Nasopharynx

factors are nickel refining, steel and textile workers. EBV and genetic host factors. 1 || lump in the neck, and chronic ulcer. 2 || are usually lymphoma. 4  || G1: Well differentiated G2: Moderately differentiated G3: Poorly differentiated 7  || Brainstem or cervical spine myelopathy 1% Hypopituitarism not common but has been reported Opthalmic side effects after 60Gy - opacities in the lens that develop after several years Retinopathy with 70 Gy 24-108 months after treatment Deafness 1%-7% 8% significant hearing impairment 3% bilateral deafness Osteonecrosis of mandible or maxilla 1% Dental decay frequently occurs Xerostomia (moderate or severe) in 75% of patients IMRT at 4% per Gy exponentially Trismus 5%-10% Fibrosis of subcutaneous tissue of the neck with doses of 50Gy 9 || T1 lesions local control 90% T2 lesions local control 85% to 90% T3 lesions local control 62% to 73% T4 lesions local control 44% to 71% 10 || Surgery is not an option since the nasopharynx is immiediatly adjacent to the base of the skull. It is impossible to have acceptable margins with surgical resection. Radical neck dissection has been preformed for neck node metastasis, but this is very rare. (Chao)
 * Epidemiology: || H & N tumors in general account for approximately 5% of the overall incidence of cancer in the U.S., and 2% of all cancer deaths.Rates are twice as high in males than in females.Higher in certain populations and geographical regions of the world (southern China, Southeast Asia, and Hong Kong). 1 ||
 * Etiology: || Primary risk factors for this disease are tobacco and alcohol. Occupations associated with greater risk
 * Signs and Symptoms: || Nasal stuffiness, dysphagia, nasal twang, decrease in hearing, ear pain., headache, and, sore throat
 * Diagnostic Procedures: || Typical diagnostic procedures for nasopharyngeal cancer are the following: a complete history and physical, nasopharyngoscopy using an endoscope and biopsy of any suspicious tissues. Imaging studies: CT and MRI using contrast. CT is better at delineating bone destruction from any cancer and MRI is better at delineating soft tissue changes. 3 ||
 * Histology: || 90% is squamous cell carcinoma (SCC) and SCC variations (epidermoid or undifferentiated carcinomas). The other 10%
 * Lymph Node Drainage: || Nodal disease can be bilateral in up to 50% of cases. Main lymphatic drainage routes: from the retropharyngeal nodes to the superior jugular nodes and into the posterior cervical nodes. 5  ||
 * Metastatic Spread: || Bone (primary metastatic site), lung, liver 6 ||
 * Grading: || Gx: Grade cannot be evaluated
 * Staging: || In 1997, the American Joint Committee on Cancer, in collaboration with the Union Internationale Contre le Cancer, updated the TNM staging system for cancers of the head and neck. Primary tumors are classified as T1 to T4. Nodal dissease as N1,N2 or N3. Distant metastasis is staged as M1, and the overall stage grouping consists of stages 1 to 1V. Stages I and II aare considered to be early cancers. Advanced stages are III and IV cancers.¹¹ __Nasopharynx T1-tumor confined to nasopharynx.T2-tumor extends to soft tissures of oropharynx and/or nasal fossa. T2a- Without parapharyngeal extension. T2b-With parapharngeal 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.__ 8 ||
 * Radiation Side Effects: || Cranial and cervical sympathetic nerve palsey 0.3-6%
 * Prognosis: || Race, age and gender rarely have prognostic significance
 * Treatments: || __Surgery__

__Chemotherapy__ Neo-adjuvant or adjuvant chemotherapy has been used for primary or recurrent nasopharynx cancer with a complete response rate of 10-20% and partial response rate of 40%. Cisplatin, Doxorubicin, Epirubicin, Bleomycin and Methotrexate have been shown to be active for this disease. The most effective combinations are cisplatin based.

__Radiation Therapy__ Opposed laterals are used to treat nasopharynx and adjacent structures. IMRT provides excellent dose distributions with doses up to 75Gy. Brachytherapy has been used to deliver a high dose to a limited volume of the nasopharynx and is frequently combined with external irradiation to treat extensive primary or recurrent carcinoma. Three-dimensional treatment planning and conformal therapy Proton therapy (Chao)

