Nasopharynx


 * **Epidemiolgy:** || Commonly found among Asians and Southern Chinese males while uncommon among Caucasians.[1] ||
 * **Etiology:** || Viral, genetic and environmental causes are attributed to this disease. Exposure to the Epstein-Barr virus has been associated with nasopharyngeal cancer and other lymphomas. This disease has also been linked and correlated with elevated levels of human leukocyte antigen (HLA) among the Chinese.[2] Lastly, environmental causes such as occupational exposures to smoke or dust, or excessive alcohol consumption are factors that can cause nasopharyngeal carcinoma. ||
 * **Signs & Symptoms:** || A lump in the nose or neck, a sore throat, trouble breathing or speaking, nosebleeds, trouble hearing, pain or ringing in the ear and headaches.[3] ||
 * **Diagnostic Procedures:** || GENERAL: An intake of the patient's thorough medical history must be performed as well as a physical examination. The physical exam is done to assess the primary tumor extent, palpate the neck node(s), test the cranial nerve(s) for assessment of vision, and inspect the tympanic membranes for hearing functions. While palpating the neck node(s) the following must be recorded: the size, laterality and lowest extent of enlarged node.
 * **Diagnostic Procedures:** || GENERAL: An intake of the patient's thorough medical history must be performed as well as a physical examination. The physical exam is done to assess the primary tumor extent, palpate the neck node(s), test the cranial nerve(s) for assessment of vision, and inspect the tympanic membranes for hearing functions. While palpating the neck node(s) the following must be recorded: the size, laterality and lowest extent of enlarged node.

ENDOSCOPIC: examinations include nasopharyngoscopy and biopsies of the nasopharynx and adjacent suspicious areas. A Panendoscopy may or may not be done as well.[4]

IMAGING: Radiographic studies of the head and neck are used to assess the locoregional extent. MRI is the study of choice because of its superior sensitivity. CT with contrast is an acceptable substitute. A Chest x-ray is done. A Bone Scan may be ordered if the patient complains of pain or tenderness. Radiographs of the bones may be ordered if the bone scan is abnormal. A Liver scan is only indicated by right upper quadrant pain, enlarged liver by palpation or elevated liver chemistries. If there is advanced locoregional disease then a PET/CT can be ordered as well.

LABS: Blood counts, blood chemistry profile, and liver function tests are ordered.[5] || GX: Grade cannot be evaluated. G1: The cells appear like normal cells (well differentiated). G2: The cells moderately differentiated. G3: The cells do not resemble normal cells (undifferentiated).
 * **Histology:** || Squamous cell or it's variants (Epidermoid or undifferentiated carcinomas) most common type, accounting for about 90%; Remaining 10% of types include lymphomas, plasmacytoma, melanoma, rhabdomyosarcoma, chordoma, and minor salivary gland origin. [6] ||
 * **Lymph node drainage:** || Bilateral drainage; Nodes involved include the Cervical, Subdigastric (Jugulodigastric), Supraclavicular, Retropharyngeal, Upper Jugular, and Spinal Accessory (Level V) ||
 * **Metastatic spread:** || Tumors can spread by three pathways: local extension through adjacent tissue, through the lymphatic system, and through the blood stream.[7] Nasopharyngeal carcinoma spreads mainly by local extension and the lymphatic system. Local extension may be into the oropharynx, orbit of the eye, nasal cavity, soft palate, or the bones of the skull. Distant metastasis of nasopharyngeal tumors are most commonly found in the bone, lungs, and brain. ||
 * **Grading:** || Grade describes how closely the cancer cells resemble normal cells microscopically. In general, lower grade tumors have a better prognosis.

The World Health Organization (WHO) has developed a histological grading system to help describe nasopharyngeal tumors.[7] Grade 1: Keratinizing squamous cell carcinoma Grade 2: Nonkeratinizing squamous cell carcinoma Grade 3: Undifferentiated carcinoma (most common)

WHO Grade 1 accounts for 20% of cases in the US and is associated with alcohol and tobacco use. WHO Grade 2 and 3 are typically seen in Southern China. Grade 3 nasopharyngeal cancers respond well to treatment. [7] ||
 * **Staging:** || Tumor Node Metastasis staging is used to classify the stage of nasopharynx tumors.[4,8]

TX-T4 describe the size and extent of the tumor. TX: Primary tumor cannot be assessed. T0: No evidence of primary tumor. Tis: Carcinoma in situ (cancer cells are present only in the surface layer of the nasopharynx but have not invaded into the deeper layers). T1: Tumor confined to the nasopharynx. The cancer may also have grown into the oropharynx and/or the nasal cavity, but no further. T2: Tumor extends to soft tissues of oropharynx and/or nasal fossa. T2a: Without parapharyngeal extension T2b: With parapharyngeal extension T3: Tumor invades bony structures and/or paranasal sinuses. T4: Tumor with intracranial extension and/or involvement of cranial nerves, infratemporal fossa, hypopharynx, or orbit.

