. http://www.entnet.org/EducationAndResearch/loader.cfm?csModule=security/getfile&pageid=20434. Accessed May 26, 2011.
 * 12) Wang XS, Hu CS, Ying HM, Ding JH, Feng Y. Patterns of retropharyngeal node metastasis in nasopharyngeal carcinoma.//Int J Radiat Oncol Biol Phys//. 2009;73(1):194.
 * 13) Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. //Int J Radiat Oncol Biol Phys//.1991;21(1):109-122.
 * 14) Journal of Clinical Pathology Website. http;//jcp.bmj.com/content/58/3/243/F11.large.jpg. Accessed May 26, 2011.//