__Treatment Borders__ Lateral treatment fields are angled 5 degrees posteriorly to allow coverage of the posterior wall of the nasopharynx while avoiding direct ipsilateral irradiation to the external and middle ear. This also reduces the irradiation to the contralateral lens. The volume to be irradiated includes the nasopharynx, adjacent parapharyngeal tissues (with a 1-2cm margin) and all the cervical lymphatics (jugular, spinal accessory and supraclavicular) Standard fields should include the posterior ethmoid cells, the posterior 1/3 of the maxillary antrum and the nasal cavity (but not the orbit unless warranted) Superior border-splits the pituitary fossa and extends anteriorly along the sphenoid plate Superior border (for base skull involvement)-1cm above pituitary fossa Anterior border-includes the posterior 2cm of the nasal cavity and maxillary antrum, the clivus is included with a 1cm margin Anterior border (extension)-the anterior border is moved forward 2cm to cover extension into the ethmoid/maxillary sinuses and occasional into the posterior orbit if warranted. Posterior border-is behind the cervical processes and should cover the mastoid and occipital lyph nodes Boost field-after 45Gy the posterior border is moved anteriorly to shield the spine. A higher energy photon should preferably be used. The posterior neck fields is supplemented with 5-15Gy with 9MeV electrons through small lateral fields. An anterior field can occasionally be added to irradiate anterior tumor extension. Lower neck and supraclavicular fossa are electively treated with a single anterior field to 50Gy given dose (45Gy at 3cm) with 2Gy daily fractions.

__Doses__ T1-T2 - 65Gy T3-T4 - 70-75Gy 45Gy reduce field to exclude spinal cord then boost to 22-27Gy T3-T4 - 50Gy for young adults age 15-30 Children older than 15 years of age, boost 10-15Gy to regional lymph nodes Brachytherapy: 5-25Gy (calculated to 0.5-1.0cm) combined with external radiation 11 || According to RTOG 0619 a volume of spinal cord larger than about 3x3x3 mm cubed would be better off having dose less than 48 Gy. Also, in non-IMRT plans any field recieving more than 40-44Gy are to have a spinal block to reach this goal. 12 Phillips who invented the NSD curve used his formula to postulate that a limit of 5000cGy was appropriate because anything above this threshold would cause radiation myelitis. Boden recognized the need for volume data when evaluating dose to the spine. A recommendation by Emami is 5500cGy to a volume of 5cm for the TD5/5. 13  __BRAIN STEM__ Bodin and Sheline have made suggestions of what the dose tolerance should be for the brain stem, however Emami believes them to be to conservative and has come up with their own theory of what the dose should be. Emami believes it should be 6000cGy for a volume of 1/3 with an ending result of necrosis. 13 According to RTOG the brain stem can recieve, "54Gy or 1% of PTV cannot exceed 60Gy." 14 __OPTIC CHIASM__ Emami decided that the appropriate TD5/5 is 50Gy due to the article written by Hammer who reported that patients who had pituitary tumors developed chiasmal necrosis after receiving 4250cGy in large fractions of 210-280cGy. 15 According to RTOG the optic chiasm can recieve, "54Gy or 1% of PTV cannot exceed 60Gy." 16  __OPTIC NERVE__ Many articles such as Parsons, Brown, and Pezner have written articles on optic nerve and blindness. Blindness was found to have occured at or below 50Gy so Emami could not justify to follow some article with the TD5/5 to be 55Gy, instead they decided to follow the TD5/5 of 50Gy. 17 According to RTOG the optic nerve can recieve, "54Gy or 1% of PTV cannot exceed 60Gy." 18  __RETINA__ The dose response curve for retina is extremely steep between 50Gy and 60Gy, so according to Emami a realistic TD5/5 is 45 Gy with an ending side effect of visual loss. 19  __LENS__ Emami states that 10Gy should be the TD5/5, but this is concluded after a Seattle group known as Deeg who checked TBI patients post irradiation for the incidences of cataracts. 19 __MANDIBLE__ In some cases the end point is necrosis, however Emami uses Osteoradionecrosis as an endpoint for determining the TD5/5 because of its significants in morbidity. Even though there is no reliable data on volume and dose to the mandible Emami believes that 1/3 should recieve 65Gy or less or anything above this volume should recieve 60Gy and below. 19 According to RTOG the mandible can recieve, "70Gy or 1cc of PTV cannot exceed 75Gy." 20
 * TD5/5: || __SPINAL CORD__