Nx-N3 describe the involvement and size of nodes. Nx: Regional lymph nodes cannot be assessed. N0: No regional lymph node metastasis. N1: Unilateral metastasis in lymph node(s), < 6 cm in greatest dimension, above the supraclavicular fossa OR spread to lymph nodes behind the throat (retropharyngeal) on either side of the neck, also <6 cm in greatest dimension. N2: Bilateral metastasis in lymph node(s), <6 cm in greatest dimension, above the supraclavicular fossa. N3: Metastasis in a lymph node: N3a: Greater than 6 cm in dimension N3b: Extension to the supraclavicular fossa.

MX-M1 describe metastasis (distant spread). MX: Distant metastasis cannot be assessed. M0: No distant metastasis. M1: Distant metastasis present.

STAGE 0 (in situ): Tis, N0, M0 http://www.cancer.net/patient/Multimedia/Medical%20Illustrations%20Gallery/Web/nasopharynx_0.jpg [9]

STAGE I: T1, N0, M0 http://www.cancer.net/patient/Multimedia/Medical%20Illustrations%20Gallery/Web/nasopharynx_I.jpg [9]

STAGE IIA: T2, N0, M0 http://www.cancer.net/patient/Multimedia/Medical%20Illustrations%20Gallery/Web/nasopharynx_IIA.jpg [9]

STAGE IIB: T1 or T2, N1, M0 http://www.cancer.net/patient/Multimedia/Medical%20Illustrations%20Gallery/Web/nasopharynx_IIB.jpg [9]

STAGE III:(T3, N0, N1, or N2, M0) or (T1 or T2, N2, M0) http://www.cancer.net/patient/Multimedia/Medical%20Illustrations%20Gallery/Web/nasopharynx_III.jpg [9]

STAGE IVA: T4, N0, N1, or N2, M0 http://www.cancer.net/patient/Multimedia/Medical%20Illustrations%20Gallery/Web/nasopharynx_IVA.jpg [9]

STAGE IVB: Any T, N3, M0 http://www.cancer.net/patient/Multimedia/Medical%20Illustrations%20Gallery/Web/nasopharynx_IVB.jpg [9]

STAGE IVC: Any T, Any N, M1 http://www.cancer.net/patient/Multimedia/Medical%20Illustrations%20Gallery/Web/nasopharynx_IVC.jpg [9] ||
 * **Radiation side effects:** || The most common short-term side effects of radiation treatment of nasopharyngeal carcinomas include sunburn-like skin changes and fatigue, both of which should resolve after the end of treatment. Long-term side effects that may be encountered include xerostomia (dry mouth) due to damage to the salivary glands, sore throat, mouth sores, voice hoarseness, difficulty with eating and swallowing (due to lack of saliva), taste changes, and weight loss. A discussion with a dentist familiar with radiation side effects and an evaluation of the patients teeth is recommended prior to radiation treatment. Additionally, damage to the bones of the skull, mandible or maxilla, nerves that are near the tumor, and the pituitary gland may be experienced, but can be minimized with proper treatment definition. Hearing and vision changes, such as lens opacity, retinopathy, deafness, or trismus may occur, depending on the extent of the tumor and the treated volume. Several years after treatment the carotid artery may narrow as a late side effect of the radiation. In the case of pediatric treatment of nasopharyngeal carcinoma, hypopituitarism may develop.[10] ||
 * **Prognosis:** || Prognostic factor include cervical lymph node involvement, extent of local infiltration and histology. Some studies have shown a worse prognosis with keratinizing histology over non-keratinizing, however there are also studies that has shown the histology to have no prognostic difference. The prognosis depends on which part of the nasopharynx is involved and the grade. Survival and local control decreases with advancing T and survival and distal failure are associated with advancing N. Most nasopharyngeal cancers are diagnosed at stage 3 or 4. There have been reports that indicate a better prognosis for patients under the age of 50 and in females.[5] For all people diagnosed with nasopharyngeal cancer, about 5 out of 10 (50%) people, live for at least 5 years. Below are some statistics for the different stages of nasopharyngeal cancer.