__PAROTID__ Emami has made an attempt to determine from literature and clinical experience what the TD5/5 should be for the parotid glands before xerostomia occurs, The TD5/5 they determined is 32Gy with the note that no significant change occurs with less than 50% of the parotid being irradiated. 21 "Mean dose is less than or equal to 26Gy in at least one gland or at least 20cc of the combined volume of both parotid glands will receive less than 20Gy or at least 50% of the gland will recieve less than 30Gy in at least one gland." 22  ||
 * [[image:nasophar.jpg width="336" height="252"]]







|| __**References**__ 1.Lenhard,E. Raymond. Jr.,MD., Osteen, T. Robert, Gansler,Ted,.MD. The American Cancer Society's Clinical Oncology. 1st edition. Atlanta,GA. 2001. 2.Chao KS, Perez CA, Brady LW. Radiation Oncology-Management Decisions. 2nd edition. Philadelphia, PA: Lippincott, Williams & Wilkins. 2002. 3. Laramore GE, Colterra MD, Hunt KJ. Tumors of the head and neck. In: Rubin P, ed. //Clinical Oncology: A Multidisciplinary Approach// //for Physicians and Students//. 8th ed.Philadelphia, PA: W.B. Saunders Company; 2001:445-446. 4. Lozano R. Head and neck cancer. In: Washington CM, Leaver D, eds. //Principles and Practice of Radiation Therapy//. 2nd ed. St. Louis, MO: Mosby; 2004:684-686. 5. Lozano R. Head and neck cancer. In: Washington CM, Leaver D, eds. //Principles and Practice of Radiation Therapy.// 2nd ed. St. Louis, MO: Mosby; 2004:684-686. 6. Chao KS, Perez CA., Brady LW. //Radiation Oncology - Management Decisions//. 2nd edition. Philadelphia, PA: Lippincott, Williams & Wilkins. 2002. 7. Tumor Grade retrieved January 9, 2010 from the American Society of Clinical Oncology website: www.cancer.net/patient/Cancer+Types/Nasopharyngeal+Cancer 8. Lenhard,E. Raymond. Jr.,MD., Osteen, T. Robert, Gansler,Ted,.MD. The American Cancer Society's Clinical Oncology. 1st edition. Atlanta,GA. 2001. 9. Chao KS, Perez CA, Brady LW//. Radiation Oncology - Management Decisions//. 2nd edition. Philadelphia, PA: Lippincott, Williams & Wilkins. 2002 10. Rodney R. Million, Nicholas J. Cassisi. //Management of Head and Neck Cancer - A Multidisciplinary Approach.// 2nd edition. Philadelphia, PA: J. B. Lippincott 1994 11. Vincent T. DeVita, Jr., MD, Samuel Hellman, MD, Steven A. Rosenberg, MD, PhD. //Cancer Principals and Practices of Oncology.// 6th edition. Philadelphia, PA: Lippincott, Williams & Wilkins. 2001 12. Ridge et al: A Randomized Phase 2 Trial of Chemoradiotherapy Versus Chemoradiotherapy and Vandetanib for High-Risk Postoperative Advanced Squamous Cell Carcinoma of the Head and Neck. RTOG 0619 2009; pg15. 13. B. Emami et al: Tolerance of Normal Tissue to Therapeutic Irradiation, //Int J. Radiat Oncol Biol Phys// 21:109-122, 1991. 14. Lee et al: A Phase 2 Study of Intensity Modulated Radiation Therapy (IMRT) Chemotherapy for Nasopharyngeal Cancer. RTOG 0225 2005; pg7. 15. B. Emami et al: Tolerance of Normal Tissue to Therapeutic Irradiation, //Int J. Radiat Oncol Biol Phys// 21:109-122, 1991. 16. Lee et al: A Phase 2 Study of Intensity Modulated Radiation Therapy (IMRT) Chemotherapy for Nasopharyngeal Cancer. RTOG 0225 2005; pg7. 17. B. Emami et al: Tolerance of Normal Tissue to Therapeutic Irradiation, //Int J. Radiat Oncol Biol Phys// 21:109-122, 1991. 18. Lee et al: A Phase 2 Study of Intensity Modulated Radiation Therapy (IMRT) Chemotherapy for Nasopharyngeal Cancer. RTOG 0225 2005; pg7. 19. B. Emami et al: Tolerance of Normal Tissue to Therapeutic Irradiation, //Int J. Radiat Oncol Biol Phys// 21:109-122, 1991. 20. Lee et al: A Phase 2 Study of Intensity Modulated Radiation Therapy (IMRT) Chemotherapy for Nasopharyngeal Cancer. RTOG 0225 2005; pg7. 21. B. Emami et al: Tolerance of Normal Tissue to Therapeutic Irradiation, //Int J. Radiat Oncol Biol Phys// 21:109-122, 1991. 22. Lee et al: A Phase 2 Study of Intensity Modulated Radiation Therapy (IMRT) Chemotherapy for Nasopharyngeal Cancer. RTOG 0225 2005; pg7.