Stage 1 70% 5 year survival Stage 2 &3 60% 5 year survival Stage 4 40% 5 year survival Overall survival rates for people with undifferentiated nasopharyngeal cancer are better than the keratinizing type.[6] ||
 * **Treatments:** || Treatment options for carcinoma of the nasopharynx are chemotherapy followed by radiation therapy. The treatment modalities are specified by the stage. Surgery is not recommended due the location of the nasopharanx, the proximity to the base of the skull, and local metastases to the cervical lymph nodes at the time of diagnosis.[4]

Stage I–IIA: Radiation Therapy alone. Stage IIB–IVB: Concurrent chemotherapy with radiation therapy. Stage IVC: Chemotherapy followed by curative or palliative radiation therapy. Local Recurrence: Re-irradiation with Intensity Modulated Radiation Therapy (IMRT), Stereotactic Radiosurgery (SRS), or brachytherapy.

Statistical comparison between combined chemotherapy with radiation therapy and radiotherapy alone did not have significant differences in overall survival rates of the patients. A recent data showed slight improvement of overall survival rate in patients diagnose with stage III and IV nasopharyngeal cancer.
 * Chemotherapy **

Two laterally parallel opposed wedge fields, which cover the primary and upper neck, with a matching low anterior neck field is treated up to 70Gy with the spinal cord blocked off at 45Gy.[4]
 * Radiation Therapy **

With the increasing use of intensity modulated radiation therapy (IMRT), the IMRT provides overall improved dose distribution over conventional radiotherapy. In IMRT treatment three different CTV volumes are treated to the total of 70Gy. In CTV70 the dose of 70Gy is delivered at 1cm margin around GTV. In CTV56-59.4, the dose of 56 to 59.4Gy is delivered at the entire nasopharynx including CTV70, all of the cervical nodes, and the adjacent parapharyngeal tissue and sinuses. The CTV54, the dose of 54Gy is delivered to CTV70, CTV56-59.4, and nearby low risk lymph nodal groups.[11]
 * IMRT **

For Stage T1, T2, and T3 tumors Anterior – 2cm outside of the tumor extension or 2cm posterior of the nasal cavity Superior – Includes the entire cavernous sinus, sphenoid sinus, and base of the skull. Posterior – Extends to the end of the spinous process to include the retropharyngeal nodes, posterior cervical nodes, and posterior pharyngeal wall.[12] Optional brachytherapy can be used as a boost treatment after external beam radiation therapy. The dose of 5 to 25Gy is delivered via intracavitary applicators. An example of intracavitary HDR is shown on figures below.[12] ||
 * Treatment Field Boarders **
 * Brahytherapy **
 * TD 5/5: || Normal tissue tolerance doses in terms of TD5/5 represent the normal tissue tolerance dose at 5% complication within 5 years post radiation therapy treatments.[12]

TD5/5 Normal Tissue Tolerances (Gy) || [2] Chan SH, Chew CT, Prasad U, et al. HLA and nasopharyngeal carcinoma in Malays. British Journal of Cancer. 1985; 51(3): 389-392. []. Accessed May 21, 2012. [3] Nasopharyngeal Cancer Treatment. National Cancer Institute. []. Accessed May 21, 2012. [4] Chao KS, Perez CA, Brady KW. //Radiation Oncology-Management Decisions.// 2nd edition. Philiadelphia: Lippincott, Williams & Wilkins. 2002 [5] Hansen E, Roach M. //Handbook of Evidence-Based Radiation Oncology//. New York: Springer 2007 [6] Washington, Charles, and Dennis Leaver. //Principles and Practices of Radiation Therapy//.St. Louis,Missouri: Mosby Elsevier, 2010 [7] National Cancer Institute website. [] Last revised February 23, 2012. Accessed May 23, 2012. [8] American Cancer Society website.[] Last revised January 11, 2012. Accessed May 23, 2012. [9] American Society of Clinical Oncology website. [] Last revised May, 2011. Accessed May 24, 2012. [10] American Cancer Society website. [] Accessed May 25, 2012. [11] Hansen KE, Roach M. Handbook of Evidence-Based Radiation Oncology. 2nd Edition. New York: Springer 2010 [12] Hoppe TR, Phillips LT, Roach M. Leibel and Phillips Textbook of Radiation Oncology. 3rd Edition. Philadelphia: Saunders, Elsevier. 2010
 * **References:** || [1] Lee N, Xia P, Quivey JM, et al. Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience. International Journal of Radiation Oncology Biology Physics. 2002; 53(1):12-22. doi:10.1016/S0360-3016(02)02724-4.

Figure 1. Coronal and Sagittal views of the nasopharynx treatment fileds.[5]

Figure2. Example of Intensity Modulated Radiation Therapy (IMRT) treatment plan of the nasopharynx.[12]

Figure3. A patient with the nasopahrynx intracavitary applicator in place.[12]

Figure4. Lateral and anterior-posterior localization films of an intracavitary applicator placement.[12] ||

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